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 -