Resveratrol-Based Drug Pulled from Clinical Trials
Compound had little effect on cancer patients and aggravated kidney issues
Stephanie Cain
GlaxoSmithKline has halted the development of SRT501, an experimental drug based on resveratrol, but that doesn’t mean the pharmaceutical firm is no longer developing medicines based on the compound.
Glaxo announced last week that it would be halting all trials of the drug, after SRT501 failed to make a significant impact on patients with cancer and even aggravated some kidney problems. “Resveratrol, which is the main ingredient of SRT501, has been studied extensively and shows multiple beneficial effects in animals,” said Melinda Stubbee, director of research and development communications at GlaxoSmithKline. “Unfortunately, the doses of this compound that have been shown to be beneficial in [animals] are relatively impractical in human studies.”
The health benefits of resveratrol have been the focus of multiple studies in recent years. Researchers discovered that the compound, found in grapes as well as other foods such as peanuts, blueberries and cranberries, can extend the lifespan of mice while protecting them from several diseases. The compound is part of the grapevine’s immune system and helps fight off invaders. Since it’s absorbed into red wine during the fermentation process, researchers have debated whether resveratrol is at least partially responsible for wine’s health benefits. Some of the first experimental drugs based on resveratrol were developed by Sirtris, a Massachusetts-based company. The results looked promising enough that Glaxo snapped the company up for $720 million in 2008.
GlaxoSmithKline recently reviewed the trial studies of SRT501, noting that after comprehensive analysis, the drug was found to be only minimally effective. Further, they reviewed the cases of renal failure in study patients. While the kidney complications were due to the underlying disease, not the drug, the drug’s side effects indirectly led to dehydration, which accelerated kidney failure.
However, GlaxoSmithKline is not discontinuing all work on resveratrol-based drugs. Stubbee explained that the company is now focusing efforts on synthetic molecules that activate the same proteins inside cells that resveratrol activates. “Currently we have two of these latest generation compounds, SRT2104 and SRT2379, in several exploratory clinical trials,” Stubbee said. “The compounds have no chemical relationship to SRT501 and more favorable drug-like properties.”
Fish with Wine: The Perfect Pairing for Heart Health?
Scientific review finds wine optimizes digestion of omega-3 fatty acids
Jacob Gaffney
Finding the perfect wine to match with fish may be challenging, but a team of French scientists has found that the pairing is worth the effort. A comprehensive review of recent research on wine and fish shows that the drink helps break down omega-3 fatty acids abundant in many types of seafood. This helps keep heart tissue stronger and healthier.
The study, published recently in the journal Current Pharmaceutical Biotechnology, found that hearts of those who regularly consume wine and omega-3 fatty acids have 20 percent more heart tissue, indicating a cardiovascular system that regenerates with regularity. The human heart contracts an average of 100,000 times every 24 hours. So its ability to rebuild is key to maintaining that constant rhythm.
The study authors work at two medical universities in France and are led by Joel de Leiris of the Heart and Nutrition research group at Joseph Fourier University. De Leiris previously worked with French cardiovascular researcher Dr. Michel de Lorgeril of Grenoble University on a 2008 study that found a beneficial cardiovascular link between wine and fish consumption. In that study, the team found that moderate consumers of alcohol had higher levels of omega-3 in their bodies compared to nondrinkers, despite consuming similar amounts of seafood.
The new study digs deeper. By analyzing data from 84 independent studies, de Leiris’ team found lower rates of heart disease among those who ate fish and drank wine regularly. "Interactions between wine consumption and the metabolism of [omega-3] polyunsaturated fatty acids might substantially contribute to the cardioprotective effect of regular and moderate wine drinking," the text read. The optimal amount of wine, they report, is around two to four glasses per day paired with fish high in omega-3 fatty acids, particularly cold water fish with oily, fatty flesh, such as anchovies, herring and mackerel. They add that the choice of wine should not greatly impact the heart benefits, but that beer and spirits drinkers are unlikely to see similar benefits.
Moderate Drinking Linked to Longer Lives, But Is It the Wine?
Two studies ask if alcohol has health benefits or if moderate drinkers have healthier lifestyles
Jacob Gaffney
Numerous studies have found a link between drinking alcohol in moderation and living a longer life. The common interpretation is that the drink itself is behind the results, that either a balanced amount of alcohol or the polyphenols found in red wine provide health benefits.
But a new study asks whether it’s the drinks or the person’s medical history that’s responsible. A team at the University of Texas found that past behavior versus current lifestyle decisions may help explain why moderate drinking is so beneficial later in life, compared to abstention or heavy drinking.
In research slated to be published in the November 2010 issue of Alcoholism: Clinical & Experimental Research, lead researcher Dr. Charles Holahan of the University of Texas at Austin and colleagues looked at outpatient data from 1,142 men and 682 women, aged 55 to 65 years, and followed them for 20 years, recording causes of death and other data. At the end they found that, compared to moderate drinkers, patients who abstained from alcohol had more than double the estimated mortality risk, while heavy drinkers and light drinkers had a 70 percent and a 23 percent higher mortality risk, respectively.
A large portion of the subjects who abstain from drinking admitted to prior problems with alcohol and/or poorer health habits. Lifetime moderate drinkers, they found, use alcohol less as a coping agent and more as a social lubricant. They also tend to exercise more often and had lower rates of obesity.
"Our findings are consistent with an interpretation that an important part of the survival effect for moderate drinking among older adults is explained by confounding factors associated with alcohol abstention," they say in the text. "Alcohol consumption of one or two drinks per day does not appear to increase the risk of cognitive impairment or decline in older adults."
But what of studies that find wine drinkers enjoy an extra benefit, presumably because of antioxidant compounds such as polyphenols found in red wine? The theory that polyphenols provide wine’s benefits has led to a growing supplement industry, with shops selling resveratrol and other polyphenols in pill form.
A recent Dutch study looked at the chemical components found in grapes and found little to support claims that polyphenols such as resveratrol provide cardiovascular benefits when acting alone. "Grapes and wine contain high amounts of polyphenols, but the effects of these have hardly been investigated in isolation," write the researchers from Unilever Research and Development in the August issue of the Journal of Nutrition.
The research team examined 35 healthy males. The men ate low-fat diets and some took daily doses of capsules containing 800 mg of grape polyphenols. The others took a placebo.
Looking at blood flow, an indicator of heart health and overall longevity, the team found that the cardiovascular health of the men did not improve with either the antioxidant capsules or the substitute pills. The scientists write that the polyphenol treatment had "no major impact" on blood flow.
But they expressed doubt over whether their findings relate to wine drinking. "Please keep in mind that we tested only the effect of grape polyphenols provided as supplements," says lead author Linda A. J. van Mierlo. "Wine also contains other substances, such as alcohol."
It may be that the sum of components in wine is stronger than any part. But further research is needed on whether the answer is wine or lifestyle.