Effects of long-term resveratrol supplementation on metabolic health

There is now a general consensus that the combination of excessive energy
intake and a low capacity to oxidize fat will lead to muscular fat accumulation
and insulin resistance. It is known for many years that physical activity and
diet therapy are the most powerful treatment to combat obesity and insulin
resistance, but it is also known that it is difficult to get people to exercise
and follow diets. A major breakthrough in this field has come from the
nutrition field, with the finding that resveratrol, a natural polyphenolic
compound, could serve as an *caloric restriction mimetic*, as a recent study of
S. Timmers et al. in Cell metabolims (2011) showed that resveratrol mimicked
the effect of caloric restriction in healthy obese man (lowering liver fat
accumulation and increasing fat oxidation, thereby improving metabolic health
in these subjects). These findings were similar to those found earlier in
animal studies, where it was found that resveratrol protected mice from many
detrimental effects of diet-induced obesity. The purpose of the current study
is to investigate if resveratrol has the same beneficial effects if resveratrol
is given for a longer period (6 months) in people with overweight/obesity. This
information can be used to develop new preventive strategies for type 2
diabetes. Therefore we will investigate the effects of long-term (6 months)
resveratrol supplementation on insulin sensitivity (estimated by Matsuda
Index). In addition we will investigate effects of resveratrol on other
(metabolic) parameters such as: body composition, intra-hepatic lipid
accumulation, resting energy expenditure, blood pressure, plasma values, muscle
strenght and quality of life.

The purpose of the study is to investigate wether long-term resveratrol
supplementation (6 months) leads to improved insulin sensitivity (estimated by
Matsuda Index) in people with overweight/obesity. In addition we will
investigate effects of resveratrol on other (metabolic) parameters such as:
body composition, intra-hepatic lipid accumulation, resting energy expenditure,
blood pressure, plasma values, muscle strenght and quality of life.

Double blind, randomised, parallel design, clinical trial in which resveratrol
supplementation will be compared to placebo

Particicpants will take 2 times a day a capsule of resversatrol (75 mg) or
placebo: 1 during lunch and 1 during the evening meal for a period of 6 months.

Before the start of the intervention potential paricipants are screened to
determine wether they are eligible for participation in the study. This
screening entails filling in a medical history questionnaire, drawing of a
fasting blood sample and determination of body weight (total duration: 1 hour).
During the 6-month intervention period the participants will visit the
university 9 times (Month 0 2x, Maand 1, 2, 3, 4, 5 and Month 6 2x). During
these visits to the university a fasting blood sample will be drawn and body
weight and blood pressure are checked. During the visits of Month 0 and Month 6
the following measurements will be performed: MRS scan (for determination of
intra-hepatic lipid content), DEXA scan, OGTT (2 times before and after 6
months), indirect calorimetri, questionnaires about food intake and habitual
physical activity, queastionnaires about quality of sleep and quality of life
and muscle stranght (timed chair stand test, 6-minute walk test and Biodex).
Participation in the entire study costs the participants about 25 hours
(including the screening).

The following risks are present:
- The blood drawings can cause a bruise and swelling
- The radiation of the DEXA scan is very low and because of this low dose the
risks on the long-term are negligible