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Niacinamide acts as an antioxidant by preventing NAD depletion during DNA repair by inhibiting poly (ADP-ribose) polymerase (PARP), which also modulates major histocompatibility complex (MHC) class II expression. Niacinamide inhibits free radical formation and facilitates beta-cell regeneration in vivo and in vitro.7,8 Additional protection from macrophage toxins may be involved in prevention of type 1 diabetes.9 Specifically, niacinamide has been shown, via PARP inhibition, to protect pancreatic islet-cell lysis after exposure to oxygen free radicals10 and nitric oxide.11,12 Niacinamide has also been found to stimulate GABA receptors, without binding to the receptor sites, thus creating a benzodiazepine-like effect.13 Anti-inflammatory action affecting neutrophil chemotaxis has been reported for niacinamide.14

Additionally, due to its inhibition of ADP-ribosylation, niacinamide has been shown to suppress cytokinemediated induction of nitric oxide synthase in a number of cells, thus effecting interleukin-1-exposed chondrocytes, resulting in decreased inflammation.

Niacinamide and niacin have been used since 1940 or earlier to treat a number of psychiatric conditions. Hoffer is a strong advocate of the use of niacinamide in the management of schizophrenia and has collected data on more than 1,000 patients given either niacinamide or niacin (1.5-6 g/day) for three months to five years duration.24

Hoffer concluded in further studies that this treatment is most effective for early and acute schizophrenics, while it appears to be ineffective, especially when given alone, for chronic sufferers. 25 A study by Mohler found niacinamide to produce an anti-anxiety effect equivalent to a highly potent benzodiazepine. Like benzodiazepines, niacinamide appears to stimulate GABA receptors without binding to receptor sites.

Because the literature on niacinamide spans more than 50 years, evaluation of toxicity is conflicting. Data on the side effects of niacinamide and niacin are often confused as earlier studies used mixtures of the two in preparations. Furthermore, the purity of niacinamide preparations varies considerably as some preparations include trace amounts of niacin.6 Older clinical studies report relatively frequent liver enzyme abnormalities;42 however, recent studies using purified niacinamide have not detected such abnormalities.17,23 Nausea is usually the first side effect noted with niacinamide. Other side effects associated with high-dose niacinamide include heartburn, vomiting, flatulence, and diarrhea. Mild headaches and dizziness have been reported after giving niacinamide parenterally.