A single dose of 250 or 500 milligrams of resveratrol was found to boost blood flow in the brain but did not affect cognitive performance, according to new findings published in the American Journal of Clinical Nutrition.
“The results of the current study provide the first indication in humans that resveratrol may be able to modulate cerebral blood flow variables,” wrote the researchers, led by David Kennedy from the Brain, Performance and Nutrition Research Centre at Northumbria University.
“Thus, it seems reasonable to suggest that the potential effects of this molecule on brain function deserve a great deal more research attention with a clear focus on both healthy humans and pathologic groups,” they added.
The promise of long life
Resveratrol, a powerful polyphenol and anti-fungal chemical, is often touted as the bioactive compound in grapes and red wine, and has particularly been associated with the so-called 'French Paradox'. The phrase, coined in 1992 by Dr Serge Renaud from Bordeaux University, describes the low incidence of heart disease and obesity among the French, despite their relatively high-fat diet and levels of wine consumption.
Interest in the compound exploded in 2003 when research from David Sinclair and his team from Harvard reported that resveratrol was able to increase the lifespan of yeast cells. The research, published in Nature, was greeted with international media fanfare and ignited flames of hope for an anti-ageing pill.
According to Sinclair’s findings, resveratrol could activate a gene called sirtuin1 (Sirt1 – the yeast equivalent was Sir2), which is also activated during calorie restriction in various species, including monkeys.
Since then studies in nematode worms, fruit flies, fish, and mice have linked resveratrol to longer lives. Other studies with only resveratrol have reported anti-cancer effects, anti-inflammatory effects, cardiovascular benefits, anti-diabetes potential, energy endurance enhancement, and protection against Alzheimer’s.
Bill Sardi, co-founder and president of Resveratrol Partners, says that: “Resveratrol has the biological effects of so many drugs wrapped up in one molecule.”.
The new randomized, double-blind, placebo-controlled, crossover study, which involved 22 healthy adults, now suggests a role for the compound in brain health.
Dr Kennedy and his co-workers randomly assigned the participants to receive placebo, or one of two doses of trans-resveratrol (250 or 500 milligrams, Biotivia Bioceuticals, Austria). Forty-five minutes after the dose, the blood flow and cognitive performance of the participants was measured over a 36 minute period.
Results showed that resveratrol produced a dose-dependent increase in cerebral blood flow, but no increase in the placebo group. The researchers also noted an increase in levels of deoxyhemoglobin after both doses of resveratrol, which they said was indicative of increased oxygen extraction and utilisation.
No effect on cognitive function was noted, however.
“One key issue regarding resveratrol and other polyphenols is that of the low bioavailability of the parent molecule in humans,” wrote the researchers. “The results here confirm that orally administered resveratrol can modulate brain function in humans.
“Whether this is as a consequence of the very low concentrations of the parent molecule seen here in plasma, the action of the much higher concentrations of its glucuronide and sulfate conjugates or other metabolites, or the conversion of these metabolites back to the parent form once they reach target tissues remains to be elucidated,” they added.
The news has not been welcomed by all. Sardi notes that a high dose as used in this study may produce problems over the long-term. Sardi told NutraIngredients last year that the compound is a chelator of copper. "Copper is found in red blood cells and collagen, amongst other places," he said. "Resveratrol is not suitable for children or pregnant women. Resveratrol would not be suitable in a food snack bar for children."
However, Dr James Betz, managing director of Biotivia - the company which supplied the resveratrol - dismissed such claims. Dr Betz told NutraIngredients: "The effects of resveratrol administration were dose dependent with the better effects associated with 500mg supplementation in a direct almost linear correlation. This would imply that a higher dosage, say 1,000mg, might produce even better results.
Dr Betz added that the company is awaiting results from several on-going human trials in Italy and Egypt which are using doses up to 5,000 mg per day.
"No significant adverse effects have been observed in human studies using as much as 5,000mg daily and animal toxicity studies using order of magnitude greater dosages have failed to produce serious side effects," added Dr Betz.
Commenting on the study's findings Dr Betz noted that the study showed that orally administered resveratrol is rapidly metabolized into glucuronide and sulfate conjugates. "This tends to support my theory that the metabolites of resveratrol are at least as critical, and probably more critical, than free resveratrol itself," he said. "This hypothesis is further supported by the fact that the level of measured metabolites in the subject's blood peaked at about 90 minutes after administration of both the 250mg and 500mg whereas the level of free resveratrol at that point in time was quite low.
"This may explain why, given the short half life of free resveratrol in blood plasma, this stilbene can be so efficacious at moderate doses. A reasonable implication from these data is that any compound such as Quercetin that inhibits or interferes with this conversion of resveratrol to its metabolites has the potential to nullify the biochemical and bio-kinetic effects of the compound when taken concurrently with resveratrol," said Dr Betz.
Source: American Journal of Clinical Nutrition
Published online ahead of print, doi:10.3945/ajcn.2009.28641
“Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation”
Authors: D.O. Kennedy, E.L. Wightman, J.L. Reay, G. Lietz, E.J. Okello, A. Wilde, C.F. Haskell