Skip to main content

Advertisement

Log in

The Role of Nutritional Supplements in the Treatment of ADHD: What the Evidence Says

  • Attention-Deficit Disorder (A Rostain, Section Editor)
  • Published:
Current Psychiatry Reports Aims and scope Submit manuscript

Abstract

Attention-deficit hyperactivity disorder (ADHD) is a common behavioral disorder in children and adolescents and may persist into adulthood. Insufficient nutritional supply of long-chain polyunsaturated fatty acids (LC-PUFAs) and other components including various minerals has been suggested to play a role in the development of ADHD symptoms. This review presents the evidence regarding the role of nutritional PUFA, zinc, iron, and magnesium supplements in the treatment of ADHD with a focus on the critical evaluation of the relevant literature published from 2014 to April 2016. The evaluation of therapeutic nutritional LC-PUFA supplementation in ADHD has shown mixed and inconclusive results and at best marginal beneficial effects. The benefits of PUFAs are much smaller than the effect sizes observed for traditional pharmacological treatments of ADHD. The effectiveness of PUFA supplements in reducing medication dosage has been suggested but needs to be confirmed. Zinc, iron, and magnesium supplementation may reduce ADHD symptoms in children with or at high risk of deficiencies in these minerals. However, convincing evidence in this regard is lacking.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Barkley RA. Attention-deficit hyperactivity disorder: a handbook of diagnosis and treatment. London: Guilford Press; 2006.

    Google Scholar 

  2. Lange KW et al. The history of attention deficit hyperactivity disorder. Atten Defic Hyperact Disord. 2010;2:241–55.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Lange KW et al. Utility of cognitive neuropsychological assessment in attention-deficit/hyperactivity disorder. Atten Defic Hyperact Disord. 2014;6:241–8.

    Article  PubMed  Google Scholar 

  4. Paule MG et al. Attention deficit/hyperactivity disorder: characteristics, interventions and models. Neurotoxicol Teratol. 2000;22:631–51.

    Article  CAS  PubMed  Google Scholar 

  5. Biederman J, Faraone S. Attention-deficit hyperactivity disorder. Lancet. 2005;366:237–48.

    Article  PubMed  Google Scholar 

  6. Wankerl B et al. Neurobiology of attention deficit hyperactivity disorder. Fortschr Neurol Psychiatr. 2014;82:9–29.

    Article  CAS  PubMed  Google Scholar 

  7. Arnsten AF. Genetics of childhood disorders: XVIII. ADHD, Part 2: Norepinephrine has a critical modulatory influence on prefrontal cortical function. J Am Acad Child Adolesc Psychiatry. 2000;39:1201–3.

    Article  CAS  PubMed  Google Scholar 

  8. Heal DJ, Smith SL, Kulkarni RS, Rowley HL. New perspectives from microdialysis studies in freely-moving, spontaneously hypertensive rats on the pharmacology of drugs for the treatment of ADHD. Pharmacol Biochem Behav. 2008;90(2):184–97.

    Article  CAS  PubMed  Google Scholar 

  9. Bymaster FP, Katner JS, Nelson DL, Hemrick-Luecke SK, Threlkeld PG, Heiligenstein JH, et al. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology. 2002;27:699–711.

    Article  CAS  PubMed  Google Scholar 

  10. Kratochvil CJ, Vaughan BS, Harrington MJ, Burke WJ. Atomoxetine: a selective noradrenaline reuptake inhibitor for the treatment of attention-deficit/hyperactivity disorder. Expert Opin Pharmacother. 2003;4:1165–74.

    Article  CAS  PubMed  Google Scholar 

  11. Arnsten AF et al. The contribution of alpha 2-noradrenergic mechanisms of prefrontal cortical cognitive function. Potential significance for attention-deficit hyperactivity disorder. Arch Gen Psychiatry. 1996;53:448–55.

    Article  CAS  PubMed  Google Scholar 

  12. Arnsten AF, Dudley A. Methylphenidate improves prefrontal cortical cognitive function through alpha2 adrenoceptor and dopamine D1 receptor actions: relevance to therapeutic effects in attention deficit hyperactivity. Behav Brain Funct: BBF. 2005;1:1.

