Relation of serum ascorbic acid to mortality among US adults

Purpose: To examine the relation between serum ascorbic acid (SAA), a marker of dietary intake (including supplements), and cause-specific mortality. Subjects and Methods: We analyzed data from a probability sample of 8,453 Americans age greater than or equal to 30 years at baseline enrolled in the Second National Health and Nutrition Examination Survey (NHANES II), who were followed for mortality endpoints. We calculated relative hazard ratios as measures of disease association comparing the mortality rates in three biologically relevant SAA categories. Results: participants with normal to high SAA levels had a marginally significant 21% to 25% decreased risk of fatal cardiovascular disease (CVD) (p for trend = 0.09) and a 25% to 29% decreased risk of all-cause mortality (p for trend < 0.001) compared to participants with low levels. Because we determined that gender modified the association between SAA levels and cancer death, we analyzed these associations stratified by gender. Among men, normal to high SAA levels were associated with an approximately 30% decreased risk of cancer deaths, whereas such SAA levels were associated with an approximately two-fold increased risk of cancer deaths among women. This association among women persisted even after adjustment for baseline prevalent cancer and exclusion for early cancer death or exclusion for prevalent cancer. Conclusions: Low SAA levels were marginally associated with an increased risk of fatal CVD and significantly associated with an increased risk for all-cause mortality. Low SAA levels were also a risk factor for cancer death in men, bur unexpectedly were associated with a decreased risk of cancer death in women. If the association between low SAA levels and all-cause mortality is causal, increasing the consumption of ascorbic acid, and thereby SAA levels, could decrease the risk of death among Americans with low ascorbic acid intakes.