As we know from previous discussions, folic acid-supplementation does not prevent all neural tube defect pregnancies (see my next post on the PONTI study). I was on 800mg of folic acid (double the recommended dosage) and I had a pregnancy with anencephaly, so at least that level of folic acid did not help me.
There is some suggestion that folic acid supplementation does not actually protect against NTDs, instead it just causes those pregnancies to end in miscarriage:
“Contrary to expectations, in a few mouse NTD models FA treatment resulted in detrimental effects, including an increased risk for NTDs and embryo loss prior to the time of NTC (29, 30). Although it is largely assumed that FA prevents NTDs by correcting the embryological defect, these findings of early embryo loss are consistent with the possibility raised back in 1997 based on miscarriage risk that embryo loss may explain some of the decrease in human NTD occurrence upon FA supplementation (31). If these unexpected findings are relevant to human NTDs, it could suggest that, for certain mutations, FA may not be protective or even neutral in its action, although the consensus is that in humans, at a population-scale, FA has a preventive effect.”
This study suggests that for some mice (and thus maybe some people), folic acid supplementation may not be beneficial. In other words, there’s a theory that if you take folic acid you’re NOT increasing your chance of having a healthy pregnancy. You’re just decreasing the chance you’ll have a pregnancy with a neural tube defect because you’re making it more likely a neural tube defect pregnancy will end in miscarriage. Interesting theory.
The same article questions whether there are some harmful effects of folic-acid fortification:
“Moreover, questions have been raised as to whether the increase in FA intake acting through the methylation cycle may predispose to allergic airway disease, although the current evidence is conflicting (33–35). With respect to NTD risk, some mutant mice showed a beneficial response to increased FA over a single gestation period but a detrimental response over multiple generations (30). This contradictory response depending on the length of FA exposure highlights the difficulties in considering how best to model human exposure to FA as currently implemented. Moreover, it raises the important but little studied question of whether there may be unexpected effects of long-term FA fortification and supplementation in humans or potential effects due to increased levels of metabolized and unmetabolized FA.”
So this article is considering exactly what I’ve worried about—what if folic acid (especially the large doses [5000mg] I was on after my anencephaly pregnancy) is actually harmful? Folic acid allegedly promotes new cell growth. What if that’s NOT desirable at some levels?
I found at least one article suggesting that high levels of folic acid in early stages of pregnancy might be harmful to the developing fetus:
“Fetuses are exposed to high concentrations of folate during early stages of development because mothers are advised to consume folate supplements during pregnancy to lower the incidence of spina bifida [89–91]. As a result, the combination of folic acid with high concentrations of circulating estrogens during early stages of development may cause an additive or synergistic effect on DNA methylation [88]. These changes in DNA methylation patterns have the potential to induce both beneficial and adverse effects on the developing genome. Future research is required to confirm whether early exposure to environmental estrogens can alter the plasma estrogen profile enough to induce long-term programming effect on the developing fetus.”
I was always worried that I was taking so much folic acid I might actually be harming my developing babies, and I think I was right to worry. Specifically, I worried if too much folic acid might cause birth defects. Maybe. Maybe.
For most “normal” people who are on normal amount of folic acid (400mg), there does not appear to be an increased risk of miscarriage:
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