Cartmel B, Dziura J, Cullen M R, Vegso S, Omenn G S, Goodman G E, Redlich C A
Department of Epidemiology and Public Health and the Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06510, USA.
Eur J Clin Nutr. 2005 Oct;59(10):1173-80. doi: 10.1038/sj.ejcn.1602229.
The Beta-Carotene and Retinol Efficacy Trial (CARET) was terminated 21 months ahead of schedule due to an excess of lung cancers. Deaths from cardiovascular disease also increased (relative risk=1.26 (95% confidence interval (CI) 0.99-1.61)) in the group assigned to a combination of 30 mg beta-carotene and 25 000 IU retinyl palmitate (vitamin A) daily. The basis for increased cardiovascular mortality is unexplained.
We analyzed data on serum lipids, available for 1474 CARET Vanguard participants who were enrolled in the two CARET pilot studies and transitioned to the Vanguard study. Total cholesterol and triglycerides were measured 2 months prior to, 4 and 12 months following randomization, and annually thereafter for up to 7 y.
In the asbestos-exposed pilot (N = 816), participants were assigned to beta-carotene and retinol or to placebo; in the smokers pilot (N = 1029), participants were assigned to beta-carotene, retinol, a combination, or placebo.
Serum cholesterol showed a decline over time in both arms; serum triglycerides had a continuous decline over time in the placebo arm, but an initial increase that persisted in the active arm. Both serum cholesterol concentrations (P < 0.0003) and serum triglycerides (P < 0.0001) were significantly higher in the participants receiving vitamin A and/or a combination of vitamin A and beta-carotene (n = 863) as compared to the placebo group (n = 611). Those in this active intervention group had an average cholesterol concentration 5.3 mg/dl (0.137 mmol/l) higher than those in the placebo arm.
The differences in cholesterol and triglyceride concentrations between the groups following randomization may account in part for the unexpected excess in cardiovascular deaths seen in the active intervention arm of CARET.
β-胡萝卜素与视黄醇功效试验（CARET）因肺癌病例过多而提前21个月终止。在每日服用30毫克β-胡萝卜素与25000国际单位棕榈酸视黄酯（维生素A）组合的组中，心血管疾病死亡人数也有所增加（相对风险=1.26（95%置信区间（CI）0.99 - 1.61））。心血管死亡率增加的原因尚不清楚。
我们分析了1474名CARET先锋研究参与者的血脂数据，这些参与者参加了两项CARET试点研究并过渡到先锋研究。在随机分组前2个月、随机分组后4个月和12个月以及此后每年测量总胆固醇和甘油三酯，最长达7年。
在石棉暴露试点（N = 816）中，参与者被分配到β-胡萝卜素和视黄醇组或安慰剂组；在吸烟者试点（N = 1029）中，参与者被分配到β-胡萝卜素、视黄醇、两者组合或安慰剂组。
两组的血清胆固醇均随时间下降；安慰剂组的血清甘油三酯随时间持续下降，但活性组最初升高且持续存在。与安慰剂组（n = 611）相比，接受维生素A和/或维生素A与β-胡萝卜素组合的参与者（n = 863）的血清胆固醇浓度（P < 0.0003）和血清甘油三酯（P < 0.0001）显著更高。该活性干预组的平均胆固醇浓度比安慰剂组高5.3毫克/分升（0.137毫摩尔/升）。
随机分组后两组之间胆固醇和甘油三酯浓度的差异可能部分解释了CARET活性干预组中心血管死亡意外增加的情况。
