I've been trying T-Res (about 200mg) for a short time. This did put my both feet on firm ground again(link to Methuslah Foundation thread). Worth spending a half hour reading and a day afterwards to absorb. No megadosing for me until more research is available. There are also my questions regarding the the design of the Sinclair study that I raised in the 500mg thread.
I was not impressed with Methuselahmouse's "paper"; his arguments against resveratrol amount to: a. certain tumors upregulate SirT1, and b. Only short-lived variants of species have shown increased life-span with resveratrol.
a. is largely irrelevant; one would expect tumors, which often have a very stressful, hypoxic micro-environment to upregulate a stress-response master regulator. I see no reason at this point to think that it's causative rather than an adaptive response in the tumor.
b. One could say the same of CR; a wild strain of mice showed no increase in life-span on CR. (In any case, humans are not a wild strain of homo sapiens.) Short of a life span study, one can only look at associated bio-markers. These look positive across species, though one can present them in a negative light.
It is clear than many genes are commonly activated by CR and by resveratrol, across many species. The anecdotal reports on this form (and elsewhere) of people taking various doses is that resveratrol supplementation reverses many markers of aging, e. g. unfavorable blood lipids, high blood pressure, arthritic symptoms. Negative effects reported have been few and far between; until Tintinet reported numbness and tingling in his extremities, the most serious symptom reported seemed to be diarrhea, and that due mostly to the emodin present in most extracts. Xanadu reported over-stimulation, but: the only reports of resveratrol as a stimulant seem to be with preparations containg OPCs, psychological symptoms such as insomnia are frequently misattributed to external factors. Those on high doses of 98% oure extract of synthetic resveratrol do not report a drug-like stimulatory effect.
I was the one who reported, months ago, that the experience of Chinese medicine with Polygonum-containing herbal preparations used to treat many conditions symptomatic of aging, implied the symptoms of chronic overdose might be the same in resveratrol: peripheral neuropathy, a numbness and tingling in the extremities, that would be reversed on cessation of supplementation. Now Tintinet has announced that on a dose of 2 grams a day he has those symptoms. Since many here have been taking similarly large doses, and at least one person I know of has been taking 6 grams a day for a year, without such symptoms, I have to ask: are Tintinet's symptoms due to resveratrol, or to another among his plethora of supplements? Or perhaps it is a synergistic effect with another of his supplements. Quercetin, perhaps? And now he tells us he is taking Benegene as well, and his symptoms started about the time he started taking Benegene and increased his dose of resveratrol. Please, Tintinet, revert to your previous regimen, and when your symptoms cease, change just one variable at a time.
In short the only reported symptom I find troubling is Tintinet's neuropathy, which may not be due to resveratrol, and is not replicated among other high-dose users. The reported stimulatory effect also does not appear to be due to resveratrol. Whether resveratrol will extend life span is unknown, but there have been sufficiently many reports of beneficial effects here and elsewhere for me to come to my own conclusion.