B Vitamins Reduce Homocysteine but not Disease in Diabetic Patients

Whenever the topic of kidney disease arises in my practice, the first thought that crosses my mind is diabetes since almost 40% will eventually have kidney problems.1 There is evidence of a correlation between homocysteine levels in diabetic patients and diseases of the kidneys, heart and eyes.2 To lower homocysteine, we have a powerful, proven way to do it, with 3 members of the B vitamin family.3 Many health care professionals have reasonably concluded that lowering homocysteine would lower the risk, degree or progression of secondary problems often seen in patients with diabetes.

Homocysteine, What is Normal?

Normal plasma homocysteine values vary widely between labs and can range from as low as 2.2 to as high as 17 micromoles per liter (abbreviated as mcmol/L or umol/L). Homocysteine increases with age and runs ~ 1.5 umol/L higher in males than females. There is a debate on what is optimal, and this too is affected by gender and age. In general, 'optimal homocysteine' ranges run from less than 10 to under 6 umol/L.

The Study

The Diabetic Intervention with Vitamins to Improve Nephropathy study followed a screened group of diabetic patients with kidney disease for 3 years each. Those who met the criteria had diabetic nephropathy, but their condition was not considered advanced.4 The 238 subjects who qualified were divided into two groups. One took 2500 mcg of folic acid, 1000 mcg of vitamin B12, and 25 mg of vitamin B6 a day. The second group took a look alike placebo. 83% of the patients were white male, 81% had type 2 (as opposed to type 1) diabetes and their mean age was 60. Plasma homocysteine levels at baseline were 16.4 umol/L and 14.7 umol/L in the placebo and B vitamin groups respectively.


Placebo B vitamins

No. of Patients 119 119

Homocysteine (umol/L) +2.6 -2.2

GFR (mL/min) -10.7 -16.5

Heart attacks 4 8

Stroke 1 6


After ~ three years of follow up, the B vitamin group had their mean homocysteine levels decline from 14.7 umol/L to 12.5 umol/L, while those assigned to placebo had their averages increase from 16.4 umol/L to 19 umol/L. However, the B vitamin group also had an accelerated rate of GFR decrease, more strokes and more heart attacks. These results were unexpected, disappointing and will undoubtedly lead to further research since the successful reduction of this biomarker had an outcome associated with it's elevation.

Unless patients with diabetes and kidney dysfunction have compelling reasons to use the levels of folic acid, vitamin B6 and vitamin B12 in this study for other, more serious co-morbidities, they should stick to RDA dosing until there is conclusive evidence to disprove or explain the findings in this study.

1. Palmer, A.J., Valentine, W.J., Chen, R., et al. A Health Economic Analysis of Screening and Optimal Treatment of Nephropathy in Patients with Type 2 Diabetes and Hypertension in the U.S.A. Nephrol Dial Transplant 2008; 23(4:1216-23)

2. Refsum, H, Nurk, E., Smith, A.D., et al. The Hordal and Homocysteine Study: A Community-Based Study of Homocysteine, its Determinants and Associations with Disease. J Nutr 2006; 136(6(suppl):1731s-1740s)

3. Andersen, G.D. Homocysteine Dynamic Chiropractic. 1998 16(7:28)

4. House, A.A, Eliasziw, M., Cattran, D.C., el al. Effects of B-Vitamin Therapy on Progression of Diabetic Nephropathy JAMA 2010 303 (16:1603-09)