The Serum : Red Cell Folate Ratio (SF/RCF%): A Tool to Quantify Age Associated Change in Folate Status

Abstract

Reduced intracellular folate availability results in DNA damage, hypomethylation, and hyperhomocysteinemia, and has been implicated in risk for age‐associated diseases including cancer and cardiovascular disease. Serum folate levels, routinely used to assess human folate status, do not distinguish between folate intake and uptake by metabolizing cells. Nucleated red cells avidly take up folate in the bone marrow but anucleated red cells also accumulate folate during circulation in folate rich serum. Serum folate concentration measured by microbological (L. casei) assay was a significant influence (p<0.0001 ANCOVA) on red cell folate concentration in healthy young (n = 50) and old (n = 60) human subjects (r = 0.503). Baseline SF/RCF% was higher (p<0.02) in old (3.4±2.7%) than young (2.5±1.2%) subjects. SF/RCF% rose higher in subgroups of old (8.06±1.14%; n=6) than young (3.95± 0.35%; n=5) subjects matched for baseline folate indices and supplemented (2 mg/day) for two weeks with folic acid (p<0.01). We propose that the SF/RCF% detects differences in folate uptake/retention and can be used to screen subjects to identify mechanisms of a presumptive age‐associated change in folate utilization. VA Grant HD14837