Skip to main content

Vitamin D levels in children and adolescents with attention-deficit hyperactivity disorder (ADHD): a meta-analysis

Abstract

The aim of this article was to assess the differences in serum 25(OH)D levels between children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and healthy controls. We used the PubMed (1966–2017), Scopus (2004–2017), ClinicalTrials.gov (2008–2017), Cochrane Central Register of Controlled Trials CENTRAL (2000–2017), and Google Scholar (2004–2017) databases. Statistical meta-analysis was performed with RevMan 5.3. Εight studies were finally included in the present meta-analysis with a total number of 11,324 children. Among them, 2655 were diagnosed with ADHD, while the remaining 8669 were recruited as healthy controls. All eight trials reported significantly lower serum concentrations of 25(OH)D in patients diagnosed with ADHD compared to healthy controls. The pooled data showed that there was a significant difference between the ADHD group and the control group (SMD = − 0.73, 95% CI [− 1.00, − 0.46]). The systematic review and meta-analysis of observational studies demonstrated an inverse association between serum 25(OH)D and young patients with ADHD. Large cohort studies are required to investigate whether vitamin D-deficient infants are more likely to develop ADHD in the future. Also, whether children with ADHD should be supplemented with higher doses of vitamin D3 remains to be confirmed through long-term controlled clinical trials.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Notes

  1. 1.

    Vitamin D as a therapeutic adjunct in the stimulant treatment of ADHD. https://clinicaltrials.gov/ct2/show/NCT03103750?term=vitamin+D&cond=ADHD&rank=1.

References

  1. Ascherio A, Munger KL, Simon KC (2010) Vitamin D and multiple sclerosis. Lancet Neurol 9(6):599–612

    PubMed  Article  Google Scholar 

  2. Autier P et al (2014) Vitamin D status and ill health: a systematic review. Lancet Diabetes Endocrinol 2(1):76–89

    CAS  PubMed  Article  Google Scholar 

  3. Avcil S et al (2017) Vitamin D deficiency and a blunted parathyroid hormone response in children with attention-deficit/hyperactivity disorder. Clin Lab 63(3):435–443

    CAS  PubMed  Google Scholar 

  4. Bala KA et al (2016) Hormone disorder and vitamin deficiency in attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASDs). J Pediatr Endocrinol Metab 29(9):1077–1082

    CAS  PubMed  Article  Google Scholar 

  5. Bener A et al (2014) Higher prevalence of iron deficiency as strong predictor of attention deficit hyperactivity disorder in children. Ann Med Health Sci Res 4(Suppl 3):S291–S297

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  6. Berridge MJ (2018) Vitamin D deficiency: infertility and neurodevelopmental diseases (attention deficit hyperactivity disorder, autism, and schizophrenia). Am J Physiol Cell Physiol 314(2):C135–C151

    PubMed  Article  CAS  Google Scholar 

  7. Braegger C et al (2013) Vitamin D in the healthy European paediatric population. J Pediatr Gastroenterol Nutr 56(6):692–701

    CAS  PubMed  Article  Google Scholar 

  8. Carvalho JTG et al (2017) Cholecalciferol decreases inflammation and improves vitamin D regulatory enzymes in lymphocytes in the uremic environment: a randomized controlled pilot trial. PLoS ONE 12(6):e0179540

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  9. Cashman KD et al (2016) Vitamin D deficiency in Europe: pandemic? Am J Clin Nutr 103(4):1033–1044

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  10. Cass WA, Smith MP, Peters LE (2006) Calcitriol protects against the dopamine- and serotonin-depleting effects of neurotoxic doses of methamphetamine. Ann N Y Acad Sci 1074:261–271

    CAS  PubMed  Article  Google Scholar 

  11. Childress AC, Sallee FR (2014) Attention-deficit/hyperactivity disorder with inadequate response to stimulants: approaches to management. CNS Drugs 28(2):121–129

