{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:49:56Z","timestamp":1792788596127,"version":"4.5.0"},"update-to":[{"DOI":"10.12688\/gatesopenres.15991.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000}}],"reference-count":37,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Gates Foundation","award":["INV-016930"],"award-info":[{"award-number":["INV-016930"]}],"id":[{"id":"https:\/\/ror.org\/0456r8d26","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["gatesopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Gates Open Res"],"abstract":"<ns3:p>\n                    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. 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\u201328 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 \u00b5g for four weeks. At the highest dose, pregnant participants are randomized to receive 50 \u00b5g once a day (Q24H) or 25 \u00b5g twice a day (Q12H). The two lower doses (2.6 and 10 \u00b5g) are given Q24H. Non-pregnant participants will receive 2.6 \u00b5g 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. Discussion 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 \u00b5g), and comparing Q12H and Q24H dosing at 50 \u00b5g. This is the first controlled feeding study to be conducted in sub-Saharan Africa. Registration ClinicalTrials.gov (\n                    <ns3:ext-link xmlns:ns4=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" ns4:href=\"https:\/\/clinicaltrials.gov\/study\/NCT05426395?term=NCT05426395&amp;rank=1\">NCT05426395<\/ns3:ext-link>\n                    , 16\/06\/2022).\n                  <\/ns3:p>","DOI":"10.12688\/gatesopenres.15991.2","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:55:09Z","timestamp":1763686509000},"page":"95","update-policy":"https:\/\/doi.org\/10.12688\/gatesopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Single-blinded, stratified, dose ranging trial to assess pharmacokinetics and identify optimal dose of vitamin B12 in pregnancy in Tanzania"],"prefix":"10.12688","volume":"8","author":[{"given":"Omar","family":"Lweno","sequence":"first","affiliation":[{"name":"Dar es Salaam Ifakara Health Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8231-8137","authenticated-orcid":false,"given":"Victoria S.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Department of Global Health, The Milken Institute School of Public Health Washington District of Columbia 20052 The George Washington University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0468-7842","authenticated-orcid":false,"given":"Matthew D.","family":"Barberio","sequence":"additional","affiliation":[{"name":"Department of Exercise and Nutrition Science, The Milken Institute School of Public Health Washington District of Columbia 20052 The George Washington University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0223-8250","authenticated-orcid":false,"given":"Kevin C.","family":"Klatt","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences and Toxicology Berkeley California 94720 University of California Berkeley"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Mugusi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Dar es Salaam Muhimbili University of Health and Allied Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathangi","family":"Gopalakrishnan","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine, School of Pharmacy Baltimore Maryland 21201 University of Maryland Baltimore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zohra","family":"Lukmanji","sequence":"additional","affiliation":[{"name":"Dar es Salaam Ifakara Health Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2416-6876","authenticated-orcid":false,"given":"Fadhlun M. Alwy","family":"Al-beity","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Dar es Salaam Muhimbili University of Health and Allied Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Homa K.","family":"Ahmadzia","sequence":"additional","affiliation":[{"name":"Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology Washington District of Columbia 20052 The George Washington University"},{"name":"Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology Falls Church VA 22042 Inova Health System"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amrita","family":"Arcot","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences University Park Pennsylvania 16802 The Pennsylvania State University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Gallagher","sequence":"additional","affiliation":[{"name":"Ross and Carol Nese College of Nursing University Park Pennsylvania 16802 The Pennsylvania State University - University Park Campus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4812-7396","authenticated-orcid":false,"given":"Leigh A.","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences University Park Pennsylvania 16802 The Pennsylvania State University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9710-0248","authenticated-orcid":false,"given":"Ali","family":"Rahnavard","sequence":"additional","affiliation":[{"name":"Computational Biology Institute, Departments of Biostatistics and Bioinformatics, The Milken Institute School of Public Health Washington District of Columbia 20052 The George Washington University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison 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The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}