Wednesday, January 3, 2018

Clinical trials on wine and health

The ever-quotable Sir Winston Churchill once said “however beautiful the strategy, you should occasionally look at the results” and that is especially true for any proposed intervention to improve health and longevity. Whether we are talking about a glass of red wine with dinner or a potential 
blockbuster drug, clinical trials are the only objective way to know if it actually works. Drugs are required to prove their safety and effectiveness through prospective, randomized, double-blind trials, meaning that potential bias is minimized.  It’s tougher to do with lifestyle interventions like drinking wine, so we have relied on other types of studies. (These include for example observational or epidemiologic studies, which track health outcomes correlating to lifestyle factors.) There are nevertheless a few clinical trials on wine and health worth noting:

In 2015 the outcome of a 2-year interventional trial comparing the effects of red or white wine vs. no alcohol was reported in subjects with type 2 diabetes.[1] The subjects followed the Mediterranean diet and were randomly assigned to a glass or red wine, white wine, or mineral water in standardized amounts each day with dinner. Those in the red wine group experienced a significant decrease in total cholesterol and an increase in HDL cholesterol, which correlates to improvement in cardiovascular risk profile. This confirms the importance of wine as an essential component of the Mediterranean diet. Both wine groups reported better sleep, and there was no adverse effect on blood sugar control.
Two studies from the University of Rome and others looked at the effects of red wine on what is called “postprandial oxidative stress” which is elevation of oxidized fats and markers of inflammation following meals. [2],[3] One of the studies included red wine with a McDonald’s meal! (I am told that this is available in European McDonald’s outlets, though I wouldn’t know.) Even with a Mediterranean diet, lower levels of oxidized fats and reduced expression of pro-inflammatory genes was documented when red wine was included with the meal.
You’ve got to hand it to the Swedes for this next one.[4] In a crossover study, meaning that each subject participated in each intervention at different times, patients with type 2 diabetes were given various meals while their blood sugars were closely tracked. The diets were either low fat, low carbohydrate, or Mediterranean, skipping breakfast. Notably, the Mediterranean diet included red wine with lunch–they apparently got the memo from the study mentioned above!  Despite a higher caloric intake, blood glucose control was similar to the low fat diet. The study authors concluded that “accumulation of caloric intake from breakfast and lunch to a single large Mediterranean style lunch-meal in NIDDM [non insulin-dependent diabetes mellitus] might be advantageous from a metabolic perspective.”
Not to be outdone (one supposes) a study from Luxembourg weighed in with a report on the Mediterranean diet, red wine, and exercise in subjects with arteriosclerosis of the carotid arteries.[5] Subjects were randomized to have either no alcohol, one glass of red wine (women), or 2 glasses of red wine (men) for 20 weeks. Although most of these patients were already on statin drugs for cholesterol control because of their disease and risk for stroke, there was improvement in cholesterol profile from red wine in an additive fashion to diet and exercise.
While a handful of prospective trials on a broad subject is not conclusive, the fact that the results are similar and consistent with other ways of evaluating wine’s connection to health is compelling. Wien with meals is a beautiful strategy indeed.
“In wine, there is wisdom; in water, germs.” – Sir Winston Churchill

[1]Effects of Initiating Moderate Alcohol Intake on Cardiometabolic Risk in Adults With Type 2 Diabetes: A 2-Year Randomized, Controlled Trial. Ann Intern Med. 2015 Oct 20;163(8):569-79.
[2] Changes in LDL Oxidative Status and Oxidative and Inflammatory Gene Expression after Red Wine Intake in Healthy People: A Randomized Trial. Mediators Inflamm. 2015;2015:317348.
[3] 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.
[4] A randomized cross-over trial of the postprandial effects of three different diets in patients with type 2 diabetes. PLoS One. 2013 Nov 27;8(11):e79324.
[5] A daily glass of red wine associated with lifestyle changes independently improves blood lipids in patients with carotid arteriosclerosis: results from a randomized controlled trial. Nutr J. 2013 Nov 15;12(1):147.

