Are The Benefits Of Resveratrol A Myth?

Is Resveratrol Dead?

Author: Dr. Stephen Chaney

Red WineIt seems like just a few years ago that the headlines were proclaiming that resveratrol, a polyphenol found in red wines, grapes and chocolate, was the latest “super nutrient”. It was going to make you younger, smarter and healthier. You probably knew that all of the claims being made at the time could not be true.

But the latest headlines are claiming that resveratrol health benefits are all a myth. Has the resveratrol bubble burst? Was it all just hype?

Before you decide that resveratrol supplements are just a waste of money, let me take you behind the scenes and evaluate the latest study objectively. Let’s talk about what it showed, and didn’t show. But, before we look at the study, let’s review the history of resveratrol.

How Did The Resveratrol Story Get Started?

The resveratrol story started in the 1990’s when Dr. Serge Renaud at Bordeaux University coined the term “French Paradox” to describe the fact that cardiovascular disease incidence was relatively low in the French population despite the fact that they consumed diets high in saturated fat and cholesterol.

People immediately started asking what could possibly explain this discrepancy between the US and French populations? In other words, what could be protecting the French population from their high fat diet? One obviously difference between the French and Americans is that the French consume a lot more red wine – or at least they did before the “French Paradox” publicity turned red wine into a health food. Based on that difference, Dr. Renaud proposed that the French Paradox was due to the high red wine consumption in France.

But, red wine is an alcoholic beverage and overconsumption of alcoholic beverages is a major health problem for many people. And, while alcohol does have some cardiovascular benefits, alcohol consumption was pretty constant across countries.

So the next logical question was what other ingredients in red wine might explain their supposed health benefits. Polyphenols appear to have numerous health benefits, and resveratrol is the major polyphenol in red wine. So resveratrol became the “poster child” for the health benefits of red wine.

Even so, for years resveratrol was a “niche” supplement. It had a loyal following, but it wasn’t a big player in the nutritional supplement market. All that changed in 2009. Dr. David Sinclair at Harvard University had been studying genes that slow the aging process. He had screened thousands of naturally occurring small molecules in hopes of finding some that could turn on those anti-aging genes.

He announced that resveratrol and a few related polyphenols were the most potent activators of those anti-aging genes, and he went on to publish studies showing that resveratrol could help obese mice live longer and lean mice be healthier. All of a sudden resveratrol became a superstar.

But, does resveratrol also work in humans? There are many clinical studies that suggest it does. That’s why I was surprised by the recent headlines proclaiming that the supposed health benefits of resveratrol were myths. So once again, let’s look at the study behind the headlines.

Are The Benefits Of Resveratrol a Myth?

The study behind the headlines (Semba et al, JAMA Internal Medicine, doi: 10.1001/jamainternalmed.2014.1582) followed 783 men and women aged 65 years or older from the Chianti region of Italy for 9 years. None of the participants were taking resveratrol supplements. The investigators estimated resveratrol intake by measuring the concentrations of resveratrol metabolites in the urine.

The investigators measured all cause mortality and the prevalence of heart disease and cancer over the 9 year period and found no correlation between those outcomes and urinary resveratrol metabolites. From those data the authors concluded that “Resveratrol levels achieved with a Western diet did not have a substantial influence on health status or mortality risk of the population in this study.”

The Strengths And Weaknesses of The Study

There are really two important questions – what are the strengths and weaknesses of the study and what does the study actually show?

What are the strengths and weaknesses of the study?

  • A major strength of the study was the measurement of urinary resveratrol metabolites rather than relying on the less accurate dietary recall – although it should be noted that the assays used are relatively new and could benefit from further validation.
  • The main weakness is that it was a relatively small study in a relatively homogeneous population. Most of the resveratrol consumed by this population came from red wine and even the group with the lowest resveratrol intake was drinking 2-3 glasses of red wine per week (You don’t find many teetotalers in the wine growing regions of Italy).

What does the study actually show?

