Sunday, April 2, 2017

The J-curve is dead. Long live the J-curve!

 There is a resurgence of debate about the validity of the J-curve, especially as it relates to alcohol and cancer. A 2014 report determined that “alcohol use was positively associated with overall mortality, alcohol-related cancers, and violent death and injuries, but marginally to CVD/CHD” (cardiovascular disease). In other words, there was little benefit if any in terms of heart disease but a big upside risk for cancer and accidental or violent demise. Gone was the French Paradox! The J curve is dead! Or not.
Though that statement may be technically true, I looked at look at the data myself and found something different: a strong confirmation of the J-curve for overall mortality, overall cancer deaths, cardiovascular disease, and all “other causes.” This held for both men and women:

    Used under creative commons license from Ferrari P, Licaj I,Muller DC, et al. Lifetime alcohol use and overall and cause-specific mortality in the European Prospective Investigation into Cancer and nutrition (EPIC) study. BMJ Open 2014;4:e005245.

How the J-curve was hidden in plain sight

The J-curve may not be immediately obvious, however, due to some interesting choices made with how the data were presented. For one, rather than taking “nondrinking” as the reference, the authors chose "moderate drinking." When we rotate the chart and draw a reference line for nondrinkers (in purple), the pattern is easier to discern. In fact, looking at the chart for women, the J-curve is strikingly apparent for both “alcohol-related” cancers, most of which would be breast, and “other cancers”:

Another noteworthy feature is the CVD/CHD relationship, which drops significantly from nondrinkers and remains low – even at levels considered heavy drinking. The uptick of the right side of the J never appears. Considering that cardiovascular disease outweighs breast cancer as a cause of death in women by very large margin, the conclusion that alcohol had only a marginal benefit seems an almost bizarre interpretation.
Consider also that this is aggregate data for all types of drinking. Beer drinkers tended to fare worse in this population than wine drinkers, but those who drank primarily spirits were not clearly separated out. For wine drinkers, the bottom line is still a J-shaped curve.

Wednesday, March 8, 2017

Quality of life is better with wine

Wine appreciation is an icon of “the good life,” but can it really be true that something as simple as a glass of wine with dinner measurably improves quality of life? There’s good evidence that it does. Quality of life (QoL) may seem a subjective concept, impossible to quantify, as irreproducible as numerical wine scores, but QoL has become a vital concept in clinical research. Everything from cancer treatments to plastic surgery can be appraised in terms of impact on quality of life. Wine drinking is no different.

Quality of Life is more than good health

The concept first appeared in the medical literature in the 1970’s, as medical and surgical treatments advanced in terms of their ability to save lives, but sometimes at the expense of significant side effects.  In a similar vein, scholarly investigations about wine consumption tended to focus on its detrimental effects until recently. Only when it became apparent that wine drinkers actually lived longer and enjoyed better health outcomes overall did it occur to look at QoL specifically. Health status is of course an aspect of QoL, but it is the larger sense of well-being, social interactions, and a sense of meaning and fulfillment that define QoL. Validated and reproducible tools for measuring QoL have been developed to facilitate this type of research.

Studies show why wine drinkers have higher quality of life

For example, a 2007 long-term study from Finland[1] tracked a group of men after identifying their preference for wine, beer, spirits, or no alcohol. After 29 years, there was a clear advantage to wine: significantly lower mortality (mostly due to better heart health) and high QoL scores. All groups tended to maintain their preferences over time, and overall alcohol consumption was similar.
It holds true even in cases of chronic heart failure, according to a 2015 study from Italy.[2] As one would expect from Italian subjects, more than half consumed at least a glass of wine per day. They found that “patients with more frequent wine consumption had a significantly better perception of health status, less frequent symptoms of depression, and lower plasma levels of biomarkers of vascular inflammation.”
Among the major components of quality of life is marital harmony. In younger couples, alcohol consumption has a significant impact (positive or negative), but in older couples it becomes even more important. A 2016 study from the University of Michigan[3] found that concordance of drinking preferences was more important than the amount of alcohol consumed for long term marital bliss. Drinkers of any type did better over time than nondrinkers, as long as both spouses had similar habits.
So here’s to happiness and health, wine not whining!