Wednesday, December 6, 2017

Healthy drinking for the holidays

The holiday season is a time of conviviality, and nothing is more celebratory than wine. As we raise our glasses to toast friendships and family, we remember that wine symbolizes health and happiness. But it is all too easy to fall out of the habits that define healthy drinking, and moderation hardly seems a festive theme. With that in mind, here are a few (science-based) tips for healthy drinking:
1.       Stick with wine. Peak blood alcohol levels are lower after wine consumption as opposed to spirits, even when the amount of alcohol is the same. (The same applies for beer, but beer lacks the beneficial polyphenols of wine.) Mixed drinks also tend to contain more calories from sugar, while calories from alcohol avoid spikes in blood sugar levels.
2.       Whenever possible have food with wine. Alcohol is absorbed much more rapidly on an empty stomach, even for wine. What’s more, wine with meals dampens down what is called “oxidative stress” from certain foods such as red meat. Wine with food actually makes the food more nutritious!
3.       Pace yourself. You don’t get credit for moderation if your total weekly consumption occurs only on the weekend. It might be justifiable mathematically but a pattern of regular drinking (with meals) is as important as the total amount of drinking. Binge drinking cancels out the health benefits.
4.       Have a glass of water between drinks. This will help with metabolism of the alcohol and help you to be mindful of total consumption.
5.       Go with quality – wines you really want to enjoy and share. You will probably take more time with them and people will be more likely to appreciate the generosity, thereby slowing the pace of drinking. This doesn’t mean replacing sociability with snobbery; sharing good wine is one of the best ways to strengthen connections with those we care about, collaborate with, and celebrate for. As the late author Clifton Fadiman once said, “A bottle of good wine begs to be shared; I have never met a miserly wine lover.”

With this last post of 2017, I offer a toast to your health, your happiness, and your friendship. Cheers!

“What is better than to sit at the end of the day and drink wine with friends,
or substitutes for friends?”
--James Joyce

Tuesday, November 14, 2017

Why Age Gets Stronger with Wine

Because physical fitness and good health go hand in hand, muscle mass and strength are markers of resistance to frailty with aging. There are important behavioral associations such as regular exercise (no surprise there) and moderate regular consumption of alcohol, especially wine (only a surprise if you haven’t been reading this blog!)
Studies on the subject are numerous and from many countries, suggesting that more than cultural factors are involved. A great example is this study[1] from Spain, which prospectively evaluated more than 2000 community-dwelling adults aged 60 and older at enrolment. The researchers were specifically interested in the Mediterranean drinking pattern, defined as moderate alcohol intake, with ≥80% of alcohol intake from wine, and drinking only with meals.  The subjects were followed regularly, with measures of muscle mass, walking speed, and endurance, and other factors. Using validated criteria, the subjects were classified as “frail” if they had low functional scores.

Wine drinkers have better muscle mass

If you are considering a retirement facility, you might want to check out the wine list before you make a decision: After only 3 ½ years, the moderate drinker group was 10% less likely to become frail, but if they were in the clique that preferred wine, the benefit increased to 25%. Those who had their wine with meals were almost 50% less likely to develop frailty.
These results are not unique. A recent meta-analysis[2] combining the results of studies from around the world evaluated the role of alcohol consumption and muscle wasting (sarcopenia) in more than 13,000 subjects. Those who consumed alcohol regularly were about 25% less likely to develop sarcopenia compared to nondrinkers. Though this type of review was not able to parse out the wine drinker subset as in the Spanish study above, the role of alcohol in general was consistently found in high quality studies.
It is also important to note that the amount of alcohol consumed is as important as the pattern of drinking. Heavy alcohol consumption is more likely to promote frailty with advancing age than to forestall it. But get regular exercise, practice lifting a glass with dinner, and things will work out.

