Genetically high plasma vitamin C, intake of fruit and vegetables, and risk of ischemic heart disease and all-cause mortality: a Mendelian randomization study

TY - JOUR

T1 - Genetically high plasma vitamin C, intake of fruit and vegetables, and risk of ischemic heart disease and all-cause mortality

T2 - a Mendelian randomization study

AU - Kobylecki, Camilla J

AU - Afzal, Shoaib

AU - Davey Smith, George

AU - Nordestgaard, Børge G

N1 - © 2015 American Society for Nutrition.

PY - 2015/6/1

Y1 - 2015/6/1

N2 - Background: 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. Objective: 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. Design: 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. Results: 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. Conclusions: 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.

AB - Background: 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. Objective: 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. Design: 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. Results: 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. Conclusions: 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.

KW - Aged

KW - Alleles

KW - Ascorbic Acid

KW - Body Mass Index

KW - Cholesterol

KW - Female

KW - Follow-Up Studies

KW - Fruit

KW - Genotyping Techniques

KW - Humans

KW - Male

KW - Mendelian Randomization Analysis

KW - Middle Aged

KW - Mortality

KW - Myocardial Ischemia

KW - Proportional Hazards Models

KW - Risk Factors

KW - Sensitivity and Specificity

KW - Sodium-Coupled Vitamin C Transporters

KW - Surveys and Questionnaires

KW - Vegetables

U2 - 10.3945/ajcn.114.104497

DO - 10.3945/ajcn.114.104497

M3 - Journal article

C2 - 25948669

SN - 0002-9165

VL - 101

SP - 1135

EP - 1143

JO - American Journal of Clinical Nutrition

JF - American Journal of Clinical Nutrition

IS - 6

ER -