ergo-log.com

Definition: "An ergogenic aid is any substance or phenomenon that enhances performance "

02.08.2013

Piceatannol for endurance athletes – the EPO effect

Endurance athletes looking for a new performance-enhancing supplement could consider trying piceatannol. We base our suggestion on a test-tube study that molecular scientists at Pusan National University in Korea published in the European Journal of Pharmacology, and from which we conclude that piceatannol supplementation may boost EPO production.

The Koreans' study actually has nothing to do with sport, but everything to do with gut problems such as Crohn's disease and ulcerative colitis, in which the intestines are chronically inflamed. Animal studies have shown that increased activity of the transcription factor Hypoxia-Inducible Factor-1-alpha [HIF-1-alpha] [structural formula shown above] reduces the inflammation associated with colitis. HIF-1-alpha arms cells against oxygen deficiency and therefore increases their survival chances.

So if you also know that the group of compounds to which piceatannol belongs boost the activity of HIF-1-alpha, then you understand the direction of the Koreans' reasoning: could piceatannol be used to activate HIF-1-alpha? If the answer is yes, piceatannol might be a substance we could use to alleviate colitis.

Piceatannol happens to be an analogue of resveratrol. Like resveratrol it's found in black grapes.

Bulk suppliers have had piceatannol in their catalogues for a number of years, so it probably won't be long before supplements containing powerful doses of piceatannol appear on the market.

Endurance athletes with a fetish for life sciences will be familiar with HIF-1-alpha. It makes the body synthesise more EPO and VEGF.

Cobalt chloride is an effective endurance drug as it induces free radical activity in the body, thereby boosting the concentration of HIF-1-alpha, and via HIF-1-alpha boosting the synthesis of EPO. [Br J Sports Med. 2005 Nov;39(11):872-3.]

Salidroside, a compound found in Rhodiola rosea, does the same - but in a way that probably has fewer health risks associated with it.

The Koreans added piceatannol [PCT] to HCT116 intestinal cells in a test tube, and observed that the compound acted as they expected. Piceatannol boosted the synthesis of HIF-1-alpha and VEGF.

The researchers discovered that piceatannol sabotages the enzyme HIF-prolyl-4-hydroxylase. This enzymes cuts proline groups off from HIF-1-alpha molecules at a critical location, after which cellular machines chop up the transcription factor into amino acid pieces.

Resveratrol had no effect on HIF-1-alpha. Piceatannol's catechol group is needed to inhibit HIF-prolyl-4-hydroxylase, the Koreans discovered. Resveratrol, which has a resorcinol group, had no effect on the enzyme.

The potential EPO-boosting properties of piceatannol are not unique. Researchers from the same group published the results of an in-vitro study in 2007, in which the flavonoid quercetin had exactly the same effect on gut cells. [Mol Pharmacol. 2007 Jun;71(6):1676-84.]

Enzymes attach sugar groups to piceatannol in the body, so that the kidneys can expel the compound. Animal studies show that the process is fast. [J Pharm Pharmacol. 2006 Nov;58(11):1443-50.] Certainly if the sugar groups attach themselves to the catechol group, you might wonder whether the compound doesn't become inactive.

There are studies however that would seem to suggest that metabolised piceatannol does remain reasonably active. One of these is an in vitro study that we wrote about in 2010. In this study a sugared analogue of piceatannol, piceatannol-3'-O-beta-D-glucopyranoside [formula shown here], boosted the NO production of kidney cells.

The pathway diagram above suggests that EPO synthesis probably also increased.

Source:
Eur J Pharmacol. 2013 Jan 15;699(1-3):124-31.

More:
Rhodiola compound boosts EPO production 07.06.2013
Astragalus membranaceus boosts EPO synthesis 22.09.2012
Chinese herbal preparation Danggui Buxue Tang boosts EPO 30.09.2010