Friday, April 2, 2010

Resveratrol: the red wine magic chemical

I try not to get too excited about memory benefits of supplements. Certainly, I only have any level of faith in formal scientific studies that are well controlled and peer reviewed. I now think that resveratrol may be one of the few supplements that could have beneficial effects on brain function.

You no doubt have heard about the French red-wine drinkers, who are more healthy than they ought to be, given that they drink too much, exercise too little, and eat too much fat (as in goose liver and cheese). In trying to figure out how this can be, scientists have homed in on a major anti-inflammatory chemical in red wine, known as resveratrol. At this writing, over 2,000 scientific papers have been published. Don't worry, I am only going to tell you about a few. Most of the protective biological actions associated with resveratrol have been associated with its intrinsic radical scavenger properties and the protective effects that it confers on the heart.

Most of this research focuses on the compound's beneficial effects on heart and blood vessels and diabetes. The compound targets multiple enzymes in multiple organs. What I am summarizing here is recent research that suggests resveratrol might be beneficial for thinking ability in general and memory in particular.

A diabetes research group in Brazil recently reported a beneficial effect of resveratrol on diabetic rats. An earlier study by another group showed that resveratrol improved glucose metabolism and promoted longevity in diabetic mice. Other research groups had reported neuroprotective effects for resveratrol. The Brazil group focused on brain damage produced by diabetes. They induced diabetes in a group of rats, observing that this impaired their ability to memorize. The cause, as indicated by other studies, is that diabetes lowers the level of a major brain neurotransmitter that promotes alertness, attentiveness, and general cognitive function, acetylcholine. As an aside, the major treatment for Alzheimer's disease is Aricept, which enhances acetylcoline function. The Brazil group found that resveratrol suppressed activity of the enzyme that destroys acetylcholine, thus tending to restore more normal acetylcholine function. Resveratrol (in a modest rat dose of 10 and 20 mg/kg per day for 30 days) prevented the impairment of memory induced by diabetes.

Added to this finding about the brain enzyme, there are other reasons to think the anti-oxidant properties of resveratrol might be beneficial to the brain. The brain has more oxygen consumption than any bodily organ, about 20% of all the body's consumption. The brain therefore produces more free-radical damage, but the brain has especially low levels of antioxidant defense enzymes.

One recent study has revealed that 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) pr day for 25 days, beginning four days before the toxin injection.
 
Another recent study examined the effect of dietary supplement on working memory in mice.  Groups of young adult and aged mice were put on a resveratrol-supplementd diet for four weeks before being injected with a cytokine to induce inflammation and accelerate aging. Mice were then tested for their ability to remember what they learned in a commonly used spatial memory task in a water maze. The dietary supplement significantly reduced memory impairment in the aged group, but not in the young adults. The lack of benefit in young adults was a little misleading, in that there was a "ceiling effect" in that the young adults, even though given cytosine, were already performing at near-mazimum levles. Cytosine had clear impairing effects in the contol aged mice, but much less so in the resveratrol-treated aged mice. In other words, aging makes an animal more susceptible to toxic chemicals, and thus there is more opportunity for any beneficial treatment to become manifest.

The memory studies have appeared only in the last year or so and are confined to laboratory animals. The beneficial effects may occur only in preventing damage, as with diabetes or other kinds of brain injury. Benefits may also be imperceptible in the young.

The open question is whether resveratrol will help cognitive function in humans, especially healthy humans.But you can be sure that research on humans will become intense. Positive memory-enhancing results in humans have alredy been published for consumption of blueberries, in which resveratrol is a major ingredient.

One of the first such randomized controlled trials of resveratrol effects on memory in normal older adults.has been launched in 2010 by Todd Manini and Steven Anton at the University of Florida's Institute of Aging.


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 any good. Highly concentrated supplements are coming on the market. 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 these high doses of resveratrol are toxic.

Sources:

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

Harkiumar, K. B., and Aggarwal, B. B. 2008. Resveratrol.. A multitargeted agent fo age-associated chronic diseases. Cell Cycle 7:8, 1020-1035.

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

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.

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