Resveratrol Side Effects: What Dr Oz Won't Tell You Pt 4

While reports of direct resveratrol side effects are not common at this point, the natural origin of this "miracle supplement" does not make it 100% safe.

When you think about drug side effects, often you aren't considering something that arises directly from the drug. One major indirect side effect of resveratrol is that it alters the way your liver handles chemicals coming in from outside. As a result, resveratrol can lead to unexpected interactions with drugs, foods, and even other supplements. In this article, we will explain how this process works.

Your body uses enzymes in your liver to chew up unwanted chemicals in the bloodstream. While this information may not be new, what you may not have know is that your liver enzyme levels are not constant. Many different foreign compounds can modify the spectrum of enzymes at work in the liver. Resveratrol is one of those compounds. Because these effects are dose- and duration-dependent, you need to be especially careful when taking large quantities of a purified compound like resveratrol supplements over prolonged periods. I predict that resveratrol side effects will relate to this issue.

Some compounds have more profound liver effects than others.
For instance, Piver et al compared the effects of resveratrol and other red wine components to extracts from white wine, grape juice, and cognac (1). Resveratrol and other red wine-based compounds showed considerably higher inhibition of the CYP enzymes in the liver than the other compounds explored. Several other studies in the literature have established that resveratrol inhibits a range of CYP enzymes (2,3).

Many drugs that are on the market now have drug-drug interactions based on CYP enzyme inhibition. As one drug alters the levels of a particular liver enzyme, another drugs that gets metabolized by the same enzyme will be removed from the bloodstream more slowly. The result can be an accumulation of a drug to harmful levels within the bloodstream. While this issue may only impact some specific cases, it is one of the more serious resveratrol side effects to worry about.

Not all CYP-inhibition is a bad thing
This situation with liver enzymes reflects another example of "it's not a bug, it's a feature." Because CYP enzymes in the liver can sometimes produce compounds more toxic than the ones they started with, CYP-inhibition has been promoted as part of anti-cancer regimen. While this idea may have some merits, I generally don't think that interfering with your body's natural metabolism process is wise. You can decide for yourself, but there is a component of this process you may not have considered...

The dark underside of liver enzyme inhibition
The funny thing about liver enzymes is that they don't discriminate between stuff you eat and compounds your body makes by itself. This means that hormones are impacted as well. Want to alter your estrogen metabolite ratio? Eat broccoli. Seriously. Cruciferous vegetables change the activity of liver CYP enzymes in a way that alters your body's handling of estrogen. While the exact issues have not been worked out by research, altered sex hormone balance is another of of the potential resveratrol side effects.

In fact, it has already been shown in the literature that resveratrol has estrogenic properties, both as a result of enzyme inhibition and direct interaction with the estrogen receptor.

Read on for a more detailed take on this aspect of resveratrol side effects

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References on resveratrol side effects
1. Piver, B, Berthou, F, Dreano, Y, Lucas, D. "Inhibition of CYP3A, CYP1A, and CYP2E1 activities by resveratrol and other non volatile red wine components." Toxicol Lett 125 (2001) 83-91.
2. Canistro, D, Bonamassa, B, Pozzetti, L, et al. "Alteration of xenobiotic metabolizing enymes by resveratrol in liver and lung of CD1 mice." Food and Chemical Toxicology 47 (2009) 454-61.
3. Yu, C, Shin, YG, Kosmeder, JW, et al. "Liquid chromatography/tandem mass spectrometric determination of inhibition of human cytochrome P450 isozymes by resveratrol and resveratrol-3-sulfate." Rapid Commun Mass Spec. 17 (2003) 307-13.