Advances in Therapy

, Volume 25, Issue 10, pp 995–1009

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

  • Mark A. Moyad
  • Maile A. Combs
  • Angelica S. Vrablic
  • Janet Velasquez
  • Benilda Turner
  • Samuel Bernal
Original Research

Abstract

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.

Keywords

ascorbic acid calcium threonate immune function vitamin C metabolites white blood cells 

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References

  1. 1.
    Padayatty SJ, Sun H, Wang Y, et al. Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann Intern Med. 2004;140:533–537.PubMedGoogle Scholar
  2. 2.
    Dehghan M, Akhtar-Danesh N, McMillan CR, Thabane L. Is plasma vitamin C an appropriate biomarker of vitamin C intake? A systematic review and meta-analysis. Nutr J. 2007;6:41.PubMedCrossRefGoogle Scholar
  3. 3.
    Galan P, Briancon S, Favier A, et al. Antioxidant status and risk of cancer in the SU.VI.MAX study: is the effect of supplementation dependent on baseline levels? Br J Nutr. 2005;94:125–132.PubMedCrossRefGoogle Scholar
  4. 4.
    Cook NR, Albert CM, Gaziano M, et al. A randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women. Results from the Women’s Antioxidant Cardiovascular Study. Arch Intern Med. 2007;167:1610–1618.PubMedCrossRefGoogle Scholar
  5. 5.
    Christen WG, Gaziano JM, Hennekens CH. Design of Physicians’ Health Study II—a randomized trial of beta-carotene, vitamins E and C, and multivitamins, in prevention of cancer, cardiovascular disease, and eye disease, and review of results of completed trials. Ann Epidemiol. 2000;10:125–134.PubMedCrossRefGoogle Scholar
  6. 6.
    Schectman G. Estimating ascorbic acid requirements for cigarette smokers. Ann N Y Acad Sci. 1993;686:335–345.PubMedCrossRefGoogle Scholar
  7. 7.
    Gueguen S, Pirollet P, Leroy P, et al. Changes in serum retinol, alpha-tocopherol, vitamin C, carotenoids, zinc and selenium after micronutrient supplementation during alcohol rehabilitation. J Am Coll Nutr. 2003;22:303–310.PubMedGoogle Scholar
  8. 8.
    Jacob RA. Assessment of human vitamin C status. J Nutr. 1990;120:1480–1485.PubMedGoogle Scholar
  9. 9.
    Benzie IF. Vitamin C: prospective functional markers for defining optimal nutritional status. Proc Nutr Soc. 1999;58:469–476.PubMedGoogle Scholar
  10. 10.
    Anderson, RA. Vitamin C. In: Hughes DA, Darlington LG, Bendich A, editors. Diet and Human Immune Function. Totowa, NJ: Humana Press, Inc.; 2004:133–148.Google Scholar
  11. 11.
    Padayatty SJ, Katz A, Wang Y, et al. Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr. 2003;22:18–35.PubMedGoogle Scholar
  12. 12.
    Shidfar F, Baghai N, Keshavarz A, Ameri A, Shidfar S. Comparison of plasma and leukocyte vitamin C status between asthmatic and healthy subjects. East Mediterr Health J. 2005;11:87–95.PubMedGoogle Scholar
  13. 13.
    Michos C, Kiortsis DN, Evangelou A, Karkabounas S. Antioxidant protection during the menstrual cycle: the effects of estradiol on ascorbic-dehydroascorbic acid plasma levels and total antioxidant plasma status in eumenorrhoic women during the menstrual cycle. Acta Obstet Gynecol Scand. 2006;85:960–965.PubMedCrossRefGoogle Scholar
  14. 14.
    Johnson TP, Mott JA. The reliability of selfreported age of onset of tobacco, alcohol and illicit drug use. Addiction. 2001;96:1187–1198.PubMedCrossRefGoogle Scholar
