Infant Rhesus Macaque Brain α-Tocopherol Stereoisomer Profile Is Differentially Impacted by the Source of α-Tocopherol in Infant Formula

Author:

Kuchan Matthew J1,Ranard Katherine M2,Dey Priyankar3,Jeon Sookyoung2,Sasaki Geoff Y3,Schimpf Karen J1,Bruno Richard S3,Neuringer Martha45,Erdman John W26

Affiliation:

1. Abbott Nutrition, Columbus, OH

2. Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, IL

3. Human Nutrition Program, The Ohio State University, Columbus, OH

4. Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR

5. Casey Eye Institute, Oregon Health & Science University, Portland OR

6. Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL

Abstract

ABSTRACTBackgroundα-Tocopherol (αT) in its natural form [2′R, 4′R, 8′R αT (RRR-αT)] is more bioactive than synthetic α-tocopherol (all rac-αT). All rac-αT is widely used in infant formulas, but its accretion in formula-fed infant brain is unknown.ObjectiveWe 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.MethodsFrom 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.ResultsAt 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).ConclusionsConsumption 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.

Funder

Abbott Nutrition through the Center for Nutrition, Learning, and Memory

CNLM

NIH

Publisher

Oxford University Press (OUP)

Subject

Nutrition and Dietetics,Medicine (miscellaneous)

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4. Distribution of α-tocopherol stereoisomers in mink (Mustela vison) organs varies with the amount of all-rac-α-tocopheryl acetate in the diet;Hymoller;Br J Nutr,2018

5. Bioavailability of α-tocopherol stereoisomers in lambs depends on dietary doses of all-rac- or RRR-α-tocopheryl acetate;Leal;Animal,2019

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