Christen W G, Gaziano J M, Hennekens C H
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Ann Epidemiol. 2000 Feb;10(2):125-34. doi: 10.1016/s1047-2797(99)00042-3.
To assess the balance of benefits and risks of supplementation with beta-carotene, vitamin E, vitamin C, and multivitamins on cancer, cardiovascular (CVD), and eye diseases.
Physicians' Health Study II (PHS II) is a randomized, double-blind, placebo-controlled trial enrolling 15,000 willing and eligible physicians aged 55 years and older. PHS II will utilize a 2 x 2 x 2 x 2 factorial design to test alternate day beta-carotene, alternate day vitamin E, daily vitamin C, and a daily multivitamin, in the prevention of total and prostate cancer, CVD, and the age-related eye diseases, cataract and macular degeneration. PRIOR RESULTS: The final results of the recently completed Physicians' Health Study I (PHS I), a randomized, double-blind, placebo-controlled trial in 22,071 healthy US male physicians, indicated that beta-carotene supplementation (50 mg on alternate days) had no significant benefit or harm on cancer or CVD during more than 12 years of treatment and follow-up. In regards to cancer, there were possible benefits on total and prostate cancer in those with low baseline levels assigned to beta-carotene, a finding compatible with the Chinese Cancer Prevention Study for combined treatment with beta-carotene, vitamin E, and selenium in a poorly nourished population. Further, with respect to CVD, there were apparent benefits of beta-carotene supplementation on subsequent vascular events among a small subgroup of 333 men with prior angina or revascularization. The currently available data from randomized trials of primary prevention are sparse and inconsistent for vitamin E and non-existent for vitamin C and multivitamins. For eye diseases, namely cataract and age-related macular degeneration, there are no completed large-scale randomized trials of antioxidant vitamins.
PHS II is unique in several respects. PHS II is the only primary prevention trial in apparently healthy men testing the balance of benefits and risks of vitamin E on cancer and CVD. In addition, PHS II is the only primary prevention trial in apparently healthy men to test the balance of benefits and risks of vitamin C, multivitamins, as well as any single antioxidant vitamin, alone and in combination, on cancer, CVD, and eye diseases. Finally, PHS II is the only trial testing a priori the hypotheses that beta-carotene and vitamin E may reduce the risks of prostate cancer. Thus, PHS II will add unique as well as importantly relevant and complementary information to the totality of evidence from other completed and ongoing large-scale randomized trials on the balance of benefits and risks of beta-carotene, vitamin E, vitamin C, and multivitamins alone and in combination on prevention of cancer, CVD and eye diseases.
评估补充β-胡萝卜素、维生素E、维生素C和多种维生素对癌症、心血管疾病（CVD）和眼部疾病的利弊平衡。
医生健康研究II（PHS II）是一项随机、双盲、安慰剂对照试验，招募了15000名年龄在55岁及以上、愿意且符合条件的医生。PHS II将采用2×2×2×2析因设计，以测试隔日服用β-胡萝卜素、隔日服用维生素E、每日服用维生素C和每日服用多种维生素对预防总体癌症和前列腺癌、CVD以及与年龄相关的眼部疾病（白内障和黄斑变性）的效果。先前结果：最近完成的医生健康研究I（PHS I）是一项针对22071名美国健康男性医生的随机、双盲、安慰剂对照试验，其最终结果表明，在超过12年的治疗和随访期间，补充β-胡萝卜素（隔日50毫克）对癌症或CVD没有显著益处或危害。关于癌症，在基线水平较低且被分配服用β-胡萝卜素的人群中，对总体癌症和前列腺癌可能有益，这一发现与中国癌症预防研究中关于在营养不良人群中联合使用β-胡萝卜素、维生素E和硒的研究结果一致。此外, 关于CVD，在333名既往有心绞痛或血运重建史的男性小亚组中，补充β-胡萝卜素对后续血管事件有明显益处。目前来自一级预防随机试验的关于维生素E的数据稀少且不一致，而关于维生素C和多种维生素的数据则不存在。对于眼部疾病，即白内障和年龄相关性黄斑变性，尚无完成的抗氧化维生素大规模随机试验。
PHS II在几个方面具有独特性。PHS II是唯一一项在表面健康男性中进行的一级预防试验，测试维生素E对癌症和CVD的利弊平衡。此外，PHS II是唯一一项在表面健康男性中进行的一级预防试验，测试维生素C、多种维生素以及任何单一抗氧化维生素单独或联合使用对癌症、CVD和眼部疾病的利弊平衡。最后，PHS II是唯一一项事先检验β-胡萝卜素和维生素E可能降低前列腺癌风险这一假设的试验。因此，PHS II将为其他已完成和正在进行的大规模随机试验的全部证据增添独特且重要的相关补充信息，这些证据涉及β-胡萝卜素、维生素E、维生素C和多种维生素单独或联合使用在预防癌症、CVD和眼部疾病方面的利弊平衡。
