Monday, December 1, 2014

A glass of red wine is worth an hour of exercise. Red wine compound resveratrol may negate health benefits of exercise. Or both. Or neither.

Once again we have dueling headlines about the effects of red wine and resveratrol: Does it enhance the effects of exercise or negate them? A study from the University of Alberta in Canada found that resveratrol supplementation in animals improved muscle and heart functions in the same way as an hour of exercise would, leading the study’s lead author Jason Dyck to postulate that “We could conceivably create an improved exercise performance in a pill." Supplement marketers already label resveratrol as an “exercise mimic,” while bloggers and wine lovers conclude that a glass of red wine would therefore do the same.
Meanwhile, at Queen’s University a few provinces over in Ontario, researchers were finding that resveratrol supplementation blunted the benefits of high-intensity interval exercise, a seemingly opposite effect. In a four-week placebo-controlled clinical trial, the data “clearly demonstrates that RSV supplementation doesn't augment training, but may impair the affect it has on the body" according to the authors.
The implications from these studies are not so opposite as they may seem, however. For one thing, the study that found resveratrol enhanced exercise results was in animals, not a human clinical trial, and animal studies frequently do not produce the same results as clinical trials. Another key difference is that the clinical study was measuring whether resveratrol could enhance the effects of intensive exercise, while the animal study was looking at whether it could replace exercise. And all studies on resveratrol are potentially confounded by the fact that it may have completely different and even opposing effects at different doses, a phenomenon known as hormesis. For all of these reasons we are still a ways off from knowing the answer to the question of resveratrol as an exercise mimic.

One thing we can say (again) is that a glass of red wine is not the same as a resveratrol pill. The doses are different, and wine has a multitude of compounds that may interact synergistically with the small amount of resveratrol in wine. Wine drinkers are healthier in part because they tend to have healthier lifestyles including regular exercise.

Wednesday, October 22, 2014

Don’t get soaked: The truth about red wine and resveratrol


Much has been made recently about pro basketballer Amar’e Stoudemire’s “vinotherapy” rehab program, which involves soaking in red wine baths. I tried it myself a few years ago at the Caudalie spa in Bordeaux, and while it was a fabulous experience I would put it more into the pampering category than physical rehab. But the practice does raise a lot of questions, and as with so many issues about wine and health there is a kernel of truth shrouded by a layer of hype.

Dr. Richard Baxter and Mathilde Thomas
For deep healing to happen, something would have to be absorbed from the wine in significant enough amounts to have an effect, and there is scant evidence that this occurs. A more realistic concept is rejuvenation of the skin, which can absorb certain compounds found in wine. Resveratrol, a powerful antioxidant, has received much attention both as a supplement and a skin care product. But just as there is not enough resveratrol in wine to explain wine’s health benefits alone, there isn’t enough in baths either.

Credit goes to Mathilde Thomas, founder of Caudalie, for connecting skin care to resveratrol. Science has backed this up too; resveratrol can be absorbed into the skin, where it provides an array of anti-aging benefits. Several large brands have now jumped on the resveratrol bandwagon, including SkinCeuticals.

The hype of the story stems from the increasingly common mistake of equating red wine’s benefits to resveratrol.  (For examples, see my recent posts here.) The reasoning goes like this: The French Paradox or some other study associates red wine with longevity, or lower rates of heart disease, or diabetes, or something else; resveratrol has been shown in lab studies to provide an explanation for these benefits; but in order to achieve levels of resveratrol  high enough for the same effect, one would have to consume dozens of bottles; so red wine must not be good for you after all. The correct interpretation of course is that it must be something other than resveratrol, or in addition to it.


Three amigos: Me, Professor Joseph Vercauteren, and David Sinclair
It’s partly my fault. In my book I set out to identify a plausible cause-and-effect relationship for each of the known benefits of moderate wine consumption, and resveratrol fits the bill. But I also emphasized that it is only one of many antioxidant polyphenols compounds in wine, and that they often work synergistically. I also pointed out the relationship of red wine consumption in moderation as a marker for many other healthy lifestyle habits. The ability to relax is probably one of those, and if soaking in a tub of wine helps, I am all for it.

Tuesday, August 19, 2014

Ten things your doctor won’t tell you about wine and health

A recent column in MarketWatch called “10 things your winemaker won’t tell you” has provoked considerable controversy, and the way I see it the statements about wine and health are particularly off base. So my response is a list of what your doctor probably won’t tell you; part of this will refute the MarketWatch piece, part of it will get at the misconceptions that underlie the problem. Author Catey Hill does make some interesting and valid points, but the question of healthy drinking is just too big to be distilled into a paragraph or two. I do know this though: it isn’t the winemaker’s job to tell you about its health benefits, and in fact the feds take a pretty dim view of that idea.

