Many people of size take metformin (a.k.a. Glucophage). They might take it for insulin resistance/PCOS issues, or they might take it for blood sugar issues....or both, since the two are often related.
This post is of particular concern to those women of childbearing age who take metformin, but anyone on metformin should know about it.
I recently ran across some research linking metformin with low levels of B vitamins, particularly vitamin B12 and Folic Acid.
Although the worst effects seem to happen with years of treatment and higher dosages, even short-term treatment (16 weeks) reduced the levels of folate and B12.
These lowered levels of folate and B12 also seem to be linked to an increase in homocysteine levels, which is commonly seen after metformin is started. Now, what significance this has, if any, is still being debated. In terms of general health, homocysteine levels may be tied to heart health; high levels are considered a risk factor for cardiovascular disease. There is some research indicating that administration of B-group vitamins reduces homocysteine levels in non-pregnant PCOS patients treated with metformin. But we don't really know yet if lowering homocysteine levels results in any meaningful reduction in long-term endpoints like decreased heart attacks or mortality.
However, we do know that some people on metformin do develop megoblastic anemia at some point during treatment. So certainly, it's seems like it's something that anyone on metformin should be aware of and monitored for periodically.
It might even be sensible to take extra B vitamins (B group complex, presumably) while on metformin, although formal studies on the value of that seem to be lacking so far. There is also one study that found that supplemental calcium may help blunt or reverse B12 malabsorption with metformin.
Implications for Pregnancy?
All this information about metformin impacting B12 and folic acid levels makes me wonder if there are special implications for women of childbearing age. We know that folic acid levels are important for preventing birth defects like neural tube defects (NTDs, like spina bifida or anencephaly). If a woman with PCOS has been on metformin for years and her folic acid levels are chronically low when she conceives, does this increase her risk for NTDs?
As far as I can tell, no one knows. There doesn't seem to be any increase in birth defects in women on metformin so far, but research is limited. Because preliminary research on metformin in pregnancy indicates that it cuts the risk for miscarriage and gestational diabetes in women with PCOS, it's likely to be used more and more often in the future, provided the research continues to be supportive.
So the question becomes, should women on metformin who are considering conceiving (or who are of childbearing age at all) be supplemented with extra folic acid and B12 (or B vitamins in general)? And if so, by how much? What about calcium, if it helps reverse the malabsorption of B12? Should levels of B12 be monitored during pregnancy?
At this point, I don't think anyone knows for sure. Anecdotally, many women on metformin do seem to be taking additional folic acid at least. Consult your care provider about this topic and what dosages might be appropriate beyond a normal prenatal vitamin. (And if you do decide to take supplemental vitamins in addition to metformin, you should probably take them at different times of day.)