Does Resveratrol Benefit Our Metabolic Health?

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Which conditions have resveratrol supplements been shown to help?

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Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.

To see if the amount of resveratrol you get from drinking red wine might be beneficial, researchers looked to the Chianti region of Tuscany to determine whether the levels achieved through diet help protect against long-term frailty, inflammation, cardiovascular disease, cancer, or death. And the answer? None of the above. The amount of resveratrol flowing through their systems didn’t correlate with any of the health outcomes studied over nine years of follow-up. This is surprising, even if only because of the confounding factors associated with wine consumption.

Wine drinkers may be less likely to smoke, and tend to have higher IQ, higher parental education levels, and higher socioeconomic status––which would be expected to correlate with better health outcomes. (In contrast, beer drinkers suffer the opposite—lower IQ, parental education, and social class. The average IQ of wine-drinking men is 113, compared to 95 among beer-drinking men). Yet still, there appeared to be no correlation between resveratrol exposure and wellbeing. This may be because wine-drinking populations may only be averaging less than a milligram of resveratrol a day.

Some “experts” recommend a daily dose of 1 gram of resveratrol, based on the dosing used in laboratory animal studies. How much red wine would you have to drink to get that much? Eight thousand glasses a day. Not a fan of red wine? A couple thousand gallons of white wine a day would do it, or 5,000 pounds of apples or grapes, 50,000 pounds of peanuts, a couple thousand pounds of chocolate, or nearly a million bottles of beer, on the wall.

The natural levels of resveratrol found in foods and beverages is not considered to be sufficient to elicit health effects, but that doesn’t necessarily mean supplements wouldn’t work. However, the bioavailability of even high-dose resveratrol has been called into question. Maximum blood levels after resveratrol supplementation can be as low as 40 nanomolar, which is more than a hundred times lower than the 5,000 to 250,000 nanomoles used in vitro to demonstrate resveratrol effects. Even a five-gram dose of resveratrol may fall short of the required level. This is in contrast to rodents, in which blood levels of 32,000 have been reported.

Resveratrol is rapidly absorbed in humans, but is rapidly metabolized in our intestine and liver. So, very little free resveratrol remains. But, there are about 20 resveratrol-derived metabolites that can end up in circulation at much higher levels, like 20,000 nanomolar, that might have biological activity of their own.

What about using the turmeric trick of adding black pepper to suppress our body’s natural detoxification mechanisms? It works in mice. The black pepper compound piperine increases maximum blood concentrations of resveratrol more than 1,000 percent. But, unfortunately, it failed to significantly alter blood levels in people.

In a 2014 medical journal editorial entitled “The resveratrol fiasco,” the editor-in-chief summarized the state of the science: “The conclusions are quite clear-cut: after more than 20 years of well-funded research, resveratrol has no proven human activity.” However, since that publication, more than 150 human clinical trials have been published. What’s the update?

Resveratrol was initially envisaged as an antioxidant, but meta-analyses of randomized controlled trials of resveratrol supplements failed to find clinically or even statistically significant effects on systemic markers of oxidative stress, helping to explain the lack of apparent DNA protection.

Maybe it only helps with the metabolically compromised? As one resveratrol review asked, “What conclusions would we draw about the efficacy of penicillin if it had been tested only among persons in the pink of condition?” Resveratrol does not appear to improve the metabolic function of nonobese, nondiabetic individuals, or even benefit overweight nondiabetics. Nor does it help people lose weight. But resveratrol may help with blood sugar control in diabetics. For almost all outcomes measured in randomized controlled trials of type 2 diabetes, metabolic syndrome, or nonalcoholic fatty liver disease, the effects of resveratrol were trivial, but a meta-analysis did find that doses ranging from 5 to 500 mg twice a day resulted in an average 20-point drop in fasting blood sugars.

There was also a significant benefit for longer-term blood sugar control, though this only appeared to be the case in shorter-term studies. What is the point of better longer-term control, if it only works in studies lasting less than three months?

Diabetic foot ulcers are the leading cause of lower-limb amputations in diabetics. A randomized, double-blind, placebo-controlled trial of 50 mg of resveratrol twice a day showed accelerated healing of diabetic foot ulcers by about 1 cm over placebo within 60 days. So, at least there’s one condition it may help. Next, I’ll cover resveratrol for joint, brain, and bone health, and then I’ll talk about the downsides.

Please consider volunteering to help out on the site.

Motion graphics by Avo Media

Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.

