In A, ~13.8 thousand donors were enrolled within the framework of the REDS III-Omics study. A single unit of blood was donated, leukofiltered and stored at 4°C for 42 days (standard blood bank conditions). At day 42, ~8,500 eligible units were tested for oxidative hemolysis (AAPH assay) and extreme hemolyzers (<5 and >95% percentile) recalled to donate a second unit. Subsequent units were processed as in phase I, though sampling occurred at storage days 10, 23 and 42 for a second measurement of oxidative hemolysis and targeted quantitation of methionine via standard UHPLC-MS metabolomics approaches. Methionine levels decreased significantly over the storage duration (n = 599; p <0.00001 ANOVA - B). In particular, methionine measurements in extreme 20 high vs low hemolzyers in the recalled cohort showed that methionine levels were the highest in high oxidative hemolyzers at storage day 10, but not in subsequent time points (C). Total methionine consumption (ΔMethionine at day 42 – day 10) was significantly higher in high oxidative hemolyzers (D). An overview of methionine metabolism is shown in E. * p < 0.05; ** p < 0.01 T-test.