[1] Alcoholic beverage preference, 29-year mortality, and quality of life in men in old age. Strandberg TE1, Strandberg AY, Salomaa VV, Pitkälä K, Tilvis RS, Miettinen TA. Gerontol A Biol Sci Med Sci. 2007 Feb;62(2):213-8.
[2] Regular wine consumption in chronic heart failure: impact on outcomes, quality of life, and circulating biomarkers. Cosmi F, Di Giulio P, Masson S, Finzi A, Marfisi RM, Cosmi D, Scarano M, Tognoni G, Maggioni AP, Porcu M, Boni S, Cutrupi G, Tavazzi L, Latini R; GISSI-HF Investigators. Circ Heart Fail. 2015 May;8(3):428-37.
[3] Drinking Patterns Among Older Couples: Longitudinal Associations With Negative Marital Quality.
Birditt KS1, Cranford JA2, Manalel JA3, Antonucci TC3.J Gerontol B Psychol Sci Soc Sci. 2016 Jun 27.

Thursday, February 9, 2017

Lost in translation: Why most reports on health and wine are erroneous

In an era of fake news, alternative facts, and conflicting advice on healthy drinking from even the most reliable sources, it is important to understand where reporting on clinical science can go awry. Does a glass of wine before bed help you to lose weight? A widely reported study last year seemed to suggest just that, at least if you only looked at the headlines. How about a glass of wine a day is as good as an hour at the gym? Both of these might be true - if you are a mouse - and substituting resveratrol for wine.

Of mice and men - and medicine

The journey from the research lab to the clinic is known as translational medicine, and the process can be long and unpredictable. Take for example the hypothesis that resveratrol alters metabolism in a way that mimics exercise (and ignore for the moment the separate idea that resveratrol supplementation is the same as drinking wine.)  There are limits on what sort of interventional studies you can do to test this idea on humans, before you determine if the doses needed are toxic or have other unexpected effects. Lab rats make a convenient model for these types of studies, and for trying out new therapeutic approaches, but they are not people. More than 9 in 10 cancer treatments that appear promising in animal studies on do not even make it to clinical trials in humans. Resveratrol supplementation in mice might keep them lean and fit, but it's a huge leap to conclude that wine does the same thing in you and me.

Studies on wine have to pass the sniff test

What we do know from human studies is that people who drink wine regularly and in moderation outlive (on average) nondrinkers and heavy drinkers – the J curve. Studies on wine, resveratrol and alcohol number in the thousands, but the majority of them are based on lab rodents or cell cultures. Clinical studies on wine can be problematic to conduct, so there are comparatively fewer of them. The ones that have been published tend to reinforce the concept of healthy drinking, with the jury still out on many aspects of resveratrol. So here’s my advice: The more attention-grabbing the headline, the less likely it is to translate into a meaningful aspect of healthy drinking. Like a freshly uncorked bottle of wine, it has to pass the sniff test; a glass of wine equating to an hour of exercise doesn’t, at least not until confirmed by actual clinical studies.

Tuesday, January 3, 2017

The J Curve explained

In order to make sense of the seemingly conflicting reports about wine and health there’s one essential thing to understand: the J-shaped curve. It’s a simple concept, universal, in plain sight, and often ignored. It goes like this: Take “nondrinking” as the baseline and plot increased or decreased relative risk of a health issue with increasing levels of daily consumption. Nondrinkers have a certain risk of, say heart attacks, moderate drinkers a lower risk, heavy drinkers a relatively higher risk. Not too complicated. The tricky parts are separating wine drinkers from drinkers in general, and daily moderate drinkers from occasional drinkers.

