Longevity in a pill: are we there yet?

Red wine: the key to longevity?

Since 60 Minutes  aired its recent story about a pill containing a nutrient called reseveratrol that could be the key to longevity, there has been a rush by some in the public to get their hands on this “wonder drug” before it has been properly tested in humans.

Suddenly even Barbra Walters and Dr. Oz are appearing on TV, radio, the internet and elsewhere touting resveratrol as the fountain of youth.

A 1992 60 Minutes spot reported that Dr. Serge Renaud, a scientist from Bordeaux University in France had observed what he called the "French paradox" - that his countrymen had a much lower incidence of heart disease despite the fact that their diets were as high in saturated fat as that of Americans. Renaud felt  the reason had to do with the high consumption of red wine in France.

Though no one at the time actually knew if this was the cause, red wine sales increased by 44% as a result of the story. Over the next few years, studies consistently showed that moderate alcohol consumption was associated with 20-30% reductions in coronary heart disease.

Ultimately, scientists isolated a specific substance in the skin of red wine grapes called resveratrol, a polyphenolic compound (also found in peanuts, spruce, eucalyptus, some Chinese herbs and some berries) and began conducting studies in the laboratory to see if it somehow affected longevity. In numerous studies, resveratrol administration has increased the lifespan of yeast, worms, fruit flies, fish, and mice fed a high-calorie diet. It has also been shown to inhibit the growth of cancer cells in culture and in some animal models. This is all very exciting.

The real question is: does it work in humans?

Despite the fact that a recent Oprah program with Dr. Oz may have given the impression that reseveratrol is the next fountain of youth, currently, no research studies exist supporting resveratrol extending life or preventing cancer in humans, We do know that, assuming the effect in humans is the same as that  seen in the lab, a human would have to drink the equivalent of 1000 bottles of the correct red wine per day which, needless to say, would lead to all sorts of alcohol related diseases in the future.

Scientists are hoping that a very concentrated amount of resveratrol in pill form or perhaps another delivery system (patch or injection) will produce the same benefits they have discovered in rodents and yeast. Finding the answer to that question will take years of properly designed, randomly controlled clinical trails.

So why are claims already being made that resveratrol will extend your life? Herbal supplements such as resveratrol are not regulated by the Food and Drug Administration (FDA) like drugs  (as long as the manufacturer makes no claims about the supplement's ability to treat specific medical conditions). That means that consumers need to beware of potential scams.

Supplements

Most resveratrol supplements available in the U.S. contain extracts of the root of Polygonum cuspidatum, also known as Hu Zhang or kojo-kon. Red wine extracts and red grape extracts containing resveratrol and other polyphenols are also available in the U.S. as dietary supplements. Resveratrol supplements may contain anywhere from 10-50 mg of resveratrol, but the effective doses for chronic disease prevention in humans are not known.

Contradictions, Precautions and Adverse Events:

Estrogen-like effects

Since resveratrol has exhibited estrogen-like properties leading to stimulation of cancer cell proliferation in test tubes and some animal studies, women with estrogen sensitive cancers such as breast, ovarian, and uterine cancers, should probably avoid resveratrol until more research in human subjects are completed.

 Anticoagulant and Antiplatelet Drugs

Resveratrol has been found to inhibit human platelet aggregation in the test tube. Theoretically, high doses could increase the risk of bleeding in humans when taken with anticoagulant drugs, such as warfarin (Coumadin); antiplatelet drugs, such as clopidogrel (Plavix) and dipyridamole (Persantine); and non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, ibuprofen, and others.

Drug Interactions

Resveratrol has been reported to inhibit the activity of an enzyme known as cytochrome P450 3A4 in lab studies. Although this interaction has not been reported in humans, resveratrol could theoretically increase the levels and toxicity of drugs that are known to be metabolized by CYP3A4 such as HMG-CoA reductase inhibitors used to lower cholesterol (atorvastatin, lovastatin, and simvastatin), calcium channel antagonists (felodipine, nicardipine, nifedipine, nisoldipine, nitrendipine, nimodipine, and verapamil), anti-arrhythmic agents (amiodarone), HIV protease inhibitors (saquinivir), immunosuppressants (cyclosporine and tacrolimus), antihistamines (terfenadine), benzodiazepines (midazolam and triazolam), and drugs used to treat erectile dysfunction (sildenafil). Anyone taking these drugs should avoid resveratrol until human clinical trials are complete and show that it is safe.

Pregnancy and Lactation

The safety of resveratrol-containing supplements during pregnancy and lactation has not been established. Since no safe level of alcohol consumption has been established at any stage of pregnancy, pregnant women should avoid consuming wine as a source of resveratrol.

Clinical Trials:

Legitimate scientific clinical trials are being conducted in the US and around the world.

After Harvard researcher Dr. Sinclar, the scientist interviewed by 60 minutes, published several studies showing positive effects of reseveratrol in animals, he set up Sirtris Pharmaceuticals pursuing treatments for diabetes, one of the leading diseases of aging. Sirtris's formulation of resveratrol has been shown in early trials to lower blood sugar and insulin in patients with type 2 diabetes, and the company is entering trials with synthetic sirtuin activators that are up to 1,000 times more potent than resveratrol.

Though 60 to 90 percent of drugs at these stages of testing ultimately fizzle out, GlaxoSmithKline bought Sirtris over the summer for $720 million. "Half a dozen major drug companies are working on sirtuins," said Dr. Christoph Westphal, CEO of Sirtris in a Newsweek article. "Because they affect many diseases of aging, the potential market is huge."

There is a long list of resverotrol clinical trials being conducting at other venues to test resveratrol in patients with various diseases of aging including Alzheimer's and cancer as well as diabetes. See the links below to find them.

Free trials

Because there is no FDA regulation of resveratrol, anyone can manufacture and sell it. Recently, there have been numerous offers of “free trials” popping up. What should you do?

The best advice is to stay clear of claims of “free trials” of the product. There are documented horror stories by consumers who signed up for these “free offers” only to be charged huge fees with no one to contact to get  refunds. There have also been self-reports of side effects such as headaches on various websites, but because these products are not tested in legitimate, supervised clinical trials, there is no database compiling the information.

 Bottom line: Should you try resveratrol for yourself? That’s an individual decision. But before you do, make sure you understand the facts and understand the possible risks.

For more information:

NIH studies 
Two studies funded by NIH looking at resevratrol’s effects on Alzheimer’s Disease:

Randomized Trial of a Nutritional Supplement in Alzheimer’s Disease 
Pilot Study of the Effects of Resveratrol Supplement in Mid-to-Moderate Alzheimer’s Disease 

Another website that lists some studies of resveratrol. Unfortunately, it only lists the studies with no results.

For a fun read:  Multiple award winning Rabbit in the Moon by Deborah & Joel Shlian is an international thriller that asks the question: what if someone in China had discovered the secret of longevity? Who would want such a discovery and what might they do to obtain it? The backdrop of the story is the 7 most tumultuous weeks in recent Chinese history: from the rise of the student democracy movement in April, 1989 to its fall at Tiananmen Square on June 4th.