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Vitamin C

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Description

What is it?

Vitamin C (ascorbic acid) is an essential, water-soluble vitamin. It is well-known for its antioxidative properties and ability to reduce free radicals by donating electrons through reduction reactions. (20) The discovery of vitamin C has been attributed to the treatment of scurvy in sailors and the potato famine in Ireland. (4)

Not to be confused with: L-threonate

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Main uses

Cardiovascular disorders
Chronic pain & inflammation
Immune function
Metabolic disorders

Formulations

Form
Bioavailability
Natural/food
Equal bioavailability to supplemental sources in humans (5)(22)
Ascorbic acid - liposomal
Relative bioavailability of liposomal-encapsulated ascorbic acid was increased by ~74% higher than unformulated ascorbic acid (7)
Ascorbic acid - unformulated
200 mg doses produces a plateau in plasma concentration, with full plasma saturation at 1000 mg (18)
Ascorbic acid - sustained-release
Conflicting evidence on bioavailability: Within 4-12 hours, single admin of fast release formulation increased relative plasma ascorbate by 94% (non-stat. signi.) than slow release. After 2-months, slow-release was 22% higher (non-stat. signi.) (24)
Single admin of slow-release formulations increased relative bioavailability of plasma ascorbate by 23-51% (stat. signi.) than fast-release tablets or solution (2)
Ascorbyl palmitate
Increased bioavailability compared with ascorbic acid in horses (28)
Calcium ascorbate
No difference in relative bioavailability in plasma ascorbate between Ester C® and standard ascorbic acid in humans, but more tolerable (10)(14)(23)
Single admin of CA increased plasma ascorbate up to 180% more than ascorbic acid in rats (3)(17)
Magnesium ascorbate
No information on bioavailability currently available
Potassium ascorbate
No information on bioavailability currently available
Sodium ascorbate
No information on bioavailability currently available
Vitamin C with bioflavonoids
No difference in bioavailability with AA or Ester C (14)

Dosing & administration

Adverse effects

Vitamin C is considered to be safe and tolerable. Exceeding the Tolerable Upper Intake Level (UL) of 2000 mg per day for adults can lead to gastrointestinal disturbances and osmotic diarrhea. The daily UL for children aged one to three is 400 mg, aged four to eight is 650 mg, and aged nine to 13 is 1800 mg. (9)

Pharmacokinetics

Absorption

  • Vitamin C predominantly exists in its reduced form, ascorbate, though it can be found in its oxidized form as dehydroascorbic acid (DHA). (21)
  • Ascorbate and DHA are efficiently interconvertible, but may be absorbed via different mechanisms. (21)
  • Ascorbate is absorbed via active transport in the small intestine through sodium-dependent vitamin C transporter 1 (SVCT1). (19)(21)(27)
  • DHA has a similar structure to glucose and is absorbed into the intestinal epithelium by glucose transporters GLUT1 and GLUT3, and into the blood by GLUT1 and GLUT2. (21)(26)

Distribution

  • Vitamin C can be primarily found circulating in plasma and erythrocytes (50-70µM), but can be found in the adrenals (4-10 µM), brain (2-10 µM), liver (~1 µM), lung (~1 µM), kidney (0.3-0.5 µM), heart (0.2-0.4 µM), and muscle (0.2-0.4 µM). (21)

Metabolism

  • Ascorbate is an electron donor, acting as an antioxidant. Ascorbate is oxidized to the stable ascorbyl free radical.
  • Intracellularly, DHA is efficiently reduced to ascorbate, recycling ascorbate pools. (21)

Excretion

  • If not absorbed back into plasma (via GLUT2 for DHA, and by an unknown mechanism for ascorbate), and not reabsorbed back into the renal epithelium (via SVCT1), vitamin C is excreted in the urine. (8)(21)

