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Ascorbic Acid to Manage Psychiatric Disorders

CNS Drugs volume 31, pages 571–583 (2017)Cite this article

Abstract

Ascorbate has critical roles in the central nervous system (CNS); it is a neuromodulator of glutamatergic, cholinergic, dopaminergic, and γ-aminobutyric acid (GABA)-ergic neurotransmission, provides support and structure to neurons, and participates in processes such as differentiation, maturation, and survival of neurons. Over the past decade, antioxidant properties of ascorbate have been extensively characterized and now it is known that this compound is highly concentrated in the brain and neuroendocrine tissues. All this information raised the hypothesis that ascorbate may be involved in neurological disorders. Indeed, the biological mechanisms of ascorbate in health and disease and its involvement in homeostasis of the CNS have been the subject of extensive research. In particular, evidence for an association of this vitamin with schizophrenia, major depressive disorder, and bipolar disorder has been provided. Considering that conventional pharmacotherapy for the treatment of these neuropathologies has important limitations, this review aims to explore basic and human studies that implicate ascorbic acid as a potential therapeutic strategy. Possible mechanisms involved in the beneficial effects of ascorbic acid for the management of psychiatric disorders are also discussed.

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References

  1. Rebec GV, Pierce RC. A vitamin as neuromodulator—ascorbate release into the extracellular fluid of the brain regulates dopaminergic and glutamatergic transmission. Prog Neurobiol. 1994;43(6):537–65.

    CAS  PubMed  Article  Google Scholar 

  2. Abdel-Wahab BA, Salama RH. Venlafaxine protects against stress-induced oxidative DNA damage in hippocampus during antidepressant testing in mice. Pharmacol Biochem Behav. 2011;100(1):59–65.

    CAS  PubMed  Article  Google Scholar 

  3. Rice ME. Ascorbate regulation and its neuroprotective role in the brain. Trends Neurosci. 2000;23(5):209–16.

    CAS  PubMed  Article  Google Scholar 

  4. Harrison FE, May JM. Vitamin C function in the brain: vital role of the ascorbate transporter SVCT2. Free Radic Biol Med. 2009;46(6):719–30.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  5. Taylor C, Fricker AD, Devi LA, Gomes I. Mechanisms of action of antidepressants: from neurotransmitter systems to signaling pathways. Cell Signal. 2005;17(5):549–57.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  6. Naidu KA. Vitamin C in human health and disease is still a mystery? An overview. Nutr J. 2003;2:7.

    PubMed  PubMed Central  Article  Google Scholar 

  7. Schreiber M, Trojan S. Ascorbic acid in the brain. Physiol Res. 1991;40(4):413–8.

    CAS  PubMed  Google Scholar 

  8. Padayatty SJ, Katz A, Wang Y, Eck P, Kwon O, Lee JH, et al. Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr. 2003;22(1):18–35.

    CAS  PubMed  Article  Google Scholar 

  9. Sies H. Strategies of antioxidant defense. Eur J Biochem. 1993;215(2):213–9.

    CAS  PubMed  Article  Google Scholar 

  10. Coyle JT, Puttfarcken P. Oxidative stress, glutamate, and neurodegenerative disorders. Science. 1993;262(5134):689–95.

    CAS  PubMed  Article  Google Scholar 

  11. Aguiar CC, Almeida AB, Araujo PV, de Abreu RN, Chaves EM, do Vale OC, et al. Oxidative stress and epilepsy: literature review. Oxid Med Cell Longev. 2012;2012:795259.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  12. Gandhi S, Abramov AY. Mechanism of oxidative stress in neurodegeneration. Oxid Med Cell Longev. 2012;2012:428010.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  13. Maes M, Galecki P, Chang YS, Berk M. A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(3):676–92.

    CAS  PubMed  Article  Google Scholar 

  14. Sorolla MA, Rodriguez-Colman MJ, Vall-llaura N, Tamarit J, Ros J, Cabiscol E. Protein oxidation in Huntington disease. Biofactors. 2012;38(3):173–85.

