The Levels of Vitamin D, Vitamin D Receptor, Homocysteine and Complex B Vitamin in Children with Autism Spectrum Disorders

Objective Autism spectrum disorder (ASD) is a complex neurodevelopmental syndrome with an increasingly prevalent etiology, yet not fully understood. It has been thought that vitamin D, complex B vitamin levels and homocysteine are associated with environmental factors and are important in ASD. The aim of this study was to examine serum vitamin D, vitamin D receptor (VDR), homocysteine, vitamin B6, vitamin B12 and folate levels in ASD. Methods In this study, serum vitamin D and VDR, homocysteine, vitamins B6, B12 and folate levels were determined in 60 patients with ASD (aged 3 to 12 years) and in 45 age-gender matched healthy controls. In addition, calcium, phosphorus and alkaline phosphatase, which are associated with vitamin D metabolism, were measured from serum in both groups. ASD severity was evaluted by the Childhood Autism Rating Scale (CARS). Results Serum vitamin D and VDR were substantially reduced in patients with ASD in comparision to control group. However, homocysteine level was significantly higher and vitamin B6, vitamin B12 and folate were also reduced in patients with ASD. Total CARS score showed a positive association with homocysteine and a negative correlation with vitamins D, B6, B12, folate and VDR. Conclusion This comprehensive study, which examines many parameters has shown that low serum levels of vitamins D, B6, B12, folate and VDR as well as high homocysteine are important in the etiopathogenesis of ASD. However, further studies are required to define the precise mechanism(s) of these parameters and their contributions to the etiology and treatment of ASD.

[1]  B. Wang,et al.  Clinical improvement following vitamin D3 supplementation in Autism Spectrum Disorder , 2017, Nutritional neuroscience.

[2]  Geir Bjorklund,et al.  Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children , 2016, Nutritional neuroscience.

[3]  A. Çim,et al.  Association of polymorphisms in the vitamin D receptor gene and serum 25-hydroxyvitamin D levels in children with autism spectrum disorder. , 2016, Gene.

[4]  J. M. Sequeira,et al.  The metabolic basis for developmental disorders due to defective folate transport. , 2016, Biochimie.

[5]  Takeo Fujiwara,et al.  Chemicals, Nutrition, and Autism Spectrum Disorder: A Mini-Review , 2016, Front. Neurosci..

[6]  C. Gottfried,et al.  Folic acid and autism: What do we know? , 2016, Nutritional neuroscience.

[7]  F. Muratori,et al.  Gastrointestinal symptoms and behavioral problems in preschoolers with Autism Spectrum Disorder. , 2016, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[8]  D. Kennedy B Vitamins and the Brain: Mechanisms, Dose and Efficacy—A Review , 2016, Nutrients.

[9]  N. Aydın,et al.  The Effects of Vitamin D3 on Brain Development and Autism , 2015 .

[10]  John H. White,et al.  Vitamin D and its receptor during late development. , 2015, Biochimica et biophysica acta.

[11]  C. Gillberg,et al.  Autism spectrum disorder and low vitamin D at birth: a sibling control study , 2015, Molecular Autism.

[12]  Ç. Uğur,et al.  Serum vitamin D and folate levels in children with autism spectrum disorders , 2014 .

[13]  M. Tosun,et al.  Vitamin D status in children with attention‐deficit–hyperactivity disorder , 2014, Pediatrics international : official journal of the Japan Pediatric Society.

[14]  T. Burne,et al.  Vitamin D as a neurosteroid affecting the developing and adult brain. , 2014, Annual review of nutrition.

[15]  T. Bourgeron,et al.  Vitamin D in the General Population of Young Adults with Autism in the Faroe Islands , 2014, Journal of Autism and Developmental Disorders.

[16]  L. Bandini,et al.  Comparison of sedentary behaviors between children with autism spectrum disorders and typically developing children , 2014, Autism : the international journal of research and practice.

[17]  D. Rossignol,et al.  Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism , 2014, Front. Physiol..

[18]  Rongbai Tong,et al.  Serum 25-hydroxyvitamin D levels in Chinese children with autism spectrum disorders , 2013, Neuroreport.

[19]  M. Michalska,et al.  A focus on homocysteine in autism. , 2013, Acta biochimica Polonica.

[20]  A. Ouhtit,et al.  Low folate and vitamin B12 nourishment is common in Omani children with newly diagnosed autism. , 2013, Nutrition.

[21]  L. Al-Ayadhi,et al.  Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: Relation to autoimmunity , 2012, Journal of Neuroinflammation.

[22]  Flora Tassone,et al.  Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study. , 2012, The American journal of clinical nutrition.

[23]  H. Amital,et al.  Low serum vitamin D concentrations in patients with schizophrenia. , 2012, The Israel Medical Association journal : IMAJ.

[24]  M. Essa,et al.  Hyperhomocysteinemia among Omani autistic children: a case-control study. , 2011, Acta biochimica Polonica.

