Plants and Food

Resveratrol is produced by several plants, apparently for its antifungal properties. It is found in widely varying amounts in grapes (primarily the skins), raspberries, mulberries, in peanuts, berries of Vaccinium species, including blueberries, bilberries, and cranberries, some pines, such as Scots pine and eastern white pine, and the roots and stalks of giant knotweed and Japanese knotweed, called hu zhang in China. Resveratrol was first isolated from an extract of the Peruvian legume Cassia quinquangulata in 1974.

The amount of resveratrol in food substances varies greatly. Ordinary non-muscadine Red wine contains between 0.2 and 5.8 mg/L [1], depending on the grape variety, whilst white wine has much less - the reason being that red wine is fermented with the skins, allowing the wine to absorb the resveratrol, whereas white wine is fermented after the skin has been removed. Wines produced from muscadine grapes, however, both red and white, may contain more than 40 mg/L.[2]. [2]

Fresh grape skin contains about 50 to 100 micrograms of resveratrol per gram.[3]

In grapes, resveratrol is found primarily in the skin and seeds. This is particularly true for muscadine grapes, whose skin and seeds have about one hundred times the concentration as the pulp.[4] The amount found in grape skins also varies with the grape cultivar, its geographic origin, and exposure to fungal infection. The amount of fermentation time a wine spends in contact with grape skins is an important determinant of its resveratrol content.[5]

Total resveratrol content of selected foods
Food Serving Total resveratrol (mg)
Peanuts (raw) 1 c (146 g) .01-0.26
Peanuts (boiled) 1 c (180 g) .32-1.28
Peanut butter 1 c (258 g) .04-0.13
Red grapes 1 c (160 g) .24-1.25

Supplements

Resveratrol is available as a nutritional supplement but not as a therapeutic agent (although it has been registered as an investigational drug in some jurisdictions). Supplements, first sourced from ground dried red grape skins and grape seeds (sometimes from residual byproducts of winemaking[14]), are now primarily derived from the cheaper, more concentrated Japanese knotweed. Capsules are sold containing from 1 mg to over 40 mg of Resveratrol, at a cost of USD $.10 to over $1.00 each. A less common form is packets of powder, which might be more convenient for frequent ingestion as suggested by the rapid metabolism in the body.[15]

Some supplement makers claim that only the trans- form matters, and that the cis- form is not useful or perhaps even a bad thing. Other makers simply report total resveratrol content -- or in some cases, just the quantity of an "extract" source, which only contains some percentage of resveratrol.

The following is an excerpt from a FDA New Dietary Ingredient Notification:

"First, trans-Resveratrol is excluded from the definition of a “dietary supplement” under 21 U.S.C. 321 (ff) (3) (B), because it is an article authorized for investigation as a new drug for which substantial clinical investigations have been instituted and made public in the U. S."

"FDA authorized trans-Resveratrol, which is also known as “resveratrol” or 3,5,4’-trihydroxystilbene, to be an Investigational New Drug on January 30, 2001. The Dietary Supplement Health and Education Act (DSHEA) of 1994 defined a “new dietary ingredient” as one that was marketed in the U.S. on or after October 15, 1994. This office does not have any information that indicates that trans-Resveratrol was legally marketed as a dietary ingredient in the U.S. before October 15, 1994."

Resveratrol is often called a nutraceutical, like other bioactive plant compounds studied for potential clinical applications: curcumin, EGCG, silibinin, etc.

In a 2004 issue of Science, Dr. Sinclair of Harvard University said resveratrol is not an easy molecule to protect from oxidation. It has been claimed that it is readily degraded by exposure to light, heat, and oxygen.[16] Other researchers indicate that resveratrol retains its health effects rather well. Most commonly-available supplements tested have no ability to stimulate the Sirtuin 1 enzymes.[citation needed]

The pharmacokinetics of resveratrol metabolism have not been investigated in humans. Rat studies, however, suggest a half life as high as 1.6 hours. In a 2002 issue of J Pharm Exper Therapeutics[17], Dr. Marier reported that rats given a single oral dose of 50 mg/kg body weight initially experienced a rapid drop in serum resveratrol levels: the half life, or T1/2, of the drug was found to be 8 minutes, meaning that blood levels had dropped to half of peak by that time. However, detectable levels of the drug remained for 12 hours, probably due to enterohepatic recirculation--that it, a release of stored resveratrol from liver tissue, yielding an overall half life of between 1.3 and 1.6 hours [Marier JF et al. J Pharm Exper Theraputics 2002;302(1):369-373]. It is expected that chemically modified resveratrol-like molecules (drugs) will have a longer half-life and thus more potency.

Adverse Effects

While the health benefits of resveratrol seem promising, one study has found that it stimulates the growth of human breast cancer cells, possibly because of resveratrol's chemical structure, which is similar to a phytoestrogen.[23] [24]

An organization called "Quackwatch" has posted their own analysis and comments on the matter [23], including this: "increased consumption of red wine to boost resveratrol intake could certainly do more harm than good... red wine and other alcoholic beverages pose health risks..."

"Reasons why recommending a population-wide increase would be premature: Little is known about the absorption and clearance of resveratrol, the identities of its metabolic products, or its effects on the liver. The research on resveratrol has focused on its short-term effects and has been mainly done on non-human models."[