Tuesday, September 22, 2015

Seeing red over breast cancer-wine reports: Why studies still get it wrong

A recent headline announcing the results of another study examining the role of alcohol and risk of breast cancer proclaimed that even a glass of wine a day “can significantly increase a woman’s cancer risk.” The connection between drinking and breast cancer has been a troublesome one, the thorn among the rosés, if you’ll pardon the metaphor. It’s not that I mean to make light of all this well-intentioned alarm bell ringing, but the way I see it research on wine and breast cancer just keeps repeating the same mistakes. When it comes to the question of wine and breast cancer, most studies still get it wrong.
That’s one reason why I can’t help but be a little bit cynical every October, when pink ribbons start sprouting everywhere, from lapels to football jerseys to cereal boxes. Increased awareness is laudable, but I wonder if these efforts do more to make us feel good than they do to actually make a difference for women with breast cancer. Case in point: the Komen Foundation, with its trademarked “for the cure” campaigns, reportedly spends less than a fifth of funds on research support to find a cure.
Advocates for breast cancer victims can’t be blamed for the misunderstandings about wine and cancer, and it’s hard to criticize the researchers - whose intentions are noble – but perspective is lacking. The Komen foundation wouldn’t even accept funds from a charitable wine auction I was involved in a few years ago when we approached the local chapter with the idea of making them a beneficiary. So we have this crazy situation where a breast cancer foundation won’t accept wine money, which may be a good thing because they don’t allocate much of it for research anyway.
Here’s the fundamental problem: When you do a study to identify which lifestyle factors are related to breast cancer (or anything else), of necessity you rely on self-reported questionnaires. With the question of drinking, there is a well-known under-reporting tendency so what subjects say they drink and what they actually drink are often not the same. This results in heavy drinking being mis-categorized as moderate drinking, with the implication that moderate drinking is riskier than it is.
When it comes to type of drinking, for example wine vs. beer or spirits, it becomes even murkier. What is well known about wine drinking and other disease conditions is that a pattern of a glass or two of wine with dinner on a daily basis is associated with lower risk than for nondrinkers. But very few people in a given North American population actually drink this way. What the studies do is ask about drinking preferences; if someone says they prefer wine with dinner, they may only do it occasionally, and sometimes have no alcoholic beverage, sometimes other types of drinks, and in varying amounts depending on circumstances. This makes it virtually impossible to know what the actual role of wine might be, even accounting for the under-reporting bias. No matter how large the study, or how long-term, it’s the same problem only amplified.
It’s clear that heavy drinking of any type is associated with higher risk, but what’s not as clear is how this extrapolates to low or moderate drinking. Generally, studies infer that a drink a day increases breast cancer risk by 10%, 2 drinks 20%, and on up. What this means (often misunderstood) is this is a percentage of baseline risk; so if you are at average lifetime risk of about 8 or 9 percent, a 10% increase is not 18 or 19%, but somewhere around 10 percent overall. (10% of 9% is 0.9%, so a 10% increase = 9.9%)
To put this in perspective it is helpful to consider that heart disease dwarfs breast cancer as a cause of death in women, and there is no question that moderate drinking (especially wine) associates with a lower risk. The same is true for diabetes, osteoporosis, and Alzheimer’s. For most women, stopping drinking to reduce breast cancer risk would result in an increased overall risk of premature death and disability.
But even that doesn’t tell the whole story. I am not convinced that moderate wine drinking contributes to even a low risk of breast cancer for the average woman. The definitive way to answer the question would be to study a population of women who only drink red wine, and in moderation as an integral part of their lifestyle. There are not very many of these studies because there are not many such populations anymore, but there is some good data. The best of these studies was done in Bordeaux a few years ago (1), and the conclusion was that wine drinkers had a substantially lower rate of breast cancer than nondrinkers.
Why should this be the case? For alcohol and breast cancer, it took years for a plausible cause-effect relationship to be put forth, and the best hypothesis is that it changes estrogen metabolism. Higher estrogen translates to greater risk of certain types of breast cancers. These types, known as estrogen-receptor positive (ER+), are often treated with drugs called aromatase inhibitors, which ramp down estrogen production. Red wine, as it turns out, is a natural aromatase inhibitor.
So forgive me if I don’t sport a pink ribbon, but I wish we had more efforts like the former Cleavage Creek Winery, which used profits to directly fund research at institutions like the Fred Hutchinson Cancer Research Center and Bastyr Naturopathic University in Seattle, bypassing “Big Pink.”  Founded by the late California winemaker Budge Brown after losing his wife of 48 years to breast cancer, Cleavage Creek donated more than $90,000 before the winery closed. So I say please do have a glass of red wine and toast to all those who are doing so much to save and improve women’s lives.

1.  Bessaoud F, Daurès JP. Patterns of alcohol (especially wine) consumption and breast cancer risk: a case-control study among a population in Southern France. Ann Epidemiol. 2008 Jun;18(6):467-75.

