(LB03-19-24) Folate Concentrations in Tissues From Infant Primates

Objectives: Folic acid (FA), a synthetic form of folate, is added to prenatal vitamins and some cereal grains to ensure adequate folate intake. To be active, FA must be converted to tetrahydrofolate (THF) and 5-methyltetrahydroflate (5-MTHF) by dihydrofolate reductase (DHFR). Humans have limited liver DHFR capacity which results in detectable FA in plasma. Tissue folate profiles have not been reported in humans or in another species with detectable plasma FA. Our initial data indicated significant FA in plasma from infant rhesus macaques consistent with limited DHFR activity. Thus, our aim was to assess levels of THF, 5-MTHF, and FA in tissues from infant rhesus macaques.

Methods: In this secondary analysis, tissue samples were analyzed from male and female infant macaques (age = 6 mo) who were mixed-fed (breastfed + maternal diet, n = 8) or fed a milk replacer (n = 15). Average FA concentration in breast milk and milk replacer was 72.2 ± 29.7 and 212.7 ± 25.7 ng/mL, respectively. The maternal diet also contained 9.6 μg/g of FA. The concentration of FA, THF and 5-MTHF were analyzed in plasma, primary organs, and multiple brain areas by LC-MS.

Results: All three folates were detected in each tissue sample, with concentrations varying across tissues. Total folates were highest in the liver, followed by the kidney, brain, heart, lung, and plasma. Total liver folate concentrations varied between the groups, as did heart and kidney FA concentrations. Brain region folate profiles differed, and in some cases, varied between the groups. 5-MTHF% was highest in heart (79%), plasma (74%), and liver (65%), while THF% was highest in brain (78%) and kidney (62%). Lung tissue had the highest percentage of FA (~42%). FA concentrations were lowest in plasma, followed by heart, liver, lung, brain, and kidney, in ascending order, with mean concentrations from 2.0–107 ng/g. In the striatum and cerebellum, FA concentration was similar to or exceeded 5-MTHF.

Conclusions: Our data reveal that tissue folate concentrations were generally similar between the mixed-fed and replacer-fed infant macaque groups. Folate profiles differed markedly among tissues and brain regions, with FA being detected in each sample and, in some cases, reaching levels similar to 5-MTHF. These findings warrant further research into tissue folate profiles.

Funding Sources: Abbott Nutrition, Oregon National Primate Research Center