Higher Levels of Resveratrol?

Q I have been taking “Life Extension” products for 30 years, ever since I read Durk Pearson & Sandy Shaw’s first book. In all my reading concerning healthy life extension, resveratrol seems to be the most promising by far, with strong data to back it. Yet all indications are that large doses are required, 4,000-5,000 mg/day. Why is Life Enhancement not offering large doses of it?

DEAN, St. Louis, MO

A There is concern that higher levels of resveratrol may be toxic. In this issue of Life Enhancement, on page 23, is the latest issue of Durk & Sandy’s Life Extension News. In the opening article titled, “EMERGING SCIENCE: Life Extension by Inhibiting Growth,” they report on their investigation of higher levels of natural products such as resveratrol for inhibiting mTOR (mammalian target of rapamycin) as a possible means of extending life.

Rapamycin is a prescription drug, administered to kidney transplant patients to prevent organ rejection. It inhibits mTOR. Durk & Sandy write, “Results in these patients have included the unexpected prevention of cancer and even cures of some pre-existing cancers. [Emphasis added.] Moreover, two years after renal transplantation, the body-mass index of patients treated with rapamycin was significantly lower than the patients treated with cyclosporine, another immunosuppressant. A study was described in which 11 healthy men were treated with 6 mg of rapamycin, with the prevention of insulin resistance that accompanies the large increase of nutrients (that ordinarily induces mTOR signaling) during feeding. At present, rapamycin is being investigated in clinical trials as a treatment for cancer.” [References left out.]

And there is much more about the benefits of rapamycin, so much so that drug companies are working to develop rapamycin derivatives for possible treatment, aside from cancer, of autoimmune disorders, type 1 and type 2 diabetes, and obesity. Rapamycin may also have an anti-Alzheimer’s disease property. To top that, last year a paper was published indicating that rapamycin given late in the lives of mice leads to increased mammalian lifespan.1

Back to your question, after searching through papers showing that resveratrol can inhibit mTOR, what confronts Durk and Sandy repeatedly is that high-dose resveratrol may be toxic, and that “Further research is needed to understand the varying effects of different doses of resveratrol in rats (and, indeed, in humans) fed different diets to determine optimal doses. It has already been found that dietary composition may affect the degree of life extension resulting from caloric restriction in fruit flies.”

That said, calculations indicate that some of the toxic reports occur at far less than your equivalent range of 4,000–5,000 mg in humans per day.

Significantly, turmeric is also an mTOR inhibitor, and may be used safely at amounts up to 4,800 mg/day.

  1. Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 2009 Jul 16;460(7253):392-5.

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