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High-dose resveratrol shows heart health for overweight and obese people: Human data

By Stephen Daniells , 13-Nov-2013
Last updated on 19-Nov-2013 at 15:03 GMT

High-dose resveratrol shows heart health for overweight and obese people: Human data

Daily supplements containing resveratrol may reduce the production of compounds responsible for the build-up of cholesterol in the body of overweight and obese people, says a new study.

Results of the small-scale randomized, double-blinded, crossover study indicated that three weeks of supplementation with resveratrol (Transmax, Biotivia) could significantly reduce the production of apolipoprotein B (ApoB), the main apolipoprotein of LDL cholesterol that is responsible for the transport of cholesterol to tissues.

ApoB exists in two forms: ApoB48 and ApoB100 – the former is produced in the small intestine, while the latter is produced in the liver.

“Increased production of triglyceride-rich lipoproteins, in the form of apolipoprotein B (apoB)-100 containing very low-density lipoprotein (VLDL) from the liver and apoB-48 containing chylomicrons [lipids transporting particles] from the gut, in conditions such as overweight/obesity and insulin resistance, may contribute to an increased risk of atherosclerotic disease,” explained researchers from the University of Toronto, Ontario.

“We report that high-dose resveratrol significantly reduced apoB-48 (by 22%) and apoB-100 (by 27%) production rates by the intestine and the liver, respectively, in overweight and obese men with relatively mild hypertriglyceridemia,” they wrote in Arteriosclerosis, Thrombosis, and Vascular Biology .

“This is the first study in humans to demonstrate beneficial effects of resveratrol administration on intestinal and hepatic triglyceride-rich lipoprotein particle production.”

Resveratrol, heart disease & diabetes

The study’s findings were welcomed by Dr James Betz, managing director of Biotivia, the company that produces the Transmax supplement used in the study. Dr Betz told NutraIngredients-USA: “In this quite high dose, relatively short term, human clinical trial resveratrol was shown to reduce the body’s production of low density lipoproteins (LDL) in the intestines and liver of the test subjects. This is important because LDLs are fat particles which are strongly associated with the development of both cardiovascular disease and type-2 diabetes in humans. 

“The findings set forth in this clinical trial are consistent with earlier animal studies which have also shown resveratrol to have a potential application as a chemo-preventative against both heart disease and diabetes, as well as the majority of human clinical trials investigating resveratrol’s potential to prevent metabolic syndrome from evolving into fully-fledged type-2 diabetes.

“In this trial the subjects were obese men, a group that is particularly susceptible to both diabetes and cardiovascular disease.  Furthermore, the absence of adverse effects observed at these high doses bodes well for the safety of resveratrol.”

Study details

The new study, led by Gary Lewis, MD, FRCPC, included eight overweight or obese people with mildly elevated triglyceride levels. The participants were studied on two separate occasions, four to six weeks apart. They were randomly assigned to receive either placebo or resveratrol at a daily dose of 1000 mg daily for one week followed by 2000 mg for a second week.

Resveratrol is a powerful polyphenol and anti-fungal chemical that is often touted as the bioactive compound in grapes and red wine. Interest in the compound exploded in 2003 when research from David Sinclair and his team from Harvard reported that resveratrol was able to increase the lifespan of yeast cells. According to Sinclair’s findings, resveratrol could activate a gene called sirtuin1 (Sirt1 – the yeast equivalent was Sir2), which is also activated during calorie restriction in various species, including monkeys. Other studies with only resveratrol have reported other benefits, including supporting heart health, blood sugar management, and energy endurance enhancement.

Results showed that, while the resveratrol intervention did not modify insulin sensitivity, or triglyceride levels, reductions in the production of both apoB-48 and apoB-100 was observed.

“This proof-of-principle study has demonstrated that short-term high-dose resveratrol administration in overweight and obese men with mild hypertriglyceridemia significantly reduces apoB-100 and apoB-48 production,” wrote Dr Lewis and his co-workers.

“The clinical relevance of these effects of high-dose resveratrol on apoB production, in a small cohort of mildly hypertriglyceridemic individuals, remains to be established,” they added. “Because there was no net change in apoB-100 triglyceride-rich lipoprotein concentration attributable to the reduced apoB-100 fractional catabolic rate, the reduced apoB-100 production rate is unlikely to be clinically significant.

“However, a recent study performed in hypercholesterolemic patients on statins demonstrated that 6 months of daily treatment with grape extract containing a low dose of resveratrol (8 mg) resulted in a modest reduction in fasting plasma apoB concentration. In our study, there was a trend toward a lower apoB-48 triglyceride-rich lipoprotein concentration with resveratrol treatment. The absence of a statistically significant reduction in apoB-48 triglyceride-rich lipoprotein concentration may be because of the small sample size, short duration of treatment, and the mild hypertriglyceridemia seen in our study participants.”

The researchers called for long-term studies with more participants to further investigate if resveratrol is beneficial for people with elevated triglyceride levels.

Source: Arteriosclerosis, Thrombosis, and Vascular Biology
Published online ahead of print, doi:
“High-Dose Resveratrol Treatment for 2 Weeks Inhibits Intestinal and Hepatic Lipoprotein Production in Overweight/Obese Men”
Authors: S. Dash, C. Xiao, C. Morgantini, L. Szeto, G.F. Lewis

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