Resveratrol Supplementation Does Not Improve Metabolic Function in Nonobese Women with Normal Glucose Tolerance

Abstract

Summary Resveratrol has been reported to improve metabolic function in metabolically-abnormal rodents and humans, but has not been studied in non-obese people with normal glucose tolerance. We conducted a randomized, double-blind, placebo-controlled trial to evaluate the metabolic effects of 12 weeks of resveratrol supplementation (75 mg/day) in non-obese, postmenopausal women with normal glucose tolerance. Although resveratrol supplementation increased plasma resveratrol concentration, it did not change body composition, resting metabolic rate, plasma lipids, or inflammatory markers. A two-stage hyperinsulinemic-euglycemic clamp procedure, in conjunction with stable isotopically-labeled tracer infusions, demonstrated that resveratrol did not increase liver, skeletal muscle, or adipose tissue insulin sensitivity. Consistent with the absence of in vivo metabolic effects, resveratrol did not affect its putative molecular targets, including AMPK, Sirt1, Nampt, and Pgc-1α, in either skeletal muscle or adipose tissue. These findings demonstrate that resveratrol supplementation does not have beneficial metabolic effects in non-obese, postmenopausal women with normal glucose tolerance.

Safety of synthetic trans‐resveratrol as a novel food pursuant to Regulation (EC) No 258/97

“…In the other RCT with (resVida ® ) intake of 75 mg trans-resveratrol of the Novel Food per day over 12 weeks was studied in 30 healthy non-obese postmenopausal women with normal glucose tolerance. No effects were observed on the resting metabolic rate, body composition, plasma lipids, inflammatory markers and insulin sensitivity (Yoshino et al, 2012). Both studies included clinical chemistry and haematological testing of blood samples and reported that no adverse effects have been observed.…”

“…Both studies included clinical chemistry and haematological testing of blood samples and reported that no adverse effects have been observed. The Panel notes the short study duration (Timmers et al, 2011) and the low dose studied by Yoshino et al (2012) compared to the use level intended by the applicant.…”

“…In addition to the study by Wong et al (2010), two other studies were conducted with the Novel Food (resVida ® ) produced by the applicant: A 4-week randomized controlled trial (RCT) with a daily dose of 150 mg trans-resveratrol by Timmers et al (2011) and the 12-week RCT with a daily dose of 75 mg by Yoshino et al (2012). In the RCT by Timmers et al (2011) with cross-over design, 11 obese but otherwise healthy men (BMI >30) consumed 150 mg trans-resveratrol per day.…”

AMPK activation—protean potential for boosting healthspan

“…Unfortunately, in humans, it is conjugated rapidly and completely following absorption; despite reasonably efficient absorption, orally administered resveratrol does not appear to achieve sustained serum levels of free resveratrol sufficient to inhibit mitochondrial ATP synthase and thereby activate AMPK (Walle et al 2004;Boocock et al 2007). Consistent with this, several recent controlled clinical studies have failed to observe an impact of oral resveratrol on insulin sensitivity, blood pressure, body composition, or other clinical parameters; in addition, AMPK activity in skeletal muscle or adipocytes was not influenced (Yoshino et al 2012;Poulsen et al 2013). However, oral resveratrol might have the potential to transiently activate AMPK in the intestinal mucosa.…”

Mitochondrial Metabolism and Insulin Action

“…Recently it was also shown that 30 days of resveratrol supplementation improved some markers of mitochondrial function in muscle of obese subjects, in parallel with improved HOMA-IR and reduced hepatic lipid levels [230]. These effects seem to be limited to metabolically compromised subjects, as resveratrol did not improve markers of glycaemic control in non-obese women with normal glucose tolerance [231]. An alternative approach to using direct SIRT1 activators to mimic calorie restriction, is to increase the intracellular levels of NAD + , the obligate co-factor for the sirtuin reaction.…”