medical Bio chemistry

Introduction
All cells undergo a division cycle during their life span. Some cells are continually dividing (e.g. stem cells), others divide a specific number of times until cell death (apoptosis) occurs, and still others divide a few times before entering a terminally differentiated or quiescent state. Most cells of the body fall into the latter category of cells. During the process of cell division everything within the cell must be duplicated in order to ensure the survival of the two resulting daughter cells. Of particular importance for cell survival is the accurate, efficient and rapid duplication of the cellular genome. This process is termed DNA replication.
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Eukaryotic Genomes
The size of eukaryotic genomes is vastly larger than those of prokaryotes. This is partly due to the complexity of eukaryotic organismScompared to prokaryotes. However, the size of a particular eukaryotic genome is not directly correlated to the organism' complexity. This is the result of the presence of a large amount of non-coding DNA. The functions of these non-coding nucleic acid sequences are only partly understood. Some sequences are involved in the control of gene expression while others may simply be present in the genome to act as an evolutionary buffer able to withstand nucleotide mutation without disrupting the integrity of the organism.
One abundant class of DNA is termed repetitive DNA. There are 2 different sub-classes of repetitive DNA, highly repetitive and moderately repetitive. Highly repetitive DNA consists of short sequences 6-10 bp long reiterated from 100,000- 1,000,000 times. The DNA of the genome consisting of the genes (coding sequences) is identified as non-repetitive DNA since most genes occur but once in an organism' haploid genome. However, it should be pointed out that several genes exist as tandem clusters of multiple copies of the same gene ranging from 50 to 10,000 copies such as is the case for the rRNA genes and the histone genes.
Another characteristic feature that distinguishes eukaryotic from prokaryotic genes is the presence of introns. Introns are stretches of nucleic acid sequences that separate the coding exons of a gene. The existence of introns in prokaryotes is extremely rare. Essentially all humans genes contain introns. A notable exception are the histone genes which are intronless. In many genes the presence of introns separates exons into coding regions exhibiting distinct functional domains.
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Chromatin Structure
Chromatin is a term designating the structure in which DNA exists within cells. The structure of chromatin is determined and stabilized through the interaction of the DNA with DNA-binding proteins. There are 2 classes of DNA-binding proteins. The histones are the major class of DNA-binding proteins involved in maintaining the compacted structure of chromatin. There are 5 different histone proteins identified as H1, H2A, H2B, H3 and H4.
The other class of DNA-binding proteins is a diverse group of proteins called simply, non-histone proteins. This class of proteins includes the various transcription factors, polymerases, hormone receptors and other nuclear enzymes. In any given cell there are greater than 1000 different types of non-histone proteins bound to the DNA.
The binding of DNA by the histones generates a structure called the nucleosome. The nucleosome core contains an octamer protein structure consisting of 2 subunits each of H2A, H2B, H3 and H4. Histone H1 occupies the internucleosomal DNA and is identified as the linker histone. The nucleosome core contains approximately 150 bp of DNA. The linker DNA between each nucleosome can vary from 20 to more than 200 bp. These nucleosomal core structures would appear as beads on a string if the DNA were pulled into a linear structure.
The nucleosome cores themselves coil into a solenoid shape which itself coils to further compact the DNA. These final coils are compacted further into the characteristic chromatin seen in a karyotyping spread. The protein-DNA structure of chromatin is stabilized by attachment to a non-histone protein scaffold called the nuclear matrix.
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Eukaryotic Cell Cycles
The cell cycle is defined as the sequence of events that occurs during the lifetime of a cell. The eukaryotic cell cycle is divided into 4 major periods. During each period a specific sequence of events occurs. The ultimate conclusion of one cell cycle is cytokinesis resulting in two identical daughter cells.
The 4 phases of a typical cell cycle and the events occurring during each phase are outlined:
· 1. M phase is the period when cells prepare for and then undergo cytokinesis. M phase stands for mitotic phase or mitosis. During mitosis the chromosomes are paired and then divided prior to cell division. The events in this stage of the cell cycle leading to cell division are prophase, metaphase, anaphase and telophase.
· 2. G1phase corresponds to the gap in the cell cycle that occurs following cytokinesis. During this phase cells make a decision to either exit the cell cycle and become quiescent or terminally differentiated or to continue dividing. Terminal differentiation is identified as a non-dividing state for a cell. Quiescent and terminally differentiated cells are identified as being in G0 phase. Cells in G0 can remain in this state for extended periods of time. Specific stimuli may induce the G0 cell to re-enter the cell cycle at the G1 phase or alternatively may induce permanent terminal differentiation.
During G1 cells begin synthesizing all the cellular components needed in order to generate two identically complimented daughter cells. As a result the size of cells begins to increase during G1.
· 3. S phase is the phase of the cell cycle during which the DNA is replicated. This is the DNA synthesis phase. Additionally, some specialized proteins are synthesized during S phase, particularly the histones.
· 4. G2 phase is reached following completion of DNA replication. During G2 the chromosomes begin condensing, the nucleoli disappear and two microtubule organizing centers begin polymerizing tubulins for eventual production of the spindle poles.
Typical eukaryotic cell cycles occupy approximately 16 - 24 hrs when grown in culture. However, in the context of the multicellular organization of organisms the cell cycles can be as short as 6 - 8 hrs to greater than 100 days. The high variability of cell cycle times is due to the variability of the G1 phase of the cycle.
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DNA Replication
Replication of DNA occurs during the process of normal cell division cycles. Because the genetic complement of the resultant daughter cells must be the same as the parental cell, DNA replication must possess a very high degree of fidelity. The entire process of DNA replication is complex and involves multiple enzymatic activities.
The mechanics of DNA replication was originally characterized in the bacterium, E. coli which contains 3 distinct enzymes capable of catalyzing the replication of DNA. These have been identified as DNA polymerase (pol) I, II, and III. Pol I is the most abundant replicating activity in E. coli but has as its primary role to ensure the fidelity of replication through the repair of damaged and mismatched DNA. Replication of the E. coli genome is the job of pol III. This enzyme is much less abundant than pol I, however, its activity is nearly 100 times that of pol I.
There have been 5 distinct eukaryotic DNA polymerases identified, a, b, g, d and e. The identity of the individual enzymes relates to its subcellular localization as well as its primary replicative activity. The polymerase of eukaryotic cells that is the equivalent of E. coli pol III is pol-a. The pol I equivalent in eukaryotes is pol-ß. Polymerase-g is responsible for replication of mitochondrial DNA.
The ability of DNA polymerases to replicate DNA requires a number of additional accessory proteins. The combination of polymerases with several of the accessory proteins yields an activity identified as DNA polymerase holoenzyme.These accessory proteins include (not ordered with respect to importance):
· 1. Primase
· 2. Processivity accessory proteins
· 3. Single strand binding proteins
· 4. Helicase
· 5. DNA ligase
· 6. Topoisomerases
· 7. Uracil-DNA N-glycosylase
The process of DNA replication begins at specific sites in the chromosomes termed origins of replication, requires a primer bearing a free 3'-OH, proceeds specifically in the 5'----->3' direction on both strands of DNA concurrently and results in the copying of the template strands in a semiconservative manner. The semiconservative nature of DNA replication means that the newly synthesized daughter strands remain associated with their respective parental template strands.
The large size of eukaryotic chromosomes and the limits of nucleotide incorporation during DNA synthesis, make it necessary for multiple origins of replication to exist in order to complete replication in a reasonable period of time. The precise nature of origins of replication in higher eukaryotic organisms is unclear. However, it is clear that at a replication origin the strands of DNA must dissociate and unwind in order to allow access to DNA polymerase. Unwinding of the duplex at the origin as well as along the strands as the replication process proceeds is carried out by helicases. The resultant regions of single-stranded DNA are stabilized by the binding of single-strand binding proteins. The stabilized single-stranded regions are then accessible to the enzymatic activities required for replication to proceed. The site of the unwound template strands is termed the replication fork.
In order for DNA polymerases to synthesize DNA they must encounter a free 3'-OH which is the substrate for attachment of the 5'-phosphate of the incoming nucleotide. During repair of damaged DNA the 3'-OH can arise from the hydrolysis of the backbone of one of the two strands. During replication the 3'-OH is supplied through the use of an RNA primer, synthesized by the primase activity. The primase utilizes the DNA strands as templates and synthesizes a short stretch of RNA generating a primer for DNA polymerase.
Synthesis of DNA proceeds in the 5'---->3' direction through the attachment of the 5'-phosphate of an incoming dNTP to the existing 3'-OH in the elongating DNA strands with the concomitant release of pyrophosphate. Initiation of synthesis, at origins of replication, occurs simultaneously on both strands of DNA. Synthesis then proceeds bidirectionally, with one strand in each direction being copied continuously and one strand in each direction being copied discontinuously. During the process of DNA polymerases incorporating dNTPs into DNA in the 5'---->3' direction they are moving in the 3'---->5' direction with respect to the template strand. In order for DNA synthesis to occur simultaneously on both template strands as well as bidirectionally one strand appears to be synthesized in the 3'---->5' direction. In actuality one strand of newly synthesized DNA is produced discontinuously.
The strand of DNA synthesized continuously is termed the leading strand and the discontinuous strand is termed the lagging strand. The lagging strand of DNA is composed of short stretches of RNA primer plus newly synthesized DNA approximately 100-200 bases long (the approximate distance between adjacent nucleosomes). The lagging strands of DNA are also called Okazaki fragments. The concept of continuous strand synthesis is somewhat of a misnomer since DNA polymerases do not remain associated with a template strand indefinitely. The ability of a particular polymerase to remain associated with the template strand is termed its' processivity. The longer it associates the higher the processivity of the enzyme. DNA polymerase processivity is enhanced by additional protein activities of the replisome identified as processivity accessory proteins.
How is it that DNA polymerase can copy both strands of DNA in the 5'---->3' direction simultaneously? A model has been proposed where DNA polymerases exist as dimers associated with the other necessary proteins at the replication fork and identified as the replisome. The template for the lagging strand is temporarily looped through the replisome such that the DNA polymerases are moving along both strands in the 3'---->5' direction simultaneously for short distances, the distance of an Okazaki fragment. As the replication forks progress along the template strands the newly synthesized daughter strands and parental template strands reform a DNA double helix. The means that only a small stretch of the template duplex is single-stranded at any given time.
The progression of the replication fork requires that the DNA ahead of the fork be continuously unwound. Due to the fact that eukaryotic chromosomal DNA is attached to a protein scaffold the progressive movement of the replication fork introduces severe torsional stress into the duplex ahead of the fork. This torsional stress is relieved by DNA topoisomerases. Topoisomerases relieve torsional stresses in duplexes of DNA by introducing either double- (topoisomerases II) or single-stranded (topoisomerases I) breaks into the backbone of the DNA. These breaks allow unwinding of the duplex and removal of the replication-induced torsional strain. The nicks are then resealed by the topoisomerases.
The RNA primers of the leading strands and Okazaki fragments are removed by the repair DNA polymerases simultaneously replacing the ribonucleotides with deoxyribonucleotides. The gaps that exist between the 3'-OH of one leading strand and the 5'-phosphate of another as well as between one Okazaki fragment and another are repaired by DNA ligases thereby, completing the process of replication.
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Additional DNA Polymerase Activities
The main enzymatic activity of DNA polymerases is the 5'---->3' synthetic activity. However, DNA polymerases possess two additional activities of importance for both replication and repair. These additional activities include a 5'---->3' exonuclease function and a 3'---->5' exonuclease function. The 5'---->3' exonuclease activity allows the removal of ribonucleotides of the RNA primer, utilized to initiate DNA synthesis, along with their simultaneous replacement with deoxyribonucleotides by the 5'---->3' polymerase activity. The 5'---->3' exonuclease activity is also utilized during the repair of damaged DNA. The 3'---->5' exonuclease function is utilized during replication to allow DNA polymerase to remove mismatched bases. It is possible (but rare) for DNA polymerases to incorporate an incorrect base during replication. These mismatched bases are recognized by the polymerase immediately due to the lack of Watson-Crick base-pairing. The mismatched base is then removed by the 3'---->5' exonuclease activity and the correct base inserted prior to progression of replication.
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Post-Replicative Modification of DNA, Methylation
One of the major post-replicative reactions that modifies the DNA is methylation. The sites of natural methylation (i.e. not chemically induced) of eukaryotic DNA is always on cytosine residues that are present in CpG dinucleotides. However, it should be noted that not all CpG dinucleotides are methylated at the C residue. The cytidine is methylated at the 5 position of the pyrimidine ring generating 5-methylcytidine.
Methylation of DNA in prokaryotic cells also occurs. The function of this methylation is to prevent degradation of host DNA in the presence of enzymatic activities synthesized by bacteria called restriction endonucleases. These enzymes recognize specific nucleotide sequences of DNA. The role of this system in prokaryotic cells (called the restriction-modification system) is to degrade invading viral DNAs. Since the viral DNAs are not modified by methylation they are degraded by the host restriction enzymes. The methylated host genome is resistant to the action of these enzymes.
The precise role of methylation in eukaryotic DNA is unclear. It was originally thought that methylated DNA would be less transcriptionally active. Indeed, experiments have been carried out to demonstrate that this is true for certain genes. For example, under-methylation of the MyoD gene (a master control gene regulating the differentiation of muscle cells through the control of the expression of muscle-specific genes) results in the conversion of fibroblasts to myoblasts. The experiments were carried out by allowing replicating fibroblasts to incorporate 5-azacytidine into their newly synthesized DNA. This analog of cytidine prevents methylation. The net result is that the maternal pattern of methylation is lost and numerous genes become under methylated. However, lack of methylation nor the presence of methylation is a clear indicator of whether a gene will be transcriptionally active or silent.
The pattern of methylation is copied post-replicatively by the maintenance methylase system. This activity recognizes the pattern of methylated C residues in the maternal DNA strand following replication and methylates the C residue present in the corresponding CpG dinucleotide of the daughter strand.
The phenomenon of genomic imprinting refers to the fact that the expression of some genes depends on whether or not they are inherited maternally or paternally. Insulin-like growth factor-2 (Igf2) is a gene whose expression is required for normal fetal development and growth. Expression of Igf2 occurs exclusively from the paternal copy of the gene. Imprinted genes are "marked" by their state of methylation. In the case of Igf2 an element in the paternal locus, called an insulator element, is methylated blocking its function. The function of the un-methylated insulator is to bind a protein that when bound blocks activation of Igf2 expression. When methylated the protein cannot bind the insulator thus allowing a distant enhancer element to drive expression of the Igf2 gene. In the maternal genome, the insulator is not methylated, thus protein binds to it blocking the action of the distant enhancer element.
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DNA Recombination
DNA recombination refers to the phenomenon whereby two parental strands of DNA are spliced together resulting in an exchange of portions of their respective strands. This process leads to new molecules of DNA that contain a mix of genetic information from each parental strand. There are 3 main forms of genetic recombination. These are homologous recombination, site-specific recombination and transposition.
Homologous recombination is the process of genetic exchange that occurs between any two molecules of DNA that share a region (or regions) of homologous DNA sequences. This form of recombination occurs frequently while sister chromatids are paired during meiosis. Indeed, it is the process of homologous recombination between the maternal and paternal chromosomes that imparts genetic diversity to an organism. Homologous recombination generally involves exchange of large regions of the chromosomes.
Site-specific recombination involves exchange between much smaller regions of DNA sequence (approximately 20 - 200 base pairs) and requires the recognition of specific sequences by the proteins involved in the recombination process. Site-specific recombination events occur primarily as a mechanism to alter the program of genes expressed at specific stages of development. The most significant site-specific recombinational events in humans are the somatic cell gene rearrangements that take place in the immunoglobulin genes during B-cell differentiation in response to antigen presentation. These gene rearrangements in the immunoglobulin genes result in an extremely diverse potential for antibody production. A typical antibody molecule is composed of both heavy and light chains. The genes for both these peptide chains undergo somatic cell rearrangement yielding the potential for approximately 3000 different light chain combinations and approximately 5000 heavy chain combinations. Then because any given heavy chain can combine with any given light chain the potential diversity exceeds 10,000,000 possible different antibody molecules.
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DNA Transposition
Transposition is a unique form of recombination where mobile genetic elements can virtually move from one region to another within one chromosome or to another chromosome entirely. There is no requirement for sequence homology for a transpositional event to occur. Because the potential exists for the disruption of a vitally important gene by a transposition event this process must be tightly regulated. The exact nature of how transpositional events are controlled is unclear.
Transposition occurs with a higher frequency in bacteria and yeasts than it does in humans. The identification of the occurrence of transposition in the human genome resulted when it was found that certain processed genes were present in the genome. These processed genes are nearly identical to the mRNA encoded by the normal gene. The processed genes contain the poly(A) tail that would have been present in the RNA and they lack the introns of the normal gene. These particular forms of genes must have arisen through a reverse transcription event, similar to the life cycle of retroviral genomes, and then been incorporated into the genome by a transpositional event. Since most of the processed genes that have been identified are non-functional they have been termed pseudogenes.
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Repair of Damaged DNA
Cancer, in most non-viral induced cases, is the severe medically relevant consequence of the inability to repair damaged DNA. It is clear that multiple somatic cell mutations in DNA can lead to the genesis of the transformed phenotype. Therefore, it should be obvious that complete understanding of DNA repair mechanisms would be invaluable in the design of potential therapeutic agents in the treatment of cancer.
DNA damage can occur as the result of exposure to environmental stimuli such as alkylating chemicals or ultraviolet or radioactive irradiation and free radicals generated spontaneously in the oxidizing environment of the cell. These phenomena can, and do, lead to the introduction of mutations in the coding capacity of the DNA. Mutations in DNA can also, but rarely, arise from the spontaneous tautomerization of the bases.
Modification of the DNA bases by alkylation (predominately the incorporation of -CH3 groups) predominately occurs on purine residues. Methylation of G residues allows them to base pair with T instead of C. A unique activity called O6-alkylguanine transferase removes the alkyl group from G residues. The protein itself becomes alkylated and is no longer active, thus, a single protein molecule can remove only one alkyl group.
Mutations in DNA are of two types. Transition mutations result from the exchange of one purine, or pyrimidine, for another purine, or pyrimidine. Transversion mutations result from the exchange of a purine for a pyrimidine or visa versa.
The prominent by-product from uvirradiation of DNA is the formation of thymine dimers. These form from two adjacent T residues in the DNA. Repair of thymine dimers is most understood from consideration of the mechanisms used in E. coli. However, several mechanism are common to both prokaryotes and eukaryotes.
Thymine dimers are removed by several mechanisms. Specific glycohydrolases recognize the dimer as abnormal and cleave the N-glycosidic bond of the bases in the dimer. This results in the base leaving and generates an apyrimidinic site in the DNA. This is repaired by DNA polymerase and ligase. Glycohydrolases are also responsible for the removal of other abnormal bases, not just thymine dimers.
Another, widely distributed activity, is DNA photolyase or photoreactivating enzyme. This protein binds to thymine dimers in the dark. In response to visible light stimulation the enzyme cleaves the pyrimidine rings. The chromophore associated with this enzyme that allows visible light activation is FADH2
Humans defective in DNA repair, (in particular the repair of uv-induced thymine dimers), due to autosomal recessive genetic defects suffer from the disease Xeroderma pigmentosum (XP). There are at least nine distinct genetic defects associated with this disease. One of these is due to a defect in the gene coding for the glycohydrolase that cleaves the N-glycosidic bond of the thymine dimers. There are two major clinical forms of XP, one which leads to progressive degenerative changes in the eyes and skin and the other which also includes progressive neurological degeneration.
Another inherited disorder affecting DNA repair in which patients suffer from sun sensitivity, short stature and progressive neurological degeneration without an increased incidence of skin cancer is Cockayne Syndrome.
Ataxia telangiectasia (AT) is an autosomal recessive disorder resulting in neurological disability and suppressed immune function. Patients develop a disabling cerebellar ataxia early in life and have recurrent infections. Patients suffering from AT have an increased sensitivity to x-irradiation suggesting a role for the AT gene in DNA repair.
Several diseases associated with defective repair of damaged DNA can be found in the Inborn Errors page.
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Chemotherapies Targeting Replication
The class of compounds that have been used the longest as anticancer drugs are the alkylating agents. The major alkylating agents are derived from nitrogenous mustards that were originally developed for use by the military. Commonly used alkylating agents include cyclophosphamide (Cytoxan, Neosar), ifosphamide, decarbazine, chlorambucil (Leukeran) and procarbazine (Matulane, Natulan).
Alkylating agents function by reacting with and disrupting the structure of DNA. Some agents react with alkyl groups in DNA resulting in fragmentation of the DNA as a consequence of the action of DNA repair enzymes. Some agents catalzye the cross-linking of bases in the DNA which prevents the separation of the two strands during DNA replication. Some agents induce mispairing of nucleotides resulting in permanent mutations in the DNA. Alkylating agents act upon DNA at all stages of the cell cycle, thus they are potent anticancer drugs. However, because of their potency, prolonged use of alkylating agents can lead to secondary cancers, particularly leukemias.
Several classes of anticancer drugs function through interference with the actions of the topoisomerases. Two of these classes are the anthracyclines and the camptothecins.
The anthracyclins were originally isolated from the fungus, Streptomyces. Doxorubicin (Adriamycin, Doxil, Rubex) and daunorubicin (Cerubidine, DaunoXome, Daunomycin, Rubidomycin) have similar modes of action, although doxorubicin is the more potent of the two and is used in the treatment breast cancers, lymphomas and sarcomas. The anthracyclins inhibit the actions of topoisomerase II whose function is to introduce double-strand breaks in DNA during the process of replication as a means to relive torsional stresses. Anthracyclines also function by inducing the formation of oxygen free radicals that cause DNA strand breaks resulting in inhibition of replication.
Another plant-derived anticancer compound that functions through inhibition of topoisomerase II is etoposide (VP-16, Vepesid, Etophos, Eposin). Etoposide is isolated from the mandrake plant and is in a class of compounds referred to as epipodophyllotoxins.
The camptothecins were originally found in the bark of the Camptotheca accuminata tree and include irinotecan (Campto, Camptosar) and topotecan (Hycamtin). Camptothecins inhibit the action of topoisomerase I, an enzyme that induces single-strand breaks in DNA during replication.
Anticancer compounds that are extracted from the periwinkle plant, Vinca rosea, are called the vinca alkaloids. These compounds bind to tubulin monomers leading to the disruption of the microtubules of the mitotic spindle fibers that are necessary for cell division during mitosis. There are four major vinca alkaloids that are currently used as chemotherapeutics, vincristine (Oncovin, Vincrex), vinblastine (Velbe, Velban, Velsar), vinorelbin (VIN, Navelbine), and vindesine (Eldisine).
The taxanes are another class of plant-derived compounds that act via interference with microtubule function. These compounds are isolated from the Pacific yew tree, Taxus brevifolia and include paclitaxel (Taxol) and docetaxel (Taxotere). The taxanes function by hyperstabilizing microtubules which prevents cell division (cytokinesis). These compounds are used to treat a wide range of cancers including head and neck, lung, ovarian, breast, bladder, and prostate cancers. Taxol has proven highly effective in the treatment of certain forms of breast cancer.
In order for DNA replication to proceed, proliferating cells require a pool of nucleotides. The class of anticancer drugs that has been developed to interfere with aspects of nucleotide metabolism is known as the antimetabolites. There are two major types of antimetabolites used in the treatment of a broad range of cancers: componds that inhibit thymidylate synthase and compounds that inhibit dihydrofolate reductase (DHFR). Both of these enzymes are involved in thymidine nucleotide biosynthesis. Drugs that inhibit thymidylate synthase include 5-fluorouracil (5-FU, Adrucil, Efudex) and 5-fluorodeoxyuridine. Those that inhibit DHFR are analogs of the vitamin folic acid and include methotrexate (Trexall, Rheumatrex) and trimethoprim (Proloprim, Trimpex).
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Return to Medical Biochemistry Page
Michael W. King, Ph.D / IU School of Medicine / miking at iupui.edu
Last modified: Friday, 27-Oct-2006 08:33:29 EDT



Buy B vitamin complex, Discussion on Benefit of B vitamin.
by Ray Sahelian, M.D. (index of hundreds of vitamin topics)
B Vitamins and Coenzymes
b vitamins, vitamin b complex, vitamin b deficiency, benefit of b vitamin
B vitamin 1 -- Thiamin Cocarboxylase
B vitamin 2 -- Riboflavin Flavin Mono Nucleotide
B vitamin 3 -- Niacin Nicotinamide NADH
B Vitamin 5 -- Pantothenic acid Pantothene
B vitamin 6 -- Pyridoxine Pyridoxal Phosphate
B vitamin 12 -- Cyanocobalamin or Methylcobalamin or Dibencozide (B12)
What you will find on this B Vitamin page:
B Vitamin information
MultiVit Rx with Vitamin B - formulated by Ray Sahelian, M.D.
B Vitamin coenzyme complex product
Mind Power Rx for healthy memory and mood - formulated by Ray Sahelian, M.D.
B Vitamins - Coronary Heart Disease - FDA allows this qualified health claim
"It is known that diets low in saturated fat and cholesterol may reduce the risk of heart disease. The scientific evidence about whether folic acid (folate), vitamin B6, and vitamin B12 may also reduce the risk of heart disease and other vascular diseases is suggestive, but not conclusive. Studies in the general population have generally found that these vitamins lower homocysteine, an amino acid found in the blood. It is not known whether elevated levels of homocysteine may cause vascular disease or whether high homocysteine levels are caused by other factors. Studies that will directly evaluate whether reducing homocysteine may also reduce the risk of vascular disease are not yet complete."
"As part of a well-balanced diet that is low in saturated fat and cholesterol, Folic Acid, Vitamin B6 and Vitamin B12 may reduce the risk of vascular disease. FDA evaluated the above claim and found that, while it is known that diets low in saturated fat and cholesterol reduce the risk of heart disease and other vascular diseases, the evidence in support of the above claim is inconclusive."
MultiVit Rx - Lasts 2 to 4 months - with B vitamins
High Quality Daily Vitamins and Minerals
120 Capsules
Physician Formulas
Developed by Ray Sahelian, M.D.
Manufactured by a FDA-approved and GMP-certified facility.
MultiVit Rx Supplement Facts:
Serving Size: 4 Capsules
Servings per Bottle: 30


Amount per Serving: %DV
Vitamin A - 10,000 IU - 200%
Beta Carotene - 7,500 IU
Retinyl Palmitate - 2,500 IU
Vitamin C with Rose hips - 500 mg - 833%
(ascorbic acid)
Vitamin D - 400 IU - 100%
Vitamin E - 200 IU - 667%
(mixed tocopherols)
Vitamin B-1 - 25 mg - 1667%
(thiamine hcl)
Vitamin B-2 - 25 mg - 1470%
(riboflavin)
Niacinamide 25 mg - 125%
Vitamin B-6 - 25 mg - 1250%
Folic acid - 400 mcg - 100%
Vitamin B12 - 100 mcg - 1667%
Biotin - 300 mcg - 100%
Pantothenic acid - 80 mg - 800%
(d-calcium pantothenate)
Calcium (citrate) - 300mg - 30%
Iodine (potassium iodine) - 150 mcg - 100%
Magnesium (oxide) - 200 mg - 50%
Zinc (oxide) - 15 mg - 100%
Selenium (amino acid chelate) - 70 mcg - 100%
Copper (amino acid chelate) - 2 mg - 100%
Manganese (carbonate) - 2 mg - 100%
Chromium - 120 mcg - 100%
(amino acid chelate)
Molybdenum - 75 mcg - 100%
(amino acid chelate)
Potassium (carbonate) - 100 mg - 3%
Green Tea (leaves) - 100 mg - *
Inulin (Jerusalem artichoke - 200 mg - *
plant fiber extract-inuflora)
N-Aceytl-L-Cysteine - 25 mg - *
Inositol - 10 mg - *
PABA - 50 mg - *
(para aminobenzoic acid)
Rutin - 30 mg - *
Citrus Bioflavonoid Complex - 30 mg - *
Choline (bitartrate) - 25 mg - *
Betaine (HCI) - 23 mg - *
Beta Glucan - 2.5 mg - *
1/3-Beta, 1/6-Glucan (insoluble form from
cell walls of Saccharomyces cerevisiae)
Lycopene (from tomato) - 500 mcg - *
Lutein (from marigold extract) - 500 mcg - *
Astaxanthin - 100 mcg - *
Zeaxanthin - 100 mcg - *
Octacosanol - 100 mcg - *
-------------------------------------------------------------
*Daily Value not established
Other ingredients: Oregano, Cloves, Cinnamon, Alfalfa, Watercress, Parsley, Hawthorne berry, Rice Bran, Lecithin, Silica, Cholesterol free Magnesium Stearate and Stearic Acid. In a base of Inuflora.
Suggested Use: Take one or two capsules a day, with breakfast or lunch.


Click here to buy MultiVit-Rx, Mind Power Rx, Eyesight Rx, or to see a complete list of products at Physician Formulas, including a free newsletter
B VITAMINS AND THEIR COENZYMES
by Ray Sahelian, M.D.
A B vitamin supplement is the cheapest, safest, and most reliable way to improve your wellbeing and overall mental abilities. I recommend the Bs to those who wish to improve their mood, mental clarity, and energy. The effects of the B vitamins are subtle, especially in the young who normally have adequate dietary intake of these nutrients. Improvements in cognitive functions from the B vitamins are particularly noticeable in middle age individuals and the elderly.

Most of the B complex products contain too high doses of the B vitamins. Two to five times the RDA is sufficient for most purposes.
In addition to discussing the B vitamins, this page will review coenzymes—the new, more activated forms of the B vitamins—and make recommendations on how to reduce levels of homocysteine, an amino acid derivative that can be harmful to the cardiovascular and neurological system when present in excess.
Coenzymated B Vitamin Complex



B Vitamin coenzyme is an activated and more powerful form of Vitamin B complex.



B Vitamin Supplement Facts:
Serving Size 1 Tablet
Servings Per Container 60

Amount Per Serving
Vitamin C - 9 mg - 15%DV
Thiamin - 6 mg - 430%DV
[Coenzymated B vitamin 1]
Riboflavin - 6 mg - 330%V
[Coenzymated B vitamin 2]
Niacin - 20 mg - 100%DV
(from inositol 34 mg, niacinamide ascorbate 30 mg, nicotinamide adenine dinucleotide 10 mg [Coenzymated])
Vitamin B 6 - 5 mg - 250%DV
(from 15 mg pyridoxal -5-phosphate [Coenzymated])
Folate (as folic acid) - 200 mcg - 50%DV
Vitamin B12 - 340 mcg - 5,000%DV
(from 1 mg dibencozide [Coenzymated])
Biotin - 75 mcg - 25%DV
Pantothenic Acid - 13 mg 125%DV
(as calcium D-Pantothenate)
Coenzyme Q10 (ubiquinone) - 6 mg *
Inositol (inositol hexanicotinate) - 4 mg *
Suggested Use: 1 tablet daily, or as directed by your health professional. Place tablet under the tongue and allow to dissolve slowly, altering the position of the tablet to avoid prolonged contact with the same area.
*Daily Value not established
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Mind Power Rx is a sophisticated cognitive formula with B vitamins and a dozen brain herbs and nutrients. It combines a delicate balance of brain circulation agents and neurotransmitter precursors with powerful natural brain chemicals that support healthy:
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The herbs in Mind Power Rx include: Ashwagandha, Bacopa, Fo-Ti, Ginkgo biloba, Ginseng, Gotu Kola, Mucuna pruriens, Reishi, and Rhodiola. The nutrients and vitamins in Mind Power Rx include Acetyl-l-carnitine, Carnitine, Carnosine, Choline, DMAE, Inositol, Methylcobalamin, Pantothenic acid, Trimethylglycine, Tyrosine, and Vinpocetine.
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Benefits of B Vitamins
Since B vitamins and their coenzymes play important metabolic roles in numerous biochemical reactions throughout the body, they can influence just about every aspect of brain and physical health. As a rule, individuals who take B vitamins notice improvements in:
Mood and energy
Alertness
Learning and memory
Speed of thinking
Verbal fluency
Concentration and focus
Visual clarity
Which Clinical Conditions are B vitamins involved in?
Because of their wide range of effects, B vitamins and their coenzymes can potentially play a role in:
Depression
Age related cognitive decline
Anxiety disorders
Addiction disorders
Chronic fatigue
Alzheimer’s disease
Parkinson’s disease

The Bs in the Brain Get an A
B vitamins help in energy production and deficiencies lead to fatigue and poor mental functioning. The increased consumption of refined foods has decreased the amounts of B vitamins present in our diet. However, on the positive note, small amounts of B vitamins are regularly added to some food products, such as cereals. The question of whether B vitamin supplementation is necessary in healthy individuals who have a normal diet has been debated ever since vitamins were discovered. The results of several studies over the past few years have influenced my decision in favor of low dose supplementation. There can be cognitive improvements from taking B vitamins. Back in 1995, Dr. D. Benton and colleagues, from the University College Swansea , in Great Britain , gave ten times the recommended daily allowance of nine vitamins (mostly the B vitamins) to healthy college students (Benton 1995). The study lasted for one year. The students reported improvement in mood and feeling more agreeable. There was also an improvement in cognitive functioning, especially in regards to concentration. Many of my patients consistently report that B vitamin supplementation improves their energy, concentration and mood while helping them handle everyday stress better.

For otherwise healthy individuals, supplementation with one to three times the recommended daily allowance of the B vitamins is suggested. Higher dosages may be required for individuals with medical, psychiatric, or neurological disorders.

Understanding Coenzymes
In the past few years, many of the B vitamins have become available in their more activated forms known as coenzymes. For instance, the B vitamin niacin is now available in a coenzyme form known as NADH. An enzyme is basically a protein that promotes chemical changes in other substances, itself remaining unchanged in the process. A coenzyme is a substance that facilitates or is necessary for the action of an enzyme.
The brain, just like a car, needs fuel. Our primary source of fuel is through fats, proteins, and carbohydrates in the diet. After digestion in the stomach, foodstuffs are absorbed into the bloodstream and circulate to various tissues and cells where they are broken down into even smaller particles. One of these particles is a two-carbon molecule known as acetyl. Enzymes help break down these fats, proteins, and carbohydrates into acetyl and they then help extract the final energy from acetyl through a process called the Krebs cycle, named after the German biochemist who defined it. This energy is in the form of ATP (adenosine triphosphate). Enzymes also need helpers, and these helpers are called coenzymes. Most of the coenzymes in the body are partly made from vitamins, such as vitamins E, C, lipoic acid, and riboflavin (vitamin B2).
The coenzyme form of a B vitamin often has a significantly more powerful effect than a regular B vitamin. The coenzyme forms of the B vitamins are an exiting addition to the field of nutrition. It is quite possible that the elderly or certain individuals with a particular biochemical deficiency may not be able to make adequate amounts of the coenzyme forms of the B vitamins despite adequate intakes of the individual B vitamins. Hence, the coenzyme forms should be seriously considered in those who do not respond to the regular B vitamins. Some companies include most of the Bs in their coenzyme form together in one pill. I think these products deserve serious consideration, especially for their use in the middle aged and the elderly.

