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Secrets of Caloric Restriction

not toxic – that have these inhibitory effects on metabolism, by creating the metabolic stress that I described, and mimicking the effects of caloric restriction, including the effects on lifespan. More importantly, I like to call these effects on ‘health-span,’ that is, improving the quality of life in later years – healthy living versus just extension of the lifespan.”

It also seems reasonable to suspect, however, that these health-span effects can be achieved as well, if not better, through nutritional supplements that increase the amount of NAD in the body. The body converts the nutrient niacin (vitamin B3), in the form of either nicotinic acid or nicotinamide, into NAD. It is also known that, although both nicotinic acid and nicotinamide produce NAD in the body, the rate of synthesis from nicotinamide is twice as great as that from nicotinic acid. In addition, the conversion of nicotinamide (but not nicotinic acid) into NAD is accelerated significantly by inorganic phosphate.8

Nicotinamide may have other benefits besides increasing levels of NAD. In addition to acting as a catalyst to Sir2p, NAD has been shown to reduce general damage to genetic material, and it protects against stress-induced apoptosis (cell suicide). In addition, NAD guards against autoimmune damage and protects pancreatic beta cells in Type 1 diabetes. It may even stave off diabetes in prediabetics.9 Many people who take nicotinamide supplements also report that they simply feel better and have more energy. This makes sense, because its traditional use, written about by Linus Pauling and others, has been effective in alleviating severe psychiatric symptoms when it is given in the range of 1.5-18 grams/day, along with 3 grams/day of ascorbic acid (vitamin C).10

The current caloric restriction research suggests that future possibilities for life extension in the area of genetics appear to be especially promising. But fully understanding the role that the Sir2 genes – and all the other genes – play in the aging process is still years away.

“Many people are focusing on genetic approaches,” said Lane, “and my own particular feeling on that is that aging is very complex. Richard Weindruch – a real leader in the field of caloric restriction – looked at about 10% of the genes in a mouse and showed that around fifty-some genes were altered by caloric restriction. So imagine, if that’s only 10% of the mouse genome, and you multiply that by ten, you’re talking about hundreds of genes that are altered during aging and may be affected by caloric restriction. So I think a pure genetic approach is a long way from yielding potential results. Our approach is to use this metabolic inhibition to get at the mechanism.”

Through the use of a high-potency nutritional supplement with nicotinamide and the proper cofactors to produce abundant NAD, you may be able to elevate the levels of NAD available in your cells, thereby enhancing Sir2p’s role in gene silencing. When this happens, it is possible to reduce the deleterious messages, prevent runaway proliferation, and “get at the mechanism” – and you can do it today, so you’re more likely to be around tomorrow, when the really big genetic breakthroughs occur. Perhaps nicotinamide and those cofactors offer the benefits of caloric restriction without the sacrifice of near-starvation.


  1. Pugh TD, Oberley TD, Weindruch R. Dietary intervention at middle age: caloric restriction but not dehydroepiandrosterone sulfate increases lifespan and lifetime cancer incidence in mice. Cancer Res 1999 Apr 1;59(7):1642-8.
  2. Weindruch R. The retardation of aging by caloric restriction: studies in rodents and primates. Toxicol Pathol 1996, Nov-Dec;24(6):742-5.
  3. Walford R. Secrets of Long Life: Dr. Roy Walford’s Plan to Live to 150.
  4. Black A, Lane M, et al. Calorie restriction reduces the incidence of proliferative disease: preliminary data from the NIA CR in nonhuman primate study. Gerontological Society of America Annual Meeting, November 17, 2000, Washington, D.C.
  5. Sohal RS, Weindruch R. Oxidative stress, caloric restriction,and aging. Science 1996;273:59-63.
  6. Lin SJ, Defossez PA, Guarente L. Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science 2000; 289(5487):2126-8.
  7. Guarente L, Kenyon C. Genetic pathways that regulate ageing in model organisms. Nature 2000 Nov 9;408(6809):255-62.
  8. Micheli V, Simmonds HA, Sestini S, Ricci C. Importance of nicotinamide as a NAD precursor in the human erythrocyte. Arch Biochem Biophys 1990;283(1):40-5.
  9. Pozzilli P. Prevention of insulin-dependent diabetes mellitus. Diabetes Metab Rev 1998;14(1):69-84.
  10. Pauling L. Orthomolecular psychiatry: varying the concentrations of substances normally present in the human body may control mental disease. Science 1968 Apr 19;160(825):265-71.

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