Piperine derived from black pepper increases the plasma levels of coenzyme Q10 following oral supplementation Vladimir Badmaev, Muhammed Majeed, and Lakshmi Prakash Sabinsa Corporation, Piscataway, NJ USA An extract from the fruits of black pepper consisting of a minimum of 98% pure piperine was evaluated in a clinical study using a double-blind design. The relative bioavailability of 90 mg and 120 mg of coenzyme Q10 administered in a single-dose experiment or in separate experiments for 14 and 21 days with placebo or with 5 mg of piperine was determined by comparing measured changes in plasma concentration. The inter-subject variability was minimized by limiting the selection of individuals to healthy adult male volunteers with (presupplementation) fasting coenzyme Q10 values between 0.30 and 0.60 mg/L. The results of the single-dose study and the 14-day study indicate smaller, but not significant, increases in plasma concentrations of coenzyme Q10 in the control group compared with the group receiving coenzyme Q10 with a supplement of piperine. Supplementation of 120 mg coenzyme Q10 with piperine for 21 days produced a statistically significant (p = 0.0348), approximately 30% greater, area under the plasma curve than was observed during supplementation with coenzyme Q10 plus placebo. It is postulated that the bioenhancing mechanism of piperine to increase plasma levels of supplemental coenzyme Q10 is nonspecific and possibly based on its description in the literature as a thermonutrient. (J. Nutr. Biochem. 11:109 –113, 2000) © Elsevier Science Inc. 2000. All rights reserved. Keywords: piper nigrum; black pepper; piperine; bioperine; coenzyme Q10; bioavailability Introduction Piperine belongs to a group of compounds known as “vanilloids,” because they are distinguished by the pres- ence of a chemical group based on the structure of vanillin. Piperine is a naturally occurring compound present as the major pungent ingredient (1–9%) in various parts of plants from the family Piperaceae. 1 Piperine, an alkaloid (1-peperoyl piperidine), has been previously evaluated for its potential to enhance the serum levels of drugs and nutrients in animals and humans. 2–9 Compounds studied include drugs such as vasicine, 2 pyrazinamide, 3 rifampicin, 4 isoniazid, 3 pro- pranolol, 5 theophylline, 5 and phenytoin, 6 and nutrients 8,9 such as fat soluble beta-carotene, water soluble vitamin B 6 , vitamin C, and the mineral selenium in the form of L-selenomethionine. The results of clinical studies of piperine with drugs indicate that piperine administered orally at a single dose of 20 to 50 mg may significantly increase serum drug levels by reducing the clearance of drugs, both naturally derived and synthetic. This effect is primarily due to piperine’s ability to inhibit (by a noncompetitive mechanism) the xenobiotic (drug) metab- olizing enzymes when administered in a high dose. 3,4 On the other hand, the increased nutrient absorption in the presence of piperine appears to be independent of the inhibition of the biotransforming enzymes and has been achieved with as little as 5 mg of piperine coadministered with the supplemented nutrient. 8,9 The purpose of the this study was to compare the serum response to the biologically important nutritional compound coenzyme Q10, administered to healthy male volunteers with piperine or a placebo under various treatment protocols. This work was funded by Sabinsa Corporation. Sabinsa is a manufacturer of piperine and coenzyme Q10. Address correspondence to Dr. Vladimir Badmaev, Sabinsa Corporation, 121 Ethel Road West, Unit 6, Piscataway, NJ USA. Received August 3, 1999; accepted October 28, 1999. J. Nutr. Biochem. 11:109 –113, 2000 © Elsevier Science Inc. 2000. All rights reserved. 0955-2863/00/$–see front matter 655 Avenue of the Americas, New York, NY 10010 PII S0955-2863(99)00074-1