The Individual B Vitamins and Their Coenzymes:
Thiamin (B1) is necessary for the metabolism of carbohydrates and amino acids to adenosine triphosphate (ATP), the primary source of energy in the human body. Thiamin is found in good amounts in milk, lean pork, legumes, rice bran, and the germ of cereal grains, but is lost during food processing and cooking. The current recommended daily allowance (RDA) by government advisory panels is about 1.5 mg.
Studies indicate that supplementation with thiamin provides cognitive benefits. Dr. Benton and colleagues gave 50 mg of thiamin daily to young adult females for a period of two months ( Benton 1997). The women reported being more clearheaded, composed, and energetic. The taking of thiamin had no influence on memory but reaction times were faster following supplementation. Prior to taking the thiamin, the women had normal blood levels of this vitamin.
Researchers at Princess Margaret Hospital in Christchurch , New Zealand , measured thiamin levels in elderly individuals before giving them 10 mg of the vitamin a day (Wilkinson 1997). Only the subjects with low thiamin concentrations showed benefits. They had an improvement in quality of life with more energy and deeper sleep, along with decreased blood pressure and weight.
Thiamin is now sold in its coenzyme form called cocarboxylase or thiamin pyrophosphate (TPP). Human studies giving TPP to evaluate cognitive functioning have not yet been published. See also Benfotiamine.
Food sources for thiamne B vitamin % of daily need
Thiamin (vitamin B1)
Pork, lean, broiled (3 oz.) 73%
Beef liver, braised (3 oz.) 18%
Enriched corn tortilla (1) 18%
Enriched rice, cooked (1/2 cup) 18%
Whole-grain bread (1 slice) 9%
Riboflavin (B2) is a yellow-colored nutrient involved in dozens of metabolic pathways leading to energy production and the making of fatty acids and sterols. Good sources are lean meats, eggs, milk, some vegetables and enriched cereals. The recommended daily intake is about 1.5 mg. You may notice your urine turning a deeper yellow color after taking riboflavin.
Riboflavin is part of two larger activated coenzymes known as flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN). FMN is now available as a supplement. One product contains 25 mg of FMN per pill. Human studies giving FAD or FMN in order to evaluate cognitive functioning have not yet been published.
Food Sources for B Vitamin Riboflavin
Riboflavin (vitamin B2)
Beef liver, braised (3 oz.) 318%
Yogurt, fat-free, (1 cup) 36%
Milk, fat-free (1 cup) 18%
Niacin (B3), also known as nicotinamide and nicotinic acid, plays essential roles in a large number of energy pathways. Perhaps as many as 200 enzymes are dependent on this nutrient. Nicotinamide is part of the coenzyme known as nicotinamide adenine dinucleotide (NADH), which is sold as a supplement. I will discuss NADH later in this chapter since several studies have been published regarding this coenzyme. Good sources of niacin are meats, legumes, fish, and some nuts and cereals. The recommended daily intake is about 15 to 20 mg.
High intake of niacin, particularly from food sources, may reduce the risk of Alzheimer's disease and age-related cognitive decline.
Niacin for diabetics
People with diabetes often have high cholesterol and triglyceride levels. They also have low HDL (the good cholesterol) levels. Niacin, a B vitamin, reduces concentrations of triglycerides and raises levels of HDL cholesterol. However, the use of niacin in patients with diabetes has been discouraged because high doses can sometimes worsen blood sugar control. Researchers at the University of Texas Southwestern Medical Center evaluated the use and safety of once-daily extended-release niacin in diabetic patients with triglyceride problems. During a 16-week, double-blind, placebo-controlled trial, 148 patients were randomized to placebo or 1000 mg a day of niacin. Many patients were also receiving therapy with statins. Patients taking niacin had an average increase in HDL by about 20 percent and reductions in triglyceride levels by about 20 percent compared to the placebo group. Rates of adverse event rates other than flushing were similar for the niacin and placebo groups. Four patients discontinued participation owing to flushing. No harm to the liver or muscles was observed. Blood sugar levels on average rose only minimally. The researchers conclude that niacin is a treatment option for patients with type 2 diabetes who have high triglyceride and low HDL levels.
Dr. Sahelian says: Some diabetics may get benefits with a lower dose of niacin, such as 200 to 500 mg a day, which would reduce the incidence of flushing. An extended release form of niacin seems to be a good option.
Food Sources for Niacin B Vitamin
Niacin
Turkey breast, roasted, (3 oz.) 43%
Peanut butter (2 tbsp.) 29%
Codfish, cooked (3 oz.) 14%
Enriched corn tortilla (1) 11%
Pyridoxine (B6), also known as pyridoxal, is widely available in most foods including vegetables, legumes, nuts, seeds, and animal products. The coenzyme form of pyridoxine is pyridoxal phosphate (PLP) and at least 100 different metabolic reactions are helped by PLP. PLP is a necessary co-enzyme in the production of brain chemicals: It helps the conversion of 5-HTP into serotonin, tyrosine into dopamine and norepinephrine, and the production of other neurotransmitters such as histamine and GABA. The recommended daily intake is about 1.5 mg. Deficiencies in B6 can lead to low mood.
Human studies with PLP in mood disorders and depression have not yet been published. PLP is available in pills ranging from 5 to 20 mg. Some individuals notice the difference between regular B6 and the coenzyme form. Joan, a 53-year old patient from Beverly Hills , California , says, "I've taken good quality B vitamins for a few years. Recently I tried the pyridoxal phosphate form of B6. It really has increased my energy, mood, and alertness."
Food Sources B Vitamin Pyridoxine
Pyridoxine (vitamin B6)
Chicken, light meat, (3 oz.) 33%
Pork, loin, roasted (3 oz.) 33%
Pantothenic acid (B5) is essential for biological reactions involving acetylation and energy production. This vitamin helps in the formation of acetylcholine, the metabolism of fatty acids, and the incorporation of fatty acids into cell membrane phospholipids. Pantothenic acid is also involved in making steroid hormones, vitamin A, vitamin D, and cholesterol. Good sources are egg yolk and fresh vegetables. The recommended daily intake is about 5 mg. Pantothenic acid is sold over the counter in dosages ranging from 5 to 250 mg.
My patients report that pantothenic acid helps improve their mood and energy. Personally, I notice an improvement in alertness, concentration, energy, and visual clarity with dosages ranging from 100 to 250 mg. I do experience insomnia, though, when I take more than 250 mg, even if I take it in the morning. Benita von Klingspor, a nutritionist in Marina Del Rey, California, says, "Pantothenic acid is one of my favorite nutrients. I know the effects of this nutrient extremely well since I’ve been taking 100 to 250 mg most mornings for more than thirty years. I often recommend it to many clients with low energy. Pantothenic acid increases their alertness and focus, improves their mood, and enhances their joy in life. They begin to have more interest in whatever they’re doing. However, if people take too much pantothenic acid, they can become overstimulated, wired, and easily aggravated."
Pantothenic acid is available in its activated form known as pantethine. Pantethine, itself, is part of coenzyme A, a very important substance that participates in the metabolism of carbohydrates, amino acids, fatty acids and dozens of other important chemical reactions. Cognitive effects of oral pantethine administration to humans have not been published. Pantethene is sold over the counter in dosages ranging from 5 to 50 mg. In my experience, a lower dosage of pantethine provides similar effects as a higher dosage of pantothenic acid.
Folic acid, also known as folate, generally functions in cooperation with vitamin B12 in many metabolic reactions, including the synthesis of DNA. Folic acid helps reduce levels of homocysteine, a substance that can increase the risk for atherosclerosis. This vitamin functions as a methyl donor. Folic acid is found in almost all foods and the recommended daily intake is about 400 micrograms. The coenzyme form of folate is called tetrahydrofolate. Folate and other B vitamins seem even more of a wonder drug than anyone suspected: Already known to prevent severe birth defects and heart attacks, they may also ward off broken bones from osteoporosis, two major studies suggest.
Folate is a water-soluble B-vitamin and enzymatic cofactor that is necessary for the synthesis of purine and thymidine nucleotides and for the synthesis of methionine from homocysteine. Impairment of folate-mediated one-carbon metabolic pathways can result from B-vitamin deficiencies and/or single nucleotide polymorphisms, and increases risk for pathologies, including cancer and cardiovascular disease, and developmental anomalies including neural tube defects.
New research hints that a suboptimal intake of folic acid may play a role in the development of colorectal cancer, which points to a possible role for folic acid supplementation in colorectal cancer prevention. In individuals with colorectal adenomas -- polyps that can be precursors to bowel cancer -- folic acid supplementation reverses so-called DNA hypomethylation.
Food Sources for B Vitamin Folic Acid
Folate (folic acid)
Fortified cereals (1 cup) 25-100%
Spinach, boiled (1/2 cup) 33%
Navy beans, boiled (1/2 cup) 31%
Orange juice (1 cup) 28%
Asparagus, boiled (4 spears) 21%
Wheat germ (1/4 cup) 20%
Avocado (1/2) 14%
Cobalamin (B12), methylcobalamin, or cyanocobalamin, has a number of important roles in metabolism, including the synthesis of DNA. This function is particularly crucial when it comes to making new red blood cells. Hence, a deficiency of B12 leads to anemia. The formation of myelin—the white sheath surrounding nerves—is partly dependent of B12. Deficiencies in B12 intake lead to nerve damage, memory loss, poor coordination, low mood, and mental slowness. This nutrient, along with folic acid and B6, helps lower levels of homocysteine. High homocysteine levels are suspected in being one of the factors causing hardening of the arteries.
The recommended daily intake of B12 is about 3 micrograms, but much higher dosages are well tolerated. B12 is found mostly in meats and fish. Vegetarians can become deficient in this vitamin if they don’t take supplements. B12 deficiency can occur in the elderly due to malabsorption from the intestinal tract. If you have gastritis, absorption problems, autoimmune disorders, insulin dependent diabetes, certain thyroid disorders, or take antacids and other medicines that reduce stomach acid, you could have problems in maintaining adequate B12 levels. Hence, monthly B12 shots, in a dose of 1mg (1,000 micrograms), could well provide you with positive cognitive benefits. Sublingual forms of B12 are also available.
There are two coenzyme forms of B12, adenosylcobalamin and methylcobalamin. Adenosylcobalamin is sold over the counter as dibencozide, in a dose of 10,000 micrograms, which is a large dose. Human studies evaluating its role in cognitive disorders have not been published. It’s quite possible that with age, nutritional deficiencies, or enzyme deficiencies, some individuals may not be able to convert B12 into its coenzyme forms.

Vitamin B12 deficiency can often be treated with oral supplements instead of giving an injection. B12 deficiency is common in patients with reduced acid secretion because acid is required to release cobalamin from food. But these patients can absorb oral supplements because the cobalamin is in the crystalline form and not bound to food. Treatment of pernicious anemia can be done with oral B!2 at 1000 mcg per day.

Mothers with low levels of vitamin B12 in their blood are at increased risk of having an infant with spina bifida -- a birth defect in which the spinal cord fails to form properly. Based on previous research, pregnancy guidelines recommend that women consume enough folic acid to reduce the risk of spina bifida and related problems. The new findings suggest that these guidelines should also include recommendations about vitamin B12.
Oral supplements of vitamin B12 appear to correct vitamin B12 deficiencies as well as B12 injections. However, the group of European researchers found that, in order to correct a deficiency, oral doses need to contain more than 200 times the recommended daily allowance (RDA) of vitamin B12. Study author Dr. Lisette C. P. G. M. de Groot of Wageningen University in the Netherlands explained that most people develop vitamin B12 deficiencies as a result of "malabsorption," in which their bodies become unable to extract vitamin B12 from food. The deficiency typically strikes older people, she added, and takes years to develop. In some instances, people who avoid animal products -- such as vegans and followers of a macrobiotic diet -- can also develop a deficiency in vitamin B12 as a result of not eating enough B12-rich foods. A vitamin B12 deficiency is typically treated by monthly, often painful, shots. To investigate whether an oral dose of vitamin B12 works, as well, they tested various daily doses of oral vitamin B12 supplements in 120 people aged 70 and older. They found that daily oral doses of 647 to 1032 micrograms of vitamin B12 appeared to correct the deficiency. The current RDA for vitamin B12 is 3 micrograms per day. SOURCE: Archives of Internal Medicine, May 23, 2005.
Food Sources for B12 B Vitamin
B12
Salmon, cooked (3 oz.) 125%
Beef tenderloin, broiled (3 oz.) 90%
Yogurt, fat-free (1 cup) 58%
Shrimp, cooked (3 oz.) 54%
Milk (1 cup) 38%
Biotin is involved in the metabolism of carbohydrates and fats. It is widely available in foods, particularly egg yolk, soybeans, cereal, legumes, and nuts. Bacteria in the gut also make it. The RDA ranges from 30 to 100 micrograms.
A study from Switzerland demonstrated a 25 percent increase in nail plate thickness in patients with brittle nails who received biotin supplementation. Analysis of all visits to a nail consultation practice over a six-month period revealed forty-four patients with this condition who had been prescribed the B-complex vitamin biotin. Of these, thirty-five who took daily supplementation were subjectively evaluated. Twenty-two of thirty-five (63 percent) showed clinical improvement and thirteen (37 percent) reported no change in their condition. The results of this small, retrospective study suggest a positive response to biotin in the treatment of brittle nails in some patients.
Food Sources for Biotin B Vitamin
Biotin
Egg, large (1) 33%
Wheat germ (1/4 cup) 20%
Oatmeal, cooked (1/4 cup) 17%
Recommendations
All of the B vitamins are important and supplementation would probably benefit most everyone. For healthy individuals, taking one to three times the RDA of the Bs would be sufficient. You will find B complex supplements that say B50 or B100 on the label. This means that many of the B vitamins, such as thiamin and riboflavin, are found in dosages of 50 or 100 mg per pill. The RDA for thiamin and riboflavin is about 1.5 mg. The average, healthy person does not need to take these high dosages. However, biochemical individuality certainly does exist. Dr. David Benton, Ph.D., who researches the influence of B vitamins on cognition says, "There can be enormous differences in the needs of vitamins. It wouldn’t be unusual for some individuals requiring 20 times the amount of a particular vitamin compared to others in a similar age group."
A Daily Dose of B Vitamins Keeps the Cardiologist Away
Scientists at the University of Michigan in Ann Arbor say that people might live longer if they take daily multivitamins containing recommended doses of the B vitamins folic acid and B12. Both nutrients help lower blood levels of homocysteine - a common substance found in the body that can harm blood vessel walls and encourage blood clotting and hardening of the arteries. Up to 10% of all heart deaths are thought to be associated with high levels of homocysteine. Clinical trials have not yet demonstrated precisely how much benefit can be derived from lowering levels of the substance, but even a small amount of benefit would make it worth taking vitamins. A computer analysis looked at the hypothetical balance between cost and benefit under several different scenarios, based on what is known about homocysteine and the effects of folic acid and vitamin B12. One scenario assumed that reducing homocysteine levels could reduce heart disease risk linked to the substance by 40%. The team found that in this situation about eight life-years could be saved per 1,000 men, and almost four life-years per 1,000 women. It did not matter if vitamins were given to all at-risk people, or just those with elevated homocysteine blood levels.
Dr. Sahelian says: Homocysteine is gradually becoming accepted as another risk factor similar to high cholesterol levels in causing hardening of the arteries. A daily dose of folic acid and B12, in amounts normally found in a multivitamin supplement, can make a significant impact in reducing a person’s risk from heart disease.
Email Questions and comments about B vitamins
Q. I should appreciate if you could comment on this NORVIT investigation:
Researchers from Norway have found that treating patients who have had a heart attack with high doses of B vitamins does not lower the risk of getting another heart attack or stroke. Contrary to expectations, B vitamins may do more harm than good. These surprising data were presented at the Hot Line Session II of the European Society of Cardiology Congress in Stockholm on 5th September 2005. NORVIT, the Norwegian Vitamin Trial, is the first trial to examine whether high doses of B vitamins prevent recurrent heart disease in patients who have had a myocardial infarction. A total of 3749 patients were recruited from 35 Norwegian hospitals. The patients were assigned to take B vitamins or placebo for more than three years in addition to standard treatments after a heart attack. Professor Kaare Harald Bnaa MD, University of Troms , Norway , principal investigator of the NORVIT trial, comments, "The results of the NORVIT trial are important because they tell doctors that prescribing high doses of B vitamins will not prevent heart disease or stroke. B vitamins should be prescribed only to patients who have B vitamin deficiency diseases." The participants in the NORVIT trial were divided at random into four groups that received either 0.8 mg folic acid (a B vitamin) per day, 40 mg vitamin B-6 per day, both 0.8 mg folic acid and 40 mg vitamin B-6 per day, or a placebo capsule per day. Those who took folic acid or vitamin B-6 alone had a small increase in the risk of cardiovascular disease. However, among those who took both vitamins the risk increased by 20 percent.
A. Thank you for bringing this B vitamin study to our attention. I really find it strange that they would waste all this money and time on a ill-thought out study. If they are going to give the B vitamins, why pick one or two in high doses and skip the rest? I would much rather they had given one or two times the RDA for all the B vitamins rather than 40 mg of B6 which is about 20 times the RDA while not giving B vitamins such as B1, B2, niacin, pantothenic acid, B12, biotin, etc.
So, this study means little except that people should not take a high dose of one B vitamin at the expense of the other B vitamins. And the researchers should go back to school and learn the basics of nutrition and biochemistry before wasting time, effort, and money on an ill-conceived study.
Q. I purchased a product Vitamin-B-Coenzyme-Complex just 3 weeks back. I am having very good results at 2 tabs/per day. i have a doubt regarding the dosage. the product contains NADH-5mg/tablet. the dosage for NADH in the book mind boosters (by dr ray sahelian) is to take 2.5-5mg of NADH only a few times a week. whereas the the bottle indicates to take 2-3 tablets daily.(which is NADH-10/15 per day). Please let me know about the safe dosage of the product Vitamin-B-Coenzyme-Complex for daily use .
A. We believe 1 tablet of B coenzyme a few times a week is sufficient. However each person is different. Some need more, others less. I prefer people use less rather than more.
Q. Do you think testing for homocysteine blood level is important?
A. I'm not really sure homocysteine levels need to be checked since taking a B vitamin complex will lower them anyway. We do so many blood tests in this country, and medical expenses are skyrocketing. Why not just take a cheap B vitamin complex? That' s my opinion, another doctor may disagree.
Q. I've just purchased some Sam-e for depression as I experience too many side-effects with anti-depressants. I have read that it is wise to take additional B vitamins, particularly B6, B12 and folic acid, when taking Sam-e in order to prevent toxic build-up of homocysteine. Apparently these vitamins assist in the breakdown of homocysteine which is formed when Sam-e breaks down.
A. We're not totally sure whether extra B vitamins are needed if someone is taking SAM-e. Perhaps it depends on one's diet and biochemistry. It would not hurt to take 1 to 3 times the RDA of the B vitamins.

Q. Interestingly, I took a B vitamin coenzyme complex you recommend on your site and I believe I feel a boost in energy, mental clarity, alertness & elevated mood. I went out to lunch w/ folks from the office and had quite a heavy meal: cheese burger w/ Lousiana sausage, some fries & a very heavy beer. I anticipated falling asleep at my desk after lunch, but I haven't really been dragging at all. This is great, I hope the effects continue! Thanks for your web site for encouraging me to start up with this stuff.
Q. You mention in your new book "Mind Boosters" about finding a B vitamin that has five to ten times the RDA amount for B vitamins. Then you mention finding another B vitamin complex that has 2 to 3 times the RDA. I have looked all over the place for B vitamin complexes with these amounts and have come up short. Do you have any name brands or generic brand b-complexes that you could refer me to with these amounts. Most B-complexes on the market seem to be B-50's or B-100's or B-25's but nothing of the dose your recommending. Thanks.
A. Yes, it's hard to find a B complex that's reasonable in its content. You may consider getting a multivitamin complex that has 1-5 times the RDA, or, get a B-25 and take about a quarter of a pill.

Q. Today in my local paper I read that excessive doses of Pyroxidine HCL (Vitamin B6) over protracted periods of time can cause serious damage to the nervous system. The paper said for a person like myself (female 31 yrs) I should be getting 1.3 mg a day.
A. B6 may cause problems in doses greater than 50 or 100 mg when taken over several months, but it is unlikely that lower doses cause any immediate or significant problems.
Q. Since B vitamins are water-soluble, how can one take "too much"? And, if they can be counter-productive, how?
A. Even though B vitamins are water soluble, they could still have a physiologic effect before they are excreted, and perhaps taking too much can throw off delicate body biochemistry for a while until the B vitamins are excreted.
Japanese discover first new vitamin in 55 years
TOKYO (Reuters) - Japanese scientists have discovered a new vitamin that plays an important role in fertility in mice and may have a similar function in humans, the research leader said on Thursday. A research team led by Takafumi Kato confirmed that pyrroloquinoline quinone (PQQ), a substance discovered in 1979, can be categorized as a vitamin. "There are many possible factors behind the drop in fertility," Kato said. "We need more research to find out exactly what is happening to these mice and what would be the effect on humans." PQQ is the first new vitamin to be discovered since 1948, the institute said. Vitamins are defined as organic substances needed in small quantities for health and growth. They must be obtained from food as they cannot be produced by the body. The best source of PQQ discovered so far is "natto," a pungent Japanese dish of fermented soybeans. Other foods rich in the substance include parsley, green tea, green peppers, kiwi fruit and papaya. PQQ is not generally included in multi-vitamin tablets available on the market, the release said. There are 13 other types of vitamin already known, and PQQ is believed to belong to the vitamin B group, the release said.



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Introduction to Vitamins
Vitamins are organic molecules that function in a wide variety of capacities within the body. The most prominent function is as cofactors for enzymatic reactions. The distinguishing feature of the vitamins is that they generally cannot be synthesized by mammalian cells and, therefore, must be supplied in the diet. The vitamins are of two distinct types:
Water Soluble Vitamins

Fat Soluble Vitamins

* Thiamin (B1)
o B1 Deficiency and Disease
* Riboflavin (B2)
o B2 Deficiency and Disease
* Niacin (B3)
o B3 Deficiency and Disease
* Pantothenic Acid (B5)
* Pyridoxal, Pyridoxamine, Pyridoxine (B6)
* Biotin
* Cobalamin (B12)
o B12 Deficiency and Disease
* Folic Acid
o Folate Deficiency and Disease
* Ascorbic Acid



* Vitamin A
o Gene Control by Vitamin A
o Role of Vitamin A in Vision
o Additional Roles of Vitamin A
o Clinical Significances of Vitamin A
* Vitamin D
o Clinical Significances of Vitamin D
* Vitamin E
o Clinical Significances of Vitamin E
* Vitamin K
o Clinical Significance of Vitamin K

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Thiamin
Thiamin structure

Thiamin is also known as vitamin B1 . Thiamin is derived from a substituted pyrimidine and a thiazole which are coupled by a methylene bridge. Thiamin is rapidly converted to its active form, thiamin pyrophosphate, TPP, in the brain and liver by a specific enzymes, thiamin diphosphotransferase.
Thiamin pyrophosphate

TPP is necessary as a cofactor for the pyruvate and a-ketoglutarate dehydrogenase catalyzed reactions as well as the transketolase catalyzed reactions of the pentose phosphate pathway. A deficiency in thiamin intake leads to a severely reduced capacity of cells to generate energy as a result of its role in these reactions.
The dietary requirement for thiamin is proportional to the caloric intake of the diet and ranges from 1.0 - 1.5 mg/day for normal adults. If the carbohydrate content of the diet is excessive then an in thiamin intake will be required.
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Clinical Significances of Thiamin Deficiency
The earliest symptoms of thiamin deficiency include constipation, appetite suppression, nausea as well as mental depression, peripheral neuropathy and fatigue. Chronic thiamin deficiency leads to more severe neurological symptoms including ataxia, mental confusion and loss of eye coordination. Other clinical symptoms of prolonged thiamin deficiency are related to cardiovascular and musculature defects.
The severe thiamin deficiency disease known as Beriberi, is the result of a diet that is carbohydrate rich and thiamin deficient. An additional thiamin deficiency related disease is known as Wernicke-Korsakoff syndrome. This disease is most commonly found in chronic alcoholics due to their poor dietetic lifestyles.
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Riboflavin
Riboflavin structure

Riboflavin is also known as vitamin B2. Riboflavin is the precursor for the coenzymes, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). The enzymes that require FMN or FAD as cofactors are termed flavoproteins. Several flavoproteins also contain metal ions and are termed metalloflavoproteins. Both classes of enzymes are involved in a wide range of redox reactions, e.g. succinate dehydrogenase and xanthine oxidase. During the course of the enzymatic reactions involving the flavoproteins the reduced forms of FMN and FAD are formed, FMNH2 and FADH2, respectively.
Structure of FAD
nitrogens 1 & 5 carry hydrogens in FADH2
The normal daily requirement for riboflavin is 1.2 - 1.7 mg/day for normal adults.
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Clinical Significances of Flavin Deficiency
Riboflavin deficiencies are rare in the United States due to the presence of adequate amounts of the vitamin in eggs, milk, meat and cereals. Riboflavin deficiency is often seen in chronic alcoholics due to their poor dietetic habits.
Symptoms associated with riboflavin deficiency include, glossitis, seborrhea, angular stomatitis, cheilosis and photophobia. Riboflavin decomposes when exposed to visible light. This characteristic can lead to riboflavin deficiencies in newborns treated for hyperbilirubinemia by phototherapy.
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Niacin

Nicotinamide

Nicotinic Acid

Niacin (nicotinic acid and nicotinamide) is also known as vitamin B3. Both nicotinic acid and nicotinamide can serve as the dietary source of vitamin B3. Niacin is required for the synthesis of the active forms of vitamin B3, nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+). Both NAD+ and NADP+ function as cofactors for numerous dehydrogenase, e.g., lactate and malate dehydrogenases.
Structure of NAD+
NADH is shown in the box insert.
The -OH phosphorylated in NADP+ is indicated by the red arrow.

Niacin is not a true vitamin in the strictest definition since it can be derived from the amino acid tryptophan. However, the ability to utilize tryptophan for niacin synthesis is inefficient (60 mg of tryptophan are required to synthesize 1 mg of niacin). Also, synthesis of niacin from tryptophan requires vitamins B1, B2 and B6 which would be limiting in themselves on a marginal diet.
The recommended daily requirement for niacin is 13 - 19 niacin equivalents (NE) per day for a normal adult. One NE is equivalent to 1 mg of free niacin).
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Clinical Significances of Niacin and Nicotinic Acid
A diet deficient in niacin (as well as tryptophan) leads to glossitis of the tongue, dermatitis, weight loss, diarrhea, depression and dementia. The severe symptoms, depression, dermatitis and diarrhea, are associated with the condition known as pellagra. Several physiological conditions (e.g. Hartnup disease and malignant carcinoid syndrome) as well as certain drug therapies (e.g. isoniazid) can lead to niacin deficiency. In Hartnup disease tryptophan absorption is impaired and in malignant carcinoid syndrome tryptophan metabolism is altered resulting in excess serotonin synthesis. Isoniazid (the hydrazide derivative of isonicotinic acid) is the primary drug for chemotherapy of tuberculosis.
Nicotinic acid (but not nicotinamide) when administered in pharmacological doses of 2 - 4 g/day lowers plasma cholesterol levels and has been shown to be a useful therapeutic for hypercholesterolemia. The major action of nicotinic acid in this capacity is a reduction in fatty acid mobilization from adipose tissue. Although nicotinic acid therapy lowers blood cholesterol it also causes a depletion of glycogen stores and fat reserves in skeletal and cardiac muscle. Additionally, there is an elevation in blood glucose and uric acid production. For these reasons nicotinic acid therapy is not recommended for diabetics or persons who suffer from gout.
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Pantothenic Acid
Pantothenic Acid

Pantothenic acid is also known as vitamin B5. Pantothenic acid is formed from b-alanine and pantoic acid. Pantothenate is required for synthesis of coenzyme A, CoA and is a component of the acyl carrier protein (ACP) domain of fatty acid synthase. Pantothenate is, therefore, required for the metabolism of carbohydrate via the TCA cycle and all fats and proteins. At least 70 enzymes have been identified as requiring CoA or ACP derivatives for their function.
Deficiency of pantothenic acid is extremely rare due to its widespread distribution in whole grain cereals, legumes and meat. Symptoms of pantothenate deficiency are difficult to assess since they are subtle and resemble those of other B vitamin deficiencies.
Coenzyme A

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Vitamin B6


Pyridoxine

Pyridoxal

Pyridoxamine

Pyridoxal, pyridoxamine and pyridoxine are collectively known as vitamin B6. All three compounds are efficiently converted to the biologically active form of vitamin B6, pyridoxal phosphate. This conversion is catalyzed by the ATP requiring enzyme, pyridoxal kinase.
Pyridoxal Phosphate

Pyridoxal phosphate functions as a cofactor in enzymes involved in transamination reactions required for the synthesis and catabolism of the amino acids as well as in glycogenolysis as a cofactor for glycogen phosphorylase. The requirement for vitamin B6 in the diet is proportional to the level of protein consumption ranging from 1.4 - 2.0 mg/day for a normal adult. During pregnancy and lactation the requirement for vitamin B6 increases approximately 0.6 mg/day.
Deficiencies of vitamin B6 are rare and usually are related to an overall deficiency of all the B-complex vitamins. Isoniazid (see niacin deficiencies above) and penicillamine (used to treat rheumatoid arthritis and cystinurias) are two drugs that complex with pyridoxal and pyridoxal phosphate resulting in a deficiency in this vitamin.
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Biotin
Biotin

Biotin is the cofactor required of enzymes that are involved in carboxylation reactions, e.g. acetyl-CoA carboxylase and pyruvate carboxylase. Biotin is found in numerous foods and also is synthesized by intestinal bacteria and as such deficiencies of the vitamin are rare. Deficiencies are generally seen only after long antibiotic therapies which deplete the intestinal fauna or following excessive consumption of raw eggs. The latter is due to the affinity of the egg white protein, avidin, for biotin preventing intestinal absorption of the biotin.
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Cobalamin
Cobalamin is more commonly known as vitamin B12. Vitamin B12 is composed of a complex tetrapyrrol ring structure (corrin ring) and a cobalt ion in the center. Vitamin B12 is synthesized exclusively by microorganisms and is found in the liver of animals bound to protein as methycobalamin or 5'-deoxyadenosylcobalamin. The vitamin must be hydrolyzed from protein in order to be active. Hydrolysis occurs in the stomach by gastric acids or the intestines by trypsin digestion following consumption of animal meat. The vitamin is then bound by intrinsic factor, a protein secreted by parietal cells of the stomach, and carried to the ileum where it is absorbed. Following absorption the vitamin is transported to the liver in the blood bound to transcobalamin II.
There are only two clinically significant reactions in the body that require vitamin B12 as a cofactor. During the catabolism of fatty acids with an odd number of carbon atoms and the amino acids valine, isoleucine and threonine the resultant propionyl-CoA is converted to succinyl-CoA for oxidation in the TCA cycle. One of the enzymes in this pathway, methylmalonyl-CoA mutase, requires vitamin B12 as a cofactor in the conversion of methylmalonyl-CoA to succinyl-CoA. The 5'-deoxyadenosine derivative of cobalamin is required for this reaction.
The second reaction requiring vitamin B12 catalyzes the conversion of homocysteine to methionine and is catalyzed by methionine synthase. This reaction results in the transfer of the methyl group from N5-methyltetrahydrofolate to hydroxycobalamin generating tetrahydrofolate (THF) and methylcobalamin during the process of the conversion.
Cyanocobalamin

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Clinical Significances of B12 Deficiency
The liver can store up to six years worth of vitamin B12, hence deficiencies in this vitamin are rare. Pernicious anemia is a megaloblastic anemia resulting from vitamin B12 deficiency that develops as a result a lack of intrinsic factor in the stomach leading to malabsorption of the vitamin. The anemia results from impaired DNA synthesis due to a block in purine and thymidine biosynthesis. The block in nucleotide biosynthesis is a consequence of the effect of vitamin B12 on folate metabolism. When vitamin B12 is deficient essentially all of the folate becomes trapped as the N5-methylTHF derivative as a result of the loss of functional methionine synthase. This trapping prevents the synthesis of other THF derivatives required for the purine and thymidine nucleotide biosynthesis pathways.
Neurological complications also are associated with vitamin B12 deficiency and result from a progressive demyelination of nerve cells. The demyelination is thought to result from the increase in methylmalonyl-CoA that result from vitamin B12 deficiency. Methylmalonyl-CoA is a competitive inhibitor of malonyl-CoA in fatty acid biosynthesis as well as being able to substitute for malonyl-CoA in any fatty acid biosynthesis that may occur. Since the myelin sheath is in continual flux the methylmalonyl-CoA-induced inhibition of fatty acid synthesis results in the eventual destruction of the sheath. The incorporation methylmalonyl-CoA into fatty acid biosynthesis results in branched-chain fatty acids being produced that may severely alter the architecture of the normal membrane structure of nerve cells
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Folic Acid
Folic Acid
positions 7 & 8 carry hydrogens in dihydrofolate (DHF)
positions 5-8 carry hydrogens in tetrahydrofolate (THF)

Folic acid is a conjugated molecule consisting of a pteridine ring structure linked to para-aminobenzoic acid (PABA) that forms pteroic acid. Folic acid itself is then generated through the conjugation of glutamic acid residues to pteroic acid. Folic acid is obtained primarily from yeasts and leafy vegetables as well as animal liver. Animal cannot synthesize PABA nor attach glutamate residues to pteroic acid, thus, requiring folate intake in the diet.
When stored in the liver or ingested folic acid exists in a polyglutamate form. Intestinal mucosal cells remove some of the glutamate residues through the action of the lysosomal enzyme, conjugase. The removal of glutamate residues makes folate less negatively charged (from the polyglutamic acids) and therefore more capable of passing through the basal lamenal membrane of the epithelial cells of the intestine and into the bloodstream. Folic acid is reduced within cells (principally the liver where it is stored) to tetrahydrofolate (THF also H4folate) through the action of dihydrofolate reductase (DHFR), an NADPH-requiring enzyme.
The function of THF derivatives is to carry and transfer various forms of one carbon units during biosynthetic reactions. The one carbon units are either methyl, methylene, methenyl, formyl or formimino groups.
Active center of tetrahydrofolate (THF). Note that the N5 position is the site of attachment of methyl groups, the N10 the site for attachment of formyl and formimino groups and that both N5 and N10 bridge the methylene and methenyl groups.
These one carbon transfer reactions are required in the biosynthesis of serine, methionine, glycine, choline and the purine nucleotides and dTMP.
The ability to acquire choline and amino acids from the diet and to salvage the purine nucleotides makes the role of N5,N10-methylene-THF in dTMP synthesis the most metabolically significant function for this vitamin. The role of vitamin B12 and N5-methyl-THF in the conversion of homocysteine to methionine also can have a significant impact on the ability of cells to regenerate needed THF.
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Clinical Significance of Folate Deficiency
Folate deficiency results in complications nearly identical to those described for vitamin B12 deficiency. The most pronounced effect of folate deficiency on cellular processes is upon DNA synthesis. This is due to an impairment in dTMP synthesis which leads to cell cycle arrest in S-phase of rapidly proliferating cells, in particular hematopoietic cells. The result is megaloblastic anemia as for vitamin B12 deficiency. The inability to synthesize DNA during erythrocyte maturation leads to abnormally large erythrocytes termed macrocytic anemia.
Folate deficiencies are rare due to the adequate presence of folate in food. Poor dietary habits as those of chronic alcoholics can lead to folate deficiency. The predominant causes of folate deficiency in non-alcoholics are impaired absorption or metabolism or an increased demand for the vitamin. The predominant condition requiring an increase in the daily intake of folate is pregnancy. This is due to an increased number of rapidly proliferating cells present in the blood. The need for folate will nearly double by the third trimester of pregnancy. Certain drugs such as anticonvulsants and oral contraceptives can impair the absorption of folate. Anticonvulsants also increase the rate of folate metabolism.
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Ascorbic Acid
Ascorbic Acid

Ascorbic acid is more commonly known as vitamin C. Ascorbic acid is derived from glucose via the uronic acid pathway. The enzyme L-gulonolactone oxidase responsible for the conversion of gulonolactone to ascorbic acid is absent in primates making ascorbic acid required in the diet.
The active form of vitamin C is ascorbate acid itself. The main function of ascorbate is as a reducing agent in a number of different reactions. Vitamin C has the potential to reduce cytochromes a and c of the respiratory chain as well as molecular oxygen. The most important reaction requiring ascorbate as a cofactor is the hydroxylation of proline residues in collagen. Vitamin C is, therefore, required for the maintenance of normal connective tissue as well as for wound healing since synthesis of connective tissue is the first event in wound tissue remodeling. Vitamin C also is necessary for bone remodeling due to the presence of collagen in the organic matrix of bones.
Several other metabolic reactions require vitamin C as a cofactor. These include the catabolism of tyrosine and the synthesis of epinephrine from tyrosine and the synthesis of the bile acids. It is also believed that vitamin C is involved in the process of steroidogenesis since the adrenal cortex contains high levels of vitamin C which are depleted upon adrenocorticotropic hormone (ACTH) stimulation of the gland.
Deficiency in vitamin C leads to the disease scurvy due to the role of the vitamin in the post-translational modification of collagens. Scurvy is characterized by easily bruised skin, muscle fatigue, soft swollen gums, decreased wound healing and hemorrhaging, osteoporosis, and anemia. Vitamin C is readily absorbed and so the primary cause of vitamin C deficiency is poor diet and/or an increased requirement. The primary physiological state leading to an increased requirement for vitamin C is severe stress (or trauma). This is due to a rapid depletion in the adrenal stores of the vitamin. The reason for the decrease in adrenal vitamin C levels is unclear but may be due either to redistribution of the vitamin to areas that need it or an overall increased utilization.
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Vitamin A
Vitamin A consists of three biologically active molecules, retinol, retinal (retinaldehyde) and retinoic acid.

