Thursday, July 6, 2017

Will the NIH trial on alcohol and health answer the question once and for all? Maybe not

What used to be accepted as gospel – that moderate drinkers are healthier than nondrinkers or heavy drinkers – has been challenged in recent years, and a new study to be conducted by the National Institutes of Health aims to settle the question once and for all. The study plans to enroll about 8,000 volunteers aged 50 or older from around the world, who will be assigned to avoid drinking or have one drink per day for 6 years. The lack of such large scale prospective studies is one reason why the question of alcohol’s influence on health and longevity remains subject to debate. However I am not sure the study will yield the answers it seeks to, but not for the reasons others are already finding to criticize the project.
 It’s an ambitious undertaking, with an equally ambitious price tag of US$100 million. The plan is for most of the money to come from the alcoholic beverage industry through grants, and $68 million has reportedly already been pledged. Skeptics point out that many of the study’s investigators have accepted money from alcohol industry groups in the past, and raise the issue of scientific influence peddling. But the study’s principal investigator, Dr. Kenneth Mukamal of Harvard, has no such ties and has authored numerous research articles on alcohol and health. As someone who has been a clinical investigator myself, I can vouch for the many levels of independent oversight that prevent any influence by investigators on the results. There's just no way to slip things through, and no reason to risk one's reputation by attempting to.
The challenges to the long held view that alcohol in moderation has a net positive benefit come largely from different types of studies, such as the one I critiqued in last month’s blog. These studies aggregate previously done observational studies (as opposed to interventional studies, like the NIH trial). The example I used last month essentially “cherry picked” the studies that met the criteria that would yield the desired findings. It's not new research, just old research repackaged to imply a different interpretation - one that fit the goals of an alcoholism treatment center.
But conflicts of interest are not the problem with the NIH trial, it is the complexities of human behavior. Volunteers willing to give up drinking will come from a specific subset of individuals that may not be representative of the average consumer. Allowing people to choose their beverage or to vary which one they drink could make it difficult to see if wine drinkers, for example, are different (evidence suggests that wine drinking is not the same as other types of drinking.) It may be that more than one drink per day is the optimal dose, and the effect too small to be statistically significant with only one. Another issue is the pattern of drinking; with wine, it is the relationship with meals. And how will the one drink per day rule be enforced? What of people who for whatever reason choose not to have a drink, or make up for it by skipping a couple of days then having several?

I do applaud the effort required to do this study, but I expect that whatever the results they will be challenged by those with an opposing ax to grind.

