Resveratrol and Enhancement? Not So Fast

Does resveratrol help healthy people become even healthier? Does it improve metabolic health and possibly even help us live longer?

A new study casts doubts on these hopes. In the October 25 issue of Cell Metabolism, researchers at Washington University School of Medicine publish the results of their study involving 29 healthy middle-aged women. They asked whether resveratrol boosts metabolic health. When they ran the tests and collected the evidence, the answer was simple: No.

The study divided the women into two groups. Fifteen were given 75 milligrams of resveratrol each day, the same as they would get in 8 liters (more than 10 bottles) of red wine. The other fourteen received a sugar-pill placebo.

Researchers measured the women's sensitivity to insulin and the rate of the glucose uptake. The result, according to Samuel Klein, senior investigator, is that "we were unable to detect any effect of resveratrol. In addition, we took small samples of muscle and fat tissue from these women to look for possible effects of resveratrol in the body's cells, and again, we could not find any changes in the signaling pathways involved in metabolism," Klein said in a press release issued by Washington University School of Medicine.

Photo Credit: Robert Boston. No usage restrictions.

This study is small, but what makes it interesting is that it involves healthy human beings. In nonhuman trials, resveratrol seems to enhance the health of healthy animals. And in human trials involving people with metabolic problems, resveratrol seems beneficial.

According to Klein, "Few studies have evaluated the effects of resveratrol in people," Klein explains. "Those studies were conducted in people with diabetes, older adults with impaired glucose tolerance or obese people who had more metabolic problems than the women we studied. So it is possible that resveratrol could have beneficial effects in people who are more metabolically abnormal than the subjects who participated in the study."

That point goes right to the heart of the human enhancement debate. Often, "enhancement" is distinguished from therapy. While therapy improves the health of the sick, enhancement improves the health of the healthy. This study seems to suggest that resveratrol may be therapeutic, but it is not an enhancement.

Right now, however, the picture is not completely clear. Those who drink red wine in moderation are less likely than others to develop heart disease and diabetes? Is it the resveratrol, the wine, or the interactions between them?

According to Klein, "We were unable to detect a metabolic benefit of resveratrol supplementation in our study population, but this does not preclude the possibility that resveratrol could have a synergistic effect when combined with other compounds in red wine."

The article, entitled "Resveratrol Supplementation Does Not Improve Metabolic Function in Nonobese Women with Normal Glucose Tolerance," appears in the October 25 issue of Cell Metabolism.

Extending Healthy Lifespans? A Pill on the Horizon?

Resveratrol, the much-hyped ingredient found in red wine and sold widely as a nutritional supplement, is known to improve the health and extend the lifespan of mice. Can it do the same for humans? Without nasty side effects? And at what dose?

A study published today in Cell Metabolism helps unravel a few more of resveratrol’s mysteries. In particular, researchers have shed new light on how resveratrol works. Key to its effectiveness is a gene known as SIRT1, found in slightly different forms in species as different as yeast and humans. SIRT1 plays many roles, some tied to core metabolic processes. The new study shows that in mice, even a low dose of resveratrol interacts with SIRT1 to improve metabolism.

What makes this study especially interesting is that researchers had to create a special strain of mice in order to test whether SIRT1 is necessary for resveratrol to work. If mice have no SIRT1, they do not develop properly. So two graduate students, Nathan Price and Ana Gomes, developed a novel strain of mice with an unusual copy of the SIRT1 gene, one that could be switched off at adulthood.

By administering a drug (tamoxifen), researchers can “induce” or switch the SIRT1 gene on and off, a strategy that will likely be used in other studies. "This is a drug inducible, whole body deletion of a gene," David Sinclair, the study's senior author, said in a press release from Harvard Medical School. "This is something that's rarely been done so efficiently. Moving forward, this mouse model will be valuable to many different labs for other areas of research."

