Wednesday, July 24, 2013

Resveratrol and exercise: a good thing or bad?

An article just out this week suggests that resveratrol actually cancels the beneficial effects of exercise in older men. This widely cited study, not yet even in print, was a randomized prospective clinical trial in which healthy but inactive men were placed on an exercise program and given either a 250 mg resveratrol supplement or placebo.  Exercise tolerance (measured by maximum oxygen uptake), improved cholesterol profiles, and blood pressure indicators in a group of men average age 65 were all improved after 6 weeks in the placebo group as compared to those taking resveratrol , who had no significant changes.  This runs counter to expectations from several previous studies (mostly on mice) that suggested the opposite. Resveratrol has even been touted as a performance-enhancing supplement!

This is one reason why use of supplements based primarily on animal studies is problematic; when tested in humans, data may be contradictory. The real questions are how and why such different effects can occur. One explanation is a phenomenon called hormesis. This is sort of the inverse of the J-shaped curve of healthy drinking, with low concentrations yielding a neutral or negative effect, increasing doses having a greater effect up to a point, then adverse or even opposite effects at doses above that. It is important to recognize that paradoxical effects can occur at concentrations either low or high, and the optimal range (in pharmacology called the “therapeutic window”) may vary with different types of tissues. So the best dose for exercise training (if any) could be entirely at odds with what brain cells or blood vessels respond to.  Also called a “biphasic response,” the effect has been seen in cancer cell cultures, osteoporosis, and other systems.

All this presumes of course that resveratrol in supplement form is evenly absorbed and distributed, which seems also to be highly variable. Even if resveratrol enhanced the beneficial aspects of exercise in men, there are the hormetic estrogen properties to sort out. If all this is enough to drive one to drink, I suggest a glass (or 2 at the most) of red wine.

Friday, July 19, 2013

From grapes to great skin: new evidence for resveratrol

When I first developed our resveratrol-based antioxidant skin care product Veraderma in conjunction with Calidora Skin Clinics in 2008, I had good reason to believe in its potent anti-aging capabilities. Resveratrol , the multipurpose miracle molecule whose most familiar source is wine grape skins (hence red wine because it is fermented with the skins), has become a bit of a sensation since then. Several major skin care companies now include wine compounds in their products, and the science continues to reinforce the role of resveratrol in healthy skin (even if its use as an oral supplement remains to be proven.)

One example comes from independent research underwritten by L’Oreal, which found that there are specific resveratrol “binding sites” in human skin cells that mediate resveratrol’s protective properties. These binding sites appear to trigger changes within the cells rendering them resistant to damage from environmental toxins. Notably, resveratrol was more effective than the green tea-derived antioxidant compound EGCG, and the resveratrol derivative piceatannol.

This latter finding may actually be the most significant aspect of the study because it makes the case for resveratrol as a skin care ingredient as opposed to a supplement. One of the concerns with use of resveratrol as a supplement is that it is rapidly metabolized into other compounds such as piceatannol, so if it ever reaches the skin through the bloodstream it may have either changed into something else or not reach high enough levels to be meaningful. (Another recent study found however that resveratrol combined with other wine polyphenols improved skin moisturization and elasticity,  and diminished skin roughness and depth of wrinkles after 60 days of taking the supplement.)

Another somewhat confused issue is whether resveratrol is a true activator of anti-aging enzymes called sirtuins. You will recall that resveratrol was hailed as an anti-aging breakthrough when it was first reported to be a situin activator –at least in yeast, roundworms, and fruitflies – and an industry was born. The picture turns out to be considerably more complicated however, but sirtuins have been recently shown to promote healthy skin. It is possible that resveratrol works via this pathway as well. There is clearly much to be learned still about resveratrol despite the hundreds of published studies, but if your skin care plan doesn’t include wine polyphenols, you may be missing out.