[25]  David Quig,et al.  Effect of a vitamin/mineral supplement on children and adults with autism , 2011, BMC pediatrics.

[26]  D. Eyles,et al.  Vitamin D in fetal brain development. , 2011, Seminars in cell & developmental biology.

[27]  D. Eyles,et al.  Vitamin D and the brain. , 2011, Best practice & research. Clinical endocrinology & metabolism.

[28]  David Quig,et al.  Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity , 2011, Nutrition & metabolism.

[29]  M. Michalska,et al.  Vitamin supplementation reduces the level of homocysteine in the urine of autistic children. , 2011, Nutrition research.

[30]  M. Michalska,et al.  Homocysteine level in urine of autistic and healthy children. , 2011, Acta biochimica Polonica.

[31]  J. Cannell On the aetiology of autism , 2010, Acta paediatrica.

[32]  J. Golding,et al.  Feeding Symptoms, Dietary Patterns, and Growth in Young Children With Autism Spectrum Disorders , 2010, Pediatrics.

[33]  M. Humble,et al.  Low serum levels of 25-hydroxyvitamin D (25-OHD) among psychiatric out-patients in Sweden: Relations with season, age, ethnic origin and psychiatric diagnosis , 2010, The Journal of Steroid Biochemistry and Molecular Biology.

[34]  N. Meguid,et al.  Reduced serum levels of 25-hydroxy and 1,25-dihydroxy vitamin D in Egyptian children with autism. , 2010, Journal of alternative and complementary medicine.

[35]  James Davis,et al.  Clinical diagnostics for homocysteine: a rogue amino acid? , 2010, Expert review of molecular diagnostics.

[36]  Yanjuan Zhou,et al.  A preliminary study on nutritional status and intake in Chinese children with autism , 2010, European Journal of Pediatrics.

[37]  S. Lorenzl,et al.  Homocysteine, folate and vitamin B12 in neuropsychiatric diseases: review and treatment recommendations , 2009, Expert review of neurotherapeutics.

[38]  W. Grant,et al.  Epidemiologic evidence for supporting the role of maternal vitamin D deficiency as a risk factor for the development of infantile autism , 2009, Dermato-endocrinology.

[39]  C. Doyen,et al.  Approches substitutive et diététique du trouble autistique de l’enfant : intérêts ou limites ? , 2008 .

[40]  B. Hollis,et al.  Use of vitamin D in clinical practice. , 2008, Alternative medicine review : a journal of clinical therapeutic.

[41]  N. Blau,et al.  Folate receptor autoimmunity and cerebral folate deficiency in low-functioning autism with neurological deficits. , 2007, Neuropediatrics.

[42]  H. Jakubowski,et al.  Mechanisms of homocysteine toxicity in humans , 2007, Amino Acids.

[43]  J. Mann,et al.  A controlled trial of homocysteine lowering and cognitive performance. , 2006, The New England journal of medicine.

[44]  B. Nemeș,et al.  High levels of homocysteine and low serum paraoxonase 1 arylesterase activity in children with autism. , 2006, Life sciences.

[45]  A. Brice,et al.  Combined vitamin B6-magnesium treatment in autism spectrum disorder. , 2005, The Cochrane database of systematic reviews.

[46]  K. Schreck,et al.  Comparing Selective Eaters with and Without Developmental Disabilities , 2005 .

[47]  N. Craddock,et al.  Vitamin D receptor variants in 192 patients with schizophrenia and other psychiatric diseases , 2005, Neuroscience Letters.

[48]  A. Bava,et al.  Vitamin B12 and folate depletion in cognition: a review. , 2004, Neurology India.

[49]  M. Mattson,et al.  Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders , 2003, Trends in Neurosciences.

[50]  T. Shea,et al.  Multiple aspects of homocysteine neurotoxicity: Glutamate excitotoxicity, kinase hyperactivation and DNA damage , 2002, Journal of neuroscience research.

[51]  C. Culmsee,et al.  Homocysteine Elicits a DNA Damage Response in Neurons That Promotes Apoptosis and Hypersensitivity to Excitotoxicity , 2000, The Journal of Neuroscience.

[52]  Santhosh K. P. Kumar,et al.  Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[53]  Salvador Marí-Bauset,et al.  Nutritional Status of Children with Autism Spectrum Disorders (ASDs): A Case–Control Study , 2015, Journal of autism and developmental disorders.

[54]  B. Olas,et al.  The disturbance of hemostasis induced by hyperhomocysteinemia; the role of antioxidants. , 2012, Acta biochimica Polonica.

[55]  K. Munir,et al.  Environmental risk factors for autism: do they help cause de novo genetic mutations that contribute to the disorder? , 2010, Medical hypotheses.

[56]  C. Doyen,et al.  [Substitutive and dietetic approaches in childhood autistic disorder: interests and limits]. , 2008, L'Encephale.

[57]  R. Obeid,et al.  Hyperhomocysteinaemia: a critical review of old and new aspects. , 2007, Current drug metabolism.