    CAS  PubMed  Article  Google Scholar 

  12. Coghill D, Hodgkins P (2016) Health-related quality of life of children with attention-deficit/hyperactivity disorder versus children with diabetes and healthy controls. Eur Child Adolesc Psychiatry 25(3):261–271

    PubMed  Article  Google Scholar 

  13. Daraki V et al (2018) High maternal vitamin D levels in early pregnancy may protect against behavioral difficulties at preschool age: the Rhea mother–child cohort, Crete, Greece. Eur Child Adolesc Psychiatry 27(1):79–88

    PubMed  Article  Google Scholar 

  14. Dawodu A, Nath R (2011) High prevalence of moderately severe vitamin D deficiency in preterm infants. Pediatr Int 53(2):207–210

    PubMed  Article  Google Scholar 

  15. DerSimonian R, Kacker R (2007) Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials 28(2):105–114

    PubMed  Article  Google Scholar 

  16. Dopfner M et al (2015) Long-term course of ADHD symptoms from childhood to early adulthood in a community sample. Eur Child Adolesc Psychiatry 24(6):665–673

    PubMed  Article  Google Scholar 

  17. Doshi JA et al (2012) Economic impact of childhood and adult attention-deficit/hyperactivity disorder in the United States. J Am Acad Child Adolesc Psychiatry 51(10):990–1002

    PubMed  Article  Google Scholar 

  18. Eyles DW et al (2009) Developmental vitamin D deficiency causes abnormal brain development. Psychoneuroendocrinology 34(Suppl 1):S247–S257

    CAS  PubMed  Article  Google Scholar 

  19. Eyles D, Burne T, McGrath J (2011) Vitamin D in fetal brain development. Semin Cell Dev Biol 22(6):629–636

    CAS  PubMed  Article  Google Scholar 

  20. Eyles DW, Burne TH, McGrath JJ (2013) Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Front Neuroendocrinol 34(1):47–64

    CAS  PubMed  Article  Google Scholar 

  21. Eyles DW et al (2014) Intracellular distribution of the vitamin D receptor in the brain: comparison with classic target tissues and redistribution with development. Neuroscience 268:1–9

    CAS  PubMed  Article  Google Scholar 

  22. Feldman HM, Reiff MI (2014) Clinical practice. Attention deficit-hyperactivity disorder in children and adolescents. N Engl J Med 370(9):838–846

    CAS  PubMed  Article  Google Scholar 

  23. Fleet JC et al (2012) Vitamin D and cancer: a review of molecular mechanisms. Biochem J 441(1):61–76

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  24. Gallo EF, Posner J (2016) Moving towards causality in attention-deficit hyperactivity disorder: overview of neural and genetic mechanisms. Lancet Psychiatry 3(6):555–567

    PubMed  PubMed Central  Article  Google Scholar 

  25. Garipardic M et al (2017) Association of attention deficit hyperactivity disorder and autism spectrum disorders with mean platelet volume and vitamin D. Med Sci Monit 23:1378–1384

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  26. Goksugur SB et al (2014) Vitamin D status in children with attention-deficit-hyperactivity disorder. Pediatr Int 56(4):515–519

    CAS  PubMed  Article  Google Scholar 

  27. Gustafsson P et al (2015) Vitamin D status at birth and future risk of attention deficit/hyperactivity disorder (ADHD). PLoS ONE 10(10):e0140164

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  28. Hawes JE et al (2015) Maternal vitamin D deficiency alters fetal brain development in the BALB/c mouse. Behav Brain Res 286:192–200

    CAS  PubMed  Article  Google Scholar 

  29. Health Quality O (2010) Clinical utility of vitamin d testing: an evidence-based analysis. Ont Health Technol Assess Ser 10(2):1–93

    Google Scholar 

  30. Holick MF (1987) Photosynthesis of vitamin D in the skin: effect of environmental and life-style variables. Fed Proc 46(5):1876–1882