All-trans-retinal

11-cis-retinal


Retinol

Retinoic Acid

Each of these compounds are derived from the plant precursor molecule, b-carotene (a member of a family of molecules known as carotenoids). Beta-carotene, which consists of two molecules of retinal linked at their aldehyde ends, is also referred to as the provitamin form of vitamin A.
Ingested b-carotene is cleaved in the lumen of the intestine by b-carotene dioxygenase to yield retinal. Retinal is reduced to retinol by retinaldehyde reductase, an NADPH requiring enzyme within the intestines. Retinol is esterified to palmitic acid and delivered to the blood via chylomicrons. The uptake of chylomicron remnants by the liver results in delivery of retinol to this organ for storage as a lipid ester within lipocytes. Transport of retinol from the liver to extrahepatic tissues occurs by binding of hydrolyzed retinol to aporetinol binding protein (RBP). the retinol-RBP complex is then transported to the cell surface within the Golgi and secreted. Within extrahepatic tissues retinol is bound to cellular retinol binding protein (CRBP). Plasma transport of retinoic acid is accomplished by binding to albumin.
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Gene Control Exerted by Retinol and Retinoic Acid
Within cells both retinol and retinoic acid bind to specific receptor proteins. Following binding, the receptor-vitamin complex interacts with specific sequences in several genes involved in growth and differentiation and affects expression of these genes. In this capacity retinol and retinoic acid are considered hormones of the steroid/thyroid hormone superfamily of proteins. Vitamin D also acts in a similar capacity. Several genes whose patterns of expression are altered by retinoic acid are involved in the earliest processes of embryogenesis including the differentiation of the three germ layers, organogenesis and limb development.
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Vision and the Role of Vitamin A
Photoreception in the eye is the function of two specialized cell types located in the retina; the rod and cone cells. Both rod and cone cells contain a photoreceptor pigment in their membranes. The photosensitive compound of most mammalian eyes is a protein called opsin to which is covalently coupled an aldehyde of vitamin A. The opsin of rod cells is called scotopsin. The photoreceptor of rod cells is specifically called rhodopsin or visual purple. This compound is a complex between scotopsin and the 11-cis-retinal (also called 11-cis-retinene) form of vitamin A. Rhodopsin is a serpentine receptor imbedded in the membrane of the rod cell. Coupling of 11-cis-retinal occurs at three of the transmembrane domains of rhodopsin. Intracellularly, rhodopsin is coupled to a specific G-protein called transducin.
When the rhodopsin is exposed to light it is bleached releasing the 11-cis-retinal from opsin. Absorption of photons by 11-cis-retinal triggers a series of conformational changes on the way to conversion all-trans-retinal. One important conformational intermediate is metarhodopsin II. The release of opsin results in a conformational change in the photoreceptor. This conformational change activates transducin, leading to an increased GTP-binding by the a-subunit of transducin. Binding of GTP releases the a-subunit from the inhibitory b- and g-subunits. The GTP-activated a-subunit in turn activates an associated phosphodiesterase; an enzyme that hydrolyzes cyclic-GMP (cGMP) to GMP. Cyclic GMP is required to maintain the Na+ channels of the rod cell in the open conformation. The drop in cGMP concentration results in complete closure of the Na+ channels. Metarhodopsin II appears to be responsible for initiating the closure of the channels. The closing of the channels leads to hyperpolarization of the rod cell with concomitant propagation of nerve impulses to the brain.
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Additional Role of Retinol
Retinol also functions in the synthesis of certain glycoproteins and mucopolysaccharides necessary for mucous production and normal growth regulation. This is accomplished by phosphorylation of retinol to retinyl phosphate which then functions similarly to dolichol phosphate.
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Clinical Significances of Vitamin A Deficiency
Vitamin A is stored in the liver and deficiency of the vitamin occurs only after prolonged lack of dietary intake. The earliest symptoms of vitamin A deficiency are night blindness. Additional early symptoms include follicular hyperkeratinosis, increased susceptibility to infection and cancer and anemia equivalent to iron deficient anemia. Prolonged lack of vitamin A leads to deterioration of the eye tissue through progressive keratinization of the cornea, a condition known as xerophthalmia.
The increased risk of cancer in vitamin deficiency is thought to be the result of a depletion in b-carotene. Beta-carotene is a very effective antioxidant and is suspected to reduce the risk of cancers known to be initiated by the production of free radicals. Of particular interest is the potential benefit of increased b-carotene intake to reduce the risk of lung cancer in smokers. However, caution needs to be taken when increasing the intake of any of the lipid soluble vitamins. Excess accumulation of vitamin A in the liver can lead to toxicity which manifests as bone pain, hepatosplenomegaly, nausea and diarrhea.
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Vitamin D
Vitamin D is a steroid hormone that functions to regulate specific gene expression following interaction with its intracellular receptor. The biologically active form of the hormone is 1,25-dihydroxy vitamin D3 (1,25-(OH)2D3, also termed calcitriol). Calcitriol functions primarily to regulate calcium and phosphorous homeostasis.

Ergosterol

Vitamin D2


7-Dehydrocholesterol

Vitamin D3

Active calcitriol is derived from ergosterol (produced in plants) and from 7-dehydrocholesterol (produced in the skin). Ergocalciferol (vitamin D2) is formed by uv irradiation of ergosterol. In the skin 7-dehydrocholesterol is converted to cholecalciferol (vitamin D3) following uv irradiation.
Vitamin D2 and D3 are processed to D2-calcitriol and D3-calcitriol, respectively, by the same enzymatic pathways in the body. Cholecalciferol (or egrocalciferol) are absorbed from the intestine and transported to the liver bound to a specific vitamin D-binding protein. In the liver cholecalciferol is hydroxylated at the 25 position by a specific D3-25-hydroxylase generating 25-hydroxy-D3 [25-(OH)D3] which is the major circulating form of vitamin D. Conversion of 25-(OH)D3 to its biologically active form, calcitriol, occurs through the activity of a specific D3-1-hydroxylase present in the proximal convoluted tubules of the kidneys, and in bone and placenta. 25-(OH)D3 can also be hydroxylated at the 24 position by a specific D3-24-hydroxylase in the kidneys, intestine, placenta and cartilage.

25-hydroxyvitamin D3

1,25-dihydroxyvitamin D3

Calcitriol functions in concert with parathyroid hormone (PTH) and calcitonin to regulate serum calcium and phosphorous levels. PTH is released in response to low serum calcium and induces the production of calcitriol. In contrast, reduced levels of PTH stimulate synthesis of the inactive 24,25-(OH)2D3. In the intestinal epithelium, calcitriol functions as a steroid hormone in inducing the expression of calbindinD28K, a protein involved in intestinal calcium absorption. The increased absorption of calcium ions requires concomitant absorption of a negatively charged counter ion to maintain electrical neutrality. The predominant counter ion is Pi. When plasma calcium levels fall the major sites of action of calcitriol and PTH are bone where they stimulate bone resorption and the kidneys where they inhibit calcium excretion by stimulating reabsorption by the distal tubules. The role of calcitonin in calcium homeostasis is to decrease elevated serum calcium levels by inhibiting bone resorption.
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Clinical Significance of Vitamin D Deficiency
As a result of the addition of vitamin D to milk, deficiencies in this vitamin are rare in this country. The main symptom of vitamin D deficiency in children is rickets and in adults is osteomalacia. Rickets is characterized improper mineralization during the development of the bones resulting in soft bones. Osteomalacia is characterized by demineralization of previously formed bone leading to increased softness and susceptibility to fracture.
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Vitamin E
a-Tocopherol

Vitamin E is a mixture of several related compounds known as tocopherols. The a-tocopherol molecule is the most potent of the tocopherols. Vitamin E is absorbed from the intestines packaged in chylomicrons. It is delivered to the tissues via chylomicron transport and then to the liver through chylomicron remnant uptake. The liver can export vitamin E in VLDLs. Due to its lipophilic nature, vitamin E accumulates in cellular membranes, fat deposits and other circulating lipoproteins. The major site of vitamin E storage is in adipose tissue.
The major function of vitamin E is to act as a natural antioxidant by scavenging free radicals and molecular oxygen. In particular vitamin E is important for preventing peroxidation of polyunsaturated membrane fatty acids. The vitamins E and C are interrelated in their antioxidant capabilities. Active a-tocopherol can be regenerated by interaction with vitamin C following scavenge of a peroxy free radical. Alternatively, a-tocopherol can scavenge two peroxy free radicals and then be conjugated to glucuronate for excretion in the bile.
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Clinical significances of Vitamin E Deficiency
No major disease states have been found to be associated with vitamin E deficiency due to adequate levels in the average American diet. The major symptom of vitamin E deficiency in humans is an increase in red blood cell fragility. Since vitamin E is absorbed from the intestines in chylomicrons, any fat malabsorption diseases can lead to deficiencies in vitamin E intake. Neurological disorders have been associated with vitamin E deficiencies associated with fat malabsorptive disorders. Increased intake of vitamin E is recommended in premature infants fed formulas that are low in the vitamin as well as in persons consuming a diet high in polyunsaturated fatty acids. Polyunsaturated fatty acids tend to form free radicals upon exposure to oxygen and this may lead to an increased risk of certain cancers.
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Vitamin K
The K vitamins exist naturally as K1 (phylloquinone) in green vegetables and K2 (menaquinone) produced by intestinal bacteria and K3 is synthetic menadione. When administered, vitamin K3 is alkylated to one of the vitamin K2 forms of menaquinone.


Vitamin K1

Vitamin K2
"n" can be 6, 7 or 9 isoprenoid groups

Vitamin K3
The major function of the K vitamins is in the maintenance of normal levels of the blood clotting proteins, factors II, VII, IX, X and protein C and protein S, which are synthesized in the liver as inactive precursor proteins. Conversion from inactive to active clotting factor requires a posttranslational modification of specific glutamate (E) residues. This modification is a carboxylation and the enzyme responsible requires vitamin K as a cofactor. The resultant modified E residues are g-carboxyglutamate (gla). This process is most clearly understood for factor II, also called preprothrombin. Prothrombin is modified preprothrombin. The gla residues are effective calcium ion chelators. Upon chelation of calcium, prothrombin interacts with phospholipids in membranes and is proteolysed to thrombin through the action of activated factor X (Xa).
During the carboxylation reaction reduced hydroquinone form of vitamin K is converted to a 2,3-epoxide form. The regeneration of the hydroquinone form requires an uncharacterized reductase. This latter reaction is the site of action of the dicumarol based anticoagulants such as warfarin.
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Clinical significance of Vitamin K Deficiency
Naturally occurring vitamin K is absorbed from the intestines only in the presence of bile salts and other lipids through interaction with chylomicrons. Therefore, fat malabsorptive diseases can result in vitamin K deficiency. The synthetic vitamin K3 is water soluble and absorbed irrespective of the presence of intestinal lipids and bile. Since the vitamin K2 form is synthesized by intestinal bacteria, deficiency of the vitamin in adults is rare. However, long term antibiotic treatment can lead to deficiency in adults. The intestine of newborn infants is sterile, therefore, vitamin K deficiency in infants is possible if lacking from the early diet. The primary symptom of a deficiency in infants is a hemorrhagic syndrome.
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Return to Medical Biochemistry Page
Michael W. King, Ph.D / IU School of Medicine / miking at iupui.edu
Last modified: Monday, 20-Nov-2006 20:49:44 EST
Enzymes by Ray Sahelian, M.D.
Enzymes are proteins produced by all living organisms, and, like all proteins, they consist of amino acids. What makes these proteins different from other proteins is how they behave in the body. By definition, enzymes are catalysts that make many essential biochemical reactions ‘happen’ and are not used up or chemically altered in the process. As a catalyst, they help a chemical reaction take place quickly and efficiently.
Subscribe to a FREE Supplement Research Update newsletter. Twice a month you will receive an email of several studies on various supplements and natural medicine topics, including enzymes, and their practical interpretation by Ray Sahelian, M.D.


Here is a list of enzymes. I will update the information as I come across more information:
Aldose reductase is an enzyme normally present in the eye and elsewhere in the body. It helps change glucose (sugar - glucose) into a sugar alcohol called sorbitol. Too much sorbitol trapped in eye and nerve cells can damage these cells, leading to retinopathy and neuropathy. Substances that prevent or slow the action of aldose reductase are being studied as a way to prevent or delay these complications of diabetes. Aldose reductase is the first enzyme in the sorbitol pathway. This pathway is responsible for the conversion of glucose to sorbitol, and of galactose to galactitol. Under conditions of hyperglycemia, sorbitol accumulation occurs. Aldose reductase inhibitors prevent the accumulation of intracellular sorbitol. One such substance is Rutin.
Aminopeptidases attack the amino terminal (N-terminal) of peptides producing amino acids.
Amylase to digest carbohydrates. Amylase is secreted by the pancreas and small amounts are also made in the salivary glands. Amylase is the enzyme that hydrolyses starch to maltose (a glucose-glucose disaccharide), as well as the trisaccharide maltotriose and small branchpoints fragments called limit dextrins.
Bromelain is found in pineapples
Carbonic anhydrase relies on zinc for proper functioning. The carbonic anhydrase enzymes in red blood cells help the body expel carbon dioxide, with the demand rising substantially during exercise.
Carboxypeptidase removes, one by one, the amino acids at the C-terminal of peptides.
Catalase
Cellulase for fruit and vegetable digestion
Chymotrypsin
Cyclooxygenase (COX-1)
Disaccharidases convert disaccharides into their monosaccharide subunits.
Elastase cuts peptide bonds next to small, uncharged side chains such as those of alanine and serine.
Ficin from figs
Lactase for milk sugar digestion
Lactate Dehydrogenase - The enzyme LDH is in many body tissues, especially the heart, liver, kidney, skeletal muscle, brain, blood cells, and lungs.
LIpase for fat digestion. The drug orlistat (Xenical) is a pancreatic lipase inhibitor that interferes with digestion of triglyceride and thereby reduces absorption of dietary fat. The health concerns regarding the use of orlistat and blocking of fat absorption are yet to be fully understood.
Lysozyme - Lysozyme is an enzyme found in a number of secretions, such as tears. This enzyme is present in in egg white. Lysozyme is a natural "antibiotic" protein found in tears and certain secretions. Although proteins are usually tasteless, there are some, such as the enzyme lysozyme, which elicit a sweet taste on the human palate. Most of the sweet-tasting proteins have a high isoelectric point, but no homology has been observed in amino acid sequences and tertiary structures.
Maltase hydrolyzes maltose into glucose.
Lipoxygenase -- 5-lipoxygenase
Nitric oxide synthase -- makes nitric oxide from the amino acid arginine.
Nucleases hydrolyze ingested nucleic acids (RNA and DNA) into their component nucleotides.
Pancreatin found in Wobenzym supplement
Papain -- Papaya enzymes
Pepsin is secreted in the stomach. Digestion of proteins is initiated by pepsin in the stomach, but the bulk of protein digestion is due to the pancreatic proteases secreted in the small intestine..
Serrapeptase
Superoxide Dismutase
Sucrase hydrolyzes sucrose (common table sugar) into glucose and fructose.
Trypsin
Xanthine oxidase
Antioxidant Enzyme
Catalase
Glutathione
Superoxide dismutase
Blood clot dissolving enzymes
Serrapeptase
Cardiac Enzymes - Heart Enzymes

Natural Digestive enzymes - Digestive Enzymes Supplement
These include proteases, amylases and lipases that are involved in the breakdown of ingested proteins, carbohydrates and lipids (fats) respectively. Proper breakdown of these ingested foods is necessary to allow proper absorption of the nutrients to occur. Digestive enzymes and digestive enzyme supplements -- Natural digestive enzymes
Digestive enzymes are produced in the pancreas and salivary glands and help to break down the protein, carbohydrate, and fat components of food for use by the body. For more details and a thorough discussion, see Digestive Enzymes.

Food enzymes
Bromelain is found in pineapples
Ficin from figs
Nattokinase enzyme
Papain -- Papaya enzymes

Liver enzymes -- High liver enzymes cause
Elevated liver enzymes high liver enzymes
Cause of elevated liver enzymes
Lactate Dehydrogenase - The enzyme LDH is in many body tissues, especially the heart, liver, kidney, skeletal muscle, brain, blood cells, and lungs. LDH catalyzes the interconversion of pyruvate and lactate. Exercising muscles convert (and red blood cells metabolize) glucose to lactate. Lactate is released into the blood and is eventually taken up by the liver. The liver converts lactate back to glucose and releases glucose into the blood. This glucose is then taken up by resting muscles, red blood cells, and other tissues.
Muscle enzymes
Papaya Enzymes

Proteolytic enzymes
Serrapeptase
Q. I am a chiropractor and often see articles suggesting that proteolytic enzymes can effectively lower cholesterol. In my practice I recommend the use of proteolytic enzymes as an anti-inflammatory in athletic injuries and have seen literature that suggests that they may be of benefit in stablizing
cardiac artery inflammation (this reducing the risk of MI). Other than testimonials, however, I've not seen research that supports the use of proteolytic enzymes to reduce serum cholesterol. Can you offer any insight?
A. We have not come across research regarding proteolytic enzymes and cholesterol.
Pancreatic Enzymes
Bromelain is found in pineapples

Proprietary Enzymes
Wobenzym
Pancreatin - 300 mg*
Papain - 180mg*
Bromelain - 135 mg*
Trypsin - 72mg*
Chymotrypsin - 3mg*
Rutosid - 150 mg*

Systemic enzymes
Serrapeptase enzyme
Enzyme Replacement Therapy
Enzyme replacement therapy for lysosomal storage diseases did not become a reality until the early 1990s when its safety and effectiveness were demonstrated in type 1 Gaucher disease. Today, ERT is a reality for Gaucher disease, Fabry disease and mucopolysaccharidosis type I (MPS I), and clinical trials with recombinant human enzymes are ongoing in Pompe disease.

Suppliers of Enzymes
There are many raw material suppliers that provide enzymes. We received an email from one of them.
BioMedico Labs has been supplying enzymes to the dietary supplement industry since the year 2005. We offer a wide variety of enzymes derived from plants, fungi, and bacteria including bromelain, protease, amylase, lactase, and lipase that can be formulated into your dietary supplement product. With a large inventory at all times and a comprehensive portfolio of enzymes, BioMedico Labs is the most sensible choice to become your supplier of enzyme preparations. BioMedico Labs will go the extra mile to offer its clients the highest quality products at a very competitive price with personalized service. We are well-acquainted with enzyme ingredients currently being marketed in dietary supplements. Our technical sales representatives are available to work with you to meet your enzyme needs. If you have specifications for a dietary supplement containing enzymes, or if you need help with formulating an enzyme-based dietary supplement, feel free to contact us for a quote or for general information. BioMedico Labs offers custom package sizes and low minimum order requirements to allow our customers maximum flexibility in their ordering.
Enzyme emails
Q. There is a lot of controversy between doctors on whether the stomach absorbs enzymes intact. Enzymes are catalyst proteins. I can see the rightness of both sides of the argument. There are clinical trials that prove something of absorbed enzymes combat inflammation and break down cysts. There is also clinical evidence that any whole protein that gets into the body that wasn't manufactured in that body, is attacked as an invader and broken down into it's amino constituents. This is proven by the fact that transplanted organs require immune inhibition drugs to keep the transplanted organ from being destroyed because antibodies view the proteins as invaders. It is also true that certain kinds of protein , such as gelatin, are digested and absorbed, and put back together as your body's kind of collagen and obviously used to improve nails, hair, skin and joints. In the face of all this evidence, I am led to believe, that indeed, all proteins including enzymes are broken down into their amino constituents, in the digestive tract. But, the amino constituents must be somehow marked for what they were part of, because they seem to be put back together, in the blood or body, as an immune acceptable form of what they once were, since they directly benefit the body for what they once were. So, it is my observation that both sides of the controversy on whether enzymes are absorbed is right. It's just that both sides are incomplete in what they are saying, because neither side has considered that amino constituents may be marked for what they once were part of and reassembled into that particular body's version of what they once were in the way of whole proteins.
A. You bring up an excellent question that is hotly debated. When I was in medical school, we were told that everything we ate in our foods, including proteins, were broken down into amino acids. Hence, it would appear that there is no point in taking certain protein enzymes of any sort since they would be broken down. However, with time, I have gradually shifted my opinion that perhaps some larger molecules are absorbed intact into the bloodstream and are not necessarily broken down into the smallest particles. As to whether there is an intelligence that reassembles enzymes back together again from their individual constituents is beyond my knowledge since I focus mostly on clinical aspects of medicine rather than the more detailed biochemical or physiological aspects of metabolism.
Q. I recently came across a press release that I was hoping you could comment on since I respect your opinon. This is it: "Ellen Cutler has a message making its way to health conscious Britons. Her newest book MicroMiracles: Discover the Healing Power of Enzymes (Rodale, 2006) has been released in the UK , with the title Enzymes for Health and Healing. Cutler is a tireless advocate of enzyme supplementation, and is regarded as one of the foremost authorities on the subject of this millennium. She was a key player in the development of the WellZymes line of digestive and systemic enzymes from Enzymes, Inc. In fact, the formulations found in the WellZymes product line are those detailed in Enzymes for Health and Healing. “Enzyme supplements from the WellZymes product line are among the most effective products on the retail market today,” explains Cutler. “They are 100% vegetarian, are stable over a wide range of pH levels, and contain only the finest enzymes and herbal extracts.” Enzymes, Inc. has been formulating enzyme based nutritional supplements used in the health care industry for over two decades. The WellZymes product line was created to provide a professional quality enzyme supplement for the health conscious consumer. While somewhat of a nascent area of healthcare, as more and more doctors and patients discover the efficacy of digestive and systemic enzyme supplementation, it is rapidly becoming more mainstream. “Poor digestion can cause a array of other kinds of problems,” said Cutler, “such as: not being able to focus, cholesterol problems, other kinds of cardiovascular situations, rashes, eczema, hair falling out, nails breaking, pain and inflammation, and mood swings.” Products from the WellZymes product line were specifically designed to assist in the treatment of many different health conditions."
A. The whole topic of enzyme supplementation is quite confusing and difficult to give any confident answers on. Without doing actual stomach acid and intestinal acid analysis or other tests, it is difficult to say whether someone is short on digestive enzymes, and if so, which. Therefore, to make a statement such as "Enzyme supplements from the WellZymes product line are among the most effective products on the retail market today," and implying that digestive enzyme supplementation will cure a number of diseases... is premature. There may be some people who may benefit from taking a digestive enzyme supplement, and there may be many more people who take these enzyme supplements that don't actually get anything for it except a hole in their pocket. Many people with various health conditions sometimes attribute their problems to poor digestion whereas the problem could be due to something else.
Q. I just happened to come across your enzyme site in my search for information about some certain enzymes, and while I did find your site to be incredibly informative, I also happened to see a question posed at the bottom of the page, Digestive Enzyme emails: Q. I wonder if you can help. I am looking for a supplement that has trypsin, chymotrypsin and carboxypeptidase in it and am not having much success in locating such a supplement. A. We don't know of such a product at this time, but if we do we will mention it in the newsletter. I am not a maker of this, nor have i even tried it, but i wanted to forward this website to you and see if you have heard of and have any information about this particular website and enzyme product. http://home.bluegrass.net/~jclark/omnizyme.htm If you could provide any information on whether or not this would be a good supplement to assist with food breakdown and as an anti-inflammatory, I would greatly appreciate it.
A. Their website says, Omnizyme Forte ( with 125 mg Trypsin and 45 mg Chymotrypsin ) 200 tablets. Simply the BEST Proteolytic Enzymes available in the world today, bar none! Digestive enzymes also called pancreatic enzymes include three classes of enzymes... Proteolytic enzymes needed to digest protein, Lipases needed to digest fat and Amylases needed to digest carbohydrates.
Comments: We become suspicious when a website claims that their product is the best in the world. We don't know this company and hence do not know the quality of their product.









Glands are small but powerful organs that are located throughout the body. They control very important body functions by releasing hormones.

* Pituitary Gland
* Hypothalmus
* Thymus
* Pineal Gland
* Testes
* Ovaries
* Thyroid
* Adrenal Glands
* Parathyroid
* Pancreas

Pituitary Gland
The pituitary gland is sometimes called the "master gland" because of its great influence on the other body organs. Its function is complex and important for overall well-being.
The pituitary gland is divided into two parts, front (anterior) and back (posterior).
The anterior pituitary produces several hormones:

* Prolactin or PRL - PRL stimulates milk production from a woman's breasts after childbirth and can affect sex hormone levels from the ovaries in women and the testes in men.
* Growth hormone or GH - GH stimulates growth in childhood and is important for maintaining a healthy body composition. In adults it is also important for maintaining muscle mass and bone mass. It can affect fat distribution in the body. (For more information go to the Growth section on this site)
* Adrenocorticotropin or ACTH - ACTH stimulates production of cortisol by the adrenal glands. Cortisol, a so-called "stress hormone," is vital to survival. It helps maintain blood pressure and blood glucose levels.
* Thyroid-stimulating hormone or TSH - TSH stimulates the thyroid gland to make thyroid hormones, which, in turn, control (regulate) the body's metabolism, energy, growth and development, and nervous system activity.
* Luteinizing hormone or LH - LH regulates testosterone in men and estrogen in women.
* Follicle-stimulating hormone or FSH - FSH promotes sperm production in men and stimulates the ovaries to release eggs (ovulate) in women. LH and FSH work together to allow normal function of the ovaries or testes.

The posterior pituitary produces two hormones:

* Oxytocin - Oxytocin causes milk letdown in nursing mothers and contractions during childbirth.
* Antidiuretic hormone or ADH - ADH, also called vasopressin, is stored in the back part of the pituitary gland and regulates water balance. If this hormone is not secreted properly, this can lead to problems of sodium (salt) and water balance, and could also affect the kidneys so that they do not work as well.

In response to over- or underproduction of pituitary hormones, the target glands affected by these hormones can produce too many or too few hormones of their own. For example, too much growth hormone can cause gigantism, or excessive growth, while too little GH may cause dwarfism, or very short stature.
Additional Resources

* Growth information
* Pituitary information
* Educational Resources

Hypothalamus
The hypothalamus is part of the brain that lies just above the pituitary gland. It releases hormones that start and stop the release of pituitary hormones. The hypothalamus controls hormone production in the pituitary gland through several "releasing" hormones. Some of these are growth hormone-releasing hormone, or (controls GH release); thyrotropin-releasing hormone, or TRH (controls TSH release); and corticoptropin-releasing hormone, or CRH (controls ACTH release). Gonadotropin-releasing hormone (GnRH) tells the pituitary gland to make luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which are important for normal puberty.



Thymus
The thymus is a gland needed early in life for normal immune function. It is very large just after a child is born and weighs its greatest when a child reaches puberty. Then its tissue is replaced by fat. The thymus gland secretes hormones called humoral factors. These hormones help to develop the lymphoid system, which is a system throughout the body that help it to reach a mature immune response in cells to protect them from invading bodies, like bacteria.

Pineal Gland
Scientists are still learning how the pineal gland works. They have found one hormone so far that is produced by this gland: melatonin. Melatonin may stop the action of (inhibit) the hormones that produce gonadotropin, which causes the ovaries and testes to develop and function. It may also help to control sleep patterns.



Testes
Males have twin reproductive glands, called testes, that produce the hormone testosterone. Testosterone helps a boy develop and then maintain his sexual traits. During puberty, testosterone helps to bring about the physical changes that turn a boy into an adult male, such as growth of the penis and testes, growth of facial and pubic hair, deepening of the voice, increase in muscle mass and strength, and increase in height. Throughout adult life, testosterone helps maintain sex drive, sperm production, male hair patterns, muscle mass, and bone mass.
Testicular cancer, which is the most common form of cancer for males between ages 15 and 35, may need to be treated by surgical removal of one or both testicles. The resulting decrease or absence of testosterone may cause decreased sexual drive, impotence, altered body image, and other symptoms.

Ovaries

The two most important hormones of a woman's twin reproductive glands, the ovaries, are estrogen and progesterone. These hormones are responsible for developing and maintaining female sexual traits, as well as maintaining a pregnancy. Along with the pituitary gonadotropins (FH and LSH), they also control the menstrual cycle. The ovaries also produce inhibin, a protein that curbs (inhibits) the release of follicle-stimulating hormone from the anterior pituitary and helps control egg development.
The most common change in the ovarian hormones is caused by the start of menopause, part of the normal aging process. It also can occur when ovaries are removed surgically. Loss of ovarian function means loss of estrogen, which can lead to hot flashes, thinning vaginal tissue, lack of menstrual periods, mood changes and bone loss, or osteoporosis.
A condition called polycystic ovary syndrome (PCOS) is caused by overproduction of male hormones in females. PCOS can affect menstrual cycles, fertility, and hormone levels, as well as cause acne, facial hair growth, and male pattern balding.
Additional Resources

* Menopause information
* Osteoporosis information
* Polycystic Ovary Syndrome information
* Educational Resources



Thyroid
The thyroid is a small gland inside the neck, located in front of your breathing airway (trachea) and below your Adam's apple. The thyroid hormones control your metabolism, which is the body's ability to break down food and store it as energy and the ability to break down food into waste products with a release of energy in the process. The thyroid produces two hormones, T3 (called tri-iodothyronine) and T4 (called thyroxine).

Thyroid disorders result from too little or too much thyroid hormone. Symptoms of hypothyroidism (too little hormone) include decreased energy, slow heart rate, dry skin, constipation, and feeling cold all the time. In children, hypothyroidism most commonly leads to slowed growth. Infants born with hypothyroidism can have delayed development and mental retardation if not treated. In adults, this disorder often causes weight gain. An enlarged thyroid, or goiter, may develop.
Hyperthyroidism (too much hormone) may result in exophthalmic goiter, or Grave's disease. Symptoms include anxiety, fast heart rate, diarrhea, and weight loss. An enlarged thyroid gland (goiter) and swelling behind the eyes that causes the eyes to push forward, or bulge out, are common.
Additional Resources

* Thyroid information
* Educational Resources


Adrenal Glands
Each adrenal gland is actually two endocrine organs. The outer portion is called the adrenal cortex. The inner portion is called the adrenal medulla. The hormones of the adrenal cortex are essential for life. The hormones of the adrenal medulla are not.