  • The level of resveratrol metabolites in this population directly correlated with alcohol consumption. And, the authors of the study concluded that since the study was done in the Chianti region of Italy, most of the resveratrol came from red wine. So the study actually suggests that red wine consumption has no effect on heart disease, cancer or longevity – in direct contradiction to Renaud’s French Hypothesis.
  • The conclusion that the amount of resveratrol one can obtain from diet alone is unlikely to provide health benefits needs to be replicated in a much larger population group with a wider range of resveratrol intakes from a wider variety of foods before it can be considered definitive.
  • Even if the amount of resveratrol in food does offer no significant health benefits, that information provides little or no guidance when we consider resveratrol supplements, which generally provide much higher levels of resveratrol.

The Bottom Line:

1)    Don’t pay too much attention to the headlines saying that the health benefits of resveratrol are a myth. The study behind the headlines was a small study in a relatively homogeneous population. If anything, it debunked the hypothesis that red wine consumption is responsible for the French Paradox.

2)    The study did suggest that the amount of resveratrol one can obtain from diet alone is unlikely to provide significant health benefits. While that may be true, it is irrelevant when considering resveratrol supplements because they provide much higher amounts of resveratrol.

3)    The clinical studies on resveratrol supplements are very encouraging, but not yet definitive (see, for example, my “Health Tips From the Professor” article on resveratrol and blood sugar control. That’s to be expected at this stage. It generally takes decades of studies before the scientific community reaches consensus on anything. In the meantime you will continue to see alternating headlines proclaiming the miracles and the myths of resveratrol.

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.

Does Resveratrol Improve Blood Sugar Control?

Is The Promise of Resveratrol True?

Author: Dr. Stephen Chaney

blood sugar testIt was just a few years ago that resveratrol was the latest “miracle nutrient”. It was featured on Dr. Oz and on 60 Minutes. It was hot! Today you see dueling headlines. The headlines one week proclaim the benefits of resveratrol. Next week’s headlines say that it’s all hype. What’s a person to believe?

Let me take you behind the headlines to look at the actual studies and answer some important questions.

1)    What do we actually know about the benefits of resveratrol?

2)    Is the evidence for beneficial effects of resveratrol where it should be considering the number of clinical studies that have been published?

3)    What additional studies need to be done before we can be sure that resveratrol is beneficial?

4)    Should you wait until we are absolutely certain resveratrol is beneficial, before you start using it? This is perhaps the most important question of all.

To answer those questions, let’s examine the study behind one of the latest headlines, namely: “Resveratrol Improves Blood Sugar Control in Diabetics”. One of the promises of resveratrol has been that it might help diabetics and pre-diabetics who struggle with blood sugar control. However, this promise was based on animal studies. The study that generated the headlines in question was a meta-analysis of recently published human clinical trials in this area (Liu et al, Am. J. Clin. Nut., 2014, doi: 10.3945/ajcn.113.082024).

Does Resveratrol Improve Blood Sugar Control?

The meta-analysis included 11 published placebo controlled double blind clinical studies looking at the effects of resveratrol supplementation on fasting blood sugar levels, insulin levels, hemoglobin A1c (a measure of blood sugar control) and insulin resistance (a measure closely associated with type 2 diabetes).

A strength of this meta-analysis is the fact that it included 11 clinical studies. However, a weakness of this analysis is that these studies utilized a wide variety of resveratrol doses (10 mg/day to 1 gram/day), a wide variety of end points and both diabetic and non-diabetic patients. That means that there were only a few studies with common population groups, resveratrol doses, and end points.

The conclusions of the study (and the headlines you may have seen) were that:

•    Resveratrol appeared to improve blood sugar control (based on improvements in fasting blood sugar levels, insulin levels, hemoglobin A1c and insulin resistance) in diabetics.

•    No consistent effect of resveratrol on blood sugar control was seen in non-diabetics.

How Good Are These Studies?

