By: David A Fein, MD CBCCT
Medical Director
“Reap the benefits of Resveratrol without the alcohol or the calories” proclaims a website touting the supplement as the “ultimate anti-oxidant” that can prevent cancer, slow aging and increase longevity. In the laboratory there are demonstrable potential benefits from resveratrol. But should you be taking it as a daily supplement?
Produced by several plants as part of their defense mechanism in response to attack by bacteria or fungi, resveratrol is most notably found in the skin of most grapes. So, both grape juice and red wine have high levels of this potent substance. The health benefits of resveratrol may be so far-reaching that some proponents believe that it is the resveratrol in wine that may explain the “French Paradox”, the belief that the French have a relatively low level of cardiovascular disease despite high fat intake and high levels of smoking.
(For more on the “French Paradox” and why it may be more myth than fact, read our newsletter article “Drink to Your Health”)
Many believe that resveratrol can add years to our life expectancy. It has been shown to increase lifespan in yeast cells. Similar results have been seen in flatworms, fruit flies and at least one species of fish. So, if you want your yeast and fruit flies to live longer then resveratrol looks like a good plan. So far, there is no data to show a comparable effect in humans.
In mice very high doses of resveratrol (equal to about 1500-2000 mgs per day in an average human) can reverse some of the effects of bad diets. When mice are fed a diet high in saturated fats, those given resveratrol had about a 30% lower mortality rate and had lower levels of blood sugar and insulin.
In laboratory cell cultures resveratrol has shown anti-cancer effects on several different cancer types. When applied to the skin of laboratory animals resveratrol appears to decrease the damage caused by ultraviolet light exposure and reduce the development of skin cancers. Resveratrol may also inhibit blood vessel growth in tumors. However, in all of these cases the concentration of resveratrol that was required in a culture dish or on the skin was much higher that the levels found in the bloodstream with an oral dose of resveratrol.
Recent data has also indicated that in animal models resveratrol may be able to reduce brain plaques that are associated with Alzheimers Disease and other degenerative disorders.
Part of the mechanism of action for resveratrol may be related to activation of a genetic pathway called Sirtuin 1 (SIRT1). This is thought to be the same pathway that is activated by very low calorie diets that have been shown to extend lifespan in some animals. This may be related to anti-oxidant or anti-inflammatory effects associated with the SIRT1 gene. The SIRT1 gene and similar metabolic pathways are also thought to be involved in the beneficial effects of exercise. However, the studies on the role SIRT1 and how resveratrol may affect this gene are still controversial and contradictory.
So, if resveratrol might be able to extend lifespan, prevent dementia, cancer, diabetes, heart disease and mimic the effects of exercise without getting off the couch, shouldn’t we all be taking it?
Well, before you head over to Google to start ordering your resveratrol capsules, a couple of problems remain.
While the studies of the effects of resveratrol are promising, none of these benefits have yet been demonstrated in humans. Beside the lack of meaningful data as to its effects in people, before you reach for resveratrol as the new fountain of youth there is one other problems to consider: it is hard to get enough resveratrol into your body.
Resveratrol is found in a variety of plant sources. Peanuts and grape skins are good sources and most people think of wine as the best source of resveratrol. (Most of the oral supplements on the market use resveratrol derived from the Japanese Knotwood plant.) Since resveratrol is found in the skin of the grape. The same grapes are used for both red and white wine. Whether the juice is fermented with or without the skins determines the color of the wine. Red wine is kept in contact with the grape skin much longer than white wine so red wines have much higher levels of resveratrol. But the level of resveratrol varies greatly from wine to wine from as little as 0.1 mg/L to over 12 mg/L. This is more than a 100-fold difference and there is no easy way to predict how much resveratrol is present in a particular wine.
The bigger problem is that even when you find a wine that is high in resveratrol, or take an oral supplement of resveratrol, very little of it makes it into your blood stream. This is because of a phenomenon known as “First Pass Metabolism”. Essentially all the blood flow from the intestines must first pass through the liver before entering the general circulation. The liver is very effective at protecting us from toxins in our food and metabolizes most substances before they can reach the rest of the body. As quickly as you can absorb the resveratrol from your gut, the liver breaks it down before it reaches the rest of the body.
An “interesting” study gave five men 600 mL (4 glasses) of wine before breakfast. Three of the “volunteers” had undetectable levels of resveratrol in their blood and the other two had only trace amounts. When volunteers were given much higher doses such as are present in most capsules only low levels of resveratrol appeared in the blood and within 4 hours it was completely gone. Researchers have concluded that it is very difficult for oral supplements to achieve blood concentrations of resveratrol that approach the levels that showed an effect in the laboratory studies. (Theoretically, there might be a small benefit in protecting against some digestive tract tumors from direct exposure to resveratrol in the gut.)
This also makes resveratrol a very unlikely candidate to explain the “French Paradox”. Even the most ardent wine drinkers are unlikely to get enough resveratrol into their bloodstream to have enough of an effect. If the “French Paradox” is at all related to wine intake (a debatable and very likely overly simplistic explanation) it is more likely to be either due to the direct effects of the alcohol or from other substances in wine. (A good candidate may be Procyanidins, the topic of our next newsletter.)
The long term effects of high doses of resveratrol in humans are not really known yet. Resveratrol may have some estrogen-like effects so we would not recommend it for women who may become pregnant and it may interfere with oral contraceptives. We would also advise against use by people under the age of 18.
Resveratrol may be beneficial or it may turn out to be of little value. There clearly seems to be little value in the usual oral capsule supplements because of the First Pass Metabolism. To circumvent this problem, resveratrol is available as lozenges. By allowing the lozenge to dissolve in the mouth, the resveratrol is absorbed directly through the lining of the mouth into the bloodstream, bypassing the liver. This can produce much higher levels of resveratrol in the blood. Since the resveratrol is rapidly removed as the blood circulates through the liver, using several smaller dose lozenges throughout the day is likely to keep more consistent levels than a single larger dose.
