Posted by Larry Hoover on August 17, 2004, at 10:16:25
In reply to Re: Protein Kinase C and Anxiety, posted by linkadge on August 16, 2004, at 18:23:09
> Fish oil, lithiumm, vitamin E, quercetin all inhibitit protein kinase C.
I knew you knew. Thanks.
> Larry, isn't megadosing B3 potentially bad for the liver ?? What doses are safe ??
>
> LinkadgeThere are numerous variables, including the form of the supplement itself. There is always a possibility of liver complications, but they are extraordinarily rare (perhaps nonexistent?) at the doses I recommend.
2,000 mg niacinamide is ever so slightly maybe exceedingly rarely potentially hepatotoxic. (The risk threshold is generally set at 3,000 mg, and also generally depends on long-term daily use.) The risk is completely alleviated by taking betaine (trimethylglycine) with niacinamide. Any liver damage is reversible, if the supplement is stopped in time. Routine liver enzyme levels should be a part of standard medical care, methinks, particularly if someone is taking a prescribed medication of any sort.
In the context of diabetes prevention (doses not mentioned in the following abstract), animal studies showed optimal prevention at a dose of 500 mg/kg body weight/day. I'm really not sure what dose is used in humans, but it is substantial (and closely monitored).
Lar
Diabetologia. 2000 Nov;43(11):1337-45.
Safety of high-dose nicotinamide: a review.Knip M, Douek IF, Moore WP, Gillmor HA, McLean AE, Bingley PJ, Gale EA; European Nicotinamide Diabetes Intervention Trial Group.
Department of Paediatrics, Medical School, University of Tampere, Finland.
Nicotinamide, the amide derivative of nicotinic acid, has over the past forty years been given at high doses for a variety of therapeutic applications. It is currently in trial as a potential means of preventing the onset of Type I (insulin-dependent) diabetes mellitus in high-risk, first-degree relatives. Nicotinamide is for regulatory purposes classed as a food additive rather than a drug and has not therefore required the formal safety evaluation normally expected of a new therapy. Because the safety of treatment with megadoses of vitamins cannot be assumed, a full literature review has been undertaken. The therapeutic index of nicotinamide is wide but at very high doses reversible hepatotoxicity has been reported in animals and humans. Minor abnormalities of liver enzymes can infrequently occur at the doses used for diabetes prevention. There is no evidence of teratogenicity from animal studies and nicotinamide is not in itself oncogenic; at very high doses it does however potentiate islet tumour formation in rats treated with streptozotocin or alloxan. There is no evidence of oncogenicity in man. Growth inhibition can occur in rats but growth in children is unaffected. Studies of its effects on glucose kinetics and insulin sensitivity are inconsistent but minor degrees of insulin resistance have been reported. The drug is well tolerated, especially in recent studies which have used relatively pure preparations of the vitamin. Experience to date therefore suggests that the ratio of risk to benefit of long-term nicotinamide treatment would be highly favourable, should the drug prove efficacious in diabetes prevention. High-dose nicotinamide should still, however, be considered as a drug with toxic potential at adult doses in excess of 3 gm/day and unsupervised use should be discouraged.
poster:Larry Hoover
thread:378027
URL: http://www.dr-bob.org/babble/alter/20040815/msgs/378630.html