Is there an association between folic acid food fortification and the risk of COVID-19 incidence or mortality?

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Folic acid fortification is a global public health intervention to prevent neural tube defects. During the pandemic, SARS-CoV-2 was postulated to “hijack” folate for viral replication, and studies showed that folic acid supplementation might decrease SARS-CoV-2 infection risk but increase risk of postinfection mortality. Given the implications of these studies, we assessed the association between country-specific folic acid intake levels and COVID-19 incidence and mortality rates. We used country-specific folic acid fortification policy status, fortification of grains, and total adjusted potential folic acid food intake from the Global Fortification Data Exchange. We obtained COVID-19 incidence and mortality data, December 2019–April 2023, from the World Health Organization. Countries were categorized into World Health Organization regions and World Bank income groups. Rate ratios (RR) and 95% confidence intervals (CI) were estimated from negative binomial regression analyses for the association between folic acid fortification and COVID-19 incidence and mortality rates per 100,000 population stratified by region and income. Propensity score analyses adjusted for gender and age distribution, population size, country-level income, and geographical region. Countries with mandatory folic acid fortification policies in Africa and Europe had approximately 70% lower COVID-19 incidence than those that did not (RR = 0·26; 95% CI: 0·11, 0·60 and RR = 0·27; 95% CI: 0·13, 0·57 respectively). Propensity score analyses showed a significant difference in COVID-19 incidence between fortification and non-fortification countries, but no statistically significant results for mortality. Folic acid fortification was associated with lower COVID-19 incidence, after adjusting for income and region, but not with mortality. Additional studies are needed to investigate this association.