       1.       Hill states “Scan any health website these days and you’re likely to find at least one article touting the health benefits of wine, among them heart health and longevity—all the more so since the recent discovery of the antioxidant resveratrol in red wine. But some studies suggest there are more risks to wine consumption—or at least fewer rewards—than recent headlines might suggest. ” We must first point out that the discovery of resveratrol is not especially recent; a PubMed search returns nearly 6,700 articles in the biomedical literature on resveratrol, hardly qualifying it as an incompletely studied novelty. The issue is whether resveratrol is actually the reason for wine’s health benefits. Evidence seems to point elsewhere, given the low amounts of resveratrol in wine or any other dietary source. Resveratrol is clearly not “all the benefits of wine without the alcohol” as touted in supplement ads.
2.       Despite this understanding that researchers familiar with wine and health have had for years, the fallacy repeated in Hill’s article (and many others) is equating resveratrol and wine as the same thing. She cites an article much ballyhooed this year in the Journal of the American Medical Association in which researchers tracked a population of men over nine years, measuring resveratrol levels in their urine as a marker for dietary resveratrol intake. The more wine and vegetables in the diet, the hypothesis went, the more resveratrol and therefore lower mortality and disease. The lack of any correlation was interpreted as meaning that wine wasn’t so good after all, despite the fact that those in the know had abandoned the idea years before the study was completed.
3.       So how did the claims to health and longevity get started in the first place? What it boils down to is this: moderate wine drinkers live longer on average than nondrinkers, they have lower rates of degenerative diseases such as diabetes, osteoporosis, and cancer; and they have higher quality of life by standard measures. Statistically, it doesn’t matter whether it is the resveratrol, the alcohol, or anything else. Individual studies looking at individual disease conditions can therefore give a false view of the bigger issue. An example of this is another study (albeit a large one) cited by Hill, which showed that alcohol consumption even in moderation was associated with an increased risk of atrial fibrillation, a marker for heart disease. But the preponderance of data, from even larger studies such as Framingham, indicates that moderate wine consumption is the single lifestyle factor most protective against heart disease other than not smoking.
4.       Red wine drinking makes for healthy teeth. On the other hand, white wine may erode tooth enamel, according to an article cited by Hill. But the polyphenols in red wine – the things that make red wine red – are potent inhibitors of the bacteria that cause plaque and cavities.
5.       What your doctor really doesn’t want to tell you is that they don’t trust you to understand what moderate drinking is. Hill cites physician and author John La Puma, who points out (correctly) that the standard measure of a glass of wine on medical studies is 5 ounces, yet most wine glasses hold more. This leads to what is known as the under-reporting bias, meaning that people drink more than they think they do (or report that they do.) But the logical conclusion of this is that wine is actually better for you than we thought; if the healthiest level of drinking (lowest point on the J-shaped curve) is two 5 ounce glasses, what that really means that it is more, because the data is based on self-reporting.
6.       Alcohol is part of the health benefit equation. Claims that you get the same benefits from grape juice are dubious, and there are several reasons why it would be so: For starters, grape juice is full of sugar, and alcohol calories are metabolized in less deleterious ways. Perhaps more importantly though, the polyphenols in the skin of the grape occur in higher concentrations in wine grapes, and are extracted and concentrated during fermentation. But alcohol in the right amounts has specific health-promoting properties, which I outline in a chapter in my book.
7.       Sulfites in wine are not the reason for allergic reactions. Hill mentions sulfites only in passing, but it is commonly believed that flushing and other symptoms relate to the sulfites in wine that are added as preservatives. But they occur naturally, and when added are still in much lower concentrations than many common foods such as dried fruit. The reactions are usually attributable to histamine-like compounds that develop during malolactic fermentation, a type of secondary fermentation mediated by bacteria rather than yeast.
8.       Wine is more than heart healthy. Because the French paradox highlighted cardiovascular disease, early research focused on that. But as knowledge of wine chemistry expanded, research extended into several areas of anti-aging health issues. But focusing on only one condition (for example atrial fibrillation in the article referenced above) can obscure the larger benefit across a range of benefits to health and longevity.
9.       Wine is good for the brain. Every major epidemiologic study of Alzheimer’s disease and age-related cognitive decline has found a strong correlation of moderate wine consumption with higher mental function during aging. [references in my book]
10.   Research on wine and health is comprehensive. A recent summary called “Mapping the scientific research on wine and health” noted that the field is highly interdisciplinary, with publications in more than 500 different scientific and biomedical journals. There are few if any aspects of health research more thoroughly investigated.

