Metformin, one of the most commonly used drugs to treat diabetes, may be causing vitamin B12 and folate deficiencies in those that take the drug. Metformin has stood up well in clinical trials, showing its potential to reduce the risk of macrovascular disease (a disease of the large blood vessels including those found near the heart, the brain, and the limbs), reduce all-cause mortality and even prevent some cancers.
However, the drug is now being blamed for contributing to the progression of diabetic peripheral neuropathy. Diabetic neuropathy is a type of nerve damage. It happens when high blood sugar, over time, damages nerve fibers. This damage can occur in the digestive system, the urinary tract, blood vessels, and the heart. Most often, however, nerves are damaged in the legs and feet.
In a recent study performed at Bethesda General Hospital in the Netherlands, researchers recruited 745 patients attending outpatient clinics at three general hospitals. All were diabetic and were being treated with insulin. The researchers received consent to add metformin to the patient’s insulin therapy. A second group acted as control.
The trial lasted for 16 weeks. Measurements of serum homocysteine, folate, vitamin B12, markers of glycemic control, and body weight were taken at baseline and at study completion. The research team found that metformin use, when compared with a placebo, was associated with an increase in homocysteine and a decrease in folate and vitamin B12. The researchers speculated that it was the increase in homocysteine that caused the patients’ folate and B12 levels to drop.
In another trial performed in China, researchers also concluded that long term use of metformin therapy increases the probability of folate and B12 deficiency and probably contributes to the progression of diabetic peripheral neuropathy. The researchers went on to say, however, that even taking metformin for a few months will result in a decrease of folate and B12. They concluded by suggesting that diabetics taking metformin need to supplement with B12.
Adequate vitamin B12 is very important in maintaining good health. Also called cobalamin, B12 contains the essential mineral cobalt. B12 is a very complex molecule and also contains carbon, oxygen, phosphorus, and nitrogen. Your body uses B12 for the metabolism of nerve tissue and to maintain the nervous system as a whole. B12 is also used in the formation of normal red blood cells. It’s often referred to as the “energy” vitamin as it can increase your energy levels. B12 injections are often used in the treatment of fatigue in older adults. As for folate, it also aids in red blood cell production and helps with the utilization and breakdown of proteins. Folic acid helps to build RNA and DNA and so has a fundamental role in the growth and reproduction of all cells.
If you are taking metformin therapy, be aware that you may need to supplement it with vitamin B12 and/or folate. To boost your intake of these two compounds through your diet, add lean meats, fish and yogurt to your weekly meals to increase your B12 intake and leafy green vegetables to increase your folic acid intake.
De Jager, J., et al., “Effects of short-term treatment with metformin on markers of endothelial function and inflammatory activity in type 2 diabetes mellitus: a randomized, placebo-controlled trial,” J Intern Med. January 2005; 257(1): 100-9.
Xu, L., et al., “Adverse effect of metformin therapy on serum vitamin B12 and folate: short-term treatment causes disadvantages?,” Med Hypotheses. August 2013; 81(2): 149-51.
Lehert, P., et al., “Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial,” J Intern Med. November 2003; 254(5): 455-63.