    CAS  PubMed  Article  Google Scholar 

  15. Yao JK, Keshavan MS. Antioxidants, redox signaling, and pathophysiology in schizophrenia: an integrative view. Antioxid Redox Signal. 2011;15(7):2011–35.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  16. Carey DJ, Todd MS. Schwann cell myelination in a chemically defined medium: demonstration of a requirement for additives that promote Schwann cell extracellular matrix formation. Brain Res. 1987;429(1):95–102.

    CAS  PubMed  Article  Google Scholar 

  17. Eldridge CF, Bunge MB, Bunge RP, Wood PM. Differentiation of axon-related Schwann cells in vitro. I. Ascorbic acid regulates basal lamina assembly and myelin formation. J Cell Biol. 1987;105(2):1023–34.

    CAS  PubMed  Article  Google Scholar 

  18. Goto K, Tanaka R. Ascorbic acid inhibition of Na, K-adenosine triphosphatase of rat forebrain without peroxidation of membrane lipids. Brain Res. 1981;207(1):239–44.

    CAS  PubMed  Article  Google Scholar 

  19. Ng YC, Akera T, Han CS, Braselton WE, Kennedy RH, Temma K, et al. Ascorbic acid: an endogenous inhibitor of isolated Na+, K+-ATPase. Biochem Pharmacol. 1985;34(14):2525–30.

    CAS  PubMed  Article  Google Scholar 

  20. Kuo CH, Yoshida H. Ascorbic acid, an endogenous factor required for acetylcholine release from the synaptic vesicles. Jpn J Pharmacol. 1980;30(4):481–92.

    CAS  PubMed  Article  Google Scholar 

  21. Levine M, Asher A, Pollard H, Zinder O. Ascorbic acid and catecholamine secretion from cultured chromaffin cells. J Biol Chem. 1983;258(21):13111–5.

    CAS  PubMed  Google Scholar 

  22. Grunewald RA. Ascorbic acid in the brain. Brain Res Brain Res Rev. 1993;18(1):123–33.

    CAS  PubMed  Article  Google Scholar 

  23. Majewska MD, Bell JA, London ED. Regulation of the NMDA receptor by redox phenomena: inhibitory role of ascorbate. Brain Res. 1990;537(1–2):328–32.

    CAS  PubMed  Article  Google Scholar 

  24. Wambebe C, Sokomba E. Some behavioural and EEG effects of ascorbic acid in rats. Psychopharmacology. 1986;89(2):167–70.

    CAS  PubMed  Article  Google Scholar 

  25. Dai F, Yang JY, Gu PF, Hou Y, Wu CF. Effect of drug-induced ascorbic acid release in the striatum and the nucleus accumbens in hippocampus-lesioned rats. Brain Res. 2006;1125(1):163–70.

    CAS  PubMed  Article  Google Scholar 

  26. Gu PF, Wu CF, Yang JY, Shang Y, Hou Y, Bi XL, et al. Differential effects of drug-induced ascorbic acid release in the striatum and nucleus accumbens of freely moving rats. Neurosci Lett. 2006;399(1–2):79–84.

    CAS  PubMed  Article  Google Scholar 

  27. Laruelle M. Schizophrenia: from dopaminergic to glutamatergic interventions. Curr Opin Pharmacol. 2014;14:97–102.

    CAS  PubMed  Article  Google Scholar 

  28. Lau CI, Wang HC, Hsu JL, Liu ME. Does the dopamine hypothesis explain schizophrenia? Rev Neurosci. 2013;24(4):389–400.

    CAS  PubMed  Article  Google Scholar 

  29. Javitt DC. Glutamate and schizophrenia: phencyclidine, N-methyl-d-aspartate receptors, and dopamine-glutamate interactions. Int Rev Neurobiol. 2007;78:69–108.

    CAS  PubMed  Article  Google Scholar 

  30. Zink M, Correll CU. Glutamatergic agents for schizophrenia: current evidence and perspectives. Expert Rev Clin Pharmacol. 2015;8(3):335–52.

    CAS  PubMed  Article  Google Scholar 

  31. Moghaddam B, Javitt D. From revolution to evolution: the glutamate hypothesis of schizophrenia and its implication for treatment. Neuropsychopharmacology. 2012;37(1):4–15.