Wednesday, May 14, 2014

Yes Red Wine is Still Good for You

Recent reports that “red wine is not great for health after all” and that “no amount of alcohol is safe” are just plain wrong. This type of misguided reporting and misinterpretation of scientific studies is one of the reasons for my book Age Gets Better with Wine. How is it that the story is still so confused?
Kicking off the latest round of hype was a report issued bythe World Health Organization’s International Agency for Research on Cancer. Noting that the risk is dose-dependent, meaning that heavy drinking has a stronger correlation with some types of cancer, the authors of the report concluded that even moderate drinking carries some degree of risk. This was followed by release of a study in Italy that looked at dietary levels of resveratrol and incidence of diseases of aging. Since the most well-known source of resveratrol is red wine, the lack of a benefit from higher resveratrol consumption was reported as casting doubt on the benefits of red wine.
So here we go again: It is well-documented that people who consume red wine in moderation, on a daily basis, live longer, have lower rates of cancer and other diseases of aging, and have better mental function and higher quality of life as compared to nondrinkers. They are also healthier than heavy drinkers, so the relationship of wine consumption and disease risk is not a linear dose-response but a J-shaped curve. One reason why this is not recognized is what is called “self-reporting bias,” which means that heavy drinkers tend to under-report their true consumption and so are categorized as moderate drinkers. Another reason is that there are comparatively few true consumers of red wine in moderation and they are hard to isolate statistically. Most people tend to drink in more erratic patterns as compared to the more traditional habitual glass of wine with dinner. These types of things confound data but lumping this group in with all drinkers and declaring alcohol a carcinogen is sloppy science and wrongheaded.
The bigger problem with this report is that it looks only at cancer risk, not overall health and longevity. Even if we ignored the evidence that moderate wine drinkers actually have lower cancer risk and assumed it was a linear dose-response relationship, the major cause of mortality is heart disease. Since moderate drinkers have a larger benefit of reduced heart disease risk than potential increase in cancer, the net result is still clearly positive. Add to that the benefits of wine on Alzheimer’s, diabetes, osteoporosis, etc. etc. and you will see my point.
But the big C is a scary thing, and a major point of emphasis in the report is breast cancer. The widely held view, based on the many studies that have been done, is that a drink a day increases risk of breast cancer by 10%; 2 drinks, 20% and so on. Lifetime risk of breast cancer is around 12%, but the risk of a daily drink (if any) would not increase risk to 22%, but rather 10% of the 12%, so the net is just over 13% -  hardly measureable by statistical standards. Add to that the self-reporting bias and it is easy to see why alarmist reporting is unjustified. And as I have pointed out many times before, in populations where women drink primarily red wine, the incidence of breast cancer is substantially lower.
Which brings us to the question of whether red wine really is different. A study 783 elderly men in the Chianti region of Italy attemptedto answer this question by measuring resveratrol metabolites in the urine, and looking for a relationship of resveratrol to observed rates of cancer and longevity. The reasoning was that red wine’s benefits are due to resveratrol, which also occurs in other foods, so total resveratrol from all dietary sources should correlate to improved health. However, the study found no such correlation.

I could have told them that before they started the study, because there is not much resveratrol in any naturally occurring food including wine, so it was never the primary reason for red wine’s benefits. Remember the whole reason for doing the study was to try to find what it is about wine that would explain why wine drinkers fare so well; but it always comes back to just drinking the wine. 

Tuesday, February 4, 2014

Wine and chocolate lower diabetes risk


A perennial topic around Valentine’s Day is the health benefits of wine and chocolate, and this year we have new evidence that they may lower the risk of type 2 diabetes. Credit is given to high levels of anthocyanins, nutritional antioxidants found in red wine, berries, and of course dark chocolate. Anthocyanins are the pigments that give these foods their color, unlike resveratrol which also comes from the skins of wine grapes.

The study, from the University of East Anglia and Kings College London, consisted of a food questionnaire of 2000 women. Those with the highest intake of anthocyanin-rich foods had lower insulin resistance – a marker for type 2 diabetes - and better blood glucose regulation. But the researchers took it a step further, and documented that this group also had lower levels of markers of inflammation, believed to be associated with a wide range of age-related diseases including cancer, diabetes, and cardiovascular problems. Sweet news for your sweetheart indeed.

