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Is a low blood level of vitamin B12 a cardiovascular and diabetes risk factor? A systematic review of cohort studies

European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

To assess the prior hypothesis that low blood vitamin B12, partly through hyperhomocysteinemia and partly through direct effects, increases the risk of cardiovascular diseases and diabetes. As background, we also extracted all-cause mortality from the studies that met our criteria.

Methods

A systematic review of prospective cohort studies identified through searching six electronic databases, screening of reference lists, and citation search. Included studies reported data on the association between vitamin B12 blood levels, or other appropriate surrogate biological markers e.g. holotranscobalamin or serum/urine methylmalonic acid, and fatal or non-fatal incident diabetes and cardiovascular events.

Results

Seven studies were included. Studies differed regarding the population studied, length of follow-up, study outcomes, and data analysis—a narrative synthesis approach was performed to examine the results. Most studies met few of the quality assessment criteria which were adapted from the Scottish Intercollegiate Guidelines Network (SIGN). Only one high-quality study reported that low B12 increased the risk of incident cerebral ischaemia (RR = 1.76; 95% CI = 1.16–2.68). After controlling for homocysteine, the association persisted although weakened (RR = 1.57; 95% CI = 1.02–2.43), suggesting that the effects of low B12 were only partly mediated by homocysteine. In two studies, higher B12 levels were associated with a greater risk of total mortality (RR = 1.00; 95% CI = 1.00–1.00 and HR = 1.15; 95% CI = 1.08–1.22, respectively) and combined fatal and non-fatal coronary events (RR = 1.00; 95% CI = 1.00–1.00). No association between study outcomes and vitamin B12 levels was found in four other studies.

Conclusions

Surprisingly, there is only very limited evidence that vitamin B12 deficiency predisposes to the risk of mortality and morbidity from either cardiovascular diseases or diabetes in adults. Current data do not support vitamin B12 supplementation to reduce the risk of cardiovascular diseases or diabetes.

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Acknowledgments

The authors wish to thank Dr Fay Crawford, University of Edinburgh, for her generous support and advice on the study methodology, and specifically on whether a meta-analysis was warranted. We also thank Marshall Dozier, Senior Liaison Librarian for the College of Medicine and Veterinary Medicine, University of Edinburgh for helping with the literature search strategy, and Smita Kulkarni, Diabetes Unit King Edward Memorial Research Center, for her valuable contribution to the literature search. Finally, we are grateful to the referees assigned to this paper for their constructive comments and suggestions that helped improve the manuscript.

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Authors and Affiliations

  1. Public Health Sciences Section, School of Clinical Sciences and Community Health and Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland, UK

    Snorri B. Rafnsson & Raj S. Bhopal

  2. Clinical Sciences Research Institute, Warwick Medical School, CSB, UHCW NHS Trust, Coventry, CV2 2DX, UK

    Ponnusamy Saravanan

  3. Diabetes Unit, KEM Hospital and Research Centre, Rasta Peth, Pune, Maharashtra, 411 011, India

    Chittaranjan S. Yajnik

Authors
  1. Snorri B. Rafnsson
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  2. Ponnusamy Saravanan
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  3. Raj S. Bhopal
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  4. Chittaranjan S. Yajnik
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Correspondence to Snorri B. Rafnsson.

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Rafnsson, S.B., Saravanan, P., Bhopal, R.S. et al. Is a low blood level of vitamin B12 a cardiovascular and diabetes risk factor? A systematic review of cohort studies. Eur J Nutr 50, 97–106 (2011). https://doi.org/10.1007/s00394-010-0119-6

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  • DOI: https://doi.org/10.1007/s00394-010-0119-6

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