[1] Ortolá R, García-Esquinas E, León-Muñoz LM, Guallar-Castillón P, Valencia-Martín JL, Galán I, Rodríguez-Artalejo F. Patterns of Alcohol Consumption and Risk of Frailty in Community-dwelling Older Adults. J Gerontol A Biol Sci Med Sci. 2016 Feb;71(2):251-8.
[2] Steffl M, Bohannon RW, Petr M, Kohlikova E, Holmerova I. Alcohol consumption as a risk factor for sarcopenia - a meta-analysis. BMC Geriatr. 2016 May 11;16:99.

Friday, October 20, 2017

Update on wine and breast cancer

With breast cancer awareness month upon us again, it’s fair to ask what we have learned about prevention and treatment, and for wine drinkers, it remains a confusing picture. It’s clear that heavy alcohol consumption increases risk, not so certain whether moderation – especially wine – is all that bad; it might even be good. On one hand, the message from the medical community is unambiguous: any level of drinking increases the odds of developing breast cancer. On the other hand, at moderate levels of drinking, cancer risk is extremely difficult to measure with confidence, even more so with wine. Here’s why I think a daily glass or two of red wine with dinner is still a healthy choice:
  •   A recent study from the University of California San Diego[1] looked at survival and recurrence after breast cancer treatment, finding that light drinking had no correlation. Moderate alcohol intake was “protective against all-cause mortality” in non-obese women.
  •   There appears to be no breast cancer risk of drinking in premenopausal women, according to a very large European study involving more than 66,000 women followed for 15 years.[2] In postmenopausal women, the risk became clear at more than 2 drinks per day, but as with other studies this was seen mostly in overweight subjects.

How red wine might protect against breast cancer

  •     In order to confirm a possible correlation between alcohol and breast cancer, a plausible cause-effect relationship needs to be demonstrated. The prevailing idea is that alcohol elevates estrogen levels via enzymes called aromatases. Aromatase inhibitors (AIs) are commonly prescribed for prevention of cancer recurrence, and interestingly red wine contains natural AIs. A clever study[3] from the Women’s Heart Center at Cedars Sinai in Los Angeles tested the idea that wine could be an anti-cancer agent by assigning women to have an 8-oz glass of either red or white wine daily for a month, while monitoring hormone levels. The two groups then switched from red to white or vice-versa. The researchers concluded that red wine is a natural AI in premenopausal women, providing an explanation for its possible protective effect. The strength of this particular study is that drinking was carefully measured and consistent, rather than reliance on self-reported questionnaires.

  •               This pattern of regular, moderate, exclusive consumption of red wine is unfortunately not typical in modern society, making it increasingly difficult to suss out from population studies whether their risk profile is distinct. The best evidence is still from a 2008 study in southern France, with a population of consistent wine drinkers.[4] There was a clear J-shaped curve, with an unequivocal benefit to moderate drinking. It was the nondrinkers most likely to get breast cancer.

Why we should make the pink ribbons red

We would do well to remember that despite all the fear and publicity around breast cancer, heart disease remains far and away the biggest threat to women’s health. Even if there was a risk of breast cancer from wine – a debatable supposition – it is almost certainly cancelled out from the benefits to heart health. Let’s make the pink ribbons red.

[1]Low to moderate alcohol intake is not associated with increased mortality after breast cancer.
Flatt SW1, Thomson CA, Gold EB, Natarajan L, Rock CL, Al-Delaimy WK, Patterson RE, Saquib N, Caan BJ, Pierce JP. Cancer Epidemiol Biomarkers Prev. 2010 Mar;19(3):681-8.
[2] Alcohol consumption and breast cancer risk subtypes in the E3N-EPIC cohort.
Fagherazzi G1, Vilier A, Boutron-Ruault MC, Mesrine S, Clavel-Chapelon F. Eur J Cancer Prev. 2015 May;24(3):209-14.
[3] Red versus white wine as a nutritional aromatase inhibitor in premenopausal women: a pilot study.
Shufelt C1, Merz CN, Yang Y, Kirschner J, Polk D, Stanczyk F, Paul-Labrador M, Braunstein GD. J Womens Health (Larchmt). 2012 Mar;21(3):281-4.
[4] Patterns of alcohol (especially wine) consumption and breast cancer risk: a case-control study among a population in Southern France.
Bessaoud F1, Daurès JP. Ann Epidemiol. 2008 Jun;18(6):467-75.

