, Volume 182, Issue 4, pp 494–498 | Cite as

Supplementation of vitamin C with atypical antipsychotics reduces oxidative stress and improves the outcome of schizophrenia

  • G. N. Dakhale
  • S. D. Khanzode
  • S. S. Khanzode
  • A. Saoji
Original Investigation



Several investigators implicated role of free radical-mediated pathology in schizophrenia. No study has ever examined the effect of vitamin C with atypical antipsychotics in the treatment of schizophrenia.


The aim of this study was to examine the effect of oral vitamin C with atypical antipsychotics on serum malondialdehyde (MDA), plasma ascorbic acid levels, and brief psychiatric rating scale (BPRS) score in schizophrenic patients.


Forty schizophrenic patients participated in a prospective, double-blind, placebo-controlled, noncrossover, 8-week study. The patients with schizophrenia were divided randomly into placebo and vitamin C group of 20 each. Serum MDA and plasma ascorbic acid were estimated by methods of Nischal and Aye, respectively.


Increased serum MDA and decreased plasma ascorbic acid levels were found in schizophrenic patients. These levels were reversed significantly after treatment with vitamin C along with atypical antipsychotics compared to placebo with atypical antipsychotics. BPRS change scores at 8 weeks improved statistically significant with vitamin C as compared to placebo.


Oral supplementation of vitamin C with atypical antipsychotic reverses ascorbic acid levels, reduces oxidative stress, and improves BPRS score, hence both the drugs in combination can be used in the treatment of schizophrenia.


Schizophrenia Vitamin C Atypical antipsychotics Oxidative stress BPRS score 


  1. Altuntas I, Aksoy H, Coskun I, Caykoylu A, Akcay F (2000) Erythrocyte superoxide dismutase and glutathion paraoxidase activities and malondealdehyde and reduced glutathione levels in schizophrenic patients. Clin Chem Lab Med 38:1277–1281CrossRefPubMedGoogle Scholar
  2. Arvindakshan M, Sitasawad S, Debsikdar V, Ghate M, Evans D, Horrobin DF, Bennett C, Ranjekar PK, Mahadik SP (2003a) Essential polyunsaturated fatty acid and lipid peroxide levels in never-medicated and medicated schizophrenia patients. Biol Psychiatry 53:56–64CrossRefPubMedGoogle Scholar
  3. Arvindakshan M, Ghate M, Ranjekar PK, Evans DR, Mahadik SP (2003b) Supplementation with a combination of omega 3 fatty acids and antioxidants (vitamin E and C) improves the outcome of schizophrenia. Schizophr Res 62:195–204CrossRefPubMedGoogle Scholar
  4. Aye K (1978) A simple colorimetric method for ascorbic acid determination in blood plasma. Clin Chim Acta 86:153–157CrossRefPubMedGoogle Scholar
  5. Blakely RD, Wages SA, Justice JB, Hernbon JB, Neill DB (1984) Neuroleptics increase striatal catecholamines metabolites but not ascorbic acid in dialyzed perfusate. Brain Res 308:1–6CrossRefPubMedGoogle Scholar
  6. Cadet JL, Brannock C (1997) Invited review-free radicals and pathobiology of brain dopamine system. Neurochem Int 32:117–131CrossRefGoogle Scholar
  7. Cadet JL, Lohr JB (1987) Free radicals and developmental biopathology of schizophrenic burnout. Integr Psychiatr 51:40–48Google Scholar
  8. Dakhale G, Khanzode SD, Khanzode SS, Saoji A, Khobragade L, Turankar A (2004) Oxidative damage and schizophrenia: the potential benefit by atypical antipsychotics. Neuropsychobiology 49:205–209CrossRefPubMedGoogle Scholar
  9. Englard S, Seifter S (1986) The biochemical functions of ascorbic acid. Annu Rev Nutr 6:365–406CrossRefPubMedGoogle Scholar
  10. Fridovich I (1983) Superoxide radical: an endogenous toxicant. Annu Rev Pharmacol Toxicol 23:239–257CrossRefPubMedGoogle Scholar
  11. Hadjiconstanttinou M, Neff NH (1983) 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 22:939–946CrossRefPubMedGoogle Scholar
  12. Kei S (1978) Lipid peroxides in cerebrovascular disorders determined by new colorimetric method. Clin Chim Acta 90:37–43CrossRefPubMedGoogle Scholar
  13. Kuloghi M, Ustundag B, Atmaca M, Canatan H, Tezean AE, Cinkiline N (2002) Lipid peroxidation and antioxidant enzyme levels in patients with schizophrenia and bipolar disorder. Cell Biochem Funct 20:171–175CrossRefPubMedGoogle Scholar
  14. Liu J, Mori A (1993) Monoamine metabolism provides an antioxidant defense in the brain against oxidant and free radical induced damage. Arch Biochem Biophys 302:118–127CrossRefPubMedGoogle Scholar
  15. Mahadik SP, Mukherjee S, Correnti I, Sheffer R (1995) Elevated levels of lipid peroxidation products in plasma from drug-naive patients at onset of psychosis. Schizophr Res 15:66–70Google Scholar
  16. Oke AI, May L, Adams RN (1987) Ascorbic acid distribution pattern in human brain. In: Bums JJ, Reverse JM, Machlin LJ (eds) Third conference on Vit C. Ann NY Acad Sci pp 1–12Google Scholar
  17. Overall JE, Gorham DR (1962) The brief psychiatric rating scale. Psychol Rep 10:799–812CrossRefGoogle Scholar
  18. Padh H (1990) Cellular functions of ascorbic acid. Biochem Cell Biol 68:1166–1173PubMedCrossRefGoogle Scholar
  19. Reddy R, Mahadik SP, Mukherjee M, Murty JN (1991) Enzymes of the antioxidant system in chronic schizophrenic patients. Biol Psychiatry 30:409–412CrossRefPubMedGoogle Scholar
  20. Sen CK, Hanninen O (1994) Physiological antioxidants. In: Sen CK, Packer L, Hanninen O (eds) Exercise and oxygen toxicity. Elsevier Science Publishers, B.V., AmsterdamGoogle Scholar
  21. Seregi A, Schaefer A, Komlos M (1978) Protective role of brain ascorbic acid content against lipid peroxidation. Experientia 34:1056–1057CrossRefPubMedGoogle Scholar
  22. Vaiva G, Thomas P, Leroux JM (1994) Erythrocyte superoxide dismutase determination in positive moments of psychosis. Therapie 49:343–348PubMedGoogle Scholar
  23. Vera JC, Rivas CI, Fischbarg J (1993) Mammalian facilitative hexose transporters mediate the transport of dehydroascorbic acid. Nature 364:79–82CrossRefPubMedGoogle Scholar
  24. Washko PW, Wanw Y, Levine M (1993) Ascorbic acid recycling in human neutrophils. J Biol Chem 268:15531–15535PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • G. N. Dakhale
    • 1
  • S. D. Khanzode
    • 1
    • 2
  • S. S. Khanzode
    • 3
  • A. Saoji
    • 4
  1. 1.Department of PharmacologyGovernment Medical CollegeNagpurIndia
  2. 2.NagpurIndia
  3. 3.Biochemist in MedicineGovernment Medical CollegeNagpurIndia
  4. 4.Department of PsychiatryGovernment Medical CollegeNagpurIndia

Personalised recommendations