Metformin is probably the most common by-mouth medication prescribed for people with diabetes. Sold as Glucophage, Glumetza, Riomet, Glumetza, Obimet, Dianben, Diabex, Diaformin and as a generic, it’s also prescribed sometimes even for people at increased risk to develop diabetes. Metformin worldwide sales exceed 1.7 billion USD each year. The adverse event (side effect) most feared with metformin is lactic acidosis, but vitamin B12 deficiency seems to be much more common.
B12 Deficiency From Decreased Absorption
The mechanism that causes B12 deficiency is thought to be decreased absorption of the vitamin by the small intestines. Normally, B12 is released from ingested food and joins with intrinsic factor secreted by the stomach. B12-intrinsic factor complex is absorbed further down the gastrointestinal tract, in the ileum. Its absorption is calcium-dependent, and that’s where metformin may have some effect, slowing down or reducing (but not stopping) absorption.
Some studies have shown that low B12 occurs in up to a third of people taking metformin long term.
B12 is necessary for protection and repair of nerves. Low B12 can lead to poor repair of nerves, interfering with their function. This can cause symptoms such as numbness, funny feelings (paresthesias), decreased sensation to touch and vibration, and weakness in the area served by the damaged nerve.
B12 also participates in making new red blood cells, which are necessary to replace worn out cells—red cells get old and are removed after around 120 days, usually by the spleen. B12 deficiency causes new cells to be imperfect, fewer, and larger. When B12 deficiency is caused by lack of intrinsic factor, the condition is pernicious anemia.
Other Causes Of B12 Deficiency
Besides metformin, other possible medications that can lead to B12 deficiency include
- H2-blockers (Pepcid, Zantac, Axid, others)
- Antacids (TUMS, Mylanta, Maalox, others)
- Proton pump inhibitors (Aciphex, Nexium, Prilosec, others)
Conditions that can lead to B12 deficiency include
- Stomach conditions (gastritis, old age)
- Pancreatic deficiency
- Malabsorption in the small intestines
Tests for B12 Deficiency
B12 levels can be measured directly in blood samples. Also, methylmalonic acid, a substance in blood that is increased in B12 deficiency, is often measured.
Metformin Lowers Blood Sugar
Diabetes is a condition in which blood glucose (a sugar) does not get into cells, robbing them of the energy source they need. Glucose piles up in the blood, and hyperglycemia or high blood sugar is the major clinical reflection of the condition.
Metformin reduces the production of glucose in the liver by a third, thereby reducing the burden of glucose in the blood. It does this by activating an enzyme in the liver, AMPK.
AMPK also affects muscle cells, increasing the efficiency of insulin, making more glucose available for energy. This additional benefit helps many people lose weight, if accompanied by diet and increased physical activity.
Is Neuropathy Dangerous?
Yes. For one thing, it can numb the feet so injuries such as cuts and sores are not felt, letting them grow to become a significant infection. In people with diabetes who may also have poor circulation, this can lead to amputation.
Advice to Metformin Users
People taking metformin should discuss this issue with their clinician. Prescriber’s Letter, a journal for clinicians, suggests patients should take a daily multivitamin that has B12, although they admit there is no proof this prevents B12 deficiency. They also suggest getting the recommended amount of calcium from diet or supplements, since that may increase B12 absorption. (Prescriber’s Letter, August, 2009)
James Cooper - I'm on the faculty of a health science department at a large university. Most of my articles derive from conferences or presentations ...
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