Wednesday, December 29, 2010

new resveratrol revelations

What a year it has been for resveratrol, the polyphenol molecule from red wine. Last year at this time it was the toast of the town, having been credited with triggering a metabolic change leading to increased lifespan in experimental models, then catapulted into the limelight as a potential cancer cure with clinical trials under the auspices of pharma giant GlaxoSmithKline. Sales of resveratrol supplements were skyrocketing, with audacious claims about weight loss, brain power, and longevity, never mind that none of this had been proven in humans. But with the new year came new controversy. Two of Glaxo’s competitors, Pfizer and Amgen, published their own studies on resveratrol, concluding that the longevity effect was false, an artifact of the testing method. What few clinical trials there are in humans revealed that it is poorly absorbed and doesn’t last very long in the body anyway. Then in November Glaxo abruptly announced the suspension of the clinical trial and all further development of their flagship resveratrol derivative, SRT501. Supplement sellers started to look more and more like snake oil peddlers, while enthusiasm began to fade in the scientific community.

Despite these setbacks, progress on the basic science front continues to reveal interesting properties of resveratrol. One line of research looks at extending lifespan of cells not through metabolic change but by repairing the caps on DNA strands that are clipped each time the cell divides. These caps, called telomeres, are sequences on the ends of the chromosomes that prevent unraveling with the replication cycle; with each division they shorten, limiting the number of times the cycle can repeat and therefore the lifespan of the cell. Cell types that require constant replenishment, such as skin and the linings of blood vessels, show their age more than others as they lose the ability to replicate. But cancer cells have figured out how to by pass this limitation and become immortal by rebuilding telomeres with an enzyme called telomerase. Control telomerase and you harness cellular immortality, and it appears resveratrol may provide the key.

The source of new cells is what are called progenitor cells, which in turn trace their lineage to stem cells. A recent study enticingly called “Immortalization of epithelial progenitor cells mediated by resveratrol” outlines the mechanism by which resveratrol pulls this off in skin cells. There is a lot that remains to be deciphered about this but it looks promising. Another paper reported on the role of resveratrol in reducing senescence of the progenitor cells that replace blood vessel lining, an important step in countering atherosclerosis, by activating telomerase. Just as important though is that resveratrol uses the same metabolic pathways to slow the growth of cancer cells.

Such is the state of affairs with resveratrol: exciting new findings on the leading edge of biomedical research, while verification of its use in clinical medicine seems ever farther off. All I can say is stay tuned.

1. Pearce VP, Sherrell J, Lou Z, Kopelovich L, Wright WE, Shay JW. Immortalization of epithelial progenitor cells mediated by resveratrol. Oncogene 2008 Apr 10;27(17):2365-74.
2. Xia L, Wang XX, Hu XS, Guo XG et al. Resveratrol reduces progenitor endothelial cells senescence through activation of telomerase activity by Akt-dependent mechanisms. Br J Pharmacol 2008 Oct;155(3):387-94.
3. Lanzilli G, Fuggetta MP, Tricarico M, Cottarelli A et al. Resveratrol down-regulates the growth and telomerase activity of breast cancer cells in vitro. Int J Oncol 2006 Mar;28(3):641-8.
4. Fuggetta MP, Lanzilli G, Tricarico M, Cottarelli A et al. Effect of resveratrol on proliferation and telomrease activity of human colon cancer cells in vitro. J Exp Clin Cancer Res 2006 Jun;25(2):189-93.

Monday, December 13, 2010

Believe in wine

Believing in Santa Claus may not be a scientifically tenable position, but it does come with benefits. As children reach the age where suspicions arise as to the veracity of the notion of a jolly visitor bearing gifts in the night, they come to understand that it is in their best interest to play along. In the case of wine, the science may be on more solid footing as to the benefits of moderate consumption, but what people believe does not always align with the facts here either. That is why it is encouraging to see recent survey data that people are finally acknowledging the connection between wine and health, even if there are still some areas of uncertainty.

London-based Mintel research recently released the results of a survey finding that some 85% of drinkers believe that wine in moderation is good for overall health, while wine drinkers hold that red wine is good for the heart. On the other hand, half of those attribute the same benefits to white wine. Given white wine’s relative lack of the polyphenol antioxidants that red wine has (extracted from the skins and seeds during fermentation of the whole grape), white is probably given more credit than it deserves here, but it is a least a step in the direction of healthy drinking. Some confusion is to be allowed here though since the degree to which red is better depends a lot on what health parameters are being studied, not to mention effects of beer or spirits consumption.

What the report didn’t evaluate is the level of penetration of knowledge about wine’s other benefits. One of the more difficult jobs that wine and health educators have is overcoming the assumption that heart health is the whole story. Sure, it’s the French paradox, I get it, people say. But that is only the beginning of a story whose conclusion is nowhere in sight. For example, every major epidemiologic survey on factors associated with Alzheimer’s disease has found the lowest incidence in wine drinkers, but we rarely hear anything about that. The other misconception out there is that it’s all about the polyphenols, so we just need to take a pill and skip the alcohol. Supplement marketers regularly claim that their brand has “all the benefits of wine” which is a misnomer because alcohol in the right amounts is also healthy (improves the high-density to low-density cholesterol ratio, among other good things.)

Another thing the Mintel report found was that people plan to drink more wine this holiday season, and that overall wine consumption is trending upward over the long-term. As for me, I believe that is a good thing. Cheers to all and best wishes for a good bottle from Santa.

Friday, December 3, 2010

Glaxo pulls the plug on resveratrol drug: end of the line?

Resveratrol, the antioxidant molecule from red wine (along with miniscule amounts from some berries and the non-edible parts of the peanut plant), took the world by storm a few years back when it was announced that it could trigger a specific metabolic change associated with significant lifespan extension. Though the phenomenon was only found at first in some strains of yeast under certain conditions, it was believed to work by activating an enzyme system known as sirtuins, which in turn control the switching on and off of genes associated with longevity and a range of diseases of aging. The potential for resveratrol-based compounds caught the attention of pharma giant GlaxoSmithKline, which acquired the rights to it for US $720 million in 2008. But this week Glaxo announced the suspension of all development of their product, known as SRT501, citing concerns about complications in a clinical trial for the blood cancer multiple myeloma. Many now wonder whether resveratrol has gone from darling to dud in only 2 short years.

Meanwhile, sales of resveratrol supplements, based on the naturally occurring and non-patentable molecule, have soared in recent years. Purveyors openly tout it as a “fountain of youth in a pill” and a miracle weight loss solution. Some advocates of natural healing are openly celebrating Glaxo’s failure, accusing them of greedily hijacking a perfectly good natural cure in the name of corporate greed by developing synthetic (and patentable) variations. Pfizer and Amgen have both weighed in recently with scientific publications casting doubt on the ability of resveratrol and its derivatives to activate sirtuins at all, pointing to evidence that the testing method was an artifact leading to false positive results. Is this the end of the road for resveratrol?

There’s support for both arguments, but don’t mark your calendars just yet for resveratrol’s funeral. For one, the natural molecule has a wide range of interesting capabilities, at least in lab studies. Clinical trials are ongoing and much remains to be learned about whether this translates to verifiable benefits in humans. (One thing that appears unlikely is the lifespan extension phenomenon via sirtuin activation, as it has not been found in mammals.) Glaxo was careful to point out that other resveratrol derivatives are being studied, and the point of synthesizing variations on the molecule is to find more potent versions with specifically targeted actions. (See the full quote below.) And without the prospect of return on investment, there is little funding available for studying the natural version. Until more results are in, my suggestion is to bear in mind that the whole thing started with red wine, which does confer longer life on average for moderate regular consumers, along with higher quality of life.

From Glaxo: ”We are focusing our efforts now on more selective SIRT1 activator compounds that have no chemical relationship to SRT501 and more favorable drug-like properties. Currently we have two of these latest generation compounds (SRT2104 and SRT2379) in several exploratory clinical trials.”

Monday, November 22, 2010

Hope for wine allergy sufferers

It seems at every talk I give on wine’s contribution to healthy living, there is at least one person in the audience who asks about wine allergies. Maybe they can’t drink red (thereby missing out on a lot of the antioxidant polyphenols), or maybe not wine at all. Sulfites are often blamed, but they are naturally present in all wines, beyond what is commonly added for preservation, and actual sulfite allergies are comparatively rare. What’s more, sulfites are higher in white wine, while allergic reactions are more common to reds. The question of why so many people have reactions to wine has remained largely unanswered until now.

A study from the Department of Biochemistry and Molecular Biology, University of Southern Denmark, and the Agricultural Research Council, Research Unit for Table Grapes and Wine Growing in Turi, Italy has identified a class of molecules called glycoproteins as the culprit. These are ubiquitous biological compounds that are comprised of a sugar portion (glyco-) attached to a protein. Examples include several hormones, connective tissue structures, and even antibodies. These molecules are commonly ensconced in the cell membrane, where they may help to identify what type of cell they are part of. Immune surveillance can be very tuned in to these molecules and so they are fairly common allergens. The Danish-Italian study identified some 28 different glycoproteins in wine with similarities to known plant allergens.

Unfortunately, glycoproteins in wine are derived from the grapes themselves as well as the yeast required for fermentation. It is possible that different strains of yeast might explain the differences in reactions to different wines (for example, people who are able to drink European wines but not the same varietal from a domestic producer), but using different yeasts would change the character of the wine. But this isn’t to say that nothing can be done. Hopefully some clever winemaker will target the market segment of those who would like to drink wine but can’t, and figure out some fining method or other means to remove glycoproteins from wine without sacrificing character. Clearly there is a lot more to learn about glycoproteins and wine allergy, but at least we now have something to go on.

