Medicinal Effect of Pyridoxine - Magnesium for the Cure of Autism Spectrum Disorder: Medicinal Effect of Pyridoxine – Magnesium in Autism

Hafiza Madiha Jaffar; Sadia  Sukhera; Syeda Aiman  Batool; Asma  Draz; Bahisht  Rizwan; Zeenat  Islam

doi:10.54393/pbmj.v6i05.866

Authors

Hafiza Madiha Jaffar University Institute of Diet & Nutritional Sciences, Faculty of Allied Health Sciences, The University of Lahore, Lahore, Pakistan
Sadia Sukhera University Institute of Physical Therapy, Faculty of Allied Health Sciences, The University of Lahore, Lahore, Pakistan
Syeda Aiman Batool University Institute of Physical Therapy, Faculty of Allied Health Sciences, The University of Lahore, Lahore, Pakistan
Asma Draz Institute of Diet & Nutritional Sciences, Government College University, Faisalabad, Pakistan
Bahisht Rizwan University Institute of Diet & Nutritional Sciences, Faculty of Allied Health Sciences, The University of Lahore, Lahore, Pakistan
Zeenat Islam University Institute of Diet & Nutritional Sciences, Faculty of Allied Health Sciences, The University of Lahore, Lahore, Pakistan

DOI:

https://doi.org/10.54393/pbmj.v6i05.866

Keywords:

Autism Spectrum Disorder (ASD), Magnesium, Vitamin B6

Abstract

Dietary interventions involving the use of magnesium and vitamin B6 supplements are considered the most commonly employed therapeutic approach for autism spectrum disorder (ASD). However, there is currently a lack of investigation into the medicinal efficacy of vitamin and mineral supplementation in improving ASD symptoms. Nonetheless, several researchers have observed a prevalence of nutritional and metabolic abnormalities among individuals with autism. While there is some evidence suggesting that nutrient and mineral supplementation may enhance these fundamental physiological processes, further research is necessary to establish their effectiveness. This review aims to explore potential direct and indirect contributions of metabolism to the primary symptoms of autism, as well as provide evidence regarding nutritional deficiencies and metabolic dysfunction. The present review systematically investigates the existing body of evidence regarding the utilization of high-dose vitamin B6-mg supplementation for the therapeutic intervention in individuals, encompassing both pediatric and adult populations, diagnosed with autism spectrum disorder

References

Bai D, Yip BH, Windham GC, Sourander A, Francis R, Yoffe R, et al. Association of genetic and environmental factors with autism in a 5-country cohort. JAMA Psychiatry. 2019 Oct; 76(10): 1035-43. doi: 10.1001/jamapsychiatry.2019.1411. DOI: https://doi.org/10.1001/jamapsychiatry.2019.1411

Blenner S and Augustyn M. Is the prevalence of autism increasing in the United States? BMJ. 2014 May; 348: g3088. doi: 10.1136/bmj.g3088. DOI: https://doi.org/10.1136/bmj.g3088

Gogou M and Kolios G. The effect of dietary supplements on clinical aspects of autism spectrum disorder: A systematic review of the literature. Brain and Development. 2017 Sep; 39(8): 656-64. doi: 10.1016/j.braindev.2017.03.029. DOI: https://doi.org/10.1016/j.braindev.2017.03.029

Fombonne E. Epidemiological trends in rates of autism. Molecular Psychiatry. 2002 Aug; 7(2): S4-6. doi: 10.1038/sj.mp.4001162. DOI: https://doi.org/10.1038/sj.mp.4001162

Bölte S and Poustka F. The relation between general cognitive level and adaptive behavior domains in individuals with autism with and without co-morbid mental retardation. Child Psychiatry and Human Development. 2002 Dec; 33: 165-72. doi: 10.1023/A:1020734325815. DOI: https://doi.org/10.1023/A:1020734325815

Buie T, Campbell DB, Fuchs III GJ, Furuta GT, Levy J, VandeWater J, et al. Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics. 2010 Jan; 125(Supplement_1): S1-8. doi: 10.1542/peds.2009-1878C. DOI: https://doi.org/10.1542/peds.2009-1878C

