New study reveals how resveratrol might work (don’t lose your SIRT)

The latest study on resveratrol, the touted polyphenol from red wine, seems at first glance to restore some lost credibility to its increasingly questioned anti-aging capabilities. It has been widely reported but we know from experience by now that a single study never tells the whole story. The whole story would take more space than I have here so here is what you need to know:

There is a unique phenomenon called caloric restriction that extends lifespan dramatically, at least in experimental animals and organisms. By limiting caloric intake severely, a metabolic change occurs that results from activation of a family of genes know as SIRT, which code for proteins known as sirtuins. Resveratrol has been reported to activate sirtuins and thereby cause lifespan extension, at least for yeast cells, fruitflies and worms. Getting it to do the same thing in mammals such as mice and men has been problematic however, casting doubt on the use of resveratrol as a miracle anti-aging tonic. Some labs have reported that resveratrol does not in fact activate SIRT. Meanwhile, the company founded to develop resveratrol-based pharmaceuticals (Sirtris) has scrambled to maintain their case.

This latest study, from Dr. David Sinclair (cofounder of Sirtris) employed a strategy using mice with the SIRT gene “knocked out.” So by testing resveratrol’s effects in knockout vs normal mice, the role of sirtuins can be determined. What they found was that metabolic measurements were healthier in the normal mice given a high-fat diet plus resveratrol, but not the SIRT knockout mice. So resveratrol’s effects do depend on SIRT, (as well as an unhealthy diet) implying that it is a sirtuin activator after all. We are still left, however, with the question of how much this relates to human health.

Recall from previous posts here that there isn’t enough resveratrol in wine to explain the well-established health benefits including longer lifespan associated with moderate consumption. There is also the problem that resveratrol is quickly transformed after ingestion into a different molecule called piceatannol.  So before concluding that this recent study confirms that resveratrol works as a supplement, have a glass of wine and mull it over.

The red wine diet to lose weight? Believe it (sort of)

If you follow the news about red wine you will have been deluged with coverage of a recent study finding that it prevents fat cells from maturing, and is therefore the latest miracle weight loss solution. The specific ingredient, a polyphenol called piceatannol, has not previously received a lot of attention. It does provide some answers to questions such as why wine drinkers are less likely to gain weight or develop type 2 diabetes, but raises some new questions too.

What the study found is that piceatannol inhibits the development of young fat cells – called preadipocytes – into permanent adult type fat cells. It accomplishes this by blocking the effect of insulin which activates genes in these cells that signal them to grow up and store fat. In theory, then, this could explain one of the benefits of a daily tipple.

The study also sheds some light on the role of resveratrol, the molecule that has received so much attention in recent years. As I pointed out in my book Age Gets Better with Wine, resveratrol doesn’t seem to last long in the blood stream after ingestion, one reason being that much of it is metabolized into piceatannol. Without knowing much about the effects of piceatannol, it is hard to give much credit to resveratrol. (Another problem still not explained is that there isn’t enough resveratrol in wine to explain the range of benefits that wine drinkers experience.)

So we are still left with a bit of a conundrum in that neither piceatannol nor resveratrol are the answer. It is just too big of a leap from treating cells in a dish in a laboratory to understanding the effects in the human body. Wine drinkers are healthier in large part because they eat better, exercise more, and tend to take a balanced approach to wine consumption. For these and other reasons, I will continue to patronize my local wine shop instead of the supplement store.

new research shows why red wine could reduce breast cancer risk

Last week's post referenced a population study that purported to show that any wine consumption even in moderation would increase the chances of getting beast cancer, but as I repeatedly point out the data is highly inconsistent. A new study further contradicts this by revealing some of the ways that resveratrol (from red wine) directly influences cancer-prone breast cells in human subjects. Researchers at the University of North Dalota recruited 39 women at increased risk for breast cancer (based on genetic analysis) and then monitored the effects of oral resveratrol supplementation for 12 weeks. Cells from the breast were sampled and analyzed, revealing that resveratrol helped activate what are called tumor suppressor genes.
This is particularly powerful information because studies of this type -prospective trials in human subjects with objectively verifiable results - provide the highest level of evidence. (In contrast, population studies such as the one referenced in last week's post are typically retrospective and based on self-reported consumption levels, which are known to be highly innaccurate.) There are certainly many things in red wine besides resveratrol, but this study reinforces the notion of healthy drinking and points to the benefits of wine.

