Side Effects of Resveratrol Supplements

If you have a condition that might benefit from resveratrol supplementation, like diabetic foot ulcers, or ulcerative colitis, or menopausal pains, and want to give resveratrol a try, are there any concerns, aside from the cost, which can exceed $10 a day? Well, although a meta-analysis of studies of resveratrol found no overall effect on LDL cholesterol levels, a couple studies found that resveratrol sometimes increased LDL levels, up to 25 percent over placebo. As cardiovascular disease is by far the leading killer of diabetics, as well as other conditions for which you might take it, if you do try resveratrol, please make sure to have your cholesterol closely monitored.

The scientific literature regarding resveratrol and cardiovascular health in general is said to be “replete with conflicting information and controversy.” There are no human studies with cardiovascular disease outcomes, but an often-overlooked study found that resveratrol caused atherosclerosis in rabbits. The study, entitled “Resveratrol promotes atherosclerosis in hypercholesterolemic rabbits,” found that the hardening of the arteries of bunnies fed dietary cholesterol was worsened by resveratrol. But, negative or null findings are often marginalized by the resveratrol research community; so, you rarely hear about them.

Though there are no long-term safety data, 450 mg a day has been considered a safe dose, at least in the short term, for a 60 kg person (that’s about 130 pounds), but supplementation at higher doses could be potentially toxic. Daily doses of resveratrol in excess of a gram commonly cause mild to moderate gastrointestinal symptoms, such as nausea, diarrhea, and abdominal pain, as well as “anal itchiness.” Unexpected renal toxicity with cases of severe kidney failure were noted in a five-gram-a-day study, but this was in the context of a cancer that is particularly hard on the kidneys.

Two studies, however, found that so-called “safe” levels of resveratrol (at 150 to 250 mg a day) may blunt some of the positive effects of exercise training. In rodents, resveratrol supplementation decreases cardiovascular risk factors and improves cardiovascular function and physical capacity. But, when it was put to the test in older men (with an average age of 65), the exact opposite was found. Specifically, combining resveratrol with athletic training abolished the reduction in blood pressure, cholesterol, and triglycerides normally associated with exercise, had a more artery-constricting effect than a dilating one, and led to a significantly lower increase in aerobic fitness. Rodents on resveratrol get enhanced exercise performance, but, in people, the resveratrol induced a 45 percent lower increase in maximum aerobic capacity compared with those taking a sugar pill. For all of their working out, the resveratrol was undercutting their efforts. An apparent impairment in peak aerobic power was also noted in young men following high-intensity interval training on resveratrol compared to placebo.

A recent review overreacted to these data by suggesting “foods containing resveratrol should not be consumed during exercise,” but to even reach the lower dose of 150 mg you’d have to eat more than a 100 pounds of grapes a day. (Though, I suppose if you did manage to stuff in a hundred pounds of grapes, it might, indeed, be a little impairing.

The exercise impairment with resveratrol supplements does make sense, though, given its purported mechanism. Sirtuin activation by resveratrol is thought to occur via the activation of the body’s fuel gauge, AMPK, by interfering with energy production in the mitochondria powerplants in our cells. Mouse cells react by increasing mitochondria to compensate, but human cells apparently do not; so, the energy-dimming effect of resveratrol may explain why the effects of exercise are impaired.

What works in animals may not necessarily work in people. Thus, concluded one review, the hype regarding resveratrol may “turn out to be nothing more than a sleight-of-hand marketing device using peer-reviewed, published, non-human research as a cover.” Although some like Dr. Oz have recommended resveratrol as a life-extending “miracle molecule,” given that evidence-based responses are sparse-and-controversial such “claims, innuendo, and hyperbole” are said to be “atrocious.”

The fitness-blunting exercise study of older adults was supported in part by a manufacturer of resveratrol supplements. To their credit, the researchers responded to an angry letter from a supplement company consultant that “quote” it is our opinion that we, as scientists, have a responsibility to report what we find and not to twist our findings to fit the commercial interests “unquote.”