Dr. Kumar’s Take:
This NIH depletion-repletion study hospitalized seven healthy volunteers for 4 to 6 months and stepped them through seven daily doses of vitamin C, from 30 mg to 2500 mg. Plasma concentration followed a sigmoid curve: the steep part sits between 30 and 100 mg daily, and the current RDA of 60 mg daily falls on the lower third of that curve. The first dose beyond the sigmoid portion was 200 mg daily, and the authors concluded the RDA should be raised to 200 mg daily, an amount you can get from fruits and vegetables. That is the number I use in clinic.
Key Takeaways:
✔ Plasma vitamin C rises steeply between the 30 and 100 mg daily doses, then flattens.
✔ Neutrophils, monocytes, and lymphocytes saturated at 100 mg daily and held concentrations at least 14-fold higher than plasma.
✔ No vitamin C appeared in the urine of six of seven volunteers until the 100 mg dose; at single doses of 500 mg and higher, the absorbed amount was excreted.
✔ Oxalate and urate excretion were elevated at 1000 mg of vitamin C daily compared to lower doses, and daily doses above 400 mg have no evident value.
Actionable Tip:
Aim for around 200 mg daily. That is the intake the authors recommend as a revised RDA, and they note it can be obtained from fruits and vegetables. Daily doses above 400 mg have no evident value, and the authors define safe doses as less than 1000 mg daily.
Brief Summary:
This NIH study measured how different vitamin C intakes affect plasma and immune cell concentrations, bioavailability, and urinary excretion. Seven healthy volunteers were hospitalized for 4 to 6 months on a diet containing less than 5 mg of vitamin C daily, then given seven daily doses ranging from 30 to 2500 mg while blood, cell, and urine measurements were taken at steady state. Plasma concentrations followed sigmoid kinetics, complete plasma saturation occurred at 1000 mg daily, and bioavailability was complete for a single 200 mg dose but declined at single doses of 500 mg and higher.
Study Design: Vitamin C Dosing, Absorption, and Excretion
- Seven healthy volunteers were hospitalized for 4 to 6 months on a diet containing less than 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.
- Cell concentrations were measured in neutrophils, monocytes, and lymphocytes.
- Bioavailability and urinary excretion were assessed, including at single doses of 200 mg, 500 mg, and higher.
Results: Plasma Levels and Urinary Loss at Different Doses
Plasma Vitamin C Levels by Dose
- Plasma concentration as a function of dose displayed sigmoid kinetics.
- The steep portion of the curve occurred between the 30 mg and 100 mg daily doses.
- The current RDA of 60 mg daily fell on the lower third of the curve.
- The first dose beyond the sigmoid portion of the curve was 200 mg daily.
- 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.
Urinary Excretion at Different Doses
- Below 100 mg/day: No vitamin C was excreted in the urine of six of seven volunteers until the 100 mg dose.
- 200 mg (single dose): Bioavailability was complete.
- 500 mg and higher (single dose): Bioavailability declined, and the absorbed amount was excreted.
- 1000 mg/day: Oxalate and urate excretion were elevated compared to lower doses.
The authors classify safe doses as less than 1000 mg daily, and state that daily doses above 400 mg have no evident value.
Vitamin C: Absorption vs. Excretion Explained
Absorption and retention are not unlimited. A single 200 mg dose is completely bioavailable, but at single doses of 500 mg and higher, bioavailability declines and whatever is absorbed gets excreted. That is the practical ceiling: past a point, taking more moves vitamin C through you rather than into you.
Related Studies and Research
Vitamin C and the Common Cold: Leucocyte Ascorbic Acid Study: Links vitamin C status to immune cell saturation and cold frequency.
Vitamin C Deficiency: Clinical Signs, Risk Factors, and Treatment: Summarizes how inadequate intake leads to subclinical and clinical deficiency.
Vitamin C Physiology: The Goldilocks Review: Highlights the balance needed for optimal vitamin C utilization and storage.
Plasma and Leucocyte Vitamin C Relationship: Insights from BMJ 1971: Explains how plasma and immune cell vitamin C are interconnected.
Frequently Asked Questions
How much vitamin C should I aim for daily?
Based on these data and Institute of Medicine criteria, the authors concluded the current RDA of 60 mg daily should be increased to 200 mg daily, which can be obtained from fruits and vegetables.
Is there any benefit to taking more than 400 mg/day?
The authors state that vitamin C daily doses above 400 mg have no evident value.
At what dose does the body start excreting vitamin C?
No vitamin C was excreted in the 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.
Can high doses cause harm?
Oxalate and urate excretion were elevated at 1000 mg of vitamin C daily compared to lower doses. The authors define safe doses of vitamin C as less than 1000 mg daily.
How can I get 200 mg of vitamin C naturally?
The authors note that 200 mg daily can be obtained from fruits and vegetables, so build the day around produce rather than a pill.
Conclusion
This study gives a clean dose-response answer: plasma vitamin C climbs steeply between 30 and 100 mg daily, immune cells saturate at 100 mg daily, and 200 mg daily is the first dose past the steep part of the curve and the intake the authors recommend as a new RDA. Above that, bioavailability falls off at single doses of 500 mg and higher, daily doses above 400 mg have no evident value, and 1000 mg daily raises oxalate and urate excretion. Food first, at about 200 mg a day.
