The Durk Pearson & Sandy Shaw^®
Life Extension News^TM
Volume 8 No. 1 • January 2005

Inhibition of COX-1 causes an important antiplatelet (anticlotting) effect by inhibiting the production of the proclotting thromboxane A2 while not affecting the ability of COX-2 to continue to produce prostacyclin, a major anticlotting substance. (See article above for potential side effects from excessive inhibition of COX-1.) A new paper¹ now reports that resveratrol and chemically related compounds (m-hydroquinones, such as catechins, epicatechins, and quercetin) found in red wines are potent inactivators of COX-1, with no similar effect on COX-2. Inhibition of COX-1 (though not selective) is, of course, a mechanism for aspirin’s antiplatelet atheroprotective effects.

The inhibition of COX-1 by resveratrol was reported to occur at low micromolar concentrations. The poor absorption of resveratrol may limit the inhibition of COX-1, but there is evidence of antiplatelet effects by red wine. It may be that the poor absorption of resveratrol is why we have never heard of hemorrhagic or ulcerative mucosal damage as a result of drinking moderate amounts of red wine. The polyphenols found in many vegetables and fruits have this COX-1-inhibiting-type structure; perhaps this is one of the mechanisms by which diets rich in fruits and vegetables help protect against cardiovascular disease. Since fruits and vegetables have been major constituents of animal diets for hundreds of millions of years, it is not surprising that the polyphenols in them do not cause gut hemorrhage at normal intakes.

1. Szewczuk and Penning. Mechanism-based inactivation of COX-1 by red wine m-hydroquinones: a structure-activity study. J Nat Prod 67i(11):1777-82 (2004).