The adrenal cortex produces glucocorticoids (such as cortisol) that help the body control blood sugar, increase the burning of protein and fat, and respond to stressors like fever, major illness, and injury. The mineralcorticoids (such as aldosterone) control blood volume and help to regulate blood pressure by acting on the kidneys to help them hold onto enough sodium and water. The adrenal cortex also produces some sex hormones, which are important for some secondary sex characteristics in both men and women.
Two important disorders caused by problems with the adrenal cortex are Cushing's syndrome (too much cortisol) and Addison's disease (too little cortisol).
The adrenal medulla produces epinephrine (adrenaline), which is secreted by nerve endings and increases the heart rate, opens airways to improve oxygen intake, and increases blood flow to muscles, usually when a person is scared, excited, or under stress.
Norepinephrine also is made by the adrenal medulla, but this hormone is more related to maintaining normal activities as opposed to emergency reactions. Too much norepinephrine can cause high blood pressure.
Additional Resources

* Pituitary information
* Educational Resources



Parathyroid
Located behind the thyroid gland are four tiny parathyroid glands. These make hormones that help control calcium and phosphorous levels in the body. The parathyroid glands are necessary for proper bone development. In response to too little calcium in the diet, the parathyroid glands make parathyroid hormone, or PTH, that takes calcium from bones so that it will be available in the blood for nerve conduction and muscle contraction.
If the parathyroids are removed during a thyroid operation, low blood calcium will result in symptoms such as irregular heartbeat, muscle spasms, tingling in the hands and feet, and possibly difficulty breathing. A tumor or chronic illness can cause too much secretion of PTH and lead to bone pain, kidney stones, increased urination, muscle weakness, and fatigue.

Pancreas
The pancreas is a large gland behind your stomach that helps the body to maintain healthy blood sugar (glucose) levels. The pancreas secretes insulin, a hormone that helps glucose move from the blood into the cells where it is used for energy. The pancreas also secretes glucagon when the blood sugar is low. Glucagon tells the liver to release glucose, stored in the liver as glycogen, into the bloodstream.
Diabetes, an imbalance of blood sugar levels, is the major disorder of the pancreas. Diabetes occurs when the pancreas does not produce enough insulin (Type 1) or the body is resistant to the insulin in the blood (Type 2). Without enough insulin to keep glucose moving through the metabolic process, the blood glucose level rises too high.
In Type 1 diabetes, a patient must take insulin shots. In Type 2 diabetes, a patient may not necessarily need insulin and can sometimes control blood sugar levels with exercise, diet and other medications.
A condition called hyperinsulinism (HI) is caused by too much insulin and leads to hypoglycemia (low blood sugar). The inherited form, called congenital HI, causes severe hypoglycemia in infancy. Sometimes it can be treated with medication but often requires surgical removal of part or all of the pancreas. An insulin-secreting tumor of the pancreas, or insulinoma, is a less common cause of hypoglycemia. Symptoms of low blood sugar include anxiety, sweating, increased heart rate, weakness, hunger, and light-headedness. Low blood sugar stimulates release of epinephrine, glucagon and growth hormone, which help to return the blood sugar to normal.
Additional Resources

* Diabetes information
* Educational Resources


<<>>

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Kidney Stones by Ray Sahelian, M.D. - Information on Urolithiasis

Stones in the urinary tract may cause pain, bleeding, obstruction of urine flow, or an infection. Depending on where a stone forms, it may be called a kidney stone or bladder stone. The process of stone formation is called urolithiasis.
Every year, about 1 out of 1,000 adults in the United States is hospitalized because of stones in the urinary tract. Stones may form because the urine becomes too saturated with salts that can form stones or because the urine lacks the normal inhibitors of stone formation. About 80 percent of the stones are composed of calcium; the remainder, of various substances, including uric acid, cystine, and struvite. Struvite stones--a mixture of magnesium, ammonium, and phosphate--are also called infection stones, because they form only in infected urine. Stones vary in size from too small to be seen with the eye alone to 1 inch or more in diameter.
Natural Supplements for Kidney Stone prevention
There's little research in this area, but when I come across more information I will make sure to update this section. For now, I found one potential supplement, IP6, that may be helpful.

Cause of Kidney Stones
Overweight individuals are more likely to have more acidic urine, as measured by a lower urinary pH, along with an increased risk of uric acid kidney stones. Low fluid intake is another cause of kidney stone. Excessive caffeine intake may increase calcium excretion through the kidneys, increasing the likelihood of a stone.
Men who work in the steel industry and are exposed to high temperatures are prone to develop kidney or urinary stones,. low levels of citrate in urine occurred more often in men in the hot-area group than those in the room-temperature group. Men in the hot-area group were also twice as likely to have low urine volumes. Both these conditions are involved in stone formation.

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Treatment of kidney stones
Small stones that aren't causing symptoms, obstruction, or an infection usually don't need to be treated. Drinking plenty of fluids increases urine production and helps wash out some stones; once a stone is passed, no other immediate treatment is needed. The pain of renal colic may be relieved with narcotic analgesics.
Often, a stone in the renal pelvis or uppermost part of the ureter that's ½ inch or less in diameter can be broken up by ultrasound waves (extracorporeal shock wave lithotripsy). The pieces of stone are then passed in the urine. Sometimes, a stone is removed through a small incision in the skin (percutaneous nephrolithotomy), followed by ultrasound treatment. Small stones in the lower part of the ureter may be removed by an endoscope (a small, flexible tube) inserted into the urethra and through the bladder.
Uric acid stones are sometimes dissolved gradually by making the urine more alkaline (for example, with potassium citrate), but other types of stones can't be removed this way. Rarely, larger stones that are causing an obstruction may need to be removed surgically.
Kidney Stone Treatment Complications
Shock wave lithotripsy (SWL) of renal and proximal ureteral stones appears to increase the risk of hypertension and diabetes on long-term follow-up. SWL may promote hypertension by causing scarring in the kidneys and altering the secretion of blood pressure-modulating hormones. The link with diabetes may relate to damage inflicted upon the pancreas, they add.
Kidney Stone Prevention -
Drink plenty of water every day.
People who are prone to kidney stones should limit their caffeine intake. When investigators gave people with a history of kidney stones a dose of caffeine equivalent to that found in two cups of coffee, they began to excrete more calcium in their urine, putting them at increased risk of forming kidney stones.
Measures to prevent the formation of new kidney stones vary, depending on the composition of the existing stones. These stones are analyzed, and urine levels of substances that can form stones are measured.
Kidney stone diet
Following a diet low in animal protein (also reduce milk, yogurt, and cheese) and low salt helps reduce the recurrence of calcium oxalate stones. Most people with calcium stones have a condition called hypercalciuria, in which excess calcium is excreted in the urine. Thiazide diuretics such as trichlormethiazide reduce new stone formation in such people. Drinking large amounts of fluids--8 glasses a day--is recommended. A high level of oxalate in the urine, which contributes to calcium stone formation, may result from excess consumption of foods high in oxalate, such as rhubarb, spinach, cocoa and chocolate, walnuts, and tea, or from certain intestinal disorders.
Rarely, calcium stones result from another disorder, such as hyperparathyroidism, sarcoidosis, vitamin D toxicity, renal tubular acidosis, or cancer. In such cases, the underlying disorder is treated.
For kidney stones that contain uric acid, a diet low in meat, fish, and poultry is recommended, because these foods increase the level of uric acid in the urine. Allopurinol may be given to reduce the production of uric acid. Potassium citrate may be given to make the urine alkaline, because uric acid stones form when urine acidity increases. Drinking large amounts of fluids also helps.
For struvite stones--which indicate a urinary tract infection--antibiotics are given.
Symptom of kidney stones
Pain, usually extreme, is the first symptom of a kidney stone. The pain may begin suddenly as a kidney stone moves in the urinary tract, causing irritation or blockage. Typically, the beginning of a kidney stone symptom starts when a person feels a sharp, cramping pain in the back and side around the area of the kidney, or in the lower abdomen. The pain may spread to the groin. Sometimes a kidney stone symptom could include nausea or even vomiting.
When the stone is too large to pass easily, the pain continues as the muscles in the wall of the tiny ureter try to squeeze the stone along into the bladder. As a stone grows or moves, blood may be found in the urine. As the stone moves down the ureter closer to the bladder, a person may feel the need to urinate more often or feel a burning sensation during urination.
Signs of a kidney stone include: extreme pain in the back or side that will not go away, blood in the urine, vomiting, and fever and chills.
Q. Does every kidney stone symptom include pain? A. Most kidneys stones are very small and pass without causing a symptom.
Q. Can a kidney stone symptom include constipation or diarrhea? A. Highly unlikely, the gastrointestinal symptom of kidney stone that occurs most commonly is nausea and sometimes vomiting.
Kidney Stone Research Update
If animal studies apply to humans, people taking the weight loss drug Xenical might have an increased likelihood of developing kidney stones, especially if they have a high intake of oxalate-containing foods. Researchers from the Federal University of Sao Paulo, Brazil, and the Karolinska Institute, Sweden, tested the effect of Xenical (known generically as orlistat) in 39 adult rats that were given a diet rich in oxalate alone or combined with fat (soy oil). With Xenical, oxalate levels in the urine were four to eight times higher than the baseline value, "elevating the risk of stone formation," the team reports in the August 2004 issue of Kidney International.
Individuals with either calcium oxalate or calcium phosphate kidney stones should not take extra calcium on their own as suggested by previous research, but should check with their doctors to determine the dietary guidelines that work best for them, researchers at UT Southwestern Medical Center at Dallas have found. Articles published by UT Southwestern researchers in the November issue of Kidney International and the December issue of the Journal of Urology showed that urinary calcium - the amount of calcium in a person's urine - is an important contributing factor in the formation of both types of kidney stones. Earlier studies had downplayed the significance of calcium when compared to the levels of oxalate in urine, and even encouraged kidney stone patients to increase their dietary intake of calcium. "We often see patients with kidney stones who tell us they have been advised to take more calcium; however, that could be a dangerous recommendation for some individuals," said Dr. Margaret Pearle, an author of the first study, professor of urology and internal medicine at UT Southwestern. "While we want to be cautious in asking anyone to restrict calcium intake because of the risk of bone disease, we also realize that urinary calcium has about the same influence as urinary oxalate in calcium oxalate kidney stone formation, and we may want to recommend calcium restriction in patients who have moderately to severely elevated intestinal calcium absorption and urinary calcium levels," she said.

Acetylcholine is a neurotransmitter
Acetyl-l-carnitine is the acetylated form of carnitine
Alternatives to Viagra are many
Avena Sativa is called wild oats
Bacopa is a memory support herb
Carnitine
Carnosine is an antioxidant
CDP-Choline is a potent form of choline
Choline
Co Q10 increases energy
Cordyceps
Creatine
Damiana
DHEA and pregnenolone are over the counter hormones
DMAE bitartrate
DMG is similar to TMG
Eurycoma longifolia
Forskolin
GABA is an amino acid
Ginkgo from China
Ginseng
Glucosamine
Horny Goat Weed
Kava
Lipoic acid
Lycopene
Maca from Andean mountains
Melatonin is a pineal hormone
Mucuna Pruriens
Muira puama
Pygeum
SAM-e, S-adenosylmethionine
Saw palmetto
Sex Pill natural alternative to pharmaceutical drugs
Stevia
Yohimbe has yohimbine
Zallouh
Tribulus terrestris
Passion flower
pygeum
beta sitosterol
female libido
erectile dysfunction
Herbs used in Urinary Tract Infections or Bladder infections
Bearberry
Kidney Stone Research
Phytate ( IP6 ) is a powerful agent for preventing calcifications in biological fluids: usefulness in renal lithiasis treatment.
Anticancer Res. 1999 Sep-Oct;19(5A):3717-22. Laboratory of Investigation into Renal Lithiasis, Faculty of Sciences, University of Illes Balears, Palma de Mallorca, Spain.
The extraordinary capacity of phytate (myo-inositol hexaphosphate), a substance present in blood, urine, interstitial and intracellular fluids, to inhibit crystallization of calcium salts (oxalate and phosphate) is discussed. Its role in preventing calcium renal stone formation is specifically presented and discussed. "In vitro" and "in vivo" experiments, as well as clinical studies clearly demonstrated that phytate plays an important role as a crystallization inhibitor of calcium salts in biological fluids and becomes a clear alternative in the treatment of calcium oxalate kidney stone.
Kidney Stone Questions
Q. How much water do you recommend drinking to prevent a kidney stone?
A. Each person is different, but 6 to 10 glasses of water a day seems reasonable to prevent a kidney stone in those who have had one in the past. Kidney stone symptom.
PYRUVATE by Ray Sahelian, M.D. Information on Calcium Pyruvate

Pyruvate is a three-carbon ketoacid produced in the end stages of glycolysis (breakdown of sugar). It can be reduced to lactate in the cytoplasm of a cell or changed to acetyl CoA in the mitochondrion. Simply, pyruvate is a product of sugar metabolism.
There have been claims that calcium pyruvate supplements help with weight loss or enhance physical endurance, however there is not enough research to confirm these claims. A rodent study indicates that pyruvate supplementation may help with the stress response. Much more research is needed with pyruvate before we know in which situations or medical condition this supplement could be useful. Pyruvate is normally sold as a supplement in the form of calcium pyruvate.
Calcium Pyruvate 1000mg - Now Foods

Some fitness enthusiasts are using pyruvate in their training regimen. This natural combination of calcium and pyruvic acid produces a highly stable element called pyruvate salt.

Calcium Pyruvate Supplement Info:
Calcium Pyruvate 1.0 gram per capsule

Calcium Pyruvate daily value not established.

Click here, Calcium Pyruvate, for more details or to subscribe to a FREE newsletter

Subscribe to a FREE Supplement Research Update newsletter. Twice a month you will receive an email with reviews of several studies on various supplements and natural medicine topics, including calcium pyruvate research, and their practical interpretation by Ray Sahelian, M.D.




Calcium Pyruvate and Athletic Performance
Several studies indicate pyruvate does not improve aerobic performance in well-trained athletes.

Calcium Pyruvate and Weight Loss
Does taking a calcium pyruvate supplement lead to weight loss? A few studies have been done with some positive results. In one study, the ingestion of 6 g of pyruvate for 6 weeks, in conjunction with mild physical activity, resulted in a decrease in body weight and fat mass. High doses of pyruvate, such as 20 to 40 gm a day, have been shown in some studies to lead to weight loss. See weight loss for natural ways to lose weight with options other than pyruvate.
Pyruvate Summary
Even if calcium pyruvate ingestion leads to weight loss, the required doses are too high, expensive, and impractical to consume or a regular basis. At this point I am not in a position to recommend the use of pyruvate either for weight loss or for athletic performance. It appears that pyruvate is not helpful for athletes. Based on my knowledge thus far, a calcium pyruvate supplement may be a waste of money. If additional research finds pyruvate helpful for weight loss or exercise performance, then I will change my position on pyruvate. However, pyruvate may have antioxidant potential.
Other Weight Loss options to consider
Little research is available on the role of a calcium pyruvate supplement in weight loss, however, the following supplements may be more reliable in suppressing appetite.
5-HTP is a nutrient that helps curb appetite in some individuals . 5-HTP, by converting into serotonin, can be used temporarily to improve will power and decrease the urge to eat until more established weight loss habits are in place.
Acetyl l Carnitine is another option. Some users notice decreased appetite.
Hoodia is a cactus plant extract from the Kalahari desert in South Africa that has been getting a lot of attention lately.
Lipoic acid
Green tea extract


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Calcium Pyruvate Side Effects
Only minor calcium pyruvate side effects have been reported thus far such as gastrointestinal symptoms including bloating and nausea.
Pyruvate Research Update
Effects of calcium pyruvate supplementation during training on body composition, exercise capacity, and metabolic responses to exercise.
Nutrition. 2005 Mar;21(3):312-9. Koh-Banerjee PK , Ferreira MP, Greenwood M, Bowden RG, Cowan PN, Almada AL, Kreider RB. Department of Preventive Medicine, University of Tennessee Medical School , Memphis , Tennessee , USA .
We evaluated the effects of calcium pyruvate supplementation during training on body composition and metabolic responses to exercise. Twenty-three untrained females were matched and assigned to ingest in a double blind and randomized manner either 5 g of calcium pyruvate or a placebo (PL) twice daily for 30 d while participating in a supervised exercise program. RESULTS: No significant differences were observed between groups in energy intake or training volume. No significant differences were observed between groups in maximal exercise responses or metabolic responses to submaximal walking. CONCLUSIONS: Results indicate that calcium pyruvate supplementation during training does not significantly affect body composition or exercise performance and may negatively affect some blood lipid levels.
Exogenous pyruvate supplement prevents stress-evoked suppression of mitogen-stimulated proliferation.
Brain Behav Immun. 2004 Sep;18(5):425-33. Departments of Neuroscience and Psychology, The Ohio State University , Columbus , OH 43210 , USA .
Psychological stress influences disease onset and progression. To test the hypothesis that energetic shortages compromise immunity, we evaluated the effectiveness of pyruvate supplement, to prevent stress-evoked suppression of mitogen-stimulated splenocyte proliferation. Male C57BL/6 mice were subjected to 2h of restraint once daily for 14 days. Consistent with previous studies, mitogen-stimulated splenocyte proliferation was reduced after restraint; in contrast, mice that received pyruvate injections immediately following each episode of restraint did not reduce splenocyte proliferation. In addition, restraint-evoked corticosterone elevation did not habituate in animals treated with pyruvate supplement, suggesting that glucocorticoids are not exclusively immunosuppressive. The ratio of pyruvate to lactate, an index of aerobic metabolism, was elevated in mice exposed to restraint suggesting that mice exposed to restraint were preferentially using aerobic metabolism and producing more ATP per unit of pyruvate than non-restrained mice. Furthermore, two of the effective doses of pyruvate (0.5 and 500.0mg/kg) altered glucose levels suggesting a metabolic function of the supplement. These results support the hypothesis that stress-evoked immunosuppression may be a function of metabolic energy shortages and can be prevented via pyruvate supplementation.

Effects of oral creatine- pyruvate supplementation in cycling performance.
Int J Sports Med. 2003 Feb;24(2):144-50.
A double-blind study was performed to evaluate the effects of oral creatine- pyruvate administration on exercise performance in well-trained cyclists. Endurance and intermittent sprint performance were evaluated before (pretest) and after (posttest) one week of creatine- pyruvate intake or placebo. It is concluded that one week of creatine- pyruvate supplementation at a rate of 7 g x d -1 does not beneficially impact on either endurance capacity or intermittent sprint performance in cyclists.

Pyruvate-enhanced cardioprotection during surgery with cardiopulmonary bypass.
J Cardiothorac Vasc Anesth. 2003 Dec;17(6):715-20.
To determine whether pyruvate -fortified cardioplegia solution provides cardioprotection superior to lactate-based cardioplegia solutions in patients undergoing elective coronary revascularization, with specific attention to post-surgical recovery of left ventricular performance as well as biochemical markers of ischemic injury. CONCLUSIONS: Pyruvate -fortified cardioplegia mitigated myocardial injury during coronary artery bypass surgery and facilitated postsurgical recovery of cardiac performance. Thus, pyruvate -enhanced cardioplegia may provide cardioprotection superior to lactate-based solutions during surgical cardiac arrest.

Pyruvate ingestion for 7 days does not improve aerobic performance in well-trained individuals.
J Appl Physiol. 2000 Aug;89(2):549-56.
The purposes of the present studies were to test the hypotheses that lower dosages of oral pyruvate ingestion would increase blood pyruvate concentration and that the ingestion of a commonly recommended dosage of pyruvate (7 g) for 7 days would enhance performance during intense aerobic exercise in well-trained individuals. Nine recreationally active subjects (8 women, 1 man) consumed 7, 15, and 25 g of pyruvate and were monitored for a 4-h period to determine whether blood metabolites were altered. Pyruvate consumption failed to significantly elevate blood pyruvate, and it had no effect on indexes of carbohydrate (blood glucose, lactate) or lipid metabolism (blood glycerol, plasma free fatty acids). As a follow-up, we administered 7 g/day of either placebo or pyruvate, for a 1-wk period to seven, well-trained male cyclists (maximal oxygen consumption, in a randomized, double-blind, crossover trial. Subjects cycled at 74-80% of their maximal oxygen consumption until exhaustion. There was no difference in performance times between the two trials (placebo, 91 +/- 9 min; pyruvate, 88 +/- 8 min). Measured blood parameters (insulin, peptide C, glucose, lactate, glycerol, free fatty acids) were also unaffected. Our results indicate that oral pyruvate supplementation does not increase blood pyruvate content and does not enhance performance during intense exercise in well-trained cyclists.

Effects of in-season (5 weeks) creatine and pyruvate supplementation on anaerobic performance and body composition in American football players.
Int J Sport Nutr. 1999 Jun;9(2):146-65.
The purpose of this investigation was to study the efficacy of two dietary supplements on measures of body mass, body composition, and performance in 42 American football players. Group 1 (n = 9) received creatine monohydrate, Group 2 (n = 11) received calcium pyruvate, Group 3 (n = 11) received a combination of calcium pyruvate (60%) and creatine (40%), and Group PL received a placebo. Tests were performed before (T1) and after (T2) the 50 week supplementation period, during which the subjects continued their normal training schedules. Compared to Pyruvate and PL, CM and creatine - pyruvate showed significantly greater increases for body mass, lean body mass, 1 repetition maximum (RM) bench press, combined 1 RM squat and bench press, and static vertical jump power output. Peak rate of force development for SVJ was significantly greater for CM compared to Pyruvate and PL. Creatine and the combination supplement enhanced training adaptations associated with body mass/composition, maximum strength, and SVJ; however, pyruvate supplementation alone was ineffective.

The effects of pyruvate supplementation on body composition in overweight individuals.
Peak Wellness, Greenwich , Connecticut 06830 , USA .
Nutrition. 1999 May;15(5):337-40.
A 6-wk, double-blinded, placebo-controlled study was done to ascertain the effects of pyruvate supplementation (6 g/d) on body weight, body composition, and vigor and fatigue levels in healthy overweight Caucasian men and women. Twenty-six individuals were randomly assigned to a placebo group (seven men, seven women) and a pyruvate -supplemented group (three men, nine women). In addition, all subjects participated in a 3 d/wk exercise program, which consisted of a 45-60 min aerobic/anaerobic routine. After 6 wk of treatment, there was a statistically significant decrease in body weight and percent body fat (23.0% pre versus 20.3% 6 wk post) in the pyruvate group. Furthermore, Profile of Mood States fatigue and vigor scores improved significantly for the pyruvate group (P<0.05) at 6 wk (vigor) and 4 and 6 wk (fatigue). There was no significant change in total lean body mass in the pyruvate group. The placebo group demonstrated a significant increase for POMS vigor at 2 and 4 wk with no changes occurring in any of the remaining parameters measured. Thus, the ingestion of 6 g of pyruvate for 6 wk, in conjunction with mild physical activity, resulted in a significant decrease in body weight and fat mass.
Pyruvate supplementation of a low-cholesterol, low-fat diet: effects on plasma lipid concentrations and body composition in hyperlipidemic patients.
Stanko RT, Reynolds HR, Hoyson R, Janosky JE, Wolf R.
Am J Clin Nutr. 1994 Feb;59(2):423-7.
The effects of the three-carbon compound pyruvate on plasma lipid concentrations and body composition were evaluated in hyperlipidemic patients consuming a low-cholesterol (165-180 mg), low-fat (22-24% of energy; 18-20% of energy as saturated fatty acid) diet (0.091-0.099 MJ.kg body wt-1 x d-1). After consuming the above diet for 4 wk, during which time plasma lipid concentrations decreased, 34 subjects were randomly assigned to receive either 22-44 g pyruvate (n = 17) or 18-35 g polyglucose (placebo, Polycose, n = 17), iso-energetically substituted for a portion of carbohydrate energy for 6 wk. Despite greater weight and fat losses with pyruvate (P < 0.05), plasma concentrations of cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride were not different between the two groups of subjects. We conclude that subsequent to diet-induced reduction in plasma lipid concentrations, pyruvate supplementation of a low-cholesterol, low-fat diet providing 6.7-7.6 MJ/d for 6 wk has no effect on plasma lipid concentrations but enhances body weight and fat losses. Pyruvate kinase.
Sodium Pyruvate Info
Anti-inflammatory activity of sodium pyruvate--a physiological antioxidant.
Indian J Physiol Pharmacol. 2000 Jan;44(1):101-4. Department of Pharmacology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi .
The anti-inflammatory activity of sodium pyruvate was evaluated in acute and chronic models of inflammation in rats. Oral administration of sodium pyruvate at three different dose levels of 125, 250 and 500 mg/kg body weight significantly inhibited the carrageenan induced acute paw edema in a dose dependent manner. The effect of 500 mg/kg sodium pyruvate was comparable to that of 12.5 mg/kg of standard diclofence. To conclude, sodium pyruvate exhibited significant anti-inflammatory activity in both the models of inflammation which could be attributed to its antioxidant properties.
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Pyruvate Enzymes
There are several enzymes that use pyruvate, including pyruvate kinase, pyruvate deaminase, pyruvate dehydrogenase, pyruvate carboxylase. Pyruvate dehydrogenase is the first component of the human pyruvate dehydrogenase complex. During prolonged exercise, carbohydrate oxidation may result from decreased pyruvate production and increased fatty acid supply, and ultimately lead to reduced pyruvate dehydrogenase activity. Pyruvate also interacts with the amino acids alanine, glutamine and glutamate whereby the decline in pyruvate production could affect TCA cycle flux as well as gluconeogenesis.
Certain metabolic deficiencies do occur, for instance there could be a pyruvate kinase deficiency or a pyruvate dehydrogenase deficiency. Pyruvate carboxylase deficiency is a rare disorder that causes developmental delay and failure to thrive starting in the neonatal or early infantile period.
Pyruvate Kinase Deficiency
Pyruvate kinase deficiency is an inherited deficiency of the enzyme pyruvate kinase, which is used by red blood cells. Without this enzyme, red blood cells break down too easily, resulting in low levels of red blood cells. the breakdown of red blood cells leads to hemolytic anemia.
Pyruvate Dehydrogenase Deficiency
Pyruvate dehydrogenase complex deficiency (PDCD) is at common neurodegenerative disorders associated with abnormal mitochondrial metabolism. The citric acid cycle is a major biochemical process that derives energy from carbohydrates. Malfunction of this cycle deprives the body of energy. An abnormal lactate buildup results in many symptoms such as severe tiredness, poor feeding, shortness of breath, especially during times of illness, stress, or high carbohydrate intake.
Pyruvate Carboxylase Deficiency
Pyruvate carboxylase deficiency is a rare genetic metabolic disorder. Pyruvate carboxylase deficiency is classified as a lactic acidemia in which the conversion of pyruvate to oxaloacetate is blocked, impairing glucose formation and resulting in an overabundance of lactic acid in the blood. Pyruvate carboxylase deficiency symptoms may include delayed development, muscle weakness, impaired ability to control voluntary movements, seizures, and vomiting.
Ethyl Pyruvate Research
Ethyl pyruvate enhances ATP levels, reduces oxidative stress and preserves cardiac function in a rat model of off-pump coronary bypass.
Heart Lung Circ. 2005 Mar;14(1):25-31. University of Pennsylvania School of Medicine, Division of Cardiothoracic Surgery, Department of Surgery, Silverstein 4, 3400 Spruce Street , Philadelphia , PA
Off-pump coronary artery bypass grafting is associated with transient periods of myocardial ischemia during revascularization resulting in myocardial contractile dysfunction and oxidative injury. The purpose of this study was to investigate the efficacy of ethyl pyruvate as a myocardial protective agent in a rat model of off-pump coronary artery bypass grafting associated with transient myocardial dysfunction without infarction. CONCLUSIONS: Ethyl pyruvate enhances myocardial ATP levels, reduces oxidative stress, and preserves myocardial function in a model of transient ischemia/reperfusion injury not subject to myocardial infarction.
Pyruvate and Lactate
There is a very rapid interconversion between lactate and pyruvate in blood.

Pyruvate emails
Q. I see pyruvate sold as calcium pyruvate or sodium pyruvate. Is there a difference?
A. Practically speaking there should not be much of a difference between the two.
Q. Are there pyruvate side effects?
A. Unless used in massive doses, calcium pyruvate supplement side effects are mino gastrointestinal symptoms.

Sleep by Ray Sahelian, M.D. - Sleep Aid Suggestions for Better Sleep

A good night's sleep enhances energy, mood, vitality, sex drive, and reduces the risk for chronic medical conditions. Deep sleep also has anti-aging benefits. This page will provide you with sleep aid ideas.
Causes of disturbed Sleep
Sleep problems can be caused by various medical disorders including asthma, COPD, heart failure, enlarged prostate, gastroesophageal reflux, chronic pain, restless leg syndrome, depression, and anxiety. Obstructive sleep apnea causes daytime fatigue.
Good Night Rx - 60 Capsules - for occasional sleep disturbance
Physician Formulas
Developed by Ray Sahelian, M.D.

Good Night Rx Supplement Facts:

Suggested Use: Take one capsule of Good Night Rx one to three hours before sleep, on an empty stomach. Good Night Rx does not work as well when taken with a meal. Good Night Rx was not formulated for those who have chronic insomnia and are already dependent on pharmaceutical sleeping pills.

For more information regarding Good Night Rx
Sign up to a FREE Supplement Research Update newsletter. Once or twice a month we email a brief abstract of several studies on various supplements and natural medicine topics - including sleep and how to have better sleep - and their practical interpretation by Ray Sahelian, M.D.
Practical Sleep Tips

1. Try to stick to a schedule, and don't sleep late on weekends. If you sleep late on Saturday and Sunday mornings, you'll get Sunday night insomnia. Instead, go to sleep and get up at about the same time every day. You may not need to rely on an alarm clock to wake up when you get enough sleep.
2. Don't eat or drink too much before bedtime sleep. Eat a light or medium sized snack about 1 to 2 hours before sleep. If you drink too much liquid before sleep, you'll wake up repeatedly in the night for trips to the bathroom.

* Don't eat too many spicy or fatty foods. They may cause heartburn and interfere with proper sleep.
* If you get the munchies, eat something that triggers serotonin, which makes you sleepy. Carbohydrates (whole grain bread, pasta with tomato sauce, potatoes, lentils, barley, fruits, or cereal) with small amount of foods containing the amino acid L-tryptophan (milk, tuna, or turkey) will do the trick. A fruit salad (with mangoes) and vegetable soup are good options. Another idea is whole grain bread with tomatoes (or salsa) and melted cheese.
* Don't drink more than one or two ounces of alcohol before sleep. It may cause you to wake up repeatedly, snore and possibly develop sleep apnea.

3. Avoid caffeine, nicotine, and stimulants. Smokers experience withdrawal symptoms at night, and they have a harder time both falling asleep and waking up. some people are so sensitive that even a cup of coffee drank at lunch can interfere with sleep.
Caffeine is found in tea (including green tea), certain soft drinks, chocolate, cocoa, and of course coffee. Caffeine is also found in certain herbs such as guarana and kola nut.
Diet pills that contain stimulants such as citrus aurantium can keep you awake. So can the nutrients phenylalanine, tyrosine, certain hormones, ginseng and other adaptogenic herbs, tongkat ali, LJ100, muira puama, maca, horny goat weed, dodder seed or cuscuta, and the anti-depressants St. John's wort and SAM-e. High doses of vitamins may act as stimulants, interfering with sleep. Take most of your supplements early in the day. Many herbs not mentioned above can cause alertness late into the night. If you have trouble sleeping, consider stopping all supplements, herbs and spices for a week to see if you sleep better.
Avoid spices and herbs in large quantities, particularly at dinner, since certain spices and herbs can influence sleep by making you too alert.
4. Exercise. If you're trying to sleep better, the best time to exercise is in the afternoon. Physical activity enhances the deep, refreshing stage of sleep. My best sleeps have been after a full day of walking, hiking, or biking. Also, take a walk in the morning to expose yourself to morning light which will help you sleep better at night. The more sun exposure you have, the deeper your sleep will be that night.
5. A slightly cool room is best for sleep. This mimics your internal temperature drop during sleep, so turn off the heat and save on fuel bills.

* If you tend to get cold, use blankets.
* If you overheat at night, wear light nightclothes and sleep under a single sheet. Use an air conditioner or fan to keep the room cool.
* Use a dehumidifier if you are bothered by moist air. Use a humidifier if you are bothered by dry air. Signs of dry air irritation include a sore throat, nosebleeds or a dry throat.

6. Sleep only at night. Daytime naps steal hours from nighttime slumber. Limit daytime sleep to 20-minute, power naps. Don't take a nap after 2 PM.

* If you work nights, keep window coverings closed so that sunlight, which interferes with the body's internal clock, doesn't interrupt your sleep.
* If you have a day job and sleep at night, but still have trouble waking, leave the window covering open and let the sun's light wake you up.

7. Keep it quiet. Silence is more conducive to sleep. Turn off the radio and TV. Use earplugs, a fan or some other source of constant, soothing, background noise to mask sound that you cannot control, such as a busy street, trains, airplanes or even a snoring partner. Double-pane windows and heavy curtains also muffle outside noise.
8. Make your bed comfortable.

* If you share your bed, make sure there is enough room for two.
* Use your bed only for sleep and sex.
* Go to bed when you are tired and turn out the lights. If you don't fall asleep in 15 minutes, get up and do something else. Go back to bed when you are tired.
* Do not agonize about falling asleep. The stress will only prevent sleep.

9. Soak and sack out. Taking a hot shower or bath an hour or two before sleep helps bring on sleep because they can relax tense muscles.
10. Don't overly rely on sleeping pills. Check with your doctor before using sleeping pills. Make sure the pills won't interact with other medications or with an existing medical condition.

* Use the lowest dosage and never mix alcohol and sleeping pills. The occasional use of prescription sleep pills should not be harmful. Regular use can lead to dependence on these sleeping pills and you could have rebound insomnia (not sleeping well) the night you stop take them.
* If you feel sleepy or dizzy during the day, talk to your doctor about changing the dosage or discontinuing the sleeping pills.
* Melatonin at a dose of 1 to 2 mg an hour or two before bed can help induce sleep. Limit use to once a week. Sometimes a lower dose such as 0.3 mg taken earlier in the evening, about 6 or 7 PM works better than a higher dose taken later.
* The herb Hops in tea or pill can also help with sleep. Hops is taken about an hour or two before bed. A Valerian/Hops combination 500mg/100mg may also work well.
* Kava taken a few hours before bed can also be helpful, so can the occasional use of 5-HTP at a dose of 50 mg an hour before bed on an empty stomach or half an hour before dinner. Another option is Tryptophan.
* Another option for occasional sleepless night is Good Night Rx which has a combination of many herbs.