    CAS  PubMed  Google Scholar 

  31. Holick MF (2007) Vitamin D deficiency. N Engl J Med 357(3):266–281

    CAS  Article  Google Scholar 

  32. Holton KF et al (2018) Evaluation of dietary intake in children and college students with and without attention-deficit/hyperactivity disorder. Nutr Neurosci. https://doi.org/10.1080/1028415X.2018.1427661

    Article  PubMed  Google Scholar 

  33. Humble MB, Gustafsson S, Bejerot S (2010) Low serum levels of 25-hydroxyvitamin D (25-OHD) among psychiatric out-patients in Sweden: relations with season, age, ethnic origin and psychiatric diagnosis. J Steroid Biochem Mol Biol 121(1–2):467–470

    CAS  PubMed  Article  Google Scholar 

  34. Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium, Ross AC, Taylor CL, Yaktine AL et al (eds) (2011) Dietary reference intakes for calcium and vitamin D. National Academies Press, Washington

  35. Kamal M, Bener A, Ehlayel MS (2014) Is high prevalence of vitamin D deficiency a correlate for attention deficit hyperactivity disorder? Atten Defic Hyperact Disord 6(2):73–78

    PubMed  Article  Google Scholar 

  36. Kaneko I et al (2015) 1,25-Dihydroxyvitamin D regulates expression of the tryptophan hydroxylase 2 and leptin genes: implication for behavioral influences of vitamin D. FASEB J 29(9):4023–4035

    CAS  PubMed  Article  Google Scholar 

  37. Kesby JP et al (2013) Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia. Front Cell Neurosci 7:111

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  38. Klein RG et al (2012) Clinical and functional outcome of childhood attention-deficit/hyperactivity disorder 33 years later. Arch Gen Psychiatry 69(12):1295–1303

    PubMed  PubMed Central  Article  Google Scholar 

  39. Lawrence DW, Sharma B (2016) A review of the neuroprotective role of vitamin D in traumatic brain injury with implications for supplementation post-concussion. Brain Inj 30(8):960–968

    PubMed  Article  Google Scholar 

  40. Le Goff C et al (2015) Measurement of circulating 25-hydroxyvitamin D: a historical review. Pract Lab Med 2:1–14

    PubMed  PubMed Central  Article  Google Scholar 

  41. Le HH et al (2014) Economic impact of childhood/adolescent ADHD in a European setting: the Netherlands as a reference case. Eur Child Adolesc Psychiatry 23(7):587–598

    PubMed  Article  Google Scholar 

  42. Leary PF et al (2017) Effect of Latitude on Vitamin D Levels. J Am Osteopath Assoc 117(7):433–439

    PubMed  Article  Google Scholar 

  43. Liberati A et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 62(10):e1–e34

    Article  PubMed  Google Scholar 

  44. Meyer T et al (2017) Attention deficit-hyperactivity disorder is associated with reduced blood pressure and serum vitamin D levels: results from the nationwide German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Eur Child Adolesc Psychiatry 26(2):165–175

    PubMed  Article  Google Scholar 

  45. Mohammadpour N et al (2018) Effect of vitamin D supplementation as adjunctive therapy to methylphenidate on ADHD symptoms: a randomized, double blind, placebo-controlled trial. Nutr Neurosci 21(3):202–209

    CAS  PubMed  Article  Google Scholar 

  46. Morales E et al (2015) Vitamin D in pregnancy and attention deficit hyperactivity disorder-like symptoms in childhood. Epidemiology 26(4):458–465

    PubMed  Article  Google Scholar 

  47. Mossin MH et al (2017) Inverse associations between cord vitamin D and attention deficit hyperactivity disorder symptoms: a child cohort study. Aust N Z J Psychiatry 51(7):703–710

    PubMed  Article  Google Scholar 

  48. Mulraney M et al (2017) ADHD symptoms and quality of life across a 12-month period in children with ADHD: a longitudinal study. J Atten Disord. https://doi.org/10.1177/1087054717707046

    Article  PubMed  Google Scholar 

  49. Partonen T (1998) Vitamin D and serotonin in winter. Med Hypotheses 51(3):267–268

    CAS  PubMed  Article  Google Scholar 

  50. Pludowski P et al (2013) Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality—a review of recent evidence. Autoimmun Rev 12(10):976–989

