In the news: Recent Resveratrol Research: Rethinking High Dose Supplementation

Reducing Calories, Increasing Lifespan?

Calorie restriction – reducing calories while maintaining adequate nutrient intake – has long been studied as a potential way to increase lifespan and reduce the risk of developing chronic diseases. So far, the two long-term studies in monkeys designed to test the effects of calorie restriction have produced seemingly contradictory results.

One of the studies reported last year that calorie restriction appears to work in these primates, while interim results from the other study cast some doubts on the ability of calorie restriction to prolong lifespan. The second study is still ongoing, however, and researchers from both studies are working together to understand the discrepancies in their findings.

While the jury is still out on calorie restriction in monkeys – and humans, too, there are a number of ways that calorie restriction may be of biological benefit: a lower production of free radicals, less chronic inflammation and better repair of damaged DNA genetic material for instance.

Resveratrol May Mimic Calorie Restriction

Over the last decade, researchers have been looking for nutrients that can mimic the effects of calorie restriction. It was proposed that sirutins – proteins that regulate important biological pathways, might underlie some of the effects of calorie restriction by influencing processes like inflammation, energy efficiency, and resistance to stress.

In 2003, a Harvard team discovered that very large amounts of resveratrol might activate production of sirutin 1 in yeast (with additional findings published in 2013). Since the discovery, a few pilot studies conducted in humans – testing resveratrol at doses of 200 mg or higher – have reported some potentially beneficial effects, though results have sometimes been conflicting.

Fundamental New Findings on Resveratrol

Enter a research team from Scripps Research Institute who have proposed a new way that resveratrol might work. Their discovery (1), published in the journal Nature, suggests that resveratrol activates a protective stress response in human cells through a pathway involving an enzyme (TyrRS), and at concentrations much lower – just a fraction of the resveratrol levels tested in prior studies, including those focused on sirutins.

According to the authors, it’s conceivable that drinking moderate amounts of red wine would give a person enough resveratrol to spur a protective effect via this pathway. Red wines typically contain a range of 0.3-2.0 mg per 5 oz glass.

Resveratrol & Grape Extract in Heart Disease

Other researchers have looked at the effects of modest supplemental levels of resveratrol, finding that it works synergistically when combined with the other polyphenols found in grapes.

In one study, men with type 2 diabetes, stable hypertension and coronary heart disease were assigned to take 350 mg whole grape extract (lacking resveratrol), the extract with 8 mg added resveratrol, or placebo for 1-yr in a triple-blind randomized trial. Compared to placebo, grape extract lowered 1 pro-inflammatory compound (a cytokine), while the enriched extract lowered 3 additional key inflammatory compounds (2).

In an earlier year long trial (3), patients with type 2 diabetes or at high risk of heart disease and already on statins were assigned to the treatments described above. In contrast to placebo and grape extract, the resveratrol-rich extract significantly lowered markers of inflammation and improved patients’ fibrinolytic status (helping to prevent blood clots from growing and becoming a problem).

What’s the take home message? While the quest for a fuller understanding of how resveratrol works continues, sit back and enjoy some red wine!

References

1. Sajish M, et al. A human tRNA synthetase is a potent PARP-1 activating effector target for resveratrol. Nature [Epub ahead of print] Dec 22, 2014.
2. Tomé J, et al. One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes & hypertensive patients with coronary artery disease. Pharmacol Res 72: 69-82, 2013.
3. Tomé-Carneiro J, et al. One-year consumption of a grape nutraceutical containing resveratrol improves the inflammatory and fibrinolytic status of patients in 1° prevention of cardiovascular disease. Am J Cardiol 110: 356-63, 2012.