11. Use ear plugs and eye shades to block noise and light. You may be amazed on how much better you'll sleep and feel in the morning when you use ear plugs since you will be able to get a deeper sleep without frequent overnight interruptions from traffic noise, airplanes, dogs barking, roommates snoring, etc.

12. Use sleep relaxation techniques.
Once you are in bed, take a deep breath and gradually let it out. Do this a few times. Then, lightly shake one of your feet, and go back to taking a couple of deep breaths. Lightly shake the other foot and then take a couple of deep breaths. Move up to your legs, hips, arms, neck, muscle around the mouth, eye muscles, etc., while going back to the breath after shaking each body part. Soon you'll be in la la land.

Being woken up and exposed to bright light at night can throw off a person's biological clock for the next few days, a new study shows. What's more, the researchers found that being woken up at night at all--even in a dark room--also disrupts the body's timing, although to a lesser degree.
13. Aromatherapy
The smell of jasmine in the bedroom has been found to help improve sleep in those who are sensitive to aromatherapy. Lavender may also help slightly.
14. Soft Music
In a paper published in the February issue of the Journal of Advanced Nursing, a team from Taiwan ’s Tzu Chi University said they studied the sleep patterns of 60 people aged between 60 and 83 who had difficulty sleeping. Half were given relaxing music to listen to for 45 minutes at bedtime and half were given no help to sleep. The team found that those who listened to a selection of soft, slow music experienced physical changes that aided restful sleep, such as lower heart and respiratory rates.
15. Avoid regular use of pharmaceutical sleep medication. Frequent use of sleep medication can lead to reliance, tolerance, and loss of memory.

Sleep Research Update
Sleep problems affects 20% of the adult population in western countries and its prevalence increases with age. There is a controversy regarding the origin of sleep disorders in elderly. Are they only due to a senile process of sleep functioning or due to other associated comorbidities? Considering the objective assessment of sleep in elderly (by polysomnography), it has been shown an increasing sleep latency, decreasing total sleep time and sleep efficiency, a lower percentage of slow wave sleep. The circadian clock is also modified by age with phase advance and a decreased amplitude of the circadian rhythms. The most relevant comorbidities found in older people are: sleep apneas, restless leg syndrome, psychiatric disorders (anxiety and depression) and the use of drugs.
Caffeine may keep adolescents perky through their early morning classes but according to a recent survey, it cuts into their nighttime sleep. The survey, published in the January issue of Pediatrics, included nearly 200 7th- through 9th-grade students who recorded their sleep patterns and their daily intake of caffeinated drinks and foods over two weeks. The average intake of caffeine was just 63 milligrams (mg)--equivalent to about one-half of a cup of coffee. Children who reported higher intakes of caffeine were found to sleep fewer hours, were more likely to wake during the night and tended to be sleepier during the day.
Researchers found that among more than a thousand third-graders, obesity, "mouth breathing" during the day, frequent sore throats and parents' smoking were all associated with a higher risk of habitual snoring.
A low-carbohydrate diet leads to modest improvements in daytime sleepiness in patients with narcolepsy.
Sleep related to disease
Sleep deprivation affected hormonal levels. Men and women had a 40% to 60% average increase in the inflammatory marker interleukin-6 (IL-6), while men alone showed a 20% to 30% increase in another marker for inflammation, tumor necrosis factor (TNF). Both IL-6 and TNF are cytokines, which are proteins the body releases in response to injury. The findings indicate that getting a full night's rest of eight hours is not a nice bonus, but necessary. In addition, the finding that lack of sleep may stimulate an increase in chronic, low-level inflammatory response is worrisome, because that state has been linked to conditions such as high blood pressure, heart disease and most recently, diabetes.
The Deep baby sleep.
Nothing seems to improve memory, mood, and overall mental health as well as regular, deep sleep.
There are many tips on how to have good sleep patterns. I recommend that patients expose themselves to morning light for at least ten to twenty minutes by either taking a walk or driving to work. Morning light exposure helps reset our daily clock. Mental activity should be stopped at least one hour before bed and the mind allowed to switch to fun reading, watching a comedy film or TV show. You could tape your favorite prime time sitcom and then watch it before bed.
Use earplugs to muffle noises. You may be surprised how many noises can potentially disturb your sleep. These could be such interruptions as a dog barking, traffic, airplanes flying overhead, birds chirping outside your room in the early morning, or a loud bed partner.
Try one or more relaxation techniques. When you are in bed lying on your back, shake and loosen a leg and foot. Take a few, slow, deep breaths by expanding your belly. Proceed to shake and loosen the other leg and foot and then return to your abdomen for a few more relaxed breaths. Proceed with this relaxation to your arms, shoulders, and neck. Now relax your facial muscles--especially the muscles around the eyes and mouth. Remember to return to your breath after relaxing each muscle group. Before you know it you'll be drifting into your adventure-filled unconscious.
In my experience as a family physician, I recommend eating carbohydrate foods an hour ot two before bedtime in order to induce sleep. Some of the suggestions that I tell my patients are to eat a fruit salad with maple syrup, whole grain cereal, potato, cheese and tomato sandwich, or pasta with tomato sauce. Carbohydrates stimulate insulin release which in turn helps the amino acid tryptophan more easily cross the blood brain barrier and in the brain tryptophan gets converted into serotonin and on to melatonin.

Sleep apnea (not sleep apnia)
People with sleep apnea stop breathing for 10 to 30 seconds at a time during sleep. These short stops in breathing can happen several hundred times every night. If you have sleep apnea, the periods of not breathing may make you wake up from deep sleep. People with obstructive sleep apnea (OSA) may find nighttime treatment with a pressurized breathing machine cumbersome, but it pays off: continuous positive airway pressure therapy -- CPAP, as it's called -- does lower the rate of heart-related deaths in such patients.
When an elderly person dies in his or her sleep, cessation of breathing related to the loss of neurons in a particular area of the brain could be a possible cause of death. A brain region called the ventrolateral medulla is critical for generating regular, rhythmic breathing, and neurons in this area show high levels of a receptor termed NK1R. A lack of NK1R-carrying neurons could underlie central sleep apnea. The most common form of sleep apnea is obstructive sleep apnea, when airway passages collapse and block breathing, but it can also arise when respiration signals from the brain are interrupted -- known as central sleep apnea. Researchers studied rats after the animals were injected with a toxin that selectively kills off neurons carrying NK1R. After 4 days, respiratory disturbances had increased from 4 to 66 episodes per hour during sleep, and the rate worsened even more over the next two days. From day 7 on, the animals developed a highly fragmented sleep pattern and reduced total sleep time. While awake, breathing became increasingly irregular. By 10 days, the rats stopped breathing immediately upon falling asleep, starting again only after they awakened. Central sleep apnea becomes more prevalent as people get older. Since these neurons slowly deteriorate, and because older individuals' heart and lungs are weaker, they become more susceptible to respiratory failure during sleep.
Mayo Clinic researchers have identified a new type of sleep apnea called "complex sleep apnea" that may be resistant to standard treatment such as continuous positive airway pressure (CPAP).

Sleep apnea symptom
If you are waking up all night long, you aren't getting enough rest from your sleep and you are likely to be exhausted the next day. A sleep apnea symptom your partner may notice is periods of not breathing which can last over half a minute. Next day sleepiness is another sleep apnea symptom. If you feel the need to drink a lot of coffee to keep you awake during the day, you may be covering up a sleep apnea symptom. In fact, drinking coffee could make you sleep worse at night.
Sleep apnea treatment
Sleep apnea treatment is not always effective but worth a try. There are four approaches one can take. There is currently no proven drug therapy for sleep apnea. However, there are 4 basic approaches 1. Try to change the circumstances which may be causing sleep apnea or making it worse. This would include weight loss, avoidance of alcohol and sedative drugs, trying to sleep only on your side and stopping smoking. 2. Use Continuous Positive Airway Pressure (CPAP) in the upper airway to support and hold the airway open. 3. One of the reasons for the upper airway to become narrowed at night is because the tongue falls backwards, especially in the supine position. Since the tongue is attached to mandible this can be a significant problem in people with retrognathia and/or a very large tongue. It is possible to use a dental splint at night that effectively prevents the jaw and tongue from moving back when someone lies down and goes to sleep. 4. A surgical operation on the back of the throat to remove redundant soft tissue in an attempt to increase the size of the upper airway can be performed to reduce sleep apnea.
Mouth devices that aid breathing during sleep can be used as the first-line treatment for people with chronic snoring or milder cases of obstructive sleep apnea. Oral appliances - similar to mouth guards used in sports - should be offered as an initial treatment to people with mild to moderate OSA. People with more severe cases, however, are advised to first try continuous positive airway pressure (CPAP), which has been shown to be more effective than oral devices.
Sleep Apnea, Snoring, and Didgeridoo
Researchers in Switzerland examined 25 patients who suffered from snoring and moderate obstructive sleep apnea syndrome, both common sleep disorders. Half the group were given daily lessons in playing the didgeridoo, a wind instrument about 1.5 meters (yards) long that originated in northern Australia and is traditionally made from the trunk of a tree hollowed out by termites. The study, published in the British Medical Journal's January 2006 edition, found that those who played the unusual instrument over a four-month trial period saw a significant improvement in their daytime sleepiness and apnea. Their partners also reported less disturbance from snoring. The researchers said training the upper airways through the breathing techniques required to play the didgeridoo was behind the improvement.

Length of sleep
The amount of sleep that a person needs to function normally depends on several factors (e.g., age). Infants sleep most of the day (about 16 hours); teenagers usually need about 9 hours a day; and adults need an average of 7 to 8 hours a day. Although elderly adults require about as much sleep as young adults, they usually sleep for shorter periods and spend less time in deep stages of sleep. About 50% of adults over the age of 65 have some type of sleep disorder, although it is not clear whether this is a normal part of aging or a result of medications that older people commonly use, or a deficiency of melatonin, or lack of adequate exercise and exposure to sunshine.

Sleep aid
Sleep aids include natural supplements, sleeping pills, ear plugs, eye shades or sleep masks, and others.

Effects of Sleep deprivation
Sleep deprivation can lead to fatigue, low mood, low motivation, and disturbed immune system leading to more colds and flu. Over the long run, chronic disturbed sleep can cause many illnesses including increasing the risk for cancer.

Sleep study
Sleep studies, or polysomnographic (PSG) studies, are a series of tests that help evaluate what happens to the body during sleep and are used if people have a sleep problem. A sleep study is done to diagnose sleep disorders.
Sleep disorder
There are a few dozen different sleep disorders that are generally classified into one of three categories:
Lack of sleep (e.g., insomnia)
Disturbed sleep (e.g., obstructive sleep apnea, sleepwalking, night terrors, sleep walking, sleep talking, bed-wetting, restless legs syndrome), and
Excessive sleep (e.g., narcolepsy.
In most cases, sleep disorders can be easily managed once they are properly diagnosed. Insomnia is the most common sleep disorder. It occurs more often in women and in the elderly. If you have a serious sleep disorder, make an appointment with a sleep expert doctor, sleep disorder center, or a sleep clinic.

Sleep medication or sleep medicine
You can find over-the-counter sleep medications such as diphenhydramine and dimenhydrinate. I don't think they work well to give a better sleep, and these sleep medications can leave you drowsy the next day, but they do not appear to be addictive. Side effects of these sleep medications include dizziness, blurred vision, and dry mouth. Other commonly used over-the-counter sleep medications include Nytol, Sleep-Eez, and Sominex. When sleeplessness is caused by minor pain, over-the-counter pain relievers such as acetaminophen (Tylenol) or a nonsteroidal anti-inflammatory drug (Advil, Motrin) can sometimes be helpful. Antihistamines have a sedating effect and may be used as mild sleep inducers. They include chlorpheniramine (Chlor-Trimeton) and diphenhydramine (Benadryl). I personally prefer the natural sleep aids.

Sleep Medication and the Elderly - risks outweigh benefits
While sedative hypnotics may improve sleep in older people with insomnia, the risks of such therapy may outweigh the benefits. The findings are based on a meta-analysis of 24 randomized, controlled trials that included 2417 subjects aged 60 or older who were treated with sedative hypnotics or placebo for insomnia. The subjects received the assigned agent for at least five consecutive nights. Compared with placebo, sedative use was associated with statistical significant improvements in sleep quality, total sleep time, and the number of nighttime awakenings. However, the effect size was small. Several adverse effects were more common with sedative hypnotics than with placebo. Sedative use was associated with a several fold increased risks of adverse cognitive events, adverse psychomotor events, and daytime fatigue. The likelihood of an untoward event was even greater in subjects who were at high risk for falls or cognitive impairment.
Types of Sleep Medication
There are several sleep medication options available, and I believe they are effective and safe when used infrequently.
Ambien
Lunesta has been approved for long term use, but I am always cautious about taking drugs for long periods of time.

REM sleep
REM sleep is a stage of sleep characterized by a number of features including rapid, low-voltage brain waves detectable on the electroencephalographic (EEG) recording, irregular breathing and heart rate and involuntary muscle jerks.
Dreams occur during REM sleep. We typically have 3 to 5 periods of REM sleep per night. They occur at intervals of 1-2 hours and are quite variable in length. An episode of REM sleep may last 5 minutes or over an hour. About 20% of sleep is REM sleep. If you sleep 7-8 hours a night, perhaps an hour and half of that time, 90 minutes, is REM sleep. By contrast, NREM (non-REM) sleep is dreamless sleep. During NREM, the brain waves on the EEG are typically slow and of high voltage, the breathing and heart rate are slow and regular, the blood pressure is low, and the sleeper is relatively still. NREM sleep is divided into 4 stages of increasing depth of sleep leading to REM sleep. About 80% of sleep is NREM sleep. If you sleep 7-8 hours a night, all but maybe an hour and a half is spent in dreamless NREM sleep.
Sleep and Memory
Skimping on sleep can slow certain types of learning, and the difficulty seems to arise from a lack of new brain neurons. Rodents that got half their normal amount of shut-eye had a harder time remembering how to navigate a maze than well-rested rats.
Sleep on it - Sleep for Major Decisions
When faced with a major decision, such as buying a car or a house, it's best to do your homework, and then forget about it for a while and let your unconscious churn through the options. According to the results of a novel study published today in the journal Science, unconscious deliberation may lead to a more satisfying choice than mere conscious deliberation alone, at least for major decisions. The human subconscious has a higher capacity to integrate more information, which can lead to better choices.
Delayed Sleep Phase Syndrome
Many teens and adults have a sleep disorder known as delayed sleep phase syndrome. Some people have a lot of trouble getting to sleep until 2 or 3 in the morning and they could have a condition known as delayed sleep phase syndrome. This is a disorder where people may think they have insomnia, but can actually sleep well as long as they sleep hours after others have gone to bed. Delayed sleep phase syndrome affects between 7 percent and 16 percent of adolescents and young adults. It is less common among older adults. Among those affected by the disorder, the body's circadian rhythm allows them to stay awake long past what may be considered a normal bedtime. There is no cure for delayed sleep phase syndrome, but it can be treated by behavioral modification, such as restricting the consumption of caffeinated beverages, not exercising during or near bedtime hours and limiting light exposure from computer screens and television screens at night. Exposure to sunlight during the day and doing lots of exercise that leads to exhaustion can be helpful. The occasional use of melatonin or kava in the evening may provide temporary benefit.
Sleep and bed wetting: see bedwetting

Sleep Emails
Q. The purpose of this email is to ask a question about Valerian and Hops for sleep. Right now I am taking 1000 mg of Valerian and 150 mg of Hops for insomnia. I had been taking a sleeping pill called Ambien and did not like the hung over feeling I had in the morning so I weaned myself off of Ambien - slowly; and then I slowly started to introduce Valerian and Hops. So far so good - but here are some nights that I simply do not sleep well. Can "tolerance" develop with these herbs?
And, Dr Sahelian, thank you so much for your hard work, dedication, and pioneering spirit in nutritional medicine! I am indeed a fan.
A. I appreciate the positive feedback. There are several herbs and nutrients that can help with insomnia, such as hops, valerian, kava, melatonin, 5-HTP, etc., unfortunately, tolerance can develop with most of them, and they are not as consistent as pharmaceutical medicines. I recommend to my patients to alternate various nutrients and herbs, and sometimes I will prescribe the occasional use of a prescription sleeping pill. It's also a good idea to take breaks and not use any pills for sleep for at least a couple of nights.
Q. Does Benadryl help a baby sleep?
A. Studies have found that the antihistamine Benadryl is not effective in helping babies sleep.
Q. I have problems sleeping at night and staying awake in the day and I'm looking for natural a solution. For energy I found Acetyl-L-Cartinine and R-Alpha lipoic Acid, which are recomended to be taken together. For sleep I found Tryptophan and 5-HTP. Which of the 2 sleep aids would be most effective and safest to take long-term?
Would it make sense to take a sleep aid and the energy boosters listed above? Would these products work against each other in some way?
A. Both acetylcarnitine and lipoic acid, in a high dose, can cause sleep problems even if they are used in the morning. So, dosages should stay low enough to not interfere with sleep. It's difficult to predict which of the two serotonin precursors, 5-HTP or tryptophan, would be a better sleep aid. Different people respond differently.
Q. I just saw an ad in a magazine for an all natural product called LipoRid PM for better sleep. I have had such a hard time with sleep since I lost my son six years ago and since entering menopause. I would really like to know if you could tell me if I should consider taking LipoRid PM. It lists the ingredients as Gymnema sylvestre, Guggulipid, and N-Acetyl L-Carnitine, Sleep enhancers combined with Fat metabolizers and Amino Acids. 5-HTP, Banaba Leaf and GABA. I take a generic precription drug for low thyroid. Could I take LipoRid PM or should I just keep looking. I have taken melatonin and also valerian root, but nothing really works. Sometimes I lay in bed for hours before falling asleep.
A. We have not heard of LipoRid PM, and do not know if it works or not for better sleep. Acetyl-l-carnitine actually causes alertness and we are not sure why this nutrient has been included in LipoRid PM sleep product.

muira puama tribulus yohimbe damiana horny goat weed maca female libido pygeum libido vervain

HAIR loss

Natural Options for Hair Loss or Thinning Hair
Subscribe to a FREE Supplement Research Update newsletter by Ray Sahelian, M.D.

Hair originates in the dermis, the skin layer just below the surface layer (epidermis).

Baldness (alopecia), or severe hair loss, is much more common in men than in women. Hair loss can result from genetic factors, aging, local skin conditions, and diseases that affect the body generally (systemic diseases). Some medications, such as those used to treat cancer, also cause hair loss. Perhaps a poor diet with lots of junk food over a period of years and decades is involved in hair loss but scientists still don't have a good understanding regarding the relationship of food and hair loss.

Standard Hair loss treatment
Most types of hair loss have no cure. A person with male-pattern or female-pattern baldness may undergo hair transplantation, in which hair follicles are removed from one part of the body and transplanted. Some medications or hair loss products, such as topical minoxidil, may promote hair growth in a small percentage of people. The oral drug finasteride may also promote hair growth. Finsateride is available as the product name Propecia 1 mg, or as Proscar 5 mg (used for enlarged prostate). It is cheaper to buy Proscar 5 mg and bite off about a fifth a day instead of buying Propecia since Proscar is only slightly more expensive than Propecia but it has 5 times as much finasteride.
Minoxidil, used topically may also be helpful at minoxidil 2% for women and minoxidil 5% for men.

Natural Hair Loss Remedy -- may be helpful for healthy hair growth
The role of diet in hair loss is not well understood, but it is possible that a diet with lots of junk food could promote inflammation and be harmful to hair growth, whereas a very healthy diet, over many years, may reduce hair loss. I'm not sure whether eating soy products, lots of vegetables, fish or taking fish oil capsules would help slow down hair loss. Perhaps they may since they thin the blood and improve circulation. I'm not aware of a hair loss vitamin that would be useful since most Americans are not severely deficient in any particular vitamin.
A molecule produced in the intestine when soy is digested stops a hormone which can fuel prostate growth or cause hair loss. Writing in the journal Biology of Reproduction, researchers said the finding could explain why Japanese men, who eat more soy, rarely have prostate cancer. They said the molecule could be used as a treatment for cancer and hair loss. The team found that the molecule, equol, "handcuffs" the male hormone DHT - a by-product of testosterone. Equol is a metabolic product of the flavonoid daidzein. The researchers say this could be particularly important for men who have been diagnosed with either an enlarged prostate (benign prostatic hyperplasia), or cancer of the prostate. DHT has also been implicated in research into the causes of male pattern hair loss.
Saw Palmetto extract is also involved blocking DHT in prostate tissue, whether it does so in hair tissue is not clear. One small study indicates the combination of saw palmetto and beta sitosterol could be helpful (see below).
Hopefully, over the next few years, we will have a clearer understanding of the role of long term dietary intake and hair health.
Dr. Sahelian has formulated a product for prostate tissue health which contains saw palmetto isoflavones such as genistein and daidzein along with beta sitosterol. Whether this product helps those with hair loss has not been evaluated. Interestingly, Prostate Power Rx users report a noticeable sexual enhancement.
Prostate Power Rx
60 Capsules
Physician Formulas
Formulated by Ray Sahelian, M.D.

With Saw Palmetto, Beta Sitosterol, Pygeum, Stinging Nettle, Quercetin, & 9 Key Ingredients. Prostate Power Rx is carefully formulated with important herbs and nutrients to provide optimal prostate health.
Saw Palmetto extract
(standardized to contain 45% fatty acids - serenoa repens fruit)
Stinging Nettle 4:1 extract
(urtica diocia root)
Quercetin
Rosemary 4:1 extract
(Rosemarinus officinales leaf)
Beta Sitosterol
Pygeum 4:1 bark extract
(Pygeum Africanum)
Daidzein
(standardized to contain 40% isoflavones)
Genistein
(standardized to contain 40% isoflavones)
Lycopene
(Lycoperscion escatatum fruit)
Click here for more information or to sign up to a FREE and extremely popular health newsletter
Subscribe to a FREE Supplement Research Update newsletter. Once or twice a month we email you a brief abstract of several new studies on various supplements and natural medicine topics, including hair regrowth and herbs that influence hair regrowth, and their practical interpretation by Ray Sahelian, M.D.
Male-pattern baldness is the most common type of hair loss affecting men. It's rare in women and children because it depends on the presence of male hormones (androgens), and levels of these hormones are high in males after puberty. Hair loss runs in families. Hair loss usually begins on the sides, near the front, or on the top of the head toward the back. Hair loss can begin at any age, even in the middle teen years. Some people lose only some hair and develop a bald spot in the back or a receding hairline; others, especially people whose hair loss begins at a young age, may go completely bald.
Researchers have found that variations in a gene related to male sex hormones may be at the root of male-pattern baldness, the most common form of hair loss. The culprit is the androgen receptor gene, and it dwells on the X chromosome, which all men inherit from their mothers. Other, yet-unidentified genes are likely involved in male-pattern baldness, possibly including ones handed down by fathers. But the new findings highlight the importance of mom's side of the family when it comes to a man's hairline.

Female-pattern baldness or female hair loss is less common than male-pattern baldness. Usually, this condition causes the hair to thin in the front, on the sides, or on the crown. It rarely progresses to total hair loss.
Gray Hair
Hair goes gray when melanocytes become depleted. The scalp contains a reservoir of adult stem cells that provide a continuous supply of these color-making cells. But as the body ages these cells become depleted and sometimes begin to develop in the wrong part of the hair follicle. I have not yet come across any credible research regarding the reversal of gray hair with vitamins or supplements.

Hair Research Update
A randomized, double-blind, placebo-controlled trial to determine the effectiveness of botanically derived inhibitors of 5-alpha-reductase in the treatment of androgenetic alopecia.
J Altern Complement Med. 2002 Apr;8(2):143-52. Prager N, Bickett K, French N, Marcovici G.
Clinical Research and Development Network, Aurora, CO, USA.
One contributing factor to androgenic alopecia is the conversion of testosterone (T) to dihydrotestosterone (DHT) via the enzyme 5-alpha reductase (5AR). This metabolism is also key to the onset and progression of benign prostatic hyperplasia (BPH). Here, we report the first example of a placebo-controlled, double-blind study undertaken in order to examine the benefit of these botanical substances in the treatment of AGA. The goal of this study was to test botanically derived 5AR inhibitors, specifically the liposterolic extract of saw palmetto and beta-sitosterol, in the treatment of androgenic alopecia. Subjects: Included in this study were males between the ages of 23 and 64 years of age, in good health, with mild to moderate AGA. RESULTS: The results of this pilot study showed a highly positive response to treatment. The blinded investigative staff assessment report showed that 60% of (6/10) study subjects dosed with the active study formulation were rated as improved at the final visit.

Melatonin increases anagen hair rate in women with androgenetic alopecia or diffuse alopecia: results of a pilot randomized controlled trial.
Br J Dermatol. 2004 Feb;150(2):341-5.
In addition to the well-known hormonal influences of testosterone and dihydrotestosterone on the hair cycle, melatonin has been reported to have a beneficial effect on hair growth in animals. The effect of melatonin on hair growth in humans has not been investigated so far. OBJECTIVES: To examine whether topically applied melatonin influences anagen and telogen hair rate in women with androgenetic or diffuse hair loss. METHODS: A double-blind, randomized, placebo-controlled study was conducted in 40 women suffering from diffuse alopecia or androgenetic alopecia. A 0.1% melatonin or a placebo solution was applied on the scalp once daily for 6 months and trichograms were performed to assess anagen and telogen hair rate. To monitor effects of treatment on physiological melatonin levels, blood samples were taken over the whole study period. RESULTS: Melatonin led to a significantly increased anagen hair rate in occipital hair in women with androgenetic hair loss compared with placebo. For frontal hair, melatonin gave a significant increase in the group with diffuse alopecia. The occipital hair samples of patients with diffuse alopecia and the frontal hair counts of those with androgenetic alopecia also showed an increase of anagen hair, but differences were not significant. Plasma melatonin levels increased under treatment with melatonin, but did not exceed the physiological night peak. CONCLUSIONS: To the authors' knowledge, this pilot study is the first to show that topically applied melatonin might influence hair growth in humans in vivo. The mode of action is not known, but the effect might result from an induction of anagen phase.
Emails regarding hair loss
Q. I read you article on Serenoa repens ( saw palmetto ) and hair loss.... What is your opinion ( I know research is lacking ) on combining Finasteride with Serenoa repens ( saw palmetto ) ---given the former is a type 2 inhibitor whereas the Serenoa repens ( saw palmetto ) is a dual inhibitor would you speculate there may be a beneficial effect on hair loss or an adverse one involving hormonal feedback loops ?
A. You ask a good question. i don't see any obvious harm adding saw palmetto to finasteride, but I honestly don't know whether there would be a synergistic effect. I still am not convinced daily use of finasteride for hair loss or prostate enlargement is safe in the long run. Finasteride may blunt sexuality, but more research is needed.
Q. I know you probably won't be able to answer me, but I am desparate. I am a 43 year old woman and took a 25 mg. DHEA supplement recommended by my doctor. He was not really clear about how long I should take it, nor did he give me any warnings about possible side effects. Unfortunately I took it for 6 months and now am experiencing pretty severe hair loss.
I have lost 50% of my hair in the last 2 months. I really had NO IDEA what I was taking and feel very stupid for not researching this before I took it. My levels were tested on June 23rd and were high (260 in a scale of 14-244). I have stopped the supplement as of 3 weeks ago. Can you give me any hope (at all!) about regaining my hair once the DHEA level drops? I know you won't recommend treatments but if you could direct me to some information I would be grateful. This is causing me unbelievable anxiety.
A. Unfortunately we have had many emails regarding hair loss associated with misuse of DHEA. There is hope that some of the hair, maybe most or all could grow back, but it is impossible to predict. Perhaps some of the herbs as mentioned above could be tried or your doctor could prescribe finasteride for hair regrowth, at least for a few weeks or months.
Q. Is there a way to test if you are an equol producer? ie.. I'm an average joe taking red clover twice a day (for hair loss) but also for prostate health. I would like to know if it's beneficial to me to keep taking this. Also, after reading a couple of the daizden articles, I believe I have experienced my first "hot flash" the other night. It felt as though I was going to be sick, I got real hot then sweat on my forehead. I just thought I had caught a touch of the flu. Anyhow, I'm now thinking that I had a hot flash, becasue I'm taking too much daizden? hard to say, there aren't any guidelines for how much to take. Are the "herbal" drug companies any closer to creating an over the counter equol supplement so us thinning hair people can combad male pattern baldness?
A. You ask good questions and we just don't have enough knowledge at this time to make any firm recommendations.
Q. I receive your Supplement Research Update. Thank you for this free information. Another drug to add to the list of harmful pharmaceuticals is Propecia (Merck) for hair loss. More and more people, myself included, are suffering from the long-term, potentially permanent side-effects of this hair restoring drug. The finasteride side-effects include impotence, loss of libido, hormonal imbalance, and problems with mental clarity. In my opinion, this is the next drug that the public will "blow the lid off of." I hope that Dr. Sahelian would comment on this further in upcoming newsletters. Furthermore, I was wondering if Dr. Sahelian has any recommendations for people who've been affected by Propecia. Is there a way to correct the hormonal imbalance that this drug has caused? Has he helped others with this issue? Is there hope? I belong to a web forum called finasteride-side-effects.com. A brief look at the messages posted here show that hundreds of people (on this site alone) have been affected.
Thanks again for your resource. Any help that you can provide would be a great blessing to many who are dealing with this devastating problem.
A. Even though long term ( 5 year ) studies thus far do not clearly indicate significant side effects from finasteride, I suspect that we will encounter some problems as you mention. A couple of options for improving libido include Passion Rx or Tongkat Ali. For mental clarity, Mind Power Rx is an option.
Q. I am 38 and searched the internet for info on herbal remedies to prevent hair loss. I found anecdotal references on benefits of saw palmetto, zinc, and vitamin B6 p-5-p (pyrodoxal, not pyrodoxine). All three were indicated to fight the effects of DHT's reaction with 5-alpha reductase which can have a harmful effect on hair follicles and cause hair loss. Have you heard anything more "official" on these three supplements for stopping hair loss?
A. As far as I know, there are, as of now, no proven herbal or nutritional therapies for androgenetic hair loss. Some over the counter hormones, such as DHEA, androstenedione, and pregnenolone may cause hair loss or hair thinning in some individuals. I am hoping that future research will indicate that certain herbs or supplements are helpful. Saw palmetto apparently blocks DHT in prostate tissue, it is not clear whether it does so in hair tissue. Fish oils can improve circulation, but I'm not sure if they would be helpful.

Q. What are your thoughts on finasteride for hair growth. Does it have any side effects?
A. Finasteride is a 5alpha-reductase inhibitor approved for the treatment of male pattern hair loss. It was originally approved in 1992 for the treatment of benign prostatic hypertrophy. Finasteride's approval was expanded in 1997 to include the treatment of androgenetic alopecia in men at a dose of 1 mg/day. Finasteride inhibits 5alpha-reductase, thereby prohibiting the conversion of testosterone to dihydrotestosterone (DHT), a hormone that in high amounts accelerates hair loss in some men. Reduction in DHT results in a significant improvement in hair growth and density. Finasteride is usually well-tolerated. The most common side effects are reduced libido, decreased ejaculate volume and gynaecomastia (enlargement of breast tissue). For those who feel they need to rely on finasteride for hair regrowth or to prevent further hair loss, but wish to minimize the side effects, you could consider taking half a 1 mg pill daily as opposed to a full pill. To boost libido, try Passion Rx (see link at top for ray sahelian)
Q. I believe that hair loss can occur due to increased DHT when a male is using testosterone replacement cream. If a person is unable to tolerate finasteride due to the side effects, what would you suggest is the next best solution to this type of hair loss?
A. We're not aware of any good natural options at this time for hair loss.
Q. I am a 56 year old woman. I have come through menopause but lately noticed that my hair is thinning in the front crown area of my head. Do you sell anything that might help it to thicken my hair again?
A. I have been looking into a good hair raising formula and thus far I have not yet found a product that I feel works effectively. But I actively looking, and if I do come across a hair raising formula, I will mention it in the newsletter.
Q. I read your newsletter with great interest. Something puzzles me: you do not mention the effect of biotin on hair growth. I am seventy, a woman, and afflicted with male pattern baldness. A dermatologist recommended 5mg (milligrams) of biotin three times a day. I confimed this with my internist, was told it was all right, but am still a bit uncomfortable with such a high dose. I would appreciate your thought.
A. We have not come across any reliable research regarding biotin supplementation leading to hair growth for those with age related hair loss. If your doctors have such information, we would be glad to review it.
Q. Hair experience - I have some personal experience with taking DHEA in 25 mg doses and also later taking finasteride (Propecia 1mg) for hair loss. There are pros and cons to each. I am a normal 44 year old Caucasian male Navy carrier pilot.
DHEA: I took this at three different times over a few years as part of a workout supplementation program. I found that it increased my energy, libido, ability to lift heavy weight in the gym, and my overall feeling of strength and well being. It also significantly increased the volume and fluidity of my ejaculate and reduced sexual recovery time, letting me "stud out." It reduced joint pain due to lifting weights and trimmed me down somewhat by reducing belly fat. But it very definitely increased the rate of my male-pattern baldness and hair thinning, so I stopped taking it. It also made me irritable, impatient, intolerant, and aggressive as you would imagine with increased testosterone.
Finasteride / Propecia: I just stopped taking this after only 13 days because it made me feel as though my prostate was drying up. It was already visibly changing my hair by increasing the area of growth, but this is not worth the negative side effects. I found it reduced my libido (which I thought would be good but felt unnatural, almost like being neutered), greatly reduced the volume of my ejaculate, induced low back pain and a sense of dryness/pain in my whole prostrate / genital region, increased my belly fat, and made me a bit lethargic.
I never took these two hormones / drugs together. They have opposite effects in my body. DHEA was better except for the hair loss and increased aggression, as well as possible long-term contribution to prostate cancer. The only benefit to finasteride was hair improvement - everything else was very negative. I have normal to high levels of DHEA and testosterone naturally in my body.
Do you plan to do further research on the link between these two drugs? It would be useful to know how one may counteract the effects of the other. I plan to take a little DHEA to get back to neutral after quitting finasteride, then not take either one and letting my body do its own natural thing.
A. We're impressed on how observant you are about the effects of dhea and finasteride. Our own experiences confirm your findings. One option is to take a sexual enhancement product without dhea, and thus get the sexual benefits without the hair loss effects of dhea. We have found in many propecia users that Passion Rx reverses the sexual side effects.
Q. I have been suffering from extreme hair loss ever since puberty. I am 30 years old and I recently got a saliva test for my hormones. My progesterone was very low(46 pg/ml) during the luteal phase, and my DHEAS was very high (15.7 ng/ml). I have been also suffering from acne, itchy scalp, horizontal ridges on my nails. I hardly have any hair left on my scalp. My doctor told me to use natural progesterone cream because my body is unable to make progesterone. I have been using the cream for 12 days a month (30 mg/day) for 3 months now and still there is no improvement.
A. We cannot make individual recommendations, but the information on this hair web page and the page on acne should be helpful to you. The prescription of hormones bases on saliva tests is no always reliable.
Q. Can a person take Passion Rx if they are taking finasteride Propecia or Avodart for hair loss? I find Propecia reduces sensation and makes me lose interest in sex.
A. Yes, we have found that Passion Rx reverses the sexual side effects from Propecia and you may take Passion Rx if your doctor approves. Avodart is also known to reduce libido and sexual drive.
Q. I saw an advertisement on the internet for a product called Advecia which is supposed to help with hair loss. Do you have an Advecia review? Does Advecia really work for hair loss?
A. We don't have an Advecia review but can comment on the ingredients in Advecia as mentioned on their website. The Advecia website claims this product is a restorative formula for bald or thinning hair. There is a question on the website that asks, "Can Advecia assist in your individual pursuit for slowing hair loss? And they answer, "Yes." I cannot find any clinical trials with Advecia mentioned on their website. The ingredients in Advecia are saw palmetto, beta sitosterol, green tea extract, lysine, arginine, and grape seed extract. These are good nutrients and herbs, but I seriously doubt whether Advecia has a significant impact on hair loss or hair growth. The burden of proof lies with the advecia sellers and they have not provided this proof before making these claims. There is not good evdience that saw palmetto can block 5 alpha reductase is a sufficient manner in hair follicles to prevent hair loss or restore hair loss. Therefore, at this time, Advecia appears like another one of those "me too" natural hair loss product heavily advertised with no proof of effectiveness. You can find the invidivual herbs sold separately for much cheaper. There seems to be a negligible amount of saw palmetto in Advecia and a high amount of green tea extract. Until Advecia sellers present a couple of human studies proving that Advecia administration reversed hair loss, your money is better spent somewhere else. There is also a possibility of Advecia side effects with too much green tea, especially when the Advecia web site recommends taking two Advecia capsules in the evening. This could cause an Advecia side effect of insomnia.
Q. I read recently that too much of a particular supplement could cause hair loss. I have noticed lately that more hair than usual is falling out. I basically take Juice Plus as my daily supplement but also take Alpha Lipoic Acid and Wild Salmon (Omega 6) oil supplement. I read that I should not take ALA and Omega 6 together and have stopped. I also read in your newsletter that I should only take 30 to 50 mg a day of ALA, I was taking 300 for several years, but recently stopped and now only take 50 mg every other day or so. I also stopped taking my calcium supplement with enzymes because I thought they were making me constipated. I read that lack of calcium could cause hair loss. I just want to nip this in the bud before too much hair falls out. I also started using nioxin hoping that would help. So please tell me if too much of what I take could cause hair loss. PS. Your newsletters are a life saver. I have gained so much more knowledge by reading them and thank you for your wisdom. I started taking ALA because Dr. Nicholas Perricone said it was great for the skin and helped aging of the skin but appreciated reading in your newsletter that less is more.
A. I hope this web page can help you with some suggestions. High doses of vitamin A can cause hair thinning. DHEA, pregnenolone, and androstenedione can cause hair loss.
Q. In the research you mentioned about use of melatonin for hair loss in women, a "melatonin solution" was applied to the scalp once daily for 6 months. How would one go about making a melatonin solution for hair loss?
A. We have not looked into this matter in any detail at this time.

hair loss
Natural Treatment Options for Migraine and Tension Headache
Subscribe to a FREE Supplement Research Update newsletter by Ray Sahelian, M.D.