Monday, August 3, 2015

Feeling blue? Drink some red

Drinking and depression have problematic relationship, so the consensus from recent studies that moderate red wine consumption correlates to lower odds of depression may seem hard to swallow. But it is clear that daily wine drinkers show a J-shaped curve for clinical depression: lower in moderation, higher in excess. Some very good data comes from a long term study called PREDIMED (“Prevención con Dieta Mediterránea” (Prevention with Mediterranean Diet)), which is a randomized, multicenter, controlled, clinical trial conducted in Spain involving more than 5500 subjects. At up to 7 years of follow-up, wine intake within the range of 2-7 drinks per week was significantly associated with lower risk of incident depression.
Resveratrol, wine’s miracle molecule, offers a potential explanation though it is likely the whole story. There is an experimental model of depression in rats, allowing for measurement of depressive symptoms in response to various drug treatments (no model yet for the effects of counseling or group therapy.) A recent study found that rats given resveratrol for one week exhibited a dose-dependent decrease in activities correlated to depression. More significantly, this effect was associated with an increase in hippocampal and frontal cortical brain-derived neurotrophic factor (BDNF), a protein implicated in chronic effects of many antidepressants.
While it is tempting to unite these findings into and conclude that wine drinkers have lower rates of depression because of the resveratrol, there is an obvious in that logic: Only moderate consumption of wine has a clinical correlation, and it is likely that much higher doses of resveratrol are needed to raise BDNF levels in the brain than what you get in a glass of wine. Both studies are true, but unrelated.

There are many other factors to consider, such as the role of alcohol, but it may be that moderate wine drinking is a marker for other lifestyle factors that relate to lower incidence of depression or elevation of BDNF in the brain. Maybe I will have a glass of wine and think about it.

Wednesday, June 24, 2015

Can red wine can help you lose weight? – Yes but not how you think

There’s nothing like a good study on red wine as a weight loss aid to get attention, but in the case of a recent study from Washington State University it’s not quite so simple. Gilliam Fuller, writing for Elite Daily, led with “Drink Up: Science Says Red Wine Can Actually Help You LoseWeight” while the Sentinel Republic headlined simply “Red wine can help you lose weight.” Meanwhile Chris Mercer reported in Decanter.com on the United Kingdom’s National Health Service weighing in with “Red wine weight loss theory is ‘nonsense’.” They’re all partly right, but mostly wrong.
The study analyzed fat metabolism in mice given resveratrol, finding that it promoted conversion of normal white fat cells into brown fat, which is associated with higher metabolism and less weight retention. It was a well done study, but findings in mice given resveratrol cannot be directly extrapolated to humans consuming wine. So UK health officials were correct in stating that “‘based on mice studies only, we don’t know whether resveratrol will have the same effect in people.” Many reports on the paper emphasized the high calorie content of wine, and suggested that we might be better off getting our antioxidants from berries and fruits.
I have so many issues with this it’s hard to know where to begin. For starters, wine is unique in the diet as a source of resveratrol, though even the most robust wines don’t have a lot. Berries and other fruits generally do not have meaningful amounts, but they do have large amounts of natural sugars. Because wine has fermented the sugars into alcohol, it wreaks less havoc with blood sugar levels. That is one reason why wine drinkers have lower rates of obesity and remains an important aspect of the Mediterranean diet. Resveratrol, at least in doses attainable from a couple of glasses of wine, probably has little if anything to do with it.

Lost in all this is the scientifically most interesting aspect of the study: brown fat. Until only a couple of years ago it was thought to exist only in babies and hibernating animals. If resveratrol can be proven to promote the formation of brown fat and hence weight loss in human clinical trials, it would be another facet to this miracle molecule. But not a reason to drink – or not drink – red wine.

Wednesday, April 29, 2015

Do larger wine glasses contribute to overdrinking and obesity? Alcohol nutrition labeling debated

The UK’s Royal Society for Public Health recently issued a warning that “the insidious increase in the size of wine glasses in bars and restaurants in the past decade” has led many of us to have “unwittingly increased the number of invisible calories we consume in alcohol.” They called for food labeling laws to include calorie content in alcoholic beverages, which are exempt. Writing in the British Medical Journal, RSPH chair Professor Fiona Sim cites a survey which found that 80% of adults did not know the calorie content of their drinks, and speculates that in addition to gargantuan glasses, this may be contributing to the obesity epidemic in the UK. According to the Professor, the average portion served is a whopping 250 ml. (8 ½ ounces!) If that’s true I can’t wait for my trip to the UK this October.
 While public health officials are right to be concerned with rising obesity rates and abuse of alcohol, in this case they have missed the mark. For one thing, if larger glasses have become fashionable it is likely because they are believed to enhance the flavors and aesthetic appreciation of the wine, in part because of the space above the pour within the glass. It seems to me that would have the effect of slowing the pace of drinking, not increasing overall drinking. I would further venture that wines ordered by the bottle are typically shared between two diners regardless of glass size, and by-the-glass pours are unlikely to be a third of a bottle – the unit economics of that don’t pencil out. On this side of the pond, I am more likely to get too small of a pour in too small of a glass.
Professor Sim goes on to compare two glasses of wine to the caloric content of a McDonald’s order of fries, and notes that it exceeds recommended daily alcohol allowance for women.  She points out that most women “do not realise that two large glasses of wine, containing 370 calories, comprise almost a fifth of their daily recommended energy intake.” But 17 ounces is a lot of wine under most circumstances, and two of the more typical 5 ounce pour of red wine contains around 250 calories, close to half of the number cited in the article.
The article justifies inclusion of alcohol calories in food labeling because “there is no reason why calories in alcohol should be treated any differently from those in food.” It does not provide evidence that labeling laws have had any influence for other foods however. Indeed, the increasing rates of obesity despite nutritional labeling mandates suggest otherwise. It would be interesting to know if the survey subjects could accurately estimate the calories in their fries any better than in their vino (I doubt it.)

