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Folate profile in frontal cortex from male human infant decedents
Matthew J Kuchan1, Stefan Ehling1, Jonathan R Draher1
1Abbott Nutrition, Columbus, OH, USA.
Insights
Human infant brains contain tetrahydrofolate (THF), 5-methyltetrahydrofolate (5-MTHF), and unmetabolized folic acid (UMFA). While THF is most abundant, UMFA was detected, suggesting further research into infant folate metabolism is needed.
Area of Science:
- Neuroscience
- Biochemistry
- Nutritional Science
Background:
- Human tissue folate profiles are primarily known for colon mucosa, epidermis, and dermis.
- Recent studies detected unmetabolized folic acid (UMFA) in infant rhesus macaque brains.
Purpose of the Study:
- To investigate the presence and levels of UMFA and other folates in the human infant brain.
- To hypothesize that human infant brains, similar to infant rhesus macaques, may contain UMFA.
Main Methods:
- Analysis of archived frontal cortex samples from 5 human infant decedents (aged 5-273 days).
- Quantification of tetrahydrofolate (THF), 5-methyltetrahydrofolate (5-MTHF), and UMFA using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).
Main Results:
- All three folates (THF, 5-MTHF, UMFA) were detected in every analyzed frontal cortex sample.
- THF was the most abundant folate, followed by 5-MTHF and UMFA, which had similar mean concentrations.
- Two infant samples showed UMFA concentrations twice as high as 5-MTHF.
Conclusions:
- The human infant brain contains THF, 5-MTHF, and UMFA, with THF being the predominant form.
- The presence of significant UMFA levels in some infants warrants further investigation into folate metabolism and status during early development.
Abstract:
Information on tissue folate profiles in human tissues is limited to colon mucosa, epidermis and dermis. Recently, infant rhesus macaques fed folic acid (FA) were reported to have unmetabolized FA (UMFA) in each of 7 brain regions tested. We hypothesized that human infant brain would also contain UMFA. Therefore, we sought to analyze the folate profile in frontal cortex from 5 human infant decedents. Archived frontal cortex samples from 5 male human infant decedents aged 5 to 273 days, without brain abnormalities or systemic pathologies were analyzed for tetrahydrofolate (THF), 5-methyltetrahydrofolate (5-MTHF) and UMFA by LC-MS/MS. All 3 folates were detected in each frontal cortex sample. THF was the most abundant folate in each sample with a mean concentration of 202 pmol/g tissue. Mean concentrations of 5-MTHF (30.3 pmol/g tissue) and UMFA (20.8 pmol/g tissue) were significantly lower (P < .0001) than THF and were not different from each other. Two decedents had UMFA concentrations that were 2-fold higher than those of 5-MTHF. In conclusion, THF, 5-MTHF, and UMFA were found in each frontal cortex sample with the order of mean values being THF > 5-MTHF = UMFA. In 2 of the 5 decedents we observed UMFA concentrations that were double those of 5-MTHF. These findings merit further research into folate metabolism and status in infants.
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