Folate Profile in Tissues from Infant Primates Fed Folic Acid

Diet-derived folic acid (FA) is found in circulation in a high percentage of United States subjects, but knowledge of tissue folate forms and concentrations in humans is limited. The infant rhesus macaque is an excellent model for the human infant and, like the human, has lower FA reductive activity than rodents.

This study explored tissue folate concentrations in FA-fed infant rhesus macaques.

Archived tissue samples from 6-mo-old infant macaques who were fed breast milk and later some maternal diet (BMD, n = 8) or were fed a milk replacer (MR, n = 15) were analyzed for tetrahydrofolate (THF), 5-methyltetrahydrofolate (5-MTHF), and unmetabolized folic acid (UMFA); other forms were not measured. Folates were analyzed in plasma, primary organs, and multiple brain regions by liquid chromatography-tandem mass spectrometry.

All 3 folates were detected in each tissue with the exception that THF was undetectable in plasma. ΣFolate (THF+5-MTHF+UMFA) concentrations were highest in the liver and kidney (P < 0.05), then heart (P < 0.05) and brain, lung, and plasma (all P < 0.05 compared with kidney) with a 100-fold difference from highest to lowest. Tissue THF and 5-MTHF followed similar but not identical patterns. UMFA concentration was highest in the kidneys and lungs (P < 0.05). Prefrontal and temporal cortices and cerebellum were higher in Σfolate than motor cortex, occipital cortex, and striatum (P < 0.05). THF was the most abundant folate measured in each brain region. Tissue and brain concentrations were similar between BMD and MR with only a few sporadic differences.

Differential tissue folate metabolism, uptake, and/or retention are suggested, and further research is necessary to explore the mechanisms involved.