The J-curve is not just about wine

The J-shaped curve is too universal to ignore once you see it. Even dietary salt intake has a J-curve; consuming too little in your diet can be as harmful as too much. For years, the American Heart Association has endorsed a 1.5 gram per day limit on sodium intake (salt is about 40% sodium), about what you get in a 6-inch sub sandwich or a bowl of vegetable soup. However, a massive multi-country review a couple of years ago found that the lowest incidence of heart disease correlated to about 4-5 grams per day, the bottom of a J-curve. Similar patterns plot out for coffee, vitamins, even water.
Wait - water? Obviously not drinking enough water is unhealthy, and questioning the benefits of hydration seems a fool’s errand. But it is possible to take it too far; in 2007 a woman participating in a water drinking contest called “Hold Your Wee for a Wii” was found dead of water intoxication. Superhydration throws electrolyte balances out of whack, with toxic and even fatal levels of water intake surprisingly easy to achieve. A  J-shaped curve.
Even lifetime happiness reportedly follows the curve. Young people generally enjoy a sense of well-being and optimism, career and family stress creates a dip through the 20’s and 30’s, then later in life happiness rises above the baseline, at least for most.

Why the J-curve is sometimes overlooked

Why is this simple model so often overlooked? One reason is that good data points are hard to come by, when it is drinking and eating habits that are being tabulated. People are unreliable self-reporters. Or researchers may have hidden agendas based on the need to publish, so that they focus on only the findings that support their hypothesis. Research on breast cancer and alcohol is particularly fraught with this problem; heavy drinking is unquestionably bad, but difficult in parsing out the subset of women who drink red wine (for example) with regularity and in moderation leads to extrapolation errors. If you simply draw a line from the heavy drinking/high risk corner of the graph down to the no drinking corner, you miss the bottom of the J. And you don’t want to miss the bottom of the J curve.

Thursday, December 15, 2016

Wine is a food group

Why are wine’s maximal health benefits related to consuming it with meals? It’s well known that wine with dinner on a regular basis is best, and understanding the role of wine as a food can help illuminate wine’s larger role in health. A central puzzle about wine and health is how much is due to biochemical substances such as resveratrol.  On the other hand, to what degree wine drinkers do other healthy things that can either compensate for the detrimental effects or amplify the good ones? People who regularly have a glass of wine with dinner more often eat in moderation, prefer healthier foods, and deal better with stress.

Wine with meals is associated with other healthy habits

A few recent studies bring clarification to the issue. One from the University of Helsinki in Finland reported the results of a long term population study evaluating drinking patterns and subjective well-being. Although a comparatively small percent of Finns have wine with dinner on a regular basis, those who did recorded better health, less psychological stress, and tended to be of higher socioeconomic status. Those who drank only wine also had fewer episodes of risky drinking behaviors such as bingeing. This type of study, while affirming the role of moderate wine drinking as a healthy thing, also suggests that lifestyle patterns are important.
It also illustrates why there are sometimes contradictory recommendations about wine and health; the pattern of drinking matters more than the amount, up to a point, but not all studies make this distinction. Another recent study, this one from the University of Split School of Medicine in Croatia, looked more deeply into the question. After reviewing available data from other studies, they found a clear correlation of wine with meals to maximal health benefits. The authors speculated that several factors such as the effect of food on alcohol absorption could be involved.

Why wine with meals makes food more healthy

The most telling evidence comes from a clinical trial conducted by the University of Rome Tor Vergata in 2014. This study measured the effects of red wine on post-meal oxidized cholesterol levels and expression of genes involved in inflammation. In order to see what the independent effects of wine were, they compared a McDonald’s meal to a Mediterranean diet meal, each with and without red wine. There was a clear benefit of wine with each meal type. So having a glass or 2 of wine makes even junk food better for you, pointing to biochemical properties of wine as the mediator of its health benefits. In other words, wine is more than a marker for a healthy lifestyle. Wine is a food.
1.       Oksanen A, Kokkonen H. Consumption of Wine with Meals and Subjective Well-being: A Finnish Population-Based Study. Alcohol Alcohol.  2016 Nov;51(6):716-722.
2.       Boban M, Stockley C, Teissedre PL, Restani P, Fradera U, Stein-Hammer C, Ruf JC. Drinking pattern of wine and effects on human health: why should we drink moderately and with meals? Food Funct. 2016 Jul 13;7(7):2937-42.

