Vitamin C metabolites, independent of smoking status, significantly enhance leukocyte, but not plasma ascorbate concentrations

Adv Ther. 2008 Oct;25(10):995-1009. doi: 10.1007/s12325-008-0106-y.


Introduction: The objective of this study was to test the effects of acute doses of vitamin C alone, calcium ascorbate with vitamin C metabolites, and placebo, on total plasma and leukocyte vitamin C concentrations over 24 hours.

Methods: A double-blind, placebo-controlled, four-way crossover study was performed consisting of four separate phases lasting 24 hours each and utilizing one of four oral 1000-mg preparations within each phase (one of vitamin C alone, two separate vitamin C formulations of calcium ascorbate with vitamin C metabolites, and placebo). There was a 7-day washout between phases, and blood draws at seven time points within each phase of the study for a total of 28 serologic measurements per subject and 420 total measurements for the entire clinical trial. Vitamin C concentration in plasma and leukocytes were measured by high-performance liquid chromatography at baseline and at six sequential time periods over 24 hours.

Results: Fifteen healthy males were enrolled, aged 18-39 years; nine were had never smoked and six were chronic smokers. No significant difference in plasma vitamin C levels was observed when comparing the different preparations. However, at 24 hours, calcium ascorbate with metabolites resulted in significantly higher concentrations of vitamin C in leukocytes (P<0.0001) compared with vitamin C alone. These results were similar for both metabolite formulations, and independent of smoking status.

Conclusion: Regardless of smoking status, vitamin C metabolites may enhance leukocyte utilization of vitamin C itself, despite no consistent difference in plasma levels among the different preparations. A larger clinical investigation is warranted to confirm these preliminary findings, and to determine the clinical relevance of this impact on overall immune function.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Ascorbic Acid / blood
  • Ascorbic Acid / pharmacokinetics*
  • Aspartic Acid / blood
  • Chromatography, High Pressure Liquid
  • Cross-Over Studies
  • Double-Blind Method
  • Humans
  • Leukocytes / metabolism*
  • Male
  • Smoking / metabolism*
  • Vitamins / pharmacokinetics*
  • Young Adult


  • Vitamins
  • Aspartic Acid
  • Ascorbic Acid