Abstract
Vitamins are necessary factors in human development and normal brain function. Vitamin C is a hydrosoluble compound that humans cannot produce; therefore, we are completely dependent on food intake for vitamin C. Ascorbic acid is an important antioxidative agent and is present in high concentrations in neurons and is also crucial for collagen synthesis throughout the body. Ascorbic acid has a role in modulating many essential neurotransmitters, enables neurogenesis in adult brain and protects cells against infection. While SVCT1 enables the absorption of vitamin C in the intestine, SVCT2 is primarily located in the brain.
Ascorbate deficiency is classically expressed as scurvy, which is lethal if not treated. However, subclinical deficiencies are probably much more frequent. Potential fields of vitamin C therapy are in neurodegenerative, cerebrovascular and affective diseases, cancer, brain trauma and others. For example, there is some data on its positive effects in Alzheimer’s disease. Various dosing regimes are used, but ascorbate is safe, even in high doses for protracted periods. Better designed studies are needed to elucidate all of the potential therapeutic roles of vitamin C.
Financial disclosure: This article is partially financed by the Ministry of Science, Republic of Serbia, Project No 175033 and 175022
REFERENCES
1. Pavlović DM. Neuropsihologija, bihevioralna neurologija i neuropsihijatrija. Beograd: Orion Art, 2012.
2. Pavlović DM, Pavlović AM. B Vitamins and Dementias. Curr Top 2013;21(1-2):39-48.
3. Nahas R, Balla A. Complementary and alternative medicine for prevention and treatment of the common cold. Can Fam Physician. 2011 Jan;57(1):31-36.
4. World Health Organization and Food and Agriculture Organization of the United Nations. Vitamin and mineral requirements in human nutrition. 2nd edition. Geneva: World Health Organization and Food and Agriculture Organization of the United Nations, 2004.
5. Harrison FE, May JM. Vitamin C function in the brain: vital role of the ascorbate transporter SVCT2. Free Radic Biol Med. 2009 Mar 15;46(6):719-730.
6. Levine M, Padayatty SJ, Espey MG. Vitamin C: a concentration-function approach yields pharmacology and therapeutic discoveries. Adv Nutr. 2011 Mar;2(2):78-88.
7. Kallner A, Hartmann D, Hornig D. Steady-state turnover and body pool of ascorbic acid in man. American Journal of Clinical Nutrition, 1979, 32:530–539.
8. May JM. The SLC23 family of ascorbate transporters: ensuring that you get and keep your daily dose of vitamin C. Br J Pharmacol. 2011 Dec;164(7):1793-801.
9. Gess B, Sevimli S, Strecker JK, Young P, Schäbitz WR. Sodium-dependent vitamin C transporter 2 (SVCT2) expression and activity in brain capillary endothelial cells after transient ischemia in mice. PLoS One. 2011 Feb 11;6(2):e17139.
10. Gess B, Röhr D, Young P. Ascorbic acid and sodium-dependent vitamin C transporters in the peripheral nervous system: from basic science to clinical trials. Antioxid Redox Signal. 2013 Dec 10;19(17):2105-2114.
11. Verhamme C, de Haan RJ, Vermeulen M, Baas F, de Visser M, van Schaik IN. Oral high dose ascorbic acid treatment for one year in young CMT1A patients: a randomised, double-blind, placebo-controlled phase II trial. BMC Med. 2009 Nov 12;7:70.
12. Jacob RA. Vitamin C. In: Shils ME, Olson Ja, Shike M, eds. Modern nutrition in health and disease, 8th ed. Philadelphia: Lea and Febiger, 1994; 432-448.
13. El-Sokkary GH Awadalla EA. The protective role of vitamin C against cerebral and pulmonary damage induced by cadmium chloride in male adult albino rat. The Open Neuroendocrinology Journal, 2011, 4, 1-8.
14. Hampl JS, Taylor CA, Johnston CS: Vitamin C deficiency and depletion in the United States: the Third National Health and Nutrition Examination Survey, 1988–1994. Am J Pub Health 2004, 94:870-875.
15. Ramakrishna T. Vitamins and brain development. Physiol Res. 1999;48(3):175-187.
16. Rice, M.E., Russo-Menna, I. 1998. Differential compartmentalization of brain ascorbate and glutathione between neurons and glia. Neuroscience 82, 1213-1223.
17. Bowman GL, Dodge H, Frei B, Calabrese C, Oken BS, Kaye JA, Quinn JF. Ascorbic acid and rates of cognitive decline in Alzheimer’s disease. J Alzheimers Dis. 2009;16(1):93-8
18. Parle M, Dhingra D. Ascorbic Acid: a promising memory-enhancer in mice. J Pharmacol Sci 2003;93:129–135.
19. Wang Y, Liu XJ, Robitaille L, Eintracht S, MacNamara E, Hoffer LJ. Effects of vitamin C and vitamin D administration on mood and distress in acutely hospitalized patients. Am J Clin Nutr 2013;98(3):705-11.