    Article  Google Scholar 

  13. Hauser J et al. The effects of the neurotoxin DSP4 on spatial learning and memory in Wistar rats. Atten Defic Hyperact Disord. 2012;4:93–9.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Pliszka SR. The neuropsychopharmacology of attention-deficit/hyperactivity disorder. Biol Psychiatry. 2005;57:1385–90.

    Article  CAS  PubMed  Google Scholar 

  15. Bussing R et al. Use of complementary and alternative medicine for symptoms of attention-deficit hyperactivity disorder. Psychiatr Serv. 2002;53:1096–102.

    Article  PubMed  Google Scholar 

  16. Howard AL et al. ADHD is associated with a “Western” dietary pattern in adolescents. J Atten Disord. 2011;15:403–11.

    Article  PubMed  Google Scholar 

  17. Milichap JG, Yee MM. The diet factor in attention-deficit/hyperactivity disorder. Pediatrics. 2012;129:330–7.

    Article  Google Scholar 

  18. Bloch MH, Mulqueen J. Nutritional supplements for the treatment of ADHD. Child Adolesc Psychiatr Clin N Am. 2014;23:883–97. doi:10.1016/j.chc.2014.05.002.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Gomez-Pinilla F. Brain foods: the effects of nutrients on brain function. Nat Rev Neurosci. 2008;9:568–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Schuchardt JP et al. Significance of long-chain polyunsaturated fatty acids (PUFAs) for the development and behaviour of children. Eur J Pediatr. 2010;169:149–64.

    Article  CAS  PubMed  Google Scholar 

  21. Bourre JM et al. The effects of dietary alpha-linolenic acid on the composition of nerve membranes, enzymatic activity, amplitude of electrophysiological parameters, resistance to poisons and performance of learning tasks in rats. J Nutr. 1989;119:1880–92.

    CAS  PubMed  Google Scholar 

  22. Yehuda S et al. Essential fatty acids are mediators of brain biochemistry and cognitive functions. J Neurosci Res. 1999;56:565–70.

    Article  CAS  PubMed  Google Scholar 

  23. Wainwright PE. Dietary essential fatty acids and brain function: a developmental perspective on mechanisms. Proc Nutr Soc. 2002;61:61–9.

    Article  CAS  PubMed  Google Scholar 

  24. Chalon S. Omega-3 fatty acids and monoamine neurotransmission. Prostaglandins Leukot Essent Fatty Acids. 2006;75:259–69.

    Article  CAS  PubMed  Google Scholar 

  25. Stevens LJ et al. Essential fatty acid metabolism in boys with attention-deficit hyperactivity disorder. Am J Clin Nutr. 1995;62:761–8.

    CAS  PubMed  Google Scholar 

  26. Colquhoun I, Bunday S. A lack of essential fatty acids as a possible cause of hyperactivity in children. Med Hypotheses. 1981;7:673–9.

    Article  CAS  PubMed  Google Scholar 

  27. Mitchell EA et al. Clinical characteristics and serum essential fatty acid levels in hyperactive children. Clin Pediatr (Phila). 1987;26:406–11.

    Article  CAS  Google Scholar 

  28. Antalis CJ et al. Omega-3 fatty acid status in attention-deficit/hyperactivity disorder. Prostaglandins Leukot Essent Fatty Acids. 2006;75:299–308.

    Article  CAS  PubMed  Google Scholar 

  29. Richardson AJ. Omega-3 fatty acids in ADHD and related neurodevelopmental disorders. Int Rev Psychiatry. 2006;18:155–72.

    Article  PubMed  Google Scholar 

  30. Burgess JR et al. Long-chain polyunsaturated fatty acids in children with attention-deficit hyperactivity disorder. Am J Clin Nutr. 2002;71:237S–330.

    Google Scholar 

  31. Chen JR et al. Dietary patterns and blood fatty acid composition in children with attention-deficit hyperactivity disorder in Taiwan. J Nutr Biochem. 2004;15:467–72.