Muhle R, Trentacoste SV, Rapin I. The genetics of autism. Pediatrics. 2004 May; 113: 72-86. doi: 10.1542/peds.113.5.e472. DOI: https://doi.org/10.1542/peds.113.5.e472

Theoharides TC and Zhang B. Neuro-inflammation, blood-brain barrier, seizures and autism. Journal of Neuroinflammation. 2011 Dec; 8(1): 1-5. doi: 10.1186/1742-2094-8-168. DOI: https://doi.org/10.1186/1742-2094-8-168

Sakai Y, Shaw CA, Dawson BC, Dugas DV, Al-Mohtaseb Z, Hill DE, et al. Protein interactome reveals converging molecular pathways among autism disorders. Science Translational Medicine. 2011 Jun; 3(86): 86ra49. doi: 10.1126/scitranslmed.3002166. DOI: https://doi.org/10.1126/scitranslmed.3002166

Al-Ayadhi LY and Mostafa GA. Low plasma progranulin levels in children with autism. Journal of Neuroinflammation. 2011 Dec; 8(1): 1-6. doi: 10.1186/1742-2094-8-111. DOI: https://doi.org/10.1186/1742-2094-8-111

Campbell DB, Sutcliffe JS, Ebert PJ, Militerni R, Bravaccio C, Trillo S, et al. A genetic variant that disrupts MET transcription is associated with autism. Proceedings of the National Academy of Sciences. 2006 Nov; 103(45): 16834-9. doi: 10.1073/pnas.0605296103. DOI: https://doi.org/10.1073/pnas.0605296103

Yoon SH, Choi J, Lee WJ, Do JT. Genetic and epigenetic etiology underlying autism spectrum disorder. Journal of Clinical Medicine. 2020 Mar; 9(4): 966. doi: 10.3390/jcm9040966. DOI: https://doi.org/10.3390/jcm9040966

Meaney MJ and Szyf M. Environmental programming of stress responses through DNA methylation: life at the interface between a dynamic environment and a fixed genome. Dialogues in Clinical Neuroscience. 2022 Apr; 7: 103-23. doi: 10.31887/DCNS.2005.7.2/mmeaney. DOI: https://doi.org/10.31887/DCNS.2005.7.2/mmeaney

Rutter M, Moffitt TE, Caspi A. Gene–environment interplay and psychopathology: Multiple varieties but real effects. Journal of child Psychology and Psychiatry. 2006 Mar; 47(3‐4): 226-61. doi: 10.1111/j.1469-7610.2005.01557.x. DOI: https://doi.org/10.1111/j.1469-7610.2005.01557.x

Mierau SB and Neumeyer AM. Metabolic interventions in autism spectrum disorder. Neurobiology of Disease. 2019 Dec; 132: 104544. doi: 10.1016/j.nbd.2019.104544. DOI: https://doi.org/10.1016/j.nbd.2019.104544

Christensen DL, Braun KV, Baio J, Bilder D, Charles J, Constantino JN, et al. Prevalence and characteristics of autism spectrum disorder among children aged 8 years—autism and developmental disabilities monitoring network, 11 sites, United States, 2012. MMWR Surveillance Summaries. 2018 Nov; 65(13): 1. doi: 10.15585/mmwr.ss6513a1. DOI: https://doi.org/10.15585/mmwr.ss6513a1

Zablotsky B, Black LI, Maenner MJ, Schieve LA, Blumberg SJ. Estimated prevalence of autism and other developmental disabilities following questionnaire changes in the 2014 National Health Interview Survey. National Health Statistics Reports. 2015 Nov; 87: 1-21.

Benevides TW, Carretta HJ, Mandell DS. Differences in perceived need for medical, therapeutic, and family support services among children with ASD. Pediatrics. 2016 Feb; 137(Supplement_2): S176-85. doi: 10.1542/peds.2015-2851P. DOI: https://doi.org/10.1542/peds.2015-2851P

Kalal BS, Pai VR, Bhat SS. Autism treatment challenges: need for accelerated research in pharmacological interventions. Clinical Biotechnology and Microbiology. 2016 Dec; 1(1): 9-10.

