G. Shoba, D. Joy, T. Joseph, M. Majeed, R. Rajendran and P.S. Srinivas

The medicinal properties of curcumin obtained from Curcuma longa L. cannot be utilized because of poor bioavailability due to its rapid metabolism in the liver and intestinal wall. In this study, the effect of combining piperine, a known inhibitor of hepatic and intestinal glucuronidation, was evaluated on the bioavailability of curcumin in rats and healthy human volunteers. When curcumin was given alone, in the dose 2 g/kg to rats, moderate serum concentrations were achieved over a period of 4 h. Concomitant administration of piperine 20 mg/kg increased the serum concentration of curcumin for a short period of 1-2 h post drug. Time to maximum was significantly increased (P < 0.02) while elimination half life and clearance significantly decreased (P < 0.02) and the bioavailability was increased by 154%. On the other hand in humans after a dose of 2 g curcumin alone, serum levels were either undetectable or very low. Concomitant administration of piperine 20 mg produced much higher concentrations from 0.25 to 1 h post drug (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h); the increase in bioavailability was 2000%. The study shows that in the dosages used, piperine enhances the serum concentration, extent of absorption and bioavailability of curcumin in both rats and humans with no adverse effects.

Vladimir Badmaev, M.D., Ph.D., Muhammed Majeed, Ph.D. and Edward P. Norkus Ph.D.

The effectiveness of an extract from the fruit of black pepper, consisting of a minimum of 98% pure alkaloid piperine was evaluated for its ability to improve serum response of beta-carotene during oral supplementation using a double-blind, crossover study design. Subjects were randomly selected to ingest a daily beta-carotene dose (15 mg) either with 5 mg of piperine or placebo during each of two 14-day supplementation periods. Inter-subject variability in pre-supplementation serum beta-carotene levels was minimized by limiting the selection of volunteers to healthy adult males with fasting serum beta-carotene values < 20 mcg/dL. The results indicate that significantly greater increases (p < 0.0001) in serum beta-carotene occurred during supplementation with beta carotene plus piperine (49.8±9.6 mcg/dL vs. 30.9±5.4 mcg/dL) compared to beta-carotene plus placebo. Supplementation with beta-carotene plus piperine for 14 days produced a 60% greater increase in area under the serum beta- carotene curve (AUC) than was observed during supplementation with beta-carotene plus placebo. We suggest that the serum response during oral beta-carotene supplementation is improved through non-specific, thermogenic property(s) of piperine described in this paper as thermonutrient action.

Vladimir Badmaev, M.D., Ph.D., Muhammed Majeed, Ph.D., and Lakshmi Prakash, Ph.D.

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 (pre-supplementation) fasting coenzyme Q10 values between 0.30 and 0.60 mg/L. The results of a 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 to the group receiving coenzyme Q10 with a supplement of piperine. Supplementation of 120 mg of coenzyme Q10 with piperine for 21 days produced a statistically significant (p=0.0348), approximately 30% greater, area under the plasma curve (AUC) than 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.