Drink a toast to Resveratrol:
Jacob Schor, ND
Our regular readers will recall resveratrol, the chemical extracted from grape skins.
I first wrote about resveratrol in the late 1990's when the three studies came out suggesting resveratrol could convince cancer cells to commit suicide. I wrote about resveratrol again a few years later. Resveratrol has a synergistic effect when administered in combination with certain chemotherapy drugs, increasing their capacity to kill cancer cells. That article is posted at:
In September 2003, the journal Nature published a study suggesting that resveratrol caused chemical effects similar to a caloric restricted diet. Animals that spend their lives hungry live significantly longer than well-fed animals. The data and theory suggested that very possibly resveratrol could extend an animal's lifespan. Read the newsletter about this:
Or link to an abstract of the study: Nature. 2003 Sep 11;425(6954):191-6.
At that point, we knew that yeast fed resveratrol lived longer. We also knew it would be several years until data on ‘real animals' was published. During this interval, one study showed up demonstrating a similar increase in lifespan for some sort of worm. Well now those several years have passed and the real animal studies are starting to be published.
On November 1, the same journal, Nature, released a study on the internet before print publishing it, titled, “Resveratrol improves health and survival of mice on a high-calorie diet.” The study looked at high dose resveratrol given to obese mice: "After six months, resveratrol essentially prevented most of the negative effects of the high calorie diet in mice. ... The 'healthspan' benefits we saw in the obese mice treated with resveratrol are positive clinical indicators and may mean we can stave of in humans age-related diseases such as type 2 diabetes, heart disease and cancer, but only time and more research will tell."
Or the abstract of the study at:
One has to admit this is exciting stuff. Given the multitude of undesirable effects of most standard cancer therapies, it is nice to find that resveratrol, which we have regularly suggested to our cancer patients for almost a decade, has a side effect like increasing life span.
Of course, it is not all good news. David Goldberg from the University of Toronto published a study in 2003 suggesting that these good chemicals like resveratrol and quercetin found in wine are not adequately absorbed to have any health benefit. [i] A study a year later suggests absorption, at least in mice, is significantly higher. [ii] The obvious argument is that if people didn't absorb enough of these chemicals to do any good then we wouldn't see all these studies coming out linking wine consumption with health benefits so I am partial to believing that we do absorb adequate amounts.
Resveratrol is not the kind of chemical a manufacturer can patent. No one should be surprised then, to discover that drug companies hard at work on resveratrol analogs hoping to find a chemical that works as well as resveratrol but which they can patent and own. Until then, we will have to settle for the real thing
Absorption of three wine-related polyphenols in three different matrices by healthy subjects.
Goldberg DM ,
Yan J ,
Soleas GJ .
Department of Laboratory Medicine and Pathobiology, University of Toronto , ON , Canada M5G 1L5 . firstname.lastname@example.org
BACKGROUND: Despite their powerful biologic activities conducive to protection against atherosclerosis, cancer and inflammatory diseases demonstrated in vitro, there is considerable doubt whether the polyphenolic constituents present in red wine and other dietary components are effective in vivo. OBJECTIVE: We have tested the absorptive efficiency of three of these constituents (trans-resveratrol, [+]-catechin and quercetin) when given orally to healthy human subjects in three different media. DESIGN: Twelve healthy males aged 25 to 45 were randomly assigned to three different groups consuming orally one of the following polyphenols: trans-resveratrol, 25 mg/70 kg; [+]-catechin 25 mg/70 kg; quercetin 10 mg/70 kg. Each polyphenol was randomly administered at 4-week intervals in three different matrices: white wine (11.5% ethanol), grape juice, and vegetable juice/homogenate. Blood was collected at zero time and at four intervals over the first four hours after consumption; urine was collected at zero time and for the following 24-h. The sums of free and conjugated polyphenols were measured in blood serum and urine by a gas-chromatographic method. RESULTS: All three polyphenols were present in serum and urine predominantly as glucuronide and sulfate conjugates, reaching peak concentrations in the former around 30-min after consumption. The free polyphenols accounted for 1.7 to 1.9% (trans-resveratrol), 1.1 to 6.5% ([+]-catechin) and 17.2 to 26.9% (quercetin) of the peak serum concentrations. The absorption of trans-resveratrol was the most efficient as judged by peak serum concentration, area-under-the curve (4 h) and urinary 24-h excretion (16-17% of dose consumed). [+]-Catechin was the poorest by these criteria (urine 24-h excretion 1.2%-3.0% of dose consumed), with quercetin being intermediate (urine 24-h excretion 2.9%-7.0% of dose consumed). Some significant matrix effects were observed for the serum polyphenol concentrations, but in the case of urine no matrix promoted significantly higher excretion than the other two. CONCLUSIONS: The absorption of these three polyphenols is broadly equivalent in aqueous and alcoholic matrices but, at peak concentrations of 10 to 40 nmol/L, is inadequate to permit circulating concentrations of 5 to 100 micromol/L consistent with in vitro biologic activity. The voluminous literature reporting powerful in vitro anticancer and antiinflammatory effects of the free polyphenols is irrelevant, given that they are absorbed as conjugates.
PMID: 12554065 [PubMed - indexed for MEDLINE]
Urinary and plasma levels of resveratrol and quercetin in humans, mice, and rats after ingestion of pure compounds and grape juice.
Meng X ,
Maliakal P ,
Lu H ,
Lee MJ ,
Yang CS .
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, New Jersey 08854, USA.
The present study investigates the bioavailability of resveratrol and quercetin in humans, mice, and rats after oral ingestion of grape juice preparations or pure aglycones. Oral administration of resveratrol and quercetin to humans yielded detectable levels of resveratrol, quercetin, and their derivatives in the plasma and urine. Urinary levels of resveratrol, quercetin, and their metabolites were observed in human subjects receiving 600 and 1200 mL of grape juice, whereas quercetin metabolites were identified in urine samples even after receiving 200 mL of grape juice. The cumulative amounts of resveratrol and quercetin excreted in the urine of mice receiving concentrated grape juice for 4 days were 2.3 and 0.7% of the ingested doses, respectively. After i.g. administration of resveratrol to rats (2 mg/kg), up to 1.2 microM resveratrol was observed in the plasma. The study demonstrates that the glycoside forms of resveratrol and quercetin in grape juice are absorbed to a lesser extent than the aglycones.
PMID: 14969553 [PubMed - indexed for MEDLINE]