Wine and breast cancer: Here we go again

Yet another article about a possible link between wine and breast cancer is in the news, and as usual it is being widely quoted without any critical analysis or perspective. The article in question, a review of previously published studies, estimates that even a glass of wine per day increases risk of breast cancer and estimates that 1-2% of all breast cancer cases are attributable to light drinking alone. Rather than pick apart the article item by item, which would take all day since there are so many issues, I will highlight a few important things.

First, there are fundamental problems with the way that these types of studies are done, and reviewing them simply magnifies the underlying mistakes. Here’s the thing: in order to know if for example a glass of wine per day affected breast cancer risk, you would have to follow a large population of women who drink only wine, only a glass per day, every day, rarely more, rarely anything other than wine, and rarely not having a drink; this would need to be compared to a similar population who never drink, another who only drink beer, and so forth. But most people have mixed drinking patterns, they under-report their true level of drinking, and there is simply no reliable way to get any meaningful information. All we really know is that heavy drinking is bad.

Secondly, there are some populations of women in France who have traditionally consumed wine in moderate amounts and in a regular pattern. Their incidence breast cancer is dramatically lower than that of nondrinkers.

Third, breast cancer is nowhere near the leading cause of premature death in women; heart disease is far and away the biggest threat. It is well established that moderate wine consumption lowers heart disease risk, the net effect being overall reduction in risk of premature death.

Moderate wine consumption is also associated with lower odds of Alzheimer’s disease, osteoporosis, diabetes, and measurably improves quality of life and well-being. Wine drinkers outlive nondrinkers by about 5 years on average, and for most even if there is a fractional increase in breast cancer risk, the smart choice favors having a glass of wine with dinner and not stressing over it.

Wine and civilization: we wouldn’t be here without it

As a physician I go to a lot of symposia, the term often used for meetings where exchange if ideas is the goal. It is interesting to note that the word “symposium” actually derives from classical Greek, meaning  “to drink together.” The tradition was that following dinner, the men would retire to a special room dedicated to the purpose of drinking and philosophical discussions. There would be toasts to the gods, ancestors, and fallen heroes, then the revelry would truly begin, often lasting until the early hours of the morning. Here’s an excerpt from Plato: “Socrates took his seat … then they turned their attention to drinking. “ A member of the party named Pausanius said “Well gentlemen, how can we arrange to drink less tonight? To be honest, I still have a hangover from yesterday. “ Hard to believe that the canons of Greek philosophy, the underpinnings of modern civilization, had such origins as this.

But going back even further, wine is what civilized our nomadic hunter-gatherer ancestors. Other crops could be re-sown each year in a new place, but vines require year-round maintenance. Pruning, shaping, harvesting, fermenting –all depended on settling in one place. But doing so posed new challenges, such as keeping drinking water sanitary when the source was in proximity to “bathroom” facilities. Here again wine played a role by countering water-borne pathogens, and the tradition of adding wine to water became a necessary tradition in seafaring, voyages of exploration, trading, and military campaigns. Wine both civilized mankind and fueled some of our less laudable actions, and we are still conflicted today.

So what of wine in the modern era? The great tendency now is to treat wine as a pharmaceutical, whether deliberating the evils of alcohol or trying to tease out the secret components that explain why it is so good for us. But doing so misses the point on both counts; alcohol in the right amounts can be a healthy thing, and many of the known health benefits attribute to the lifestyle pattern that defines healthy drinking. So while the science of resveratrol and the long list of polyphenol antioxidants in wine is impressive, it isn’t the whole story and likely never will be.

Is alcohol necessary for wine’s health benefits?

