Thiamine Status of Supplemented, Lactating Mothers in Rural Cambodia: A Randomized Controlled Trial

Abstract Objectives Thiamine deficiency is a cause of infant morbidity and mortality throughout Southeast and South Asia. Maternal intake influences human milk thiamine concentrations, thus mother's intake must be improved to combat infant deficiency. However, the dose of supplemental thiamine required by lactating mothers is unknown. We aimed to estimate the maternal oral thiamine dose required to optimize milk thiamine concentrations, and to investigate the impact of various doses on thiamine status biomarkers. Methods This was a double-blind, four-parallel arm randomized controlled dose-response trial. At 2 weeks postpartum, healthy mothers were randomized to consume one capsule daily for 22 weeks, containing either 0 mg (placebo, n = 83), 1.2 mg (estimated average requirement, n = 86), 2.4 mg (n = 81), or 10 mg (n = 85) thiamine. Human milk total thiamine, whole blood thiamine diphosphate, and erythrocyte transketolase activity coefficient (ETKac) were assessed. An Emax curve, estimated using a non-linear least squares model, was plotted for human milk. Linear mixed-effects models were used to test for differences between treatment groups for milk and blood biomarkers. Results A maternal supplemental dose of 2.35 (95% CI 0.58, 7.01) mg/d was estimated to reach 90% of the maximum average human milk total thiamine concentration of 191 µg/L. The mean (SD) milk thiamine concentration was significantly higher in all intervention groups (183 (91), 190 (105), and 206 (89) µg/L, for 1.2, 2.4, and 10 mg, respectively) compared to placebo (153 (85) µg/L; p < 0.0001), and did not differ from each other. Blood biomarkers followed similar group trends, except for infant ETKac, where only the 10 mg (mean [SD]: 1.18 [0.10]) and placebo (1.12 [0.06]) groups differed significantly (p = 0.003). Conclusions While an estimated maternal dose of 2.35 (0.58, 7.01) mg/d was required to reach a milk thiamine concentration of 191 µg/L in Emax dose analyses, group comparisons suggest a daily dose of 1.2 mg/d is sufficient to improve maternal biomarkers to levels similar to higher doses (2.4 and 10 mg/d) and consistent with thiamine-replete populations. However, a higher maternal dose of 10 mg/d was required to improve infant ETKac status compared to other dose groups. Funding Sources Bill & Melinda Gates Foundation, The New York Academy of Sciences.