Synergistic effect of tocotrienol-rich fraction (TRF25) of rice bran and lovastatin on lipid parameters in hypercholesterolemic humans

Tocotrienols exert hypocholesterolemic action in humans and animals. Lovast atin is widely used for that purpose. Both agents work by suppressing the a ctivity of beta -hydroxy-beta -methylglutaryl coenzyme A reductase through different mechanisms, post-transcriptional vs competitive inhibition. A hum an study with 28 hypercholesterolemic subjects was carried out in 5 phases of 35 days each, to check the efficacy of tocotrienol-rich fraction (TRF25) of rice bran alone and in combination with lovastatin. After placing subje cts on the American Heart Association (AHA) Step-1 diet (phase II), the sub jects were divided into two groups. A and B. The AHA Step-1 diet was contin ued in combination with other treatments during phases III to V. Group A su bjects were given 10 mg lovastatin, 10 mg lovastatin plus 50 mg TRF25, 10 m g lovastatin plus 50 mg alpha -tocopherol per day, in the third, fourth, an d fifth phases, respectively. Group B subjects were treated exactly to the same protocol except that in the third phase, they were given 50 mg TRF25 i nstead of lovastatin. The TRF25 or lovastatin plus AHA Step-1 diet effectively lower serum total cholesterol (14%, 13%) and LDL-cholesterol (18%, 15% P < 0.001), respective ly, in hypercholesterolemic subjects. The combination of TRF25 and lovastat in plus AHA Step-1 diet significantly reduces of these lipid parameters of 20% and 25% (P < 0.001) in these subjects. Substitution of TRF25 with alpha -tocopherol produces insignificant changes when given with lovastatin. Esp ecially significant is the increase in the HDL/LDL ratio to 46% in group (A ) and 53% (P < 0.002) in group (B). These results are consistent with the s ynergistic effect of these two agents. None of the subjects reported any si de-effects throughout the study of 25-weeks. In the present study, the incr eased effectiveness of low doses of tocotrienols (TRF25) as hypocholesterol emic agents might be dire to a minimum conversion to alpha -tocopherol. The report also describes in vivo the conversion of gamma-[4-H-3]-, and [C-14] -desmethyl (d-P-21-T3) tocotrienols to alpha -tocopherol. (C) 2001 Elsevier Science Inc. All rights reserved.