While these studies are very promising, they are bot definitive.  There were only 3 published clinical studies in diabetics. While all 3 of the studies showed a positive effect of resveratrol supplementation:

•    The doses used were different in each study (ranging from 10 mg/day to 1 gram/day)

•    Each study measured different end points (one measured blood glucose, insulin levels, hemoglobin A1c and insulin resistance, one measured blood glucose and hemoglobin A1c and the third measured insulin resistance).

As a research scientist I would like to see more studies done at comparable doses and measuring the same end points – we scientists always want more studies.

Similarly, there was not enough consistency in the studies with non-diabetics to draw a firm conclusion. (3 were with obese patients, 3 were with patients with cardiovascular disease, 1 was with patients with metabolic syndrome and 1 was with perfectly healthy subjects.)

If you really wanted to see if something like resveratrol helps non-diabetics with blood sugar control, you would want to start with people who are already experiencing some difficulties with blood sugar control (pre-diabetics or patients with metabolic syndrome) and follow them for a couple of years to see if resveratrol reduces the number of them who become diabetic.

Are The Headlines Just Hype?

Newspaper HeadlinesDoes that mean that the blood sugar benefits of resveratrol are just hype? The answer is no. There is a difference between “very promising, but not yet definitive” and “hype”. We shouldn’t be surprised that human studies on the health benefits of resveratrol are not yet definitive. Science moves slowly. It often takes decades of scientific research before promising concepts are widely accepted by the scientific community.

When a research area is as young as this one, we sometimes need to go beyond the clinical studies and look at the totality of evidence. In this case:

•    In mice resveratrol exerts its beneficial effects by turning on a specific anti-aging gene called SIRT1 (Cell Metabolism, 15: 675-690, 2012). In humans, resveratrol appears to activate the same genetic pathways as in mice (Journal of Clinical Endocrinology & Metabolism, 96: 1409-1414, 2011).

•    In obese mice resveratrol improves markers of blood sugar control (Nature, 444: 337-342, 2006). Published clinical studies in diabetic humans also show improvements in blood sugar control (Journal of Clinical Nutrition, 2014, doi: 10.3945/ajcn.113.082024).

So while more and better clinical studies are needed to be absolutely certain that resveratrol helps improve blood sugar control, the evidence supporting that effect is substantial.

What Should You Do?

The ONLY important question for each of you is probably: “Should I wait a decade or two until we are absolutely sure about the health benefits of resveratrol before I take a resveratrol supplement?” That question is ultimately yours to answer. It’s all about benefits and risk.

Benefits – In animal studies resveratrol clearly improves blood sugar control. The human clinical studies published to date are consistent with the animal studies.

Risk – Current data suggest that resveratrol appears to be safe, even at high doses. For example, one recent study indicated that up to 5 gm/day is safe (Cancer Epidemiology BioMarkers & Prevention, volume 16:1246-1262, 2007), but I wouldn’t personally recommend exceeding 100-200 mg/day.

The Bottom Line:

1)     Don’t get too excited about the headlines suggesting that resveratrol might help improve blood sugar control in diabetics. The few human clinical studies that have been published to date are consistent with previous animal studies. That is very promising, but more studies are needed before we can be absolutely confident that resveratrol supplementation is beneficial for diabetics.

2)     Similarly, don’t be discouraged by the headlines suggesting that resveratrol does not help with blood sugar control in non-diabetics. Those results are preliminary as well.

3)     That doesn’t mean that the headlines are just hype. It takes decades to accumulate definitive proof that any kind of food or nutrient offers proven benefits, and the bulk of human clinical research on reveratrol has occurred in the last couple of years. We are exactly where we should expect to be at this point in time.

4)     With something as promising as resveratrol, the real question becomes whether you can afford to wait a decade or two until you know whether the potential benefits have been definitely proven. That question is up to you. On the plus side, current data suggest that resveratrol is highly promising for blood sugar control. In addition, resveratrol appears to be safe, even at high doses, but I wouldn’t personally recommend exceeding 100-200 mg/day.

