Researchers in Croatia investigated folate levels in children living in the Mediterranean region of Croatia and examined whether these levels were associated with atopic diseases and asthma.
Conditions like asthma, eczema, and allergic rhinitis happen when the immune system becomes overly sensitive to harmless triggers (like pollen or dust).
The researchers noted that allergic diseases have risen sharply in developed countries over recent decades. Because this increase is too rapid to be explained by genetic change, they focused on environmental and epigenetic factors such as allergens, infections, pollutants, diet, stress and immune influences.
Folic acid is of particular interest because it supplies methyl groups for DNA methylation and may therefore influence gene regulation linked to allergy development. However, its role is debated, with some evidence suggesting that folic acid fortification could contribute to rising allergy rates, while other studies indicate that low folate levels may worsen inflammation and increase atopy, meaning folate could also protect against allergic disease.
Folate deficiency associated with elevated immune markers in children
The researchers used a cross-sectional design to assess 292 children recruited from the University Hospital Split and a primary care paediatric clinic between January 2024 and January 2025. Physicians selected children who were either diagnosed with atopic diseases such as asthma, allergic rhinitis, or atopic dermatitis, or healthy children who served as controls.
The researchers assessed clinical history, laboratory markers, lung function tests, skin prick testing, total IgE, eosinophil counts, vitamin B12 levels, and folate levels.
Results indicated children with atopic diseases or asthma were more likely to have folic acid deficiency compared with healthy controls. Folate deficiency was also associated with older age, higher eosinophil counts, and higher IgE levels, which the researchers suggested was linked to allergic inflammation. Further analysis confirmed that folic acid levels decreased with age and were slightly lower in children with higher IgE levels, while relationships with eosinophils and vitamin B12 were not significant.
After accounting for age, the association between folate and asthma disappeared, but the link with broader atopic disease remained significant, which the researchers noted indicated that age is a major confounding factor, but that folate may still be related to allergic conditions in general.
Is folic acid fortification necessary?
The authors suggest that modern dietary changes in Mediterranean populations such as increased processed food intake and reduced folate-rich foods may contribute to deficiency.
Globally, around 60 countries, including the United States, Canada, Australia, parts of Latin America and Africa currently mandate folic acid fortification, and the UK recently announced it would make the same move in the latter half of 2026.
Dr. Harry Jarrett, director of science and research at UK supplement brand Heights, recently told NutraIngredients that modern diets provide fewer micronutrients than previous generations had access to, noting that government guidelines should evolve to reflect the diet and food system people actually live with today.
“Croatia does not implement mandatory folic acid fortification of staple foods, which may further explain the high prevalence of deficiency observed in our cohort,” the researchers noted.
They added that biologically, folate is important for DNA methylation and immune regulation, so low levels could influence immune development and increase allergic sensitivity.
They concluded that folate deficiency is very common in this population and is linked to markers of allergic disease, but causality cannot be proven due to the study design; therefore, they recommend further research, including dietary data and intervention studies, to clarify whether improving folate status could influence allergic disease outcomes in children.
Journal: Nutrients; “Folic Acid Level of Children with Atopy/Asthma and Children Without Chronic Allergic Disease—Should We Consider Nutritional Fortification?” doi: https://doi.org/10.3390/nu18091368 Authors: Rogulj, et al.
