Levine · Proceedings of the National Academy of Sciences of the United States of America 2001 · inpatient depletion-repletion trial · n=?

A new recommended dietary allowance of vitamin C for healthy young women.

Cited 495 times in the scientific literature.

Level 3 - non-randomized controlled study

Prospective inpatient dose-ranging depletion-repletion pharmacokinetic study without reported randomization.

PubMed 11504949 · doi:10.1073/pnas.171318198 · record verified 2026-08-30

What was done

Healthy young women were hospitalized for an inpatient depletion-repletion study lasting 186 ± 28 days. Participants were given daily vitamin C doses ranging from 30 mg to 2,500 mg. Researchers measured steady-state plasma concentrations, intracellular saturation in circulating cells, urinary excretion, and biomarkers of endogenous oxidative stress (plasma and urine F2-isoprostanes and a major urine metabolite).

What was found

The relationship between vitamin C dose and steady-state plasma concentration was sigmoidal, with doses above 100 mg daily moving beyond the linear phase of absorption. Plasma and circulating cells saturated at 400 mg daily, with higher doses excreted in urine. Vitamin C supplementation at all tested doses (30–2,500 mg/day) caused no changes in plasma or urinary F2-isoprostanes or their metabolites. Based on these kinetics, the authors recommended increasing the female RDA to 90 mg daily.

Why it matters

It establishes female-specific pharmacokinetic saturation curves for vitamin C rather than extrapolating women's nutritional requirements from male datasets.

Limits

The abstract does not disclose the sample size. The study evaluated only healthy young women in a strictly controlled inpatient setting, and only one biomarker pathway of oxidative stress (lipid peroxidation via F2-isoprostanes) was assessed.

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