Viagra Works by Inhibiting Phosphodiesterase 5; Certain Grape Polyphenols Also Inhibit Phosphodiesterase 5: Grapes and Red Wine as Functional Orgy Foods

The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 8 No. 2 • April 2005


Viagra Works by Inhibiting Phosphodiesterase 5; Certain Grape Polyphenols Also Inhibit Phosphodiesterase 5: Grapes and Red Wine as Functional Orgy Foods

Mechanisms tell you a lot about how a drug or natural substance works. It is perfectly legal to provide label information on mechanisms (structure-function claim) so long as you do not also point out on the label when that mechanism might be involved in the treatment of disease. The battle for First Amendment freedom of speech concerning the communication by manufacturers or vendors of dietary supplements (or foods) of truthful and nonmisleading information concerning when they may be useful in treating current disease (not just reducing the risk of getting the disease in the future) continues unabated since we initiated litigation against the FDA in 1994. In the meantime, we hope to see more information on mechanisms as structure-function claims on labels. When information is important enough, the public will eventually make the connection.

A new paper1 reports that a mixture of anthocyanins (colored—usually blue or purple—flavonoids widely distributed in fruits, vegetables, and red wines) inhibits phosphodiesterase-5, an enzyme that is inhibited by Viagra with well-known results. The authors note that “In vivo red wine-derived polyphenolic compounds were able to reduce blood pressure in normo- and hypertensive rats, and the amplitude of vasorelaxation changed as a function of the variability of wine constituents according to grape varieties, cultivar, and methods for obtaining wine.” They also mention that several studies have reported that the red wine- and grape-enhanced endothelial relaxation occurred via increased generation or biological activity of NO (nitric oxide). Knowing that the cyclic GMP in vascular smooth muscle cells is regulated by phosphodiesterase-5, which determines the duration and extent of vasorelaxation, they looked into the possibility that the enzyme was also involved in the vasorelaxing effects of the red wine and grape polyphenols.

The authors tested the effects on phosphodiesterase-5 activity of six anthocyanins isolated from cabernet sauvignon. The results showed that the mixture inhibited PDE5 (this test used a recombinant form of human PDE5A1 isoenzyme). The statistically significant inhibition began at 1 µM, and at 100 µM the inhibition was almost complete. The IC50 (concentration required to inhibit enzyme activity by 50%) was 11.6 µM, which the authors explain is very close to that of the PDE5 inhibitor drug zaprinast (9.8 µM). Malvidin-3-O-beta-glucoside (a blue anthocyanin also found in blueberries) was the most active compound in the mixture, with an IC50 of 35.4 µM. The degree of inhibition of the glucosides and aglycones followed malvidin > peonidin = delphinidin > petunidin > pelargonidin = cyanidin.

The authors conclude that “Pharmacological dosing, as might occur when dietary polyphenols are consumed as supplements, might lead to AC [anthocyanin] levels compatible with the range at which anthocyanins exert vasorelaxation through PDE inhibition.”

So the next time you see an advertisement for a dietary supplement product that claims to be “the natural alternative” to Viagra, just ask yourself whether it inhibits phosphodiesterase-5. If it doesn’t, it is not “the natural alternative” to Viagra, but just a mimic (assuming that it works at all).

Reference

  1. Dell’Agli et al. In vitro inhibition of human cGMP-specific phosphodiesterase-5 by polyphenols from red grapes. J Agric Food Chem 53:1960-5 (2005).

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