Palmisano G, Antonacci D, Larsen MR. Glycoproteinomic profile in wine: A sweet molecular renaissance. J Protenome Res 2010 Oct 1; [epub ahead of print]

Friday, November 12, 2010

Madeira for malaria?

Of all of the scourges of mankind, malaria ranks near the top of the list, affecting more people worldwide that the entire population of the U.S. It has been notoriously resistant to vaccines, in part because of the complex life cycle of the parasite, which spends part of its development in the mosquito and part inside the red blood cells of people. It is this latter part that raises an interesting possibility for treatment with the red wine compound resveratrol, as reported at a recent meeting of tropical medicine specialists.

You may be familiar with the antibiotic properties of resveratrol and other polyphenol molecules from red wine. These compounds come from the skins, where the grapes form them as part of their natural environmental defense. Plants, and especially ripening fruit, are vulnerable to bacteria, viruses and fungus just as animal are, and this explains the broad spectrum of antibiotic capabilities of resveratrol. Wine’s use as a means of purifying drinking water over the past few thousand years is likely based as much on this as its alcohol content. Parasites such as the malaria bug are more difficult to suppress, and so the activity of resveratrol was unexpected.

One reason for this is that resveratrol’s inhibition of malaria works indirectly, by altering the red blood cells that contain the bug. In order for the more sever manifestations of malaria to occur, the blood cells need to adhere to the lining of the blood vessels, which resveratrol prevents (this is actually related to how it helps prevent heart attacks). So the idea isn’t that resveratrol can eradicate the parasite, but rather to mitigate the more severe effects of it while treating with anti-malarial drugs.

Since malaria is most common in tropical climates and developing countries, any effect of wine consumption would be a difficult association to discover. The British, during the Raj turned to quinine and the now-classic gin & tonic rather than claret for the same practical reasons. It is a bit difficult to picture fine Bordeaux becoming the standard prophylaxis in sub-Saharan Africa, but it may well hold the key to minimizing a lot of suffering.

Saturday, October 30, 2010

Something new to chew on: Resveratrol chewing gum

My what a long way we have come since I first started lecturing and writing about wine and health a decade ago. For one, few had heard of resveratrol, the potent antioxidant in red wine, and many of those who had didn’t know how to pronounce it. Flash forward a few years and a few thousand research articles and now resveratrol is the flavor of the month, appearing in everything from diet pills to energy drinks. The discovery that it may activate the enzymes responsible for enhanced longevity normally associated with caloric deprivation catapulted resveratrol into the spotlight. Ads unabashedly tout it as the new fountain of youth. The latest version is a chewing gum, from a company called Gumlink A/S.

A few cautionary notes here, but there are also some good reasons why it might not be such a bad idea. Firstly, resveratrol hasn’t been able to explain all of the benefits associated with moderate wine consumption, and serious doubts have been advanced about whether it is truly capable of activating the longevity effect seen in lab experiments. So a healthy measure of skepticism is advised about any product, with or without resveratrol, that claims to deliver all the benefits of wine. But resveratrol is a remarkable molecule with many potentially useful capabilities for anti-aging. Several clinical trials are ongoing, though few have been completed.

So supplementation with resveratrol might not be a bad idea, we just don’t know enough to say for sure. One big problem with supplements is that resveratrol is poorly absorbed from the digestive tract, so most of it may be wasted. But research has shown that it is absorbed better from the lining of the mouth (oral mucosa) and I have speculated that wine drinkers who savor and swirl might be taking advantage of this without even trying. Another interesting line of research points to benefits of resveratrol in dental health. So assuming the resveratrol gum is sugar-free it just might be the ticket. Especially if it helps whiten those purple teeth from wine drinking.

Thursday, October 21, 2010

Wine and breast cancer: an update

With October being the annual exercise in breast cancer awareness, our attention turns to the ongoing issue of drinking and breast cancer risk. What we usually hear is the established advice that alcohol consumption in any form contributes to the risk of developing breast cancer, in a direct ratio of about one daily drink to a 10% increase. But if you have been following my posts here, you will know that the question of wine consumption and breast cancer is considerably more nuanced, and it remains entirely possible-even likely, in my analysis-that red wine decreases risk, in the right amounts. A recent study from the Fred Hutchinson Cancer Research Center here in Seattle, in collaboration with major cancer centers around the country, helps to shed some light on the subject.

But first we need to revisit the question of why alcohol could contribute to cancer in the first place. As I point out in my book, a scientifically provable basis for alcohol leading to the cellular changes that progress to cancer remains elusive. The best idea out there is that it somehow interacts with estrogen receptors, which would imply that only certain types of breast cancer (know as estrogen-receptor positive) would correlate with drinking. However, no large studies had previously looked at drinking and breast cancer subtypes before the recent Hutch project. What they found was a relationship of ER positive cancer only in an uncommon variant called lobular carcinoma, but not the much more common ductal type. This particular study did not evaluate subcategories of drinking, however, but it nevertheless raises more questions than it answers. Here’s why:

If alcohol contributes to breast cancer via the only plausible mechanism proposed, by interacting with estrogen receptors, the risk would not correlate only to an uncommon subtype that also happened to be ER positive. So we still lack a plausible cause-effect explanation for the role of alcohol in breast cancer. One reason why these studies give such conflicting results is the reliance on self-reporting, which is wildly unreliable when it comes to the question of drinking habits. Another is that drinking habits tend to be erratic; few have only wine, only a glass or two a day, and always with dinner. Studies from populations that do have more traditional wine drinking patterns show a reduction in breast cancer risk. As these populations become more and more modernized, the opportunity to get meaningful data from population studies diminishes. So pink may be the theme color for breast cancer awareness, but I prefer to call it rosé.

Tuesday, October 5, 2010

Wine and breast cancer risk with BRCA mutation

One of the more significant developments in the understanding of breast cancer risk factors was the discovery of two inheritable genetic mutations, BRCA1 and BRCA2, that dramatically increase the lifetime risk of breast cancer. These mutations are aberrant forms of a class of genes called “tumor suppressors” so when they don’t function normally, cancers are more likely to develop and spread. (Tests are available for these mutations and many women with BRCA are opting for prophylactic mastectomy and reconstruction.)

Since alcohol consumption is generally regarded as a risk factor for breast cancer, it is important to know how it might affect women with BRCA. Given all of the confusion about whether wine consumption increases or decreases risk, it becomes even more important to know what to recommend. Surely, the knowledge of a high risk of cancer and not being able to have a glass of wine with dinner seems like double punishment. Fortunately a recent study helps to provide some guidance.

The study, from a collaboration called the Hereditary Breast Cancer Clinical Study Group, analyzed matched pairs of breast cancer patients with and without each type of BRCA mutation, according to a range of lifestyle factors. It’s a powerful study because of the numbers of patients surveyed, nearly 2 thousand, and its broad reach from several countries, though most were from Canada and the U.S.

After statistical adjustments for other known factors, there was no increase in risk from moderate alcohol consumption. Some studies have actually found decreased odds of developing cancer among moderate drinkers with BRCA, but in this study the reduction was only seen in wine drinkers. The implication of this is that it is the wine that is responsible for lowering the risk seen in previous analyses where drinking could not be accurately subdivided by type of beverage. This meshes well with findings on breast cancer risk without the BRCA mutation.

Several compounds unique to red wine have impressive anti-cancer properties, specifically for breast cancer. Clinical trials using some of these compounds in conjunction with traditional therapy are underway. But if you or someone close to you has a strong family history of breast cancer, getting tested for the BRCA gene can save their life. The good news is that they can still share a glass of wine with you and not add to their worries.

Dennis J, Ghadirian P, Little J, Lubinski J, Gronwald J, Kim-Sing C, Foulkes W, Moller P, Lynch HT, Neuhausen SL, Domchek S, Armel S, Isaacs C, Tung N, Sweet K, Ainsworth P, Sun P, Krewski D, Narod S; the Hereditary Breast Cancer Clinical Study Group. Alcohol consumption and the risk of breast cancer among BRCA1 and BRCA2 mutation carriers. The Breast 2010;e-pub.

Saturday, September 25, 2010

Well hello kitty: Are you really old enough to drink?

If you are a fan of the Hello Kitty products (the smiling kitten face icon from Japan) then you will want to know that there is now a hello Kitty brand of pink sparkling wine. Produced by the Italian wine producer Tenimenti Castelrotto in partnership with luxury goods company Camomilla, Hello Kitty spumante is currently available only in the U.S., Russia, and Singapore. According to winemaker Patrizia Torti, “'Hello Kitty … is a recognised cult fashion icon among teenagers and adults around the world.” Is Hello Kitty really grown up enough to be in the wine business? What should the minimum drinking age be anyway?

We are dealing with some pretty sticky issues here. We are conflicted about marketing alcoholic beverages to young people (not that Hello Kitty is exclusively a young brand) and there are definitely mixed mesages on drinking. In the U.S. the debate has centered around whether the legal drinking age should be 18 or 21. here’s a brief summary of the arguments:

Against lower drinking age: Teens are undergoing a multitude of physical and mental changes, combined with peer pressure and other factors, which can lead to abusive drinking patterns. Studies show that teens who drink have a greater probability of binge drinking and academic failure.

