Dose-dependent cholesterolemic activity of tocotrienols

Tocotrienols and tocopherols are isoforms of vitamin E. Vitamin E may exhibit antioxidant, prooxidant and non-antioxidant activities depending upon circumstances. In this study, the effect of tocotrienols and a-tocopherol on the activities of HMG CoA reductase and cholesterol 7 a-hydroxylase was investigated. Pure tocotrienols were isolated from palm fatty acid distillate and pure a-tocopherol was obtained commercially. Guinea pigs were treated with different dosages of tocotrienols and a-tocopherol. After the treatment period, animals were sacrificed and liver microsomes were prepared. HMG CoA reductase and cholesterol 7a-hydroxylase were assayed using tracer techniques. Our results showed that the effects of tocotrienols and a-tocopherol on the activities of both the enzymes were dose-dependent. At low dosages, both tocotrienols and a-tocopherol exhibited an inhibitory effect on both the enzymes. Moreover, tocotrienols were a much stronger inhibitors than a-tocopherol. At high dosages, on the other hand, tocotrienols and a-tocopherol showed opposite effects on the enzymes. While tocotrienols continued to exhibit an inhibitory effect, a-tocopherol actually exhibited a stimulatory effect on both the enzymes. A possible explanation for this observation is suggested.