Phytate (myo-inositol hexakisphosphate) is a polyphosphate found in plant-based foods whose intestinal absorption mechanisms are insufficiently understood. Due to its high affinity for calcium, phytate can deplete extracellular calcium and potentially affect tight junction integrity, which could increase paracellular permeability. This study investigated the permeation of phytate across Caco-2 cell monolayers depending on calcium concentration. Differentiated Caco-2 cells were cultured on semi-permeable membranes and incubated with various phytate concentrations (0.17–1.66 mM) in media with low (2.1 µM) or normal (1.8 mM) calcium concentration. Phytate permeability and tight junction integrity were analyzed using HPLC and Lucifer yellow as a paracellular marker. At low calcium concentration, significant permeability was observed starting from 0.55 mM phytate (~60% at 1.66 mM), while at normal calcium concentration, significant permeability was only detectable at 1.66 mM. The increased Lucifer yellow permeation correlated with phytate permeation and confirmed tight junction disruption. Phytate that reached the basolateral side at physiological calcium concentration precipitated completely as insoluble calcium–phytate complex. These results demonstrate that phytate can pass intestinal epithelium via the paracellular pathway and increase the paracellular permeability, especially at low apical concentrations of calcium.
Bäuerle et al. (2026) studied this question.