Joe: My doctor told me to give up drinking, smoking, and fatty foods.

Sam: What will you do?

Joe: I think I’ll give up my doctor.

I try not to get too excited about memory benefits of supplements, because too often the claims are not substantiated by studies that are well controlled and peer reviewed. I now think resveratrol may be one of the few supplements that benefits brain function. 

When I wrote my first blog on research on resveratrol benefits for brain function and memory, there were over 2,000 scientific papers.[1] Don't worry; I am only going to tell you about a few studies.

Resveratrol is an active ingredient in red wine. This compound has been credited for explaining why red-wine drinkers in France, who drink more wine than most people, are healthier than would be predicted by their lifestyle of little exercise and eating lots of cheese. The problem is most studies suggest you would have to drink a 100 or more glasses of red wine a day to get much resveratrol effect (and that effect would obviously be negated by a toxic dose of alcohol). An obviously more healthful choice is the highly concentrated pill forms of resveratrol that are now on the market.

Most of the protective biological actions associated with resveratrol have been associated with its scavenger properties for free radicals and the protective effects that it confers on the heart and diabetes. 

One important study comes from a diabetes research group in Brazil recently who reported a beneficial effect of resveratrol on diabetic rats.[2] Resveratrol (in a modest rat dose of 10 and 20 mg per kilogram per day for 30 days) prevented the impairment of memory induced by diabetes. An earlier study by another group showed resveratrol improved glucose metabolism and promoted longevity in diabetic mice.

Another benefit of resveratrol is the anti-oxidant property. The brain produces more free-radical damage than other organs, and compared with other organs the brain has especially low levels of antioxidant defense enzymes. 

One recent study has revealed resveratrol had protective effects against brain damage caused by a chemical that kills acetylcholine neurons. Injection of this toxin into the brain of rats impaired their memory performance in two kinds of maze tasks. The impairment was significantly reduced by repeated injection of resveratrol (10 and 20 mg/kg) per day for 25 days, beginning four days before the toxin injection.[3]

Another recent study examined effects on working memory in mice fed a resveratrol-supplemented diet for four weeks before being injected with a cytokine to induce inflammation and accelerate aging. Resveratrol significantly reduced memory impairment in the aged group, but not in the young adults[4]. The lack of benefit in young adults was a little misleading, in that there was a "ceiling effect" in that the young adults were not impaired by the cytokine injection.

The practical issue for us is whether resveratrol will help cognitive function in humans, especially healthy humans. It seems likely because other substances that have strong anti-oxidant properties seem to improve memory capability. Because animal studies have shown promise for resveratrol in preventing or treatment several different conditions associated with aging, several human clinical trials have been initiated.[5] 

An impressive new study of older humans, male and female, has just been reported.[6] Twenty-three healthy, but overweight people completed 6 months of daily resveratrol intake (200 mg ― the commercial brand I take has 300 mg/capsule). A paired control group got placebo pills. A double-blind design assured that neither the subjects nor the experimenters knew which individuals were in each group during data processing. 

Memory tests of word recall revealed significant improvement in the resveratrol group. Resveratrol also increased brain-scan measures of functional connectivity, which identified  linked neural activity between the hippocampus and several areas of cerebral cortex.

Because others had shown that resveratrol increased insulin sensitivity in humans, these authors examine several markers important to diabetes. Resveratrol decreased the standing levels of sugar-bound hemoglobin, a standard marker for glucose control.  

What foods besides red grapes have resveratrol? The most likely other sources you would eat or drink are blueberries, cranberries, and peanuts. It is not likely that you could drink or eat enough of such substances to get enough resveratrol to do much good. Because of the scientifically documented benefits of resveratrol, highly concentrated supplements are now on the market (I have been taking it for a couple of years) I haven't given up my two glasses of red wine each day, but I have started taking one of the supplements. I haven't seen any reports that high doses of resveratrol are toxic.

[1] April 4, 2010.

[2] Schmatz R, et al. (2009). Resveratrol prevents memory deficits and the increase in acetylcholinesterase activity in streptozotocin-induced diabetic rats. Eur J Pharmacol. 2009 May 21;610(1-3):42-8. Epub 2009 Mar 19.

[3] Kumar, A. et al. 2007. Neuroprotective effects of resveratrol against intracerebroventricular colchicine-induced cognitive impairment and oxidative stress in rats. Pharmacology.79 (1): 17-26. DOI: 10.1159/000097511

[4] Abraham, J., and Johnson, R. W. 2009. Consuming a diet supplemented with resveratrol reduced infection-related neuroinflammation and deficits in working memory in aged mice. Rejuvenation research. 12 (6): 445-453.  DOI: 10.1089/rej.2009.0888

[5] Smoliga, J. M. et al. (2011). Resveratrol and health – a comprehensive review of human clinical trials. Mol. Nutrition Food Res. 55: 1129-1141

[6] Witte, A. V., et al. (2014) Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults. J. Neuroscience. 34 23): 7862-7870.


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