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

ABSTRACT

Background

α-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.

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 2 R stereoisomers (SYNTH-2 R) 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-2 R stereoisomers were 2-fold higher in MF than SYN-F ( P < 0.0001). The plasma percentage of SYNTH-2 R 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.