by Ben Best
[Many of the facts below come from TOXICOLOGY LETTERS 102-103:5-18 (1998)]
RDA = Recommended Daily Allowance based on preventing acute nutrient deficiency disease conditions rather than based on amounts producing optimum health.
Folic acid deficiency increases accumulation of homocysteine, which can cause neurological defects in the fetus of a pregnant woman. Homocysteine also damages endothelial cells (lining blood vessels) and is thus implicated in heart disease.
Folic acid is necessary for the methylation of uracil to thymine. Without this methylation, uracil rather than thymine may be incorporated into DNA -- which can lead to chromosome breaks during DNA repair. Supplementation with folic acid above the RDA levels minimizes chromosome breaks. Similarly, ingestion of less than 50% of the RDA of Vitamins B6 and B12 causes high levels of uracil incorporation in DNA and consequent chromosome breaks.
The major dietary source of Vitamin B12 is animal foods. Vegans are frequently deficient in Vitamin B12. As with folic acid, Vitamin B12 is necessary for uracil to be methylated to thymine. Again, supplementation with Vitamin B12 above the RDA will minimize chromosome breakage. Homocysteine also accumulates with Vitamin B12 deficiency because Vitamin B12 is require to methylate homocysteine to methionine -- making Vitamin B12 deficiency a risk factor for heart disease.
TMG (TriMethylGlycine) converts homocysteine to methionine. Methionine can combine
with ATP
to form S-AdenosylMethinine (SAMe,
methinine-adenosine), the
principal source of methyl groups in the body. Methylation is essential for DNA &
RNA synthesis. Much of the SAMe in the liver is converted to the water-phase
antioxidant glutathione. TMG helps prevent homocysteine accumulation and thus
protects against heart disease.
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Zinc is an essential component of many enzymes and proteins, including the anti-oxidant enzyme Cu/Zn-SOD (SuperOxide Dismutase) and p53 tumor-suppressor protein. So-called zinc fingers are loops of 12 or 13 amino acids (residues) centered on zinc which is bound to pairs of Cysteine (C) or Histidine (H) residues. Zinc fingers are found on steroid receptors and transcription factors (enabling the factors to bind to DNA). Two zinc fingers are found in the DNA-binding domain of the DNA-repair enzyme PARP -- Poly (ADP-Ribose) Polymerase.
Zinc deficiency can lead to impairment of many hormones, including thyroid, corticosterone, growth hormone and sex hormones. Insulin output can be reduced while there is an increase in insulin resistance. Zinc can counteract the inhibition of DNA synthesis by the toxic, carcinogenic metal cadmium [NUCLEIC ACID RESEARCH; Nocentini,S; 15(10):4211-4225 (1987)].
The immune system is severely impaired by zinc deficiency, due to both reduction in cell division rate and reduced Cu/Zn-SOD. The thymus & spleen are smaller, and lymphoid tissues show more reduced mass than other tissues. The functions of lymphocytes, neutrophils and natural killer (NK) cells are all impaired. Diabetic patients are often supplemented with zinc to improve immune function.
Shellfish and red meats are rich sources of zinc. Nearly 80% of zinc is lost in making flour from wheat during the milling process. Phytate in whole grains binds to zinc thereby aggrevating the risk of zinc deficiency for vegetarians.
| NIACIN | NIACINAMIDE |
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![[ NIACIN ]](niacin.jpg)
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![[ NIACINAMIDE ]](niacinamide.jpg)
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Niacin and its amide, niacinamide, are called vitamers, because both equivalently act as a vitamin. The terms nicotinic acid and nicotinamide are also used for the vitamers. "Niacin" is also a generic term describing both vitamers together.
Niacin can be synthesized from tryptophan, but tryptophan is an essential amino acid that cannot be synthesized. An intake of 60 mg of tryptophan might result in one mg of niacin, because most tryptophan is used by the body for protein maintenance. Riboflavin (Vitamin B2) and pyridoxine (Vitamin B6) are essential cofactors in synthesizing niacin from tryptophan. The niacin-deficiency disease pellagra was first recognized in 1735 by a Spanish physician among people living on corn (maise), a vegetable that is low in both niacin and tryptophan. It wasn't discovered until 1937 that niacin could cure pellagra. The RDA (Recommended Daily Allowance) of 13-20 mg per day is based on the amount required to prevent pellagra.
Niacin forms the core of the nucleotide coenzyme NAD (Nicotinamide Adenine Dinucleotide) and it phosphate coenzyme NADP. NAD and NADP are essential for energy production, electron transport and antioxidant function through hydrogen acceptance (NADH & NADPH) and donation.
A dose of 1.5 to 3 grams of niacin per day can lower LDL cholesterol and elevate HDL cholesterol. NAD+ is required by the DNA-repair enzyme PARP -- Poly (ADP-Ribose) Polymerase. Niacin doses equivalent in a human to 3 to 6 grams per day in rats have been shown to elevate PARP, NAD+ and reduce cancer susceptibility in a dose-dependent manner [JOURNAL OF NUTRITION; Boyonoski,N; 132(1):115-120 (2002)].
An observational study of over 6,000 people 65 years of age and older found that compared to people in the lowest fifth of niacin intake, those with higher intake had between 20% to 50% the risk of getting Alzheimer's Disease. This result was after adjustment for age, sex, race, education, ApoE type and intake of vitamins E & C as well as beta-carotene. The effect was specific to niacin, as opposed to the other B vitamins [JOURNAL OF NEUROLOGY, NEUROSURGERY, AND PSYCHIATRY; Morris,MC; 75(8):1093-1099 (2004)].
Centrophenoxine (Lucidril) & DMAE (DiMethylAminoEthanol) function to protect against free-radical oxidation. DMAE (which is found in high concentrations in sardines & anchovies) is claimed to facilitate production of the neurotransmitter acetylcholine (as is phospatidyl choline). Because acetylcholine (primarily from the nucleus of Meynert in the basal forebrain) acts as a neurotransmitter to stimulate the hippocampus, memory function can be improved somewhat by substances that facilitate acetylcholine production -- particularly in Alzheimer's Disease patients. No cholinergic agonists have been successful in simulating this effect, but some acetylcholinesterase (acetylcholine-destroying enzyme) antagonists like tacrine have been.
DMAE is metabolized in the brain to form phosphatidyl-DMAE which becomes incorporated in nerve cell membranes where it is highly protective against hydroxyl free-radical damage. Loss of permeability of cell membranes with aging is correlated with dehydration, declining enzyme activity and increasing lipofuscin accumulation. This is most serious in the brain & heart because the cells in these tissues are non-dividing.
Centrophenoxine is an ester (carboxyl-linked dimer, ie, two molecules linked to a C=O group by a -O- connection) of p-chlorophenoxyacetic acid and DMAE. Centrophenoxine crosses the blood-brain barrier (BBB) much more effectively than DMAE alone, and once across the BBB the DMAE can be released by hydrolysis. Some early studies claimed that centrophenoxine reverses lipofuscin concentration in the frontal cortex and hippocampus in treated mice (lipofuscin concentration normally increases particularly dramatically in the CA3 cells of the hippocampus). Although there is evidence that centrophenoxine can significantly reduce the rate of lipofuscin accumulation, a more recent study concluded that already-formed lipofuscin cannot be eliminated [JOURNAL OF ANTI-AGING MEDICINE; Terman, A; 2(3):265-273 (1999)].
Procaine (an ingredient of Gerovital, GH-3) is broken-down in the body into para-aminobenzoic acid (PABA, sometimes called a B-vitamin) and DEAE (DiEthylAminoEthanol), which may function similarly to DMAE.
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