As with all population-based studies of this type, there are a few caveats. For one, dark chocolate high in anthocyanins and flavonoids is not what you would typically find in an assortment of confections, and high sugar or butterfat content may cancel out much of the benefits. And with wine of course, it is consumption in moderation that is the key to healthy drinking. And perhaps just as important, food intake surveys of this type may show more about what unhealthy foods are not being consumed, not just what is.

I’m looking for studies on the benefit of giving roses with chocolate and wine (I’m sure it has to contribute something) but for now we will have to take that on faith.

Tuesday, November 12, 2013

Lost in translation: Why resveratrol supplements are not the same as drinking wine


Resveratrol, the miracle molecule from red wine, has rocketed from relative obscurity to celebrity status in the supplement market. Its multiple anti-aging properties are given credit for this, and I used resveratrol research in my book “Age Gets Better with Wine” to explain why moderate regular consumption of red wine is a healthy thing. Supplement marketers now proclaim that resveratrol pills have “all the benefits of wine without the alcohol” and tout their own special formulas. Yet there remains a lack of large well-controlled clinical studies to back up these claims.

A relatively new field of medical science called translational medicine helps explain the problem. Often called “bench to bedside” research, translational medicine seeks to bridge the gap between laboratory studies and validated clinical treatments. The challenge of translational medicine is enormous, given that more than 90% of treatments (say for example a drug or supplement) fail in human trials after successful runs in animal studies. It’s an astonishing  statistic, but this percentage has actually been increasing despite improvements in methodology. Dr. Richard Klausner, former Director of the National Cancer Institute, summed up the problem: “We have cured cancer in mice for decades—and it simply didn’t work in humans.”

So what does this mean for resveratrol? Despite the thousands of scholarly publications on resveratrol, it is still not clear. If you are a fruit fly, then resveratrol will activate your anti-aging sirtuin genes and you will live longer (and apparently have a more vigorous sex life.) If you are a mouse on a high fat diet, resveratrol is what you want in order to set your metabolism in order. But translating these findings to humans is deceptively difficult. A recent article highlighted some of the problems: Natural compounds such as resveratrol afford no intellectual property that could be leveraged to fund the large clinical trials needed to determine their effectiveness; nutraceutical companies complicate the problem further by developing their own proprietary blends with multiple ingredients; and resveratrol has multiple therapeutic “targets” each with its own dose-response curve, tissue affinity, and metabolism.

Resveratrol research may still pan out however, and some therapeutic applications are well validated, such as in skin care. Evidence is certainly adequate to continue with clinical research on resveratrol on a wide range of conditions, including Alzheimer’s disease, diabetes, and cardiovascular disease. But a glass of red wine with dinner is still a good thing and likely to remain so.

Tuesday, October 22, 2013

Versatile Resveratrol Part 2: The ultimate skin care ingredient?


What would the ideal anti-aging skin care product look like? To begin with, it would need to provide protection against sun damage from UV exposure.[i] Of course any sunscreen does that, so what we really want is something that can help reverse the effects of UV exposure, which include mutations in the DNA of skin cells. This is where the idea of working at a molecular level comes into play. While many products talk about “DNA repair” the evidence for a role for resveratrol is particularly strong. There are several ways that resveratrol functions in this regard, the best known of which is its powerful antioxidant effects.

Healthier DNA means not only more attractive skin but a lower risk of skin cancers. The use of antioxidants such as resveratrol to lower risk of skin cancer is known as chemoprevention. There is evidence that it may help prevent many other types of cancer as well.

Another measure of aging has to do with integrity of sequences on the ends of the chromosome known as telomeres[ii]. Each time a cell replicates, the DNA must “unzip” to provide a template for the chromosomes in the new cell. It is prevented from unraveling by telomeres, which are sort of like the caps on shoelaces, but with each cycle the telomeres get shorter.. Restoring telomeres is a major effort in anti-aging, and it appears that resveratrol may activate the enzyme that restores telomeres (telomerase), thereby improving cellular health and longevity.

Nothing will magically undo every DNA mutation or the visible manifestations of them in the skin (such as discoloration, wrinkles, and other blemishes) so our ideal product should help with those too. One way that resveratrol improves skin is by inhibition of the enzyme that makes pigment, which results in lightening of dark spots and overall brightening[iii] of the skin.

