Piperine (figure 1) is an alkaloid derived from black pepper (Piper spp.) that is added to some weight loss supplements because manufacturers claim it increases the bioavailability of some components of the formula. Research using animal and cell culture models has shown that peperine increases the bioavailability of epigallocatechin-3-gallate (EGCG), a flavon-3-ol flavonoid found in high concentrations in green tea. Supplement manufacturers may be interested in this research because ingestion of EGCG has been shown to increase fat oxidation and may be beneficial in the long term maintenance of healthy weight. However, the use of peperine in supplements shows a lack of understanding on the metabolism of polyphenols in humans because it makes the assumption that selectively increasing the circulating levels of EGCG is beneficial. Evidence in the literature does not support this contention.
Figure 1. The molecular structure of piperine.
Flavon-3-ols ingested from green tea are absorbed into the intestinal mucosa where they undergo extensive phase II metabolism to form glucuronide and sulfate metabolites using the enzymes UDP-glurcuronosyltransferase and sulfurtransferase respectively. Some of these metabolites then enter the hepatic circulation and are transported to the liver where they are further metabolised using phase II enzymes. Some falvon-3-ols are absorbed from the colon after bacterial metabolism to phenolic acids and then further metabolised in the liver. The end result is that the circulating levels of non-metabolised tea flavon‑3‑ols are low compared to the metabolised counterparts, such that the urinary excretion of metabolites exceeds that of the parent compounds (here). These data would tend to suggest that the biological effects of flavan-3-ols (and other flavonoids) are exerted by the phase II metabolites of the parent flavonoid.
Piperine increases bioavailability of the parent tea polyphenols because it interferes with phase II metabolism in enterocytes. Animal models suggest that glucuronidation of EGCG is decreased by 40 % in the presence of piperine. The result is that more of the parent flavonoid is absorbed across the intestinal mucosa, with lower levels of metabolites. Therefore, piperine likely inhibits the UDP-glucuronosyltranferase enzymes in enterocytes in some way. For example, administration of 70.2 µmol / kg piperine with 163.8 µmol / kg EGCG caused a 1.3 fold increase in plasma area under the curve compared to mice treated with EGCG alone1. However, there is no firm evidence that increasing the parent flavonoid plasma concentrations would increase fat oxidation in humans. In fact, evidence suggests that it is the metabolites that are biologically active, not the parent flavonoids.