Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.


Vitamin B6, B9 and B12 in diabetic nephropathy—beware

Combination therapy with vitamins B6, B9 and B12 is a therapeutic intervention to decrease levels of plasma homocysteine and the risk of cardiovascular disease. However, a recent trial found that cosupplementation with these vitamins exacerbated the decline in renal function and increased the risk of vascular disease in patients with diabetic nephropathy. Confidence in this high-dose vitamin supplement is shaken.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it


Prices may be subject to local taxes which are calculated during checkout


  1. House, A. A. et al. Effect of B-Vitamin therapy on progression of diabetic nephropathy: A randomized controlled trial. JAMA 303, 1603–1609 (2010).

    Article  CAS  PubMed  Google Scholar 

  2. Lonn, E. et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N. Engl. J. Med. 354, 1567–1577 (2006).

    Article  CAS  PubMed  Google Scholar 

  3. Jamison, R. L. et al. Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: A randomized controlled trial. JAMA 298, 1163–1170 (2007).

    Article  CAS  PubMed  Google Scholar 

  4. Ebbing, M. et al. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA 302, 2119–2126 (2009).

    Article  CAS  PubMed  Google Scholar 

  5. Williams, M. E. et al. Effects of pyridoxamine in combined phase 2 studies of patients with type 1 and type 2 diabetes and overt nephropathy. Am. J. Nephrol. 27, 605–614 (2007).

    Article  CAS  Google Scholar 

  6. Lajer, M. et al. Plasma concentration of asymmetric climethylarginine (ADMA) predicts cardiovascular morbidity and mortality in type 1 diabetic patients with diabetic nephropathy. Diabetes Care 31, 747–752 (2008).

    Article  CAS  PubMed  Google Scholar 

  7. Koyama, K. et al. Randomized controlled trial of the effect of short-term coadministration of methylcobalamin and folate on serum ADMA concentration in patients receiving long-term hemodialysis. Am. J. Kidney Dis. 55, 1069–1078 (2010).

    Article  CAS  PubMed  Google Scholar 

  8. Zhao, R., Gao, F. & Goldman, I. D. Reduced folate carrier transports thiamine monophosphate: an alternative route for thiamine delivery into mammalian cells. Am. J. Physiol. Cell Physiol. 282, C1512–C1517 (2002).

    Article  CAS  PubMed  Google Scholar 

  9. Thornalley, P. J. The potential role of thiamine (vitamin B1) in diabetic complications. Curr. Diabetes Rev. 1, 287–298 (2005).

    Article  CAS  PubMed  Google Scholar 

  10. Rabbani, N. et al. High dose thiamine therapy for patients with type 2 diabetes and microalbuminuria: a pilot randomised, double-blind, placebo-controlled study. Diabetologia 52, 208–212 (2009).

    Article  CAS  PubMed  Google Scholar 

Download references


The authors thank Diabetes UK and the British Heart Foundation for supporting their research on diabetes mellitus and cardiovascular disease.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Paul J. Thornalley.

Ethics declarations

Competing interests

The authors declare an association with the following company: Merck Serono. P. J. Thornalley received a research grant from Merck Serono for the project “Epidemiological cross-sectional study on B-vitamin acid status in South-East Asian diabetic patients” conducted in 2008–2009. P. J. Thornalley and N. Rabbani have received speakers honoraria from Merck Serono.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Thornalley, P., Rabbani, N. Vitamin B6, B9 and B12 in diabetic nephropathy—beware. Nat Rev Endocrinol 6, 477–478 (2010).

Download citation

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing