Resveratrol appears to make fat men fitter

The plant extract resveratrol, found in red wine, has been found to improve… (Evans Caglage/Dallas Morning News/MCT)

November 03, 2011|By Melissa Healy, Los Angeles Times / For the Booster Shots blog

The first clinical trial to test the effects of resveratrol -- the plant compound plentiful in red wine and grapes -- on humans has found that a small daily dose of a purified resveratrol supplement lowered blood pressure and improved a wide range of human health measures in a small group of obese men.

The study, conducted in the Netherlands and published this week in the journal Cell Metabolism, found that men taking 150 milligrams of resveratrol daily for 30 days looked for all the world as if they were either dieting successfully or were engaged in endurance training. (That dose is about the equivalent of the resveratrol in 100 glasses of red wine, so don't pull that cork just yet.)

Without changing their diet or exercise habits, the mens' metabolic function improved, evidence of inflammation declined, fat deposits in their livers decreased and circulating triglyceride levels fell. While their bodies burned up the same amount of energy over a 24-hour period, their bodies' resting and sleeping metabolic rate declined and their muscles' use of fuel became more efficient -- signs that they were using and storing calories more like athletes in training than obese couch potatoes.

There was just one incongruity in the picture researchers gleaned from the clinical tests of the men taking resveratrol: although clearly healthier, they were not losing weight.

The first of roughly a dozen human clinical trials of resveratrol, the Dutch study suggested that the plant extract may provide obese people some protection from the health consequences of their extra poundage, including elevated risks of type-2 diabetes, high blood pressure, heart disease, certain cancers and dementia. Virtually all of those conditions are linked to factors that responded favorably to resveratrol in the current study, including inflammation, metabolic disturbance and high levels of circulating glucose and triglycerides.

Resveratrol has earned an almost mythic reputation as a life-extending agent, despite the fact its benefits have largely been demonstrated in animal and test-tube studies. Dietary supplement manufacturers aggressively market the plant extract in a wide range of doses (including some far higher than that used in the Dutch trial), although its long-term safety and effective dosages have not been established by human trials.

Still, the promise of resveratrol -- both as a nutritional supplement and a model for future disease-fighting medications -- has excited widespread interest among researchers. Currently, about 25 clinical trials are recruiting or already underway to test resveratrol's effectiveness against diseases as diverse as colon cancer, diabetes, Alzheimer's disease, cardiovascular disease, melanoma and multiple myeloma.

The 11 participants in the Dutch study were obese but otherwise healthy men, who served as their own control group. A participant who took a placebo supplement for 30 days would wait a month and then take a resveratrol supplement for 30 days. Another who took resveratrol first would get a placebo after a month's "wash-out" period. The 150-milligram dose given to the men was actually much smaller, pound for pound, than doses routinely given to mice in past experiments, yet yielded similar blood concentrations of the plant extract.

The men were given a broad panel of routine clinical tests each week in an effort to detect adverse reactions. There were none, the researchers reported.

"Although most of the effects we observed were modest, they were very consistently pointing toward beneficial metabolic adaptations," wrote the authors, whose study was underwritten by TI Nutrition, a public-private research partnership of food manufacturers, universities and the Dutch government. They added that future studies should test the long-term safety of resveratrol supplementation, as well as whether better results could safely be gained at lower or higher dosages than 150 milligrams.

Alzheimer's disease researcher Philippe Marambaut of the Feinstein Institute for Medical Research in Long Island, N.Y., called the findings "very promising." Marambaut, who was not involved in the current study, said the beneficial metabolic effects appeared "impressive," and added that "they will certainly motivate additional clinical trials for other conditions associated with a deregulated metabolism, such as diabetes or some age-related neurodegenerative conditions like Alzheimer's disease."

25 clinical trials

Battling inflammation, disease through food

Though it's an emerging field, proponents of anti-inflammatory diets point to growing evidence that foods like vegetables and fish can ease an overactive immune system.

If you want to live longer -- avoid heart disease, Alzheimer's disease and cancer -- then pick and choose your foods with care to quiet down parts of your immune system.