In favor of a lower drinking age: At age 18, most of the priviledges of adulthood are conferred including voting and military service. Prohibiting teens from drinking in bars, restaurants, and public locations has the effect of forcing them to drink in unsupervised places such as fraternity houses or house parties. A higher legal drinking age actually encourages abuse by sending the message that drinking conveys maturity. A lower legal age makes it less taboo and creates a more favorable environment for teaching moderation and responsible consumption. It is this failure to model healthy drinking that fosters binge drinking.

Statistics are tossed back and forth about whether traffic accidents are increased or decreased by a lower drinking age, but my personal view is that the wheels started to come off the cart when we divorced wine with dinner. There is no healthier way to consume alcohol that to make wine a food, and if you have been paying attention at all here you know that it is an impressively healthy thing indeed. The age-old European practice of serving the young people watered down wine with family meals cannot be considered by any stretch of the imagination as a step toward alcohol abuse.

But Hello Kitty, you may be a special case. Are you sweet and silly or a real grown-up drink?

Monday, September 13, 2010

Better red than dead, wine drinkers outlive teetotalers

Wine drinkers outlive nondrinkers, or so the studies show. But nondrinkers are not all created equal, and that along with other factors makes it difficult to draw firm inferences about healthy drinking. For example, an oft-cited problem is what is called the “sick quitter” hypothesis, which holds that among the nondrinkers are those with a history of problem drinking. Their health having already suffered, the comparison may be unfair by lumping them in with healthier folks who abstain for religious or other personal reasons. Moderate wine drinkers may differ socioeconomically or in other important demographic variables. Anti-alcohol advocates are quick to point out such problems with population studies.

So while there are several studies showing greater average lifespan in wine drinkers, more needs to be done. One good study out this summer may give comfort to wine drinkers and help dispel some of the critics. The project, a joint effort of Stanford University and the University of Texas, looked at all-cause mortality over a 20-year period, comparing various factors to death rates, beginning with a study cohort of individuals aged 55-65. As we have come to expect from such studies, death rate was twice as high in nondrinkers compared to moderate drinkers, and 70% higher in heavy drinkers. This is the classic J-shaped curve that defines just about any disease condition when plotted against wine consumption.

What’s different about this latest report is that the researchers went to great lengths to adjust for the effects of previous problem drinkers and socioeconomic factors. Taking all of this into account, the differences were less dramatic but still clear, with moderate drinkers still only about half as likely to die of any cause compared to teetotalers.

Ultimately the question of how drinking affects lifespan is too complicated to reduce to a simple mathematical formula anyway. Alcohol remains a part of whatever the formula is, just in the right amounts. Wine drinkers do a lot of other healthy things, and have a higher quality of life in old age too. Viva vino!

Holahan CJ, Schutte KK, Brennan PL, Holahan CK, Moos BS, Moos RH. Late-Life Alcohol Consumption and 20-Year Mortality. Alcohol Clin Exp Res. 2010 Aug 24.

Friday, September 3, 2010

What is responsible drinking?

The paper today featured a full-page ad exhorting us to drink responsibly over the Labor Day weekend, good advice to be sure. The main point was an emphasis on the equivalency of different forms of drinking in terms of the total amount of alcohol: One 12-oz beer = one cocktail = one 5-oz glass of wine. Perhaps the thinking is that people lose track of the true amount they are consuming with lower-alcohol beverages. Just a couple of beers or a few glasses of wine, not like hitting the hard liquor, right? The tagline was “It’s not just what you drink, it’s how much.” Useful information I suppose but perhaps an oversimplification when it comes to wine, as we have seen so many times before.

My advice here would be to look at the question of not just how much you drink, but how you drink. Beer may be consumed with meals but is marketed as a “party” drink, or refreshment while watching TV or sporting events. Historically (and I mean a very long time ago) it was considered to be a sort of food, a way to get nutrition from grains in a relatively non-perishable form. But I would guess that today beer consumption with meals is only a fraction of the whole. With cocktails it is more clearly all about the drinking for many people (which may explain why this ad was sponsored by the distilled spirits council.)

But when it comes to wine, the pattern of how people consume it is different. While wine may be consumed without food, often it is part of the evening meal. Drinking with food both slows down the absorption of the alcohol and the pace of drinking. A great many other healthy behaviors are linked to wine consumption too, placing wine at the center of a healthy lifestyle. Simply comparing alcohol dosing to beer and distilled spirits misses this very important point about healthy drinking, by presuming that all forms of consumption are equally harmful. It frames wine as a drug instead of a food.

I would suggest that we replace the phrase “responsible drinking” with “healthy drinking” so that we frame the discussion in a more positive light. As long as we view alcohol through a lens that shows only the detrimental aspects of drinking, we paradoxically encourage the view of alcohol as a drug. But moderate drinkers outlive nondrinkers and are healthier, especially with wine. Responsible drinking is healthy drinking, and the “how” and “what” do make a difference.

Monday, August 23, 2010

Resveratrol: natural supplement or pharmaceutical breakthrough?

Before we delve into this too deeply, keep in mind that the answer might be neither one. Resveratrol, the antioxidant polyphenol from red wine that I dubbed the “miracle molecule” in my book, has had an interesting career. It first came into the spotlight in the early 1990’s following the “French paradox” story on the CBS-TV show “60 Minutes” as a potential explanation for the effect. Research attention ramped up quickly, and there seemed to be no end to the list of beneficial properties on health and longevity. The real breakthrough was the discovery that resveratrol was an activator of an enzyme called sirtuin, responsible for a specific metabolic change associated with dramatically increased longevity. Overnight an obscure field of biochemistry research blossomed into a massive supplement industry.

But an interesting thing happened on the way to the marketplace. The scientist who is credited with the discovery of resveratrol’s sirtuin-activating abilities, Christoph Westphal, parlayed the finding into a biotech company that was quickly picked up by pharma giant Glaxo. A more potent resveratrol derivative, dubbed SRT501, is being developed as a prescription diabetes drug, but the ability or resveratrol to activate sirtuins has been widely questioned and may turn out to be less than impressive. Sirtuin activators unrelated to resveratrol are the focus of development at Glaxo now.

Much of this came to light recently with the revelation that Westphal and a Glaxo director of development were peddling resveratrol online through a nonprofit organization called the Healthy Lifespan Institute. Glaxo was none too pleased.

So where does that leave resveratrol? Despite wide acclaim and marketing hype, evidence is still fairly scant that it brings the same benefits in a pill that moderate wine drinkers enjoy. Specifically, the promise of meaningful lifespan extension through sirtuin activation has not been demonstrated in laboratory animals other than worms and fruitflies. There are questions about its bioavailability – the absorption and metabolism in the body – and purity of the various supplements. Despite the thousands of research papers on resveratrol, much remains to be learned about how it works in the human body. Stay tuned, but for now your best bet is to stick with wine.

Wednesday, August 11, 2010

Is wine-fed beef a healthier choice?

Leave it to those crazy Canadians to come up with the idea of feeding wine to beef cattle. While so many stockyards are filled with cows standing knee-deep in their own droppings, bloated from a corn-based diet, these bovine bon vivants are sipping red wine and eating organic. According to Jandince Ravndahl of Sezmu Meats in British Columbia, “They moo at one another a little more and seem more relaxed. There are a few that lap it up out of the pail. After they've had it for a while, when they see us coming with the pitchers, they don't run, but they come faster than usual.” Do pre-marinated cows make healthier beef?

Apparently it is at least more tender and has a sweeter taste, though I have not had the opportunity to try it myself. I can however think of many reasons why it would be healthier. Pairing red wine with beef has a specific health advantage, in that the iron in the hemoglobin – this is what makes red meat red – is a potent oxidant neatly counteracted by red wine’s antioxidants. The fats from beef are also tempered in their cholesterol-promoting tendencies by wine polyphenols. Whether these wine benefits are enhanced by wine in the cows’ diet is a matter of speculation, but there’s more.

Again, this is just an idea, but wine polyphenols have natural antibiotic capabilities and so they alter the demographics of intestinal bacteria. With E. coli being such a concern this could translate into a real asset. Then there is the possibility that less stressed cows develop healthier meat, due to stress hormones or other factors.

There are potential environmental benefits too. One little-appreciated fact is that cattle are a major source of methane, a greenhouse gas, so there is a large carbon footprint from every steak and burger. Under normal circumstances, cows expel up to 50 gallons of gas a day, and one calculation puts an estimate of 17% of all greenhouse gas emissions from cattle ranching. But wine cows are believed to produce less methane (perhaps related to an alteration in their intestinal bacteria?).

I don’t know if ranch hands are about to morph into sommeliers, but if this catches on I propose that we update “caballero” to “cabernero.” What do you think?

Wednesday, August 4, 2010

Why the proposed ban on direct wine shipping would be harmful to public health

A number of convoluted laws came into place following prohibition, many of which are based on the same faulty reasoning that led to curbs on alcohol sales in the first place. Although wine remained somewhat available during prohibition (people took a lot of sacramental wine it seems), a ban on direct shipping to consumers remained for a number of years. These regulations varied from state to state, with many states allowing wineries to ship directly to their customers within the state, but gradually a system of reciprocity between states with such allowances developed and was confirmed in a 2005 Supreme Court ruling. An echo of prohibition rang out this year however with the proposal in Congress (H.R. 5034) to ban such sales.