High on the list of controversies about wine and health is the alcohol question, one I get asked about every time I do a seminar on the subject. Why not grape juice, or for that matter wine's goodness in a pill?

New research from the University of Barcelona took the question head on and it's good news for wine drinkers.

There are so many thousands of papers on wine and health now that you can be forgiven for not keeping up (which I am taking care of for you here) but in order to understand the implications of this latest study we need a little background. For one, as I said in the book, wine is not just grape juice without the alcohol; the content of polyphenols antioxidants is much higher in wine for several reasons (for another, grape juice is high in sugar.) There is a great temptation to assume that we could just take the polyphenols from grapes and put them into supplement form, which indeed many have. For non drinkers and occasions where wine consumption is inappropriate, it may not be such a bad idea. But does alcohol make a positive, independent contribution to health?

In terms of cardiovascular health, it is known that alcohol in moderation improves the HDL/LDL cholesterol ratio, and it is tempting to assume that is the end of the story. But atherosclerosis is a much more complex phenomenon than simply sludged up pipes from a high fat diet. Chronic inflammation, at least as biologists use the term, is the important underlying factor. So the scientists in Spain designed a clever clinical study in which volunteers were assigned to three groups: one consumed a standardized amount of red wine daily, another an equivalent amount of de-alcoholized wine, and a third had gin, standardized to the same alcohol amount as the wine group, for 4 weeks. They then measured 25 separate inflammatory biomarker levels. These molecules go by an alphabet soup of names, but the implications of the study were clear: Both alcohol and red wine polyphenols independently improved (“down-regulated”) inflammatory marker levels, and though there was some overlap they generally worked differently.

So is alcohol an anti-inflammatory compound? At least where cardiovascular disease is concerned, it would appear so. That would explain why alcohol from any source appears to offer some benefit, though not as much as when it is in wine. Another important aspect of this study is that it is a randomized prospective clinical trial, meaning we can take very high-level confidence in the results. Not that I had any real doubts.

New evidence that red wine lowers risk of breast cancer

Does drinking red wine increase risk of breast cancer? If you have been following the news over the past few years, you might have a hard time justifying that glass of wine with dinner, as we are told that even in moderation the risk of breast cancer increases. But as I have said here before (see post from Nov 2 2011), the whole topic is widely misunderstood and oversimplified, despite the declarations of medical authorities. But a new study helps to shed some light on the subject.

So why is the party line so negative on wine? At first glance, the evidence seems overwhelming: dozens of studies showing that consumption of alcohol in any form – red or white wine, beer, spirits – increases chances of developing breast cancer by about 10% per drink per day. Some of these studies are quite large, with thousands of women surveyed. A closer analysis reveals some serious problems however. To begin with, any time there are dozens of population studies all looking at the same question, we may fairly ask why the question is so difficult to answer. A quick glance reveals one obvious problem: not all the studies find an association of alcohol consumption with breast cancer. Another, more pernicious problem, has to do with a fundamental weakness of population studies: they rely on self reporting, which in the case of alcohol consumption is notoriously unreliable. The result is that heavy drinkers are misclassified as moderate drinkers, suggesting that low levels of drinking are unsafe.

More to the point is the fundamental question of whether red wine is different in terms of risk than other alcoholic drinks. Since women in the U.S. and Britain tend to have mixed drinking patterns – for example, minimal drinking during the week, and a variety of different drinks when they do – it becomes impossible for all practical purposes to know what the effect of regular, moderate consumption of red wine would be. 

It is also difficult to pin down exactly what alcohol does to increase breast cancer risk, but the theory seems to be that it promotes estrogen and so it is primarily estrogen-dependent tumors that account for most of the problem. This latest study attempted to address that by evaluating the effect of compounds in red wine that inhibit an enzyme called aromatase, which converts testosterone into estrogen. Using what is called a crossover prospective trial, they were able to show that consumption of red wine in volunteers had a positive effect, concluding that “red wine is a nutritional [aromatase inhibitor] and may explain the observation that red wine does not appear to increase breast cancer risk.” (emphasis added). So enjoy a glass of red wine with dinner and enjoy life.