Low-dose thiamine supplementation of lactating Cambodian mothers improves human milk thiamine concentrations: a randomized controlled trial.
The American Journal of Clinical Nutrition 2020 ; 114: 90-100.
Gallant J, Chan K, Green TJ, Wieringa FT, Leemaqz S, Ngik R, Measelle JR, Baldwin DA, Borath M, Sophonneary P, Yelland LN, Hampel D, Shahab-Ferdows S, Allen LH, Jones KS, Koulman A, Parkington DA, Meadows SR, Kroeun H, and Whitfield KC
DOI : 10.1093/ajcn/nqab052
PubMed ID : 33829271
PMCID : PMC8246599
Infantile beriberi-related mortality is still common in South and Southeast Asia. Interventions to increase maternal thiamine intakes, and thus human milk thiamine, are warranted; however, the required dose remains unknown.
We sought to estimate the dose at which additional maternal intake of oral thiamine no longer meaningfully increased milk thiamine concentrations in infants at 24 wk postpartum, and to investigate the impact of 4 thiamine supplementation doses on milk and blood thiamine status biomarkers.
In this double-blind, 4-parallel arm randomized controlled dose-response trial, healthy mothers were recruited in Kampong Thom, Cambodia. At 2 wk postpartum, women were randomly assigned to consume 1 capsule, containing 0, 1.2 (estimated average requirement), 2.4, or 10 mg of thiamine daily from 2 through 24 weeks postpartum. Human milk total thiamine concentrations were measured using HPLC. An Emax curve was plotted, which was estimated using a nonlinear least squares model in an intention-to-treat analysis. Linear mixed-effects models were used to test for differences between treatment groups. Maternal and infant blood thiamine biomarkers were also assessed.
In total, each of 335 women was randomly assigned to1 of the following thiamine-dose groups: placebo (n = 83), 1.2 mg (n = 86), 2.4 mg (n = 81), and 10 mg (n = 85). The estimated dose required to reach 90% of the maximum average total thiamine concentration in human milk (191 µg/L) is 2.35 (95% CI: 0.58, 7.01) mg/d. The mean ± SD milk thiamine concentrations were 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 with the placebo group (153 ± 85 µg/L; P < 0.0001) and did not significantly differ from each other.
A supplemental thiamine dose of 2.35 mg/d was required to achieve a milk total thiamine concentration of 191 µg/L. However, 1.2 mg/d for 22 wk was sufficient to increase milk thiamine concentrations to similar levels achieved by higher supplementation doses (2.4 and 10 mg/d), and comparable to those of healthy mothers in regions without beriberi. This trial was registered at clinicaltrials.gov as NCT03616288.
Thiamine (vitamin B1) is essential for normal growth, development and energy metabolism. Thiamine is found in a wide-range of foods and deficiency is not usually a problem with a varied diet. However, in some populations, with diets that consist mostly of thiamine-poor white, polished rice, there may be an increased risk of thiamine deficiency. In particular, mothers with low dietary thiamine intake produce thiamine-poor breastmilk, putting their breastfed infants at risk of developing a potentially fatal deficiency disease called infantile beriberi.
The NIHR Cambridge BRC Nutritional Biomarker Laboratory was responsible for the blood analysis of two thiamine biomarkers for a recently published study led by Dr Kyly Whitfield (Mount Saint Vincent University, Canada). The aim of the study was to investigate the amount of supplemental thiamine intake required to optimise breastmilk thiamine concentrations and mother and infant blood thiamine status.
In the study, 335 mothers in rural Cambodia were randomised to one of four daily thiamine supplementation doses (0, 1.2, 2.4, or 10 mg per day) from 2 weeks to 6 months postpartum. At the end of the intervention period, blood samples were collected from mothers and infants, and breastmilk from mothers to estimate the optimal thiamine dose to improve thiamine status.
The results showed that women taking any of the thiamine-containing supplements had significantly higher thiamine content in their milk compared to the placebo group. Both mothers and infants had improved blood thiamine status after supplementation. In the study, a dose of 1.2 mg thiamine/day improved the thiamine status of breastfeeding mothers and their infants, normalising thiamine status, and may reduce the risk of thiamine deficiency and infantile beriberi. We hope the results of this study will inform a future thiamine fortification program in Cambodia, and elsewhere in South and Southeast Asia where thiamine deficiency remains a public health concern.