    Article  CAS  PubMed  Google Scholar 

  32. • Hawkey E, Nigg J. Omega-3 fatty acid and ADHD: blood level analysis and meta-analytic extension of supplementation trials. Clin Psychol Rev. 2014;34:496–505. The findings of this meta-analysis suggest that nutritional omega-3 PUFA supplements lead to modest improvements in ADHD symptoms.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Lange KW et al. Polyunsaturated fatty acids in the treatment of attention deficit hyperactivity disorder. Funct Foods Health Disease. 2014;4:245–53.

    CAS  Google Scholar 

  34. Widenhorn-Muller K et al. Effect of supplementation with long-chain omega-3 polyunsaturated fatty acids on behavior and cognition in children with attention deficit/hyperactivity disorder (ADHD): a randomized placebo-controlled intervention trial. Prostaglandins Leukot Essent Fatty Acids. 2014;91:49–60.

    Article  PubMed  Google Scholar 

  35. Matsudaira T et al. Biochemical and psychological effects of omega-3/6 supplements in male adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, clinical trial. J Child Adolesc Psychopharmacol. 2015;25:775–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bos DJ et al. Reduced symptoms of inattention after dietary omega-3 fatty acid supplementation in boys with and without attention deficit/hyperactivity disorder. Neuropsychopharmacology. 2015;40:2298–306.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. • Salehi B et al. Omega-3 and zinc supplementation as complementary therapies in children with attention-deficit/hyperactivity disorder. J Res Pharm Pract. 2016;5:22–6. This randomized, double-blind, 8-week clinical trial showed that zinc supplementation as add-on to the main treatment significantly improved the symptoms of the attention-deficit disorder subtype of ADHD. Omega-3 supplementation was superior to both zinc and placebo in the clinical improvement of ADHD.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Parletta N et al. Omega-3 and omega-6 polyunsaturated fatty acid levels and correlations with symptoms in children with attention deficit hyperactivity disorder. PLoS One. 2016;11:e0156432. doi:10.1371/journal.pone.0156432.

    Article  PubMed  PubMed Central  Google Scholar 

  39. • LaChance L et al. Omega-6 to omega-3 fatty acid ratio in patients with adhd: a meta-analysis. J Can Acad Child Adolesc Psychiatry. 2016;25:87–96. The meta-analysis assessed the relationship between ADHD symptoms and the blood omega-6/omega-3 ratio and suggests that an increase in this ratio might represent the underlying disturbance in EFA levels in ADHD.

    PubMed  PubMed Central  Google Scholar 

  40. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV. Washington, DC: American Psychiatric Publ; 1994.

    Google Scholar 

  41. Bloch MH, Qawasmi A. Omega-3 fatty acid supplementation for the treatment of children with attention-deficit/hyperactivity disorder symptomatology: systematic review and meta-analysis. J Am Acad Child Adolesc Psychiatry. 2011;50:991–1000.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Gillies D et al. Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Cochrane Database Syst Rev. 2012;7:CD007986.

    Google Scholar 

  43. Sonuga-Barke EJ et al. Nonpharmacological interventions for ADHD: systematic review and meta-analyses of randomized controlled trials of dietary and psychological treatments. Am J Psychiatry. 2013;170:275–89.

    Article  PubMed  Google Scholar 

  44. • Cooper RE et al. Omega-3 polyunsaturated fatty acid supplementation and cognition: a systematic review and meta-analysis. J Psychopharmacol. 2015;29:753–63. This meta-analysis of randomized controlled trials found that omega-3 PUFAs did not improve cognitive performance measures in typically developing children and ADHD and related disorders. Supplementation improved short-term memory in individuals with low omega-3 PUFA status.

    Article  CAS  PubMed  Google Scholar 

  45. • Puri BK, Martins JG. Which polyunsaturated fatty acids are active in children with attention-deficit hyperactivity disorder receiving PUFA supplementation? A fatty acid validated meta-regression analysis of randomized controlled trials. Prostaglandins Leukot Essent Fatty Acids. 2014;90:179–89. This meta-analysis of randomized clinical trials in ADHD provides modest evidence of PUFA effectiveness for inattention symptoms in ADHD.

    Article  CAS  PubMed  Google Scholar 

  46. Cooper RE et al. The effect of omega-3 polyunsaturated fatty acid supplementation on emotional dysregulation, oppositional behaviour and conduct problems in ADHD: a systematic review and meta-analysis. J Affect Disord. 2016;190:474–82.

