# Single-blinded, stratified, dose ranging trial to assess pharmacokinetics and identify optimal dose of vitamin B12 in pregnancy in Tanzania

## TL;DR

This study in Tanzania tests different vitamin B12 doses in pregnant women to determine the optimal amount for maintaining healthy levels during pregnancy.

## Contribution

The first controlled feeding study of vitamin B12 supplementation in pregnancy conducted in sub-Saharan Africa.

## Key findings

- The study will assess how different vitamin B12 doses affect serum and holotranscobalamin concentrations in pregnant and non-pregnant participants.
- It will generate high-quality data on vitamin B12 absorption and steady-state levels during pregnancy.
- The trial will compare the effectiveness of once-daily and twice-daily dosing at the highest vitamin B12 level.

## Abstract

Vitamin B12 is an essential cofactor for two enzymes that have critical functions in pregnancy, both for maternal health and fetal development. However, the optimal supplemental dosage and its correlation with vitamin B12 status during pregnancy remain inadequately understood due to limited data.

This is a single-blinded, stratified, dose-ranging trial of vitamin B12 supplementation that will be conducted at the Ifakara Health Institute Bagamoyo Clinical Trial Unit in Bagamoyo, Tanzania. We will enroll 40 pregnant participants (gestational age 25–28 weeks) and 10 non-pregnant participants, stratified based on baseline vitamin B12 status (sufficient and insufficient). Pregnant participants are sequentially assigned to one of three doses: 2.6, 10, and 50 µg for four weeks. At the highest dose, pregnant participants are randomized to receive 50 µg once a day (Q24H) or 25 µg twice a day (Q12H). The two lower doses (2.6 and 10 µg) are given Q24H. Non-pregnant participants will receive 2.6 µg Q24H. The trial includes a four week in-patient phase for daily assessment and controlled feeding, with pregnant participants assessed once postpartum. Primary endpoints include serum B12 concentrations, holotranscobalamin concentrations, and their ratio after four weeks of daily supplementation.

This study aims to deepen our understanding of nutrient requirements in pregnancy by generating high-quality, high-dimensional data. We will answer questions about how pre-supplementation vitamin B12 status and dosage impact vitamin B12 saturable absorption and steady-state over the course of four weeks. Limitations include our inability to assess pharmacokinetic changes across gestation, the impact of vitamin B12 status or supplementation on pregnancy and fetal/newborn health, comparing vitamin B12 effects between pregnant and non-pregnant individuals above the recommended dietary allowance (2.6 µg), and comparing Q12H and Q24H dosing at 50 µg. This is the first controlled feeding study to be conducted in sub-Saharan Africa.

ClinicalTrials.gov (
NCT05426395, 16/06/2022).