Complications
Large doses of intravenous folic acid have been reported to exacerbate seizures in patients with underlying seizure disorders.[89]
Intravenous folic acid use is often limited to treatment of severe malabsorption disorders and certain inborn errors of folate metabolism.
Inadequately treated or untreated patients will have megaloblastic anaemia, leukopenia, and thrombocytopenia.
Folate deficiency in pregnant women increases the incidence of fetal neural tube defects.[29][30][31] This can be effectively prevented by increasing folic acid intake pre-conceptually and during pregnancy.[15][31][43] For women who are planning to conceive or who are capable of becoming pregnant, pre-conception folic acid supplementation is recommended at a dose of 400-800 micrograms/day, with higher doses (up to 5 mg/day) recommended for certain risk groups.[32][33][34] The UK National Institute for Health and Care Excellence recommends 5 mg/day in certain risk groups.[35][36]
In the US, the recommended dietary allowance for folate during pregnancy and lactation varies from 400-800 micrograms/day depending upon factors such as diet, inclusion of food fortified with folic acid, socio-economic status, and individual medical history. US Department of Agriculture and US Department of Health and Human Services: dietary guidelines for Americans, 2020-2025 Opens in new window NIH: dietary supplement fact sheet - folate Opens in new window
Moderate elevation of plasma homocysteine is associated with cardiovascular disease, stroke, and venous thrombosis.[77][78] Although folic acid supplementation may reduce plasma homocysteine levels, there is insufficient evidence to show that homocysteine-lowering interventions can reduce the risk of cardiovascular and cerebrovascular diseases.[79][80]
High folate levels inhibit malignant transformation, but high folate levels may also enhance the growth of established malignancies.[81]
Some studies have suggested a possible link between low folate status and colorectal cancer.[81] Other studies suggest a temporal association between folic acid fortification and an increase in colorectal cancer and prostate cancer.[82][83]
Evidence is not sufficiently clear to recommend increased folate intake for populations at risk for developing colorectal cancer.[84][85]
Evidence is emerging of possible toxicities associated with excess folate intake as a result of folic acid food fortification and use of dietary supplements containing folic acid.[90] Toxicities include progressive neurological damage, cognitive impairment (particularly in individuals with concomitant vitamin B12 [cobalamin] deficiency), and enhanced growth of malignant tumours (specifically colonic tumours).[87][88][90][91]
A prospective observational study noted a 'U-shaped' relationship between maternal multivitamin intake and risk of autism spectrum disorder (ASD). High maternal plasma folate levels (>60.3 nanomol/L [>26.5 nanograms/mL]) and vitamin B12 levels (≥536.8 picomol/L [≥0.23 nanograms/mL]) at birth were also associated with increased risk of ASD (hazard ratio 2.5, 95% CI 1.3 to 4.6).[92]
Low serum folate level is associated with a higher risk of developing schizophrenia spectrum disorders.[96] One meta-analysis identified significantly lower serum folate levels in patients with a first episode of psychosis compared with healthy controls.[97] One randomised controlled trial found that vitamin B12 and folic acid supplements reduced the negative symptoms of schizophrenia in patients with low-functioning folate hydrolase 1 polymorphisms, compared with placebo.[98]
Use of this content is subject to our disclaimer