Friday, September 1, 2017

Is wine a probiotic? More than a gut feeling

That “gut feeling” you sometimes get may be more literal than you think: research continues to reveal the importance of the bacteria in our digestive tract, called the “gut microbiome.”  This symbiotic population of microbes affects health and well-being in often unexpected ways. The microbiome sends signals to the central nervous system, regulates inflammation, even influences cardiovascular health. Wine’s impact on health appears to depend significantly on the microbiome, and we are now learning that it may not actually be the constituents of wine that make it healthy for us; it is the things that the microbiome transforms them into.

How wine promotes a healthy microbiome

Wine’s relationship with the microbiome is a two-way street: Recent studies[1]  demonstrate how wine consumption influences the composition of the various bacteria, while other research demonstrates how the microbiome metabolizes wine into components that boost the immune system.[2] The idea that wine’s health benefits may not derive directly from what’s in it is revolutionary, and it is re-jiggering the field of nutrition and aging. For nearly 200 years we have gone by the words of the famous 19th century gastronome Anthelme Brillat-Savarin, who wrote "Tell me what you eat, and I will tell you what you are,” but that is turning out to be only half right, at least in the physiologic sense.

How the microbiome enhances the health effects of wine

Here’s how it works: wine encourages a healthy microbiome, which returns the favor by enhancing what is called bioavailability, the absorption and transport to the tissue where the active ingredient or nutrient in a food or drug is to have an effect. Wine’s effects are attributed to its antioxidant polyphenols, but their poor absorption gives them low bioavailability.  This is one reason why effects in tissue cultures and lab studies don’t predict what happens in people: you can’t get the same levels in the target organ as you can in cells in a Petri dish.  But think of a healthy microbiome as a sort of Amazon Prime for wine: it metabolizes wine polyphenols into compounds that are taken up and delivered, rapidly and often in a more potent form.
An elegant example of this was published by researchers from Washington University School of Medicine, who detailed how this phenomenon helps wine fight influenza. They showed how flavonoids, a class of immune-boosting polyphenols present in red wine, are altered by a specific type of bacterium in the colon into a molecule called DAT. This in turn signals the production of the immune modulator interferon, which then enhanced the survival of mice inoculated with the flu virus. Inflammation in the lungs was correspondingly lessened as well.
Similar examples abound for a variety of diseases. One study demonstrated wine’s influence on gut bacteria in obese subjects with a condition called metabolic syndrome. After a period of regular wine consumption, strains of bacteria known as “intestinal barrier protectors” proliferated, while those producing markers of inflammation diminished.[3]  So if “you are what you eat,” in the updated interpretation of Brillat-Savarin’s maxim, you are equally what you drink, and with wine all the better for it.

[1] Carolina Cueva , Irene Gil-Sánchez , Begoña Ayuda-Durán , Susana González-Manzano , Ana María González-Paramás , Celestino Santos-Buelga , Begoña Bartolomé  and M. Victoria Moreno-Arribas . An Integrated View of the Effects of Wine Polyphenols and Their Relevant Metabolites on Gut and Host Health. Molecules. 2017 Jan 6;22(1).
[2] The microbial metabolite desaminotyrosine protects from influenza through type I interferon. Steed AL,, Christophi G, Kaiko GE, Sun L, Goodwin VM, Jain U, Esaulova E, Artyomov MN, Morales DJ, Holtzman MJ, Boon ACM, Lenschow DJ, Stappenbeck TS. Science. 2017 Aug 4;357(6350):498-502.
[3] Red wine polyphenols modulate fecal microbiota and reduce markers of the metabolic syndrome in obese patients. Moreno-Indias I, Sánchez-Alcoholado L, Pérez-Martínez P, Andrés-Lacueva C, Cardona F, Tinahones F, Queipo-Ortuño MI. Food Funct. 2016 Apr;7(4):1775-87.

