Wine is safer than beer for minimizing risk of heart condition

by Crispin Savage, University of Adelaide

Credit: CC0 Public Domain

Drinking less than six Australian-standard glasses of alcohol a week is associated with the lowest risk of developing atrial fibrillation, but not all alcohol is created equal, new research from the University of Adelaide shows.

01 august 2021--Atrial fibrillation (AF) is an irregular and rapid heart rate that can increase risk of stroke, heart failure and other heart-related complications. Symptoms include heart palpitations, shortness of breath and weakness.

Past research has shown that binge drinking and consumption of large amounts of alcohol increases your risk of developing atrial fibrillation but it was not clear whether consumption of low amounts of alcohol increases your risk of developing AF.

This study, published today in JACC: Clinical Electrophysiology , used data from the UK Biobank, a large-scale research database with health information collected from half a million UK volunteers.

Lead author Samuel Tu from the University of Adelaide's Centre for Heart Rhythm Disorders, said researchers found that those who consumed less than six Australian standard drinks of alcohol per week had the lowest risk of developing AF.

"We also found that beer and cider consumption was associated with a greater risk of atrial fibrillation, compared to red wine and white wine consumption,'' he said.

"Our findings suggest that responsible consumption of alcohol up to six drinks per week is safe in terms of minimizing your risk of atrial fibrillation. For those currently consuming alcohol, drinking red or white wine could potentially be a safer alternative to other types of alcoholic beverages."

"Importantly, these findings do not apply to people who already suffer from atrial fibrillation, who may find that cutting down their alcohol consumption may reduce their symptoms."

Researchers also investigated whether the recommended number of drinks per week differed for men and women.

"A key question that we sought to answer in this study is whether the effect of alcohol is different in women and men in terms of developing atrial fibrillation,'' Mr Tu said.

"The answer to that is no—less than six drinks per week is the cut-off for both men and women."

---

More information: Samuel J. Tu et al, Risk Thresholds for Total and Beverage-Specific Alcohol Consumption and Incident Atrial Fibrillation, JACC: Clinical Electrophysiology (2021). DOI: 10.1016/j.jacep.2021.05.013

Provided by University of Adelaide 

Drinking red wine for heart health? read this before you toast

For years, studies have shown a relationship between drinking a moderate amount of red wine and good heart health, but experts say it's important to understand what that means before you prescribe yourself a glass or two a day.

28 may 2019--No research has established a cause-and-effect link between drinking alcohol and better heart health. Rather, studies have found an association between wine and such benefits as a lower risk of dying from heart disease.

It's unclear whether red wine is directly associated with this benefit or whether other factors are at play, said Dr. Robert Kloner, chief science officer and director of cardiovascular research at Huntington Medical Research Institutes and a professor of medicine at the University of Southern California.

"It might be that wine drinkers are more likely to have a healthier lifestyle and a healthier diet such as the Mediterranean diet, which is known to be cardioprotective," he said.

But you may not even have to drink red wine to get the benefit, Kloner said. Moderate amounts of beer and spirits also have been linked to a lower risk of heart disease.

It's a common assumption that red wine may be good for the heart because it contains antioxidants such as resveratrol, which is primarily found in the skin of grapes but also peanuts and blueberries. Some studies suggest resveratrol can reduce cholesterol and lower blood pressure.

"There's a debate about whether resveratrol is really cardioprotective or not," Kloner said. "In addition, there is debate about the amount of resveratrol you would need to ingest to get a protective effect. To get the equivalent of the amount of resveratrol that has been reported to be protective would probably mean ingesting an excess of wine."

Federal guidelines and the American Heart Association recommend that if you do drink alcohol, do so in moderation. That means no more than one to two drinks per day for men and one drink per day for women. (According to the AHA, one drink is 12 ounces of beer, 4 ounces of wine, 1.5 ounces of 80-proof spirits or 1 ounce of 100-proof spirits.)

Studies have found that moderate alcohol consumption may have some health benefits, including raising "good" HDL cholesterol levels and lowering the risk of diabetes. However, excessive drinking can lead to a host of health problems, including liver damage, obesity and some types of cancer and stroke, not to mention its negative effect on the heart.

"Alcohol in excess is really bad for the heart," Kloner said. "It can cause high blood pressure and promote arrhythmias. It can cause cardiomyopathy where the alcohol is actually toxic to the heart muscle cells, and that can lead to heart failure."

