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Metformin and Vitamin B12 Deficency: Dr. Javaid Iqbal


The American Diabetes Association (ADA) recommends a combination of healthy diet, exercise, and metformin as soon as a patient is diagnosed with diabetes. Metformin is the drug most often prescribed for type 2 diabetes and may also help to reduce the risk of heart.

Side Effects of Metformin:
The common side effects of metformindr-javail-profile-pic are gastrointestinal and can be overcomed by initiating metformin therapy at a lower dose and slowly increasing the dose, by giving metformin after meals, or by utilizing a slow-release metformin preparation.A potentially damaging, and well-documented complication of metformin is —vitamin B12 malabsorption—is poorly recognized and not screened for or treated prophylactically by the majority of physicians who prescribe metformin.

Role of VIT. B12 in Body:
Vitamin B12 is required for DNA and myelin synthesis and is a cofactor in the production of methionine from homocysteine, which has been linked to cognitive decline. It is also required for the conversion of methylmalonic acid (MMA), an organic acid with potential neurotoxic properties, to succinyl-CoA (an intermediate in the Krebs cycle).

Proposed mechanisms for cognitive decline associated with vitamin B12 deficiency include inadequate methylation in the central nervous system, accumulation of homocysteine and/or MMA, and demyelination of white matter.

Clinical Features in Patients with Vit B12 Deficiency:
A deficiency of vitamin B12 can lead to vitamin B12 deficiency anemia. A mild deficiency may cause only mild, if any, symptoms. But as the anemia worsens it may causes symptoms such as:

  • Weakness, tiredness or light-headedness 
  • Rapid heartbeat and breathing
  • Pale skin
  • Sore tongue
  • Easy bruising or bleeding, including bleeding gums
  • Stomach upset and weight loss
  • Diarrhea or constipation

If the deficiency is not corrected, it can damage the nerve cells. If this happens, vitamin B12 deficiency effects may include:

  • Tingling or numbness in fingers and toes
  • Difficulty walking
  • Mood changes or depression
  • Memory loss, disorientation, and dementia

While the anemia of vitamin B12 deficiency is reversible, the progress of the neuropathy is only arrested and not reversed with initiation of vitamin B12 therapy.

There are many cases of metformin-induced vitamin B12 deficient neuropathy that are misdiagnosed as diabetic neuropathy.

Since Both homocysteine and MMA accumulate in serum  with vitamin B12 deficiency So  Suspected vitamin B12 deficiency should be evaluated with MMA levels, homocysteine levels, or both. Measurement of serum vitamin B12 levels often produces both false-negative and false-positive results and is unreliable for diagnosis.

Consider vitamin B12 supplementation in patients receiving metformin, particularly for older patients and other patients at risk for reduced dietary vitamin B12 absorption, and for patients who have received metformin for several years.

Perhaps a more practical and cost-effective approach would be to give every patient on metformin an annual 1000 microgram injection of vitamin B12 which is sufficient to cover vitamin B12 needs for at least a year.

Vitamin B12 deficiency can be treated with oral supplements or intramuscular injections depending on type and severity of deficiency.

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