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Folate Profile in Tissues from Infant Primates Fed Folic Acid
Matthew J Kuchan1, Avinash Pokala1, Stefan Ehling1
1Division of Nutrition, Abbott Laboratories, Columbus, OH, United States.
Insights
Tissue folate concentrations were explored in infant macaques, revealing highest levels in the liver and kidney. Folate distribution varied across brain regions, with tetrahydrofolate (THF) being most abundant in all brain areas studied.
Area of Science:
- Nutritional Science
- Primate Research
- Biochemistry
Background:
- Dietary folic acid (FA) is common in circulation, but human tissue folate forms and concentrations are poorly understood.
- Infant rhesus macaques, with lower FA reductive activity than rodents, serve as a relevant model for human infants.
- Limited data exists on tissue-specific folate distribution in developing primates.
Purpose of the Study:
- To investigate tissue folate concentrations in infant rhesus macaques fed folic acid.
- To compare folate levels in various organs and brain regions between different infant feeding groups.
- To identify the predominant folate forms (tetrahydrofolate, 5-methyltetrahydrofolate, unmetabolized folic acid) in primate tissues.
Main Methods:
- Analysis of archived tissue samples from infant macaques (n=23) fed either breastmilk/maternal diet (BMD) or milk replacer (MR).
- Quantification of tetrahydrofolate (THF), 5-methyltetrahydrofolate (5-MTHF), and unmetabolized folic acid (UMFA) using LC-MS/MS.
- Measurement of folates in plasma, primary organs (liver, kidney, heart, lung), and multiple brain regions.
Main Results:
- All measured folates were detected in tissues, except THF in plasma. Total folate (Σfolate) concentrations were highest in liver and kidney, followed by heart, brain, lung, and plasma, showing a 100-fold range.
- Kidney and lung exhibited the highest concentrations of unmetabolized folic acid (UMFA).
- Within the brain, prefrontal and temporal cortices, and cerebellum showed higher Σfolate than motor cortex, occipital cortex, and striatum, with THF being the most abundant folate form in all brain regions. Feeding groups (BMD vs. MR) showed minimal differences in tissue and brain folate concentrations.
Conclusions:
- Significant variations in tissue folate metabolism, uptake, and/or retention are indicated across different organs and brain regions.
- Further research is warranted to elucidate the underlying mechanisms governing these observed folate distribution patterns.
- The findings contribute to understanding primate folate dynamics, relevant for human infant nutrition and development.
Background:
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.
Objectives:
This study explored tissue folate concentrations in FA-fed infant rhesus macaques.
Methods:
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.
Results:
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.
Conclusions:
Differential tissue folate metabolism, uptake, and/or retention are suggested, and further research is necessary to explore the mechanisms involved.
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