Unsurprisingly, the bill was put forth by wholesalers, who would stand to lose by being bypassed. But rather than draw attention to the real reasons behind the proposal, the lobbying campaign in support of it trots out the same tired public health arguments that harken back to a bygone era. Children and minors will have easier access to alcohol, they say, and direct shipping encourages alcohol abuse. As if minors are going to order boutique wines from small producers, and wait a couple of weeks for it, all the while hoping it will be delivered while their parents aren’t home, and that the shipper won’t demand a signature from someone over 21 as clearly stated on the large heavy box also labeled “contains alcoholic beverages.” If you really believe that, I have to ask what you have been smoking.

So are there public health consequences to direct shipping? If there are, I would place them squarely on the benefit side. People who buy wine direct tend to be interested in the wine for its aesthetic attributes more than its anesthetic properties. There are cheaper and more convenient ways to imbibe. Drinking wine because you enjoy the particular qualities of the wine means that it becomes more like a food, part of a meal, a component of a healthy lifestyle.

More information and resources on this issue at

Wednesday, July 21, 2010

Wine is a food: New USDA Guidelines

There is a chapter in my book “Age Gets Better with Wine” called “Wine is a Food” because what I found in my research for the book that having wine with meals is key to unlocking its healthful properties. There is no question that people use food as a drug, hence the term “comfort food.” I would even make the case that. Given the epidemic of morbid obesity, the effects of food abuse far outweigh those of alcohol abuse. So if wine is indeed a food, what is the recommended daily allowance?

Though authorities have long shied away from explicitly recommending that people drink wine for better health, the U.S. Department of Agriculture recently updated its policy recommendations to reflect the ever-increasing evidence of wine’s health benefits. Notably, mentions of the benefits of moderate drinking have begun to replace the admonishments about the ill effects of alcohol abuse. These two drinking patterns are distinct and separate, though it seems to have taken some time to reach the point where a discussion of this type occurs with federal agencies. Much remains to be done, but baby steps toward recognition of the epidemiologic evidence that moderate drinkers outlive nondrinkers on average are certainly more than welcome.

Wine drinkers not only live longer but are healthier too. A study sponsored by Medicare a few years ago clearly demonstrated that drinkers have lower health care costs, with wine drinkers in the lowest health care expenditure category. Dr. Curtis Ellison, a foremost authority on wine and health, has stated that the single most effective thing a person can do to reduce their odds of heart disease other than not smoking is to take up having a drink or two with dinner. When considering how hard it is to get people to eat a healthy diet, exercise, and take their blood pressure medication, that’s a pretty powerful and simple recommendation.

So if wine is a food, then what is the recommended daily allowance? It may be a good thing to have as part of a meal but I wouldn’t hold your breath waiting for an RDA recommendation on the label. Wine’s nutritional value isn’t based on the traditional data that other foods are, but I would wager that wine does a lot more good than the vitamin and supplement pills that so many people take. Drink real wine, eat whole food. What could be better than that?
The USDA guidelines are available at:

Thursday, July 15, 2010

The weight is over: new hope for the wine diet

I write this post with a bit of trepidation, because anytime we get in to the topic of wine and weight loss the inevitable controversy about resveratrol diet pills comes up. In fact it is the most recent findings about resveratrol and diet that prompted me to write this, and like so many previous reports it seems to have been widely over-interpreted. Supplement manufacturers are all over it despite the fact that like nearly every previous study, it wasn’t done on humans.

The study in question was however done on lemurs, a type of primate, so in theory they are closer to humans than lab mice or fruit flies. There is however an important difference, in that these lemurs have a variable body temperature regulation system such that their metabolism varies with the time of year. In winter they gain weight, which provided researchers with a convenient model to study the effects of resveratrol. What was found with resveratrol supplementation was increased satiety (i.e. less hunger and eating), with faster metabolism and less weight gain during their “seasonal fattening period.”* Given the pattern that many of us humans experience during the winter holidays this sounds like good news indeed.

But alas we are not lemurs, and honestly we have little to blame our seasonal weight gain on other than a change in behavior. It may be of some comfort however to bear in mind that resveratrol is a red wine polyphenol, and evidence that wine drinkers maintain a health weight as compared to nondrinkers is reasonably substantial. Clinical trials on the use of oral resveratrol supplements on the other hand can practically be counted on, well, the other hand. Encouraging though this recent study is to resveratrol supplement peddlers, it is by no means clear that the same effect will be observed in humans. As for me, I will continue to take my “medicine” in red liquid form, as I believe nature intended. Call it the wine diet if you like.

*Dal-Pan A, Blanc S, Aujard F. Resveratrol suppresses body mass gain in a seasonal non-human primate model of obesity. BMC Physiol. 2010 Jun 22;10(1):11. [Epub ahead of print]

Tuesday, July 6, 2010

Eye believe: resveratrol may prevent blindness

Here’s a word that you should know: angiogenesis. Sounds like a cover of a classic Rolling Stones song by Phil Collins’ former band, but what it refers to is the growth of new blood vessels. Sometimes this is a good thing, sometimes not. In the case of some causes of blindness, abnormal angiogenesis is a very bad thing indeed.

Resveratrol, the superstar molecule from red wine, has long been known to inhibit angiogenesis. This may be one of the reasons why it fights cancer, since tumors rely on ingrowth of new blood vessels in order to expand. Abnormal angiogenesis is also involved in some causes of age-related blindness such as diabetic retinopathy and macular degeneration, conditions affecting thousands each year. A recent study suggests that resveratrol’s ability to inhibit angiogenesis might help to save eyesight for many.

Like many such studies, this one was done in mice. These poor subjects had laser treatments to destroy some of the blood vessels in their retinas. Normally, the body would respond by sending signals to stimulate angiogenesis in order to restore the blood flow to the injured eyes, but resveratrol was noted to interfere with this process through specific molecular interactions that the research team was able to decipher. The implication was that protection against disorders related to abnormal angiogenesis might be achieved with resveratrol, though it is important to note that there is a lot to prove in order to apply it in humans.

One case study reported last year did provide some encouragement that oral supplementation with resveratrol might be able to help eyesight. The subject was an 80 year old man with progressively worsening night blindness, despite taking extra lutein and omega-3 fatty acids. This was correlated with deposits of a material called lipofuscin, a substance correlated with age-related loss of vision, in the retina. After 5 months of taking oral supplements containing resveratrol and other wine polyphenols, the subject’s vision improved by objective measurements and the lipofuscin deposits correspondingly decreased. While a case report lacks the heft of an actual clinical trial, it does suggest a potentially fruitful avenue of further research.

There are several other reports demonstrating the protective effects of resveratrol and wine polyphenols against oxidative damage and chemical toxicity of retinal cells, and even some benefits on inhibiting cataract formation. Wine appears to be unique among alcoholic beverage consumption in protecting against cataracts, which implies a role for the polyphenol antioxidants. I’ll keep an eye on the topic for you.

Khan AA, Dace DS, Ryazanov AG, Kelly J, Apte RS. Resveratrol Regulates Pathologic Angiogenesis by a Eukaryotic Elongation Factor-2 Kinase-Regulated Pathway. Am J Pathol. 2010 May 14. [Epub ahead of print]

Richer S, Stiles W, Thomas C. Molecular medicine in ophthalmic care. Optometry. 2009 Dec;80(12):695-701.

Monday, June 28, 2010

Drink to your health: The wine-medical research connection

As I discovered in researching my book Age Gets Better with Wine, from ancient times it has been wed to health care and healthy living. In modern times, wine has come to support medical research more directly, through charity auctions and direct funding. Credit the granddaddy of them all, the Hospices de Beaune, for showing the way. But some wineries are taking it a step further.

A few years ago I had the singular pleasure of attending the Staglin festival, which raises money for mental health research. What a glorious experience! All the top wineries in Napa participate, and although we had more wine that day than was strictly necessary for medical purposes, it was definitely a boon to my state of mind. Congrats to the Staglin family for raising awareness of an issue that many find uncomfortable and which suffers from a lack of research funding as a result. (The event is held every September, info on the Staglin website.)

Ehlers Estate is another winery that ties its profits directly to medical research, in this case heart health. Held in trust by the nonprofit Leducq Foundation, 100% of its proceeds go directly to fund research in cardiovascular diseases. Despite tremendous advances in treatment and prevention of heart disease (and an increasingly detailed understanding of the positive role of wine), it remains a leading cause of death worldwide.

“Live to Love Life” is the motto of the winery with my favorite name, Cleavage Creek. (Talk about the perfect wine for a plastic surgeon!) Profits from Cleavage Creek go to support breast cancer research, “one glass at a time.” Owner Budge Brown, who lost his wife Arlene to breast cancer in 1995, has made it his personal mission to do whatever he can to find a cure. Though I am sure that it was not what he expected when he started Cleavage Creek, it may very well turn out that wine holds one of the keys to winning that battle. We still have a long way to go, and ongoing funding remains crucial.

So drink to the health of your loved ones, celebrate life, and toast to those who are leading the way - preferably with a glass of Staglin, Cleavage Creek, or Ehlers Estate.

Saturday, June 19, 2010

Wine and colon health: More than a gut feeling

The status of your intestinal tract may not be the sexiest of topics, but for those with problems such as inflammatory bowel disease it is of overriding importance. Whether or not you have a life-changing inflammatory disease, colon health deserves to be taken seriously - at least seriously enough to consider how wine and resveratrol fit in. It’s more good news, as you will have come to expect.