Tuesday, June 20, 2017

The whole truth about wine and heart health: Point-counterpoint

For this post I decided to address what I see as a neo-prohibitionist and paternalistic trend in medical advice about drinking, with a point-counterpoint on a blog that appeared recently on self.com. I believe the author made a sincere attempt to get the story right but was misinformed by the physicians she quotes. What was not disclosed is that the meta-analysis that this story references was done under the auspices of the Centre for Addictions Research of British Columbia, University of Victoria, an institution with a presumed anti-alcohol bias. An invited commentary with the original publication  came from the Alcohol Research Group in Emeryville, CA, whose mission “seeks to reduce alcohol-related harms.” They lauded the findings, saying that it could help fight back against “renewed calls from certain medical commentators to prescribe moderate drinking.” Disclosure: I count myself among those medical commentators.
The Truth About Whether Red Wine Actually Helps Your Heart Health
This isn't the most delightful news ever.
People love to talk about how red wine is good for your heart—and they usually do it while they’re drinking red wine, which is only natural. But research on the subject has been mixed, and even most positive findings have stopped short of actually recommending that people go out of their way to have a glass to prevent heart disease. Now, a large new meta-analysis is adding to the conversation, concluding that there's not much to support the idea that you should be drinking red wine to benefit your heart health.
For the analysis, which was published in the Journal of Studies on Alcohol and Drugs on May 21, scientists examined 45 studies on alcohol and heart health and found the conclusion that alcohol—especially red wine—is good for your heart are misleading.
Previous individual studies have suggested that moderate drinkers, defined as having at most one drink a day for women and two drinks for men, have lower heart disease rates than people who don’t drink. But researchers in this meta-analysis point out that a good portion of the people who don’t drink are teetotalers either because they have a problematic history with alcohol or have health problems that prevent them from drinking—not just because they choose not to drink for no reason. So, although healthiness and moderate drinking have been linked in past research, these studies have usually compared drinkers with people who already had health issues of some sort. When the researchers behind this new meta-analysis addressed this by controlling for heart health, they found no significant evidence that drinking moderate amounts of alcohol protects your heart.
RAB: This is known as the “abstainer bias” or the “sick quitter” hypothesis. In order to determine the validity of a hypothesis, it needs to be tested; additional observational data does not answer the question. The way to do this is to ask “What happens to lifelong abstainers who start drinking, and what happens to healthy moderate drinkers who quit?” This was addressed in a large study from Australia that followed 13,000 female subjects for 12 years. They found that when healthy moderate drinkers either increased or quit drinking, their health status declined. They further found that the health of recent abstainers and lifelong abstainers was the same, disproving the sick quitter hypothesis.
There's historically been a lot of confusion around the idea of red wine being healthy for your heart.
As you can see, it’s complicated, and somewhere along the line, the message got muddled. "The American Heart Association and other organizers have never recommended that a person has a daily allotment of alcohol," Richard Becker, M.D., director and physician-in-chief of the University of Cincinnati Heart, Lung and Vascular Institute, tells SELF. "If a person [stays within the moderate-drinking recommendations], that may be acceptable, but there's never been a recommendation to consume alcohol for heart health."
While the American Heart Association acknowledges that some research has shown that there may be a benefit to drinking wine due to components like flavonoids and other antioxidants that can help lower your heart disease risk, they also point out that these can be found in other foods, like grapes, and that the wine is likely not the key component here. “The [health and drinking] linkage reported in many of these studies may be due to other lifestyle factors rather than alcohol,” the organization states. “Such factors may include increased physical activity, and a diet high in fruits and vegetables and lower in saturated fats.” And, the American Heart Association notes, there have been no direct comparison trials to determine the specific effect of wine or other forms of alcohol on the risk of developing heart disease or stroke.
RAB: There should be no confusion. It would be more accurate to say that a substantial body of research supports a connection between moderate wine drinking and overall good health and longevity. Additional research documents an independent association of moderate alcohol consumption and heart health specifically. What is important to recognize is that the relationship is nonlinear, but follows a J-shaped curve: lower risk with moderate consumption, increased risk with heavy drinking compared to nondrinking. Moderate regular wine consumption is associated with other healthy lifestyle factors but these do not fully account for the observed benefits.
George S. Abela, M.D., chief of the division of cardiology at Michigan State University, tells SELF that alcohol and heart health can be a “double-edged sword.” On the one hand, moderate alcohol intake can raise your levels of HDL ("good") cholesterol, which is great for your heart health, he says. It also may help you de-stress here and there, and stress is a risk factor for heart disease.
On the other, when you drink in extreme excess or if you have a genetic condition, alcohol can damage your heart muscle and cause an abnormal heartbeat. It can also increase your blood pressure. “I’ve had patients that I’ve had to get off of alcohol completely to control their blood pressure,” Abela says. And, if you have a strong family history of high blood pressure, stroke, or weakening of the heart, Becker points out that you should talk to your doctor—they may advise that you shouldn't be drinking alcohol at all.
RAB: Again, the relationship is a J-shaped curve. Stating that heavy drinking is bad does not discredit the benefits of moderate drinking.  
There's also the nutritional aspect to think about. “I’m not a big supporter of alcohol being cardio-protective,” Nicole Weinberg, M.D., a cardiologist at Providence Saint John's Health Center in Santa Monica, California, tells SELF. “When I look at wine, I think it’s just a big glass of sugar." While indulging is a huge part of what makes life great, overdoing it on alcohol can lead to inflammation, weight gain, and an increased risk of diabetes—all of which are risk factors for heart disease, she says.
RAB: The statement that wine is the same as a “big glass of sugar” is nonsense. In wine, the sugar has fermented into alcohol, which is metabolized in a way that avoids the spike in blood sugar levels that sugary drinks such as grape juice have. The high sugar content and lower antioxidant polyphenols levels are among the reasons that grapes and grape juice do not have the same benefits as wine. Sugar is a notorious pro-inflammatory substance and responsible for much more cardiovascular disease than alcohol. Wine drinkers have lower markers of inflammation, are less likely to be overweight, and have a lower incidence of diabetes.
It's understandable that this "double-edged sword" concept can be frustrating, Malissa Wood, M.D., co-director of the Corrigan Women's Heart Health Program at Massachusetts General Hospital, tells SELF. But one of the main problems with alcohol, she says, is that people often drink more than they say they do—and drinking more than a moderate amount clearly isn’t great for your heart.
RAB: This points out a primary weakness in the studies on which the meta-analysis was done and a fault in how they are interpreted. Since people tend to under-report their actual drinking, what this actually means is that the benefits of moderate drinking apply to higher levels of consumption.
Luckily, this doesn’t mean you have to choose between pinot noir and your heart if you're healthy.
You can still drink alcohol and live a healthy life. “It’s a complicated situation, and I don’t think there’s a clear message that small amounts of alcohol are bad for your heart,” Wood says. Instead, experts recommend keeping your drinking in check. “A glass of wine here and there is perfectly reasonable, and so is going out on the weekend and having a few drinks with dinner,” Weinberg says. “But when it starts to become regular or heavy use, I tell people to dial back.”
Also, know this: If you prefer beer or cocktails, you don’t have to become a wine person to be “healthier.” “At the end of the day, the body only sees alcohol,” Abela says.