    Article  CAS  PubMed  Google Scholar 

  47. Jensen PS et al. ADHD comorbidity findings from the MTA study: comparing comorbid subgroups. J Am Acad Child Adolesc Psychiatry. 2001;40:147–58.

    Article  CAS  PubMed  Google Scholar 

  48. Kodas E et al. Reversibility of n-3 fatty acid deficiency-induced changes in dopaminergic neurotransmission in rats: critical role of developmental stage. J Lipid Res. 2002;43:1209–19.

    CAS  PubMed  Google Scholar 

  49. Mahmoud MM et al. Zinc, ferritin, magnesium and copper in a group of Egyptian children with attention deficit hyperactivity disorder. Ital J Pediatr. 2011;29:37–60. doi:10.1186/1824-7288-37-60.

    Google Scholar 

  50. Villagomez A, Ramtekkar U. Iron, magnesium, vitamin D, and zinc deficiencies in children presenting with symptoms of attention-deficit/hyperactivity disorder. Children (Basel). 2014;1:261–79.

    Google Scholar 

  51. Takeda A. Zinc homeostasis and functions of zinc in the brain. BioMetals. 2001;14:343–51.

    Article  CAS  PubMed  Google Scholar 

  52. Bekaroglu M et al. Relationships between serum free fatty acids and zinc, and attention deficit hyperactivity disorder: a research note. J Child Psychol Psychiatry. 1996;37:225–7.

    Article  CAS  PubMed  Google Scholar 

  53. Golub MS et al. Activity and attention in zinc-deprived adolescent monkeys. Am J Clin Nutr. 1996;64:908–15.

    CAS  PubMed  Google Scholar 

  54. Toren P et al. Zinc deficiency in attention-deficit hyperactivity disorder. Biol Psychiatry. 1996;40:1308–10.

    Article  CAS  PubMed  Google Scholar 

  55. Scassellati C et al. Biomarkers and attention deficit/ hyperactivity disorder: a systematic review and meta-analyses. J Am Acad Child Adolesc Psychiatry. 2012;51:1003–19.

    Article  PubMed  Google Scholar 

  56. • Zhou F et al. Dietary, nutrient patterns and blood essential elements in Chinese children with ADHD. Nutrients. 2016. doi:10.3390/nu8060352. This study found a negative association of blood zinc levels with ADHD and showed that a fish-white meat dietary pattern and mineral-protein nutrient pattern may have beneficial effects on ADHD in Chinese children.

    Google Scholar 

  57. Bilici M et al. Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28:181–90. doi:10.1016/j.pnpbp.2003.09.034.

    Article  CAS  PubMed  Google Scholar 

  58. Akhondzadeh S et al. Zinc sulfate as an adjunct to methylphenidate for the treatment of attention deficit hyperactivity disorder in children: a double blind and randomized trial [ISRCTN64132371]. BMC Psychiatry. 2004;4:9.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Arnold LE et al. Zinc for attention-deficit/hyperactivity disorder: placebo-controlled double-blind pilot trial alone and combined with amphetamine. J Child Adolesc Psychopharmacol. 2011;21:1–19. doi:10.1089/cap.2010.0073.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Zamora J et al. Zinc in the therapy of the attention-deficit/hyperactivity disorder in children. A preliminary randomized controlled trial. Arch Latinoam Nutr. 2011;61:242–6.

    CAS  PubMed  Google Scholar 

  61. Burhans MS et al. Iron deficiency: differential effects on monoamine transporters. Nutr Neurosci. 2005;8:31–8.

    Article  CAS  PubMed  Google Scholar 

  62. Cortese S et al. Brain iron levels in attention-deficit/hyperactivity disorder: a pilot MRI study. World J Biol Psychiatry. 2012;13:223–31.

    Article  PubMed  Google Scholar 

  63. Romanos M et al. No cross-sectional and longitudinal association of ferritin and symptoms of attention-deficit-/hyperactivity disorder in a large population-based sample of children: results from the GINIplus and LISAplus studies. J Atten Defic Hyperact Disord. 2013;5:313–20. doi:10.1007/s12402-013-0108-8.

