Metformin is a prescription medication for the treatment of type 2 diabetes. It lowers blood glucose by limiting glucose absorption from food, diminishing the output of glucose from the liver and enhancing the body's response to the insulin that is available. Prolonged use of metformin, however, may lead to vitamin B-12 deficiency because metformin can hinder the absorption of B-12 from the small intestine.
Mechanism of B-12 Absorption
Digestive enzymes and acids in the stomach separate food from vitamin B-12 so that as the liberated B-12 travels through the small intestine, it can eventually form a complex with a protein called intrinsic factor. Special sites called receptors in the small intestine pick up the B-12-intrinsic factor complex in a process mediated by calcium produced in the pancreas. Certain proteins then transport the complex from the small intestine into the bloodstream, which carries it to cells in the body that require vitamin B-12. Vitamin B-12 promotes the health of nerve cells and red blood cells and is a part of DNA synthesis.
Metformin and Malabsorption
In the March 2006 issue of "Age and Ageing," researchers described vitamin B-12 deficiencies that occurred with two diabetic patients on metformin therapy, and discussed the role of metformin in the malabsorption of vitamin B-12. The absorption of vitamin B-12 can't occur unless the B-12-intrinsic factor complex gets taken up by receptors in the small intestine. This uptake is dependent on the presence of calcium, and the researchers note that metformin is known to influence receptors that depend on calcium. Based on these facts, the researchers conclude that metformin causes B-12 malabsorption by preventing receptors in the small intestine from taking up the B-12-intrinsic factor complex.
Effect of B-12 Malabsorption
Chronic metformin-induced B-12 malabsorption and resulting B-12 deficiency can cause permanent damage to nerves in peripheral regions such as the feet, legs and arms, a condition called peripheral neuropathy. Symptoms may include numbness and a tingling or burning feeling in the affected area. Doctors may have difficulty diagnosing neuropathy due to B-12 deficiency in diabetic patients because the symptoms are similar to those of diabetic neuropathy, nerve damage due to high blood sugar levels.
Prevention/Solution
There are two approaches that diabetic patients on long-term metformin therapy can take to prevent the occurrence of vitamin B-12 deficiency, according to Dr. David S.H. Bell of the University of Alabama School of Medicine. First, they can consult their doctor at least once a year to have their B-12 levels checked. A second and more attractive approach is to arrange for an annual injection of vitamin B-12 that will provide more B-12 than patients on metformin therapy will need in one year.
References
- MedlinePlus: Metformin
- Drugs.com: Metformin Disease Interactions
- Oregon State University, Linus Pauling Institute: Micronutrient Information Center: Vitamin B12: Deficiency
- "Age and Ageing"; Metformin-Related Vitamin B12 Deficiency; Kin Wah Liu, et al.; March 2006
- Endocrinetoday.com: Resource Center: Type 2 Diabetes: Vitamin B12 Deficiency: A Chronic Complication of Metformin Therapy That Can Cause Irreversible Neuronal Damage
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