Proving moderate alcohol use causes better heart health would be tricky, Kloner said. Ideally, it would require a large prospective study that not only randomly assigns people to a no-drinking group versus a moderate-drinking group, but that also compares different types of alcohol—red wine, white wine, beer, spirits—to determine if one really is better.

"And then you'd have to control for various factors—age, gender, cardiovascular risk, their diet. You'd have to follow them for many years," he said, noting the added ethical dilemma of taking people who are not drinkers and telling them to become drinkers.

For now, the message certainly isn't to go out and start drinking, Kloner said. "But if you do drink, drinking in moderation is the way to go."

---

Red wine with dinner can improve cardiovascular health of people with type 2 diabetes

A glass of red wine every night may help people with type 2 diabetes manage their cholesterol and cardiac health, according to new findings from a two-year randomized controlled trial (RCT) led by researchers at Ben-Gurion University of the Negev (BGU). Additionally, both red and white wine can improve sugar control, depending on alcohol metabolism genetic profiling.

13 oct 2015--In this first long-term alcohol study, just published in the prestigious Annals of Internal Medicine, the researchers aimed to assess the effects and safety of initiating moderate alcohol consumption in diabetics, and sought to determine whether the type of wine matters.
People with diabetes are more susceptible to developing cardiovascular diseases than the general population and have lower levels of "good" cholesterol. Despite the enormous contribution of observational studies, clinical recommendations for moderate alcohol consumption remain controversial, particularly for people with diabetes, due to lack of long-term, randomized controlled trials, which are the "holy grail" of evidence-based medicine.
"Red wine was found to be superior in improving overall metabolic profiles, mainly by modestly improving the lipid profile, by increasing good (HDL) cholesterol and apolipoprotein A1 (one of the major constituents of HDL cholesterol), while decreasing the ratio between total cholesterol and HDL cholesterol," the researchers explain.
The researchers concluded that "initiating moderate wine intake, especially red wine, among well-controlled diabetics, as part of a healthy diet, is apparently safe, and modestly decreases cardio-metabolic risk. The differential genetic effects that were found may assist in identifying diabetic patients in whom moderate wine consumption may induce greater clinical benefit."
The researchers also found that only the slow alcohol-metabolizers who drank wine achieved an improvement in blood sugar control, while fast alcohol-metabolizers (with much faster blood alcohol clearance) did not benefit from the ethanol's glucose control effect. Approximately one in five participants was found to be a fast alcohol-metabolizer, identified through ADH enzyme genetic variants tests.
Wine of either type (red or white) did not effect change in blood pressure, liver function tests, adiposity, or adverse events/symptoms. However, sleep quality was significantly improved in both wine groups, compared with the water control group. All comparisons were adjusted for changes in clinical, medical and drug therapy parameters occurring among patients during the years of the study.
The two-year CArdiovaSCulAr Diabetes and Ethanol (CASCADE) randomized controlled intervention trial was performed on 224 controlled diabetes patients (aged 45 to 75), who generally abstained from alcohol. They gradually initiated moderate wine consumption, as part of a healthy diet platform, and not before driving. The trial completed with an unprecedented adherence rate of 87 percent after two years.
According to BGU's Prof. Iris Shai, principal investigator of the CASCADE trial, and a member of the Department of Public Health in the Faculty of Health Sciences, "The differences found between red and white wine were opposed to our original hypothesis that the beneficial effects of wine are mediated predominantly by the alcohol. Approximately 150ml of the dry red or white tested wines contained ~17g ethanol and ~120kCal, but the red wine had sevenfold higher levels of total phenols and 4 to 13-fold higher levels of the specific resveratrol group compounds than the white wine. The genetic interactions suggest that ethanol plays an important role in glucose metabolism, while red wine's effects additionally involve non-alcoholic constituents. Yet, any clinical implication of the CASCADE findings should be taken with caution with careful medical follow-up."
The study was performed in collaboration with Prof. Meir Stampfer from Harvard University, USA, and with colleagues from University of Leipzig, Germany and Karolinska Institute, Sweden.
In the new study that followed the research group's three-month alcohol pilot RCT findings (Shai I, et al., Diabetes Care 2007), the patients were randomized into three equal groups according to whether they consumed a five-ounce serving (150ml) of mineral water, white wine or red wine with dinner every night for two years. Wine and mineral water were provided free of charge for the purposes of the study. Compliance with alcohol intake was tightly monitored, with patients returning their empty wine bottles and receiving their new supplies. All groups followed a non-calorie-restricted Mediterranean diet (following the group's previous two-year dietary RCT findings; Shai I, et al., NEJM 2008). Adherence was monitored using several validated assessment tools.
During the study, subjects underwent an array of comprehensive medical tests, including continuous monitoring of changes in blood pressure, heart rate and blood glucose levels, and follow-up for the dynamic of atherosclerosis and fat by ultrasound and MRI tests.