On the question, of labeling, we may have an answer soon. As of this year, in the U.S. all restaurant chains with more than 20 outlets will have to provide calorie counts for alcoholic beverages in addition to food items.  So if McDonald’s decides to offer wine to augment their fine dining experience (happy meal for mom and dad?), you will be able to make an informed decision. I expect you will find wine a more nutritional choice than a 17-ounce cola.

Saturday, March 21, 2015

Hangover-free wine from engineered yeast? Good wine is already hangover-free.

The promise of hangover-free wine has been in the news this week, based on new gene splicing techniques to manipulate the yeast used in fermentation. Using an enzyme called a “genome knife” researchers have been able to remove redundant copies of certain genes that produce compounds associated with hangovers, and what’s more, add in copies of genes that code for resveratrol.  All of this assumes of course that you don’t mind genetically modified yeast in your wine, and that these compounds are the main culprit in wine hangovers.
To the second point, there is a long tradition of wine consumption in moderation with food. This in turn leads to slower consumption, less intoxication, and less propensity for hangovers. The real issue is compounds called biogenic amines which are associated with headaches and allergic –type symptoms. (Histamine is a biogenic amine for example, which is why you take anti-histamines for allergies.) Biogenic amines typically develop in wine during malolactic fermentation, a secondary stage. Malolactic fermentation is driven by bacteria, because the yeast typically die off as alcohol levels rise; so the price winemakers pay for smoother wines is sometimes higher levels of headache-causing compounds. A fewyears ago a genetically modified yeast was developed that spliced the gene for catalyzing malolactic fermentation into the yeast, giving greater control over the process and promising an era of headache-free and delicious wines.

For some reason, the idea never took off. People became suspicious of GMO foods even if, in this case, they would be healthier. This latest development tinkers with the yeast genome even further, with possibly even healthier and tastier wines as a result. The role of different yeast strains in making wines with identifiable terroir and specific characteristics is vitally important (the same applies for beer and really any fermented food.) Will this new super yeast lead to an era of cleaner, headache-free, and hangover-free wines? Only if traditions hold, and we continue to see wine as a part of a healthy diet.

Thursday, February 26, 2015

Remember to drink your wine: It’s good for memory

Did you remember to have a glass of wine last night? If not, it may be because you didn't have a glass of wine to help you remember. The association of wine consumption and better memory has long been suspected, especially as it relates to cognitive decline with advancing age. Studies consistently find a correlation between long term moderate wine consumption and better mental function in older populations, but clinical studies – where one group is prospectively compared to another – are still hard to come by.
One such study comes from the Max Planck Institute for Human Cognitive and Brain Sciences in Berlin. They compared 23 older adults given resveratrol for 26 weeks to an equal number given placebo. Before and after the study period, subjects underwent memory tasks and neuroimaging to assess volume and functional neural connectivity of the hippocampus, a key region implicated in memory. The resveratrol group had improvements in memory retention and increased neural connectivity over the placebo group.
These findings corroborate a study in rats, also evaluating the effects of resveratrol on the hippocampus. (Rats also suffer from declining memory with age, due to deterioration of hippocampal function.) After 4 weeks of either resveratrol or placebo, middle-aged rats showed improved learning and memory function with resveratrol but impairments in the control group animals. Resveratrol-treated animals also displayed increased neurogenesis and microvasculature.
But is it just resveratrol? A study from Columbia University compared drinking patterns in a multiethnic group of nearly 600 New Yorkers over age 65 to actual brain volume using MRI scans. Light-to-moderate drinkers, particularly wine, had significantly larger average brain volume than nondrinkers. This fits with the several population studies where wine drinkers have comparatively better cognitive performance (and not with what we were told about alcohol killing brain cells!)

One person who would not have been surprised by all this is the 13th century court physician Arnoldo da Villanova, one of the earliest to recommend wine as medicine. He published a special “wine for memory” recipe purported to be good for forgetfulness along with other beneficial properties.

Monday, December 1, 2014

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

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

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