Migraine and tension headaches are among the most common medical problems. Some people have frequent headaches, while others hardly ever have them. Both chronic and recurring headaches may be painful and distressing but rarely reflect a serious medical condition. However, a change in the pattern or nature of headaches -- for instance, from rare to frequent headache, or from mild to severe -- could signal a serious problem and calls for prompt medical attention.
Cause of Frequent Headaches
Emotional or physical stress, genetic, hormone level fluctuations, weather changes, glare/flickering lights, premenstrual syndrome, lack or excess sleep, missed meals, alcohol, chocolate, birth control pills, menstruation all can cause headache. Drugs such as antibiotics (tetracycline, Bactrim) corticosteroids, Accutane, tamoxifen, Tagamet are also known to cause frequent headache.
Most chronic headaches are muscle tension headaches, migraines, or head pain with no obvious cause. Many headaches are related to problems with the eyes, nose, throat, teeth, and ears. Most chronic headaches attributed to eyestrain are actually tension headaches; a new, severe pain in or around the eyes may signal high fluid pressure (glaucoma) in the eye and is a medical emergency. High blood pressure may produce a throbbing sensation in the head, but high blood pressure rarely causes chronic headaches. Estrogen is likely in involved in migraine headaches.

Migraine Headache Treatment -- simple suggestions for headache relief
Wake up at the same time each morning.
Exercise at least 3 times a week. Exercise stimulates endorphins.
No smoking, no caffeine after 3 pm.
No artificial sweeteners.
No MSG (monosodium glutamate).
Reduce or eliminate red wine, cheese, alcohol, chocolate, and caffeine.
Try a gluten free diet.

Nutrients and Herbs potentially helpful in migraine headache
I am currently not aware of any herbs or supplements that are a headache cure

Petasites also known as butterbur
5-HTP may be helpful (see below)
Feverfew may help a small percentage of users. 1 capsule 3-4 x/day for one month, then decrease dosage to 25 mg of dried herb twice daily.
Magnesium
CoQ10 - see study below
Melatonin may reduce migraine headaches.
Biofeedback
Aspirin may help in acute migraine headache

Subscribe to a FREE Supplement Research Update newsletter. Twice a month we email you a brief abstract of several new studies on various supplements and natural medicine topics, including migraine and tension headache, and their practical interpretation by Ray Sahelian, M.D. See link at top of page.
Headache Diagnosis
Usually a doctor can determine the cause of a headache from the patient's medical history and a physical examination. However, occasionally blood tests may be needed to detect an underlying illness. Only rarely are chronic headaches caused by brain tumors, brain injuries, or lack of oxygen to the brain. If the doctor suspects a tumor, stroke, or other problem with the brain, computed tomography (CT) scanning or magnetic resonance imaging (MRI) may be ordered to provide images of the brain.
Exercise Your Head
An exercise program that helps retrain the muscles of the head, neck and shoulder area reduce the frequency, intensity and duration of tension headaches. The exercises are easy to perform and take little time, and are effective. Many people treat such headaches with over-the-counter pain relievers, putting themselves at risk for experiencing "rebound" headaches when the medication is stopped. A craniocervical training program (CTP), in which a person performs a series of exercises to restore effective control of the muscles in the head, neck and shoulders, could be helpful against tension headaches. Researchers randomized 81 tension headache sufferers to six weeks of physiotherapy including massage and other techniques (the control group), or to the same physiotherapy program plus CTP (the experimental group). People in the craniocervical training group underwent 15 minutes of instruction on the technique, which involves flexing the head and neck with light resistance supplied by a latex band. They were then told to perform the exercises at home for 10 minutes twice daily. During the six-week program, headache frequency, intensity and duration fell in both groups, with no significant between-group differences. However, headaches had worsened among people in the control group by six months after the end of the exercise program. At the end of the exercise program, 52 percent of people in the control group experienced a 50 percent or more reduction in headache frequency, but just 35 percent had this amount of reduction in headache frequency six months later. In the CTP group, however, 82 percent saw a reduction of 50 percent or more in headache frequency at the end of the exercise program, and 85 percent saw this reduction six months later. Six months after the program, people in the CTP group were taking 65 percent less medication than they were before the study, while the control group showed no reduction in painkiller intake. Cephalalgia, August 2006.

Medical Treatment of Headache
Excedrin migraine
Beta blockers
Tricyclic antidepressants
Prochlorperazine
Cafergot
NSAIDs
Triptans - There are several so-called triptan drugs designed for treating migraines -- and if one doesn't work, another might.

5-HTP beneficial for headaches
Serotonin is a brain chemical involved in mood, appetite control, sleep, and a number of other important functions. Many antidepressants, such as Prozac, and other medicines have their effects by influencing levels of this brain chemical. Interestingly, there is an over the counter nutrient called 5HTP, which stands for -5-hydroxytryptophan, that also influences serotonin levels. When you take a 5-HTP pill, it makes its way to the brain where it can be converted into serotonin. In addition to having a role to play in mood disorders and weight control, 5-HTP has been found to be helpful in headaches. In a study conducted at the University of Coimbra in Portugal , 65 patients with chronic tension-type headaches were treated with 5-HTP or placebo for 8 weeks. In comparison with the group treated with placebo, there was no statistically significant change in the number of days with headache or in headache intensity in the group treated with 5-HTP; however, there was a significant decrease in the consumption of pain killers. During the 2 weeks after treatment, there was a significant decrease in the number of days with headache and reports from patients indicated that they were pleased with the benefits from 5-HTP. Previous studies have also indicated that 5-HTP may be helpful in the prevention or reduction in severity of migraine-type headaches.
Dr. Sahelian comments: 5-HTP is appropriate for those who have headaches associated with mild depression and poor appetite control. The daily dose is best limited to less than 50 mg. Take a break from use two days a week and one week per month.
Tension Headache and Migraine Headache Research Update
A type of movement therapy designed to promote relaxation may help chronic headache sufferers deal with their pain. The study of 33 adults with frequent tension-type headaches or migraine found that the therapy -- known as the Trager approach -- appeared to reduce bouts of head pain and help patients cut back on medication. The Trager method, named for its founder, Dr. Milton Trager, is a mind-body type of movement therapy that aims to reduce the tension that people unconsciously hold in their bodies. It involves massage-like sessions in which a practitioner certified in the technique gently moves and stretches the muscles and joints to try to relax the body. Patients are also taught sequences of movements to do at home. The Trager approach is promoted for treating lower back pain and other musculoskeletal woes, but the new study is the first to evaluate its effectiveness against chronic headache.
Efficacy of coenzyme Q10 in migraine headache prophylaxis: a randomized controlled trial.
Neurology. 2005 Feb 22;64(4):713-5.
Riboflavin, which improves energy metabolism similarly to coenzyme Q10 (CoQ10), is effective in migraine headache prophylaxis. We compared CoQ10 (3 x 100 mg/day) and placebo in 42 migraine headache patients in a double-blind, randomized, placebo-controlled trial. CoQ10 was superior to placebo for attack-frequency, headache -days and days-with-nausea in the third treatment month and well tolerated; 50%-responder-rate for attack frequency was 14.4% for placebo and 47.6% for CoQ10 (number-needed-to-treat: 3). CoQ10 is efficacious and well tolerated for migraine headache.
A combination of riboflavin, magnesium, and feverfew for migraine prophylaxis: a randomized trial.
Headache. 2004 Oct;44(9):885-90.
To determine the efficacy for migraine prophylaxis of a compound containing a combination of riboflavin, magnesium, and feverfew. Previous studies of magnesium and feverfew for migraine prophylaxis have found conflicting results, and there has been only a single placebo-controlled trial of riboflavin. Randomized double-blind placebo-controlled trial of a compound providing a daily dose of riboflavin 400 mg, magnesium 300 mg, and feverfew 100 mg. The placebo contained 25 mg riboflavin. The study included a 1-month run-in phase and 3-month trial. The protocol allowed for 120 patients to be randomized, with a preplanned interim analysis of the data after 48 patients had completed the trial. RESULTS: Forty-nine patients completed the 3-month trial. For the primary outcome measure, a 50% or greater reduction in migraines, there was no difference between active and "placebo" groups, achieved by 10 (42%) and 11 (44%), respectively (P=.87). Similarly, there was no significant difference in secondary outcome measures, for active versus placebo groups, respectively: 50% or greater reduction in migraine days (33% and 40%, P=.63); or change in mean number of migraines, migraine days, migraine index, or triptan doses. Compared to baseline, however, both groups showed a significant reduction in number of migraines, migraine days, and migraine index. This effect exceeds that reported for placebo agents in previous migraine trials. CONCLUSION: Riboflavin 25 mg showed an effect comparable to a combination of riboflavin 400 mg, magnesium 300 mg, and feverfew 100 mg. The placebo response exceeds that reported for any other placebo in trials of migraine prophylaxis, and suggests that riboflavin 25 mg may be an active comparator. There is at present conflicting scientific evidence with regard to the efficacy of these compounds for migraine prophylaxis.
Endometriosis -- caused when tissue that normally lines the uterus grows at other sites -- may produce more than pelvic pain. It seems to increase the risk of migraine headache. Previous reports have linked endometriosis with a variety of disabling conditions, such as autoimmune diseases, chronic fatigue syndrome, and fibromyalgia.

Types of Headache
Cluster headache
Sinus headache
Migrane headache

Migraine Headache
Certain weather conditions indeed appear to increase the risk of migraine, but people still tend to overestimate weather's influence on their headache. The most common conditions people believed caused their migraines included rain, bright sunshine, high humidity and hot temperatures.
New research involving male-to-female transsexuals lends further credence to the theory that sex hormones, such as estrogens, are involved in migraine generation. It is well known that migraine headaches are more common in women than men. Questionnaires were sent regarding headache symptoms and frequency to 50 transsexuals who had recently undergone sex reassignment surgery, all of whom were taking hormonal therapy. Thirteen (26 percent) fulfilled criteria for migraine or probable migraine, similar to the number of cases of migraine in genetic females that would be expected. In contrast, the expected number of cases of migraine headache in genetic males is significantly lower.
People who suffer from migraine headaches appear to express more genes that produce platelets, the specialized components in blood that are involved in clotting.

Migraine Headache symptom
A migraine headache is a severe head pain, often on one side of the head, and frequently described as throbbing in nature. Migraine attacks may include nausea and vomiting, photophobia (intolerance to light) and sometimes intolerance to noise. Migraines are usually recurrent and episodes can last anywhere between several hours to 3 days. A migraine attack has the potential to temporarily disable a person, and can interfere with work or interpersonal relationships.
Airplane Headache
Severe headaches that develop during airplane travel appear to be the result of rapid changes in pressure, rather than the high altitude or other causes.
Headache emails
Q. Just thought I'd thank you for your advice on 5-HTP and chronic > headaches. I have had these periodically for much of my adult life. (I am now 55.) They seem to come in cycles--or at least when they effect me if will be each day for a few weeks, then they mysteriously will go away for a few months. I have NEVER found anything that will remove them, and I've tried lots-- Fish oil, Evening Primrose, Vit C, B-complex, E, calcium, magnesium -in large doses beyond just regular amounts; over-the -counter drugs; caffeine; no caffeine, anti-histamines, avoidance of foods, etc. (Never tried prescription meds for this as I stay away from them , if I can help it.) Ginkgo,
Feverfew.... Etc. Etc. Etc!
With this headache pain, which always starts early in the morning (and sometimes goes away by evening, only to be back again the next day,) there would be stiffness down the back of my neck and shoulders; mild depression, fuzzy and backward thinking; tiredness, sadness, lack of motivation and self-esteem; loss of creativity (hard to cope with as I am artistic by nature and trade;) any aches and pains seemed amplified. I could always function with basic duties, but could not think beyond that. This took chunks of time out of my life and made me unproductive beyond the basics. I also get restless legs,( which I have had since childhood,) tho not always at the same time as the chronic headache. I have one daughter (out of 4 children) who experiences very similar symptoms but more migraine headaches, plus more depression and occasional anxiety attacks and sleep problems (this was worse during puberty She is 18 now.). Different forms of mental problems run in my mother's side of the family--Bi-polar, Anxiety, Obsessive/compulsive, Depression, in several relatives. HOWEVER, we tried 5-HTP and both of us found a very marked and rapid difference. I opened a capsule of 50 mg. and took it sublingually. In about 45 minutes it made such a difference! My mood brightened, energy was boosted, and most of the pain in my neck and shoulders and head went away (I had had this for about 4-5 days this time.) I took another 50 mg. All pain and other symptoms were soon gone. That was the first day. Since then I have used only 50 mg, some times splitting it into 2 doses. (This was because it was back again in the morning.) I am mindful of warnings not to overdo taking 5-HTP, also I don't want it to stop working, or build up a tolerance, or an increased need, etc. . I intend to only use it when I am in these cycles, and only the smallest dose necessary. (Sublingual method works best for this.) My daughter took 150 mg, divided, the first day, and 100 or 50 mg. on subsequent days. She will, I think, need to experiment a bit, BUT--she had had a migraine for three days and the first day's dosage removed it so that she was migraine free the next day. She has tried (reluctantly, esp. on my part) several migraine remedies, and 13 (Yes, 13!) anti-depressants over a few years, which gave her bad side effects and never helped the problems.
So you can see that we are excited about 5-HTP! I did a lot of reading about it and information on serotonin deficiency , and some people's receptors being too short and thus not sensitive (and how this can be genetic,) etc. We intend to be prudent with its useage, so it can continue working well for us, as it is the ONLY thing that
has helped. I myself have had this headache come and go for 30 years, so I am happy to find something that made a difference. And as a parent, I am thrilled to have found something that can help my daughter not experience such disturbing symptoms. Perhaps this can help someone else, too. Thank You!
A. We are really glad 5-htp is working for you and it appears you are using it prudently. Please keep us updated.

Frequent Headache
Hormone by Ray Sahelian, M.D. (natural medicine and health database)
Hormones are chemical messengers that control and coordinate the functions of all tissues and organs. Each hormone is secreted from a particular gland and distributed throughout the body to act on tissues at different sites.
A number of natural hormones regulate body functions, including growth and development, metabolism, and reproduction. Numerous glands throughout the body produce hormones. The hypothalamus produces several releasing and inhibiting hormones that act on the pituitary gland, stimulating the release of pituitary hormones. Of the pituitary hormones, several act on other glands located in various regions of the body, whereas other pituitary hormones directly affect their target organs. Other hormone -producing glands throughout the body include the adrenal glands, which primarily produce cortisol; the gonads (i.e., ovaries and testes), which produce sex hormones such as estrogen and testosterone; the thyroid, which produces thyroid hormone; the parathyroid, which produces parathyroid hormone; and the pancreas, which produces insulin and glucagon. Many of these hormones are part of regulatory hormonal cascades involving a hypothalamic hormone, one or more pituitary hormones, and one or more target gland hormones.
Subscribe to a FREE Supplement Research Update newsletter. Twice a month you will receive an email of several studies on various supplements and natural medicine topics, including hormone research, and their practical interpretation by Ray Sahelian, M.D.



Alphabetical listing of Hormones:

Adiponectin - Low levels of a hormone secreted by fat cells, independent of body mass index (BMI) -- a measure of obesity -- are associated with an increased risk of colorectal cancer in men. Previous reports have linked body fat and insulin resistance with colorectal cancer risk. Adiponectin, an insulin-related hormone secreted by fat cells, is inversely associated with both these factors.
Adrenocorticotropic hormone ACTH -
Agouti related peptide
Aldosterone
Amylin is a hormone released by the pancreas. Amylin is released during meals, and exogenous amylin leads to a dose-related reduction in meal size. Amylin has a rapid onset and brief duration of action.
Amylase
Androgen hormones such as androstenedione, testosterone, and DHT - Excess androgen hormones can lead to hair loss and acne.
Androstenedione is a steroid hormone made from DHEA. Androstenedione can convert into testosterone and estrogen.
Angiotensin hormone from kidney
Antidiuretic hormone
Atrial natriuretic peptide used for therapy of heart failure
Cholecystokinin - CCK -
Calcitonin is a naturally occurring peptide hormone which acts via specific receptors to strongly inhibit osteoclast function. It has been used in the treatment of osteoporosis for many years. Historically, calcitonin was administered as a parenteral injection, but the intranasal formulation is now the most widely used because of its improved tolerability.
Corticotropin-releasing hormone - CRH -
Cortisol - this adrenal gland hormone - also called the stress hormone - is available synthetically under various names including dexamethasone, prednisone, triamcinolone, fluocinolone. High levels of cortisol can lead to a condition known as Cushing's syndrome. Stress releases more cortisol which makes it more likely to succumb to infections, even as simple as yeast infections. Those with Addison's disease have little or no cortisol production.
Desmopressin
DHEA hormone - Secreted by the adrenal cortex, the hormone DHEA - dehydroepiandrosterone - exerts its action either indirectly in peripheral tissues after its conversion to androgens and estrogens, or directly as a neurosteroid through the interaction with neuronal receptors. Analyses of randomized studies show that treatment with DHEA improves well-being and fatigue in patients with adrenal insufficiency and reduces disease activity in women with systemic lupus erythematosus. Interesting results with this hormone have also been observed in the treatment of depressive disorders, but these studies require confirmation. In contrast, there is neither justification for DHEA supplementation in healthy elderly subjects nor clear evidence for beneficial effects of DHEA on muscle function, bone metabolism or cognition. Finally, there is no guarantee with regard to the quality of this hormone product or its safety during long term use.
Dihydrotestosterone - also known as DHT, this hormone is a metabolite of testosterone. High DHT hormone levels could lead to hair thinning and hair loss.
Erythropoietin
Estrogen hormone -- This female hormone, actually men have estrogen also, is quite controversial when it comes to hormone therapy or replacement. Excess estrogen can lead to blood clots and increased risk of breast cancer. Reduction in the use of estrogen hormone (such as Premarin) by post menopausal women could potentially reduce the risk of breast cancer. There are several estrogen hormones including estradiol, estrone, and estriol. Estrogen is called the female hormone even though men have estrogen in their bodies, too.
Follicule Stimulating Hormone or Follicular stimulating hormone - FSH hormone. Older women are more likely to conceive twins because rising concentrations of ollicle stimulating hormone (FSH) over-stimulate their ovaries. Identical twins come from a fertilized egg dividing to develop two babies. Non-identical twins occur when two eggs are fertilized at the same time.
Gastrin
Ghrelin-- Small synthetic molecules called growth hormone secretagogues (GHSs) stimulate the release of growth hormone from the pituitary gland. Scientists have purified an endogenous ligand for GHS-R from rat stomach and named it "ghrelin," after a word root ("ghre") meaning "grow." Ghrelin is a peptide hormone in which the third amino acid, usually a serine but in some species a threonine, is modified by a fatty acid; this modification is essential for ghrelin's activity. The discovery of ghrelin indicates that the release of growth hormone from the pituitary might be regulated not only by hypothalamic growth hormone -releasing hormone, but also by ghrelin derived from the stomach. In addition, ghrelin stimulates appetite by acting on the hypothalamic arcuate nucleus, a region known to control food intake. Ghrelin is secreted from the stomach and circulates in the bloodstream under fasting conditions, indicating that it transmits a hunger signal from the periphery to the central nervous system. Taking into account all these activities, ghrelin plays important roles for maintaining growth hormone release and energy homeostasis.
Gonadotrophin - human chorionic gonadotropin - HCG serves to maintain progesterone production by the corpus luteum in the early part of pregnancy. By the time HCG drops at the beginning of the second trimester, the placenta can make sufficient progesterone to maintain the endometrium. HCG also stimulates the development of fetal gonads and synthesis of androgens by the fetal testes. HCG has a similar to function to LH in stimulating secretion of estrogen and development of the placenta.
Gonadotropin-releasing hormone -
Glucagon
HCG hormone
Human Growth Hormone -- HGH -- This controversial hormone has gotten a lot of press. Over the counter human growth hormone supplements or products are worthless since only the prescription human growth hormone injection is effective. Even then, hormone replacement with aging with human growth hormone is risky, expensive, and it may even lead to premature death. Excess growth hormone leads to a condition known as acromegaly. Additional human growth hormone side effects include elevated blood sugar and carpal tunnel syndrome. Human growth hormone releasers have not been studied enough to come to firm recommendations. Growth hormone deficiency can occur in children, and in this case human growth hormone therapy is appropriate. Growth hormone releaser supplements are marketed widely but little proof exists of any long term benefit.
Inhibin B - In adult men, inhibin B regulates follicle stimulating hormone secretion by a negative feedback.
Insulin - this hormone is released by the pancreas.
insulin-like growth factor -- The insulin/insulin-like growth factor 1 (IGF-1) signaling pathway is evolutionarily conserved in diverse species including C.elegans, saccharomyces cerevisiae, Drosophila melanogaster, rodents and humans. Insulin-like growth factor is involved in many interrelated functions that are necessary for metabolism, growth and reproduction. Interestingly, more and more research has revealed that insulin/IGF-1 signaling pathway plays a pivotal role in the regulation of longevity. Generally, disruption of the power of this pathway will extend longevity in species ranging from C.elegans to humans.
Leptin - leptin is a hormone that is secreted from adipocytes (fat cells) and functions to suppress appetite and increase energy expenditure. Leptin is a proinflammatory cytokine.
Lipase
Luteinizing hormone
Luteinizing hormone releasing hormone
Melanin concentrating hormone
Melanocortins
Melatonin - called the sleep hormone
Motilin
Neuropeptide Y
Neurotensin
Obestatin - Researchers from Stanford University School of Medicine in California have discovered a hormone, which they call obestatin, that suppresses appetite and produces weight loss in rats. Interestingly, the hormone is derived from the same gene that gives rise to ghrelin, a well-known appetite-inducing hormone.
Orexins
Oxyntomodulin hormone - Oxyntomodulin is a hormone found in the gut could help reduce appetite and increase physical activity in overweight and obese people. Injections of oxyntomodulin to 15 overweight but healthy volunteers aged 23 to 49. Those given oxyntomodulin hormone by injection ate fewer calories.
Oxytocin hormone - Exposing people to the hormone Oxytocin makes them more willing to bond with others. The same people exposed to the hormone but faced with a computer did not show increased willingness to take risks. specifically affects an individual's willingness to accept social risks arising through interpersonal interactions. It is hardly surprising. Oxytocin -- also known as the "cuddle" hormone -- is released by both men and women at sexual orgasm, and the bloodstream levels have been shown to rise during massage but fall with recollection of a negative emotion. Intranasal administration of Oxytocin causes a substantial increase in trusting behavior.
Parathyroid hormone
Peptide YY
Pheromones
Pregnenolone hormone-
Progesterone - this hormone is available in a synthetic form known as progestin
Prolactin hormone is one of the reproductive hormones
Renin from kidney
Secretin
Somatostatin
Somatropin - human growth hormone
Steroid hormones include all natural hormones made by the adrenal gland, such as pregnenlone, DHEA, testosterone, cortisol, etc. Steroid hormones also include many synthetic hormones.
Substance P
Testosterone hormone - high amounts of testosterone hormone, especially during hormone replacement in men, may increase the risk for prostate cancer. Testosterone is called the male hormone even though women have this hormone, too.
Thyroid gland hormone - thyroid hormones T4 and T3, also known as thyroxine. Too little thyroid hormone leads to hypothyroidism, and too high a level of thyroid hormone leads to hyperthyroidism.
Thyroid stimulating hormone
Vasopressin
Hormone Replacement Therapy
Hormone replacement therapy is controversial, and there are no clear cut widely acceptable guidelines. Each person, whether male or female, is unique in their requirement for hormone replacement with aging. Most people do not need hormone replacement, and if they do, tiny amounts of natural hormone DHEA or pregnenolone should be adequate. Bioidentical - or bio identical - hormones are preferable to synthetic hormones. For instance, natural hormone replacement with estrogen is preferable than using estrogen from animals, such as horse estrogens (Premarin) or synthethic estrogens.

Hormone imbalance
Hormone imbalance has many causes including obesity, drugs, supplements, herbs, stress, or various medical or psychiatric conditions. Hormone imbalance symptom varies depending on which hormones are out of balance. Certain hormone levels can be measured.

Hormone saliva test -- Hormone Testing
Since different labs have somewhat different standards for hormone saliva tests, sometimes the results of hormone tests are difficult to interpret. A hormone doctor - an endocrinologist - is an expert on hormone test interpretation.
Adrenal Hormones
Androstenedione
Cortisol
DHEA
Pregnenolone
Progesterone
Testosterone
Hypothalamic Peptide Hormones
The hypothalamus produces several releasing and inhibiting hormones that act on the pituitary gland, stimulating the release of pituitary hormones. Neuropeptide Y (NPY), Melanocortins, Agouti related peptide (AGRP), Cocaine and amphetamine regulated transcript (CART), Melanin concentrating hormone (MCH), Orexins and endocannabinoids.

Kidney Hormones
Angiotensin
Renin

Pancreatic Hormones
Insulin
Glucagon

Pituitary Gland Hormones
Of the pituitary hormones, several act on other glands located in various regions of the body, whereas other pituitary hormones directly affect their target organs.
Pituitary tumors cause symptoms by secreting hormones (prolactin, PRL, responsible for amenorrhea-galactorrhea in women and decreased libido in men; growth hormone, GH, responsible for acromegaly; adrenocorticotropic hormone, ACTH, responsible for Cushing's syndrome; thyroid-stimulating hormone, TSH, responsible for hyperthyroidism), depressing the secretion of hormones (hypopituitarism), or by mass-related effects (headaches, visual field abnormalities...). As you can see, the pituitary gland makes many hormones.
Adrenocorticotropic hormone
Growth hormone
Melatonin
Prolactin
Thyroid-stimulating hormone
Pro hormone
A pro hormone is a hormone that converts into another hormone.

Pregnancy hormone
There are two types of pregnancy tests - blood and urine tests. Both tests look for the presence of hCG - human chorionic gonadotropin -, the pregnancy hormone. Today, many women use a urine test, or home pregnancy test (HPT), to find out if they are pregnant. HPTs do not cost a lot, are easy to use, can be done at home, and are private.

Hormone pill
People normally refer hormone pill to mean estrogen or progesterone for hormone replacement therapy during hormone change after menopause. However many hormones come in pill form.