References

Aïm, F., Klouche, S., Frison, A., Bauer, T., & Hardy, P. (2017). Efficacy of vitamin C in preventing complex regional pain syndrome after wrist fracture: A systematic review and meta-analysis. Orthopaedics & Traumatology: Surgery & Research, 103(3), 465-470.
Bhagavan, H. N., & Wolkoff, B. I. (1993). Correlation between the disintegration time and the bioavailability of vitamin C tablets. Pharmaceutical Research, 10(2), 239-242.
Bush, M. J., & Verlangieri, A. J. (1987). An acute study on the relative gastro-intestinal absorption of a novel form of calcium ascorbate. Research Communications in Chemical Pathology and Pharmacology, 57(1), 137-140.
Carpenter, K. J. (2012). The discovery of vitamin C. Annals of Nutrition & Metabolism, 61(3), 259-269.
Carr, A., Bozonet, S., Pullar, J., Simcock, J., & Vissers, M. (2013). A randomized steady-state bioavailability study of synthetic versus natural (kiwifruit-derived) vitamin C. Nutrients, 5(9), 3684-3695.
Chen, S., Roffey, D. M., Dion, C., Arab, A., & Wai, E. K. (2016). Effect of perioperative vitamin C supplementation on postoperative pain and the incidence of chronic regional pain syndrome. The Clinical Journal of Pain, 32(2), 179-185.
Davis, J. L., Paris, H. L., Beals, J. W., Binns, S. E., Giordano, G. R., Scalzo, R. L., Schweder, M. . . . Bell, C. (2016). Liposomal-encapsulated ascorbic acid: Influence on vitamin C bioavailability and capacity to protect against ischemia–reperfusion injury. Nutrition and Metabolic Insights, 9, 25-30.
Eck, P., Kwon, O., Chen, S., Mian, O., & Levine, M. (2013). The human sodium-dependent ascorbic acid transporters SLC23A1 and SLC23A2 do not mediate ascorbic acid release in the proximal renal epithelial cell. Physiological Reports, 1(6).
Food and Nutrition Board, Institute of Medicine, & National Academy Press. (2000). Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Retrieved from https://www.nap.edu/read/9810/chapter/1
Gruenwald, J., Graubaum, H., Busch, R., & Bentley, C. (2006). Safety and tolerance of Ester-C® compared with regular ascorbic acid. Advances in Therapy, 23(1), 171-178.
Hemilä, H., & Chalker, E. (2013). Vitamin C for preventing and treating the common cold. Cochrane Database of Systematic Reviews, (1), CD000980.
Hemilä, H., & Suonsyrjä, T. (2017). Vitamin C for preventing atrial fibrillation in high risk patients: A systematic review and meta-analysis. BMC Cardiovascular Disorders, 17(1), 49.
Jensen, N. H. (2003). Reduced pain from osteoarthritis in hip joint or knee joint during treatment with calcium ascorbate. A randomized, placebo-controlled cross-over trial in general practice. Ugeskrift for Laeger, 165(25), 2563-2566.
Johnston, C. S., & Luo, B. (1994). Comparison of the absorption and excretion of three commercially available sources of vitamin C. Journal of the American Dietetic Association, 94(7), 779-781.
Juraschek, S. P., Guallar, E., Appel, L. J., & Miller, E. R. (2012). Effects of vitamin C supplementation on blood pressure: A meta-analysis of randomized controlled trials. The American Journal of Clinical Nutrition, 95(5), 1079-1088.
Juraschek, S. P., Miller, E. R., & Gelber, A. C. (2011). Effect of oral vitamin C supplementation on serum uric acid: A meta-analysis of randomized controlled trials. Arthritis Care & Research, 63(9), 1295-1306.
Lee, J., Jung, S., Lee, S., Han, J., Jo, E., Park, H., . . . Myung, C. (2018). Alleviation of ascorbic acid-induced gastric high acidity by calcium ascorbate in vitro and in vivo. The Korean Journal of Physiology & Pharmacology, 22(1), 35-42.
Levine, M., Conry-Cantilena, C., Wang, Y., Welch, R. W., Washko, P. W., Dhariwal, K., . . . Cantilena, L. R. (1996). Vitamin C pharmacokinetics in healthy volunteers: Evidence for a recommended dietary allowance. Proceedings of the National Academy of Sciences, 93(8), 3704-3709.
Luo, S., Wang, Z., Kansara, V., Pal, D., & Mitra, A. K. (2008). Activity of a sodium-dependent vitamin C transporter (SVCT) in MDCK-MDR1 cells and mechanism of ascorbate uptake. International Journal of Pharmaceutics, 358(1-2), 168-176.
Lykkesfeldt, J., Michels, A. J., & Frei, B. (2014). Vitamin C. Advances in Nutrition, 5(1), 16-18.
Lykkesfeldt, J., & Tveden-Nyborg, P. (2019). The Pharmacokinetics of Vitamin C. Nutrients, 11(10), 2412.
Mangels, A. R., Block, G., Frey, C. M., Patterson, B. H., Taylor, P. R., Norkus, E. P., & Levander, O. A. (1993). The bioavailability to humans of ascorbic acid from oranges, orange juice and cooked broccoli is similar to that of synthetic ascorbic acid. The Journal of Nutrition, 123(6), 1054-1061.
Moyad, M. A., Combs, M. A., Vrablic, A. S., Velasquez, J., Turner, B., & Bernal, S. (2008). Vitamin C metabolites, independent of smoking status, significantly enhance leukocyte, but not plasma ascorbate concentrations. Advances in Therapy, 25(10), 995-1009.
Nyyssönen, K., Poulsen, H., Hayn, M., Agerbo, P., Porkkala-Sarataho, E., Kaikkonen, J., . . . Salonen, J. (1997). Effect of supplementation of smoking men with plain or slow release ascorbic acid on lipoprotein oxidation. European Journal of Clinical Nutrition, 51(3), 154-163.
Ran, L., Zhao, W., Wang, J., Wang, H., Zhao, Y., Tseng, Y., & Bu, H. (2018). Extra dose of vitamin C based on a daily supplementation shortens the common cold: A meta-analysis of 9 randomized controlled trials. BioMed Research International, 2018, 1-12.
Rumsey, S. C., Kwon, O., Xu, G. W., Burant, C. F., Simpson, I., & Levine, M. (1997). Glucose transporter isoforms GLUT1 and GLUT3 transport dehydroascorbic acid. Journal of Biological Chemistry,272(30), 18982-18989.
Savini, I., Rossi, A., Pierro, C., Avigliano, L., & Catani, M. V. (2008). SVCT1 and SVCT2: Key proteins for vitamin C uptake. Amino Acids, 34(3), 347-355.
Snow, D., & Frigg, M. (1989). Oral administration of different formulations of ascorbic acid to the horse. Journal of Equine Veterinary Science, 9(1), 30-33.