    CAS  PubMed  Article  Google Scholar 

  32. Peleg-Raibstein D, Yee BK, Feldon J, Hauser J. The amphetamine sensitization model of schizophrenia: relevance beyond psychotic symptoms? Psychopharmacology. 2009;206(4):603–21.

    CAS  PubMed  Article  Google Scholar 

  33. Powell SB, Geyer MA, Preece MA, Pitcher LK, Reynolds GP, Swerdlow NR. Dopamine depletion of the nucleus accumbens reverses isolation-induced deficits in prepulse inhibition in rats. Neuroscience. 2003;119(1):233–40.

    CAS  PubMed  Article  Google Scholar 

  34. White LK, Maurer M, Kraft ME, Oh C, Rebec GV. Intrastriatal infusions of ascorbate antagonize the behavioral response to amphetamine. Pharmacol Biochem Behav. 1990;36(3):485–9.

    CAS  PubMed  Article  Google Scholar 

  35. Giannini AJ, Loiselle RH, DiMarzio LR, Giannini MC. Augmentation of haloperidol by ascorbic acid in phencyclidine intoxication. Am J Psychiatry. 1987;144(9):1207–9.

    CAS  PubMed  Article  Google Scholar 

  36. Tolbert LC, Thomas TN, Middaugh LD, Zemp JW. Effect of ascorbic acid on neurochemical, behavioral, and physiological systems mediated by catecholamines. Life Sci. 1979;25(26):2189–95.

    CAS  PubMed  Article  Google Scholar 

  37. Heikkila RE, Cabbat FS, Manzino L. Differential inhibitory effects of ascorbic acid on the binding of dopamine agonists and antagonists to neostriatal membrane preparations: correlations with behavioral effects. Res Commun Chem Pathol Pharmacol. 1981;34(3):409–21.

    CAS  PubMed  Google Scholar 

  38. Tolbert LC, Thomas TN, Middaugh LD, Zemp JW. Ascorbate blocks amphetamine-induced turning behavior in rats with unilateral nigro-striatal lesions. Brain Res Bull. 1979;4(1):43–8.

    CAS  PubMed  Article  Google Scholar 

  39. Dorris RL. Ascorbic acid reduces accumulation of [3H]spiperone in mouse striatum in vivo. Proc Soc Exp Biol Med. 1987;186(1):13–6.

    CAS  PubMed  Article  Google Scholar 

  40. Hadjiconstantinou M, Neff NH. Ascorbic acid could be hazardous to your experiments: a commentary on dopamine receptor binding studies with speculation on a role for ascorbic acid in neuronal function. Neuropharmacology. 1983;22(8):939–43.

    CAS  PubMed  Article  Google Scholar 

  41. Basse-Tomusk A, Rebec GV. Corticostriatal and thalamic regulation of amphetamine-induced ascorbate release in the neostriatum. Pharmacol Biochem Behav. 1990;35(1):55–60.

    CAS  PubMed  Article  Google Scholar 

  42. Gardiner TW, Armstrong-James M, Caan AW, Wightman RM, Rebec GV. Modulation of neostriatal activity by iontophoresis of ascorbic acid. Brain Res. 1985;344(1):181–5.

    CAS  PubMed  Article  Google Scholar 

  43. Grunewald RA, O’Neill RD, Fillenz M, Albery WJ. The origin of circadian and amphetamine-induced changes in the extracellular concentration of brain ascorbate. Neurochem Int. 1983;5(6):773–8.

    CAS  PubMed  Article  Google Scholar 

  44. O’Neill RD, Grunewald RA, Fillenz M, Albery WJ. The effect of unilateral cortical lesions on the circadian changes in rat striatal ascorbate and homovanillic acid levels measured in vivo using voltammetry. Neurosci Lett. 1983;42(1):105–10.

    PubMed  Article  Google Scholar 

  45. Wagner GC, Carelli RM, Jarvis MF. Ascorbic acid reduces the dopamine depletion induced by methamphetamine and the 1-methyl-4-phenyl pyridinium ion. Neuropharmacology. 1986;25(5):559–61.