That's the principle promoted by the founders and followers of anti-inflammatory diets, designed to reduce chronic inflammation in the body.

Dozens of books filled with diets and recipes have flooded the market in the last few years, including popular ones by dermatologist Dr. Nicholas Perricone and Zone Diet creator Barry Sears.

Those who frequent message boards that discuss arthritis or acne trade tips on which pro- or anti-inflammatory foods may help or trigger their symptoms -- urging co-sufferers to try cherries for their rheumatoid arthritis or avoid gluten for their psoriasis.

But proponents claim the benefits go far beyond that, fighting not just pain from inflamed joints or skin flare-ups but also life-threatening diseases.

"If your future currently looks bleak because of high levels of silent inflammation, don't worry, because you can change it within thirty days," Barry Sears promises in his book, "The Anti-Inflammation Zone."

There's still a lot of science to be done. And should you try such a diet, you probably shouldn't expect any 30-day miracles. But there may be something to eating in an anti-inflammatory way.

"[Chronic inflammation] is an emerging field," says Dr. David Heber, a UCLA professor of medicine and director of the university's Center for Human Nutrition. "It's a new concept for medicine."

The point of an anti-inflammation diet is not to lose weight, although it is not uncommon for its followers to shed pounds. The goal: to combat what proponents call "chronic silent inflammation" in the body, the result of an immune system that doesn't know when to shut off.

The theory goes that long after the invading bacteria or viruses from some infection are gone, the body's defenses remain active. The activated immune cells and hormones then turn on the body itself, damaging tissues. The process continues indefinitely, occurring at low enough levels that a person doesn't feel pain or realize anything is wrong. Years later, proponents say, the damage contributes to illnesses such as heart disease, neurological disorders like Alzheimer's disease or cancer.

In general terms, following an anti-inflammatory diet means increasing intake of foods that have anti-inflammatory and antioxidant properties. (Antioxidants reduce the activity of tissue-damaging free radicals at sites of inflammation.) The diet includes vegetables, whole grains, nuts, oily fish, protein sources, spices such as ginger and turmeric and brightly colored fruits such as blueberries, cherries and pomegranates.

Foods that promote inflammation -- saturated fats, trans fats, corn and soybean oil, refined carbohydrates, sugars, red meat and dairy -- are reduced or eliminated.

It would seem logical that a diet that could dampen an overactive immune system could help prevent or slow diseases that are caused or exacerbated by inflammation. And evidence is certainly mounting that such diseases include heart disease, cancer and Alzheimer's. (See related story online.)

Studies with animals suggest that the diet's followers may be on to something.

"If you feed rodents different diets, you can very strongly modulate inflammation," says Dr. Andrew Greenberg, the director of the Obesity and Metabolism Laboratory at the Human Nutrition Research Center on Aging at Tufts University in Boston. "Fish oil, for example, ameliorates inflammation in rodents."

Resveratrol, found in grape skin and red wine, has been shown to improve blood vessel function and slow aging in rats.

Pomegranate juice decreases atherosclerosis development in mice with high cholesterol. Garlic improves blood vessel functioning in the hearts of rats with high blood pressure.

And curcumin (an antioxidant chemical found in turmeric) improves ulcerative colitis, rheumatoid arthritis and pancreatitis in mice and has anti-cancer effects in the animals too.

Curcumin has also been shown to ease the symptoms of rheumatoid arthritis in people, reducing joint swelling, morning stiffness and walking time. In India, turmeric is used to promote wound healing and reduce inflammation. But though curcumin's effects are being tested in several clinical trials addressing various diseases, rigorous human results are lacking -- as is the case for most anti-inflammatory foods.

Large, careful human clinical trials are expensive and few have been designed to test dietary interventions. Small trials on individual supplements have been done, though. And scientists have learned a lot from studying populations -- chronicling the natural habits of people and seeing what diseases they get and which they don't.

The drug factor

It makes sense that anti-inflammatory diets might help the heart, says Dr. Robert H. Eckel, a past president of the American Heart Assn. and professor of physiology and biophysics at University of Colorado Denver's Health Sciences Center.