Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance

Levine M, Conry-Cantilena C, Wang Y, Welch RW, Washko PW, Dhariwal KR, Park JB, Lazarev A, Graumlich JF, King J, Cantilena LR · Proceedings of the National Academy of Sciences

The study that mapped the dose-concentration curve, and it explains why 1 g/day is a different proposition from 200 mg/day rather than five times as much of the same thing. Plasma concentration is sigmoid against dose: the steep part runs from 30 to 100 mg, the curve flattens by 200 mg, and plasma is completely saturated at 1,000 mg. White cells saturate at 100 mg. Bioavailability is complete at a single 200 mg dose and declines from 500 mg upward, with the absorbed excess excreted. Oxalate and urate excretion were elevated at 1,000 mg/day compared with lower doses. The authors' conclusion is explicit: safe doses are under 1,000 mg daily and doses above 400 mg have no evident value.

Population

Healthy men hospitalized for 4-6 months on a diet containing under 5 mg vitamin C daily

Intervention

Seven sequential daily doses from 30 mg to 2,500 mg, with steady-state plasma and tissue measurement at each

Limitations

Seven men, and the tissue measurements are circulating cells rather than cartilage. It measures concentration and excretion, not clinical outcomes, so 'no evident value' above 400 mg is an inference from saturation rather than a trial result. Depletion-repletion, no control group. NIH intramural.