McCarty Mark F
NutriGuard Research, 1051 Hermes Avenue, Encinitas, CA 92024, USA.
Med Hypotheses. 2005;64(3):636-45. doi: 10.1016/j.mehy.2003.12.051.
Although many risk factors influence atherogenesis, LDL appears to play a primary role in this process. In prospective epidemiology, coronary risk increases as LDL cholesterol increases, throughout the entire range of concentrations encountered in healthy humans. Coronary risk is minimal in individuals and populations whose serum cholesterol remains quite low throughout life. Thus, practical strategies for achieving large reductions of LDL cholesterol in the general population could have a dramatic impact on coronary mortality rates. Dietary measures have limited potential in this regard; modest restriction of saturated fat has a rather trivial effect on LDL cholesterol, and the very-low-fat quasi-vegan diets that do have a notable effect in this regard currently have little appeal to the majority of the population. With respect to pharmacotherapy, most available hypolipidemic agents with reasonably potent activity entail side effects or compliance difficulties that would render their use too expensive or impractical for population-wide application. However, two agents may have great potential in this regard: policosanol and ezetimibe. The former, a mixture of long-chain alcohols derived from sugar cane wax, has effects on serum lipids comparable to those of statins, and may work by down-regulating expression of HMG-CoA reductase. However, unlike statins, policosanol appears to be devoid of side effects or risks. Ezetimibe is a newly approved drug that is a potent and highly specific inhibitor of an intestinal sterol permease; in daily doses as low as 10 mg, it suppresses intestinal absorption of cholesterol and decreases serum LDL cholesterol by approximately 18%. No side effects have been seen in clinical doses, and the fact that its hypolipidemic activity is additive to that of statins has generated considerable interest. Both policosanol and ezetimibe can be administered once daily. Future studies should determine whether policosanol, like statins, interacts additively with ezetimibe. If so, it may be feasible someday to produce a tablet combining policosanol and ezetimibe that could reduce LDL cholesterol by about 40%, without side effects, and that could be recommended to virtually anyone whose LDL cholesterol levels were not already ideal.
尽管有许多风险因素影响动脉粥样硬化的发生，但低密度脂蛋白（LDL）似乎在这一过程中起主要作用。在前瞻性流行病学研究中，在健康人群所遇到的整个浓度范围内，随着LDL胆固醇水平的升高，冠心病风险也随之增加。在血清胆固醇一生都保持相当低水平的个体和人群中，冠心病风险最小。因此，在普通人群中大幅降低LDL胆固醇的实用策略可能会对冠心病死亡率产生巨大影响。饮食措施在这方面的潜力有限；适度限制饱和脂肪对LDL胆固醇的影响相当微不足道，而在这方面确实有显著效果的极低脂肪类纯素饮食目前对大多数人几乎没有吸引力。关于药物治疗，大多数现有的具有相当强效活性的降血脂药物都有副作用或依从性问题，这使得它们因使用成本过高或不切实际而无法用于广泛的人群。然而，有两种药物在这方面可能具有巨大潜力：聚多卡醇和依折麦布。前者是一种从甘蔗蜡中提取的长链醇混合物，对血脂的影响与他汀类药物相当，可能通过下调HMG - CoA还原酶的表达起作用。然而，与他汀类药物不同，聚多卡醇似乎没有副作用或风险。依折麦布是一种新批准的药物，是一种强效且高度特异性的肠道固醇通透酶抑制剂；每日剂量低至10毫克时，它可抑制肠道对胆固醇的吸收，并使血清LDL胆固醇降低约18%。临床剂量下未见副作用，而且其降血脂活性与他汀类药物具有相加作用这一事实引起了广泛关注。聚多卡醇和依折麦布都可以每日服用一次。未来的研究应确定聚多卡醇是否像他汀类药物一样与依折麦布具有相加作用。如果是这样，也许有一天有可能生产出一种将聚多卡醇和依折麦布结合的片剂，它可以在无副作用的情况下将LDL胆固醇降低约40%，并且几乎可以推荐给任何LDL胆固醇水平不理想的人。
