Revisiting resveratrol: new findings rekindle anti-aging debate

Just when we thought the bloom was off the rosé for resveratrol, the anti-oxidant polyphenol from red wine with multiple anti-aging properties, along comes new research giving life to the debate. But first a bit of background: As I detailed in my book Age Gets Better with Wine, it is well-documented that wine drinkers live longer and have lower rates of many diseases of aging. Much or the credit for this has been given to resveratrol, though there isn’t nearly enough of it in wine to explain the effects. Nevertheless, I dubbed it the “miracle molecule” and when it was reported to activate a unique life-extension phenomenon via a genetic trigger called SIRT, an industry was born, led by Sirtris Pharmaceuticals, quickly acquired by pharma giant Glaxo. The hope was that resveratrol science could lead to compounds enabling people to live up to 150 years and with a good quality of life.

But alas, researchers from other labs could not duplicate the results, and clinical studies disappointed. After a few short years, Glaxo pulled the plug on the project. But SIRT still seemed to be a key to lifespan extension even if resveratrol was not a direct activator of it. But the latest study from the Sirtris/Glaxo scientists suggests that maybe resveratrol may play a role here after all, at least on individual cells under laboratory conditions. Whether this applies to clinical use of resveratrol (or routine use of resveratrol supplements) remains speculative however.

Which brings us back to the central question of wine and health. Because the amount of resveratrol in wine is much lower than levels required to produce effects on cells in the lab, whatever benefits accrue to wine consumption cannot be attributed to resveratrol. So for now I will continue to take my medicine in the liquid and more palatable form.

Is red wine a performance-enhancing drug?

Lance Armstrong’s doping revelation aside, a recent study added controversy to the question of whether quercetin, a red wine-derived substance, can boost athletic performance by boosting testosterone levels. Though it was a test-tube study not backed up by any human subject data, the researchers thought it significant enough to inform the World Anti-Doping Agency. Quercetin has been reported in reputable publications to enhance oxygen uptake and endurance, and since many of these have come out since my review in "Age Gets Better with Wine," so I thought it might be worth another look.

For starters, quercetin is an antioxidant bioflavanoid that can be found in foods other than wine (apples for instance.) It first caught researchers’ attention as a component of red wine, being a possible contributor (along with other compounds such as resveratrol) to the famous “French paradox.” Like other wine-derived compounds, quercetin seems to alter energy metabolism at a cellular level. But does this translate to measureable changes in athletes? The data is conflicting. One well-designed clinical trial examined the effects of a quercetin + vitamin C supplement on 60 male athletes. After 8 weeks of using the supplement, no changes in exercise endurance were found, but there were slightly reduced markers of post-exercise muscle damage and a reduction in body fat (compared to placebo.) Another study by the U.S. Army evaluated a high-dose quercetin supplement on aerobically demanding soldier performance. No measurable benefit was found, though this was a shorter trial (just over a week.) Still another trial on endurance runners found no benefit.

One way to troll for meaningful data from conflicting study results is what is called a meta-analysis, which combines the results of all properly designed published studies. The School of Applied Physiology at Georgia Institute of Technology in Atlanta conducted such a review, concluding that “On average, quercetin provides a statistically significant benefit in human endurance exercise capacity (VO2max and endurance exercise performance), but the effect is between trivial and small.” So whether red wine or quercetin supplements boost testosterone or not, the effect seems unlikely to be enough to affect the outcome of the Tour de France or explain the French paradox by itself. There are plenty enough healthy reasons to have a glass of wine anyway.

A fond farewell to the father of the French Paradox

This has been a year of continued affirmation of the role of wine as a central component of healthy living, but rather than a review I would like to pay tribute to Serge Renaud, considered by many to be the father of the “French paradox.” It was a seminal moment in 1991, on the CBS-television show “60 Minutes” when Dr. Renaud offered that “A moderate and regular wine consumption of one to three drinks per day, which is common in France, protects us” from the much higher incidence of heart disease in America.  Dr. Renaud collapsed walking to the beach near his Mediterranean home on October 28 at age 85.

Though born the son of a winemaker, Renaud’s early studies focused on dietary factors comprising what would later come to be known as the Mediterranean Diet. There were important differences in the composition of dietary fats -specifically omega -3 and 6 fatty acids - that seemed to hold the key. Over time however it became apparent that regular wine consumption was a critical part of the diet, and provided an explanation for lower rates of heart disease in parts of France where the diet included more fatty foods. The French Paradox thusly became an iconic symbol and opened a rich vein of research. Publications on the subject now number in the thousands and new discoveries are reported almost daily.