Packer A. Neocortical neurogenesis and the etiology of autism spectrum disorder. Neuroscience & Biobehavioral Reviews. 2016 May; 64: 185-95. doi: 10.1016/j.neubiorev.2016.03.002. DOI: https://doi.org/10.1016/j.neubiorev.2016.03.002

Nardone S and Elliott E. The interaction between the immune system and epigenetics in the etiology of autism spectrum disorders. Frontiers in Neuroscience. 2016 Jul; 10: 329. doi: 10.3389/fnins.2016.00329. DOI: https://doi.org/10.3389/fnins.2016.00329

Cannell JJ. Vitamin D and autism, what’s new? Reviews in Endocrine and Metabolic Disorders. 2017 Jun; 18(2): 183-93. doi: 10.1007/s11154-017-9409-0. DOI: https://doi.org/10.1007/s11154-017-9409-0

Vancassel S, Durand G, Barthelemy C, Lejeune B, Martineau J, Guilloteau D, et al. Plasma fatty acid levels in autistic children. Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA). 2001 Jul; 65(1): 1-7. doi: 10.1054/plef.2001.0281. DOI: https://doi.org/10.1054/plef.2001.0281

Sharp WG, Berry RC, McCracken C, Nuhu NN, Marvel E, Saulnier CA, et al. Feeding problems and nutrient intake in children with autism spectrum disorders: a meta-analysis and comprehensive review of the literature. Journal of Autism and Developmental Disorders. 2013 Sep; 43: 2159-73. doi: /10.1007/s10803-013-1771-5. DOI: https://doi.org/10.1007/s10803-013-1771-5

Zimmer MH, Hart LC, Manning-Courtney P, Murray DS, Bing NM, Summer S. Food variety as a predictor of nutritional status among children with autism. Journal of Autism and Developmental Disorders. 2012 Apr; 42: 549-56. doi: 10.1007/s10803-011-1268-z. DOI: https://doi.org/10.1007/s10803-011-1268-z

Ma NS, Thompson C, Weston S. Brief report: scurvy as a manifestation of food selectivity in children with autism. Journal of Autism and Developmental Disorders. 2016 Apr; 46: 1464-70. doi: 10.1007/s10803-015-2660-x. DOI: https://doi.org/10.1007/s10803-015-2660-x

Lai WW, Goh TJ, Oei TP, Sung M. Coping and well-being in parents of children with autism spectrum disorders (ASD). Journal of Autism and Developmental Disorders. 2015 Aug; 45: 2582-93. doi: 10.1007/s10803-015-2430-9. DOI: https://doi.org/10.1007/s10803-015-2430-9

Stewart PA, Hyman SL, Schmidt BL, Macklin EA, Reynolds A, Johnson CR, et al. Dietary supplementation in children with autism spectrum disorders: common, insufficient, and excessive. Journal of the Academy of Nutrition and Dietetics. 2015 Aug; 115(8): 1237-48. doi: 10.1016/j.jand.2015.03.026. DOI: https://doi.org/10.1016/j.jand.2015.03.026

Arnold LE, Hurt EA, Mayes T, Lofthouse N. Ingestible alternative and complementary treatments for attention-deficit/hyperactivity disorder. In: Treating attention deficit hyperactivity disorder: Assessment and intervention in developmental context. Kingston, NJ: Civic Research Institute; 2011.

Höfer J, Hoffmann F, Bachmann C. Use of complementary and alternative medicine in children and adolescents with autism spectrum disorder: A systematic review. Autism. 2017 May; 21(4): 387-402. doi: 10.1177/1362361316646559. DOI: https://doi.org/10.1177/1362361316646559

Masi A, Lampit A, Glozier N, Hickie IB, Guastella AJ. Predictors of placebo response in pharmacological and dietary supplement treatment trials in pediatric autism spectrum disorder: a meta-analysis. Translational Psychiatry. 2015 Sep; 5(9): e640. doi: 10.1038/tp.2015.143. DOI: https://doi.org/10.1038/tp.2015.143

Bertoglio K, Jill James S, Deprey L, Brule N, Hendren RL. Pilot study of the effect of methyl B12 treatment on behavioral and biomarker measures in children with autism. The Journal of Alternative and Complementary Medicine. 2010 May; 16(5): 555-60. doi: 10.1089/acm.2009.0177. DOI: https://doi.org/10.1089/acm.2009.0177