    CAS  PubMed  Article  Google Scholar 

  46. Wagner GC, Carelli RM, Jarvis MF. Pretreatment with ascorbic acid attenuates the neurotoxic effects of methamphetamine in rats. Res Commun Chem Pathol Pharmacol. 1985;47(2):221–8.

    CAS  PubMed  Google Scholar 

  47. Desole MS, Miele M, Enrico P, Fresu L, Esposito G, De Natale G, et al. The effects of cortical ablation on d-amphetamine-induced changes in striatal dopamine turnover and ascorbic acid catabolism in the rat. Neurosci Lett. 1992;139(1):29–33.

    CAS  PubMed  Article  Google Scholar 

  48. Koga M, Serritella AV, Sawa A, Sedlak TW. Implications for reactive oxygen species in schizophrenia pathogenesis. Schizophr Res. 2016;176(1):52–71.

    PubMed  Article  Google Scholar 

  49. Cabungcal JH, Preissmann D, Delseth C, Cuenod M, Do KQ, Schenk F. Transitory glutathione deficit during brain development induces cognitive impairment in juvenile and adult rats: relevance to schizophrenia. Neurobiol Dis. 2007;26(3):634–45.

    CAS  PubMed  Article  Google Scholar 

  50. Dadheech G, Mishra S, Gautam S, Sharma P. Oxidative stress, alpha-tocopherol, ascorbic acid and reduced glutathione status in schizophrenics. Indian J Clin Biochem. 2006;21(2):34–8.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  51. Suboticanec K, Folnegovic-Smalc V, Turcin R, Mestrovic B, Buzina R. Plasma levels and urinary vitamin C excretion in schizophrenic patients. Hum Nutr Clin Nutr. 1986;40(6):421–8.

    CAS  PubMed  Google Scholar 

  52. D’Souza B, D’Souza V. Oxidative injury and antioxidant vitamins E and C in schizophrenia. Indian J Clin Biochem. 2003;18(1):87–90.

    PubMed  PubMed Central  Article  Google Scholar 

  53. Dakhale GN, Khanzode SD, Khanzode SS, Saoji A. Supplementation of vitamin C with atypical antipsychotics reduces oxidative stress and improves the outcome of schizophrenia. Psychopharmacology. 2005;182(4):494–8.

    CAS  PubMed  Article  Google Scholar 

  54. Heiser P, Sommer O, Schmidt AJ, Clement HW, Hoinkes A, Hopt UT, et al. Effects of antipsychotics and vitamin C on the formation of reactive oxygen species. J Psychopharmacol. 2010;24(10):1499–504.

    CAS  PubMed  Article  Google Scholar 

  55. Sandyk R, Kanofsky JD. Vitamin C in the treatment of schizophrenia. Int J Neurosci. 1993;68(1–2):67–71.

    CAS  PubMed  Article  Google Scholar 

  56. Beauclair L, Vinogradov S, Riney SJ, Csernansky JG, Hollister LE. An adjunctive role for ascorbic acid in the treatment of schizophrenia? J Clin Psychopharmacol. 1987;7(4):282–3.

    CAS  PubMed  Article  Google Scholar 

  57. Bentsen H, Osnes K, Refsum H, Solberg DK, Bohmer T. A randomized placebo-controlled trial of an omega-3 fatty acid and vitamins E + C in schizophrenia. Transl Psychiatry. 2013;3:e335.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  58. Berton O, Nestler EJ. New approaches to antidepressant drug discovery: beyond monoamines. Nat Rev Neurosci. 2006;7(2):137–51.

    CAS  PubMed  Article  Google Scholar 

  59. Binfare RW, Rosa AO, Lobato KR, Santos AR, Rodrigues AL. Ascorbic acid administration produces an antidepressant-like effect: evidence for the involvement of monoaminergic neurotransmission. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(3):530–40.

    CAS  PubMed  Article  Google Scholar 

  60. Moretti M, Budni J, Freitas AE, Neis VB, Ribeiro CM, de Oliveira Balen G, et al. TNF-alpha-induced depressive-like phenotype and p38(MAPK) activation are abolished by ascorbic acid treatment. Eur Neuropsychopharmacol. 2015;25(6):902–12.

