McCarty M F
Pantox Laboratories, San Diego 92109, USA.
Med Hypotheses. 2002 Sep;59(3):268-79. doi: 10.1016/s0306-9877(02)00226-8.
Many of the wide-ranging health benefits conferred by statin therapy are mediated, not by reductions in LDL cholesterol, but rather by inhibition of isoprenylation reactions essential to the activation of Rho family GTPases; this may be the mechanism primarily responsible for the favorable impact of statins on risk for ischemic stroke, senile dementia, and fractures, as well as the anti-hypertensive and platelet-stabilizing actions of these drugs. Indeed, the extent of these benefits is such as to suggest that most adults would be wise to take statins; however, owing to the significant expense of statin therapy, as well as to the potential for dangerous side effects that mandates regular physician follow-up, this strategy appears impractical. However, policosanol, a mixture of long-chain aliphatic alcohols extractable from sugar cane wax, has shown cholesterol-lowering potency comparable to that of statins, and yet appears to be devoid of toxic risk. Recent evidence indicates that policosanol down-regulates cellular expression of HMG-CoA reductase, and thus has the potential to suppress isoprenylation reactions much like statins do. Consistent with this possibility, the results of certain clinical and animal studies demonstrate that policosanol has many effects analogous to those of statins that are not likely explained by reductions of LDL cholesterol. However, unlike statins, policosanol does not directly inhibit HMG-CoA reductase, and even in high concentrations it fails to down-regulate this enzyme by more than 50% - thus likely accounting for the safety of this nutraceutical. In light of the fact that policosanol is quite inexpensive and is becoming available as a non-prescription dietary supplement, it may represent a practical resource that could enable the general public to enjoy health benefits comparable to those conferred by statins. In a long-term clinical study enrolling patients with significant symptomatic coronary disease, Esselstyn has demonstrated that a low-fat, whole-food vegan diet, coupled with sufficient statin therapy to maintain serum cholesterol below 150 mg/dL, can stop the progression of coronary disease and virtually eliminate further risk for heart attack. A comparable regimen, in which policosanol is used in place of statins, may represent a practical strategy whereby nearly everyone willing to commit to health-protective eating can either prevent coronary disease, or prevent pre-existing coronary disease from progressing to a life-threatening event.
他汀类药物治疗带来的诸多广泛健康益处，并非由低密度脂蛋白胆固醇的降低介导，而是通过抑制对Rho家族GTP酶激活至关重要的异戊二烯化反应来实现；这可能是他汀类药物对缺血性中风、老年痴呆症和骨折风险产生有利影响的主要机制，也是这些药物的抗高血压和血小板稳定作用的主要机制。事实上，这些益处的程度表明，大多数成年人服用他汀类药物可能是明智的；然而，由于他汀类药物治疗费用高昂，以及存在需要定期医生随访的潜在危险副作用，这种策略似乎不切实际。然而， policosanol，一种可从甘蔗蜡中提取的长链脂肪醇混合物，已显示出与他汀类药物相当的降胆固醇效力，且似乎没有毒性风险。最近的证据表明，policosanol下调HMG-CoA还原酶的细胞表达，因此有可能像他汀类药物一样抑制异戊二烯化反应。与这种可能性一致，某些临床和动物研究结果表明，policosanol具有许多与他汀类药物类似的作用，而这些作用不太可能由低密度脂蛋白胆固醇的降低来解释。然而，与他汀类药物不同，policosanol并不直接抑制HMG-CoA还原酶，即使在高浓度下，它也不会使该酶下调超过50%——因此这可能说明了这种营养保健品的安全性。鉴于policosanol价格相当便宜，且正作为非处方膳食补充剂上市，它可能是一种实用资源，能使普通大众获得与他汀类药物相当的健康益处。在一项纳入有明显症状冠心病患者的长期临床研究中，埃塞尔斯坦证明，低脂、全食物纯素饮食，再加上足够的他汀类药物治疗以维持血清胆固醇低于150mg/dL，可以阻止冠心病的进展，并几乎消除进一步的心脏病发作风险。一种类似的方案，即用policosanol代替他汀类药物，可能是一种实用策略，几乎每个愿意坚持健康保护饮食的人都可以借此预防冠心病，或防止已有的冠心病发展为危及生命的事件。
