N Engl J Med. 1994 Apr 14;330(15):1029-35. doi: 10.1056/NEJM199404143301501.
Epidemiologic evidence indicates that diets high in carotenoid-rich fruits and vegetables, as well as high serum levels of vitamin E (alpha-tocopherol) and beta carotene, are associated with a reduced risk of lung cancer.
We performed a randomized, double-blind, placebo-controlled primary-prevention trial to determine whether daily supplementation with alpha-tocopherol, beta carotene, or both would reduce the incidence of lung cancer and other cancers. A total of 29,133 male smokers 50 to 69 years of age from southwestern Finland were randomly assigned to one of four regimens: alpha-tocopherol (50 mg per day) alone, beta carotene (20 mg per day) alone, both alpha-tocopherol and beta carotene, or placebo. Follow-up continued for five to eight years.
Among the 876 new cases of lung cancer diagnosed during the trial, no reduction in incidence was observed among the men who received alpha-tocopherol (change in incidence as compared with those who did not, -2 percent; 95 percent confidence interval, -14 to 12 percent). Unexpectedly, we observed a higher incidence of lung cancer among the men who received beta carotene than among those who did not (change in incidence, 18 percent; 95 percent confidence interval, 3 to 36 percent). We found no evidence of an interaction between alpha-tocopherol and beta carotene with respect to the incidence of lung cancer. Fewer cases of prostate cancer were diagnosed among those who received alpha-tocopherol than among those who did not. Beta carotene had little or no effect on the incidence of cancer other than lung cancer. Alpha-tocopherol had no apparent effect on total mortality, although more deaths from hemorrhagic stroke were observed among the men who received this supplement than among those who did not. Total mortality was 8 percent higher (95 percent confidence interval, 1 to 16 percent) among the participants who received beta carotene than among those who did not, primarily because there were more deaths from lung cancer and ischemic heart disease.
We found no reduction in the incidence of lung cancer among male smokers after five to eight years of dietary supplementation with alpha-tocopherol or beta carotene. In fact, this trial raises the possibility that these supplements may actually have harmful as well as beneficial effects.
流行病学证据表明，富含类胡萝卜素的水果和蔬菜的高摄入饮食，以及血清中高含量的维生素E（α-生育酚）和β-胡萝卜素，与肺癌风险降低相关。
我们进行了一项随机、双盲、安慰剂对照的一级预防试验，以确定每日补充α-生育酚、β-胡萝卜素或两者是否会降低肺癌及其他癌症的发病率。来自芬兰西南部的29133名年龄在50至69岁的男性吸烟者被随机分配到四种方案之一：单独使用α-生育酚（每日50毫克）、单独使用β-胡萝卜素（每日20毫克）、α-生育酚和β-胡萝卜素两者、或安慰剂。随访持续了五至八年。
在试验期间诊断出的876例肺癌新病例中，接受α-生育酚的男性肺癌发病率没有降低（与未接受者相比发病率变化为-2%；95%置信区间为-14%至12%）。出乎意料的是，我们观察到接受β-胡萝卜素的男性肺癌发病率高于未接受者（发病率变化为18%；95%置信区间为3%至36%）。我们没有发现α-生育酚和β-胡萝卜素在肺癌发病率方面存在相互作用的证据。接受α-生育酚的人诊断出的前列腺癌病例比未接受者少。β-胡萝卜素对除肺癌以外的其他癌症发病率几乎没有影响。α-生育酚对总死亡率没有明显影响，尽管接受这种补充剂的男性中因出血性中风死亡的人数比未接受者多。接受β-胡萝卜素的参与者的总死亡率比未接受者高8%（95%置信区间为1%至16%），主要是因为肺癌和缺血性心脏病导致的死亡更多。
在对男性吸烟者进行五至八年的α-生育酚或β-胡萝卜素膳食补充后，我们没有发现肺癌发病率降低。事实上，这项试验提出了这些补充剂可能既有有害影响又有有益影响的可能性。