    CAS  PubMed  Article  Google Scholar 

  61. Moretti M, Budni J, Ribeiro CM, Rodrigues AL. Involvement of different types of potassium channels in the antidepressant-like effect of ascorbic acid in the mouse tail suspension test. Eur J Pharmacol. 2012;687(1–3):21–7.

    CAS  PubMed  Article  Google Scholar 

  62. Moretti M, Freitas AE, Budni J, Fernandes SC, Balen Gde O, Rodrigues AL. Involvement of nitric oxide-cGMP pathway in the antidepressant-like effect of ascorbic acid in the tail suspension test. Behav Brain Res. 2011;225(1):328–33.

    CAS  PubMed  Article  Google Scholar 

  63. Moretti M, Budni J, Dos Santos DB, Antunes A, Daufenbach JF, Manosso LM, et al. Protective effects of ascorbic acid on behavior and oxidative status of restraint-stressed mice. J Mol Neurosci. 2013;49(1):68–79.

    CAS  PubMed  Article  Google Scholar 

  64. Moretti M, Colla A, de Oliveira Balen G, dos Santos DB, Budni J, de Freitas AE, et al. Ascorbic acid treatment, similarly to fluoxetine, reverses depressive-like behavior and brain oxidative damage induced by chronic unpredictable stress. J Psychiatr Res. 2012;46(3):331–40.

    PubMed  Article  Google Scholar 

  65. Meredith ME, May JM. Regulation of embryonic neurotransmitter and tyrosine hydroxylase protein levels by ascorbic acid. Brain Res. 2013;1539:7–14.

    CAS  PubMed  Article  Google Scholar 

  66. Duman RS, Li N, Liu RJ, Duric V, Aghajanian G. Signaling pathways underlying the rapid antidepressant actions of ketamine. Neuropharmacology. 2012;62(1):35–41.

    CAS  PubMed  Article  Google Scholar 

  67. Moretti M, Budni J, Freitas AE, Rosa PB, Rodrigues AL. Antidepressant-like effect of ascorbic acid is associated with the modulation of mammalian target of rapamycin pathway. J Psychiatr Res. 2014;48(1):16–24.

    PubMed  Article  Google Scholar 

  68. Rosa PB, Neis VB, Ribeiro CM, Moretti M, Rodrigues AL. Antidepressant-like effects of ascorbic acid and ketamine involve modulation of GABAA and GABAB receptors. Pharmacol Rep. 2016;68(5):996–1001.

    CAS  PubMed  Article  Google Scholar 

  69. Gariballa S. Poor vitamin C status is associated with increased depression symptoms following acute illness in older people. Int J Vit Nutr Res. 2014;84(1–2):12–7.

    Article  CAS  Google Scholar 

  70. DeSantis J. Scurvy and psychiatric symptoms. Perspect Psychiatr Care. 1993;29(1):18–22.

    CAS  PubMed  Article  Google Scholar 

  71. Chang CW, Chen MJ, Wang TE, Chang WH, Lin CC, Liu CY. Scurvy in a patient with depression. Dig Dis Sci. 2007;52(5):1259–61.

    PubMed  Article  Google Scholar 

  72. Khanzode SD, Dakhale GN, Khanzode SS, Saoji A, Palasodkar R. Oxidative damage and major depression: the potential antioxidant action of selective serotonin re-uptake inhibitors. Redox Rep. 2003;8(6):365–70.

    CAS  PubMed  Article  Google Scholar 

  73. Brody S. High-dose ascorbic acid increases intercourse frequency and improves mood: a randomized controlled clinical trial. Biol Psychiatry. 2002;52(4):371–4.

    CAS  PubMed  Article  Google Scholar 

  74. Oishi J, Doi H, Kawakami N. Nutrition and depressive symptoms in community-dwelling elderly persons in Japan. Acta Medica Okayama. 2009;63(1):9–17.