To see if the amount of resveratrol you get from drinking red wine might be beneficial, researchers looked to the Chianti region of Tuscany to determine whether the levels achieved through diet help protect against long-term frailty, inflammation, cardiovascular disease, cancer, or death. And the answer? None of the above. The amount of resveratrol flowing through their systems didn’t correlate with any of the health outcomes studied over nine years of follow-up. This is surprising, even if only because of the confounding factors associated with wine consumption.

Wine drinkers may be less likely to smoke, and tend to have higher IQ, higher parental education levels, and higher socioeconomic status––which would be expected to correlate with better health outcomes. (In contrast, beer drinkers suffer the opposite—lower IQ, parental education, and social class. The average IQ of wine-drinking men is 113, compared to 95 among beer-drinking men). Yet still, there appeared to be no correlation between resveratrol exposure and wellbeing. This may be because wine-drinking populations may only be averaging less than a milligram of resveratrol a day.

Some “experts” recommend a daily dose of 1 gram of resveratrol, based on the dosing used in laboratory animal studies. How much red wine would you have to drink to get that much? Eight thousand glasses a day. Not a fan of red wine? A couple thousand gallons of white wine a day would do it, or 5,000 pounds of apples or grapes, 50,000 pounds of peanuts, a couple thousand pounds of chocolate, or nearly a million bottles of beer, on the wall.

The natural levels of resveratrol found in foods and beverages is not considered to be sufficient to elicit health effects, but that doesn’t necessarily mean supplements wouldn’t work. However, the bioavailability of even high-dose resveratrol has been called into question. Maximum blood levels after resveratrol supplementation can be as low as 40 nanomolar, which is more than a hundred times lower than the 5,000 to 250,000 nanomoles used in vitro to demonstrate resveratrol effects. Even a five-gram dose of resveratrol may fall short of the required level. This is in contrast to rodents, in which blood levels of 32,000 have been reported.

Resveratrol is rapidly absorbed in humans, but is rapidly metabolized in our intestine and liver. So, very little free resveratrol remains. But, there are about 20 resveratrol-derived metabolites that can end up in circulation at much higher levels, like 20,000 nanomolar, that might have biological activity of their own.

What about using the turmeric trick of adding black pepper to suppress our body’s natural detoxification mechanisms? It works in mice. The black pepper compound piperine increases maximum blood concentrations of resveratrol more than 1,000 percent. But, unfortunately, it failed to significantly alter blood levels in people.

In a 2014 medical journal editorial entitled “The resveratrol fiasco,” the editor-in-chief summarized the state of the science: “The conclusions are quite clear-cut: after more than 20 years of well-funded research, resveratrol has no proven human activity.” However, since that publication, more than 150 human clinical trials have been published. What’s the update?

Resveratrol was initially envisaged as an antioxidant, but meta-analyses of randomized controlled trials of resveratrol supplements failed to find clinically or even statistically significant effects on systemic markers of oxidative stress, helping to explain the lack of apparent DNA protection.

Maybe it only helps with the metabolically compromised? As one resveratrol review asked, “What conclusions would we draw about the efficacy of penicillin if it had been tested only among persons in the pink of condition?” Resveratrol does not appear to improve the metabolic function of nonobese, nondiabetic individuals, or even benefit overweight nondiabetics. Nor does it help people lose weight. But resveratrol may help with blood sugar control in diabetics. For almost all outcomes measured in randomized controlled trials of type 2 diabetes, metabolic syndrome, or nonalcoholic fatty liver disease, the effects of resveratrol were trivial, but a meta-analysis did find that doses ranging from 5 to 500 mg twice a day resulted in an average 20-point drop in fasting blood sugars.

There was also a significant benefit for longer-term blood sugar control, though this only appeared to be the case in shorter-term studies. What is the point of better longer-term control, if it only works in studies lasting less than three months?

Diabetic foot ulcers are the leading cause of lower-limb amputations in diabetics. A randomized, double-blind, placebo-controlled trial of 50 mg of resveratrol twice a day showed accelerated healing of diabetic foot ulcers by about 1 cm over placebo within 60 days. So, at least there’s one condition it may help. Next, I’ll cover resveratrol for joint, brain, and bone health, and then I’ll talk about the downsides.

Please consider volunteering to help out on the site.

Motion graphics by Avo Media

Doctor's Note

This is the second in a four-video series on resveratrol. Does Resveratrol Make You Live Longer? was the first one. Stay tuned for Resveratrol Tested for Alzheimer’s, Arthritis, and Osteoporosis and Side Effects of Resveratrol Supplements.

What about just drinking wine? See Is It Better to Drink a Little Alcohol Than None at All?.

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