Supplementation and Mortality

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Vitamin C Supplement Use

All-cause mortality in a sample of the U.S. population [National Health and Nutrition Examination Survey (NHANES) I participants, n = 10,550; 749 deaths] was inversely related to vitamin C intake [standardized mortality ratio as a function of the dietary vitamin C index, 0.58; 95% confidence interval (CI), 0.36-0.80] (4). The vitamin C index ranged from persons consuming <50 mg vitamin C daily to those consuming >50 mg vitamin C daily from diet alone and those consuming >50 mg vitamin C daily from diet plus an average of ~800 mg daily from supplementation. After adjustment for age, sex, and 10 potentially confounding variables (race, history of serious disease, education, cigarette smoking, recreational exercise, alcohol consumption, energy consumed, fat, serum cholesterol, and dietary vitamin A), the inverse relationship of vitamin C intake to mortality remained strong (standardized mortality ratio, 0.62; 95% CI, 0.36-0.88). This inverse relation of total mortality to vitamin C intake was stronger and more consistent in this population than the relation of total mortality to serum cholesterol and dietary fat intake (4). In a separate population, there were no differences in mortality between individuals consuming above and below 250 mg vitamin C/d; however, those consuming >750 mg vitamin C/d experienced only 40% of the total cohort death rate during the 10-y study period (3).

In the NHANES II Mortality Study (n = 8453; 1327 total deaths), all-cause mortality was reduced 29% (P < 0.001) in individuals with high serum ascorbate (serum values >1.1 mg/dL) after multivariate adjustment for potential confounding variables, but vitamin C supplement use was not significantly associated with mortality (P = 0.19) (5). The risk of cardiovascular disease death was reduced 25% (P = 0.09) in individuals with high serum ascorbate, but this risk reduction was not related to the use of vitamin C supplements (5). However, the risk of cancer death in men specifically using vitamin C supplements was reduced 65% (P = 0.046) compared with a 31% reduction in men with high serum ascorbate. Fatal cancer risk was not associated with vitamin C supplement use in women. In an American Cancer Society cohort (n = 711,891; 4404 deaths from colorectal cancer), long-term vitamin C supplementation (>10 y) lowered risk of rectal cancer mortality (-60%) but did not affect risk of colon cancer mortality (6).

Losconzy et al. (7) reported no significant effect of vitamin C supplementation on all-cause mortality, coronary disease mortality, or cancer mortality, yet vitamin supplement use may have been underreported because subjects completed questionnaires for nonprescription medications only, not vitamin supplementation specifically. Two other large, prospective population studies did not specifically address vitamin C supplementation use, yet men in the highest stratum for vitamin C status, also representing the greatest number of vitamin C supplement users, had significantly reduced risk of all-cause mortality, cardiovascular disease mortality, and cancer mortality (8,9). Women in the highest stratum for vitamin C status had reduced risk of all-cause mortality and cardiovascular disease in one of these studies (8) but not the other (9). These data indicate the general safety of vitamin C in that mortality end points for the major causes of death in the United States are either unaltered or perhaps favorably affected by high-dose vitamin C ingestion.

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