Thiamine pharmacokinetics in Cambodian mothers and their breastfed infants

Background: Thiamine deficiency is common in parts of Asia and causes beriberi. Pharmacokinetics of thiamine in deficient populations are unknown. Objective: We characterized thiamine pharmacokinetics in Cambodian mothers and their breastfed infants. Design: Total plasma thiamine, whole-blood thiamine diphosphate (TDP), and breast milk total thiamine were measured in 16 healthy Cambodian mothers and their infants before and after mothers received oral thiamine hydrochloride (100 mg for 5 d). Assays were also performed in 16 healthy American mothers. Results: On day 1, Cambodian mothers were thiamine deficient, with median (range) total plasma thiamine and TDP concentrations of 2.4 nmol/L (0-4.4 nmol/L) and 58.0 nmol/L (27-98 nmol/L), respectively. After a single oral dose, the mean ± SD maximal concentration of thiamine and net area under the thiamine concentration-time curve were 73.4 ± 45.6 nmol/L and 465 ± 241 h · nmol · L^-1. Day 6 median maternal total plasma thiamine and TDP concentrations were normal [18.6 nmol/L (13.4-25.3 nmol/L) and 76.5 nmol/L (48-107 nmol/L), respectively; P ≤ 0.001 compared with day 1]. Median Cambodian total breast milk thiamine concentration increased from 180 nmol/L (85-359 nmol/L) on day 1 to 403 nmol/L (314-415 nmol/L) on day 2 and 503 nmol/L (360-808 nmol/L) on day 6; the corresponding American breast milk value was 500 nmol/L (114-622 nmol/L). Median Cambodian infant total plasma thiamine and TDP concentrations increased from 3.0 nmol/L (0-7.3 nmol/L) and 38.5 nmol/L (23-57 nmol/L), respectively, on day 1 to 5.6 nmol/L (0-9.7 nmol/L) and 45.5 nmol/L (32-70 nmol/L), respectively, on day 6. Conclusions: Thiamine-deficient Cambodian mothers effectively absorb oral thiamine, with sharp increases in breast milk thiamine concentrations, but their breastfed infants remain thiamine deficient after 5 d of maternal supplementation. Longer-term maternal supplementation may be necessary to correct thiamine deficiency in breastfed infants. This trial was registered at clinicaltrials.gov as NCT01864057.