Inflammatory bowel disease is a chronic, relapsing, tissue-destructive disorder for which there is no definitive cure. Patients typically undergo multiple surgeries and are on medication most of the time. It is also a difficult thing to study, but there is a model in mice in which the condition can be created by giving them a toxic compound called DSS. Various treatments can then be tested and markers of inflammation measured.

A series of recent reports indicate that resveratrol and other wine polyphenols (again resveratrol shouldn’t get all the credit) can be quite helpful. Using resveratrol in doses attainable through dietary means, mice with DSS-induced colitis in one study were able to reverse the loss in body weight and decrease several markers of inflammation. Evidence from this and other studies indicates that the wine-derived molecules act at a genetic level, fundamentally altering the inflammatory process. The implications for humans with inflammatory bowel disease are significant, but remain to be tested and proved. But based on what is known about wine and how it alters inflammation in other diseases, this is very encouraging news indeed.

I couldn’t help but notice another theme in these studies that seems to characterize much of the research in this field. The reports I reference here are from South Korea, Italy, and the U.S., highlighting the international nature of wine research. Who knows, it may be wine science that helps build connections between people around the world, much as wine brings friends and family together around the table. Cheers to that.

Wednesday, June 9, 2010

Exercise your red wine habit for healthy aging

It seems there is no end to the list of benefits to red wine. One of the more interesting facets being explored is the question of how red wine compounds might work synergistically with other anti-aging behaviors to amplify the effect. We all know, for instance, that regular exercise is an important part of slowing down the aging process, but who would think of having a tipple before hitting the weight room? It’s not such a far-fetched idea according to some recent studies.

Exercise, like most things that are good for us, must also be taken in moderation; too much and the overstressed muscles start releasing lactic acid and other deleterious compounds. With age the problem becomes worse, resulting in more oxidative stress which counteracts the benefits of working out in the first place! A study comparing oxidative stress in young vs old mice given resveratrol showed how this wine extract helps protect against these changes. Using several serum markers for oxidative stress, a group from the Division of Exercise Physiology at West Virginia University School of Medicine found that resveratrol given orally for one week dramatically reduced these signs of muscle stress after exercising the mice by electrically stimulating certain muscles to standardize the amount of exercise. The effect was more dramatic in the aged mice but held for the youngsters as well.

Another research group from Japan looked at mice bred for accelerated aging (“senescence-accelerated prone”). In this case, they were looking at slowing age-related decline in physical endurance. Even with exercise, their exercise capacity slowed over the 12 weeks of the test, but with resveratrol supplementation it remained significantly higher. The researchers pinned the effect to improved oxygen metabolism in a muscle cell component called the mitochondrium. (Mitochondria are in all cells and believed to be important in red wine’s myriad anti-aging properties.)

Resveratrol isn’t the whole story though. Another wine polyphenol, quercetin, has been tested in humans for effects on exercise. On recent study a double-blind, placebo-controlled, crossover examination of maximal exercise tolerance, noted improvements in the quercetin group after only one week of supplementation. This affirms earlier studies. No doubt there are other compounds in wine and elsewhere that contribute to the benefits of exercise and diet, so for now the best advice is to hedge your bets and have a glass of wine, maybe after each workout.

Monday, May 31, 2010

The Prohibition Hangover: What a Headache!

One of the unanticipated joys of having a book in publication is meeting other like-minded authors. I had the opportunity to do just that at a book event held at the St. Helena Library in Napa Valley a couple of weeks ago, where the topic was wine books. It’s an annual event, designed to showcase the library’s extensive collection of wine literature. As it turns out, a theme for all three authors’ talks was prohibition. Attorney Richard Mendelson’s book, From Demon to Darling: A Legal History of Wine in America, describes the conflicted state of affairs that prohibition spawned. As I discuss in my book, temperance wasn’t always interpreted as abstinence, especially where wine was concerned. But banning all forms of alcohol outright turned out to be akin to trying to slay the Hydra of mythology, a multi-headed beast who grew two when one was cut off. The concept of healthy drinking, based on a tradition of wine with dinner, was lost.

The history of wine and drinking is another one of the joys I discovered in doing research for my book. When I am giving a PowerPoint lecture, I often include an image from Dr. Benjamin Rush, Jefferson’s correspondent when he wrote “Like my good friend the doctor, I have eaten little animal food  I double, however, the doctor’s glass and a half of wine, even treble it with a friend.” The image is a “Moral and Physical Thermometer” of temperance, allowing that wine or cider in moderation beget cheerfulness and strength, while toddies, morning drams and rum define the road to perdition, with melancholy, hatred of government, even the gallows. It appears to have been adapted from an English doctor’s version, shown above. It was certainly clear on both sides of the Atlantic that wine was a good thing from the point of view of both social welfare and public health. Somehow this not-so-subtle message was lost. So cheers to wine, and check out Mendelson’s book, along with Vivienne Sosnowski's book, When the Rivers Ran Red: An Amazing Story of Courage and Triumph in America’s Wine Country.

Wednesday, May 19, 2010

Study Challenges Health Benefits of Alcohol: A Rebuttal

The news today is a study from France challenging the beneficial effects of alcohol, adding fuel to a debate we thought had flickered out some time ago. Dr. Boris Hansel of the Hopital de la Pitie in Paris, a specialist in cardiovascular disease prevention, acknowledged in an article in the European Journal of Clinical Nutrition that while moderate drinkers are in fact healthier, the alcohol doesn’t deserve the credit. The study was an analysis of lifestyle factors of nearly 150,000 adults, and largely confirmed the long-held theory that moderate drinkers (especially wine drinkers) are healthier. But Dr. Hansel’s conclusion was that the benefit was due to associated lifestyle factors, not the alcohol. Moderate drinkers do a lot of other healthy things too, such as exercise more and eat healthier diets, again most particularly wine drinkers. (

Is it really as simple as that? Not likely. For starters, the emphasis of the study was on cardiovascular disease, now known to be only a small part of the wine and health formula. But even within the category, there are specific physiological effects to credit: alcohol increases HDL cholesterol, the beneficial kind, and wine polyphenols work in several ways to counteract the formation of cholesterol plaques.

The bigger issue is the notion that with a large enough study, we can finally get to the heart of the problem, and figure out what’s really going on. But studies of this type rely on self-reporting of quantity and type of alcohol consumed, which is notoriously unreliable, so the resulting inacurracies in data become magnified. It is far more meaningful to study a small but very-well characterized population, such as a particular town where everyone drinks the local wine and a traditional lifestyle is practiced consistently. This type of study is where the original French paradox was born. The paradox now is why the French are turning their backs on their own revelation to the world about healthy living.

Statisticians may bemoan the difficulty in trying to decipher how much of the French paradox is lifestyle and how much to credit the effects of alcohol and polyphenol biochemistry, but in my way of thinking it is ultimately a useless exercise. The distinction between wine as a pharmacologic supplement and wine as a component of a healthy lifestyle is an intillectual argument that does little to help us lead happier and healthier lives. For the record though, there are several good studies to support the separate contribution of wine to health, and this most recent report provides little evidence to contradict a recommendation to drink wine with dinner whenever possible.

Thursday, May 13, 2010

The Australian Heart Foundation blows the call on health benefits of wine

In a case of opinions in the rear-view mirror appearing larger than the mountain of evidence right in front of them, the Australian Heart Foundation recently released a position paper announcing that there are no health benefits to wine or dark chocolate. According to a spokesperson, the AHF is ''concerned about people thinking that in having red wine or dark chocolate that they are actually doing something to treat or prevent cardiovascular disease when the evidence doesn't support that.” The recommendation is based on a review of more than 100 studies over the past 10 years, and supposedly “puts to rest the popular belief that red wine, coffee and chocolate can keep cardiovascular problems at bay.”

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They couldn’t have gotten it more wrong. The thing is, there are more than 3,000 articles over the past 30 years or so on the subject, and I have looked at most of them for my book “Age Gets Better with Wine.” It is true that most of these are not clinical trials per se, and it would be nice to have more of these, but the patterns are consistent: wine and chocolate have a range of distinct benefits in countering heart disease and many other conditions. The focus of the article was on the antioxidants in wine and chocolate, which is too narrow of a view in my opinion. Supplements of antioxidant from wine or vitamins are indeed without evidence of their usefulness, but wine and dark chocolate work in other more specific ways. Dark chocolate has been shown to lower blood pressure and reduce the inflammatory processes that contribute to cardiovascular disease, and wine works in its own numerous and potent ways.

I am reminded of what happened when the data on alcohol consumption and heart disease was first analyzed from the Framingham Heart Study, the granddaddy of all such studies. In reviewing the 25-year data back in the 1970’s, a clear relationship between moderate drinking and lowered risk of heart disease was found. But the study sponsors at the U.S. National Institutes of Health issued a written directive to the authors of the study that it was to state that there was “no significant relationship of alcohol intake to the incidence of coronary heart disease,” citing concerns that it would be “socially undesirable.” Better to quote R. Curtis Ellison, MD, Professor of Medicine and Public Health at Boston University: “…only stopping smoking would have a larger beneficial effect on heart disease than for a nondrinker to begin having a drink or two each day.”

Wednesday, May 5, 2010

Time to reverse course with resveratrol?

It’s been an interesting week in the news for resveratrol. On the one hand, a new publication on how resveratrol affects the brain came out, adding to the very few clinical trials on the use of it as a supplement. On the other, Glaxo halted a clinical trial on resveratrol over safety concerns. Meanwhile, my piece in Web MD ( garnered quite a lot of attention and brings us back to the question of whether we aren’t just better off drinking wine instead anyway.