Provided by American Associates, Ben-Gurion University of the Negev

Wine only protects against CVD in people who exercise

Wine only protects against cardiovascular disease (CVD) in people who exercise, according to results from the In Vino Veritas (IVV) study presented at ESC Congress today by Professor Milos Taborsky from the Czech Republic.

02 sept 2014--Professor Taborsky said: "This is the first randomised trial comparing the effects of red and white wine on markers of atherosclerosis (1) in people at mild to moderate risk of CVD. We found that moderate wine drinking was only protective in people who exercised. Red and white wine produced the same results."

Evidence suggesting that mild to moderate consumption of wine protects against cardiovascular disease has been accumulating since the early 1990s. In particular, retrospective studies have found that wine increases levels of HDL, the "good"cholesterol. But until now there has been no long-term, prospective, randomised study comparing the effects of red and white wine on HDL cholesterol and other markers of atherosclerosis.

The IVV study (2) is the first long-term, prospective randomised trial comparing the effect of red and white wine on markers of atherosclerosis. The study included 146 people with mild to moderate risk of cardiovascular disease according to the HeartScore (3). Participants were randomised to one year of moderate consumption of red wine (Pinot Noir) or white wine (Chardonnay-Pinot) from the same year and wine region of the Czech Republic.

Moderate consumption was the World Health Organization definition of 0.2 L for women and 0.3 L for men, a maximum of five times a week. The primary endpoint was the level of HDL cholesterol at one year. Secondary endpoints were levels of other markers of atherosclerosis including LDL cholesterol. Participants consumed their usual diet.

Participants kept a logbook on their consumption of wine and other alcoholic beverages, medication use, and amount and type of exercise. They were required to return the corks from the wine bottles to confirm that they had drank the wine rather than sold it.

The researchers found that there was no difference between HDL cholesterol levels at the beginning of the study compared to one year in either the red or white wine groups. LDL cholesterol was lower in both groups at one year while total cholesterol was lower only in the red wine group.

Professor Taborsky said: "A rise in HDL cholesterol is the main indication of a protective effect against CVD, therefore we can conclude that neither red or white wine had any impact on study participants as a whole."

He added: "The only positive and continuous result was in the subgroup of patients who took more exercise, which means regular exercise at least twice a week, plus the wine consumption. In this group HDL cholesterol increased and LDL and total cholesterol decreased in the

red and white wine groups. There may be some synergy between the low dose of ethyl alcohol in wine and exercise which is protective against CVD."

He continued: "In a future study we will compare the effects of red and white wine on markers of atherosclerosis in patients at high risk for CVD who take statins and do regular exercise. We hope to find that moderate wine consumption is safe in these patients."

Professor Taborsky concluded: "Our current study shows that the combination of moderate wine drinking plus regular exercise improves markers of atherosclerosis, suggesting that this combination is protective against cardiovascular disease."

More information: References:

(1) Atherosclerosis is a condition in which the arteries become clogged with fatty substances including cholesterol. Atherosclerosis is a major risk factor for cardiovascular disease.

(2) Taborsky M, Ostadal P, Petrek M. A pilot randomized trial comparing long-term effects of red and white wines on biomarkers of atherosclerosis (in vino veritas: IVV trial). Bratisl Lek Listy. 2012;113(3):156-158. (full paper available in the press kit)

(3) HeartScore is an interactive tool for predicting and managing the risk of heart attack and stroke. See www.heartscore.org for more information.

Provided by European Society of Cardiology

Non-alcoholic red wine may help reduce high blood pressure

Men with high risk for heart disease had lower blood pressure after drinking non-alcoholic red wine every day for four weeks, according to a new study in the American Heart Association journal Circulation Research.