20. Candelario-Jalil E, Akundi RS, Bhatia HS, Lieb K, Appel K, Muñoz E, Hüll M, Fiebich BL. Ascorbic acid enhances the inhibitory effect of aspirin on neuronal cyclooxygenase-2-mediated prostaglandin E2 production. J Neuroimmunol. 2006 May;174(1-2):39-51.
21. Pavlovic DM, Pavlovic AM, Žugić S. Patogeneza Alzheimerove bolesti. Vojnosanit Pregl. 2007 Nov;64(11):765-772.
22. Cheng F, Cappai R, Ciccotosto GD, Svensson G, Multhaup G, Fransson LÅ, Mani K. Suppression of amyloid beta A11 antibody immunoreactivity by vitamin C: possible role of heparan sulfate oligosaccharides derived from glypican-1 by ascorbate-induced, nitric oxide (NO)-catalyzed degradation. J Biol Chem. 2011 Aug 5;286(31):27559-72.
23. Zandi PP, Anthony JC, Khachaturian AS, Stone SV, Gustafson D, Tschanz JT, Norton MC, Welsh-Bohmer KA, Breitner JC; Cache County Study Group. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study. Arch Neurol. 2004 Jan;61(1):82-88
24. Wengreen HJ, Munger RG, Corcoran CD, Zandi P, Hayden KM, Fotuhi M, et al. Antioxidant intake and cognitive function of elderly men and women: the Cache County Study. J Nutr Health Aging. 2007 May-Jun;11(3):230-237.
25. Bowman GL. Ascorbic acid, cognitive function, and Alzheimer’s disease: a current review and future direction. Biofactors. 2012 Mar-Apr;38(2):114-122
26. Fotuhi M, Zandi PP, Hayden KM, Khachaturian AS, Szekely CA, Wengreen H, et al. Better cognitive performance in elderly taking antioxidant vitamins E and C supplements in combination with nonsteroidal anti-inflammatory drugs: the Cache County Study. Alzheimers Dement. 2008 May;4(3):223-227.
27. Harrison FE, Hosseini AH, McDonald MP, May JM. Vitamin C reduces spatial learning deficits in middle-aged and very old APP/PSEN1 transgenic and wild-type mice. Pharmacol Biochem Behav. 2009 Oct;93(4):443-450.
28. Harrison FE. A critical review of vitamin C for the prevention of age-related cognitive decline and Alzheimer’s disease. J Alzheimers Dis. 2012;29(4):711-726.
29. Riordan NH, Riordan HD, Casciari JP. Clinical and experimental experiences with Intravenous Vitamin C. Journal of Orthomolecular Medicine 2000 Vol. 15, No. 4, 201-213.
30. Pavlović AM, Pekmezović T, Zidverc-Trajković J, Jovanović Z, Mijajlovic M, Pavlović D, Tomić G, Sternić N. What are the differences between younger and older patients with symptomatic small vessel disease? Clin Neurol Neurosurg. 2011;113(9):762-767.
31. Chen GC, Lu DB, Pang Z, Liu QF. Vitamin C intake, circulating vitamin C and risk of stroke: a meta-analysis of prospective studies. J Am Heart Assoc. 2013 Nov 27;2(6):e000329.
32. Razmkon A, Sadidi A, Sherafat-Kazemzadeh E, MD, Mehrafshan A, Jamali M, Malekpour B, Saghafinia M. Administration of Vitamin C and Vitamin E in Severe Head Injury: A Randomized Double-blind Controlled Trial. Clinical Neurosurgery 2011; 58, 133-137.
33. Pastor P, Cisternas P, Salazar K, Silva-Alvarez C, Oyarce K, Jara N, Espinoza F, Martínez AD, Nualart F. SVCT2 vitamin C transporter expression in progenitor cells of the postnatal neurogenic niche. Front Cell Neurosci. 2013 Aug 13;7:119.
34. Ye Z, Song H. Antioxidant vitamins intake and the risk of coronary heart disease: meta-analysis of cohort studies. Eur J Cardiovasc Prev Rehabil 2008;15(1):26-34.
35. Food and Drug Administration. Food labeling: Health claims and label statements: Antioxidant vitamins and cancer; final rule. Federal register 1993; 58:2622-2660.
36. Thiagarajan R, Manikandan R. Antioxidants and cataract. Free Radic Res. 2013 May;47(5):337-45.
37. Miller DR, Hayes KC. Vitamin excess and toxicity. In: Hathcock JN, ed. Nutritional toxicology, vol. 1. New York: Academic Press, 1982; 81-133.
38. Bendich A, Langseth L. The health effects of vitamin C supplementation: A review. J am Coll Nutr 1995; 14:124-136.
39. Food and Nutrution Board. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. Washington, DC: National Academy Press, 2000.
40. Pavlović DM, Pavlović AM. Deficit vitamina B12 u neurologiji. Srp arh celok lek 2003;131:412-418.
41. Cathcart RF. Vitamin C: the nontoxic, nonrate-limited, antioxidant free radical scavenger. Med Hypotheses 1985;18:61–77.