Wednesday, August 9, 2017

Alcohol and skin cancer: When the devil is ignoring the details

Summer has me thinking about skin cancer (I am a plastic surgeon after all) and recent reports that drinking alcohol increases the risk of skin cancer are not helping to ease my mind. "Drinking just one glass of beer or wine a day could give you skin cancer, scientists have warned," reports Britain’s Mail Online.  Researchers reached this conclusion by analyzing pooled results from previous studies (the notorious meta-analysis; see last month’s post.) It seems that every drink increases your odds of developing non-melanoma skin cancer by around 10 percent. But just as blending random wines together may produce something drinkable but lacking nuance, pooling results of different types of studies may obscure crucial details. With the specific question of wine consumption and skin cancer risk, the details are especially important.

Is skin cancer risk the same with all types of alcohol?

Granted, some of the studies are very well done and should not be dismissed out of hand. These results were widely characterized as applying to all types of drinking. But here’s the first important detail: only white wine and liquor consumption were associated with basal cell skin cancer (BCC), the most prevalent type. BCC being strongly associated with UV exposure from sunlight, it is possible that white wine and cocktail drinkers simply spent more time outdoors. It is also possible that red wine has completely different effects.
Results from the Nurses Health Study, involving nearly 168,000 women whose health and lifestyle were tracked for decades, align with findings from the more than 43,000 men in the Health Professionals Follow-Up Study: when analyzed for non-melanoma skin cancer: alcohol consumption had a clear correlation.[i]
But not all studies conclude that alcohol is associated with skin cancer. In fact most do not; a review from the UK’s University of Nottingham looked at 22 publications on lifestyle and skin cancer risk, and found no relationship to drinking of any type.[ii]

How red wine might protect against skin cancer

There’s actually good evidence for red wine having a protective effect against skin cancer. A very large study from Australia – where skin cancer is particularly prevalent – looked at diet and lifestyle factors associated with pre-cancerous lesions known as Actinic Keratoses.[iii] The lowest rate of AK’s was in the group that drank the most wine, specifically red. Other studies point to a reason for this, according to another Australian report.[iv] Consumption of foods rich in polyphenol antioxidants – wine, tea, fruits and vegetables – confers protection against UV damage to the skin. This was documented in an interesting study from Germany, in which they found that consumption of red wine diminished redness of the skin from standardized doses of UV light.[v] (This is the same method used to test sunscreens, which measures the time to produce redness, known as the Minimal Erythema Dose or MED.) Interestingly, this group also studied topical application of red wine, finding minimal benefit; you have to drink it.

So slather on the sunscreen, have a glass of (red) wine and enjoy the sunshine.

[i] Wu S, Li WQ, Qureshi AA, Cho E. Alcohol consumption and risk of cutaneous basal cell carcinoma in women and men: 3 prospective cohort studies. Am J Clin Nutr. 2015 Nov;102(5):1158-66.
[ii] Leonardi-Bee J, Ellison T, Bath-Hextall F. Lifestyle factors of smoking, BMI and alcohol on the risk of Non-Melanoma Skin Cancer in adults: a systematic review. JBI Libr Syst Rev. 2012;10(6):352-398.
[iii] Hughes MC, Williams GM, Fourtanier A, Green AC. Food intake, dietary patterns, and actinic keratoses of the skin: a longitudinal study. Am J Clin Nutr. 2009 Apr;89(4):1246-55.
[iv] Chen AC, Damian DL, Halliday GM. Oral and systemic photoprotection. Photodermatol Photoimmunol Photomed. 2014 Apr-Jun;30(2-3):102-11.
[v] Moehrle M, Dietrich H, Patz CD, Häfner HM. Sun protection by red wine? J Dtsch Dermatol Ges. 2009 Jan;7(1):29-32, 29-33.

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.