Qureshi A A., Sami S A., Salser W A., Khan F A.
Advanced Medical Research, 8251 Raymond Road, 53719, Madison, WI, USA
J Nutr Biochem. 2001 Jun;12(6):318-329. doi: 10.1016/s0955-2863(01)00144-9.
Tocotrienols exert hypocholesterolemic action in humans and animals. Lovastatin is widely used for that purpose. Both agents work by suppressing the activity of beta-hydroxy-beta-methylglutaryl coenzyme A reductase through different mechanisms, post-transcriptional vs competitive inhibition. A human study with 28 hypercholesterolemic subjects was carried out in 5 phases of 35 days each, to check the efficacy of tocotrienol-rich fraction (TRF(25)) of rice bran alone and in combination with lovastatin. After placing subjects on the American Heart Association (AHA) Step-1 diet (phase II), the subjects were divided into two groups, A and B. The AHA Step-1 diet was continued in combination with other treatments during phases III to V. Group A subjects were given 10 mg lovastatin, 10 mg lovastatin plus 50 mg TRF(25), 10 mg lovastatin plus 50 mg alpha-tocopherol per day, in the third, fourth, and fifth phases, respectively. Group B subjects were treated exactly to the same protocol except that in the third phase, they were given 50 mg TRF(25) instead of lovastatin.The TRF(25) or lovastatin plus AHA Step-1 diet effectively lower serum total cholesterol (14%, 13%) and LDL-cholesterol (18%, 15% P < 0.001), respectively, in hypercholesterolemic subjects. The combination of TRF(25) and lovastatin plus AHA Step-1 diet significantly reduces of these lipid parameters of 20% and 25% (P < 0.001) in these subjects. Substitution of TRF(25) with alpha-tocopherol produces insignificant changes when given with lovastatin. Especially 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 synergistic effect of these two agents. None of the subjects reported any side-effects throughout the study of 25-weeks. In the present study, the increased effectiveness of low doses of tocotrienols (TRF(25)) as hypocholesterolemic agents might be due to a minimum conversion to alpha-tocopherol. The report also describes in vivo the conversion of gamma-[4-3H]-, and [14C]-desmethyl (d-P(21)-T3) tocotrienols to alpha-tocopherol.
生育三烯酚在人和动物中具有降胆固醇作用。洛伐他汀广泛用于此目的。两种药物都通过不同机制抑制β-羟基-β-甲基戊二酰辅酶A还原酶的活性，即转录后抑制与竞争性抑制。对28名高胆固醇血症患者进行了一项人体研究，分为5个阶段，每个阶段35天，以检查米糠富含生育三烯酚的组分（TRF(25)）单独使用以及与洛伐他汀联合使用的疗效。在让受试者采用美国心脏协会（AHA）第一步饮食（第二阶段）后，将受试者分为A组和B组。在第三至第五阶段，AHA第一步饮食与其他治疗联合继续进行。A组受试者在第三、第四和第五阶段分别每日给予10毫克洛伐他汀、10毫克洛伐他汀加50毫克TRF(25)、10毫克洛伐他汀加50毫克α-生育酚。B组受试者的治疗方案完全相同，只是在第三阶段给予50毫克TRF(25)而非洛伐他汀。TRF(25)或洛伐他汀加AHA第一步饮食分别可有效降低高胆固醇血症患者的血清总胆固醇（14%，13%）和低密度脂蛋白胆固醇（18%，15%，P<0.001）。TRF(25)与洛伐他汀加AHA第一步饮食联合可使这些受试者的这些血脂参数显著降低20%和25%（P<0.001）。α-生育酚替代TRF(25)与洛伐他汀合用时产生的变化不显著。特别显著的是，A组的高密度脂蛋白/低密度脂蛋白比值增加至46%，B组增加至53%（P<0.002）。这些结果与这两种药物的协同作用一致。在整个25周的研究中，没有受试者报告任何副作用。在本研究中，低剂量生育三烯酚（TRF(25)）作为降胆固醇药物有效性增加可能是由于其向α-生育酚的转化最少。该报告还在体内描述了γ-[4-³H]-和[¹⁴C]-去甲基（d-P(21)-T3）生育三烯酚向α-生育酚的转化。