Song L, Luo X, Jiang Q, Chen Z, Zhou L, Wang D, et al. Vitamin D supplementation is beneficial for children with autism spectrum disorder: a meta-analysis. Clinical Psychopharmacology and Neuroscience. 2020 May; 18(2): 203. doi: 10.9758/cpn.2020.18.2.203. DOI: https://doi.org/10.9758/cpn.2020.18.2.203

Lavretsky H, Yang H, Eyre H, Leaver A, Narr K, Khalsa D. M1. Changes in the Functional Brain Connectivity and Verbal Memory Performance Following Yoga or Memory Training in Older Adults with Subjective Memory Complaints. Neuropsychopharmacology. 2015 Dec; 40: S106-271.

Li YJ, Ou JJ, Li YM, Xiang DX. Dietary supplement for core symptoms of autism spectrum disorder: Where are we now and where should we go? Frontiers in Psychiatry. 2017 Aug; 8: 155. doi: 10.3389/fpsyt.2017.00155. DOI: https://doi.org/10.3389/fpsyt.2017.00155

Bobrowski-Khoury N, Ramaekers VT, Sequeira JM, Quadros EV. Folate receptor alpha autoantibodies in autism spectrum disorders: diagnosis, treatment and prevention. Journal of Personalized Medicine. 2021 Jul; 11(8): 710. doi: 10.3390/jpm11080710. DOI: https://doi.org/10.3390/jpm11080710

Elder JH, Shankar M, Shuster J, Theriaque D, Burns S, Sherrill L. The gluten-free, casein-free diet in autism: results of a preliminary double blind clinical trial. Journal of Autism and Developmental Disorders. 2006 Apr; 36: 413-20. doi: 10.1007/s10803-006-0079-0. DOI: https://doi.org/10.1007/s10803-006-0079-0

Pennesi CM and Klein LC. Effectiveness of the gluten-free, casein-free diet for children diagnosed with autism spectrum disorder: based on parental report. Nutritional Neuroscience. 2012 Mar; 15(2): 85-91. doi: 10.1179/1476830512Y.0000000003. DOI: https://doi.org/10.1179/1476830512Y.0000000003

Altura BM. Basic biochemistry and physiology of magnesium: a brief review. Magnesium and Trace Elements. 1991 Jan; 10(2-4): 167-71.

Johnson S. Micronutrient accumulation and depletion in schizophrenia, epilepsy, autism and Parkinson’s disease? Medical Hypotheses. 2001 May; 56(5): 641-5. doi: 10.1054/mehy.2000.1302. DOI: https://doi.org/10.1054/mehy.2000.1302

Kidd PM. Autism, an extreme challenge to integrative medicine. Part 1: The knowledge base. Alternative Medicine Review. 2002 Aug; 7(4): 292-316.

Franceschi D, Bachir, Galacteros, Tchernia, Cynober, Neuberg, et al. Oral magnesium pidolate: effects of long‐term administration in patients with sickle cell disease. British Journal of Haematology. 2000 Feb; 108(2): 284-9. doi: 10.1046/j.1365-2141.2000.01861.x. DOI: https://doi.org/10.1046/j.1365-2141.2000.01861.x

Nilius B. TRP channels in disease. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2007 Aug; 1772(8): 805-12. doi: 10.1016/j.bbadis.2007.02.002. DOI: https://doi.org/10.1016/j.bbadis.2007.02.002

Dakshinamurti K, Dakshinamurti S, Czubryt MP. Vitamin B6: effects of deficiency, and metabolic and therapeutic functions. In: Handbook of Famine, Starvation, and Nutrient Deprivation. Springer; 2017 Sep: 1-23. doi: 10.1007/978-3-319-40007-5_81-1. DOI: https://doi.org/10.1007/978-3-319-40007-5_81-1

