Resveratrol Information

Resveratrol is a phytoalexin found in the skins of red grapes, in peanuts, blueberries, and in Japanese knotweed (polygonum cuspidatum). Most of the commercially available resveratrol is from Japanese knotweed and contains emodin, a laxative. Resveratrol has many purported benefits, though most studies in vitro use concentrations above those achieved in plasma following oral dosing with the supplement. Resveratrol may cause the effects of caloric restriction in humans, as it has in mice. Trans-resveratrol is the active form of the supplement.

According to the Linus Pauling Institute at Oregon State University, resveratrol is rapidly metabolized and eliminated following its absorption, and its absorption is good.1 Mega-doses of resveratrol or other methods may be required to reach therapeutic plasma levels for some diseases. Effects of such doses are unresearched and may be cost prohibiting for many people. Most resveratrol supplements contain 50% trans resveratrol extracted in Japanese knotweed.

Studies on Resveratrol, Ulcerative Colitis, and Colon Cancer

10mg/kg of resveratrol was as effective at reducing ulceration in rats as sulfasalazine was when given in a TNBS (trinitrobenzenesulphonic acid) model2. Doses of 20ppm and 1ppm of resveratrol were found to ameliorate DSS colitis in mice.5,6 Mice given 300 ppm resveratrol in their chow had significant reductions of many parameters of disease activity in a DSS model of colitis. When the same dose was given to mice in a model of human carcinogenesis, the incidence of tumors was 60% lower in the group receiving resveratrol compared to the control group which received the standard diet.4 The equivalent dose for humans based on these studies remains unknown, and its unlikely that any humans will be taking DSS anytime soon. The long term effects of resveratrol in humans and test animals remain largely unstudied; the reductions in tumor incidence in the short term could be reversed in the long term. Sulfasalazine has largely been replaced with mesalamine in the treatment of ulcerative colitis. These studies all apparently fail to study the effects of herbal combinations on ulcerative colitis.

In a TNBS model of colitis, resveratrol at 10mg/kg reduced COX-2, PGE2, neutrophil infiltration, and TNF-alpha levels.7 These markers of disease state and inflammation are reduced by many substances in models of colitis in mice, but efficacy in humans for the substances may be minimal.

An experiment similar to the one above was carried out in 2004. One observation was that treatment with resveratrol didnt change COX-1 levels in affected mice colons.8 Changes in COX-1 activity may be related to the formation of ulcers, though it could be that other mechanisms could reduce ulceration even if cox-1 was increased.

Resveratrol was reported to decrease upregulation of NF-kB in DSS treated mice.9 Decrease of NF-kB activation is a halmark of anti-inflammatory medications, though this may be an insignificant contribution of resveratrol to ameliorate colitis in mice.

17% of the resveratrol eaten by rats fed 300 ppm resveratrol in their chow was recovered in their feces.11 How much resveratrol that is consumed by humans reaches the colon and is active there? The answer may depend on many factors. Maybe there will be a resveratrol pill that releases resveratrol in the colon one day.

References

(1) http://lpi.oregonstate.edu/infocenter/phytochemicals/resveratrol/resverarefs.html#ref82

(2) Dalaal Abdalla et al. Resveratrol abrogates adhesion molecules and protects against TNBS-induced ulcerative colitis in rats. Canadian Journal of Physiology and Pharmacology, 2011, 89(11): 811-818, 10.1139/y11-080

(3) Yao J. et al. Anti-oxidant effects of resveratrol on mice with DSS-induced ulcerative colitis. Arch Med Res. 2010 May;41(4):288-94.

(4) Xiangli Cui et al. Resveratrol suppresses colitis and colon cancer associated with colitis. Cancer Prev Res (Phila). 2010 April; 3(4): 549–559.

(5) Sánchez-Fidalgo S, et al. Dietary supplementation of resveratrol attenuates chronic colonic inflammation in mice. Eur J Pharmacol. 2010 May 10;633(1-3):78-84. Epub 2010 Feb 2 .

(6) Larrosa M. et al. Effect of a low dose of dietary resveratrol on colon microbiota, inflammation and tissue damage in a DSS-induced colitis rat model. J Agric Food Chem. 2009 Mar 25;57(6):2211-20.

(7) Martín AR et al. The effects of resveratrol, a phytoalexin derived from red wines, on chronic inflammation induced in an experimentally induced colitis model. Br J Pharmacol. 2006 Apr;147(8):873-85.

(8) Martin AR. Et al. Resveratrol, a polyphenol found in grapes, suppresses oxidative damage and stimulates apoptosis during early colonic inflammation in rats. Biochem Pharmacol. 2004 Apr 1;67(7):1399-410.

(9) Youn J. et al. Resveratrol and piceatannol inhibit iNOS expression and NF-kappaB activation in dextran sulfate sodium-induced mouse colitis. Nutr Cancer. 2009;61(6):847-54.

(10) Lorne J. Hofseth et al. Taming the beast within: resveratrol suppresses colitis and prevents colon cancer. Aging (Albany NY). 2010 April; 2(4): 183–184.

(11) Wenzel, E., Soldo, T., Erbersdobler, H. and Somoza, V. (2005), Bioactivity and metabolism of trans-resveratrol orally administered to Wistar rats. Mol. Nutr. Food Res., 49: 482–494. doi: 10.1002/mnfr.200500003