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Effect of physiological doses of oral vitamin B12 on plasma homocysteine: a randomized, placebo-controlled, double-blind trial in India

European Journal of Clinical Nutrition volume 64, pages 495–502 (2010)Cite this article

Subjects

Abstract

Background/Objectives:

Vitamin B12 (B12) deficiency is common in Indians and a major contributor to hyperhomocysteinemia, which may influence fetal growth, risk of type II diabetes and cardiovascular disease. The purpose of this paper was to study the effect of physiological doses of B12 and folic acid on plasma total homocysteine (tHcy) concentration.

Subjects/Methods:

A cluster randomized, placebo-controlled, double-blind, 2 × 3 factorial trial, using the family as the randomization unit. B12 was given as 2 or 10 μg capsules, with or without 200 μg folic acid, forming six groups (B0F0, B2F0, B10F0, B0F200, B2F200 and B10F200). Plasma tHcy concentration was measured before and after 4 and 12 months of supplementation.

Results:

From 119 families in the Pune Maternal Nutrition Study, 300 individuals were randomized. There was no interaction between B12 and folic acid (P=0.14) in relation to tHcy concentration change and their effects were analyzed separately: B0 vs. B2 vs. B10; and F0 vs. F200. At 12 months, tHcy concentration reduced by a mean 5.9 (95% CI: −7.8, −4.1) μmol/l in B2, and by 7.1 (95% CI: −8.9, −5.4) μmol/l in B10, compared to nonsignificant rise of 1.2 (95% CI: −0.5, 2.9) μmol/l in B0. B2 and B10 did not differ significantly. In F200, tHcy concentration decreased by 4.8 (95% CI: −6.3, −3.3) μmol/l compared to 2.8 (95% CI: −4.3, −1.2) μmol/l in F0.

Conclusion:

Daily oral supplementation with physiological doses of B12 is an effective community intervention to reduce tHcy. Folic acid (200 μg per day) showed no additional benefit, neither had any unfavorable effects.

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Acknowledgements

We are grateful to the community, in particular the children and their families from the PMNS, for taking part in this study and to NuLife Pharmaceuticals Ltd, India for free supply of the study medicine. We thank Dr K J Coyaji, Director, KEM Hospital for providing facilities. We are grateful to Pallavi C Yajnik, the staff at Diabetes Unit and the paramedical field workers for practical assistance during the trial, to Professor Elaine Rush for her comments and to Carole Johnston for help in laboratory analysis. The study was supported by funds from the Wellcome Trust, London, UK.

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Authors and Affiliations

  1. Diabetes Unit, King Edward Memorial Hospital Research Centre, Pune, Maharashtra, India

    U S Deshmukh, C V Joglekar, H G Lubree, L V Ramdas, D S Bhat, S S Naik, P S Hardikar, D A Raut, T B Konde, A S Nanivadekar & C S Yajnik

  2. MRC Epidemiology Resource Centre, University of Southampton, Southampton General Hospital, Southampton, UK

    A K Wills & C H Fall

  3. Institute of Human Nutrition, University of Southampton, Southampton General Hospital, Southampton, UK

    A A Jackson

  4. Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK

    H Refsum

  5. Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

    H Refsum

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  1. U S Deshmukh
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Correspondence to C S Yajnik.

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The authors declare no conflict of interest.

Additional information

Contributors: CSY, CHF, HR, ASN and AAJ planned the study. USD supervised the study operations that were contributed by HGL, LVR, DSB, SSN, PSH, DAR and TBK; CVJ and AKW performed the statistical analysis; USD, CSY, ASN, CHF and HR wrote the paper.

Supplementary Information accompanies the paper on European Journal of Clinical Nutrition website

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Deshmukh, U., Joglekar, C., Lubree, H. et al. Effect of physiological doses of oral vitamin B12 on plasma homocysteine: a randomized, placebo-controlled, double-blind trial in India. Eur J Clin Nutr 64, 495–502 (2010). https://doi.org/10.1038/ejcn.2010.15

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