As I have mused about here before, clinical trial data on the use of resveratrol is all but absent, and what there is tends to show that it isn’t very well absorbed. So anyone bringing some clinical science to the field is to be congratulated. The study out this week actually measured blood flow to the brain during cognitive tasks, in other words things require thinking and concentration. Resveratrol improved blood flow and raised levels of the type of hemoglobin that has released its oxygen, implying higher oxygen extraction in the brain and therefore more processing power. The study was done in comparison to a placebo group, an important requirement for objectivity. The association of wine and IQ has long been known, whether it is due to smart people preferring wine or wine making people smart, so this study would add evidence to the latter explanation.

Not many people even thought about taking resveratrol supplements, however, until a few years ago when it was reported to activate enzymes known as sirtuins, which are involved in enhancing longevity. The biotech company Sirtris was founded to exploit this phenomenon, and was acquired by Glaxo a short time later. They soon developed several derivatives for treatment of cancer, diabetes, and other conditions, and clinical trials were launched on several fronts. This week a trial of resveratrol as an adjunctive treatment for a type of cancer called multiple myeloma was halted because of adverse safety events. However, the condition, a problem with the kidneys, is known to occur with the disease and seems unlikely to be related to the resveratrol. Nonetheless, it was a setback for those awaiting more potent versions of resveratrol to come to market.

For now, I’ll continue to take my medicine in liquid form, with dinner.

Wednesday, April 7, 2010

Does the type of wine matter?

Questions that seem to come up frequently when I am lecturing about wines include “Does it have to be red in order to get the health benefits?” and “Which types of wine have the highest amount of the healthful polyphenols?” To answer the first, red wines do have much higher levels of resveratrol and other beneficial compounds for several reasons. Since these compounds come from the skins and seeds, the whole grape (berry) must be fermented together in order for optimal extraction. White wines are made by pressing out the juice and then fermenting it without contact of the skins and seeds. So yes, it has to be red for the full dose, and it has to be wine not grape juice.

The second question is a bit trickier. There are natural variations among the different varietals of grapes that wine is made from, but the terroir (local conditions) and methods of viticulture probably have more to do with it. To understand why this is the case, consider why grapes make resveratrol and other polyphenols in the skins in the first place: it is for protection against environmental stress. That is of course the reason why they are such potent antioxidants and anti-microbial agents.

One grape that seems to struggle mightily is pinot noir, so pinots are known to have high levels. One Oregon producer of pinot noir wines has petitioned for permission to state resveratrol content in the wines, which the government has resisted because people might start thinking that wine is actually a healthy beverage (it is.) But other reds have healthy polyphenol content too, and there are several studies now comparing the amount of resveratrol in similar wines from different parts of the world and with different traditions of winemaking.

In the end it may not be all that important, since the evidence that resveratrol explains all of the benefits of wine is pretty scant; for one thing, even wines with high resveratrol levels still don’t have much compared to the amounts used in laboratory studies. Other studies point to the combination of all of the compounds in wine working together as the key, including alcohol. So the answer is drink whatever kind of red wine you enjoy, and if you don’t like red maybe you should continue looking for one that you can at least suffer through.

Thursday, April 1, 2010

More good news about chocolate and wine

Just in time for your Easter egg hunt, more news that chocolate is good for you. A report out just this week from the German Institute of Human Nutrition in Potsdam confirmed that people consuming chocolate on a regular basis had lower rates of heart attack and stroke. The study was impressive in scope, monitoring nearly twenty thousand subjects over a ten-year period, after a dietary assessment at the beginning. It was part of a large project called the European Investigation into Cancer and Nutrition. Those in the top chocolate consumption group had 40% fewer heart attacks and strokes over the course of the study as compared to the low chocolate consumers. A reduction in blood pressure was identified as the reason.

It has been known for some time that compounds called polyphenols, found in both chocolate and wine, are able to relax blood vessels and thereby lower blood pressure. A study from the Institute of Food Safety in the Netherlands (why are the Europeans having all the fun with wine and chocolate studies?) identified exactly how this occurs. A molecule called Nitric Oxide, or NO, is the chemical signal for blood vessels to relax, and certain compounds from wine and chocolate have the specific ability to stimulate NO release. Among these are resveratrol (from wine) and compounds in a family of molecules called catechins, from both wine and chocolate.

These molecules are in much higher quantities in dark chocolate and red wine, so the chocolate eggs in your Easter basket might not be the best way to get the health benefits. Go for something dark and leave the milk chocolate goodies for the kids. And my recommendation for the wine with your ham (a problem match because of the saltiness) is Grenache.

Friday, March 26, 2010

Wine boosts the body’s antioxidant system

It’s hardly news that wine contains powerful antioxidants, just like other superfoods including blueberries, acai, and pomegranates. What isn’t so obvious though is how these compounds are absorbed into the body and whether or not they actually do any good. This problem of how food-derived nutrients, along with drugs and supplements, are taken up and delivered to “target” tissues throughout the body is called “bioavailability.” There are numerous compounds that perform miracles in a test tube but just aren’t absorbed very well from the digestive tract when taken orally. Resveratrol is a classic example of this; with more than 3,000 research articles published, it’s considered a fountain of youth in a pill (or a glass of wine) by many, but it turns out to have poor bioavailability. There must be something else in wine that explains its long list of health benefits.

Researchers at 2 universities in Spain provided some insight into the role of wine as an antioxidant in a recent study. They used eight volunteers who consumed a standardized diet low in antioxidants, and compared the antioxidant capacity of their blood plasma with and without the addition of red wine to the diet. Samples were taken at days 2 and 7 of the regimen, during the week with wine and without. A significant increase in antioxidant capacity was observed with wine in the diet, as one would hope. (A similar study was done in Chile several years ago, with similar findings and also noting that wine was better than vegetables high in antioxidant vitamins.) This proves that something in the wine is being absorbed and circulated through the body, and having a positive effect. It is probably not resveratrol though, as previous studies of this type have shown that it does not achieve significant levels in the blood after oral ingestion.

Interestingly, dark chocolate is another superfood that has measurable effects when eaten. In this case, it causes the blood vessels to relax and lowers the blood pressure. The cocoa-derived compounds responsible are much the same as antioxidant molecules found in red wine, known as flavonoids. What is important here is to distinguish between studies that actually test what happens in a clinical experiment from what occurs in a laboratory test. Too many supplements are rushed to market based on an incomplete understanding of how they actually work in the human body. It seems we always come back to the point where drinking wine and eating the right foods works better than popping pills. Who would have thought?

Thursday, March 18, 2010

Wine may help breast cancer patients receiving radiation

Despite advances in screening and early diagnosis of breast cancer, little has changed in how it is treated over the past ten or twenty years. For most women, it comes down to a choice of mastectomy or removal of the tumor (lumpectomy) and radiation. If it has spread, then chemotherapy is recommended. The good news for women choosing mastectomy is that breast reconstruction techniques have improved substantially, but for patients opting for “breast conserving therapy” an ordeal of several weeks of radiation treatment is still standard treatment. And despite the fact that the breast is conserved, the radiation causes irreversible changes and even some disfigurement on top of the dent left after the lumpectomy. But now there is some evidence that wine may help prevent some of these changes, despite lingering controversy about the role of alcohol in breast cancer risk.

The data comes from a study from the Catholic University in Campobasso, Italy, a center where wine and health research has been particularly fruitful in recent years. The researchers assessed skin toxicity (redness, irritation) from radiation in each of 3 groups of women receiving different treatment doses. Overall, women who drank wine had a lower incidence of skin toxicity compared to nondrinkers (22% vs. 38%), and the amount of daily drinking had an influence as well. Women who drank a half a glass or less had a 32% incidence, while only14% of those consuming a glass a day experience significant skin irritation. However, the percentage increased as drinking increased above a glass a day, with 2 glasses about as high as none. Those who are familiar with my book Age Gets Better with Wine will recognize this as a J-shaped curve, where moderate drinkers enjoy benefits not associated with abstinence or heavy drinking.

Earlier reports on various types of cancer have revealed that polyphenol molecules in wine, including but not limited to resveratrol, have the effect of protecting cells from the toxic effects of radiation while simultaneously sensitizing cancer cell to it. That would provide an explanation to the findings of this clinical study. What isn’t known, and cannot be directly inferred from this type of study is whether supplements of wine-derived compounds will have the same effect. Clinical trials should provide the answers within the next few years.

Tuesday, March 9, 2010

Is red wine the new women's diet drink?

Why is it that we act so surprised when each new study showing that wine is a healthy drink comes out? This week it was a very large study from Brigham and Women’s Hospital in Boston, showing that women who drink red wine are less likely to gain weight. To be fair, although there are several studies already pointing in that direction, this one adds heft to the data because of its size (nearly 20,000 women) and length of follow-up (nearly 13 years.) But if you have read my book or have been following my posts here, your response is more likely to be “well, duh.”

Here are the particulars: The study, published in the Archives of Internal Medicine, identified a population of middle-aged women of normal weight and recorded their lifestyle habits as a baseline. Over the period of follow-up, some 42% became overweight and 4% obese, as determined by Body Mass Index. After statistically adjusting for factors such as exercise habits, smoking, and non-alcohol caloric intake, they found that moderate drinkers were much less likely to gain weight as compared to nondrinkers. The pattern was most dramatic for women who drank red wine.