    Article  Google Scholar 

  64. • Bener A et al. Higher prevalence of iron deficiency as strong predictor of attention deficit hyperactivity disorder in children. Ann Med Health Sci Res. 2014;4:S291–7. The findings of this case-control study suggest that low serum iron, ferritin levels, and vitamin D deficiency may be associated with ADHD.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. • Percinel I et al. Iron deficiency parameters in children and adolescents with attention-deficit/hyperactivity disorder. Child Psychiatry Hum Dev. 2016;47:259–69. No significant differences between ADHD patients and healthy controls were observed in terms of iron deficiency parameters. Hyperactivity scores were negatively correlated with the serum ferritin level in the ADHD group.

    Article  PubMed  Google Scholar 

  66. Konofal E et al. Impact of restless legs syndrome and iron deficiency on attention-deficit/hyperactivity disorder in children. Sleep Med. 2007;8:711–5.

    Article  PubMed  Google Scholar 

  67. Adisetiyo V, Helpern JA. Brain iron: a promising noninvasive biomarker of attention-deficit/hyperactivity disorder that warrants further investigation. Biomark Med. 2015;9:403–6.

    Article  CAS  PubMed  Google Scholar 

  68. Cortese S et al. Iron and attention deficit/hyperactivity disorder: What is the empirical evidence so far? A systematic review of the literature. Expert Rev Neurother. 2012;12:1227–40.

    Article  CAS  PubMed  Google Scholar 

  69. Adisetiyo V et al. Multimodal MR imaging of brain iron in attention deficit hyperactivity disorder: a noninvasive biomarker that responds to psychostimulant treatment? Radiology. 2014;272:524–32.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Torimitsu K et al. Role of magnesium in nerve tissue. Clin Calcium. 2012;22:1197–203.

    CAS  PubMed  Google Scholar 

  71. Cardoso CC et al. Evidence for the involvement of the monoaminergic system in the antidepressant-like effect of magnesium. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33:235–42.

    Article  CAS  PubMed  Google Scholar 

  72. Curtis LT, Patel K. Nutritional and environmental approaches to preventing and treating autism and attention deficit hyperactivity disorder (ADHD): a review. J Altern Complement Med. 2008;14:79–85.

    Article  PubMed  Google Scholar 

  73. Archana E et al. Altered biochemical parameters in saliva of pediatric attention deficit hyperactivity disorder. Neurochem Res. 2012;37:330–4.

    Article  CAS  PubMed  Google Scholar 

  74. Starobrat-Hermelin B, Kozielec T. The effects of magnesium physiological supplementation on hyperactivity in children with attention deficit hyperactivity disorder (ADHD). Positive response to magnesium oral loading test. Magnes Res. 1997;10:149–56.

    CAS  PubMed  Google Scholar 

  75. Mousain-Bosc M et al. Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. I. Attention deficit hyperactivity disorders. Magnes Res. 2006;19:46–52.

    CAS  PubMed  Google Scholar 

  76. • El Baza F et al. Magnesium supplementation in children with attention deficit hyperactivity disorder. Egypt J Med Hum Genet. 2016;17:63–70. This study assessed the effects of magnesium supplementation as an add-on treatment in magnesium-deficient children with ADHD and found significantly reduced ADHD symptoms following an 8-week magnesium supplementation.

    Article  Google Scholar 

  77. Huss M et al. Supplementation of polyunsaturated fatty acids, magnesium and zinc in children seeking medical advice for attention-deficit/hyperactivity problems—an observational cohort study. Lipids Health Dis. 2010;9:105.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Ghanizadeh A. A systematic review of magnesium therapy for treating attention deficit hyperactivity disorder. Arch Iran Med. 2013;16:412–7.

    PubMed  Google Scholar 

  79. Furman L. What is attention-deficit hyperactivity disorder (ADHD)? J Child Neurol. 2005;20:994–1002.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Klaus W. Lange.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Attention-Deficit Disorder

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lange, K.W., Hauser, J., Lange, K.M. et al. The Role of Nutritional Supplements in the Treatment of ADHD: What the Evidence Says. Curr Psychiatry Rep 19, 8 (2017). https://doi.org/10.1007/s11920-017-0762-1

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11920-017-0762-1

Keywords

Navigation