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 first dose past the sigmoid portion is 200 mg, and plasma is completely saturated at 1,000 mg. Neutrophils, monocytes and lymphocytes saturate at 100 mg and hold at least 14 times the plasma concentration. 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 paper's stated conclusion is a recommended dietary allowance of 200 mg daily, obtainable from fruit and vegetables, with safe doses under 1,000 mg daily and no evident value above 400 mg.

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 aged 20-26, and the tissue measurements are circulating cells rather than cartilage. The authors say the pharmacokinetics are incomplete for women, ill patients, smokers and the elderly, and that no woman qualified for the study. 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.