We do know of course that people who drink red wine regularly and in moderation have other healthy habits, but a significant aspect of this study is that those factors were neutralized. There is clearly something more to the red wine connection than just being a marker for a better diet or regular exercise. This study doesn’t tell us what that might be, but we have some ideas, don’t we?

Monday, March 8, 2010

Is resveratrol the new aspirin for heart attacks?

The newswires are abuzz this month about a recent report suggesting that resveratrol, the polyphenol molecule from red wine, helps restore blood flow and limit muscle damage after heart attack. The typical headline reads something like “Red wine component pill successful during heart attacks” or something similar, with the clear implication that some sort of clinical trial has been done. In fact, it was a study in mice, and while the results were impressive it is only one small step toward the giant leap of clinical practice. What happens in mice doesn’t always happen in humans, so we are no where near the point where your cardiologist is going to give you a resveratrol pill when you show up in the E.R. with chest pain.

Nevertheless, the results are encouraging. What happens in a heart attack is that the plaques that build up in the coronary arteries that feed the heart muscle cause a clot to form, completely obstructing the vessel and depriving the heart of oxygen. It’s similar to what happens to the brain in a stroke. This oxygen starvation is called “ischemia” and when the clot is dissolved and blood flow re-established, it is called “reperfusion.” Paradoxically, this rush of blood flow releases toxins that have built up in the cells, resulting in what is called “ischemia-reperfusion injury.” Transplant surgeons deal with a related issue. The ability of resveratrol to counteract the detrimental effects of ischemia-reperfusion has been well documented in numerous studies, and the recent one in mice confirms those findings. But a mouse heart is tiny, and the question of whether the same effect applies in the large muscle mass of the human heart remains speculative.

A likely scenario is that one of the synthetic derivatives of resveratrol, many of which are much more potent, will emerge as a viable therapy for heart attack and stroke. But clinical studies on resveratrol are few in number, as I have pointed out here recently.

Thursday, March 4, 2010

The politics of drinking: is there room for moderation?

Much political hay has been made after President Obama’s recent physical exam, with the doctor’s recommendation of “moderation of alcohol intake.” The polarized lens through which American political debate is viewed sees this as an indictment of the president’s drinking habits, as though any level of alcohol consumption sets a bad example, and there is no middle ground between alcohol abuse and abstinence. But as we know, at least in the case of wine, the healthiest place to be is moderate drinking (see “modern view of moderation” posted February 15.) Abstinence and excess share the same risk profile for heart disease and many other conditions; it’s the moderates who are the clear winners here, but I will leave it up to you to interpret the political parallels.
The president’s cholesterol has been creeping up too, and dietary changes were recommended. Here’s where the opportunity for what is called these days a “teachable moment” was missed. Moderate drinking, especially wine with meals, is one of the more effective means of improving cholesterol profiles. In fact, in the words of Dr. R. Curtis Ellison, Professor of Medicine and Public Health at Boston University School of Medicine, “…only stopping smoking would have a larger beneficial effect on heart disease than for a non-drinker to begin having a drink or two each day.” But our government has a long and proud tradition of suppressing information about healthful drinking, as I describe in my book.
See the full report on the president’s exam here:

Saturday, February 27, 2010

Is wine a health food?

I often joke that wine is a health food, but it actually is when looked at objectively. Of course in order to be a health food, it must be a food, which would in turn require that there be some nutritional value. The calories in dry wines are from alcohol, which is processed by the body in a different way than other carbohydrates, such that it tends not to cause a spike in blood sugar levels. So right away it has benefits over other calorie sources, since these blood sugar variations are believed to contribute to weight gain. Wine drinkers tend to have less of an issue with being overweight, so perhaps this is one of the reasons.

We all know, or have been told often enough to believe, that alcohol is detrimental and that such adverse effects more than counteract any potential benefits. But interestingly, our bodies come equipped with an enzyme called alcohol dehydrogenase, which does nothing but metabolize alcohol. The ability to consume alcohol is programmed in our DNA, so if we aren’t meant to then it is quite a mystery.

So what of the other elements in wine? One thing that recurs in research on wine’s health benefits is the importance of consuming it with meals. There are several explanations for this, such as the fact that the antioxidants in red wine blunt the effects of oxidizers in food, especially such offenders as red meat. Wine actually makes the other foods in the meal healthier. Another reason is that wine with food slows the absorption of alcohol, thereby reinforcing the whole concept of wine as food rather than alcohol consumption as a drug. People who drink in this way have a range of other healthy habits that all mutually reinforce their respective benefits. For this reason, the healthy Mediterranean diet, so prominently featuring daily wine consumption, is best viewed as a lifestyle, a way of living, rather than a menu of prescribed foods.

One could almost make a case for red wine as a vitamin.

Thursday, February 18, 2010

Should your doctor prescribe wine? Answer to NY Times piece

The New York Times online has a Q&A feature which today addressed the question of "prescribing" wine. Dr. Mark Willenbring of the National Institute on Alcohol Abuse and Alcoholism addresses the question. (His answer and my comments here: The good doctor does allow that it might be helpful in very limited amounts for some people, but dismisses the data as "correlational." In other words, finding a correlation between moderate drinking and health is insufficient to draw conclusions. I agree, but there is so much more than correlational data to draw on. In my book Age Gets Better with Wine I use what I call the skeptic's checklist for that very reason; we need plausible cause-and-effect explanations and evidence to support those explanations. I will leave you to read about it in the book, which is extensively referenced with peer-reviewed scientific and medical literature. Wine is not only safe in moderation for those without susceptibility for alcohol abuse, it is a powerful health food.

Monday, February 15, 2010

A modern view of moderation

We hear so much about wine being healthy in moderation. Then there is the popular (and cynical) saying, “all things in moderation, including moderation.” If you are drinking wine for your health, and who doesn’t, it is actually quite important to define the term “moderation” if we are to get the maximum benefit. If you drink for purely aesthetic reasons, or anesthetic reasons for that matter, then you have other considerations to deal with. But here’s the deal on moderation:
Studies on wine drinking and health in populations often use weekly alcohol consumption as a convenient measure. From data like that we get the familiar J-shaped curve, showing that maximum health benefits are associated with about 2-3 glasses of wine a day for men and half that for women, and disease risk about equal to that of nondrinkers at about double that level of consumption (the bottom loop of the “J”.) But we also know that binge drinking is particularly bad, so the pattern of daily drinking is critical. You can’t do all your drinking on the weekend and expect any health benefit, despite the inconveniences that can occur during a busy workweek.
Integrating your wine consumption with meals seems to be important as well. This slows the absorption of alcohol, but also provides antioxidant capacity to counteract many of the harmful compounds that are found in the modern diet. There have been some interesting clinical studies on this point and it seems to have scientific validity. Perhaps just as important is that drinking with meals sets an example of wine as food rather than alcohol as a drug, reinforcing the concept of healthy drinking.
So how big are these glasses of wine? I know what you are thinking, if I have to limit myself to only 2 glasses, I’ll just get bigger glasses. But for purposes of research, a drink has to be defined so for wine it is a 5-oz. pour. Unfortunately, that makes a standard 750 ml bottle a bit much for a man and a woman to split. On the other hand, the half-bottles (375) don’t really fill the bill either; any winemakers out there want to do a 500 ml bottle?

Monday, February 8, 2010

Wine and Chocolate: a not-so-silly Valentine

Silly me, I thought I could write up a simple blog post about the health effects of wine and chocolate, just in time for Valentine’s Day. So I go online to search the recent medical literature on the health effects on cocoa, and find that there are now more than 2000 articles on the subject. Needless to say, my comments here are based on a selected list. (You should know by now that wine and chocolate contain many of the same antioxidant molecules that have proven to be so beneficial, and that it has to be in the form of dark chocolate. There are a lot of studies now on how cocoa polyphenols lower blood pressure and help keep arteries clean, and the latest ones provide confirmation of the earlier reports.)

One article out just last month caught my eye. It turns out that simply smelling dark chocolate can provide a sense of satisfaction. The researchers proved this by comparing blood levels of insulin and the satiety hormone ghrelin in volunteers who either ate or just smelled dark chocolate, and both had a similar response. It reminds me of how enticing the “bouquet” of a great wine can be; sometimes I just want to enjoy that for a while before drinking it. Of course we already knew that wine and chocolate make for a sensory experience but it’s good to know that science is on the job here.

We also know that chocolate helps put one in the mood, so to speak, but now we have confirmation from a different study that cocoa not only makes us smarter but improves mood in scientifically verifiable ways. Using standardized assessments and cognitive performance testing, researchers documented significant improvements following ingestion of dark chocolate, along with measures of mood. Similar results have been found for red wine polyphenols, so it makes sense.

This last item is a bit more obscure, but I had to include it because I love the terminology used to describe the category of things like chocolate: “hedonic foods.” I’m not sure having a glass of wine or a piece of chocolate fully qualifies as hedonism, but they definitely give pleasure so we’ll accept the term. Researchers from the Department of Neurobiology at the University of Chicago observed that animals experiencing pain react often by eating rather than avoidance, a phenomenon called “ingestion analgesia.” Through a series of experiments on rats they were able to show that the behavior is controlled at the level of the brain stem, meaning that it is a primitive reflex not subject to motivation, and powerful enough to overcome strong incentives to not eat. Major implications for obesity and eating disorders here.

All I know is that wine and chocolate are health foods of the first order, regardless of whatever part of my brain is telling me so, and I am not about to try and get by with a sniff  instead of a sip.