09 sept 2012--Non-alcoholic red wine increased participants' levels of nitric oxide, which helped decrease both systolic and diastolic blood pressure, researchers said. Nitric oxide is a molecule in the body that helps blood vessels relax and allows more blood to reach your heart and organs.

Researchers studied 67 men with diabetes or three or more cardiovascular risk factors who ate a common diet plus one of the following drinks: about 10 ounces of red wine, non-alcoholic red wine or about 3 ounces of gin. All of the men tried each diet/beverage combination for 4 weeks.

The red wine and nonalcoholic wine contained equal amounts of polyphenols, an antioxidant that decreases blood pressure.

During the red wine phase, the men had very little reduction in blood pressure and there was no change while drinking gin. However, after drinking non-alcoholic red wine, blood pressure decreased by about 6mmHg in systolic and 2mmHg in diastolic blood pressure—possibly reducing the risk of heart disease by 14 percent and stroke by as much as 20 percent.

Researchers concluded that the alcohol in red wine weakens its ability to lower blood pressure. But polyphenols—still present after alcohol is removed from wine—are likely the beneficial element in wine.

Provided by American Heart Association

Is it the alcohol or polyphenols in red wine that decreases cardiovascular disease?

Observational epidemiologic studies relating wine and alcohol to health all suffer from the fact that they, of necessity, compare people who prefer certain beverages, but not the beverages themselves. While there have been many intervention trials in animals, randomized trials in humans are less common. Randomized crossover trials, in which each subject receives all interventions in sequence, can be especially important as they tend to avoid baseline differences among subjects and can detect effects of different interventions with smaller numbers of subjects.

23 jan 2012--This study by Chiva-Blanch G et al, just published in the American Journal of Clinical Nutrition, included 67 male volunteers in Spain who were considered to be at "high-risk" of cardiovascular disease on the basis of increased BMI, smoking, diabetes, hypertension, or other risk factors. About one half of the individuals were taking ACE inhibitors, statins, aspirin, and/or oral hypoglycemic drugs, so the results of this study may be especially relevant for patients in the real world.

The subjects agreed to not consume any alcohol for a baseline period, then for three one-month periods consumed 30 g/day of alcohol as red wine or as gin, or an equivalent amount of phenolics from dealcoholized red wine. The polyphenol contents of the RW and the DRW interventions were the same. A very high degree of compliance of the subjects with the assigned interventions is evidenced by results of counting numbers of empty bottles of the intervention beverage returned, dietary records, urinary metabolites, etc. Further, there is good evidence that there were no important changes between periods in diet or exercise habits. The effects of each intervention on a large number of adhesion molecules and chemokines that affect inflammation and relate to the development of vascular disease were evaluated.

The key results of the study were that both ethanol and nonalcoholic compounds in red wine have potentially protective effects that may reduce the risk of vascular disease. Specifically, the authors conclude that "the phenolic content of red wine may modulate leukocyte adhesion molecules, whereas both ethanol and polyphenols of red wine may modulate soluble inflammatory mediators in patients at high risk of cardiovascular disease."

Specific comments on the study: Most reviewers considered this to be a well-done, comprehensive study. As one reviewer commented: "This is an excellent paper. The results strongly indicate an effect of wine polyphenols on inflammation (in broad and modern terms) and this is just what we expect from the biochemistry and nutritional effects of fruits and vegetables. The effect of ethanol, on the other hand, likely fits a hormetic mechanism, where low doses regularly supplied are protective while high doses in a single shot are worsening the progression of disease." Another reviewer added: "We need more information on separating the effects of beer, wine, and various types of spirits. Some spirits like brandy and whisky can have useful antioxidant effects, so distinguishing effects among different types of beverages may be informative."

Another Forum reviewer commented: "This is a very interesting paper that goes a way towards answering the question whether it is the alcohol or polyphenols in red wine that confer the health benefits. The trial was well conducted and controlled, with very detailed analyses. It would have been interesting to analyse any changes in conventional risk factors after the interventions. It would also have been interesting in the study to determine the effects on vascular function by, for example, brachial artery activity (flow mediated dilatation)."