Facial redness[iv] is another manifestation of the type of inflammation associated with accelerated aging. Resveratrol has also been shown to reduce facial redness with a twice daily application for 6 weeks, and continued improvement beyond that.

We all know that good skin is built by good collagen and elastin (a type  of collagen.) These proteins are constantly being rebuilt by enzymes known as matrix metalloproteinases, referred to as “MMP’s.” Regulation of MMP activity is critical to skin health and aging. It should come as no surprise then that resveratrol is implicated in regulation of MMP via SIRT activation[v], improving the skin’s stress response to UV exposure. This translates into healthier collagen and more elastic skin.

Sometimes however collagen rebuilding is overly exuberant, resulting in thickened scars. An extreme form of scarring is keloid, and treatment of keloids remains a challenge for plastic surgeons. An effective weapon   may be found in resveratrol, which has been shown to inhibit the cells (fibroblasts) that are overly active in keloids, while having no adverse effect on normal fibroblasts.[vi]

Acne is another common problem, and not one limited to teenagers. While there are effective treatments for acne such as benzoyl peroxide and tretinoin (Retin-A), these can cause irritation. Resveratrol is proving to be a useful adjunct to acne treatment,[vii] with more than one mode of action: It is antibacterial with specific effects on the type of bacteria associated with acne, while its anti-inflammatory properties reduce the redness and irritation.

A later life issue is changes in the skin with menopause. These include thinning due to lowered collagen production, dryness due to lessened moisture retention, and others. Given the controversies with estrogen replacement therapy, the need for a product providing estrogen-like effects in the skin is substantial. Resveratrol is one of the few ingredients capable of stimulating collagen production through estrogen-like effects.[viii]

If resveratrol is going to accomplish all of these anti-aging feats in a skin care product, it has to permeate the skin and reach the cells active in regeneration (bioavailability.) resveratrol is uniquely suited to traverse the barrier of hardened surface cells known as the stratum corneum because of a few features. One is the small size of the molecule, probably the smallest of the antioxidant polyphenols; the other is that it is hydrophobic, meaning that it is more comfortable in lipids (fatty molecules.) These types of molecules are able to penetrate better.



[i] Nichols JA, Katiyar SK. Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms. Arch Dermatol Res. 2010 Mar;302(2):71-83
[ii] Xia L, Wang XX, Hu XS, Guo XG, Shang YP, Chen HJ, Zeng CL, Zhang FR, Chen JZ. Resveratrol reduces endothelial progenitor cells senescence through augmentation of telomerase activity by Akt-dependent mechanisms. Br J Pharmacol. 2008 Oct;155(3):387-94.
[iii] Park J, Boo YC. Isolation of Resveratrol from Vitis Viniferae Caulis and Its Potent Inhibition of Human Tyrosinase. Evid Based Complement Alternat Med. 2013;2013:645257
 
[iv] Ferzil G, Patel M, Phrsai N, Brody N. Reduction of facial redness with resveratrol added to topical product containing green tea polyphenols and caffeine. J Drugs Dermatol. 2013 Jul 1;12(7):770-4.
 
[v] Lee JS, Park KY, Min HG, Lee SJ, Kim JJ, Choi JS, Kim WS, Cha HJ. Negative regulation of stress-induced matrix metalloproteinase-9 by Sirt1 in skin tissue. Exp Dermatol. 2010 Dec;19(12):1060-6.
 
[vi] Ikeda K, Torigoe T, Matsumoto Y, Fujita T, Sato N, Yotsuyanagi T. Resveratrol inhibits fibrogenesis and induces apoptosis in keloid fibroblasts. Wound Repair Regen. 2013 Jul-Aug;21(4):616-23.
 
[vii] Fabbrocini G, Staibano S, De Rosa G, Battimiello V, Fardella N, Ilardi G, La Rotonda MI, Longobardi A, Mazzella M, Siano M, Pastore F, De Vita V, Vecchione ML, Ayala F. Resveratrol-containing gel for the treatment of acne vulgaris: a single-blind, vehicle-controlled, pilot study. Am J Clin Dermatol. 2011 Apr 1;12(2):133-41.
 
[viii] Giardina S, Michelotti A, Zavattini G, Finzi S, Ghisalberti C, Marzatico F. [Efficacy study in vitro: assessment of the properties of resveratrol and resveratrol + N-acetyl-cysteine on proliferation and inhibition of collagen activity]. Minerva Ginecol. 2010 Jun;62(3):195-201.