Resveratrol Side Effects: What Dr Oz Won't Tell You Pt 5

One of the most pernicious and poorly understood of all resveratrol side effects is related to it's role as an endocrine-disrupting compound. Endocrine disruptors can act directly on hormone receptors, or can influence the synthesis or metabolism of the hormones themselves. The available evidence suggests that resveratrol functions as a phytoestrogen by acting on the estrogen receptor directly and also by altering estrogen metabolism

Resveratrol as a phytoestrogen
One of the major concerns for resveratrol side effects stems for it's function as a partial agonist for the estrogen receptor. This issue has been looked at from many different angles and is the primary reason why resveratrol is a described as "phytoestrogen" in the literature (Gehm). Whole animal studies, however, have been less supportive of this hypothesis (Turner). As we have seen before, this issue suffers from the same test-tube-versus-living-creature dilemma that plagues most resveratrol research.

While the notion of a resveratrol boogey man turning up the dial on your estrogen receptors making men grow breasts is real, but perhaps overstated, a more insidious scenerio can play out...

Resveratrol influences estrogen metabolism
Whether you are a man or a woman, your body is constantly churning out both estrogen and testosterone. Your liver is also constantly chewing up those compounds, turning them into new compounds called metabolites in the process. Since many of these metabolites look quite a bit like the original hormones, they have similar endocrine activities. Many hormone metabolites, however, have no endocrine activity. And this is where the fun starts.

Since your liver enzymes levels can vary based on any number of factors (like smoking, alcohol consumption or resveratrol supplementation, for example), your hormone metabolites shift around accordingly. Fuminsky et al showed that resveratrol potently inhibits the sulfation of estrogen compounds in the liver (3). Hanet et al also showed that resveratrol and other phytoestrogen compounds alter levels of enzymes that process estrogen (4).

What does all this data mean?
In these cases, studies have yet be done measuring the hormone-related resveratrol side effects. It is, however, quite likely that high-dose resveratrol supplementation will impact sex hormone levels. Moreover, these effects will be subtle and are not likely to be picked up in the scientific literature for a while. On a simple level, ask yourself-- who is motivated to do an expensive study on this? Not the drug or supplement companies.

The issue of resveratrol side effects via endocrine disruption cuts deeply into the case against resveratrol supplements. In short: why offer yourself as a human guinea pig when there is no solid evidence that anything positive is happening?

In the final article in this series, we look at human clinical trials to measure whether resveratrol side effects are worth it.

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1. Gehm, BD, McAndrews, JM, Chien, PY, Jameson, JL. "Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor." Proc Natl Acad Sci USA 94 (1997) 14138-43.
2. Turner, RT, Evans, GL, Zhang, M, et al. "Is resveratrol an estrogen agonist in growing rats?" Endocrinology 140 (1999) 50-4.
3. Furminsky, AM, Green, CE, Sharp, LEH, et al. "Effect of Resveratrol on 17b-Estradiol Sulfation by Human Hepatic and Jejunal S9 and Recombinant Sulfotransferase 1E1." Drug Metab Disp 36 (2008) 129-36.
4. Hanet, N, Lancon, A, Delmas, D, et al. "Effects of endocrine disruptors on genes assoicated with 17b-estradiol metabolism and excretion." Steroids 73 (2008) 1242-51.