Rethinking Folic Acid: Evolutionary Adaptation, Epigenetic Risks, a Metabolic Switch and the Case for Personalised Nutrition

Population-specific variations in folate metabolism, influenced by evolutionary pressures, challenge the universal application of standardised dietary folate recommendations. This paper examines historical folate intake, the impact of fortification, and the role of a metabolic switch in nucleotide synthesis, proposing that mandatory fortification may pose risks for populations unadapted to high folic acid exposure. Some diets, specifically the diet of Indigenous Australian’s, were historically rich in animal protein, providing sufficient natural folate. The transition to fortified foods, has led to excessive folic acid intake, potentially resulting in toxicity with epigenetic consequences. Additionally, formula-fed infants receive significantly higher folic acid levels than breastfed infants, compounded by maternal supplementation and processes foods being fortified, also raising concerns about excessive exposure. Emerging technologies, including biophysical modelling and deep learning, offer promising avenues for personalised nutrition and precision healthcare.