Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 1996 Apr 16;93(8):3704-9.
doi: 10.1073/pnas.93.8.3704.

Vitamin C Pharmacokinetics in Healthy Volunteers: Evidence for a Recommended Dietary Allowance

Free PMC article
Clinical Trial

Vitamin C Pharmacokinetics in Healthy Volunteers: Evidence for a Recommended Dietary Allowance

M Levine et al. Proc Natl Acad Sci U S A. .
Free PMC article


Determinants of the recommended dietary allowance (RDA) for vitamin C include the relationship between vitamin C dose and steady-state plasma concentration, bioavailability, urinary excretion, cell concentration, and potential adverse effects. Because current data are inadequate, an in-hospital depletion-repletion study was conducted. Seven healthy volunteers were hospitalized for 4-6 months and consumed a diet containing <5 mg of vitamin C daily. Steady-state plasma and tissue concentrations were determined at seven daily doses of vitamin C from 30 to 2500 mg. Vitamin C steady-state plasma concentrations as a function of dose displayed sigmoid kinetics. The steep portion of the curve occurred between the 30- and 100-mg daily dose, the current RDA of 60 mg daily was on the lower third of the curve, the first dose beyond the sigmoid portion of the curve was 200 mg daily, and complete plasma saturation occurred at 1000 mg daily. Neutrophils, monocytes, and lymphocytes saturated at 100 mg daily and contained concentrations at least 14-fold higher than plasma. Bioavailability was complete for 200 mg of vitamin C as a single dose. No vitamin C was excreted in urine of six of seven volunteers until the 100-mg dose. At single doses of 500 mg and higher, bioavailability declined and the absorbed amount was excreted. Oxalate and urate excretion were elevated at 1000 mg of vitamin C daily compared to lower doses. Based on these data and Institute of Medicine criteria, the current RDA of 60 mg daily should be increased to 200 mg daily, which can be obtained from fruits and vegetables. Safe doses of vitamin C are less than 1000 mg daily, and vitamin C daily doses above 400 mg have no evident value.

Similar articles

See all similar articles

Cited by 241 articles

See all "Cited by" articles


    1. Clin Pharmacol Ther. 1981 Mar;29(3):318-21 - PubMed
    1. Nutr Rev. 1994 Aug;52(8 Pt 1):266-70 - PubMed
    1. N Engl J Med. 1986 Apr 3;314(14):892-902 - PubMed
    1. Am J Clin Nutr. 1982 Aug;36(2):332-9 - PubMed
    1. Epidemiology. 1992 May;3(3):194-202 - PubMed

Publication types

LinkOut - more resources