Folic acid food fortification linked to lower COVID-19 incidence in country-level analysis

Countries that mandate folic acid fortification of foods reported substantially lower COVID-19 incidence than countries without such policies, according to a peer-reviewed study published in BMC Public Health. In analyses stratified by World Health Organization region, mandatory fortification in Africa and Europe was associated with roughly 70 percent lower COVID-19 incidence, while no statistically significant association emerged for mortality. The research team, led by Wendy N. Nembhard and colleagues, set out to test a hypothesis that circulated widely during the pandemic: that SARS-CoV-2 might co-opt folate metabolism to support viral replication.

Some earlier studies had suggested that folic acid supplementation could decrease the risk of SARS-CoV-2 infection while potentially increasing the risk of death after infection, prompting the authors to examine whether population-level folic acid intake through food fortification was associated with COVID-19 outcomes at the country level. To conduct the analysis, the team drew country-specific data on folic acid fortification policy status, the extent of grain fortification, and total adjusted potential folic acid food intake from the Global Fortification Data Exchange. COVID-19 incidence and mortality data covering December 2019 through April 2023 came from the World Health Organization.

Countries were grouped into WHO regions and World Bank income classes to account for the enormous differences in health systems, demographics, and pandemic trajectories across the globe. The statistical approach centered on negative binomial regression, a model suited to count data such as infection and death counts, which the researchers used to estimate rate ratios and 95 percent confidence intervals for COVID-19 incidence and mortality per 100,000 population. These estimates were stratified by region and income group, allowing the authors to compare fortification status within, rather than across, broadly similar groupings of countries.

Because countries that fortify foods differ systematically from those that do not, in wealth, age structure, population size, and geography, the researchers also performed propensity score analyses. These models adjusted for gender and age distribution, population size, country-level income, and geographical region, attempting to mimic the balance of a controlled experiment by comparing fortification and non-fortification countries that were otherwise similar on measured characteristics. The headline result held in both Africa and Europe: countries with mandatory folic acid fortification policies had approximately 70 percent lower COVID-19 incidence than countries without such policies, with a rate ratio of 0.26 in Africa (95 percent confidence interval 0.11 to 0.60) and 0.27 in Europe (95 percent confidence interval 0.13 to 0.57).

When the propensity score models pooled countries across regions and adjusted for income and other covariates, the difference in COVID-19 incidence between fortification and non-fortification countries remained statistically significant. Mortality told a different story. Across the analyses, including the propensity score models, the researchers found no statistically significant association between folic acid fortification and COVID-19 mortality.

The authors concluded that folic acid fortification was associated with lower COVID-19 incidence after adjusting for income and region, but not with mortality, and they emphasized that additional studies are needed to investigate the association further. The study's design carries important limitations that the authors and readers must weigh. This is an ecological, country-level comparison rather than a study of individuals, so it cannot establish that folic acid intake caused any person's infection risk to fall.

Unmeasured differences between countries, from testing capacity and reporting practices to pandemic timing and public health measures, could contribute to the observed patterns, and the fortification exposure reflects potential intake at the population level rather than measured individual consumption. The findings therefore stand as an observational signal, one that the researchers say warrants further investigation rather than a demonstration of protective effect.

Subject of Research: Association between folic acid food fortification and COVID-19 incidence and mortality across countries

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

Article References: Nembhard, W. N., Famuyide, L., Du, R., Zohoori, N., Kennedy, J. L., Boehme, K. W., Forrest, J. C., & Amick, B., III (2026). Is there an association between folic acid food fortification and the risk of COVID-19 incidence or mortality?. BMC Public Health. https://doi.org/10.1186/s12889-026-29441-3

Image Credits: AI Generated

DOI: 10.1186/s12889-026-29441-3

Keywords: folic acid, food fortification, COVID-19, SARS-CoV-2, incidence, mortality, neural tube defects, Global Fortification Data Exchange, negative binomial regression, propensity score, BMC Public Health, ecological study