Given that the effects of both alcohol and polyphenols on physiologic factors (e.g., platelet function, fibrinolysis) are transient, generally lasting for no more than 24 hours, it was appropriate that the subjects in this study were instructed to consume the intervention substance (RW, gin, DRW) on a daily basis. When drinking is moderate, there is no evidence that having "alcohol-free days" is beneficial to health. Indeed, most epidemiologic studies show better health effects from daily consumption rather than from drinking on a few days per week.

Concerns about the present study: One Forum reviewer stated: "This appears to be a carefully designed and well executed study, but I have four concerns: (1) The study has been undertaken in high-risk individuals, more than half of whom are hypertensive, a quarter dyslipidaemic, and a quarter diabetic. It is not described what happened to the conventional risk factors during the interventions. (For example, any improvement in inflammatory markers may have come at the cost of higher blood pressure with the alcohol interventions.) (2) Was there any weight change that could have confounded any of the outcomes? (3) Both polyphenol and alcohol biomarkers were measured – did the change in these biomarkers correlate with the changes in any of the inflammatory markers; i.e., any suggestion of a dose response relationship? (4) Even though at least 30 outcome variables were assessed, the authors do not describe any correction for multiple comparisons."

Another Forum reviewer: "This is a well conducted study, and adds to our understanding of the potential cardiovascular benefits of alcohol and the non-alcoholic compounds of alcoholic beverages. However, in this study more than one-half of the high-risk subjects consumed drugs with known anti-inflammatory effects, which could be a confounding factor. The anti-inflammatory effects of these pharmaceuticals may be responsible for the beneficial results, and may not be related to the RW, DRW and gin interventions." However, others think that this concern is unlikely to be important since this was a crossover study, and there were no changes in lifestyle or medication use between the intervention periods.

The key results of the study were that both ethanol and nonalcoholic compounds in red wine have potentially protective effects that may reduce the risk of vascular disease. Specifically, the authors conclude that "the phenolic content of red wine may modulate leukocyte adhesion molecules, whereas both ethanol and polyphenols of red wine may modulate soluble inflammatory mediators in patients at high risk of cardiovascular disease." Thus, this study provides important new mechanistic evidence that the reduced risk of cardiovascular disease among red wine drinkers observed in most epidemiologic studies may result from a combination of both the alcohol and the polyphenols in the wine.

More information: Chiva-Blanch G, Urpi-Sarda M, Llorach R, Rotches-Ribalta M, Guillèn M, Casas R, Arranz S, Valderas-Martinez P, Portoles O, Corella D, Tinahones F, Lamuela-Raventos RM, Andres-Lacueva C, Estruch R. Differential effects of polyphenols and alcohol of red wine on the expression of adhesion molecules and inflammatory cytokines related to atherosclerosis: a randomized clinical trial. Am J Clin Nutr 2012. doi: 10.3945/ajcn.111.022889

Provided by Boston University Medical Center

First clinical trial of red wine ingredient shows metabolic shifts

When obese men take a relatively small dose of resveratrol in purified form every day for a month, their metabolisms change for the better. In fact, the effects appear to be as good for us as severe calorie restriction. Resveratrol is a natural compound best known as an ingredient in red wine.

04 nov 2011--"We saw a lot of small effects, but consistently pointing in a good direction of improved metabolic health," said Patrick Schrauwen of Maastricht University in The Netherlands.

The findings in the November issue of the Cell Press journal Cell Metabolism are the first to report the clinical effects of resveratrol.

Earlier studies in animals had shown that resveratrol alleviates insulin resistance and protects against the ill effects of a high-fat diet, among other benefits, he explained. The effects are comparable to what happens when animals or humans significantly restrict the number of calories they consume, a diet plan shown to delay the onset of age-related diseases. Still, no studies had systematically examined the metabolic effects of resveratrol in humans.

To fill that gap, the researchers gave 11 obese but otherwise healthy men a dietary supplement containing 150 milligrams of a 99 percent pure trans-resveratrol (trade name resVida) for 30 days while they measured the amount of energy they expended, the amount of fat they were storing and burning, and more.

The data show that, like calorie restriction, resveratrol supplements lower energy expenditure and improve measures of metabolism and overall health. Those changes include a lower metabolic rate, less fat in the liver, lower blood sugar levels and a drop in blood pressure. Trial participants also experienced changes in the way their muscles burned fat.

"The immediate reduction in sleep metabolic rate was particularly striking," Schrauwen said. Of course, in the case of obesity, it's not entirely clear whether burning fewer calories is a good or a bad thing. It does suggest that participants' cells were operating more efficiently, as they do following calorie restriction.

