Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance.
Level 3 - non-randomized controlled study
Prospective, non-randomized within-subject pharmacokinetic depletion-repletion study
PubMed 8623000 · doi:10.1073/pnas.93.8.3704
What was done
Seven healthy volunteers were hospitalized for 4–6 months on a vitamin C-depleted diet (<5 mg daily). Researchers evaluated steady-state plasma and tissue concentrations, bioavailability, urinary excretion, and adverse metabolic markers across seven daily vitamin C doses ranging from 30 to 2500 mg.
What was found
Steady-state plasma concentrations followed a sigmoid curve with the steepest rise between 30 and 100 mg daily; the existing 60 mg RDA fell on the lower third of this curve. Complete plasma saturation occurred at 1000 mg daily, while neutrophils, monocytes, and lymphocytes saturated at 100 mg daily at concentrations at least 14-fold higher than plasma. Bioavailability was 100% at a single 200 mg dose but declined at 500 mg and higher. Six of seven volunteers excreted no vitamin C in urine until reaching the 100-mg dose. Oxalate and urate urinary excretion increased at 1000 mg daily.
Why it matters
This landmark study provided the primary pharmacokinetic basis for updating dietary intake recommendations, showing that 200 mg daily achieves near-maximal plasma and immune cell saturation without excessive urinary excretion or increased oxalate output.
Limits
The study included only seven participants, did not report demographic details or sex distribution in the abstract, and was conducted in a tightly controlled inpatient setting that may not reflect varied free-living populations with different metabolic demands.
Cited by
- context The plasma half-life of supplemental vitamin C is approximately 1.5 hours.