Clinical Briefs

With Comments from Russell H. Greenfield, MD

Oral Vitamin C

Source: Padayatty SJ, et al. Vitamin C pharmacokinetics: Implications for oral and intravenous use. Ann Intern Med 2004;140: 533-537.

Goal: To determine whether route of administration has a significant impact on plasma levels of vitamin C.

Design: Depletion-repletion, with dose concentration studies and pharmacokinetic modeling.

Subjects: Seventeen healthy volunteers (7 men, 10 women, aged 19-27 years) hospitalized for 3-6 months at an academic medical center.

Methods: Subjects adhered to a diet containing < 0.005 g vitamin C; once a state of depletion had been assured, vitamin C was administered orally in a dose of 0.015 mg twice daily. After a steady state was attained, subjects received successive oral daily vitamin C doses of 0.03 g, 0.06 g, 0.1 g, 0.2 g, 0.4 g, 1.0 g, and 2.5 g until a steady state was achieved for each dose. Bioavailability sampling was conducted at various doses, with blood samples obtained almost hourly. Intravenous administration of similar doses of vitamin C occurred at 250 mg/min, again with frequent blood sampling during the first hour following administration, and then over the subsequent 10 hours. Plasma vitamin C concentrations were calculated for a dose range of 1-100 g.

Results: Plasma concentrations of vitamin C were significantly higher over all dosages with intravenous administration. At the largest vitamin C dose used, mean peak serum values were 6.6-fold higher with intravenous administration. Peak plasma vitamin C levels increased with increasing dosages when administered intravenously, but reached a plateau with increasing oral dosages. Urine levels of vitamin C also were higher with intravenous administration across all doses.

Conclusion: Only intravenous vitamin C produces high plasma and urine levels. When ingested orally, plasma concentrations of vitamin C are tightly controlled, even at very high dosage.

Study strengths: Controlled setting with precise intakes of vitamin C; diligent blood sampling.

Study weaknesses: The conditions used for the study severely limit generalizability; very small sample size and no mention of race; only male subjects were used to construct the pharmacokinetic model.

Of note: In vitro data suggest that vitamin C in an extracellular concen- tration > 1,000 mmol/L kills cancer cells via oxidative damage that normal cells may be able to repair; using their pharmacokinetic model, the authors suggest that a single oral dose of 3 g vitamin C will produce a peak plasma level of 206 mmol/L and that repeated administration every four hours will result in almost no increase in plasma concentration, whereas intravenous administration of 3 g vitamin C will produce a peak plasma level of 1,760 mmol/L; some CAM practitioners use intravenous vitamin C in a dose of 60 g daily; how did they identify volunteers to spend 3-6 months in the hospital?(!)

Did you know?: Retrospective, non-blinded trials of oral and intravenous high-dose vitamin C (10 g daily) have shown clinical benefits for people with terminal cancer; placebo-controlled trials of patients with cancer using a daily oral dose of 10 g of vitamin C found no benefit to patients; vitamin C-rich foods often contain up to 200 mg of vitamin C.

Clinical import: This is one of the first papers to evaluate the difference in plasma vitamin C levels obtained with intravenous vs. oral administration. Whether there is clinical import to this finding, or therapeutic efficacy in the setting of cancer or wound healing as has been proposed, is yet to be proven. Of note, the authors suggest that plasma vitamin C concentrations from food intake compare favorably with those associated with oral supplemental vitamin C. It is already well-established that regular consumption of fruits and vegetables confers significant health benefits above and beyond vitamin C content.

Together, these statements speak against the need for vitamin C supplementation if fruits and vegetables are enjoyed on a frequent basis. Intravenous vitamin C and the resultant high plasma levels obtained, however, may have clinical implications.

What to do with this article: Keep a hard copy in your file cabinet.

Dr. Greenfield, Medical Director, Carolinas Integrative Health Carolinas HealthCare System Charlotte, NC, is Executive Editor of Alternative Medicine Alert.