I was fortunate to have met Dr. Renaud on two occasions. He was gracious and generous. It is hard to overestimate the influence he had, both from his many years of research and his vigorous defense of the French paradox. The idea of wine as health food was radical, but he leaves a legacy of science at its best – finding the unexpected just because that’s where the evidence leads. I like to think that he is enjoying his allocation of the angels’ share.

Red wine headaches syndrome: Why is it still a problem?

If you are prone to headaches from red wine, would you drink wine made from genetically modified yeast if you knew you wouldn’t react to it? The problem of headaches from wine is one of the most frequent questions I get at lectures on wine and health. From an anti-aging point of view, evidence clearly points to red wine as a healthy habit. But if it gives you headaches, it just isn’t worth it. The good news is that we know what causes the headaches and how to make wine that doesn’t provoke them; the bad news is that almost no one is making wine that way.  The reasons behind this are enough to cause befuddle the brain and cause a headache all over again.

You can thank University of British Columbia Biotechnology Professor Hennie van Vuuren for developing the solution. A sufferer of the red wine syndrome himself, Dr. van Vuuren has been working on the solution for some 15 years. The problem stems from compounds called biogenic amines, which include histamine and some rather nasty sounding compounds called cadaverine and putrescine, among others. In addition to headaches, symptoms such as flushing, dirarrhea, and nausea can occur. Some biogenic amines are even considered carcinogenic.

Biogenic amines develop during a secondary fermentation process called malolactic, in which somewhat tart malic acid is converted to softer lactic acid. Most red wines are made this way, and some white wines such as chardonnay, and it generally improves the wine. The problem is that it can be tricky to control because it is catalyzed by bacteria, not the yeast that guides primary fermentation. The solution that Dr. van Vuuren developed was to splice the necessary gene from the bacteria into the yeast, thereby bypassing the need for bacterial fermentation altogether. But controversy abounds with genetically engineered foods, deserved or not.

The malolactic yeast, called ML01, has been in testing and limited use for nearly a decade now, but it is still not widely available or apparently much in demand. It has received FDA approval in the U.S. and Health Canada, and it is likely that many have consumed ML01 wines without knowing it (labeling laws regarding genetic modification are another controversy.) My take on it is that we are better of without biogenic amines in wines, and that genetic modification has been in use for hundreds of years through selective crossbreeding. Science has simply accelerated and refined the process, to our benefit.

Resveratrol, wine, and cancer: an update

A recent study on the effects of resveratrol on prostate cancer highlights one of the tantalizing aspects of this red wine antioxidant: a long list of potential anti-cancer properties. It must be pointed out however that nearly all of the evidence for this comes from laboratory research, and though there are some clinical trials in progress it is premature to claim anti-cancer benefits for resveratrol supplements. But if any of it pans out it could lead to significant breakthroughs.

One of the things that make resveratrol so intriguing as an anti-cancer agent is that it not only suppresses cancer cell growth but seems to protect normal cells from the toxic effects of cancer treatment. Radiation treatment is a particularly troublesome therapy because of lasting effects on healthy cells in the treatment zone. But several lines of evidence suggest that resveratrol may pull off the ultimate hat trick: protecting the healthy cells while sensitizing cancerous cells to radiation.

This most recent study evaluated resveratrol as a ‘radiosensitizing” agent on a “radioresistant” clone of prostate cancer cells in culture.  (Again, not an animal study or human clinical trial.) This confirms findings of earlier studies on prostate cancer, but other tumor lines exhibit a similar response to resveratrol. One intriguing example is glioblastoma, a particularly aggressive form of brain cancer. [reference]  Melanoma cells may do likewise [reference] as do some types of lung cancer [reference].

Clinical evidence however points to a role for wine consumption. In a large series  from Italy,  patients undergoing radiation treatment for breast cancer had less irritation of the skin (called radiodermatitis) if they consumed red wine regularly. What is notable about this is that there isn’t enough resveratrol in wine to explain the effect. This is in fact the central dilemma about resveratrol as a candidate for all the healthy things that red wine does: lab studies show a plausible cause-effect explanation for observed inverse correlations between wine and disease, yet the amounts required to produce the effect are far more than what is available by consuming wine.

