It’s only 18 months since I last wrote about the remarkable phytonutrient, resveratrol (Nutrition & Healing Vol 5, Issue 3, March 2011). You might recall I was extolling its virtues as a supplement that can mimic the beneficial effects of calorie restriction in the human body: so you can eat your cake but not have it. (‘It’ being the negative consequences of too much fat and carbohydrate in our diets.)
Not that I am at all suggesting resveratrol is a new way we can continue to indulge and not pay the price. Instead, its real value should be in making a good diet even healthier, especially minimising the negative consequences of an occasional lapse.
Now there is human clinical evidence to back this up. This trial, published earlier in 2011, revealed some intriguing results. In this double-blind, randomised, crossover study, 10 normal, healthy men and women were given a high-fat, high-carbohydrate (HFHC) meal (930 kcal) either with a placebo or a product containing 100mg of resveratrol from the herb Polygonum cuspidatum plus 75mg of total polyphenols from a grape extract. Profound anti-inflammatory, detoxifying and antioxidant effects were observed.
Most importantly, the herbal combination significantly suppressed the induced elevations of plasma endotoxin (lipopolysaccharide, LPS) induced by the HFHC meal. There was a significant, steady increase in the plasma concentration of LPS in the placebo group of about 50 per cent. In contrast, plasma LPS decreased significantly for the herbal group, being 28 per cent below the baseline reading at one hour and then gradually rising to around 10 per cent above baseline thereafter.
In terms of antioxidant and detoxifying effects, the key master switch of cellular defensive responses, namely the Nrf2/ARE (antioxidant response element) pathway was clearly activated in white blood cells. (I will be discussing the profound new implications of this recently discovered pathway in a subsequent column.) DNA binding activity of the antioxidant transcription factor Nrf2 was significantly increased by around 50 per cent over baseline at three hours after meal and supplement intake, whereas meal consumption in the placebo group resulted in a significant reduction in Nrf2 binding activity at five hours. Additionally, significant increases in the Nrf2 target genes for important phase II detoxifying enzymes NQO-1 and GST-P1 were observed after the meal plus herbal supplement, whereas there was no change for the placebo.
Another remarkable trial found that relatively small doses of resveratrol could improve the metabolism of obese men in a manner similar to calorie restriction. In a double-blind, randomised, placebo-controlled crossover study, 11 healthy but obese men (average BMI around 31.5) received 150mg/ day of resveratrol for 30 days. Like calorie restriction, resveratrol significantly reduced systolic blood pressure, plasma insulin, insulin resistance, fasting plasma glucose, triglycerides, leptin and sleeping and resting metabolic rates (without changing overall energy expenditure).
Inflammatory markers were also substantially lower while the men were taking resveratrol, with significant or near-significant reductions for C-reactive protein, interleukin-6, tumour necrosis factor alpha and white blood cell count.
In muscle tissue biopsies from the men, resveratrol:
- favourably activated AMPK (see sidebar);
- increased Sirt1 activity (which is also increased by calorie restriction, see my earlier columns);
- improved muscle mitochondrial respiration.
All these effects are compatible with resveratrol acting like calorie restriction on the most important tissue we have for utilising energy and balancing our sugar metabolism and metabolic rate: skeletal muscle.
When it was initially discovered, resveratrol was thought to have quite low bio-availability, and hence it was assumed that very large doses would be needed for clinical effects. The above studies show that this is not the case, probably because the liver metabolites of resveratrol are still active (resveratrol is well absorbed, but undergoes rapid liver metabolism). One recent study found that even VERY low doses of resveratrol can still have a profound clinical effect. Nineteen men with type 2 diabetes participated in a randomised, double-blind trial: 10 received resveratrol (10mg/day) and nine received a placebo for four weeks. All patients were taking either angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker drugs for hypertension.
Treatment with even just 10 mg/day of resveratrol improved insulin resistance, decreased blood glucose levels and delayed the appearance of glucose peaks after a test meal. The decrease in insulin resistance after four weeks was significantly different compared to the placebo group. Treatment with resveratrol also significantly decreased oxidative stress.
To your better health,
Nutrition & Healing
Volume 6, Issue 10 – October 2012
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