AutismHow does vitamin D work?

As reviewed by Cannell, Kalueff et al1 suggested vitamin D offers ‘‘neuroprotection, antiepileptic effects, immunomodulation, possible interplay with several brain neurotransmitter system and hormones, as well as regulation of behaviors”. Subsequently, Kalueff and Tuohimaa2 concluded ‘‘stress the importance of prenatal, neonatal, and postnatal vitamin D supplementation for normal brain functioning’’.

While no association with prenatal exposure to influenza has been reported [Dassa, 1995], there is evidence that maternal immune activation alters fetal brain development through interleukin-6 (IL-6)3 4.

Vitamin D must have many beneficial effects in the brain as every cell in the brain has vitamin D receptors5. These vitamin D receptors control the expression of many genes.

Cannell pointed out that infection during pregnancy could increase the risk of autistic birth6. Some adverse birth outcomes such as schizophrenia are associated with maternal infection such as influenza during pregnancy7. Low serum 25(OH)D level is an important risk factor for influenza8 9. Influenza infection during pregnancy raises maternal body temperature, which can have adverse effects on the developing fetus10.

One of the hallmarks of autism is oxidative stress11 12 13. There are many papers in the journal literature reporting that vitamin D reduces oxidative stress14 15 16 17 18.

Kinney et al19 reviewed evidence that DNA damage to spermatocytes and ova can contribute to risk of autism and noted that vitamin D can both prevent and repair DNA damage. A number of papers support a role of vitamin D in protecting against DNA damage20 21 22 23.

Page last edited: 17 May 2011

References

  1. Kalueff, A. V. Minasyan, A. Keisala, T. Kuuslahti, M. Miettinen, S. Tuohimaa, P. The vitamin D neuroendocrine system as a target for novel neurotropic drugs. CNS Neurol Disord Drug Targets. 2006 Jun; 5 (3): 363-71.
  2. Kalueff, A. V. Tuohimaa, P. Neurosteroid hormone vitamin D and its utility in clinical nutrition. Curr Opin Clin Nutr Metab Care. 2007 Jan; 10 (1): 12-9.
  3. Smith, S. E. Li, J. Garbett, K. Mirnics, K. Patterson, P. H. Maternal immune activation alters fetal brain development through interleukin-6. J Neurosci. 2007 Oct 3; 27 (40): 10695-702.
  4. Parker-Athill, E. C. Tan, J. Maternal immune activation and autism spectrum disorder: interleukin-6 signaling as a key mechanistic pathway. Neurosignals. 2010; 18 (2): 113-28.
  5. McCann, J. C. Ames, B. N. Is there convincing biological or behavioral evidence linking vitamin D deficiency to brain dysfunction?. FASEB J. 2008 Apr; 22 (4): 982-1001.
  6. Cannell, J. J. On the aetiology of autism. Acta Paediatr. 2010 Aug; 99 (8): 1128-30.
  7. McGrath, J. J. Pemberton, M. R. Welham, J. L. Murray, R. M. Schizophrenia and the influenza epidemics of 1954, 1957 and 1959: a southern hemisphere study. Schizophr Res. 1994 Dec; 14 (1): 1-8.
  8. Cannell, J. J. Vieth, R. Umhau, J. C. Holick, M. F. Grant, W. B. Madronich, S. Garland, C. F. Giovannucci, E. Epidemic influenza and vitamin D. Epidemiol Infect. 2006 Dec; 134 (6): 1129-40.
  9. Urashima, M. Segawa, T. Okazaki, M. Kurihara, M. Wada, Y. Ida, H. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr. 2010 May; 91 (5): 1255-60.
  10. Edwards, M. J. Hyperthermia in utero due to maternal influenza is an environmental risk factor for schizophrenia. Congenit Anom (Kyoto). 2007 Sep; 47 (3): 84-9.
  11. Mostafa, G. A. El-Hadidi, E. S. Hewedi, D. H. Abdou, M. M. Oxidative stress in Egyptian children with autism: relation to autoimmunity. J Neuroimmunol. 2010 Feb 26; 219 (1-2): 114-8.
  12. Sajdel-Sulkowska, E. M. Xu, M. Koibuchi, N. Increase in cerebellar neurotrophin-3 and oxidative stress markers in autism. Cerebellum. 2009 Sep; 8 (3): 366-72.
  13. Sajdel-Sulkowska, E. M. Xu, M. McGinnis, W. Koibuchi, N. Brain region-specific changes in oxidative stress and neurotrophin levels in autism spectrum disorders (ASD). Cerebellum. 2011 Mar; 10 (1): 43-8.
  14. El-Ansary, A. Al-Daihan, S. Al-Dbass, A. Al-Ayadhi, L. Measurement of selected ions related to oxidative stress and energy metabolism in Saudi autistic children. Clin Biochem. 2010 Jan; 43 (1-2): 63-70.
  15. Cohen-Lahav, M. Shany, S. Tobvin, D. Chaimovitz, C. Douvdevani, A. Vitamin D decreases NFkappaB activity by increasing IkappaBalpha levels. Nephrol Dial Transplant. 2006 Apr; 21 (4): 889-97.
  16. Kalueff, A. V. Eremin, K. O. Tuohimaa, P. Mechanisms of neuroprotective action of vitamin D(3). Biochemistry (Mosc). 2004 Jul; 69 (7): 738-41.
  17. Kolusari, A. Adali, E. Kurdoglu, M. Yildizhan, R. Cebi, A. Edirne, T. Demir, H. Yoruk, I. H. Catalase activity, serum trace element and heavy metal concentrations, vitamin A, vitamin D and vitamin E levels in hydatidiform mole. Clin Exp Obstet Gynecol. 2009; 36 (2): 102-4.
  18. Li, L. Prabhakaran, K. Zhang, X. Zhang, L. Liu, H. Borowitz, J. L. Isom, G. E. 1Alpha,25-dihydroxyvitamin D3 attenuates cyanide-induced neurotoxicity by inhibiting uncoupling protein-2 up-regulation. J Neurosci Res. 2008 May 1; 86 (6): 1397-408.
  19. Kinney, D. K. Barch, D. H. Chayka, B. Napoleon, S. Munir, K. M. Environmental risk factors for autism: do they help cause de novo genetic mutations that contribute to the disorder?. Med Hypotheses. 2010 Jan; 74 (1): 102-6.
  20. Chatterjee, M. Vitamin D and genomic stability. Mutat Res. 2001 Apr 18; 475 (1-2): 69-87.
  21. Tremezaygues, L. Seifert, M. Tilgen, W. Reichrath, J. 1,25-dihydroxyvitamin D(3) protects human keratinocytes against UV-B-induced damage: In vitro analysis of cell viability/proliferation, DNA-damage and -repair. Dermatoendocrinol. 2009 Jul; 1 (4): 239-45.
  22. Fedirko, V. Bostick, R. M. Long, Q. Flanders, W. D. McCullough, M. L. Sidelnikov, E. Daniel, C. R. Rutherford, R. E. Shaukat, A. Effects of supplemental vitamin D and calcium on oxidative DNA damage marker in normal colorectal mucosa: a randomized clinical trial. Cancer Epidemiol Biomarkers Prev. 2010 Jan; 19 (1): 280-91.
  23. Peng, X. Vaishnav, A. Murillo, G. Alimirah, F. Torres, K. E. Mehta, R. G. Protection against cellular stress by 25-hydroxyvitamin D3 in breast epithelial cells. J Cell Biochem. 2010 Aug 15; 110 (6): 1324-33.