    CAS  PubMed  Article  Google Scholar 

  51. Schoenrock SA, Tarantino LM (2016) Developmental vitamin D deficiency and schizophrenia: the role of animal models. Genes Brain Behav 15(1):45–61

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  52. Shang-Guan LL, Zhao YR (2015) Serum levels of 25-hydroxyvitamin D in children with attention deficit hyperactivity disorder. Zhongguo Dang Dai Er Ke Za Zhi 17(8):837–840

    CAS  PubMed  Google Scholar 

  53. Sharif MR et al (2015) The relationship between serum vitamin D level and attention deficit hyperactivity disorder. Iran J Child Neurol 9(4):48–53

    PubMed  PubMed Central  Google Scholar 

  54. Shin JS et al (2010) Vitamin D effects on pregnancy and the placenta. Placenta 31(12):1027–1034

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  55. Snellman G et al (2010) Determining vitamin D status: a comparison between commercially available assays. PLoS ONE 5(7):e11555

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  56. Souza JP, Pileggi C, Cecatti JG (2007) Assessment of funnel plot asymmetry and publication bias in reproductive health meta-analyses: an analytic survey. Reprod Health 4:3

    PubMed  PubMed Central  Article  Google Scholar 

  57. Stang A (2010) Critical evaluation of the Newcastle–Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25(9):603–605

    Article  Google Scholar 

  58. Strom M et al (2014) Vitamin D measured in maternal serum and offspring neurodevelopmental outcomes: a prospective study with long-term follow-up. Ann Nutr Metab 64(3–4):254–261

    CAS  PubMed  Article  Google Scholar 

  59. Subcommittee on Attention-Deficit/Hyperactivity Disorder et al (2011) ADHD: clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics 128(5):1007–1022

    Article  Google Scholar 

  60. Telford C et al (2013) Estimating the costs of ongoing care for adolescents with attention-deficit hyperactivity disorder. Soc Psychiatry Psychiatr Epidemiol 48(2):337–344

    PubMed  Article  Google Scholar 

  61. Turner KM et al (2013) Cognitive performance and response inhibition in developmentally vitamin D (DVD)-deficient rats. Behav Brain Res 242:47–53

    CAS  PubMed  Article  Google Scholar 

  62. Wacker M, Holick MF (2013) Vitamin D—effects on skeletal and extraskeletal health and the need for supplementation. Nutrients 5(1):111–148

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  63. Wallace AM et al (2010) Measurement of 25-hydroxyvitamin D in the clinical laboratory: current procedures, performance characteristics and limitations. Steroids 75(7):477–488

    CAS  PubMed  Article  Google Scholar 

  64. Wang Y, Zhu J, DeLuca HF (2012) Where is the vitamin D receptor? Arch Biochem Biophys 523(1):123–133

    CAS  PubMed  Article  Google Scholar 

  65. Wang T et al (2016) Serum concentration of 25-hydroxyvitamin D in autism spectrum disorder: a systematic review and meta-analysis. Eur Child Adolesc Psychiatry 25(4):341–350

    PubMed  Article  Google Scholar 

  66. Webb AR, Kline L, Holick MF (1988) Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. J Clin Endocrinol Metab 67(2):373–378

    CAS  PubMed  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Evangelia Kotsi.

Ethics declarations

Conflicts of interest

None to declare.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Statement on the welfare of animals

This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in all studies in our review.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kotsi, E., Kotsi, E. & Perrea, D.N. Vitamin D levels in children and adolescents with attention-deficit hyperactivity disorder (ADHD): a meta-analysis. ADHD Atten Def Hyp Disord 11, 221–232 (2019). https://doi.org/10.1007/s12402-018-0276-7

Download citation

Keywords

  • Vitamin D
  • ADHD
  • Children
  • Adolescents
  • Attention-deficit hyperactivity disorder