Can Resveratrol Help Reduce the Negative Effects of Obesity?

A number of animal studies and human clinical trials suggest that resveratrol may be an important supplement to help counteract the serious health risks associated with excess body weight. Obesity is a growing epidemic around the world, and is known to be associated with an increased risk of infection and cancer. And while animal studies have shown that calorie restriction increases lifespan, the increased risk of serious diseases linked to obesity decreases human longevity. In fact, heart disease, cancer, and type-2 diabetes related to obesity account for about 300,000 deaths in the United States alone.^15,89

And now research suggests that in addition to obesity’s negative influence on the development of conditions caused by inflammation and free radical damage, it also has a harmful effect on the immune system.⁸⁹ Obesity adds to the fat deposits normally made in the thymus and accumulate as we age.⁹⁰ This causes the organ to shrink prematurely, resulting in inhibited T-cell production and impaired immune function.⁹⁰

Recent lab, animal, and human research has demonstrated the following connections between obesity, excess body fat, and disease development:

• As mentioned above, obesity negatively affects the immune system by causing a slowing down of thymus functioning and lower T-cell production. Even without type-2 diabetes, middle-aged people suffering from obesity showed significantly accelerated aging in the thymus glands. This was demonstrated by a study showing that lower levels of immune system markers (indicating impaired ability to generate immune T-cells to fight disease and infection) were strongly and negatively correlated to higher BMI. In other words, the higher the BMI, the lower the levels of immune system markers and the greater the potential for impaired immune function and inability to resist disease or infection.⁸⁹
• Abdominal fat is now thought to contribute to the development of insulin resistance.⁹¹ This is possibly because abdominal fat cells do not respond to insulin’s inhibitory effects on the release of fatty acids, the majority of which end up in the liver. This may in turn result in increased production of cortisol,⁹¹ which raises blood glucose levels.⁹²
• Population studies indicate that there is a significant correlation between BMI and thyroid cancer. In a pooled analysis and follow-up with more than 800,000 adults for an average of over 10 years, 768 women and 388 men developed thyroid disease. After accounting for other factors, those who were overweight or obese had a higher risk of thyroid cancer compared to normal-weight adults, with obesity representing a much greater risk for the disease.⁹³

How Does It Work?

Resveratrol has many properties that exert anti-inflammatory and anti-cancer effects. It is also known to help regulate hormones and the immune system. All of these may have a role to play in counteracting the unhealthy effects of obesity. Animal studies suggest that resveratrol may also help by doing the following:

• Activating the sirtuin gene SIRT3, lack of which has been shown in animal studies to negatively impact mitochondrial function in the liver and leads to a number of metabolic effects—including development of a fatty liver.⁹⁴
• Acting as an appetite suppressant.⁴⁴
• Decreasing fat accumulation in the liver and thymus by stimulating AMPK enzyme activity, which could help protect against obesity-related non-alcoholic fatty liver disease and impaired immune functioning.⁹⁰
• Increasing resting metabolic rate.⁴⁴
• Increased metabolic energy expenditure by increasing SIRT1 activity and increasing mitochondrial activity.⁹⁵
• Reducing fatty tissue in the body by lowering levels of lipase, the enzyme in the body that breaks down fats in food so they can be absorbed.⁹⁶ The diet drug orlistat is used to treat obesity and works in a similar fashion by blocking lipase and decreasing fat absorption.⁹⁷
• Stimulating the breakdown of fat while inhibiting the production of fat cells—possibly by activating SIRT1 genes.⁹⁸

Evidence of Benefit

In 2010 a review and analysis of lab and animal studies conducted to assess the effects of resveratrol on obesity and diabetes was published. In terms of body fat, the two studies noted showed that resveratrol reduced body fat in both mice on a high fat diet with oral daily doses of 400 mg/kg of weight for 15 weeks and when delivered via tube to the stomach of obese Zucker rats at daily dosage levels of 10 mg/kg over eight weeks.⁹⁹

Body Fat and Immune System Effect

Animal studies reported elsewhere indicated that adding resveratrol to a high-fat diet helped significantly lower body and thymic weight and reduced body fat in comparison to rats who consumed a high-fat diet without resveratrol. There were also positive measurable effects on T-cell output in the resveratrol-treated rats, despite the high fat intake.⁹⁰

A randomized, controlled animal study demonstrated that daily treatment of 30 mg of resveratrol per kg of body weight performed similarly to orlistat, an anti-obesity drug that inhibits fat absorption from the diet. After six weeks of treatment, examination showed that while the treatment rats did not lose weight, they had significantly less body fat then rats in the control group—even though both had been fed the same fattening diet.⁹⁶

Weight Loss or Comparative Weight Gain

On the other hand, the 2010 review listed five recent controlled animal studies using mice and rats (generally accepted as research models on obesity and weight)—most of which the authors noted as showing no difference in body weight between the animals given resveratrol and the untreated control group.⁹⁹

However, a closer look at the review chart and individual study details revealed the following information, suggesting that higher doses of resveratrol in human diets containing less than 60% fat could very well protect against at least some of the weight gain associated with a high-fat diet:

Differences in dosages per % of fat in diet.

The two studies that are listed as showing that resveratrol resulted in less weight gain on high fat diets used higher doses of resveratrol (20 and 400 mg/kg of animal body weight daily) per % of fat in the high-fat diet mix fed to the animals to induce obesity compared to the other studies listed (two of which showed dosages of 1-10 mg/kg).⁹⁹

Unrealistic amount of dietary fat.

Although one of the studies listed as “unchanged” (meaning resveratrol did not affect weight) used a resveratrol dose averaging 22.4 mg/kg of animal body weight, the animals were fed a diet of 60% fat, compared to the animals given 20 mg/kg of resveratrol on a diet of 40% fat.^95,100 This difference in dietary fat content is significant. In fact, the senior scientist from the company that manufactures the high fat diets used in experimental models notes that a 60% fat diet would be considered extreme in terms of human nutrition, and is typically only used in rodent studies because it allows the animals to quickly gain weight and shorten the experiment time.¹⁰¹ Thus this experimental model may not be a true indicator of the effects of a drug or neutraceutical, and may also present difficulties in preventing or reversing the effects of this extreme diet which may not be present in real-life human circumstances.¹⁰¹

Unreported weight loss.

Details of the three studies indicating no effect on weight from resveratrol actually showed that although the weight differences were not considered significant by the researchers, in all three test the resveratrol-treated groups of animals had lower body weights than the control group fed the same diet and not given resveratrol. This included the experiment where the mice were fed a diet of 60% fat and the one using obese Zucker rats genetically designed without the leptin gene (which controls hunger).^99-100,102

Increased metabolic rate and decreased body fat over time even in regular diets.

Interestingly, one of the studies indicated that resveratrol-supplemented regular diets in normal weight animals resulted in a less weight gain over time than the regular diet, non-obese control group—without any decrease in calorie intake. Further investigation showed that resveratrol supplementation decreased body fat and increased metabolic rates of energy usage.⁹⁵

Recently published data from another study conducted on grey mouse lemurs, which are primates (as are humans) provides additional evidence that resveratrol can improve metabolism and also decrease appetite. Six lemurs were given 200 mg/kg a day of oral resveratrol diet supplements during the four winter weeks these primates typically conserve energy and gain weight. Instead, the lemurs ate 13% less and their resting metabolic rate increased by almost 30%.⁴⁴