RAB: This is demonstrably false. Multiple studies document an association of regular, moderate wine consumption with improved health and longevity that are not observed with other drinks. The pattern of drinking is important; wine with dinner on a regular basis has the strongest benefit, limiting drinking to weekends or drinking different forms of alcohol and in varying amounts is associated with increased risk. 

Thursday, May 25, 2017

Understanding the risk of drinking (or not drinking) wine: Meet micromort

Whether we are talking about driving a car, drinking wine, or any other routine activity, most of us are not very good at calculating risk. Life insurance company actuaries devote careers to these sorts of calculations, but even they will tell you it gets really muddled when assessing small risks of prematurely dying from everyday endeavors. With nutrition and lifestyle choices it’s practically impossible. That doesn’t stop us from trying though, and one approach is unit of measurement called the micromort. A micromort is a one in a million chance of dying (mort from mortality.) If nothing else, it is useful in placing things in perspective; there’s even an app for tracking your micromorts as you consider lifestyle choices.
Take scuba diving, for example:  5 micromorts. It is said that 3 glasses of wine equals eating 100 char-broiled steaks or spending an hour in a coal mine, for a micromort each. Really? That sounds bad, and frankly didn’t make sense to me when I heard the term recently. So I decided to look into it.
The term dates to the 1970’s and is attributed to physics professor Richard Wilson, then at Harvard. I tracked down the original reference, or at least the earliest I could find, in the journal Technology Review. Interestingly, the article contains no references but does have a detailed list. For example add a micromort for traveling 6 minutes by canoe, 10 miles by bicycle, or 300 miles by car. Smoke 1-1/2 cigarettes or live with a smoker for a month. Spend 2 months in Denver (more cosmic radiation at higher altitude.) Oh and there is wine – right alongside the risk of living near a nuclear power plant.
If these are all small risks, what is the problem? It’s this: describing risk this way assumes that it is a linear relationship, meaning a little is not so bad, a lot really bad. This is true for many of the choices we make, but we now know that the risk with wine is a J-shaped curve. Unlike smoking, moderate consumption is less risky compared to teetotaling. We forgive the professor because we could not have expected this more nuanced perception in the era before the French Paradox and all the research that occurred in its wake. But the thinking pattern persists, and references to wine and its micromort factor continue to be bandied about. It’s this kind of thinking that underscores policy recommendations, for example Britain’s chief health officer’s recent admonition that any amount of drinking is unsafe. Or breast cancer researchers, seeing only risk and raising alarm without looking at overall health and longevity.

Celebrate National Wine Day

What we need is macro-life, a way of seeing the big picture. We need to consider quality of living as much as quantity. Today, May 25, has been designated National Wine Day, and I say cheers to that. And subtract a micromort if you care – spend it on a plane flight (1000 miles).
Nothing is more useful than wine for strengthening the body, and also more detrimental to our pleasure if moderation is lacking.

-              Pliny the Elder

Thursday, May 4, 2017

Of Wine, Charity and Health

Although wine has been associated with health since the dawn of civilization, the relationship was consummated in 1859 with the founding of the Hospices de Beaune annual charity wine auction. Built in 1443 as an almshouse and hospital for the poor, the Hospice was and is to this day supported by vineyard holdings. The auction serves to create a market for the wines, and has become a huge annual event in Burgundy. Following this lead, charity wine auctions are now held throughout the world, benefiting health care and a range of worthy causes. Some wineries now devote their profits directly to health care charities, and I would like to highlight a few of them here.
Napa Valley winery Ehlers Estate is actually owned by a charitable trust, Fondation Leducq. The vineyard dates to the 1880’s, and produces 100% organic wines. The foundation, based in France, sponsors internationally collaborative research in cardiovascular and neurovascular disease.  Their grants have gone to more than 100 institutions in 18 countries.
Another California winery, J Lohr Vineyards & Wines, honors the legacy of Carol Waldorf Lohr, who passed away from breast cancer in 2008.  Their Touching Lives program, now in its eight year, aims to make early detection possible for thousands of women by helping women get access to mammograms. A portion of proceeds from every bottle sold of J. Lohr Carol’s Vineyard Cabernet Sauvignon benefits the National Breast Cancer Foundation.
Walla Walla winery Vital Wines produces wines that, in the words of founder Ashley Trout, “complete a circle” by supporting healthcare for vineyard workers. All proceeds go to the SOS Clinic, a free, non-profit health care clinic. Because vineyard work is seasonal, access to healthcare can be a challenge for this population.
Napa’s ONEHOPE Wine was founded on the basis of charitable giving, with a variety of wines each benefiting a specific cause. Their Rutherford Estate Sauvignon Blanc supports Napa farmworkers with on-site medical care and health education, and the Napa Valley Reserve Merlot “helps provide life changing medical care to patients around the world.”

This sense of charity pervades the wine industry throughout the world, perhaps more than any other business category. Generosity of spirit is linked to good health, wine is a cornerstone of healthy living, and the synergy of the two is powerful. So let’s fill a glass with one of these generous offerings and toast to health and long life!

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.