Pharmacokinetic perspectives on megadoses of ascorbic acid

Ascorbic acid (vitamin C) is commonly used as a dietary supplement, often in megadoses. However, as the daily oral dose is increased, the concentration, of ascorbic acid in the plasma and other body fluids does not increase proportionally, but instead tends to approach an upper limit. For example, when the daily dose is increased from 200 to 2500 mg (from 1.1 to 14.2 mmol the mean steady state plasma concentration increases only from ≃12 to 15 mg/L (from 68.1 to 85.2 μmol/L). Published data were reanalyzed with an integrated modeling approach to shed new quantitative light on this phenomenon. This analysis is based on the renal clearance of ascorbic acid, which rises sharply with increasing plasma concentrations as a result of saturable tubular reabsorption. The analysis indicates that both saturable gastrointestinal absorption and nonlinear renal clearance act additively to produce the ceiling effect in plasma concentrations. As a consequence of this ceiling effect, there is no pharmacokinetic justification for the use of megadoses of ascorbic acid.