From the Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark (CJK, SA, and BGN); the Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (CJK, SA, and BGN); the Medical Research Council Integrative Epidemiology Unit at the University of Bristol, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (GDS); and the Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Frederiksberg, Denmark (BGN).
Am J Clin Nutr. 2015 Jun;101(6):1135-43. doi: 10.3945/ajcn.114.104497. Epub 2015 May 6.
High intake of fruit and vegetables as well as high plasma vitamin C concentrations have been associated with low risk of ischemic heart disease in prospective studies, but results from randomized clinical trials have been inconsistent.
We tested the hypothesis that genetically high concentrations of plasma vitamin C, such as with high intake of fruit and vegetables, are associated with low risk of ischemic heart disease and all-cause mortality.
We used a Mendelian randomization approach and genotyped for solute carrier family 23 member 1 (SLC23A1) rs33972313 in the sodium-dependent vitamin C transporter 1 in 97,203 white individuals of whom 10,123 subjects had ischemic heart disease, and 8477 subjects died. We measured plasma vitamin C in 3512 individuals and included dietary information on 83,256 individuals.
The SLC23A1 rs33972313 G allele was associated with 11% higher plasma vitamin C. The multivariable adjusted HRs for highest compared with lowest fruit and vegetable intakes were 0.87 (95% CI: 0.78, 0.97; P = 0.01) for ischemic heart disease and 0.80 (95% CI: 0.73, 0.88; P < 0.001) for all-cause mortality. Corresponding HRs for rs33972313 GG (93%) compared with AA plus AG (7%) genotypes were 0.95 (95% CI: 0.88, 1.02; P = 0.21) and 0.96 (0.88, 1.03; P = 0.29), respectively. In an instrumental variable analysis, the OR for genetically determined 25% higher plasma vitamin C concentrations was 0.90 (95% CI: 0.75, 1.08; P = 0.27) for ischemic heart disease and 0.88 (0.72, 1.08; P = 0.22) for all-cause mortality.
High intake of fruit and vegetables was associated with low risk of ischemic heart disease and all-cause mortality. Although the 95% CI for genetically high plasma vitamin C concentrations overlapped 1.0, which made certain statistical inferences difficult, effect sizes were comparable to those for fruit and vegetable intake. Thus, judging by the effect size, our data cannot exclude that a favorable effect of high intake of fruit and vegetables could in part be driven by high vitamin C concentrations.
前瞻性研究表明，摄入大量水果和蔬菜以及血浆维生素 C 浓度较高与缺血性心脏病风险较低有关，但随机临床试验的结果并不一致。
我们检验了这样一种假设，即血浆维生素 C 浓度高（如摄入大量水果和蔬菜）与缺血性心脏病和全因死亡率较低有关。
我们使用孟德尔随机化方法，对溶质载体家族 23 成员 1（SLC23A1）中的 rs33972313 进行基因分型，该基因是钠离子依赖的维生素 C 转运体 1 中的基因。在 97203 名白人个体中，有 10123 名个体患有缺血性心脏病，8477 名个体死亡。我们测量了 3512 名个体的血浆维生素 C，并对 83256 名个体的饮食信息进行了评估。
SLC23A1 rs33972313 的 G 等位基因与血浆维生素 C 升高 11%相关。与最低水果和蔬菜摄入量相比，最高摄入量的多变量调整 HR 为缺血性心脏病 0.87（95%CI：0.78，0.97；P = 0.01），全因死亡率 0.80（95%CI：0.73，0.88；P < 0.001）。与 rs33972313 GG（93%）相比，AA 加 AG（7%）基因型的相应 HR 为 0.95（95%CI：0.88，1.02；P = 0.21）和 0.96（0.88，1.03；P = 0.29）。在一项工具变量分析中，遗传决定的血浆维生素 C 浓度增加 25%的 OR 为缺血性心脏病 0.90（95%CI：0.75，1.08；P = 0.27），全因死亡率 0.88（0.72，1.08；P = 0.22）。
摄入大量水果和蔬菜与缺血性心脏病和全因死亡率较低有关。尽管遗传高血浆维生素 C 浓度的 95%CI 重叠 1.0，这使得某些统计推断变得困难，但效应大小与水果和蔬菜摄入量相当。因此，根据效应大小，我们的数据不能排除高水果和蔬菜摄入量的有利影响部分可能是由高维生素 C 浓度驱动的。
