Thiamine deficiency, beriberi, and maternal and child health: why pharmacokinetics matter.

In this issue of the Journal, Coats et al (1) describe short-term thiamine pharmacokinetics in nursing women from Cambodia who received a therapeutic course of oral thiamine for 5 d. Before supplementation, the mothers and infants were biochemically thiamine deficient. Treatment normalized thiamine status in the mothers but not in the infants, although thiamine concentrations in breast milk increased rapidly with supplementation. The authors characterized thiamine status in the mothers and their breastfed infants before and after thiamine administration and compared their findings with blood samples from healthy nursing American mothers who were age-matched to their Cambodian counterparts. The data provide important insights on the nutritional pathophysiology of thiamine depletion, repletion, and therapeutics and a sobering reminder that nutritional deficiency disease, including beriberi, persists as an important cause of morbidity and mortality globally. Several aspects of the study are worth further consideration, including the study design, the analytic approach used to assess thiamine status, and implications for global maternal and child health. This study adds to the limited literature on pharmacokinetic data for thiamine; most of the previously published data come from healthy, well-nourished subjects (2). Coats et al used a standard approach to examine thiamine disposition in 16 healthy nursing Cambodian women from a district in Prey Vang Province, where previous work showed endemic thiamine deficiency among mothers and infants (1, 3). The thiamine dose used (100 mg thiamine hydrochloride tablet/d for 5 d, 500 mg total), although far above the Recommended Dietary Allowance (1.4 mg/d for lactating women) and higher than the usual therapeutic regimen for ‘‘mild’’ thiamine deficiency (5–30 mg/d in single or divided doses for 1 mo), was similar to doses typically used for severe deficiency [ 300 mg/d (4)] and within the range used in a previous pharmacokinetics study (2). The present study shows high maternal bioavailability of this pharmacologic dose but only modest improvements in the thiamine status of the infants after 5 d of maternal treatment. The authors appropriately note that supplementation for longer periods or with higher or more frequent doses should be considered and, most importantly, that symptomatic infants should be treated directly (1). The findings of Coats et al indicate rapid normalization of circulating maternal plasma thiamine and thiamine monophosphate by day 6, and rapid normalization of breast-milk thiamine, but slower normalization of blood thiamine diphosphate (1). The information on breast-milk thiamine is of great value in a thiamine-deficient population and provides unique data to estimate the benefit to the infant if only the mother receives supplementation, data that were not available previously. A recent report on a longer-term thiamine supplementation regimen (100 mg/d during pregnancy and lactation) at antenatal clinics in a refugee camp showed that thiamine status in lactating women 12 wk postpartum was within the range observed in well-nourished women and that thiamine measurements in breast milk provided useful information on maternal thiamine status (5). The analytic approach used to assess thiamine status has evolved over time. The traditional indirect approach, not used in this study but still in use (6), is to measure erythrocyte transketolase activity as a functional test that reflects the adequacy of body stores and is sensitive to marginal thiamine deficiency. However, advances in laboratory techniques and the availability of HPLC instrumentation have facilitated the use of the direct approach to measure thiamine and its phosphate esters by use of sensitive and specific fluorometric detection (1, 5, 7). Furthermore, this direct approach can be applied to a wide range of matrices (serum, whole blood or erythrocytes, urine, and breast milk) that are not all accessible to the functional test. Regardless of the approach, however, tests to assess thiamine status are not conducted widely enough to justify establishing an external proficiency testing program. It is therefore vital that each laboratory establishes its own internal quality assessment program to ensure high-quality measurements (8). What factors account for the persistence of thiamine deficiency, especially in postpartum women and their breastfed infants? Despite recognition of its public health significance for .100 y, beriberi remains prevalent in Southeast Asia, where it has long been associated with consumption of polished rice and numerous foods containing antithiamine activity as well