While an earlier published rodent study showed that ultra-high doses of resveratrol (1565 milligram human dose), equivalent to 1500 bottles of wine or many dietary supplement capsules, successfully overcame the adverse effects of a high-fat diet, the lowest dose that genetically mimics a calorie restricted diet went undetermined, till now.
Now an authoritative gene array study, conducted by researchers at the William S. Middleton Memorial Veterans Hospital and Lifegen Technologies in Madison, Wisconsin, shows that a dose of resveratrol (rez-vair-aw-trawl) 343 milligrams per day (4.9 mg per kilogram of body weight) produces a gene activation profile similar to a calorie restricted diet. Supra-high doses (greater than 500 milligrams) are not required and may produce side effects.
Both calorie restriction and resveratrol have been shown to prolong the life of all life forms, ranging from single-cell organisms (yeast cells) to more complex forms of life (fruit flies, roundworms) and warm-blooded mammals (laboratory rats).
Consumers never heard that a far lower human equivalent dose than 1565 milligrams ( 360 milligrams) was employed with undisclosed success in a landmark rodent study published in 2006. The lower-dose data were never published. [Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006 Nov 16; 444: 337-42]
Drawbacks of supra-high doses
"Once mega-doses of resveratrol (more than 500 mg) began to be employed, side effects like anemia, Achilles heel tendonitis, anxiety reactions, numbness in the fingers, began to be reported," says Bill Sardi, spokesperson for Longevinex (long-jev-in-ex), a leading brand resveratrol dietary supplement. "This is probably because resveratrol is a copper chelator and excessive chelation will impair the availability of copper which is needed for collagen formation and nerve regeneration," he says. "Resveratrol is relatively safe, but not absolutely safe at any dosage. There are drawbacks," he adds.
Some online suppliers of resveratrol pills, who have no medical training, irresponsibly recommend up to 7000 milligrams of resveratrol a day. There is also evidence that supra-high dose resveratrol inhibits the absorption of folic acid (vitamin B9), an essential nutrient needed for DNA repair. [European Journal Nutrition 46: 329-36, 2007] High doses have not been tested in humans for long-term use.
Advertising claims by resveratrol supplement makers that their pills exert greater stimulation of the Sirtuin 1 DNA-repair gene should also be regarded with caution since an animal study shows over-stimulation (greater than 7.5 fold) of this gene induces heart failure in animals. [Circulation Research 2007; 100: 1512-21]
Not just resveratrol
The health and longevity benefits of red wine are not easily explained by the low dose of resveratrol provided in a glass of wine, but are more easily explained by the total milligrams of polyphenolic molecules (resveratrol, quercetin, catechin, kaempferol, ferulic acid), about 60 milligrams per glass of aged red wine, says Sardi. The healthy range for red wine drinking is 3 to 5 glasses, or about 180 to 300 milligrams of polyphenols. Dietary supplements should provide about the same dosage range. Mega-doses are not required and may be problematic.
Red wine is a fermented concentrate of grape skin which provides an array of beneficial molecules which magnify its effect, says Sardi. A resveratrol- based nutraceutical matrix that closely mimics the effect of red wine without the alcohol, calories and preservatives is what Longevinex is.
Factors that determine safe dosage
Age, gender, diet and iron stores determine the resveratrol dosage required for optimal health. Red wine resveratrol pills are not appropriate for growing children or menstruating females, who have higher demand for minerals. However, Sardi explains that some consumers may benefit from a higher loading dose and a lower long-term maintenance dose.
Consumers need to recognize the health benefits of resveratrol and related molecules emanate from their mineral chelating (removal) properties, which then influence the genome, says Sardi. [BMC Genomics 8: 379, 2007; Biochmica Biophysica Acta 1619: 113-24, 2003] Middle-aged males and postmenopausal females have accumulated stores of excess iron and calcium which can be removed by natural mineral chelators, like those provided in Longevinex.
"A middle-aged male will typically have a higher load of stored iron and calcium and may benefit from a higher loading dose of mineral chelators, to speed along their removal, followed by a lower dose for long-term maintenance," says Sardi. He also suggests a relatively low iron and calcium diet to accompany a dietary supplement regimen intended to produce longevity. Humans live longer in countries where calcium and iron intake are low, such as Japan, he says.
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