    CAS  PubMed  Google Scholar 

  75. Payne ME, Steck SE, George RR, Steffens DC. Fruit, vegetable, and antioxidant intakes are lower in older adults with depression. J Acad Nutr Diet. 2012;112(12):2022–7.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  76. Prohan M, Amani R, Nematpour S, Jomehzadeh N, Haghighizadeh MH. Total antioxidant capacity of diet and serum, dietary antioxidant vitamins intake, and serum hs-CRP levels in relation to depression scales in university male students. Redox Rep. 2014;19(3):133–9.

    CAS  PubMed  Article  Google Scholar 

  77. Cocchi P, Silenzi M, Calabri G, Salvi G. Antidepressant effect of vitamin C. Pediatrics. 1980;65(4):862–3.

    CAS  PubMed  Google Scholar 

  78. Amr M, El-Mogy A, Shams T, Vieira K, Lakhan SE. Efficacy of vitamin C as an adjunct to fluoxetine therapy in pediatric major depressive disorder: a randomized, double-blind, placebo-controlled pilot study. Nutr J. 2013;12:31.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  79. Aburawi SM, Ghambirlou FA, Attumi AA, Altubuly RA, Kara AA. Effect of ascorbic acid on mental depression drug therapy: clinical study. J Psychol Psychother. 2014;4:1000131.

    Article  Google Scholar 

  80. Mazloom Z, Ekramzadeh M, Hejazi N. Efficacy of supplementary vitamins C and E on anxiety, depression and stress in type 2 diabetic patients: a randomized, single-blind, placebo-controlled trial. Pak J Biol Sci. 2013;16(22):1597–600.

    CAS  PubMed  Article  Google Scholar 

  81. Sahraian A, Ghanizadeh A, Kazemeini F. Vitamin C as an adjuvant for treating major depressive disorder and suicidal behavior, a randomized placebo-controlled clinical trial. Trials. 2015;16:94.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  82. Muneer A. Staging models in bipolar disorder: a systematic review of the literature. Clin Psychopharmacol Neurosci. 2016;14(2):117–30.

    PubMed  PubMed Central  Article  Google Scholar 

  83. Peng L, Li B, Verkhratsky A. Targeting astrocytes in bipolar disorder. Expert Rev Neurother. 2016;16(6):649–57.

    CAS  PubMed  Article  Google Scholar 

  84. Rakofsky JJ, Dunlop BW. Review of nutritional supplements for the treatment of bipolar depression. Depress Anxiety. 2014;31(5):379–90.

    CAS  PubMed  Article  Google Scholar 

  85. El-Mallakh RS, El-Masri MA, Huff MO, Li XP, Decker S, Levy RS. Intracerebroventricular administration of ouabain as a model of mania in rats. Bipolar Disord. 2003;5(5):362–5.

    CAS  PubMed  Article  Google Scholar 

  86. Sani G, Napoletano F, Forte AM, Kotzalidis GD, Panaccione I, Porfiri GM, et al. The wnt pathway in mood disorders. Curr Neuropharmacol. 2012;10(3):239–53.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  87. Gould TD, Dow ER, O’Donnell KC, Chen G, Manji HK. Targeting signal transduction pathways in the treatment of mood disorders: recent insights into the relevance of the Wnt pathway. CNS Neurol Disord Drug Targets. 2007;6(3):193–204.

    CAS  PubMed  Article  Google Scholar 

  88. Huang L, Wu S, Xing D. High fluence low-power laser irradiation induces apoptosis via inactivation of Akt/GSK3beta signaling pathway. J Cell Physiol. 2011;226(3):588–601.

    CAS  PubMed  Article  Google Scholar 

  89. Milner G. Ascorbic acid in chronic psychiatric patients—a controlled trial. Br J Psychiatry. 1963;109:294–9.

    Article  Google Scholar 

  90. Naylor GJ, Smith AH. Vanadium: a possible aetiological factor in manic depressive illness. Psychol Med. 1981;11(2):249–56.

    CAS  PubMed  Article  Google Scholar 

  91. Kay DS, Naylor GJ, Smith AH, Greenwood C. The therapeutic effect of ascorbic acid and EDTA in manic-depressive psychosis: double-blind comparisons with standard treatments. Psychol Med. 1984;14(3):533–9.