Those metabolic effects of resveratrol also came with no apparent side effects.

Schrauwen said they chose to study obese individuals given their increased risk for type 2 diabetes. In future studies, he hopes to explore the effects of resveratrol in people who have already progressed to diabetes.

ResVida and other resveratrol supplements are already widely available, but more work is needed to establish whether they indeed have the potential to overcome the metabolic aberrations associated with obesity and aging, according to the researchers.

"I don't see a reason for particular caution, but we do need long-term studies," Schrauwen says.

Provided by Cell Press

Moderate drinking, especially wine, associated with better cognitive function

21 aug 2010--A large prospective study of 5033 men and women in the Tromsø Study in northern Norway has reported that moderate wine consumption is independently associated with better performance on cognitive tests. The subjects (average age 58 and free of stroke) were followed over 7 years during which they were tested with a range of cognitive function tests. Among women, there was a lower risk of a poor testing score for those who consumed wine at least 4 or more times over two weeks in comparison with those who drink <>

It has long been known that "moderate people do moderate things." The authors state the same thing: "A positive effect of wine . . . could also be due to confounders such as socio-economic status and more favourable dietary and other lifestyle habits.

The authors also reported that not drinking was associated with significantly lower cognitive performance in women. As noted by the authors, in any observational study there is the possibility of other lifestyle habits affecting cognitive function, and the present study was not able to adjust for certain ones (such as diet, income, or profession) but did adjust for age, education, weight, depression, and cardiovascular disease as its major risk factors.

The results of this study support findings from previous research on the topic: In the last three decades, the association between moderate alcohol intake and cognitive function has been investigated in 68 studies comprising 145,308 men and women from various populations with various drinking patterns. Most studies show an association between light to moderate alcohol consumption and better cognitive function and reduced risk of dementia, including both vascular dementia and Alzheimer's Disease.

Such effects could relate to the presence in wine of a number of polyphenols (antioxidants) and other micro elements that may help reduce the risk of cognitive decline with ageing. Mechanisms that have been suggested for alcohol itself being protective against cognitive decline include effects on atherosclerosis ( hardening of the arteries), coagulation ( thickening of the blood and clotting), and reducing inflammation ( of artery walls, improving blood flow).

###

Study source: Arntzen KA, Schirmer H, Wilsgaard T, Mathiesen EB. Moderate wine consumption is associated with better cognitive test results: a 7 year follow up of 5033 subjects in the Tromsø Study. Acta Neurol Scand 2010; Suppl 190:23-29.

