Infant rhesus macaque brain α-tocopherol stereoisomer profile is differentially impacted by the source of α-tocopherol in infant formula

Matthew J. Kuchan, Katherine M. Ranard, Priyankar Dey, Sookyoung Jeon, Geoff Y. Sasaki, Karen J. Schimpf, Richard S. Bruno, Martha Neuringer, John W. Erdman

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Background: α-Tocopherol (αT) in its natural form [2R, 4R, 8R αT (RRR-αT)] is more bioactive than synthetic αtocopherol (all rac-αT). All rac-αT is widely used in infant formulas, but its accretion in formula-fed infant brain is unknown. Objective: We sought to compare αT and stereoisomer status in infant rhesus macaques (Macaca mulatta) fed infant formula (RRR-αT or all rac-αT) with a reference group fed a mixed diet of breast milk and maternal diet. Methods: From 1 d after birth until 6 mo of age, infants (n = 23) were either nursery reared and exclusively fed 1 of 2 formulas by staff personnel or were community housed with their mothers and consumed a mixed reference diet of breast milk (69 mL/d at 6 mo) transitioning to monkey diet at ∼2 mo (MF; n = 8). Formulas contained either 21 μmol RRR-αT/L (NAT-F; n = 8) or 30 μmol all rac-αT/L (SYN-F; n = 7). Total αT and αT stereoisomers were analyzed in breast milk at 2, 4, and 6 mo and in monkey plasma and liver and 6 brain regions at 6 mo of age. α-Tocopherol transfer protein (α-TTP), lipoprotein αT, and urinary α-carboxyethyl-hydroxychroman (α-CEHC) were measured. One-way ANOVA with Tukey’s post-hoc test was used for analysis. Results: At study termination, plasma, liver, lipoprotein, and brain total αT did not differ between groups. However, the NAT-F–fed group had higher RRR-αT than the SYN-F–fed group (P < 0.01) and the MF group (P < 0.0001) in plasma (1.7- and 2.7-fold) and brain (1.5- and 2.5-fold). Synthetic αT 2R stereoisomers (SYNTH-2R) were generally 3- and 7-fold lower in brain regions of the NAT-F group compared with those of the SYN-F and MF groups (P < 0.05). SYNTH-2R stereoisomers were 2-fold higher in MF than SYN-F (P < 0.0001). The plasma percentage of SYNTH-2R was negatively correlated with the brain percentage of RRR-αT (r = −0.99, P < 0.0001). Brain αT profiles were not explained by α-TTP mRNA or protein expression. Urine α-CEHC was 3 times higher in the NAT-F than in the MF group (P < 0.01). Conclusions: Consumption of infant formulas with natural (NAT-F) compared with synthetic (SYN-F) αT differentially impacted brain αT stereoisomer profiles in infant rhesus macaques. Future studies should assess the functional implications of αT stereoisomer profiles on brain health. J Nutr 2020;150:2305–2313.

Original languageEnglish (US)
Pages (from-to)2305-2313
Number of pages9
JournalJournal of Nutrition
Issue number9
StatePublished - Sep 1 2020


  • All rac-α-tocopherol
  • Breast milk
  • Infant
  • Lactation
  • Macaca mulatta
  • RRR-α-tocopherol
  • Rhesus macaque
  • Stereoisomer
  • Vitamin E
  • α-tocopherol

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics


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