Folic acid fortification and safety at high intakes
What it found
Expert reviews in people found no conclusive evidence that folic acid fortification causes harm, though high intakes from supplements above 1000 micrograms a day still need more study.
What they found
Studies in people
Birth defects prevented
Randomized controlled trials in the 1980s and 1990s showed that mothers taking multivitamins with folic acid had fewer neural tube defects in their babies. The U.S. Preventive Services Task Force says the benefit for women planning or able to become pregnant is substantial.
Cancer risk in people
A meta-analysis of randomized controlled trials with over 50,000 people found no significant effect of folic acid supplements at a median dose of 2.0 mg per day on cancers of the large intestine, prostate, lung, breast or any other site. Cancer death rates have continued to fall since mandatory fortification began in the United States.
Diabetes and thyroid
One study in India linked high maternal folate and low vitamin B 12 to insulin resistance in 6-year-old children, but a randomized trial in Nepal found children of mothers given 400 micrograms of folic acid daily had lower risk of metabolic syndrome. The U.S. panel found no consistent evidence that high folic acid affects diabetes risk or glucose metabolism.
Allergies and asthma
Observational studies have looked at childhood asthma and allergy, but the U.S. panel said data on high folic acid intakes and asthma sensitization were limited and called for rigorous controlled studies in pregnant women and children.
Animal and lab studies
Cancer in animals
Rodent studies on folic acid and colon cancer have given inconsistent results. Some show less tumor growth and others show more, and many used folic acid doses 10 times higher than what is adequate for mouse chow.
Studies in people and animals
Thinking and memory
Observational studies in older people found links between high folate levels, low vitamin B 12 and cognitive problems, but controlled trials have not tested this and animal data do not support it. The UK committee concluded folic acid had no significant effect on cognitive decline in intervention trials.
What the authors conclude
“Additional research is needed to assess the health effects of folic acid supplement use when the current upper limit for folic acid is exceeded.”
Also in their conclusions
- They say the totality of the evidence fully supports the benefits of mandatory folic acid fortification in preventing neural tube defects.
- They state there are no established risks for adverse consequences from existing mandatory folic acid fortification programs.
- They call for additional research on the health effects of folic acid supplement use when the current upper limit of 1000 micrograms a day is exceeded.
How it was done
Countries add folic acid to flour and grains to prevent birth defects, and questions have been raised about whether higher intakes could cause unintended harm.
The authors reviewed two major expert assessments, the U.S. National Toxicology Program report from 2015 and the UK Scientific Advisory Committee on Nutrition draft from 2016, plus newer studies on cancer, thinking and memory, diabetes, thyroid disease and allergies.
What it can’t tell you
- Many studies on cancer were not designed or powered to detect changes in cancer incidence, and cancer takes many years to develop.
- Observational studies can show links but cannot prove that folic acid causes the outcomes seen.
- The effects of unmetabolized folic acid in the blood are not established.
Who paid
- Funding
- Funded by NICHD NIH HHS; NIDDK NIH HHS (from the PubMed record).
- Authors work at
- Cornell University, New York
The paper
- Title
- Safety of folic acid
- Type
- ReviewThe authors read earlier studies and describe what they found. It isn’t a new study.
- Evidence
- Studies in people · animals · lab
- Summarised from
- Full text
- Cite
- Field MS, Stover PJ (2018). Safety of folic acid. Annals of the New York Academy of Sciences. doi:10.1111/nyas.13499Free full textPubMed 29155442DOI
Summary written 26 Sep 2026. Check it against the paper before it changes what you eat. How we summarise papers · Report an error