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High-dose, Low-dose Resveratrol Confer No Improvement In Metabolic Syndrome Markers

Feb 15, 2017

In middle-aged men with metabolic syndrome, treatment with resveratrol did not improve markers for inflammation, glycemic control or lipid metabolism, whereas high-dose resveratrol therapy increased lipid and fructosamine levels vs. placebo, according to findings from a randomized controlled trial.

“From preclinical studies in cell models and animal models, it has repeatedly been shown that resveratrol possesses beneficial effects on several of the biochemical pathways involved in obesity-associated morbidity,” Thomas Nordstrom Kjær, of the department of endocrinology at Aarhus University Hospital in Denmark, and colleagues wrote. “Resveratrol inhibits inflammation, improves insulin sensitivity, inhibits hepatic fat accumulation, possesses anti-cancer activity and improves endothelial function. However, ... translation of the preclinical findings into human clinical practice has been cumbersome and inconclusive.”

Kjaer and colleagues analyzed data from 66 men aged 30 to 60 years with metabolic syndrome, but otherwise healthy (mean age, 50 years; mean BMI, 33.8 kg/m²; mean baseline waist circumference, 115 cm) randomly assigned to 75-mg resveratrol twice daily (n = 21), 500-mg twice-daily resveratrol (n = 21) or placebo (n = 24) for 16 weeks. Primary outcome was change in high-sensitivity C-reactive protein; secondary outcomes included changes in homeostatic model of insulin resistance (HOMA-IR), expression of inflammatory genes and body composition, including visceral fat (measured by MRI) and ectopic fat deposition.

At 16 weeks, researchers found that high- and low-dose resveratrol had no effect on high-sensitivity C-reactive protein vs. placebo; similarly, there were no observed between-group differences in interleukin-6, adiponectin or soluble urokinase-type plasminogen activator receptor levels. Men assigned to either dose of resveratrol saw no change in serum insulin or HOMA-IR; however, in post-hoc analysis, men in the high-dose group had increased levels of fructosamine vs. placebo (mean difference, 11.8 µmol/L; 95% CI, 2.04-21.5).

Compared with placebo, men in the high-dose group also had increases in total cholesterol (mean difference, 0.69 mmol/L; 95% CI, 0.22-1.16) and LDL cholesterol (mean difference, 0.61 mmol/L; 95% CI, 0.15-1.08). Serum leptin, HDL cholesterol and triglyceride levels remained unchanged by resveratrol therapy.

“An interesting observation is the significant increase in fructosamine as well as total and

LDL cholesterol in the [high-dose] resveratrol group,” the researchers wrote. “This may suggest that high doses of resveratrol can have detrimental effects on glucose and cholesterol metabolism, whereas data from our recent publication on resveratrol effects in bone revealed that the highest resveratrol dose induced the largest increase in [bone mineral density]. Consequently, these data suggest that the optimal dosage of resveratrol depends on the target tissue.” – by Regina Schaffer

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