Endocrine - hormones arrive by blood stream, secreted from a distant site
Insulin- controls glucose metabolism
Gastrin- stimulates gastric acid secretion and promotes growth of gastric and intestinal cells
Secretin- stimulates pancreatic secretion of fluid and bicarbonate, the liver to produce bile, and the stomach to produce pepsin
Motilin- regulates peristalsis and secretion between meals
Paracrine- hormones released locally
Substance P- influences secretion, absorption, blood flow, motility, and immunology
Hormones that can act as endocrine or paracrine substances
CCK- signal for gallbladder contraction, pancreatic secretion (and growth), & satiety
Somatostatin- inhibits secretion by gut cells, nerves, and hormone secreting cells
Neurotensin- increases blood flow & stimulates secretion.
What is a Prohormone? Some people spell it as Pro Hormone
A prohomoneis a substance that can be converted into a hormone. A prohormone usually is much less potent than the hormone it converts into. The term prohormone has been used in medical science probably since the 1950s. Examples of prohormones include proinsulin and pro-opiomelanocortin. Some people consider DHEA to be a prohormone although this is controversial.
In the last three decades, prohormone has also been used in the subculture of athletic, and nonmedical use of anabolic steroids and other hormones to refer to a product sold with the expectation of conversion after ingestion to an active hormone. Some marketers of prohormone supplements mislead the buyer to assume this prohormone product will provide the benefits of taking an anabolic steroid with less risk than taking the actual hormone. A typical prohormone is marketed to the consumer as a precursor of an anabolic steroid like testosterone, which is taken in order to boost the body’s available hormone supply.
Hormones and Food Intake
Gastrointestinal tract (GIT) and nervous system, both central (CNS) and enteric (ENS), are involved in two-way extrinsic communication by parasympathetic and sympathetic nerves, each comprising efferents fibers such as cholinergic and noradrenergic, respectively, and afferent sensory fibers required for gut-brain signaling. Afferent nerves are equipped with numerous sensors at their terminals in the gut related to visceral mechano- chemo- and noci-receptors, whose excitations may trigger a variety of visceral reflexes regulating GIT functions, including the appetitive behavior. Food intake depends upon various influences from the CNS as well as from the body energy stores (adipocytes) that express and release the product of Ob gene, leptin hormone, in proportion to fat stored and acting in long-term regulation of food intake. Leptin hormone acts through receptors (Ob-R) present in afferent visceral nerves and hypothalamic arcuate nucleus (ARC), whose neurons are capable of expressing and releasing neuropeptide Y (NPY) and agouti related protein (AgRP) that activate the ingestive behaviour through paraventricular nucleus (PVN) (iVfeeding centerli). In addition, to this long-term regulation, a short-term regulation, on meal-to-meal basis, is secured by several gut hormones, such as cholecystokinin (CCK), peptides YY (PYY) and oxyntomodulin (OXM), released from the endocrine intestinal cells and acting via G-protein coupled receptors (GPCR) either on afferent nerves or directly on ARC neurons, which in turn inhibit expression and release of food-intake stimulating NPY and AgRP, thereby inducing satiety through inhibition of PVN. In contrast, during fasting, the GIT, especially oxyntic mucosa, expresses and releases appetite stimulating (orexigenic) factors such as ghrelin and orexins (OX) -A and OX-B, and cannabinoid CB1 agonist. Ghrelin activates growth-hormone secretagogue receptor (GHS-R) in hypothalamic ARC and stimulates growth hormone (GH) release and in vagal afferents to promote the expression and release of hypothalamic NPY and AgRP stimulating PVN and driving ingestive behaviour. The balance and interaction between anorexigenic (CCK, PYY, OXM) and orexigenic (ghrelin and OX) factors originating from GIT appears to play an important role in short-term regulation of food intake and growth hormone (GH) release. An impairment of this balance may result in disorders of feeding behaviour and weight gain (obesity) or weight loss (cachexia).
Insect hormones
Ecdysteroids are compounds related to 20-hydroxyecdysone, the insect moulting hormone. See ecdysterone for more information.
Hormone Research Update

Estrogen Hormone Research
Plasma sex hormone concentrations and subsequent risk of breast cancer among women using postmenopausal hormones.
J Natl Cancer Inst. 2005 Apr 20;97(8):595-602.
BACKGROUND: Sex hormone concentrations are associated with breast cancer risk among women not using postmenopausal hormones. We conducted a prospective, nested case-control study within the Nurses' Health Study (NHS) cohort to examine the association between plasma sex hormone concentrations and postmenopausal breast cancer among women using post menopausal hormones at blood collection. CONCLUSION: Although women using hormones have a different hormonal profile than those not using hormones, plasma sex hormone concentrations appear to be associated with breast cancer risk among post menopausal hormone users.
Human Growth Hormone Research
One year of Human growth hormone replacement therapy with a fixed low-dose regimen improves body composition, bone mineral density and lipid profile of GH-deficient adults.
Eur J Endocrinol. 2005 Jan;152(1):67-75.
We have studied the effects on body composition and metabolism of a fixed low dose of Human growth hormone, 0.6 IU (0.2 mg)/day, administered for 12 months to Human growth hormone-deficient adults. DESIGN AND METHODS: Prospective open-label study, using 18 Human growth hormone deficient patients (11 women, 7 men; aged 21-58 years). All investigations were performed at baseline and after 12 months. Body composition was determined by dual energy X-ray absorptiometry. RESULTS: Total body fat decreased (-1.74+/-2.87%) and lean body mass (LBM) increased (1.27+/-2.08 kg) after therapy. Changes in truncal fat did not reach statistical significance, but a decrease varying from 0.72 to 2.78kg (1 to 8.7%) was observed in 13 (72%) patients. Bone mineral density (BMD) increased at lumbar spine, total femur and femoral neck (P < 0.05). Levels of total and low-density lipoprotein (LDL)-cholesterol were lower after therapy (P < 0.05), and their changes were directly associated with values at baseline. Insulin levels increased and the insulin resistance index worsened at 12 months (P < 0.05). Side effects were mild and disappeared spontaneously. CONCLUSIONS: One-year of a fixed low-dose Human growth hormone regimen in Human growth hormone deficient adults resulted in a significant reduction in body fat, total cholesterol and LDL-cholesterol, and a significant increase in LBM and BMD at lumbar spine and femur, regardless of normalization of IGF-I levels. This regimen led to an elevation of insulin levels and a worsening of the insulin resistance index. Human growth hormone treatment attenuates age-related changes in hippocampal short-term plasticity and spatial learning.
Hypothalamic Hormones
The hypothalamus and obesity.
Curr Drug Targets. 2005 Mar;6(2):225-40.
Obesity, a condition already at epidemic proportions in the developed world, is largely attributable to an indulgent lifestyle. Biologically we feel hunger more acutely than feeling "full-up" (satiety). The discovery over a decade ago of leptin, an adiposity signal, revolutionised our understanding of hypothalamic mechanisms underpinning the central control of ingestive behaviour. The structure and function of many hypothalamic peptides (Neuropeptide Y (NPY), Melanocortins, Agouti related peptide (AGRP), Cocaine and amphetamine regulated transcript (CART), Melanin concentrating hormone (MCH), Orexins and endocannabinoids) have been characterised in rodent models. The pharmacological potential of several endogenous peripheral peptides released prior to, during and/or after feeding are being explored. Short-term signal hormones including Cholecystokinin (CCK), Ghrelin, Peptide YY (PYY(3-36)) and Glucagon-like peptide 1 (GLP-1) control meal size via pathways converging on the hypothalamus. Long-term regulation is provided by the main circulating hormones leptin and insulin. These systems among others, implicated in hypothalamic appetite regulation all provide potential "drugable" targets by which to treat obesity.
Alternative Hormone Therapy
U.S. regulators have issued warnings in November 2005 to dozens of companies that are promoting unproven "alternative" hormone therapies for women. The government has sent letters to about 50 firms and Web sites that market supplements and creams as alternatives to hormone replacement therapy, warning them against making baseless claims that the treatments can help with serious diseases such as cancer, heart disease and osteoporosis. Hormone Replacement Therapy (HRT) aims to replace hormones diminished by menopause and is prescribed to women to relieve menopause symptoms such as hot flushes, night sweats and mood swings. However, millions of women have stopped taking the therapy and sought alternatives after learning in recent years that HRT can raise the risk of heart attack, stroke, breast cancer and other serious conditions. The FDA said it sent 16 letters to companies marketing alternative therapies, telling them that it considers the products unapproved new drugs, which require FDA approval before they can be sold. Many of the alternatives claim to be either natural progesterone creams or dietary supplements that contain plant-based hormones. Among the unproven claims cited in the warning letters, the FDA said, are that the therapies can reverse osteoporosis-related bone loss and increase bone density; reduce or arrest the growth of cancer cells; protect against fibroids, ovarian, and endometrial cancers; and treat various forms of arthritis.
Bioidentical hormones
Hormones influence fish
Researchers have found male fish with eggs in their testes and female sex traits off the coast of Southern California and believe that chemicals in sewage may be the cause. Changes appeared in fish such as English sole and California halibut, both of which are bottom dwellers, in water near where sewage is released. High levels of estrogen, both natural and man-made formulations used in birth control pills, are thought to cause such abnormalities in fish. Estrogen makes its way into sewage water and then the ocean through women's excretions.
Nerve growth factor and Love
Your heartbeat accelerates, you have butterflies in the stomach, you feel euphoric and a bit silly. It's all part of falling passionately in love -- and chances are the feeling won't last more than a year. The powerful emotions that bowl over new lovers are triggered by a molecule known as nerve growth factor (NGF), according to Pavia University researchers. The Italian scientists found far higher levels of NGF in the blood of 58 people who had recently fallen madly in love than in that of a group of singles and people in long-term relationships. But after one year with the same lover, the quantity of the "love molecule" in their blood had fallen to the same level as that of the other groups. The Italian researchers, publishing their study in the journal Psychoneuroendocrinology, said it is not clear how falling in love triggers higher levels of NGF, but the molecule clearly has an important role in the "social chemistry" between people at the start of a relationship.
Hormone questions
Q. I have a friend who says she takes herbal pills for hormone balance or to correct female hormone imbalance. What does hormone balance mean?
A. Hormone balance is a term used by lay people who do not understand the complexities of hormones in the body. As you can see from the hormone list on this page, there are hundreds of hormones, any many of them interact with each other. To take a supplement and claim that it leads to hormone balance does not make sense to me since it is impossible to measure all the hormone levels in the body at one time, and even if the hormones were measured, the levels could be quite different a few days or a few weeks later.
Q. What is your opinion on hormone glandulars?
A. See glandulars for more information.
Q. Hi I am 36 having a complete hysterectomy and would like to know what you would recomend for replacing hormones i wont take the ones the dr said he wanted me to take my mother had cancer and the risks are too high. I am not sure what hormone or other option is the best for me.
A. Unfortunately, we are not in a position to make individual recommendations, but we can refer you to this web page menopause. Good luck with the hysterectomy surgery and we hope everything goes well.
Q. Is DHEA a pro hormone?
A. In my opinion DHEA is a hormone, but some people consider it to be a pro hormone. Perhaps it is both a prohormone and a hormone.
Q. I am a 50 year old woman. I have recently been diagnosed, and am being treated for, polyglandular autoimmune syndrome. I have had severe hypothyroidism for some time (currently balanced with T4 and T3 hormone) and now partial hypopituitarism (tested with stimulation tests). I am on human growth hormone replacement therapy, and have also tested low (saliva test) in DHEA hormone, progesterone, and cortisol. My adrenal gland can make its hormones, as proved by a stimulation test, but my pituitary can't stimulate them to do so. My doctor has just recommended I take 15 mg of DHEA hormone twice a day, which he says can contribute to the production of progesterone and cortisol. I am excited to see the benefits of DHEA on your website, since I have had a problem with low energy and low libido for some time, among many other issues. My concern is the hair loss issues I've seen on your DHEA page. I have noticed hair loss in the top front center of my scalp for several months now. I had hoped that getting my hormones balanced would help this problem, but if DHEA supplements will make it worse, I'm very concerned. Is it possible that too low DHEA (or very low in the other hormones I've mentioned) would cause hair loss, that getting them balanced again can correct?
A. You present a complicated case, and it is difficult to say. My guess is that DHEA hormone use may make hair loss worse, but I can't be sure.
Q. Do you think the nanoliposomal delivery of DHEA, & pregnenolone hormone is better than the ingestion?
A. We have not seen any studies comparing the benefit and risks of different dhea and pregnenolone hormone preparations, and we actually do not know what they mean by nanoliposomal delivery since the prefix nano appears to be more of a marketing gimmick. Please use caution with these hormones.
Hormone Replacement Therapy .
Prohormone or pro hormone

Irritable bowel syndrome info by Ray Sahelian, M.D. health food and healing information

Irritable bowel syndrome is a problem with the intestines. In people with Irritable bowel syndrome, the intestines squeeze too hard or not hard enough and cause food to move too quickly or too slowly through the intestines. Irritable bowel syndrome is also called functional bowel syndrome, irritable colon (the large intestine is also called the colon), spastic bowel and spastic colon. It's not the same as inflammatory bowel diseases like Crohn's disease.
Patients with irritable bowel syndrome are at increased risk for migraine, depression or fibromyalgia.

Natural Treatment for irritable bowel syndrome
Studies of some natural alternatives have had promising results, but none are proven. Thus far, research suggests that certain nutrients may be beneficial in reducing symptoms of irritable bowel syndrome in certain individuals. These nutrients include turmeric, or curcumin, certain probiotics, and artichoke leaf extract. Food allergy elimination should also be tried, see below.

Subscribe to a FREE Supplement Research Update newsletter by Ray Sahelian, M.D. We discuss new irritable bowel syndrome info.

Irritable bowel syndrome symptom
Irritable bowel syndrome is characterized by a group of symptoms — crampy abdominal pain, bloating, constipation, and diarrhea.

Irritable bowel syndrome diet
It's difficult to come up with a diet that would work in most people with irritable bowel syndrome. However, consider making some of the following diet changes: cut back on sugar, cut back on dairy products, especially milk, and consider eliminating certain foods.
People with irritable bowel syndrome have high levels of antibodies that indicate they are allergic to common foods like wheat, beef, pork, and lamb. The idea of food allergy as a cause is supported by studies that systematically eliminated certain dietary components and then reintroduced them to see how symptoms were affected. In one study, researchers compared levels of antibodies to common foods in 108 patients with irritable bowel syndrome and a comparison group of 43 unaffected "control" subjects. As well as the antibody measurements, the researchers also conducted skin prick testing to 16 common foods including milk, eggs, cheese, wheat, rice, potatoes, various meats, and soya beans. Antibody levels to wheat, beef, pork, lamb and soya beans were significantly higher in IBS patients, and tended to be higher for egg yolk and egg white. However, there was no significant correlation between symptom severity and frequency and antibody levels. Nonetheless, the researchers note that elevated levels of food-specific antibodies have been seen in asthma, which suggests there could be a similar process going on in irritable bowel syndrome. SOURCE: American Journal of Gastroenterology, July 2005.

Irritable bowel syndrome treatment
Many people turn to natural treatments to relieve irritable bowel syndrome symptoms because there is no one treatment for irritable bowel syndrome that works for everyone.

Cause of irritable bowel syndrome
Scientists have yet to pinpoint the exact cause of irritable bowel syndrome, but food allergies are one possibility. Irritable bowel syndrome (IBS) is a condition causing constipation or diarrhea (or sometimes both, cyclically), cramping and generalized gut discomfort. Because no clear physical cause has been discovered, it has been thought that stress and mental disorders play a role.

Irritable bowel syndrome and pelvic pain
Researchers have observed in rats that acute irritation of the urinary bladder leads to increased sensitivity in the colorectum, and conversely, irritation of the colorectum leads to sensitization of the urinary bladder. There appears to be neural cross-talk and bidirectional cross-sensitization of the colon and lower urinary tract. This cross-sensitization may account for the substantial overlap of chronic pelvic pain disorders. Irritable bowel syndrome and interstitial cystitis are two very common clinical conditions that affect primarily women of reproductive age. While these two conditions are often treated as separate entities, in actuality, as many as 40% of women suffer from both conditions.

Irritable Bowel Syndrome Research Info
A "probiotic" preparation containing the beneficial microbe Bifidobacterium infantis relieves symptoms of irritable bowel syndrome, a common problem that usually involves cramping, diarrhea and constipation, new research shows. In contrast, treatment with another probiotic microbe, Lactobacillus salivarius, appears to have no effect. Previous studies of probiotic preparations have been small and yielded inconsistent results. For the current study, 75 irritable bowel syndrome patients were randomly assigned to take L. salivarius or B. infantis mixed in a malted milk drink or the malted milk drink alone every morning for 8 weeks. Patients kept track of their symptoms on diary cards collected weekly for analysis. The B. infantis mixture was better than the malted drink alone at reducing overall symptoms, abdominal pain and discomfort, and bloating. In contrast, the L. salivarius mixture was no better than the malted drink alone in reducing symptoms. The investigators point out that the symptom relief achieved with B. infantis was comparable to that seen with Zelnorm (tegaserod) and Lotronex (alosetron), two drugs that have been recently approved for the treatment of irritable bowel syndrome. SOURCE Gastroenterology, March 2005.

Turmeric extract may improve irritable bowel syndrome symptomology in otherwise healthy adults: a pilot study.
J Altern Complement Med. 2004 Dec;10(6):1015-8.
To assess the effects of turmeric (Curcuma longa) extract on irritable bowel syndrome symptomology in otherwise healthy adults. Design: Partially blinded, randomized, two-dose, pilot study. Subjects: Five hundred (500) volunteers were screened for irritable bowel syndrome using the Rome II criteria. Two hundred and seven (207) suitable volunteers were randomized. Interventions: One or two tablets of a standardized turmeric extract taken daily for 8 weeks. Outcomes measures: irritable bowel syndrome prevalence, symptom-related quality of life and self-reported effectiveness. Results: irritable bowel syndrome prevalence decreased significantly in both groups between screening and baseline (41% and 57%), with a further significant drop of 53% and 60% between baseline and after treatment, in the one- and two-tablet groups respectively. A post-study analysis revealed abdominal pain/discomfort score reduced significantly by 22% and 25% in the one- and two-tablet group respectively, the difference tending toward significance. There were significant improvements in all bar one of the irritable bowel syndrome quality of life scales of between 5% and 36% in both groups, approximately two thirds of all subjects reported an improvement in symptoms after treatment, and there was a favorable shift in self-reported bowel pattern. There were no significant differences between groups. Conclusions: Turmeric may help reduce irritable bowel syndrome symptomology. Placebo controlled trials are now warranted to confirm these findings.

Artichoke leaf extract reduces symptoms of irritable bowel syndrome and improves quality of life in otherwise healthy volunteers suffering from concomitant dyspepsia: a subset analysis.
J Altern Complement Med. 2004 Aug;10(4):667-9.
Does artichoke leaf extract ameliorate symptoms of Irritable bowel syndrome in otherwise healthy volunteers suffering concomitant dyspepsia? METHODS: A subset analysis of a previous dose-ranging, open, postal study, in adults suffering dyspepsia. Two hundred and eight (208) adults were identified post hoc as suffering with irritable bowel syndrome. Irritable bowel syndrome incidence, self-reported usual bowel pattern, and the Nepean Dyspepsia Index (NDI) were compared before and after a 2-month intervention period. RESULTS: There was a significant fall in irritable bowel syndrome incidence of 26.4% after treatment. A significant shift in self-reported usual bowel pattern away from "alternating constipation/diarrhea" toward "normal" was observed. NDI total symptom score significantly decreased by 41% after treatment. Similarly, there was a significant 20% improvement in the NDI total quality-of-life (QOL) score in the subset after treatment. CONCLUSION: This report supports previous findings that Artichoke leaf extract ameliorates symptoms of irritable bowel syndrome, plus improves health-related QOL.

Artichoke leaf extract reduces symptoms of irritable bowel syndrome in a post-marketing surveillance study.
Phytother Res. 2001 Feb;15(1):58-61.
Irritable bowel syndrome is a problem reported to affect 22% of the general population. It is characterized by abdominal pain and altered bowel habit, but has so far defied elucidation of its pathogenesis and proved difficult to treat. There is a growing body of evidence which indicates therapeutic properties for artichoke leaf extract. Dyspepsia is the condition for which the herb is specifically indicated, but the symptom overlap between dyspeptic syndrome and IBS has given rise to the notion that artichoke leaf extract may have potential for treating irritable bowel syndrome as well. A sub-group of patients with IBS symptoms was therefore identified from a sample of individuals with dyspeptic syndrome who were being monitored in a post-marketing surveillance study of artichoke leaf extract for 6 weeks. Analysis of the data from the irritable bowel syndrome sub-group revealed significant reductions in the severity of symptoms and favourable evaluations of overall effectiveness by both physicians and patients. Furthermore, 96% of patients rated artichoke leaf extract as better than or at least equal to previous therapies administered for their symptoms, and the tolerability of artichoke leaf extract was very good. These results provide support for the notion that artichoke leaf extract has potential value in relieving irritable bowel syndrome symptoms and suggest that a controlled trial is justified.

Enteric-coated peppermint-oil capsules in the treatment of irritable bowel syndrome: a prospective, randomized trial.
J Gastroenterol. 1997 Dec;32(6):765-8.
To determine the efficacy and tolerability of an enteric-coated peppermint-oil formulation (Colpermin), we conducted a prospective, randomized, double-blind, placebo-controlled clinical study in 110 outpatients (66 men/44 women; 18-70 years of age) with symptoms of irritable bowel syndrome. Patients took one capsule (Colpermin or placebo) three to four times daily, 15-30 min before meals, for 1 month. Thus, in this trial, Colpermin was effective and well tolerated.

Irritable Bowel Syndrome questions
Q. I have heard some reports of people taking yacon to help with dealing with irritable bowel syndrome symptoms> Is there any research with yacon and this condition?
A. I have not come across any research regarding irritable bowel syndrome and yacon. A Medline search was done with these words and no research studies came up.

Irritable bowel syndrome info
GABA Supplement by Ray Sahelian, M.D. (Natural Medicine Comprehensive List)

GABA or gamma-aminobutyric acid, discovered in 1950, is the most important and widespread inhibitory neurotransmitter in the brain. Excitation in the brain must be balanced with inhibition. Too much excitation can lead to restlessness, irritability, insomnia, and even seizures. GABA is able to induce relaxation, analgesia, and sleep. Barbiturates and benzodiazepines are known to stimulate GABA receptors, and hence induce relaxation. Several neurological disorders, such as epilepsy, sleep disorders, and Parkinson’s disease are affected by this neurotransmitter.
GABA is made in the brain from the amino acid glutamate with the aid of vitamin B6. GABA is available as a supplement in vitamin stores, but taking it in pill form is not always an effective way to raise brain levels of this neurotransmitter because GABA cannot easily cross the blood-brain barrier. Companies are searching for ways to place GABA in an oil base in order to ease its entry across this barrier.

GABA Summary
I have not come across any research regarding the use of GABA supplements for anxiety in humans. I don't have a strong opinion regarding the effectiveness of GABA supplements at this time. I think GABA may work better when combined with other anti-stress supplements. Other options for anxiety and tension that may be more effective include kava, 5-HTP, and passionflower. For tension relief and better sleep at night, see Good Night Rx below.
GABA supplement, 250 mg, 60 Capsules - Enzymatic Therapy

GABA is an important amino acid neurotransmitter in the brain.
Recommendations: One, two, or three GABA capsules once or twice daily.




GABA Supplement Facts:
Amount per Capsule
GABA (Gamma-aminobutyric acid) - 250 mg *

* GABA daily value not established

Click here to learn more about GABA, Good Night Rx, Mind Power Rx, or to subscribe to a very popular and FREE newsletter
Subscribe to a FREE Supplement Research Update newsletter. Twice a month we email a brief abstract of several studies on supplements and natural medicine topics, including GABA, and their practical interpretation by Ray Sahelian, M.D.
Good Night Rx with GABA
Physician Formulas
Developed by Ray Sahelian, M.D.

Good Night Rx Supplement Facts:
Serving size: One Capsule
Servings per container: 60

Suggested Use: Take one capsule of Good Night Rx one to three hours before sleep, preferably on an empty stomach. Good Night Rx does not work as well when taken with a meal.

For more information regarding Good Night Rx
Mind Power Rx - Formulated by Ray Sahelian, M.D.
Mind Power Rx is a sophisticated cognitive formula. It combines a delicate balance of brain circulation agents and neurotransmitter precursors with powerful natural brain chemicals that support:

Memory and Mood
Mental clarity
Concentration
Alertness & Focus


Why buy all the individual herbs and nutrients separately -- at great expense -- when you can buy this excellent combination?

The herbs in Mind Power Rx include: Ashwagandha, Bacopa, Fo-Ti, Ginkgo biloba, Ginseng, Mucuna pruriens, Rhodiola, and Reishi. The nutrients and vitamins in Mind Power Rx include Acetyl-l-carnitine, Carnitine, Carnosine, Choline, DMAE, Inositol, Methylcobalamin, Pantothenic acid, Trimethylglycine, Tyrosine, and Vinpocetine.
Click GABA above in blue
GABA side effects
As of now, no significant GABA side effects have been reported with the use of GABA supplement.
GABA and Relaxation
Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans.
Biofactors. 2006;26(3):201-8. Department of Research and Development, Pharma Foods International Co. Ltd., Kyoto , Japan .
The effect of orally administrated gamma-aminobutyric acid ( GABA ) on relaxation and immunity during stress has been investigated in humans. Two studies were conducted. The first evaluated the effect of GABA intake by 13 subjects on their brain waves. Electroencephalograms (EEG) were obtained after 3 tests on each volunteer as follows: intake only water, GABA, or L-theanine. After 60 minutes of administration, GABA significantly increases alpha waves and decreases beta waves compared to water or L-theanine. These findings denote that GABA not only induces relaxation but also reduces anxiety. The second study was conducted to see the role of relaxant and anxiolytic effects of GABA intake on immunity in stressed volunteers. Eight acrophobic subjects were divided into 2 groups (placebo and GABA). All subjects were crossing a suspended bridge as a stressful stimulus. Immunoglobulin A (IgA) levels in their saliva were monitored during bridge crossing. Placebo group showed marked decrease of their IgA levels, while GABA group showed significantly higher levels. In conclusion, GABA could work effectively as a natural relaxant and its effects could be seen within 1 hour of its administration to induce relaxation and diminish anxiety. Moreover, GABA administration could enhance immunity under stress conditions.
GABA Research Update
Alcohol effects on gamma-aminobutyric acid type A receptors: are extrasynaptic receptors the answer?
Life Sci. 2004 Nov 19;76(1):1-8.
GABA (A) receptors have long been implicated in mediating at least part of the actions of ethanol in mammalian brain. However, until very recently, reports of the actions of ethanol on recombinant receptors have required very high doses of ethanol and animals lacking receptor subunits shown to be important for ethanol actions in vitro did not support the view that these subunits are crucial in ethanol actions. Recombinant GABA (A) receptors are uniquely sensitive to ethanol, with a dose-response relationship mirroring the well known effects of alcohol consumption on the human brain. Receptors containing the delta subunit are thought to be located extrasynaptically and it will be important to determine if these extrasynaptic GABA (A) receptor subunit combinations mediate low dose alcohol effects in vivo.
GABA inhibits T cell autoimmunity and the development of inflammatory responses in a mouse type 1 diabetes model.
J Immunol. 2004 Oct 15;173(8):5298-304.
Gamma-aminobutyric acid ( GABA ) is both a major inhibitory neurotransmitter in the CNS and a product of beta cells of the peripheral islets. Our previous studies, and those of others, have shown that T cells express functional GABA A receptors. However, their subunit composition and physiological relevance are unknown. In this study, we show that a subset of GABA A receptor subunits are expressed by CD4+ T cells, including the delta subunit that confers high affinity for GABA and sensitivity to alcohol. GABA at relatively low concentrations down-regulated effector T cell responses to beta cell Ags ex vivo, and administration of GABA retarded the adoptive transfer of type 1 diabetes in mice. Furthermore, treatment with low dose of GABA dramatically inhibited the development of proinflammatory T cell responses and disease progression in diabetes-prone mice that already had established autoimmunity. Finally, GABA inhibited TCR-mediated T cell cycle progression in vitro, which may underlie GABA's therapeutic effects. The immunoinhibitory effects of GABA on T cells may contribute to the long prodomal period preceding the development of T1D, the immunological privilege of the CNS, and the regulatory effects of alcohol on immune responses. Potentially, pharmacological modulation of GABA A receptors on T cells may provide a new class of therapies for human diabetes as well as other inflammatory diseases.
Effect of a gamma-aminobutyric acid-enriched dairy product on the blood pressure of spontaneously hypertensive and normotensive Wistar-Kyoto rats.
Br J Nutr. 2004 Sep;92(3):411-7.
We investigated the blood-pressure-lowering effects of gamma-aminobutyric acid (GABA) and a GABA-enriched fermented milk product (FMG) by low-dose oral administration to spontaneously hypertensive (SHR/Izm) and normotensive Wistar-Kyoto (WKY/Izm) rats. FMG was a non-fat fermented milk product produced by lactic acid bacteria, and the GABA contained in FMG was made from the protein of the milk during fermentation. A single oral dose of GABA or FMG (5 ml/kg; 0.5 mg GABA/kg) significantly (P<0.05) decreased the blood pressure of SHR/Izm from 4 to 8 h after administration, but did not increase that of WKY/Izm rats. The hypotensive activity of GABA was dose-dependent from 0.05 to 5.00 mg/kg in SHR/Izm. During the chronic administration of experimental diets to SHR/Izm, a significantly slower increase in blood pressure with respect to the control group was observed at 1 or 2 weeks after the start of feeding with the GABA or FMG diet respectively (P<0.05) and this difference was maintained throughout the period of feeding. The time profile of blood-pressure change due to administration of FMG was similar to that of GABA. FMG did not inhibit angiotensin 1-converting enzyme. Furthermore, an FMG peptide-containing fraction from reverse-phase chromatography lacked a hypotensive effect in SHR/Izm rats. The present results suggest that low-dose oral GABA has a hypotensive effect in SHR/Izm and that the hypotensive effect of FMG is due to GABA.
Molecular structure and physiological functions of GABA (B) receptors.
Physiol Rev. 2004 Jul;84(3):835-67.
GABA (B) receptors are broadly expressed in the nervous system and have been implicated in a wide variety of neurological and psychiatric disorders. The cloning of the first GABA (B) receptor cDNAs in 1997 revived interest in these receptors and their potential as therapeutic targets. With the availability of molecular tools, rapid progress was made in our understanding of the GABA(B) system. This led to the surprising discovery that GABA (B) receptors need to assemble from distinct subunits to function and provided exciting new insights into the structure of G protein-coupled receptors (GPCRs) in general. As a consequence of this discovery, it is now widely accepted that GPCRs can exist as heterodimers. The cloning of GABA (B) receptors allowed some important questions in the field to be answered. It is now clear that molecular studies do not support the existence of pharmacologically distinct GABA (B) receptors, as predicted by work on native receptors. Advances were also made in clarifying the relationship between GABA (B) receptors and the receptors for gamma-hydroxybutyrate, an emerging drug of abuse. There are now the first indications linking GABA (B) receptor polymorphisms to epilepsy. Significantly, the cloning of GABA (B) receptors enabled identification of the first allosteric GABA (B) receptor compounds, which is expected to broaden the spectrum of therapeutic applications. Here we review current concepts on the molecular composition and function of GABA (B) receptors and discuss ongoing drug-discovery efforts.
Acupuncture-mediated inhibition of ethanol-induced dopamine release in the rat nucleus accumbens through the GABA B receptor.
Neurosci Lett. 2004 Oct 21;369(3):234-8.
Clinical trials are currently underway to determine the effectiveness of acupuncture in the treatment of drug abuse. However, there are still many unanswered questions about the basic mechanisms of acupuncture. Studies have shown that the GABA (B) receptor system may play a significant modulatory role in the mesolimbic system in drug abuse, including ethanol. The in vivo microdialysis study was designed to investigate the effect of acupuncture on acute ethanol-induced dopamine release in the nucleus accumbens and the potential role of the GABA (B) receptor system in acupuncture. Male Sprague-Dawley rats were administered with the highly selective GABA (B) antagonist SCH 50911 (3 mg/kg, i.p.) 1h prior to an intraperitoneal injection of ethanol (1 g/kg). Immediately after ethanol treatment, acupuncture was given at bilateral Shenmen (HT7) points for 1min. Acupuncture at the specific acupoint HT7, but not at control points (PC6 or tail) significantly decreased dopamine release in the nucleus accumbens. Inhibition of dopamine release by acupuncture was completely prevented by SCH 50911. These results suggest that stimulation of specific acupoints inhibits ethanol-induced dopamine release by modulating GABA (B) activity and imply that acupuncture may be effective in blocking the reinforcing effects of ethanol.
GABA pharmacology-what prospects for the future?
Biochem Pharmacol. 2004 Oct 15;68(8):1537-40.
Following the recognition of GABA as an inhibitory neurotransmitter, the discovery of high affinity GABA uptake, and the characterisation of GABA receptors great progress has been made in developing GABA pharmacology. Tiagabide, the first marketed GABA uptake inhibitor may be followed by new and more selective uptake inhibitors. Knowledge of the molecular pharmacology of GABA-A receptors, both synaptic and non-synaptic, may lead to improved anti-anxiety/anticonvulsant agents devoid of the sedative and dependence liabilities of earlier compounds and new hypnotics. Gaboxadol (THIP) is an example of a novel hypnotic that acts on GABA-A receptors by a non-benzodiazepine mechanism. Exploiting neurosteroid interactions with GABAergic mechanisms also holds much future promise.
A role for GABA mechanisms in the motivational effects of alcohol.
Biochem Pharmacol. 2004 Oct 15;68(8):1515-25.
Low doses of ethanol have been hypothesized to act directly via proteins that form ligand-gated receptor channels, such as the gamma-aminobutyric acid (GABA) receptor complex, to allosterically alter function, particularly in specific brain areas such as those hypothesized to be involved in ethanol reinforcement. At the pharmacological level, one can antagonize the effects of ethanol with GABA antagonists, particularly its sedative, anxiolytic-like and acute reinforcing actions. Brain sites involved in the GABA ergic component of ethanol reinforcement include the ventral tegmental area, elements of the extended amygdala (including the central nucleus of the amygdala), and the globus pallidus. Chronic administration of ethanol sufficient to produce dependence and increased ethanol intake are associated with increased GABA release in the amygdala and increased sensitivity to GABA agonists. A hypothesis is proposed that GABA ergic interactions with the brain stress neurotransmitter corticotropin-releasing factor in specific elements of the extended amygdala may be an important component for the motivation for excessive drinking associated with the transition from social drinking to addiction.
[Comparative study of the effect of picamilone and piracetam on learning in rats in a radial maze]
Farmakol Toksikol. 1989 Jul-Aug;52(4):14-7.
During four weeks rats were learned to visit consequently 4 baited arms in the 8-armed radial maze. Picamilone ( nicotinoyl- GABA ) in a dose of 10 mg/kg daily accelerated rats to reach 80% level of learning (to 20-28 trials). After picamilone injections rats obtained the maximal level of short-term memory as just 3-5 trials. Piracetam in a dose of 200 mg/kg daily exerted no effects on long-term and short-term memory of rats in the radial maze.
GABA Emails, questions and answers
Q. I was just reading over your info re: GABA. I bought some GABA earlier this year based on reading about burning fat. I'm not sure that I've seen any results in that area. I work our at Curves so I have been losing weight and toning. The one thing I did notice is the relaxation that soothes me to sleep and stay asleep. I had no idea that this was to be a benefit. I struggle with sleeping all night. I take 3 - 750mg capsules each night before bed. When I am taking it and for several days after I sleep all night. If I waken I am so relaxed I go right back to sleep. I just wanted to pass this to you. After I noticed this benefit I searched the net for info and found some claims of this effect. GABA has certainly been a blessing to me!

Q. I am a little concerned with some conflicting reports I have seen on GABA since I have started taking it. On the one hand a at first glance it sounded like a miracle supplement but the claims of increases in growth hormone I was slightly suspicious off, most adverts steal results and quotes from clinical drugs trials report "Increase HGH levels by 550%" etc When I read the more independent research on it, the doctors say, Yourself included (funnily enough this is not found in the commercial adverts) that GABA as a sport supplement, in powder form cannot transgress easily the brain/blood barrier so in reality, the GABA in your head, is the stuff your body produces naturally and nothing else. - Certainly amongst the guys I know taking it nobody taking it seemed to be turning into the hulk over night.
Q. I recently read an article on body building that claimed using Gaba in the amount of 5 grams daily will act to reduce body fat. Gaba was praised as the ultimate fat burner. During your research have you discovered Gaba to have any body fat reducing capabilities?
A. I have not come across this research with GABA.

Q. I have found a significant amount of literature on the net saying that taking GABA between 2-5 grams per day leads to significant increases in HGH in the blood stream. I was wondering if this is true, and if so what the risks would be in taking it at such high levels.
A. Long term risks of high dose gaba intake are unknown, and even if supplements of gaba raise hgh levels, we don't know for certain that raising hgh levels is beneficial or harmful in the long run.
Q. In one of the your books that I read I remember you writing that you didnt find the supplement gamma-aminobutyric acid (GABA) to be very effective for relieving anxiety by itself and that this was most likely because GABA does not cross the blood-brain barrier easily. I agree that Kava Kava or 5-HTP are probably better for anxiety for most people but can you tell me whether at higher doses and/or more frequent dosing GABA could penetrate the blood-brain barrier and increase intracellular GABA levels significantly?
A. Higher doses may lead to GABA crossing the blood brain barrier, but I have not personally tested this on myself or with patients.

Q. How long does it take for gaba to start working in you blood stream?
A. GABA is readily and quickly absorbed into the bloodstream, but it has difficulty in crossing the blood-brain barrier and hence, at its present form sold over the counter, is not a reliable way to relieve anxiety.

Q. Are there any reasons to be cautious about using GABA as a sleep aid? Because it is an essential amino acid, I wonder if there are any potential negative effects of taking GABA supplements (I've seen them from 100-750mg).
A. My clinical experience with GABA does not indicate this nutrient to have much of an effect on sleep since it doesn't seem that it crosses the blood brain barrier that well.
Q. I have read what you have to say about the supplement GABA and am wondering why you don't speak of Picamilone (I believe this is GABA bonded together with Niacin, in order to cross the blood-brain barrier). Is this not a natural supplement? I know very little about it except that it is said to be wonderful for reducing anxiety. I have tried all kinds of herbs and also GABA powder for my anxiety, but nothing has been too noticeable. Any comments on Picamilone?
A. I found one study on GABA and picamilone as listed a few paragraphs above, besides this I know very little about it and have not had a chance to try it myself to see if it works.
Q. Can one use GABA for anxiety?
A. I am not impressed with GABA for anxiety. Having said this, I have spoken to a few people who feel that GABA reduces anxiety. One user takes GABA in the morning and says it takes the edge off his anxiety, and the effects are noticed a few hours later. I have not personally noticed much of an effect from a GABA supplement, but I have not experimented with a GABA supplement for an extended time.
Q. Do you know of GABA side effects?
A. I have not come across any noteworthy GABA side effects from a supplement.
Q. What is the right GABA dosage?
A. GABA dosage could vary between one to three pills of 250 mg each.
Q. I'm doing a paper in my psychology class in college and its on the effects of GABA and how it improves you focus and other thing s do you have anything manily about the focus effects of GABA.
A. All the info we have about GABA is on our web page. Many other nutrients help focus much more than GABA, such as DMAE, acetylcarnitine, SAM-e, Mind Power Rx, etc.
Q. Is GABA helpful for weight loss?
A. I seriously doubt if GABA helps weight loss.
Q. Please advice regarding increasing GABA binding. Is there is any good aproach to increase GABA binding with out using benzodiazepines. I have
leaned that KAVA KAVA has some efect to increase GABA binding but in same time there is posible problem with liver. What about diet is there any diet aproach to increase GABA binding
A. I am not aware of research with diet and the role of diet in influencing GABA receptors although I am certain that different foods will influence the binding or activity of various receptors.

