Complete loss of 5-methyltetrahydrofolate in wheat during simulated gastric digestion

Folate deficiency affects over one billion people globally, driving widespread cereal fortification programs. 5-methyltetrahydrofolate (5-MTHF), the predominant natural folate form, is emerging as a safer alternative to traditional folic acid for fortification. However, conflicting reports exist regarding its digestive stability. Here we demonstrate that 5-MTHF undergoes an apparent complete loss in wheat matrices during simulated gastric digestion. This loss occurred across all wheat fractions tested and exhibited concentration-dependent kinetics, with folate retention improving from undetectable levels to 80 % when wheat flour concentration was reduced fifty-fold. Ascorbic acid provided substantial protection, whereas gallic acid showed negligible effects. Nitrogen purging failed to prevent the phenomenon, and enzymatic analysis of digestion residues confirms that it was not attribute to simple physical absorption. These findings suggest endogenous wheat components promote a rapid, largely oxygen-insensitive loss of 5-MTHF, challenging existing fortification paradigms and underscoring the necessity for protective strategies in cereal-based folate delivery systems.