Monday, February 1, 2010

No Sir thing with wine-derived drugs

Pharmaceutical giant Glaxo made headlines two years ago with their purchase of biomedical startup Sirtris for $720 million, following reports that Sirtris was making progress with resveratrol-based compounds that might extend lifespan. But doubts are now being cast on the question of whether wine-derived molecules even work for anti-aging the way that scientists at Sirtris believe. It’s an important story for consumers as well as investors, given that use of resveratrol supplements continues to rise. (Consumer Lab reports that resveratrol use by consumers surged some 66% last year.)

If you have been following the wine and health story, you know why resveratrol is such an exciting compound. It has impressive anti-cancer properties (in lab studies), fights heart disease (again, not clinically proven), diabetes (if you happen to be a lab rat), and the list goes on. What is really interesting is that it appears to activate enzymes called sirtuins (the corresponding genes are called Sir1-7), which trigger a metabolic change that prolongs the lifespan of laboratory organisms such as yeast and fruitflies. If the effect could be replicated in humans, we could perhaps expect to live well into our 150’s.

The problem is, it might not work that way, either in humans or primitive organisms. Concerns about an artifact of the testing method that leads to false-positive results have been expressed by skeptics such as Matt Kaeberlein here in Seattle (at the University of Washington), and now studies from Glaxo’s rivals cast further doubts. Amgen published a report this past fall provocatively titled “Resveratrol is not a direct activator of SIRT1 activity.” Pfizer has weighed in with a similar sentiment. So given the lack of clinical data supporting the use of resveratrol supplements, it is fair to say that a lot of work remains to be done.

It’s pretty complicated stuff, but there are some simple truths in which we can take comfort. One is that wine drinkers outlive teetotalers, enjoy better health, and have a higher quality of life according to published studies. The sentiment was aptly expressed in one of the iconic wine & health studies published in 1979. In considering the possibility that wine’s benefits might be attributable to some as-yet unidentified compound, the authors observed that “The medicine is already in a highly palatable form.” (St. Leger, Cochrane, and Moore)

Tuesday, January 26, 2010

American Heart Association drops the bottle on lifestyle recommendations

In a drastic lurch back to Victorian era temperance, the American Heart Association came out this month with lifestyle recommendations intended to promote “ideal cardiovascular health.” Their list of “Life’s Simple Seven” includes:
• Never smoked or quit more than one year ago;
• Body mass index less than 25 kg/m2 (I.e., not overweight)
• Physical activity of at least 150 minutes (moderate intensity) or 75 minutes (vigorous intensity) each week;
• Four to five of the key components of a healthy diet consistent with current American Heart Association guideline recommendations;
• Total cholesterol of less than 200;
• Blood pressure below 120/80;
• Fasting blood glucose less than 100.

Not much to quibble with there it would seem, but as always the devil is in the details. Let’s look more closely at the “healthy diet” components:

• Vegetables and fruits are high in vitamins, minerals and fiber — and they’re low in calories. Eating a variety of fruits and vegetables may help you control your weight and your blood pressure.
• Unrefined whole-grain foods contain fiber that can help lower your blood cholesterol and help you feel full, which may help you manage your weight.
• Eat fish at least twice a week. Recent research shows that eating oily fish containing omega-3 fatty acids (for example, salmon, trout, and herring).

So far, so good, we have heard all that before. But as we approach the twentieth anniversary of the French Paradox, where does the AHA stand on wine?

• If you drink alcohol, drink in moderation. That means one drink per day if you’re a woman and two drinks per day if you’re a man.

That’s it? With the thousands of research paper attesting to the cardiovascular benefits of red wine consumption, nary a mention other than be careful not to drink too much? It’s not like there is a lack of data upon which to base a recommendation. According to the widely recognized expert Dr. R. Curtis Ellison, professor of Medicine and Public Health at Boston University, “ ... only stopping smoking would have a larger beneficial effect on heart disease than for a nondrinker to begin having a drink or two each day.” This recommendation is supported by the prestigious Framingham study, the bedrock of research on the lifestyle factors in cardiovascular disease. But the Framingham scientists have been studiously neglecting the data about drinking and health since the 1970’s when the role of alcohol was first evaluated. One of the scientists involved in the study, Dr. Carl Seltzer, revealed later that the senior staff at the National Institutes of Health demanded that the data be altered to remove any suggestion of a beneficial effect from alcohol, citing concerns that it would be “socially undesirable.” To this day the official Framingham website omits any reference to the alcohol studies. This is what they call science?

The thing is, most of know better and so the “updated” recommendations from the AHA lose credibility. It reinforces perceptions of the medical establishment as paternalistic. Time to start treating us like adults.

For more including detailed references check out my book Age Gets better with Wine.

Monday, January 18, 2010

Wine and the Happiness Connection

One of the more interesting things I came across when I was researching the factors influencing longevity for Age Gets Better with Wine was the fact that happy, connected people live longer. It makes sense intuitively of course, but what makes it particularly encouraging is that nurturing our connections to community and friends, something we can simply decide to do, has a large influence on lifespan. Throw in a little wine, some exercise, and healthy eating and you’ve got it made.

It turns out that connectedness is linked to happiness too. In their book Connected: The Surprising Power of Social Networks and How They Shape Our Lives, researchers Nicholas Christakis and James Fowler reveal that networks wield more control over our lives than we realize. Through our social networks, even beyond our circles of friends, we tend to be either overweight, happy, sad, successful or not in measurable ways. Knowing happy people increases the odds of you being happy by 9%, while having unhappy people around lowers it by 7%. Being geographically close helps too, upping the odds of contagious happiness by as much as 25% if they live within a mile or so. What is interesting is that the people you don’t know, but those with whom you associate do, also measurably impact your sense of well being.

What we can’t seem to escape entirely is our genetically determined happiness “set point.” Apparently this is the most important factor, contributing half of whatever it is that gives our spirits a lift. Another 40% relates to our choices; what we choose to do and how we decide to live our lives (This is where wine and friends come in; see also my post on Dec. 21 about how wine might combat depression.) A mere 10% apparently relates to circumstances, such as wealth and health.

So big surprise, money can’t buy happiness. But deciding to have happy people in your life gets it for free.

Tuesday, January 12, 2010

Resveratrol clinical trials: What’s the evidence?

If you are interested in anti-aging, or just the science behind healthy wine drinking, you must have seen the ads for resveratrol supplements. “All the benefits of wine without the alcohol” they might say, implying that the science is in and the matter decided. There is an impressive dossier of resveratrol research, now totaling some 3,000 research papers, and the beneficial effects of this wine-derived molecule are myriad. There is good reason why I dubbed resveratrol the “miracle molecule” in my book Age Gets Better with Wine.
In the book I also introduced what I call the “skeptic’s checklist,” a useful tool for evaluating claims about medical interventions and miracle supplements. The reason this is important is that while data from laboratory studies can reveal interesting properties and lines of research, what happens in a test tube is meaningless unless the effect can be documented in a clinical trial in humans. In order to obtain FDA clearance, for example, clinical trials need to document both safety and objectively measured effectiveness. But since herbal supplements do not fall under the FDA’s purview, there is wide leeway for frequently misleading often outrageous and claims. So without evidence from clinical trials (not the same thing as "clinically tested"), there is no way of knowing whether the product is doing any good or if it is in fact harmful.
There are a few clinical trials underway for resveratrol, and a very small number of published reports. Of the 12 papers that I found on a Medline search using “clinical trial” and “resveratrol,” 3 were not actual clinical trials but studies on blood or tissue in a lab. Another 3 used a wine extract with resveratrol along with the whole family of wine polyphenols, and the rest were what are called pharmacokinetics studies. These types of studies evaluate what is called “bioavailability” or the absorption and distribution of resveratrol after oral ingestion. Without exception they all found low but variable levels, even at high doses.
So it doesn’t appear that resveratrol alone explains the benefits of drinking wine. Synthetic derivatives, up to a thousand times more potent, are being developed so it may turn out that resveratrol opened the door to a new and powerful anti-aging products even if it isn’t the answer alone. For now, a skeptical approach seems the way to go.

Tuesday, January 5, 2010

What causes those wine headaches? Hope for a solution

It seems like every time I give a talk about wine and health there is at least one person in the audience who asks about headaches. They would like to drink wine, they say, but sometimes it gives them a headache. Or another frequent question relates to why they didn’t get headaches drinking wine in Europe but domestic wines do; is it the sulfites?

The good news is that scientists are developing a good understanding of what triggers headaches for some people, and it doesn’t seem to be sulfites; all wines contain them. It probably isn’t the alcohol, unless you are prone to migraines or to imbibing too much. The culprit for most people is a class of compounds called biogenic amines, the most familiar of which is histamine. These are not products of the wine itself, but of bacterial contaminants. Fortunately there are fairly quick tests that can be done do measure the levels of biogenic amines, though these aren’t routinely done.

But without testing, the inherent variability of amine production during wine fermentation makes it difficult to predict which wines will be a problem for people susceptible to them. There aren’t any sensory clues, since they tend to have little effect on the taste or smell of the wine. Why there should be a difference between European and domestic wines remains a matter of speculation. Perhaps it relates to the long history of winemaking, with traditional methods naturally sorting out the processes that make drinkable wine and environments naturally free of the offending bacteria. Or maybe it’s just that domestic wines have a higher alcohol content.

In any case, a solution should be achievable now that the cause of the problem is known. It is up to the industry to invest in the technology.