Bowton E, Saunders C, Reddy IA, Campbell NG, Hamilton PJ, Henry LK, et al. SLC6A3 coding variant Ala559Val found in two autism probands alters dopamine transporter function and trafficking. Translational Psychiatry. 2014 Oct; 4(10): e464. doi: 10.1038/tp.2014.90. DOI: https://doi.org/10.1038/tp.2014.90

Bast N, Poustka L, Freitag CM. The locus coeruleus–norepinephrine system as pacemaker of attention–a developmental mechanism of derailed attentional function in autism spectrum disorder. European Journal of Neuroscience. 2018 Jan; 47(2): 115-25. doi: 10.1111/ejn.13795. DOI: https://doi.org/10.1111/ejn.13795

Cellini B, Montioli R, Oppici E, Astegno A, Voltattorni CB. The chaperone role of the pyridoxal 5′-phosphate and its implications for rare diseases involving B6-dependent enzymes. Clinical Biochemistry. 2014 Feb; 47(3): 158-65. doi: 10.1016/j.clinbiochem.2013.11.021. DOI: https://doi.org/10.1016/j.clinbiochem.2013.11.021

Clayton PT. B 6-responsive disorders: a model of vitamin dependency. Journal of Inherited Metabolic Disease. 2006 Apr; 29: 317-26. doi: 10.1007/s10545-005-0243-2. DOI: https://doi.org/10.1007/s10545-005-0243-2

Ramos RJ, Pras-Raves ML, Gerrits J, van der Ham M, Willemsen M, Prinsen H, et al. Vitamin B6 is essential for serine de novo biosynthesis. Journal of Inherited Metabolic Disease. 2017 Nov; 40: 883-91. doi: 10.1007/s10545-017-0061-3. DOI: https://doi.org/10.1007/s10545-017-0061-3

Mousain-Bosc M, Roche M, Polge A, Pradal-Prat D, Rapin J, Bali JP. Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. Magnesium Research. 2006 Mar; 19(1): 46-52.

Lofthouse N, Hendren R, Hurt E, Arnold LE, Butter E. A review of complementary and alternative treatments for autism spectrum disorders. Autism Research and Treatment. 2012 Oct; 2012: 870391. doi: /10.1155/2012/870391. DOI: https://doi.org/10.1155/2012/870391

Yip J, Soghomonian JJ, Blatt GJ. Decreased GAD67 mRNA levels in cerebellar Purkinje cells in autism: pathophysiological implications. Acta Neuropathologica. 2007 May; 113: 559-68. doi: 10.1007/s00401-006-0176-3. DOI: https://doi.org/10.1007/s00401-006-0176-3

Zafeiriou DI, Ververi A, Vargiami E. The serotonergic system: its role in pathogenesis and early developmental treatment of autism. Current Neuropharmacology. 2009 Jun; 7(2): 150-7. doi: 10.2174/157015909788848848. DOI: https://doi.org/10.2174/157015909788848848

Tolbert LC, Haigler T, Waits MM, Dennis T. Brief report: lack of response in an autistic population to a low dose clinical trial of pyridoxine plus magnesium. Journal of Autism and Developmental Disorders. 1993 Mar; 23(1): 193-9. doi: 10.1007/BF01066428. DOI: https://doi.org/10.1007/BF01066428

Rizzo MR, Barbieri M, Marfella R, Paolisso G. Reduction of oxidative stress and inflammation by blunting daily acute glucose fluctuations in patients with type 2 diabetes: role of dipeptidyl peptidase-IV inhibition. Diabetes Care. 2012 Oct; 35(10): 2076-82. doi: 10.2337/dc12-0199. DOI: https://doi.org/10.2337/dc12-0199

Nye C and Brice A. Combined vitamin B6‐magnesium treatment in autism spectrum disorder. Cochrane Database of Systematic Reviews. 2005 Oct; 4: CD003497. doi: 10.1002/14651858.CD003497.pub2. DOI: https://doi.org/10.1002/14651858.CD003497.pub2

Fernandes P, Haley M, Eagan K, Shattuck PT, Kuo AA. Health needs and college readiness in autistic students: The freshman survey results. Journal of Autism and Developmental Disorders. 2021 Jan; 51: 3506-13. doi: 10.1007/s10803-020-04814-8 DOI: https://doi.org/10.1007/s10803-020-04814-8