    CAS  PubMed  Article  Google Scholar 

  92. Dixit S, Bernardo A, Walker JM, Kennard JA, Kim GY, Kessler ES, et al. Vitamin C deficiency in the brain impairs cognition, increases amyloid accumulation and deposition, and oxidative stress in APP/PSEN1 and normally aging mice. ACS Chem Neurosci. 2015;6(4):570–81.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  93. Murakami K, Murata N, Ozawa Y, Kinoshita N, Irie K, Shirasawa T, et al. Vitamin C restores behavioral deficits and amyloid-beta oligomerization without affecting plaque formation in a mouse model of Alzheimer’s disease. J Alzheimers Dis. 2011;26(1):7–18.

    CAS  PubMed  Article  Google Scholar 

  94. Wang C, Liu L, Zhang L, Peng Y, Zhou F. Redox reactions of the alpha-synuclein-Cu(2+) complex and their effects on neuronal cell viability. Biochemistry. 2010;49(37):8134–42.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  95. Acuna AI, Esparza M, Kramm C, Beltran FA, Parra AV, Cepeda C, et al. A failure in energy metabolism and antioxidant uptake precede symptoms of Huntington’s disease in mice. Nat Commun. 2013;4:2917.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  96. Rebec GV, Conroy SK, Barton SJ. Hyperactive striatal neurons in symptomatic Huntington R6/2 mice: variations with behavioral state and repeated ascorbate treatment. Neuroscience. 2006;137(1):327–36.

    CAS  PubMed  Article  Google Scholar 

  97. Olajide OJ, Yawson EO, Gbadamosi IT, Arogundade TT, Lambe E, Obasi K, et al. Ascorbic acid ameliorates behavioural deficits and neuropathological alterations in rat model of Alzheimer’s disease. Environ Toxicol Pharmacol. 2017;50:200–11.

    CAS  PubMed  Article  Google Scholar 

  98. Levine M, Rumsey SC, Daruwala R, Park JB, Wang Y. Criteria and recommendations for vitamin C intake. JAMA. 1999;281(15):1415–23.

    CAS  PubMed  Article  Google Scholar 

  99. Curhan GC, Willett WC, Rimm EB, Stampfer MJ. A prospective study of the intake of vitamins C and B6, and the risk of kidney stones in men. J Urol. 1996;155(6):1847–51.

    CAS  PubMed  Article  Google Scholar 

  100. Cook JD, Watson SS, Simpson KM, Lipschitz DA, Skikne BS. The effect of high ascorbic acid supplementation on body iron stores. Blood. 1984;64(3):721–6.

    CAS  PubMed  Google Scholar 

  101. Monsen ER. Dietary reference intakes for the antioxidant nutrients: vitamin C, vitamin E, selenium, and carotenoids. J Am Diet Assoc. 2000;100(6):637–40.

    CAS  PubMed  Article  Google Scholar 

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  1. Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, 88040-900, Brazil

    Morgana Moretti, Daiane Bittencourt Fraga & Ana Lúcia S. Rodrigues

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  1. Morgana Moretti
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  2. Daiane Bittencourt Fraga
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  3. Ana Lúcia S. Rodrigues
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Correspondence to Morgana Moretti.

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Dr. Rodrigues is a “National Counsel of Technological and Scientific Development (CNPq)” Research Fellow. Dr. Rodrigues’ studies are supported by Grants from CNPq (Grant Numbers #308723/2013-9 and #449436/2014-4), Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior (CAPES), and NENASC Project (PRONEX-FAPESC/CNPq) #1262/2012-9.

Conflicts of interest

Morgana Moretti, Daiane Bittencourt Fraga, and Ana Lúcia S. Rodrigues declare that no financial support or compensation has been received from any individual or corporate entity over the past 3 years for research or professional service and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest.

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Moretti, M., Fraga, D.B. & Rodrigues, A.L.S. Ascorbic Acid to Manage Psychiatric Disorders. CNS Drugs 31, 571–583 (2017). https://doi.org/10.1007/s40263-017-0446-8

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