What are the benefits and risks of folic acid fortification?

Folic acid fortification refers to the addition of folic acid to the food supply — most commonly through the enrichment of wheat, rice, and corn — in an attempt to reduce the potential consequences of folate deficiency. Fortification became mandatory in the United States and Canada in 1998, and today over 80 countries follow similar practices.^[1][2]

The rationale for fortification was to prevent NTDs — a group of potentially fatal birth defects that can occur within the first four weeks of pregnancy, particularly in the context of folate deficiency. To reap the benefits, a woman ideally needs to start supplementing at least 4 weeks before conception, and because many pregnancies are unplanned, fortification ensures that women are universally exposed to folic acid. Observational research suggests that countries that introduced mandatory fortification have seen 30 to 60% reductions in the rates of NTDs.^[1][3][4][5] Compared to regions without fortification, rates of NTDs are generally observed to be lower in countries with fortification; however, differences in monitoring strategies between countries make it difficult to draw accurate conclusions.^[3]

Fortification may have had other positive consequences, including reductions in rates of anemia and reduced levels of homocysteine, which may have translated to a small reduction in the rate of strokes.^{[6][5][7][8][9]}

Alternatively, fortification may have led to some unintended negative health consequences. Folic acid fortification has been associated with an increased risk of cognitive impairment in older adults with concurrent low vitamin B12 levels.^[10][11] This could be because folic acid can mask the clinical signs of a vitamin B12 deficiency, meaning the deficiency may go untreated, potentially leading to irreversible cognitive impairment in the long term.^[10]

Additionally, when folic acid fortification was being implemented in North America between 1996 and 1998, a short-term increase in the rate of colorectal cancer was observed (approximately 4 to 6 additional cases per 100,000 people).^[12] While research has generally found folic acid intake to have a neutral or beneficial effect on colorectal cancer risk,^[13][14][15] there is evidence that high intakes of folate might exacerbate preexisting precancerous lesions.^[16][17] However, colorectal cancer rates returned to normal after 1998, which calls into question whether fortification was truly the factor driving the short-term increase.^[18]

Lastly, there is concern that increased exposure to unmetabolized folic acid (UMFA) at a population level may have negative health consequences. UMFA occurs when the amount of folic acid ingested exceeds the body's ability to convert it to a usable form of folate, and UMFA has been found in the serum of nearly all Americans post-fortification.^[19] Currently, there is very little evidence for or against the safety of UMFA and further research is needed.