*2.1. Passive Diffusion*

In solution at physiological pH, vitC predominantly attains its ionized form, ASC. Because of a relatively low hydrophobicity, ASC and DHA do not easily cross biological membranes and primarily rely on the interaction with transporter molecules anchored in the cell membrane [41,42]. However, both ASC and DHA can, to a small extent, move by passive diffusion, and DHA diffuses through cellular membranes more willingly than ASC [43]. It has also been suggested that during intestinal uptake and in renal reabsorption, ASC leaves the epithelial cells from the basolateral membranes down a concentration gradient by passive diffusion [44]. Moreover, being a week acid with a pKa of 4.2 [21], the theoretical equilibrium between blood and tissue favors plasma with a ratio of 2.5 to one. Regardless, the fraction by which passive diffusion contributes to the overall regulation of vitC homeostasis at physiological conditions is believed to be of minor importance [40].
