Novel tocotrienols of rice bran modulate cardiovascular disease risk parameters of hypercholesterolemic humans

Abstract

Tocotrienols inhibit cholesterol synthesis by post-transcriptionally suppressing β-hydroxy-β-methylglutaryl-coenzyme A reductase activity. A double blind, 12-week study was performed to investigate the effect of a novel tocotrienol-rich fraction (TRF 25; obtained by molecular distillation from specially processed rice bran oil) on cardiovascular disease risk factors of hypercholesterolemic human subjects (serum total cholesterol >5.69 mmol/L). After acclimation to an alcohol-free regimen (baseline) participants were assigned to the National Cholesterol Education Program (NCEP) Step-1 diet (saturated fat <19%, total fat <30% of total calories and cholesterol <7.76 mmol/L). The participants were evaluated after 4 weeks of exposure to the NCEP Step-1 diet; one group of 21 participants was continued on the NCEP Step-1 diet for 4 weeks receiving an additional 1.2 gm corn oil (placebo group) and a second group of 20 received 200 mg TRF 25 dissolved in 1.0 gm corn oil (TRF 25 group). Serum total cholesterol and LDL-cholesterol levels of all the participants, stable during the baseline phase of the study, decreased 5% and 8%, respectively, during the 4-week NCEP Step-1 diet. Placebo continuing on the NCEP Step-1 diet for an additional 4 weeks experienced additional but modest decreases in serum total cholesterol (2%) and LDL-cholesterol (3%), yielding significant ( P < 0.05) decreases when compared with the baseline values. These responses confirm the cholesterol-lowering action of a low fat, low cholesterol diet. Participants receiving TRF 25 had 12% and 16% reductions ( P < 0.05) in total cholesterol and LDL-cholesterol levels during the 4-week experimental phase; during the two phases (NCEP Step-1 diet plus treatment) the serum total cholesterol and LDL-cholesterol levels of these participants were decreased ( P < 0.05) by 17% and 24%, respectively. TRF 25-mediated decreases in Apo B, Lp(a), platelet factor 4 and thromboxane B 2 (15%, 17%, 14%, and 31%, respectively) were significant ( P < 0.05). There was no change in the levels of HDL-cholesterol and apolipoprotein A-I by this treatment. The treatments also resulted in remarkable increases in the levels of LDL-bound antioxidants, especially tocotrienols, which have substantially greater antioxidant activity than vitamin E.