Global evaluation of the impact of food fortification with folic acid on rates of schizophrenia

Background: Low folate status is one of the multiple factors thought to contribute to the development of schizophrenia. As of 2023, over 70 countries have implemented mandatory fortification of foods with folic acid, a public health measure aimed at reducing neural tube defects; however, the impact of such policy on schizophrenia has not been comprehensively investigated. Method: We assessed the impact of mandatory folic acid fortification on changes in the schizophrenia rates in 194 jurisdictions between 1990 and 2019 using publicly available data. We used weighted regression models adjusted for sociodemographic and sociopolitical factors, experience of natural disasters, and baseline schizophrenia rate. Results: Age-adjusted prevalence and incidence of schizophrenia increased marginally between 1990 and 2019. In all geographic regions, schizophrenia prevalence and incidence per 100,000 positively correlated with countries' sociodemographic index and were lower with fortification. Schizophrenia burdens were higher among males compared to females. Lower prevalence and incidence of schizophrenia were associated with having mandatory fortification with modest magnitudes. Duration of fortification or the fortification dose did not appear to have a strong impact. However, in the 15–39 year age-group, both mandatory fortification (β = −13·14 (−22·60, −3·68)) and duration of fortification (β = −0·82 (−1·40, −0·23)) were significantly associated with lower schizophrenia with larger magnitude in both sexes. The highest dose tertile was reported to have the lowest incidence and the smallest increase in prevalence in this age-group. Conclusion: Folic acid fortification may be a beneficial intervention in lowering schizophrenia among adolescents and young adults.