Photo by R. Cole-Turner

In this case, the switchable SIRT1 mouse provided proof that SIRT1 is key to resveratrol’s effectiveness. Why is that important? Because resveratrol is a complex molecule that interacts with the body in many unknown ways. While it may be beneficial, it may have unwanted side effects. So researchers are trying to design a more simple molecule that provides the benefits of resveratrol without all the risks. One strategy is to boost SIRT1 activity. By proving that SIRT1 is involved, this study provides support for that strategy, which is already being pursued by pharmaceutical firms.

"The results were surprisingly clear," said. "Without the mitochondria-boosting gene SIRT1, resveratrol does not work."

Are we any nearer a magic pill that slows aging or promotes longevity? Perhaps. The headline of the press release from the publisher, Cell Press, claims that this work “restores hope for anti-aging pill.” Remember, of course, that the work reported here is entirely with mice.

Even so, the paper itself concludes with this statement: “This model supports the enticing possibility of designing and developing potent small molecules that provide the health benefits of resveratrol by activating SIRT1 and downstream pathways to treat metabolic and other age-related diseases.”

The treatment of age-related diseases, including diabetes, is a huge target for pharmaceutical firms. But beyond that lies that even bigger market for human enhancement, specifically for enhancing the span of healthy decades.

The study, "SIRT1 Is Required for AMPK Activation and the Beneficial Effects of Resveratrol on Mitochondrial Function," appears in the May 1, 2012 issue of Cell Metabolism.

Resveratrol and Human Enhancement

The debate over human enhancement may just have entered a new phase. Resveratrol, the natural compound found in red wine, has now been shown to improve the metabolism of human beings. While the word "enhancement" does not appear in the published report, the research will almost certainly be read by many as evidence that the use of resveratrol enhances human health and may even increase the human lifespan.

In the more prosaic language of the report, the news is simply this: Resveratrol, the natural compound found in red wine, has now been shown to improve the metabolism of human beings.

In the 2 November 2011 issue of the journal Cell Metabolism, researchers in the Netherlands and Switzerland report that a 30-day course of resveratrol brought about significant improvement in the basic metabolic functions of obese men.

Research using animals has shown that resveratrol can have a number of benefits related to how the body uses energy. In some species, resveratrol has been shown to increase average longevity. In other experiments involving lab animals, a reduction of 30-50% in calorie intake below what the animals normally eat has been shown to benefit the metabolism and extend the lifespan. Others studies show that resveratrol seems to mimic the effects of calorie restriction.

Now come hints that resveratrol may have some of these same effects on human beings. In the Cell Metabolism article, researchers report that the men who received the 150mg/day dose of resveratrol showed a number of changes that mimic what happens with calorie reduction. 150mg is about 100 times the amount of resveratrol found in an ordinary glass of red wine.

One of the researchers, Patrick Schrauwen, commented on the study in a press release issued by Maastricht University in the Netherlands: “We saw a lot of small effects, but consistently pointing in a good direction of improved metabolic health.” The study was concluded after 30 days, and so long-term benefits or side-effects are not known.

In particular, no one knows whether resveratrol has the capacity to extend the human lifespan. But the positive results published on 2 November will surely intensify the debate over the effects and the ethics of resveratrol.

In this study, resveratrol was administered to men who were obese but otherwise healthy. One way some bioethicists distinguish between morally legitimate “therapy” and morally questionable biomedical “enhancement” is by insisting that medicine must stick to treating those with disease. It is unethical, these bioethicists argue, to “enhance” people by using medicine to benefit those who are not sick. Their views are challenged by others who believe that technology should be used for human enhancement.

While this study may have observed that moral limit of treating only those with a “disease,” there is little reason to believe that the metabolic benefits of resveratrol are limited to those who are obese. On the contrary, there is every reason to think that this study will be used by advocates of human enhancement. In particular they will see this as the best evidence yet that resveratrol can be used to extend the human lifespan.

My prediction is that this study will encourage more widespread use of resveratrol. Most who use it will be seeking some form of enhancement if not an increase in longevity.

The article, “Calorie restriction-like effects of 30 days of resveratrol (resVidaTM) supplementation on energy metabolism and metabolic profile in obese humans,” appears in the 2 Nov 2011 issue of Cell Metabolism, where it is available free to the public.