In recent years, clinicians and researchers have begun to observe vitamin B12 deficiency in Metformin users. First thought to be a short term problem, researchers are now finding that with long term metformin use not only does the B12 deficiency persist, but it grows. Left alone long enough, vitamin B12 deficiency leads to a host of conditions, many that Metformin was supposed to prevent, including:
- Increased rates peripheral neuropathy (nerve pain and numbness that leads to all sorts of problems for diabetics)
- Pernicious anemia (the body can’t make enough red blood cells because of a B12 deficiency; can be fatal if not treated).
- Cognitive deficits with associated white matter hyperintensities and total brain volume decline
- Elevated homocysteine levels (marker for cardiovascular disease and stroke)
For women, especially of reproductive age, B12 deficiency can be particularly troubling, if not downright dangerous. Vitamin B12 deficiency during pregnancy leads to an increased incidence of neural tube defects and anencephaly (the neural tube fails to close during gestation – anencephaly pictured above) . Once thought to be solely related to folate or folic acid deficiency (vitamin B9), researchers are now finding that B12 has a role in neural tube defects as well. Many women on Metformin are coming into pregnancy vitamin B12 deficient.
This is where it gets tricky. Metformin is used in women with PCOS to reduce insulin sensitivity. Metformin also tends to regulate ovulation for PCOS women and was believed to help women get pregnant (though the data here are mixed here as well). Without regular ovulation, conceiving is near impossible and so the fact that Metformin might have helped with ovulation had been seen as a breakthrough for previously infertile PCOS women. Reproductive endocrinologist embraced this new found fertility tool and as one might expect, the requisite studies (read marketing documents) flooded the esteemed peer-reviewed journals to proclaim the benefits of this new wonder drug. No wait, Metformin is not a drug, it’s a new vitamin – Vitamin M.
We now have a drug that is given liberally to women who become pregnant and then continued across the pregnancy. The drug crosses the placental barrier and there are no studies to indicate either its safety or harm to the fetus. The drug causes significant vitamin B12 deficiency, which alone poses great risk to fetal development (neural tube defects) but who knows what vitamin B12 deficiency plus the endocrine disrupting effects Metformin will have on the developing fetal insulin or cardiovascular systems. Are we looking at more transgenerational effects? Metformin does not prevent maternal gestational diabetes (as was widely speculated) and increases pre-eclampsia, pulmonary embolism and other nasty pregnancy complications. And yet, the major patient organizations advocate for its use across pregnancy.
Photo credit: Centers for Disease Control and Prevention, National Center on Birth Defects and Developmental Disabilities