5)     We already know that weight control, exercise and a healthy diet improve blood sugar control. You should think of resveratrol as something you may wish to add to a healthy lifestyle, not as a substitute for a healthy lifestyle.

6)     If you are diabetic and decide to try a resveratrol supplement, be sure to work with your physician so they can modify your dose of insulin or blood sugar medication as necessary.

7)     Finally, you may be asking whether resveratrol supplements are even necessary. Can’t you just get all the resveratrol you need from a glass or two of red wine? Stay tuned. I’ll have the answer to that question in a couple of weeks.

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.

Are Dietary Polyphenols Associated With Longevity?

Are Polyphenols The Fountain of Youth?

Author: Dr. Stephen Chaney

Merlot Grapes HDRYou’ve probably heard that resveratrol and other polyphenols in red wine can help mice live longer. But what about us? Are dietary polyphenols associated with longevity in humans?

Until recently nobody knew the answer to that question. However, a recent study (Zamora-Ros et al, J. Nutr. 143: 1445-1450, 2013) suggests that polyphenols may just help us live a bit longer.

Of course, the news headlines make it sound like a sure thing, and many of the manufacturers of polyphenol-containing supplements are already citing the study as “proof” that their products will make you live forever.

Polyphenols Are Everywhere:

So, let me give you some background information before I start diving into the study.

  • The term polyphenols includes some names you may recognize, such as flavonoids, isoflavones, anthrocyanidins and resveratrol, and many more that might look like the kind of names you might expect to find on a processed food label.
  • Polyphenols don’t just come from red wine. There are several hundred polyphenols in edible foods. Many fruits, vegetables (including beans like soybeans) and whole grains – the kinds of foods that every expert recommends for a healthy diet – are also great sources of polyphenols.
  • Most polyphenols are excellent antioxidants. Studies suggest that they may also exert antiinflammatory effects and may reduce the risk of heart disease, neurodegenerative disease and cancer. So it is not unreasonable to assume that they might enhance longevity.

An In-Depth Analysis Of The Study:

The study enrolled 807 men and women over the age of 65 (average age = 74, range = 67-81) from the Chianti region of Italy and followed them for 12 years. At the beginning of the study polyphenol intake of the participants was analyzed from a dietary recall form (polyphenol intake based on what they remembered eating) and from a 24 hour urine specimen (actual polyphenol intake).

During the 12 year follow-up, 34% of the participants died. Based on the dietary recall, there was no association between dietary polyphenol intake and mortality. However, based on urinary polyphenol content there was a 30% decrease in mortality for those with the highest dietary polyphenol intake (>650 mg/day) compared to those with the lowest polyphenol intake (<500 mg/day).

Strengths of the Study:

  • This is the very first study to actually investigate the relationship between dietary polyphenols and longevity in a meaningful way. The study was well designed and well executed.
  • The measurement of urinary polyphenol content is a strength of this study. Dietary recalls are often inaccurate. In fact, this study suggests that dietary recalls should probably not be used to estimate dietary polyphenol intake in future studies.

Weaknesses of the Study:

  • This was a first study of its kind, and like any other first study it needs to be confirmed by additional studies.
  • The study only measured associations, not cause and effect. Of course, it would be almost impossible to conduct a double blind, placebo controlled study of this duration – especially if one is using urinary excretion as a measure of polyphenol intake.
  • The study did not report the dietary sources of the polyphenols, although this information was presumably available from the dietary recalls. Because the study was conducted in the Chianti region of Italy it is probably pretty safe to assume that red wine contributed to the polyphenol intake. However, people in that region of Italy also tend to consume diets rich in fruits and vegetables. Hopefully, future studies will help determine whether some polyphenols are more important for longevity than others.

The Bottom Line:

1)     Eat lots of fresh fruits and vegetables. They’ll make you healthier, and you just may live longer.

2)     If you like red wine, drink it in moderation. Just don’t assume that it can substitute for a healthy diet. This study measured total polyphenols, not just red wine polyphenols.

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.

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