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Vitamin D supplementation in breastfed infants from Montréal, Canada: 25-hydroxyvitamin D and bone health effects from a follow-up study at 3 years of age



Whether infant vitamin D supplementation may have long-term bone benefits is unclear. In this study, breastfed infants who received vitamin dosages greater than 400 IU/day did not have higher bone mineralization at 3 years. This study provides important data to inform pediatric public health recommendations for vitamin D.


North American health agencies recommend breastfed infants should be supplemented with 400 IU of vitamin D/day to support bone health. Few studies examined the long-term benefits of early life vitamin D supplementation on bone mineralization. The objective of this study was to determine if a dose-response relationship exists between infant vitamin D supplementation, vitamin D status, and bone outcomes at 3 years of age.


This was a double-blind randomized trial of 132, 1-month-old healthy, breastfed infants from Montréal, Canada, between 2007 and 2010. In this longitudinal analysis, 87 infants (66 %) returned for follow-up at 3 years of age, between 2010 and 2013. At 1 month of age, participants were randomly assigned to receive oral cholecalciferol (vitamin D3) supplements of 400, 800, 1200, or 1600 IU/day until 12 months of age. Lumbar spine vertebrae 1–4 (LS) bone mineral density (BMD), LS and whole body bone mineral content (BMC), and mineral accretion were measured by dual-energy x-ray absorptiometry at 3 years.


At follow-up, the treatment groups were similar in terms of diet, sun exposure, and demographics. There were no significant differences among the groups in LS or whole body BMC, BMD, or accretion. Although, 25(OH)D concentrations were not different among the groups, higher doses (1200 and 1600 IU/day) achieved higher 25(OH)D area under the curve from 1 to 36 months vs. 400 IU/day.


This is the first longitudinal follow-up of an infant vitamin D dose-response study which examines bone mineralization at 3 years of age. Dosages higher than 400 IU/day do not appear to provide additional benefits to the bone at follow-up. Larger studies with more ethnically diverse groups are needed to confirm these results.

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The authors would like to thank Dr. Ali Khamessan, PhD Europharm International Canada Inc., for the design of the study product. We thank McGill University graduate student Sade Hayes RD, MSc for the help with study measurements and analysis of the dietary data. Finally, we would like to thank all the families who agreed to participate in the original and current follow-up study and the Mary Emily Clinical Nutrition Research Unit of the School of Dietetics and Human Nutrition.

Research funding was provided by the Canadian Institutes of Health Research and Nutricia Research Foundation, Europharm International Canada Inc. provided in-kind support of supplements. The sponsors were not involved in the design, conduct of the study, collection, management, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript. Dr. Hope A. Weiler, RD PhD is a Canada Research Chair with infrastructure funding from the Canadian Foundation for Innovation. Drs. Sina Gallo and Hope Weiler had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Author information

Correspondence to H. A. Weiler.

Ethics declarations

McGill University and George Mason University institutional review boards provided ethical approval for the study.

Conflicts of interest

Sina Gallo, Tom Hazell, Catherine A. Vanstone, Sherry Agellon, Glenville Jones, Mary L’Abbé, and Celia Rodd declare that they have no conflict of interest. Hope Weiler is a Canada Research Chair with infrastructure funding from the Canadian Foundation for Innovation.

Sources of support

Canadian Institutes of Health Research and the Nutricia Research Foundation for research funding, and Europharm International Canada Inc. for the in-kind support of supplements.

Additional information

Trial registration clinical trials.gov Identifier NCT00381914

Electronic supplementary material

Below is the link to the electronic supplementary material.


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Gallo, S., Hazell, T., Vanstone, C.A. et al. Vitamin D supplementation in breastfed infants from Montréal, Canada: 25-hydroxyvitamin D and bone health effects from a follow-up study at 3 years of age. Osteoporos Int 27, 2459–2466 (2016). https://doi.org/10.1007/s00198-016-3549-z

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  • 25-hydroxyvitamin D
  • Bone mineral
  • Bone mineral accretion
  • Dual-energy x-ray absorptiometry
  • Infants
  • Pediatrics
  • Supplementation
  • Vitamin D