Nature Medicine | Spoonful of Medicine

Small resveratrol trial shows metabolic benefits, and might give hope to drug developers

resVida.jpg

A small study has lent much hoped-for support to the idea that resveratrol — a natural organic compound found in red wine — can positively affect the metabolism of obese individuals through the activation of the sirtuin-1 gene. These findings give new hope to pharmaceutical drug developers that have been stymied by years of debate about the compound’s efficacy and how exactly it works.

Last year, GlaxoSmithKline-owned Sirtris Pharmaceuticals, based in Cambridge, Massachusetts, abandoned its resveratrol-based drug SRT501 designed to treat multiple myeloma, after kidney failure was seen in patients involved in their phase 2 trial of the compound. Other trials seeking to show its ability to aid weight-loss have similarly fumbled, and researchers had a tough time demonstrating that it acted on the sirtuin-1 gene as purported.

The new study, published today in Cell Metabolism, involved 11 obese men, who received resVida, a resveratrol pill produced by DSM Nutritional Products and widely available as a supplement. Study author Patrick Schrauwen from the University of Maastricht in the Netherlands and his colleagues measured the volunteers’ liver fat and blood sugar, among other things. After taking resVida, the 11 participants experienced a drop in levels of liver fat and blood glucose. Systolic blood pressure also fell by 4% compared with the participants’ blood pressure when on the placebo pill.

Notably, while participants didn’t lose weight, protein analysis indicated that resveratrol increased sirtuin-1 levels and improved mitochondrial function, mirroring the metabolic effects of exercise and restricted calorie intake.


“The results were much more positive than we expected,” says Schrauwen. “Long term [results] will show the sustained health benefits, but this is a very promising start.”

The study is the first to show that resveratrol targets and activates sirtuin-1 in human muscle cells — a pathway that several drug developers are targeting with their current pipeline drugs. “I believe [GSK] is aiming at the same pathway, so I imagine this is good news for them and other pharmaceuticals,” says Schrauwen.

GSK’s Sirtris recently completed a phase 2 trial of its small molecule drug SRT2104, which, like resveratrol, works by activating sirtuin-1 and modulates metabolic markers in type 2 diabetes patients.

The findings of the new study validate what scientists have seen in animal testing, according to Rafael de Cabo, a researcher at the US National Institutes of Health who studies aging. “I was very excited when I read this paper,” says de Cabo. “I think it’s a fantastic stepping stone to looking at improving health in obese individuals.”

Image Credit: DSM Nutritional Products

Comments

  1. Report this comment

    Trent Nichols said:

    Chronic inflammation and antioxidant property in Resveratrol

    Obesity is associated with chronic low-grade inflammation with an abnormal production of proinflammatory cytokines such as TNF-alpha in adipose tissue and muscle. Investigators in Milan found that TNF-alpha down-regulated e NOS with a concomitant reduction of mitochondrial biogenesis and function in white and brown adipose tissue and soleus muscle of 3 different animal models of obesity.

    Adipose tissue IL-6 expression is increased in obesity and is a strong predictor of abnormalities in adipocyte and systemic metabolism. A study demonstrated that IL-6 impairs insulin signaling in both 3T3-L1 model of adipocyte model system and human adipocytes.

    Dick and Davidge at the University of Alberta published in Diabetes in 2011 that by administering Resveratrol to young offspring of lab rats after weaning, the metabolic syndrome was prevented.

    Resveratrol was demonstrated to inhibit the over expression of the inflammatory factors TNF alpha, Il- beta and IL-6 in an experimental mice model by Li J, Wang S and associates recently. Resveratrol also modulates adipokine expression and improves insulin sensitivity in adipocytes, relative to inhibition of the inflammatory response as reported by Kang L, Hang W et al. In Biochimie 2010.