RRR-α-Tocopherol Is the Predominant Stereoisomer of α-Tocopherol in Human Milk

BACKGROUND: The naturally occurring α-tocopherol (α-T) stereoisomer, RRR-α-tocopherol (RRR-α-T), is known to be more bioactive than all-rac-α-tocopherol (all-rac-α-T), a synthetic racemic mixture of 8 stereoisomers. There is widespread use of all-rac-α-T in maternal supplements. OBJECTIVE: The aim of the study was to thoroughly describe the α-T stereoisomer profile of human milk. METHODS: We measured the α-T stereoisomer profile in milk from 2 cohorts of women: a cohort of 121 women who provided milk on days 30 and 60 of lactation (study 1) and a separate cohort of 51 women who provided milk on days 10, 21, 71, and 120 of lactation (study 2). RESULTS: RRR-α-T was the predominant stereoisomer (P < 0.0001) in all samples in both studies despite a large intrasubject range in total α-T (0.7–22 μg/mL). On average, RRR-α-T comprised 73–76% of total α-T, but average values for the synthetic stereoisomers were RRS, 8–14%; RSR, 6–8%; RSS, 5–6%; and the sum of 2S stereoisomers (Σ2S), 3–5%. Despite the predominance of RRR-α-T, the sum of the synthetic stereoisomers comprised as much as 48% of total α-T. We calculated the ratio of RRR to the sum of the synthetic 2R (RRS + RSR + RSS) stereoisomers (s2R) to assess the degree to which RRR is favored in milk. Consistent with discrimination among 2R stereoisomers in mammary tissue, RRR/s2R values ranged from 2.8 to 3.6, as opposed to the expected ratio of 0.33 if there was no discrimination. However, the RRR to s2R ratio did not correlate with milk α-T concentration, but both components of the ratio did. CONCLUSIONS: RRR-α-T is the predominant stereoisomer in human milk, concentrations of synthetic 2R stereoisomers were notable, and the relation between milk total α-T and stereoisomer profile is complex. Due to the wide range found in milk α-T stereoisomer profile, investigation into its impact on α-T status and functional outcomes in breastfed infants is warranted.