So what conclusion can we draw from this? First, much work needs to be done in the laboratory and the clinic before we can say definitively that resveratrol (or a derivative) is a useful adjunct to cancer treatment. Wine consumption generally correlates with reduced risk of cancer, in a J-shaped curve with the maximum benefit at moderate levels of consumption and increased risk with heavy consumption. It just doesn’t appear that this has much to do with resveratrol.

New study on resveratrol supplements widely misinterpreted

Quote: “A new study is hinting women may want to think twice before picking up a glass and toasting to their health. Health Magazine is reporting that researchers from Washington University School of Medicine have discovered that healthy middle-aged women do not benefit from taking resveratrol supplements.” (from Fox News)

Am I the only one who sees that those two sentences do not make sense? What the study showed is that taking a particular supplement does no good, not that drinking red wine is bad. Seems pretty simple to me but it points out a common misconception that needs to be dispelled (again). The thinking goes like this: We know from a multitude of studies that red wine consumption in moderation is linked to a long list of health benefits. These include lower rates of cardiovascular disease, osteoporosis, Alzheimer’s, and diabetes, to name just a few. But alcohol is of course bad for you, so the whole benefit must be from something else.

Enter resveratrol, the miracle molecule (as I dubbed it in my book Age Gets Better with Wine: New Science for a Healthier, Better, and Longer Life.)  In lab studies, resveratrol seems to do just about everything; it’s a potent antioxidant, reverses many of the harmful effects of a high-fat diet, prevents cancer, you name it. Because resveratrol comes from the skins of red wine grapes, it must therefore be the reason for wine’s health benefits. So just take resveratrol in a pill and skip the alcohol from red wine, and you’re all set. Resveratrol supplement makers proudly proclaim “all the benefits of wine without the alcohol” and pitch it as the next breakthrough weight loss secret and fountain of youth.

But there are fatal flaws with this reasoning. Most importantly, red wine doesn’t have enough resveratrol in it to explain the health benefits of drinking. The researchers in the study cited above acknowledge that the doses were equivalent to drinking gallons of wine a day, and still no measurable benefit. Another reason is that alcohol is not entirely deleterious, and in small amounts – levels that correspond to a glass or two of red wine with dinner – it is probably beneficial when all factors are taken into consideration.

Is de-alcoholized wine better for health?

Over the past few weeks there has been a flurry of news coverage over a clinical study finding that de-alcoholized red wine lowered blood pressure, but not whole wine. The usual interpretation was that wine without the alcohol was probably a better choice for health, with the blood pressure drop projected to equate to about a 14% decrease in heart disease risk. Supplement makers proclaimed that their wine-derived resveratrol pills were therefore a smarter choice, others concluded that grape juice would do the trick. But other studies out on alcohol found unique benefits, and as you have seen here before a broader view is needed in order to see the picture clearly.

As with most studies, the blood pressure experiment had problems. For one, there was no “control” group for comparison. But the bigger question always is whether these findings translate into anything meaningful in terms of overall health and longevity. It is not reasonable to assume that a single parameter such as blood pressure tells the whole story with heart health and drinking, even less so when considering the range of healthful effects of moderate wine consumption. What it does do is confirm that the non-alcohol components of wine, taken as a whole, have independent positive effects.

So what of the alcohol? Consider a recent study on the effects of moderate drinking on bone density (a measure of osteoporosis).  Using a cohort of 300 women with an average age of 67, a consistent correlation of alcohol intake and better bone density was found. These finding are in line with previous studies. Another study found lowered rates of rheumatoid arthritis among moderate drinkers. (In my book Age Gets Better with Wine I cite findings from a lab study showing how this might work.) The researchers concluded that this was one of “multiple studies that have shown that alcohol can have a beneficial effect on risk for rheumatoid arthritis.”

So even if alcohol does not contribute directly to heart health, there are other areas where it appears to provide benefit. Heavy consumption is well-known to increase blood pressure, but in moderation as in the study cited above it seemed to be benign. As with all studies occupying the media spotlight for their 15 minutes of fame, nothing here is as bad (or in other cases as good) as it sounds. I am reminded of Michael Pollan’s book on healthy eating called In Defense of Food, subtitled “Eat food, mostly vegetables, not too much.” The same could apply for wine: Drink wine, mostly red, not too much (and I would add not too little.) And by the way, grape juice is not just wine without the alcohol; it has a lot of sugar and lower levels of antioxidant polyphenols.