  15. 15.
    Lee MM, Whittemore AS, Lung DL. Reliability of recalled physical activity, cigarette smoking, and alcohol intake. Ann Epidemiol. 1992;2:705–714.PubMedCrossRefGoogle Scholar
  16. 16.
    Huerta M, Chodick G, Balicer RD, Davidovitch N, Grotto I. Reliability of selfreported smoking history and age at initial tobacco use. Prev Med. 2005;41:646–650.PubMedCrossRefGoogle Scholar
  17. 17.
    Kuczmarski MF, Kucmarski RJ, Najjar M. Effects of age on validity of self-reported height, weight, and body mass index: findings from the Third National Health and Nutrition Examination Survey, 1988–1994. J Am Diet Assoc. 2001;101:28–34.PubMedCrossRefGoogle Scholar
  18. 18.
    Charlson, M, Szatrowski, TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47:1245–1251.PubMedCrossRefGoogle Scholar
  19. 19.
    Som S, Basu S, Mukherjee D, et al. Ascorbic acid metabolism in diabetes mellitus. Metabolism. 1981;30:572–577.PubMedCrossRefGoogle Scholar
  20. 20.
    Ness AR, Khaw KT, Bingham S, Day NE. Vitamin C status and undiagnosed angina. J Cardiovasc Risk. 1996;3:373–377.PubMedGoogle Scholar
  21. 21.
    Fazio V, Flint DM, Wahlqvist ML. Acute effects of alcohol on plasma ascorbic acid in healthy subjects. Am J Clin Nutr. 1981;34:2394–2396.PubMedGoogle Scholar
  22. 22.
    Lecomte E, Herbeth B, Pirollet P, et al. Effect of alcohol consumption on blood antioxidant nutrients and oxidative stress indicators. Am J Clin Nutr. 1994;60:255–261.PubMedGoogle Scholar
  23. 23.
    Canoy D, Wareham N, Welch A, et al. Plasma ascorbic acid concentrations and fat distribution in 19068 British men and women in the European Prospective Investigation into Cancer and Nutrition Norfolk cohort study. Am J Clin Nutr. 2005;82:1203–1209.PubMedGoogle Scholar
  24. 24.
    Levine M, Conry-Cantilena C, Wang Y, et al. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc Natl Acad Sci U S A. 1996;93:3704–3709.PubMedCrossRefGoogle Scholar
  25. 25.
    Basu TK: Vitamin C-aspirin interactions. Int J Vitam Nutr Res Suppl. 1982;23:83–90.PubMedGoogle Scholar
  26. 26.
    Vinson JA, Bose P. Comparative bioavailability to humans of ascorbic acid alone or in a citrus extract. Am J Clin Nutr. 1988;48:601–604.PubMedGoogle Scholar
  27. 27.
    Johnston CS, Luo B. Comparison of the absorption and excretion of three commercially available sources of vitamin C. J Am Diet Assoc. 1994;94:779–781.PubMedCrossRefGoogle Scholar
  28. 28.
    Gibson SL, Moore FM, Goldberg A. Measurement of leukocyte ascorbic acid. BMJ. 1966;1:1152–1153.PubMedCrossRefGoogle Scholar
  29. 29.
    Iwase H, Ono I. Determination of ascorbic acid in human plasma by high-performance liquid chromatography with electrochemical detection using a hydroxyapatite cartridge for precolumn deproteinization. J Chromatogr B Biomed Appl. 1994;655:195–200.PubMedCrossRefGoogle Scholar
  30. 30.
    Selby SM. Standard Mathematical Tables. 20th edition. Cleveland, Ohio: CRC Press; 1972.Google Scholar
  31. 31.
    Douglas RM, Hemilä H, Chalker E, Treacy B. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev. 2007;(3):CD000980.Google Scholar
  32. 32.
    Moyad MA, Combs MA. Vitamin C dietary supplements: an objective review of the clinical evidence. Part I. Sem Prev Alt Med. 2007;3:25–35.Google Scholar
  33. 33.
    Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: ARED Report No. 8. Arch Ophthalmol. 2001;119:1417–1436.Google Scholar
  34. 34.
    Hercberg S, Galan P, Preziosi P, et al. The SU.VI.MAX study: a randomized, placebocontrolled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med. 2004;164:2335–2342.PubMedCrossRefGoogle Scholar
  35. 35.
    Coleman H, Chew E. Nutritional supplementation in age-related macular degeneration. Curr Opin Ophthalmol. 2007;18:220–223.PubMedCrossRefGoogle Scholar
  36. 36.
    Stoltzfus RJ. Iron deficiency: global prevalence and consequences. Food Nutr Bull. 2003;24(suppl. 4):99–103.Google Scholar
  37. 37.
    Lozoff B, Georgieff MK. Iron deficiency and brain development. Semin Pediatr Neurol. 2006;13:158–165.PubMedCrossRefGoogle Scholar
  38. 38.
    Zollinger PE, Tuinebreijer WE, Breederveld RS, Kreis RW. Can vitamin C prevent complex regional pain syndrome in patients with wrist fractures? A randomized, controlled, multicenter dose-response study. J Bone Joint Surg Am. 2007;89:1424–1431.PubMedCrossRefGoogle Scholar
  39. 39.
    Zollinger PE, Tuinebreijer WE, Kreis RW, Breederveld RS. Effect of vitamin C on frequency of reflex sympathetic dystrophy in wrist fractures: a randomised trial. Lancet. 1999;354:2025–2028.PubMedCrossRefGoogle Scholar
  40. 40.
    Levine M, Rumsey SC, Daruwala R, Park JB, Wang Y. Criteria and recommendations for vitamin C intake. JAMA. 1999;281:1415–1423.PubMedCrossRefGoogle Scholar
  41. 41.
    Padayatty SJ, Doppman JL, Chang R, et al. Human adrenal glands secrete vitamin C in response to adrenocorticotrophic hormone. Am J Clin Nutr. 2007;86:145–149.PubMedGoogle Scholar
  42. 42.
    Anderson R, Oosthuizen R, Maritz R, Theron A, Van Rensburg AJ. The effects of increasing weekly doses of ascorbate on certain cellular and humoral functions in normal volunteers. Am J Clin Nutr. 1980;33:71–76.PubMedGoogle Scholar
  43. 43.
    Wintergerst ES, Maggini S, Hornig DH. Immune-enhancing role of vitamin C and zinc and effect on clinical conditions. Ann Nutr Metab. 2006;50:85–94.PubMedCrossRefGoogle Scholar
  44. 44.
    Stadler N, Eggermann J, Voo S, Kranz A, Walternberger J. Smoking-induced monocyte dysfunction is reversed by vitamin C supplementation in-vivo. Arterioscler Thromb Vasc Biol. 2007;27:120–126.PubMedCrossRefGoogle Scholar
  45. 45.
    Hornig D. Distribution of ascorbic acid, metabolites and analogues in man and animals. Ann N Y Acad Sci. 1975;258:103–118.PubMedCrossRefGoogle Scholar
  46. 46.
    Li Y, Schellhorn HE. New developments and novel therapeutic perspectives for vitamin C. J Nutr. 2007;137:2171–2184.PubMedGoogle Scholar

Copyright information

© Springer Healthcare Communications 2008

Authors and Affiliations

  • Mark A. Moyad
    • 1
    • 2
  • Maile A. Combs
    • 1
    • 2
  • Angelica S. Vrablic
    • 1
    • 2
  • Janet Velasquez
    • 1
    • 2
  • Benilda Turner
    • 1
    • 2
  • Samuel Bernal
    • 1
    • 2
  1. 1.Department of UrologyUniversity of Michigan Medical CenterAnn ArborUSA
  2. 2.San Fernando Valley Program, Sepulveda VA Medical CenterUniversity of CaliforniaLos AngelesUSA
  3. 3.Jenkins/Pokempner Director of Preventive & Alternative MedicineUniversity of Michigan Medical Center, Department of UrologyAnn ArborUSA

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