HAPPINESS - The Intelligent Pursuit of Happiness
The Pursuit of Happiness
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What is the secret to happiness?
Back in 1994, after returning from an enchanting one month hiking trip to Machu Pichu in Peru , I set out to write my first book. I called it Be Happier Starting Now. Little did I know that writing Be Happier would eventually lead me to become a bestselling author, not with a happiness book, but books on health and natural supplements. I put 2 years into this happiness book, day and night, and weekends... the most intense endeavor I have taken upon myself since medical school and residency. I wanted to create a unique work or written art. A happiness book that combined philosophy, poetry, science, humanism, pragmatism, openness, warmth, and love. The pursuit of happiness led me to write this happiness book.
Although I have not promoted this happiness book much, it is very special to me and it has touched many lives. Sometimes when I'm feeling a little down I pick up to read my own book, and it really does make me happier! I had not planned on placing it on this page for sale until recently when a dear friend of mine read it and was so moved by it that she encouraged me to share the wisdom to a wider audience. "You can help so many people be happier," she said.

If you would like a copy of Be Happier, please feel free to order it and our office staff will ship it to you.


Be Happier Starting Now has ten chapters:

1. DEVELOPING A HEALTHY PERSONALITY
2. CULTIVATING A SENSE OF CONNECTION
3. HEALING OLD WOUNDS
4. SETTING GOALS TO FOLLOW OUR DREAMS
5. FINDING SATISFYING WORK
6. BEING FINANCIALLY SECURE
7. PURSUING PLEASURE... INTELLIGENTLY
8. NURTURING PHYSICAL AND MENTAL HEALTH
9. LEARNING & CREATING
10. DEVELOPING A PERSONAL TRUTH
PLUS: THE ONE MINUTE HAPPINESS QUIZ
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Ray Sahelian, M.D.
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Subscribe to a free Supplement Research Update newsletter. Twice a month we email you a brief abstract of several new studies on various supplements and natural medicine topics and their practical interpretation by Ray Sahelian, M.D. See link at top of page.
The One-Minute Happiness Quiz
by Ray Sahelian, M.D.
Circle a number in each category. The higher, the truer.

1. I have a healthy personality with high self-esteem, strong willpower, and a positive attitude. 1 2 3 4 5
2. I feel connected with and have loving relationships with family, pets, friends, spouse, or lover. 1 2 3 4 5
3. Old or new emotional wounds have healed. I harbor no grudges. 1 2 3 4 5
4. I have meaningful goals that I'm passionately pursuing. 1 2 3 4 5
5. Work (and/or school) is satisfying. 1 2 3 4 5
6. I am financially secure. 1 2 3 4 5
7. I have many interests and pleasures. 1 2 3 4 5
8. I am physically healthy, I exercise, sleep well, eat well, and have low stress. 1 2 3 4 5
9. I enjoy learning and acquiring knowledge. Furthermore, I use my creative talents. 1 2 3 4 5
10. I have a personal truth or belief system that provides a meaning to my life. 1 2 3 4 5

Score: Total _________
Quiz score interpretation:

10-15 Double your Prozac dose
16-25 There's room for improvement
26-35 Very good. You can learn to be happier.
36-49 Congratulations. Consider writing your own book on happiness.
50 Incredible! Hold on to something. You may be levitating at any moment.

Be Happier was written 10 years ago, but i still stand by most of what I wrote... the thoughts and emotions seem timeless. If I were to update it, I would change the part about pharmaceutical medicines for mood enhancement. At the time I didn't know about SAM-e, St. John's wort , 5-HTP and other mood enhancing herbs and nutrients. SAM-e can be helpful for the temporary relief of anhedonia.

Review of Be Happier Starting Now
Be Happier Starting Now: A Medical Doctor Explores the Fascinating Field of Happiness
Reviewed by Sharon Presley
Happiness quote:
"There is no point in holding on to cobwebs of archaic creeds if they are not enhancing your quality of life. Just because you were taught something as a child does not mean it is correct . . . . This age requires us to keep an open mind, revise, review, and readjust our thinking patterns . . . ." - Ray Sahelian, M.D.
"Holistic" may be a clichéd term but I like it. It's a good word to describe Dr. Ray Sahelian's approach to charting the path to a happier life. Unlike the stereotyped physician only trained to treat the body, not the whole person, Sahelian integrates ideas from psychology, medicine, philosophy, nutrition, science, spirituality, and other sources. He understands what psychologists have known for years but many physicians (and scientific materialists) scoff at or simply ignore - there really is a connection between the mind and body, with each affecting the other in complex ways.
Let me make one thing clear from the start. Sahelian is not some New Age flake pushing tofu, out-of-body experiences and inner-child weekends. Not in my review! Not even close. There are no wild-eyed claims, no psychobabble, no mysticism. Just sensible, balanced suggestions based mainly on medical and psychological research journals and books. An annotated bibliography is included for those who want to read the original research.
On the other hand, just because this book cites research, don't expect a dry, distancing catalog of mere facts. There's a real human being writing this book. Sahelian's style is gentle, joyful and exuberant, with a sweetly poetic flair that many will find charming (while some will decide it's not their cup of tea). It's possible to be poetic and scientific at the same time.
Here's what topics are included: developing a healthy personality, cultivating a sense of connection, healing the wounds, setting goals to follow our dreams, finding satisfying work, being financially secure, pursuing pleasure intelligently, nurturing physical and mental health, learning and creating, and developing a personal truth. An appendix discussing natural supplements that improve mood and describing mood-improving medicines is also included. (Not everyone will agree with his position on Prozac.)
Sahelian weaves together specific information and suggestions with his own personal experiences and his observations of others in a style that is easy to read but not fluffy. Though basic rather than encyclopedic, his book provides an integrated nondogmatic overview that does an excellent job of putting happiness into a proper perspective. No one thing brings you happiness; there is no one "magic answer." But a lot of things that help can be found in this book.
Start being happier now, here's a bit of advice from Dr. Sahelian: "Be timid no more. Life's a sumptuous banquet. Sample! Explore! Expand!"
Sharon Presley, Ph.D. is a social psychologist who writes and speaks frequently on topics relevant to critical and independent thinking. She is executive director of Resources for Independent Thinking.
Denmark - The Happiest Country?
If you're looking for happiness, move to Denmark . According to Adrian White, an analytical social psychologist at the University of Leicester in central England , Denmark is the happiest country in the world while Burundi in Africa is the most miserable. Adrian White based his study on data from 178 countries and 100 global studies from the likes of the United Nations and the World Health Organization. The main factors that affect happiness were health provision, wealth and education, according to Adrian White who said his research had produced the "first world map of happiness." Following behind Denmark came Switzerland , Austria , Iceland and the Bahamas . At the bottom came the Democratic Republic of Congo , Zimbabwe and Burundi . The United States came in at 23rd, Britain was in 41st place, Germany 35th and France 62nd. Countries involved in conflicts, such as Iraq , were not included. Countries in Asia scored low, with China 82nd, Japan 90th, and India 125th. These are countries that are thought as having a strong sense of collective identity which other researchers have associated with well-being.
Collecting data based on well-being is not an exact science. Other researchers may come to different happiness rankings.
Happiness and the Common Cold
Staying positive through the cold season could be a good defense against getting sick. In an experiment that exposed healthy volunteers to a cold or flu virus, researchers found that people with a generally sunny disposition were less likely to fall ill. The findings, published in the journal Psychosomatic Medicine, build on evidence that a "positive emotional style" can help ward off the common cold and other illnesses. Researchers believe the reasons may be both objective -- as in happiness boosting immune function -- and subjective -- as in happy people being less troubled by a scratchy throat or runny nose.

Happiness Research Update
I have collected some research articles I have come across. I hope you enjoy them. I'm still working on this page to make it more organized.
Older adults with a bright outlook on the future may live longer than those who take a dimmer view.
Researchers in the Netherlands found that older men and women judged to have optimistic personalities were less likely to die over the nine-year study period than those with pessimistic dispositions. Much of this reduced risk was due to lower rates of death from cardiovascular disease among the most optimistic men and women in the study. They were 77 percent less likely to die of a heart attack, stroke or other cardiovascular cause than the most pessimistic group-regardless of factors such as age, weight, smoking and whether they had cardiovascular or other chronic diseases at the study's start.

Feeling a little down? Maybe you can fake your way into happiness! You may have more control over your mood than you think. According to new research, people who choose to act more outgoing or assertive can actually improve their outlook on life. The research is published in a recent issue of the Journal of Personality and Social Psychology.
Brain rewards us for laughing: study They say laughter is the best medicine, and a new study may help explain how laughter makes us feel good. Researchers report that humor seems to activate brain networks that are involved in rewards. Humor is no laughing matter, according to Dr. Allan L. Reiss of Stanford University in California , who led the research. "Humor has significant ramifications for our psychological and physical health," he told Reuters Health. Our sense of humor, he said, "often dictates if, how and with whom we establish friendships and even long-lasting romantic relationships." Humor is also a "universal coping mechanism" for dealing with stress. Reiss added.Despite the importance of humor, Reiss said that little is known about the brain mechanisms that underlie humor. The Stanford researcher noted that most people are drawn to humor and that it makes people feel good. "We seem to feel rewarded" by humor, he said. Now, Reiss and his colleagues report that they have zeroed in on the brain's reward system for humor. In the study, volunteers had their brain activity monitored as they read a series of cartoons. Some of the cartoons were supposed to be funny, but others had the funny cues omitted.
After viewing each strip, participants pushed a button if they thought the comic was funny. Researchers found that when a cartoon made a person laugh, a brain network that is known to be involved in reward was activated. In fact, the areas activated by humor have been shown previously to be activated by amphetamines and cocaine, according to a report in the December 4th issue of the journal Neuron. "I believe that understanding humor is fundamental to understanding many aspects of 'normal' human social behavior," Reiss said. Learning more about the brain mechanisms that underlie humor may also help scientists who study depression, according to Reiss. He noted that the loss of the ability to appreciate humor is a common symptom of depression. "We believe that utilizing studies such as this may be one way to more specifically identify individuals at risk for depressive disorders," Reiss said. The research may also be useful in measuring a person's response to treatment for depression, according to Reiss. The humor reward system in the brain may come "on line" even before symptoms of depression change, he said.
The research may also help explain "humorless" people, who, Reiss noted, may have serious problems in relationships. "Perhaps they are missing this reward link in their circuitry," he said. Finally, humor is known to play a role in the sleeping disorder narcolepsy and other conditions, Reiss said.
SOURCE: Neuron, December 4, 2003.
Smiling at strangers can be a thankless exercise in some British cities, where a survey has revealed the famous stiff upper lip is rarely likely to crack a grin in return. Psychology students spent an hour smiling at 100 strangers in 14 British cities as part of the Comic Relief fundraising campaign, according to a report in The Guardian newspaper. Only 4% of people in Edinburgh , 12% in Nottingham and 18% in London returned the students' smiles. On the other hand, the residents of Bristol smiled back 70% of the time, and 68% of Glasgow citizens were cheery enough to raise the corners of their mouths. Pat Spungin, a psychologist who led the research, told the paper that social setting played a large role in smiling, which might explain why Londoners scored so low. "With a population of 7 million, which is very mixed and very mobile, it is difficult to feel a sense of community with other Londoners," he said.
Over time, people "catch mood" of friends, lovers
Laugh and the world laughs with you, the saying goes, and this is especially true for couples and roommates, the results of a new study suggest. It seems that couples and roommates tend to have similar emotional reactions as time goes by. So if your roommate or lover laughs out loud at movies or gets weepy over hurt puppies, you may too -- given time.
This so-called emotional convergence seems to be beneficial to friendships and romantic relationships, making them stronger and longer lasting. Everyday experience suggests that people are capable of "catching" the mood of a spouse or friend, said lead author Dr. Cameron Anderson. But he told Reuters Health that he was surprised by the extent to which peoples' emotions converged in his study, which is reported in the Journal of Personality and Social Psychology.
"The romantic partners and roommates were virtually becoming the same emotional person over time," said Anderson, a visiting assistant professor of management and organizations at the Kellogg School of Management at Northwestern University in Evanston , Illinois . In the first part of the study, 60 heterosexual couples at the University of Wisconsin in Madison answered questions about their personality, their satisfaction with their relationship and the balance of power within it.
To test emotional convergence, partners discussed positive and negative situations -- such as a recent success or an ongoing worry. Then each partner privately reported his or her feelings regarding the issue. Six months later, the 38 couples that were still together repeated the experiment. The couples maintained distinct personalities, but they were more closely attuned emotionally than they had been at the start of the study, the researchers found.
Although couples' emotions converged over time, similar emotions might have drawn them together in the first place. Couples that stayed together during the study were more emotionally similar than couples that broke up, the researchers point out. Anderson 's team also found that the partner who had less power in the relationship did most of the changing in terms of emotions.
In other experiments, which involved college students who lived together in dormitories, the researchers found that roommates tended to have more similar emotional responses towards the end of the school year. The researchers gauged emotion by having students watch film clips that tend to elicit laughs or tears. Roommates whose emotions converged the most during the school year tended to become closer friends than roommates whose emotions did not become as similar, according to the report. The study also found that the roommate who had a lower social status in the dormitory tended to change more than popular roommates. Anderson said these results show that "people's emotional responses to events are not completely fixed and rigid." According to the Illinois researcher, emotional similarity could be helpful in assembling the most productive corporate team, and might be an important consideration when searching for love or friendships.
Study: Marriage won't guarantee happiness Though individuals can enjoy a lifetime of happiness from marriage, the difference between them and singles is smaller than expected, a study released Sunday suggests. Researchers led by Richard Lucas, assistant professor of psychology at Michigan State University in East Lansing , examined data on more than 24,000 people in Germany who participated in a survey and then were followed from 1984 to 1995. Of the participants, nearly half were residents of the former West Germany , about 5,000 were residents of the former East Germany , 4,000 were foreigners living in West Germany and 3,000 were East Germans who had emigrated to West Germany . The study sample also included widows and widowers.
Participants were asked to rate their level of happiness on a scale of zero to 10, with zero signifying total unhappiness. The answers then were compared to the respondents' marital status. Researchers found although married individuals generally reported a higher level of happiness, this satisfaction with life was not as high as expected -- averaging only about 1-10th of 1 point on the 10-point scale.
The findings indicate although a person can enjoy a happy boost from marriage, the person tends to return to his or her prior level of happiness, whatever that level might have been before saying "I do," researchers said. "Married people are happier than these other groups, but they were happy when they were single," Lucas told United Press International. "It's not that everybody who gets married has a big positive change that happens after marriage." As reported in the March issue of the Journal of Personality and Social Psychology, the results also showed marriage or divorce does not have the same implications for everyone. A person who was lonely before marriage can gain much from a marriage, while a happily married person whose spouse dies can lose a great deal, and someone who had been unhappily married and then goes through a divorce might not feel much of a loss. "These levels of happiness do tend to be steady over time even in the face of change of life circumstances," Lucas added.
Based on the findings, people appear to have a core level of happiness and although that level can fluctuate over time, people typically return to it, he continued. So if a person was grossly unhappy with his or her life prior to marriage, wedding bells are unlikely to alter that person's sense of satisfaction. "There's definitely a component that seems to be related to personality" in determining happiness, Lucas said. For example, sociable, outgoing individuals tend to report being happier. "There's no magic ticket to happiness," Dorian Solot, executive director of the Alternatives to Marriage Project, an education and advocacy group in Boston, told UPI. "Wedding bells might do it for some people (but) happiness is about you and your own life."
Solot called the findings "interesting," adding, "If you're going to have a happily-ever-after life, it probably starts before you get married." Previous studies have suggested married people generally are happier and live healthier lives, and some research even has reported married individuals have lower rates of depression, heart attack and stroke, Solot noted, but added being happy and healthy "may have less to do with your legal marital status. It's whether you have supportive relationships in your life."
The formula for happiness?
If you're happy and you know it then it's clearly a result of: P + 5E + 3H. A pair of British researchers said Monday they had worked out a simple equation to quantify happiness that could put an exact figure on the emotional state. After interviewing 1,000 people, the researchers--a psychologist and a self-styled "life coach"--concluded that happiness equals P + 5E + 3H. In the equation, P stands for Personal Characteristics (outlook on life, adaptability and resilience); E for Existence (health, friendships and financial stability) and H represents Higher Order (self-esteem, expectations and ambitions). Psychologist Carol Rothwell co-authored the report with Pete Cohen. They asked interviewees--a mix of men and women all over 18 years old--to choose five scenarios that made them more happy or less happy from a list of 80 different situations. They also asked a series of questions about their own natures, outlooks and situations. Not surprisingly, the results showed that men and women found happiness in different ways. Sunny weather, being with family and losing weight were more of an influence on women's happiness, while romance, sex, hobbies and victories by their favorite sports teams were more important to men. "This is the first equation that enables people to put a figure on their emotional state," Rothwell said. "The findings show that certain events, such as job promotion, can impact positively on your overall happiness." The study was commissioned by a holiday company that wanted to understand what made people happier.
Life liberty and the pursuit of happiness
5-htp
ahcc
carnosine
coq10
Graviola
impotence
Mangosteen
serrapeptase
saw palmetto
sexual enhancement
Sitosterol
Vinpocetine
Healthy diet
The pursuit of happiness with natural supplements and herbs
OSTEOPOROSIS information by Ray Sahelian, M.D.

Osteoporosis is a public health problem affecting 75 million persons in the United States , Europe and Japan , including one third of postmenopausal women and most of the elderly in the United States , Europe and Japan . Osteoporosis results in more than 1.3 million fractures annually in the United States .
Cause of Osteoporosis
Osteoporosis is a condition characterized by micro-architectural deterioration of bone tissue leading to decreased bone mass and bone fragility. The major cause for osteoporosis is poor bone mass acquisition during adolescence and accelerated bone loss in persons during the sixth decade (the perimenopausal period in women). Both processes are regulated by genetic and environmental factors. Reduced bone mass is the result of varying combinations of hormone deficiencies, inadequate nutrition, decreased physical activity, and the effects of medications used to treat various unrelated medical conditions. In rare cases, a cause of osteoporosis can be gluten intolerance.
Natural Osteoporosis Treatment and Osteoporosis Prevention
Below I discuss a natural remedy for osteoporosis. Discuss with your doctor before you implement any of these natural remedy for osteoporosis options:
Eat more fruits and vegetables - For osteoporosis, the evidence from a combination of observational, experimental, clinical, and intervention studies strongly points to a positive link between fruit and vegetable consumption and bone health.
Reduce alcohol
Reduce caffeine
Reduce or stop smoking
Reduce cola intake - Intake of cola is associated with low bone mineral density in women.
Weight bearing exercises are tremendously helpful as an osteoporosis treatment and osteoporosis prevention
Calcium supplements are the mainstay for osteoporosis prevention and treatment. Calcium can be taken at mealtime with dinner
Vitamin D-- foods rich in vitamin D include milk, cheese, sardines, cooked greens. Exposure to sun a few minutes a day. Or, take a multivitamin mineral supplement. Several randomized, prospective, placebo-controlled clinical trials have documented that a supplementation with vitamin D (400-1,000 IU per day) together with calcium (800-1,200 mg per day) may reduce the risk of falls and fall-related fractures in the elderly.
Magnesium is not discussed as much, but this mineral could also be helpful.
Soy isoflavones such as genistein may be helpful
Reduce or avoid soft drinks due to their phosphorus content.
Estrogen replacement -- use lowest amount of natural estrogens for the least period of time
Hip Protectors - Padded undergarments designed to cushion a fall may offer an inexpensive way to prevent hip fractures in the elderly
Subscribe to a FREE Supplement Research Update newsletter at Physician Formulas. Twice a month you will receive an email on various supplements and natural medicine topics -- including osteoporosis -- and their practical interpretation by Ray Sahelian, M.D. We will mention osteoporosis as more research becomes available.
Osteoporosis Diet
To reduce your risk for osteoporosis, have a diet that contains adequate protein and calcium. For a list of foods that have calcium, see the link above.
Standard Medical Osteoporosis treatment - Osteoporosis medication
Osteoporosis often is undertreated and underrecognized, in part because it is a clinically silent disease until it manifests in the form of fracture. Sufficient recognition of osteoporosis and its appropriate medical and nonmedical treatment are essential. Osteoporosis drug treatments -- besides calcium and vitamin D -- include the medication bisphosphonates, estrogen, selective estrogen receptor modulators, calcitonin, parathyroid hormone, balance and exercise training programs, and the minimally invasive spine procedures vertebroplasty and kyphoplasty comprise a comprehensive multidisciplinary approach in the treatment of osteoporosis. There is controversy regarding the long term benefit and risks of certain osteoporosis drugs. Biphosphanate use may leas to osteonecrosis of the jaw bone and potentially other serious conditions.

Osteoporosis in Men
Although osteoporosis is often regarded as a disease of women, 30% of osteoporotic fractures occur in men. Risk factors for osteoporosis or fractures in men include previous fragility fractures, maternal history of fragility fracture, hypogonadism, low body mass index, smoking, high alcohol consumption, low calcium intake, corticoid therapy, physical inactivity, and the presence of conditions such as hyperthyroidism, hyperparathyroidism, hypercalciuria or chronic inflammatory diseases.
Osteoporosis Exercise
Any type of movement helps strengthen bones. If your bones are weak, try swimming first. Walking is great for lower extremities, but the best osteoporosis exercise is weight lifting. if you are concerned about osteoporosis, you have to be physically active, preferably throughout life. Walk, dance, do pushups, do yoga or stretching for flexibility, reduce smoking, and, if possible join a gym where you lift weights using all muscle groups. If you can't join a gym, buy a few cheap barbells and lift weights at home, do gardening, or lift rocks in your backyard... anything to make your muscles work. When muscles contract, they pull tendons that are attached to the bones, and this tells the bones to deposit calcium and thus bones become stronger and less apt to fracture. Bone is a living tissue that responds to exercise by becoming stronger. Just as a muscle gets stronger and bigger with use, a bone becomes stronger and denser when it is called upon to bear weight. Taking lots of calcium without being physically active is not going to be as effective.
Osteoporosis and Vitamin D Supplements
Vitamin D deficiency is quite common in cases of hip fractures. A look-back study of 548 patients older than 60 years of age who were admitted at South Glasgow University Hospital in Scotland in the previous 4 years, showed that 97 percent of the patients had vitamin D levels below normal. Dr. Stephen Gallacher, lead researcher and consultant endocrinologist at the hospital said: ''Although the numbers were too small to justify extensive subgroup analyses the study appears to demonstrate that vitamin D inadequacy represents a significant correctable risk factor for fragility fracture and perhaps specifically for the hip."
Dr. Sahelian comments: Most elderly patients do not get enough vitamin D through sun exposure, particularly in cold climates with long winters. Vitamin D can be supplemented by taking a multivitamin and mineral complex, or through cod liver oil. A dosage of 400 to 800 units should be adequate. Sitting by the window or taking walks outside could be helpful.
Osteoporosis Pain
Osteoporosis may cause painful fractures, which can take many months to heal. In many cases, the pain starts to go away as the fracture heals. Pain that continues after a few month is considered chronic pain. One cause of chronic pain is vertebral fractures. When a vertebra breaks, some people have no pain, while others have intense pain and muscle spasms that last long after the fracture has healed.
Osteoporosis Medication - Biphosphonate side effects
Bisphosphonates - Side effects for alendronate, ibandronate and risedronate include gastrointestinal problems, abdominal or musculoskeletal pain, nausea, heartburn, or irritation of the esophagus. There have been a few reports of osteonecrosis of the jaw and of visual disturbances.
Alendronate Sodium (brand name Fosamax®) - Alendronate is approved for both the prevention (5 mg per day or 35 mg once a week) and treatment (10 mg per day or 70 mg once a week or 70 mg once a week plus D) of postmenopausal osteoporosis.
Ibandronate Sodium (brand name Boniva®) - Ibandronate is approved for the prevention and treatment of postmenopausal osteoporosis. Taken as a once-a-month pill (150 mg), ibandronate should be taken on the same day each month.
Risedronate Sodium (brand name Actonel®) - Risedronate Sodium with 500 mg of Calcium Carbonate (brand name Actonel® or Actonel® with Calcium) - Risedronate is approved for the prevention and treatment of postmenopausal osteoporosis. Taken daily (5 mg dose) or weekly (35 mg dose or 35 mg dose with calcium). Risedronate also is approved for use by men and women to prevent and/or treat glucocorticoid-induced osteoporosis that results from long-term use of these medications (i.e., prednisone or cortisone).
Osteoporosis Medication - Calcitonin side effects
Calcitonin-salmon (Calcimar, Miacalcin) calcitonin-human (Cibacalcin) - Side effects of the calcitonin nasal spray may include runny nose or nasal discomfort, nausea and skin redness (flushing). Side effects of the calcitonin shot may include nausea and/or vomiting, diarrhea, inflammation at the site of the shot, skin redness (flushing), and increased urination or increased number of bowel movements.
Osteoporosis Medication - Raloxifene side effects
Raloxifene is used to help prevent and treat thinning of the bones (osteoporosis) in postmenopausal women. Raloxifene works like an estrogen to stop the bone loss that can develop in women after menopause, but it does not increase the bone density as much as daily 0.625 mg doses of conjugated estrogens. Raloxifene will not treat hot flashes of menopause and may cause hot flashes to occur. Also, raloxifene does not stimulate the breast or uterus as estrogen does. Raloxifene side effects include bloody or cloudy urine; chest pain; difficult, burning, or painful urination; fever; frequent urge to urinate; infection, including body aches or pain, congestion in throat, cough, dryness or soreness of throat, and loss of voice; runny nose ; leg cramping; skin rash ; swelling of hands, ankles, or feet; vaginal itching. Bloody cough may also occur.
Osteoporosis Research Update
Depo-Provera, an injectable contraceptive, will come with a special warning that links prolonged use of the drug with bone density loss possibly leading to osteoporosis.

Onions can spice up your meals -- and maybe strengthen your bones. Investigators from the University of Bern in Switzerland found that after eating a small fraction of an ounce of onion with their food, rats became significantly less likely to lose bone. These findings suggest that adding onion to food may help people fight off the bone-thinning disease osteoporosis.

Some people develop osteoporosis, the mineral loss disease that leads to brittle bones, because their bodies cannot tolerate wheat flour. Gluten intolerance, called celiac disease, can be treated, so the damage done by osteoporosis can be reversed in such patients, says the report published in the March 2005 issue of the Archives of Internal Medicine. As many as three to four percent of patients who have osteoporosis have the bone disease as a consequence of having celiac disease, which makes them unable to absorb normal amounts of calcium and vitamin D.
Prevention and management of osteoporosis.
World Health Organ Tech Rep Ser. 2003;921:1-164,
Bone is hard tissue that is in a constant state of flux, being built up by bone-forming cells called osteoblasts while also being broken down or resorbed by cells known as osteoclasts. During childhood and adolescence, bone formation is dominant; bone length and girth increase with age, ending at early adulthood when peak bone mass is attained. Males generally exhibit a longer growth period, resulting in bones of greater size and overall strength. In males after the age of 20, bone resorbtion becomes predominant, and bone mineral content declines about 4% per decade. Females tend to maintain peak mineral content until menopause, after which time it declines about 15% per decade. Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased susceptibility to fractures, especially of the hip, spine, and wrist. Osteoporosis occurs primarily as a result of normal ageing, but can arise as a result of impaired development of peak bone mass (e.g. due to delayed puberty or undernutrition) or excessive bone loss during adulthood (e.g. due to estrogen deficiency in women, undernutrition, or corticosteroid use). Osteoporosis-induced fractures cause a great burden to society. Hip fractures are the most serious, as they nearly always result in hospitalization, are fatal about 20% of the time, and produce permanent disability about half the time. Fracture rates increase rapidly with age and the lifetime risk of fracture in 50 year-old women is about 40%, similar to that for coronary heart disease. In 1990, there were 1.7 million hip fractures alone worldwide; with changes in population demographics, this figure is expected to rise to 6 million by 2050. To help describe the nature and consequences of osteoporosis, as well as strategies for its prevention and management, a WHO Scientific Group meeting of international experts was held in Geneva , which resulted in this technical report. This monograph describes in detail normal bone development and the causes and risk factors for developing osteoporosis. The burden of osteoporosis is characterized in terms of mortality, morbidity, and economic costs. Methods for its prevention and treatment are discussed in detail for both pharmacological and non-pharmacological approaches. For each approach, the strength of the scientific evidence is presented. The report also provides cost-analysis information for potential interventions, and discusses important aspects of developing national policies to deal with osteoporosis.

Depo-Provera (depot medroxyprogesterone), a popular birth control injection, seems to promote bone loss or osteoporosis, and the effects increase over a 2-year period.
Effect of Rehmannia glutinosa Libosch extracts on bone metabolism.
Clin Chim Acta. 2003 Aug;334(1-2):185-95.
Rehmannia glutinosa Libosch extracts were investigated to determine if they play roles in osteoporosis and bone metabolism. CONCLUSIONS: Rehmannia stimulates the proliferation and activities of osteoblasts, while inhibiting the generation and resorptive activities of osteoclasts. It also shows preventive effects on osteoporotic bone loss induced by an ovariectomy. Although the active substances have not yet been identified, it is believed that rehmannia seems to contain active components that have a potential to enhance the bone metabolism in osteoporosis.
glucomannan
lemon balm
curcumin
fenugreek
Osteoporosis Treatment questions
Q. How much calcium is appropriate for osteoporosis treatment?
A. A wide range of calcium dosages have been recommended for osteoporosis treatment, ranging from 1000 to 2000 mg a day.

Q. What's the first or most common osteoporosis symptom ?
A. Without your realizing it, osteoporosis leaks calcium from your bones, leaving them so brittle and frail that a minor fall or strain could cause the osteoporosis symptom or sign of a hip or spine fracture. That nagging back pain or dowager's hump might be one of the first osteoporosis symptom a person could have. Another osteoporosis symptom could be back pain, along with vertebral fractures and loss of height.

Q. I have postmenopausal osteoporosis. Is hormone replacement with estrogen still recommended>
A. Depending on the severity of your postmenopausal osteoporosis, estrogen may be used in low doses - in addition to calcium and vitamin D - as long as you don't have an estrogen sensitive tumor or have a family history of breast cancer. There is no overall agreement in the medical community on the estrogen dosage to be used, the form of estrogen, and whether to take occasional breaks from use.

Q. Is magnesium a natural osteoporosis remedy ?
A. This is a good question. Calcium is, of course, but I don't know if magnesium supplementation is also considered a natural remedy for osteoporosis.

Q. Can calcium by itself by an osteoporosis cure ?
A. I doubt it. To cure or remedy osteoporosis, several things have to be done in addition to calcium and vitamin D. The most important is exercise, preferably weight bearing exercise to stimulate calcium deposition in bone.
Q. I've heard that heavy exercise is a cause of osteoporosis.
A. You're probably thinking about osteoarthritis where running marathons could increase the risk, perhaps, of knee and hip pain. Exercise is not a cause for osteoporosis, in fact, lack of exercise is a common cause of osteoporosis.
Q. What's the relation between vitamin A and osteoporosis ?
A. There are reports that megadosing with vitamin A, such as 50,000 to 100,000 units a day could interfere with bone formation and be a cause of osteoporosis.
Q. How common is osteoporosis in a man and what is the cause?
A. Osteoporosis in men is now recognized as an increasingly important public health issue. One in eight men older than 50 years will have an osteoporotic fracture. Because of their greater peak bone mass, men usually present with hip, vertebral body, or distal wrist fractures a decade later than women. Major risk factors for osteoporosis in a man are glucocorticoid use for longer than six months, a history of nontraumatic fracture, hypogonadism, and advancing age.
Q. Is CoQ10 a natural osteoporosis remedy?
A. I have not come across research indicating the role of CoQ10 in osteoporosis.
Q. I read your newsletters cover to cover with great interest and have learned a lot. Your perspective is very refreshing. However, I was disappointed in your commentary (April 2006) on taking calcium. I believe you were remiss in not mentioning the necessity of taking magnesium (50% of calcium) as well as vitamin D with calcium, or for mentioning the benefits of calcium citrate versus calcium carbonate. Just recently I found out we cannot absorb more than 500mg calcium at a time, so now I take 500mg morning and evening. It seems plausible that avoiding a daily overload could help us all avoid the risk of kidney.
A. We appreciate your email and your input. Please reread the newsletter and you will see that vitamin D is mentioned. As to the different forms of calcium, no research is available long term to determine which form over several years leads to better bone strength. And you make a good point about spreading the dose of the calcium over the day to minimize kidney stone formation, although research is needed to find out which way leads to better bone deposition -- small amounts a few times a day or high amounts once or twice. Often we think we know answers to questions based on a short term lab study, but the body behaves quite differently over a long period of supplementation
Also, a link is provided for osteoporosis information which mentions magnesium and other potentially beneficial supplements for osteoporosis.
Q. In your newsletter of April 2006. presumably for the public, I am surprised that you did not mention the nutritional co-factors to calcium supplementation for the purpose of bone building, particularly magnesium, which is one of the most effective therapies for preventing calcium renal stones. also, you dont mention the poor absorption qualities of calcium carbonate, which was used in the studies. I am a medical doctor.
A. When I write a newsletter, I don't mention everything possible due to limited space, but if you notice there is a link to osteoporosis at the end of the newsletter where magnesium is mentioned. If you know of long term human studies with other forms of calcium that led to a decrease in fractures, please point these out to us, we would appreciate it. If there was an increase in kidney stones with calcium carbonate, one would assume that the calcium was absorbed well. If other forms of calcium get absorbed better, hypothetically there is a risk for more kidney stones.