3.       Di Renzo L, Carraro A, Valente R, Iacopino L, Colica C, De Lorenzo A. Intake of red wine in different meals modulates oxidized LDL level, oxidative and inflammatory gene expression in healthy people: a randomized crossover trial. Oxid Med Cell Longev. 2014;2014:681318.

Monday, November 7, 2016

The French paradox at 25

 November 17 2016 will mark twenty-five years since the CBS television show 60 Minutes christenedthe term “French paradox” and ushered in the modern era of research on wine and health. It was a provocative idea at the time, attributing the French custom of regular imbibing to health and well-being. It still has its naysayers; as recently as 2015, England’s chief medical officer Sally Davies scorned the idea and proclaimed it an “old wives’ tale.” (She suggested a cup of tea instead, presumably with pinky finger raised.) Then there are those who reduce the idea to a simple question of nutritional biochemistry and proclaim that all of wine’s health benefits can be put into a pill, conveniently and properly skipping the alcohol. Is there still a useful truth underlying the paradox?

Why the French Paradox is still true

As with many questions in the realm of lifestyle and health, the answers are often nuanced and conditional. Government authorities in both America and Europe challenged the authors of the French Paradox –Curt Ellison in Boston and the late Serge Renaud in Bordeaux – who were challenged to defend the idea. Their work drew from both epidemiology and basic science, laying the groundwork for a legion of researchers who followed. The French paradox is now so well ingrained that it risks becoming a cliché and its true meaning lost. Despite all of the advances in understanding the components of wine and how they contribute to health, at its heart the paradox is a reflection of a lifestyle. Wine is a food, squarely affixed in the quotidian rituals of the Mediterranean diet.
The science that grew from the seed planted by the French paradox idea has grown far beyond what any of the early researchers could have predicted. Polyphenols from the skins of wine grapes have emerged as vitally important elements of an anti-aging diet. Among the best known is resveratrol, about which there were 2 articles in the scientific literature in the year of the original broadcast of the story; there a more than 2 every day now. Resveratrol provides a handy explanation for why wine drinkers have lower odds of developing Alzheimer’s, diabetes, osteoporosis, and pretty much all of the diseases of aging. It helps break up the protein plaques in the brain associated with Alzheimer’s, prevents cholesterol from aggregating into concretions in the arteries, kills cancer cells (while protecting normal ones), even improves insulin sensitivity in diabetics. Resveratrol certainly appears to be a miracle molecule, as I dubbed it in my book Age Gets Better with Wine. There are huge international conferences on resveratrol, and tomes on resveratrol market conditions.

It's not just resveratrol

But there remains a problem with giving resveratrol all the credit: there isn’t very much of it in wine, and less in anything else we might consume. Resveratrol has little if anything to do with the French paradox. Data still support the benefits of regular wine consumption, but is lacking when it comes to the use of resveratrol in supplement form. This brings us back to the role of wine as a lifestyle factor. Wine drinkers tend to do a lot of health things besides having a daily tipple with dinner, and wine contains a lot more than the pittance of resveratrol, including alcohol. It is the synergies of these various things that release the power of the paradox. 
In 1979 a paper was published in the famous medical journal The Lancet.(1) The article found a clear correlation of average wine consumption by country to lowered rates of heart disease, and it became an iconic reference. No one knew at the time why this should be so, but the authors concluded the article by observing that if the ingredient in wine should ever be identified, “we consider it almost a sacrilege that this constituent be isolated. The medicine is already in a highly palatable form (as every connoisseur will confirm.)”
1    1. St Leger AS, Cochrane AL, Moore F. Factors associated with cardiac mortality in developed countries with particular reference to the consumption of wine.  Lancet. 1979 May 12;1(8124):1017-20.

