PHARMACOKINETIC PERSPECTIVES ON MEGADOSES OF ASCORBIC-ACID

Ascorbic acid (vitamin C) is commonly used as a dietary supplement, of ten in megadoses. However, as the daily oral dose is increased, the co ncentration of ascorbic acid in the plasma and other body fluids does not increase proportionally, but instead tends to approach an upper li mit. 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 in creases only from approximate to 12 to 15 mg/L (from 68.1 to 85.2 mu m ol/L). Published data were reanalyzed with an integrated modeling appr oach 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 gastrointest inal absorption and nonlinear renal clearance act additively to produc e the ceiling effect in plasma concentrations. As a consequence of thi s ceiling effect, there is no pharmacokinetic justification for the us e of megadoses of ascorbic acid.