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

Sep 28, 2026

Vitamin B12 is an essential cofactor for enzymes critical to pregnancy outcomes, yet the optimal supplemental dosage and its relationship to maternal vitamin B12 status during pregnancy remain insufficiently defined due to limited data. This single-blinded, stratified dose-ranging trial will evaluate vitamin B12 pharmacokinetics in pregnant women in Tanzania and compare post-supplementation serum B12 metrics with nonpregnant participants using controlled feeding.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages20

Reading Time50 min

AccessFree to download

Abstract

Background

Methods

Trial design and dosing

Discussion

Objectives and limitations

Registration

Corresponding author

Gates Open Research Gates Open Research 2024, 8:95 Last updated: 31 DEC 2025 STUDY PROTOCOL Single-blinded, stratified, dose ranging trial to assess pharmacokinetics and identify optimal dose of vitamin B12 in pregnancy in Tanzania [version 1; peer review: 2 approved with reservations] Omar Lweno 1, Victoria S. Reynolds 2, Matthew D. Barberio 3, Kevin C. Klatt 4, Sabina Mugusi5, Mathangi Gopalakrishnan6, Zohra Lukmanji 1, Fadhlun M. Alwy Al-beity 7, Homa K. Ahmadzia8,9, Amrita Arcot 10, Kelly Gallagher 11, Leigh A. Martin 10, Ali Rahnavard 12, Alison D. Gernand 10, Brooke Langevin6, Honorati Masanja 1, Emily R. Smith 2,3 1Ifakara Health Institute, Dar es Salaam, Tanzania 2 Department of Global Health, The Milken Institute School of Public Health, The George Washington University, Washington, District of Columbia, 20052, USA 3 Department of Exercise and Nutrition Science, The Milken Institute School of Public Health, The George Washington University, Washington, District of Columbia, 20052, USA 4 Department of Nutritional Sciences and Toxicology, University of California Berkeley, Berkeley, California, 94720, USA 5 Department of Clinical Pharmacology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania 6Center for Translational Medicine, School of Pharmacy, University of Maryland Baltimore, Baltimore, Maryland, 21201, USA 7 Department of Obstetrics and Gynecology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania 8 Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, The George Washington University, Washington, District of Columbia, 20052, USA 9 Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Inova Health System, Falls Church, VA, 22042, USA 10 Department of Nutritional Sciences, The Pennsylvania State University, University Park, Pennsylvania, 16802, USA 11 Ross and Carol Nese College of Nursing, The Pennsylvania State University-University Park Campus, University Park, Pennsylvania, 16802, USA 12Computational Biology Institute, Departments of Biostatistics and Bioinformatics, The Milken Institute School of Public Health, The George Washington University, Washington, District of Columbia, 20052, USA v1 First published: 04 Sep 2024, 8:95 [https://doi.org/10.12688/gatesopenres.15991.1](https://doi.org/10.12688/gatesopenres.15991.1) [Latest published:](Latest published: 17 Sep 2025)[ 17 Sep 2025](Latest published: 17 Sep 2025), 8:95 [https://doi.org/10.12688/gatesopenres.15991.2](https://doi.org/10.12688/gatesopenres.15991.2) Abstract Background 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. Open Peer Review | Approval Status | | | | | --- | --- | --- | --- | | 1 | | 2 | 3 | | version 2
(revision)
17 Sep 2025
version 1
04 Sep 2024 |
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view view | | | 1. Yuan Jiang , Karolinska Institutet, Solna, Gates Open Research Gates Open Research 2024, 8:95 Last updated: 31 DEC 2025 Methods 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 nonpregnant 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. Atthe 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 Q24

FAQs

What is the primary goal of the trial?

To assess pharmacokinetics after vitamin B12 supplementation and identify the optimal dose in pregnancy in Tanzania.

How are participants assigned to dosing groups?

Pregnant participants are stratified by baseline vitamin B12 status and sequentially assigned to three doses (2.6, 10, 50 µg) and randomized at the 50 µg dose to Q24H or Q12H; nonpregnant participants receive 2.6 µg Q24H.

What are the primary endpoints?

Serum B12 concentrations, holotranscobalamin concentrations, and their ratio after four weeks of daily supplementation.

Sep 28, 2026

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