Friday, September 9, 2016

Should colleges teach drinking 101?

A quick glance at statistics on alcohol abuse in American colleges and universities reveals a huge problem, and I believe that tackling the issue will require a new and perhaps controversial strategy. Various approaches have failed, so in this “back to school” edition I take a look at the question and offer a sensible, if counterintuitive, alternative. The majority of young people who choose to drink need to be taught that there is such a thing as healthy drinking. The drinking 101 curriculum has to include “how drinking can be healthy” and not just “don’t drink.”
First the numbers: According to the National Institute on Alcohol Abuse and Alcoholism, as many as 1800 students die each year from alcohol-related causes. More than a half million more are injured while drunk, and tens of thousands become victims of sexual assault attributable to alcohol.  Tellingly, more than half of the 80% of students who consume alcohol engage in binge drinking, and this lies at the heart of most of the problems.

Party Culture Reinforces the Role of Alcohol as a Drug

Cultural factors make the problem of college drinking intractable to the usual approaches based primarily on enforcement of drinking restrictions. As the song goes, students are willing to fight for their right to party, and it’s the party culture that reinforces the role of alcohol as a drug. According to a 2014 New York Times article, the nation’s #1 party school Syracuse University faced a revolt over efforts to curtail drinking on campus. Students labeled the school a police state, and officials backed off. On many campuses, problem drinking is endemic to the Greek system, not directly under university control.
One clue hidden in plain sight is that the abuse is almost entirely in the form of beer and liquor. This reflects a trend in how we view beer and liquor consumption as a society. A 2015 study analyzing content of beer and liquor TV commercials revealed that “partying” has become the primary theme, while not identified in ads from 20 years ago. (1) Even Dos Equis, the last holdout of a mature approach to beer marketing with their “most interesting man in the world," just replaced  him with a younger jock in order to appeal to more youthful consumers.
There is evidence-based guidance on reducing problem drinking on college campuses, but the efforts are still narrowly focused on overall reduction rather than type of alcohol. The NIAAA’s “College Alcohol Intervention Matrix” rates 60 strategies on their effectiveness, with skills training in the top tier. None of this training appears to include a discussion of wine as healthy part of a meal. Alcohol is alcohol, be aware of how much, and drink less or none. Other recommendations include higher taxes on alcohol, banning Sunday sales, and limiting happy hour promotions.

Wine Offers a Positive Alternative Model

Aside from political campaigns, negative messages generally don’t move the needle on human behavior as much as positive ones. Offering a positive healthy way to consume (at the appropriate age) seems likely to work better than stronger enforcement of prohibitions. Perhaps I was lucky in this regard; my wine “epiphany” came during a summer when I was doing a research project at UCLA, when someone brought a bottle of Chambolle-Musigny to a pre-concert picnic at the Hollywood Bowl. It enlightened me to the aesthetic virtues of drink over the anesthetic properties of alcohol. It would be years before I had the budget for good wine on a regular basis, but I saw immediately that there could be a positive and healthy approach to drinking. Obviously we can't expect to create an entire student body of wine snobs, but it is also obvious that we need a different approach. We need to promote a culture of healthy drinking.

"The dipsomaniac and the abstainer make the same mistake: They both regard wine as a drug and not as a drink."
G.K. Chesterton (1874-1936)

1. Content Themes of Alcohol Advertising in U.S. Television-Latent Class Analysis.
Morgenstern M, Schoeppe F, Campbell J, Braam MW, Stoolmiller M, Sargent JD.
Alcohol Clin Exp Res. 2015 Sep;39(9):1766-74.