New Hints Seen That Red Wine May Slow Aging

By NICHOLAS WADE
05 june 2008--Red wine may be much more potent than was thought in extending human lifespan, researchers say in a new report that is likely to give impetus to the rapidly growing search for longevity drugs.
The study is based on dosing mice with resveratrol, an ingredient of some red wines. Some scientists are already taking resveratrol in capsule form, but others believe it is far too early to take the drug, especially using wine as its source, until there is better data on its safety and effectiveness.
The report is part of a new wave of interest in drugs that may enhance longevity. On Monday, Sirtris, a startup founded in 2004 to develop drugs with the same effects as resveratrol, completed its sale to GlaxoSmithKline for $720 million.
Sirtris is seeking to develop drugs that activate protein agents known in people as sirtuins.
“The upside is so huge that if we are right, the company that dominates the sirtuin space could dominate the pharmaceutical industry and change medicine,” Dr. David Sinclair of the Harvard Medical School, a co-founder of the company, said Tuesday.
Serious scientists have long derided the idea of life-extending elixirs, but the door has now been opened to drugs that exploit an ancient biological survival mechanism, that of switching the body’s resources from fertility to tissue maintenance. The improved tissue maintenance seems to extend life by cutting down on the degenerative diseases of aging.
The reflex can be prompted by a faminelike diet, known as caloric restriction, which extends the life of laboratory rodents by up to 30 percent but is far too hard for most people to keep to and in any case has not been proven to work in humans.
Research started nearly 20 years ago by Dr. Leonard Guarente of the Massachusetts Institute of Technology showed recently that the famine-induced switch to tissue preservation might be triggered by activating the body’s sirtuins. Dr. Sinclair, a former student of Dr. Guarente, then found in 2003 that sirtuins could be activated by some natural compounds, including resveratrol, previously known as just an ingredient of certain red wines.
Dr. Sinclair’s finding led in several directions. He and others have tested resveratrol’s effects in mice, mostly at doses far higher than the minuscule amounts in red wine. One of the more spectacular results was obtained last year by Dr. John Auwerx of the Institute of Genetics and Molecular and Cellular Biology in Illkirch, France. He showed that resveratrol could turn plain vanilla, couch-potato mice into champion athletes, making them run twice as far on a treadmill before collapsing.
The company Sirtris, meanwhile, has been testing resveratrol and other drugs that activate sirtuin. These drugs are small molecules, more stable than resveratrol, and can be given in smaller doses. In April, Sirtris reported that its formulation of resveratrol, called SRT501, reduced glucose levels in diabetic patients.
The company plans to start clinical trials of its resveratrol mimic soon. Sirtris’s value to GlaxoSmithKline is presumably that its sirtuin-activating drugs could be used to treat a spectrum of degenerative diseases, like cancer and Alzheimer’s, if the underlying theory is correct.
Separately from Sirtris’s investigations, a research team led by Tomas A. Prolla and Richard Weindruch, of the University of Wisconsin, reports in the journal PLoS One on Wednesday that resveratrol may be effective in mice and people in much lower doses than previously thought necessary. In earlier studies, like Dr. Auwerx’s of mice on treadmills, the animals were fed such large amounts of resveratrol that to gain equivalent dosages people would have to drink more than 100 bottles of red wine a day.
The Wisconsin scientists used a dose on mice equivalent to just 35 bottles a day. But red wine contains many other resveratrol-like compounds that may also be beneficial. Taking these into account, as well as mice’s higher metabolic rate, a mere four, five-ounce glasses of wine “starts getting close” to the amount of resveratrol they found effective, Dr. Weindruch said.
Resveratrol can also be obtained in the form of capsules marketed by several companies. Those made by one company, Longevinex, include extracts of red wine and of a Chinese plant called giant knotweed. The Wisconsin researchers conclude that resveratrol can mimic many of the effects of a caloric-restricted diet “at doses that can readily be achieved in humans.”
The effectiveness of the low doses was not tested directly, however, but with a DNA chip that measures changes in the activity of genes. The Wisconsin team first defined the pattern of gene activity established in mice on caloric restriction, and then showed that very low doses of resveratrol produced just the same pattern.
Dr. Auwerx, who used doses almost 100 times greater in his treadmill experiments, expressed reservations about the new result. “I would be really cautious, as we never saw significant effects with such low amounts,” he said Tuesday in an e-mail message.
Another researcher in the sirtuin field, Dr. Matthew Kaeberlein of the University of Washington in Seattle, said, “There’s no way of knowing from this data, or from the prior work, if something similar would happen in humans at either low or high doses.”
A critical link in establishing whether or not caloric restriction works the same wonders in people as it does in mice rests on the outcome of two monkey trials. Since rhesus monkeys live for up to 40 years, the trials have taken a long time to show results. Experts said that one of the two trials, being conducted by Dr. Weindruch, was at last showing clear evidence that calorically restricted monkeys were outliving the control animals.
But no such effect is apparent in the other trial, being conducted at the National Institutes of Health.
The Wisconsin report underlined another unresolved link in the theory, that of whether resveratrol actually works by activating sirtuins. The issue is clouded because resveratrol is a powerful drug that has many different effects in the cell. The Wisconsin researchers report that they saw no change in the mouse equivalent of sirtuin during caloric restriction, a finding that if true could undercut Sirtris’s strategy of looking for drugs that activate sirtuin.
Dr. Guarente, a scientific adviser to Sirtris, said the Wisconsin team only measured the amount of sirtuin present in mouse tissues, and not the more important factor of whether it had been activated.
Dr. Sinclair said the definitive answer would emerge from experiments, now under way, with mice whose sirtuin genes had been knocked out. “The question of how resveratrol is working is an ongoing debate and it will take more studies to get the answer,” he said.
Dr. Robert E. Hughes of the Buck Institute for Age Research said there could be no guarantee of success given that most new drug projects fail. But, he said, testing the therapeutic uses of drugs that mimic caloric restriction is a good idea, based on substantial evidence.