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Role of dietary supplementation in attention-deficit hyperactivity disorder

  • Priya Rajyaguru (a1) and Miriam Cooper (a1)

Dietary constituents have been increasingly researched as both potential aetiological factors and interventions for attention-deficit hyperactivity disorder (ADHD) symptoms. Although the involvement of dietary factors in ADHD is biologically plausible, the literature to date does not indicate causality and there are no grounds yet for the routine recommendation of dietary manipulation in ADHD.

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Corresponding author
Miriam Cooper, Child & Adolescent Psychiatry Section, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, 4th Floor, Main Building, Heath Park, Cardiff CF14 4XN, UK. Email:
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1 National Institute for Health and Clinical Excellence. Attention Deficit Hyperactivity Disorder: Diagnosis and Management of ADHD in Children, Young People and Adults. NICE Clinical Guideline 72. NICE, 2008.
2 Black, MM. Micronutrient deficiencies and cognitive functioning. J Nutr 2003; 133 (suppl 2): 3927–31S.
3 White, JW Wolraich, M. Effect of sugar on behavior and mental performance. Am J Clin Nutr 1995; 62 (suppl 1): 242–7S.
4 Sinn, N. Nutritional and dietary influences on attention deficit hyperactivity disorder. Nutr Rev 2008; 66: 558–68.
5 Pelsser, L Frankena, K Toorman, J Savelkoul, H Dubais, A Pereira, RR et al Effects of a restricted elimination diet on the behaviour of children with attention-deficit hyperactivity disorder (INCA study): a randomised controlled trial. Lancet 2011; 377: 494503.
6 Konofal, E Lecendreux, M Deron, J Marchand, M Cortese, S Zaïm, M et al Effects of iron supplementation on attention deficit hyperactivity disorder in children. Pediatr Neurol 2008; 38: 20–6.
7 Bilici, M Yildirim, F Kandil, S Bekaroğlu, M Yildirmiş, S Deĝner, O 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.
8 Johnson, M Ostlund, S Fransson, G Kadesjö, B Gillberg, C Omega-3/omega-6 fatty acids for attention deficit hyperactivity disorder: a randomized placebo-controlled trial in children and adolescents. J Atten Disord 2009; 12: 394401.
9 Huss, M Völp, A Strauss-Grabo, M 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.
10 Thapar, A Cooper, M Eyre, E Langley, K Practitioner review: what have we learnt about the causes of ADHD? J Child Psychol Psychiatry 2013; 54: 316.
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The British Journal of Psychiatry
  • ISSN: 0007-1250
  • EISSN: 1472-1465
  • URL: /core/journals/the-british-journal-of-psychiatry
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Role of dietary supplementation in attention-deficit hyperactivity disorder

  • Priya Rajyaguru (a1) and Miriam Cooper (a1)
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Response to Rucklidge et al

Miriam Cooper, Clinical lecturer
01 July 2013

We write in response to the letter of Rucklidge et al. We thank the authors for their comments but would contest the view that our editorial actively promotes the premise that a single nutrient could consistently ameliorate ADHD symptoms. We have summarised the literature to date and highlight that the single nutrient literature is complicated by methodological heterogeneity and inadequately rigorous study designs, making overall interpretation difficult. But before dismissing the potential contribution of single agents in isolation it should be borne inmind that such methodological factors, as well as a potential genuine lackof effect, may also go some way to explaining why single nutrient approaches have not yielded notable benefits.

ADHD is a complex, multifactorial disorder and we agree with the authors that serum levels may not reflect the complex metabolic requirements of the brain. Indeed we emphasise in our article that it is unclear whether serum levels considered most favourable for general healthwould be optimal for improving brain function in ADHD, and that it needs to be further understood how we would determine such levels. However, caution should be exercised in dismissing the importance of serum levels, as this lack of clarity, and the interlinked action between nutrients thatthe authors highlight whereby supplementing with one alone may lead to decreases in another, make it even more important to measure a range of serum levels when investigating supplements in the absence of baseline levels below standard reference ranges. Whatever the optimal levels of nutrients are for brain functioning in ADHD, 'flooding the system with high doses of nutrients' has the potential to confer risk to physical health. Potentially serious adverse outcomes of nutrient excess are documented (1,2) and although nutritional interventions can be perceived as safer than stimulants we should first ensure we are doing no harm. There is no conclusive evidence to date that suboptimal nutrition is an aetiological factor in mental illness in general, however dietary factors are biologically plausible agents and as such the field would certainly benefit from carefully designed trials, be that of single nutrients or of nutrient complexes.

1. Rutkowski M, Grzegorczyk K. Adverse effects of antioxidative vitamins. Int J Occup Med Environ Health 2012; 25: 105-21.

2. Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ,Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005; 142: 37-46.

Declaration of interest: None.

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Conflict of interest: None declared

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Single bullet madness - why do we continue to perpetuate this fallacy?

Julia J. Rucklidge, Clinical Psychologist
06 June 2013

We write in response to the editorial on dietary supplementation for the treatment of ADHD. While Rajyaguru and Cooper adequately reviewed someof the literature, they missed an opportunity to challenge current methodologies and they simultaneously perpetuated an outdated model of disease pathophysiology.

These authors promote the idea that one single nutrient can effect a consistent change in ADHD symptoms. However, such magic bullet thinking isat odds with human physiology (which requires the ingestion of many nutrients in balance) and largely explains why the single nutrient strategy has yielded only modest benefits (1). Supplementing with broad spectrum formulations ensures the patient's safety as the combination prevents imbalances, such as one nutrient causing a deficiency in another (e.g., taking zinc alone may cause copper deficiency). Recommending that researchers first understand how one nutrient functions on its own, in isolation, ignores the inevitable changes and potential for harm occurringin other nutrient levels.

In the authors' brief review of nutrients as part of a complex formula, they failed to highlight that this multi-ingredient method has the potential to be more beneficial for treating mental health symptoms than any one nutrient (2). The concept underlying the use of micronutrients for the amelioration of mental health symptoms is that mental illness may be a manifestation of suboptimal nutrition, relative togenetically-determined needs for optimal brain metabolic activity (3). Neurotransmitters go through many metabolic steps to ensure synthesis, uptake, and breakdown. Each step requires enzymes, and every enzyme is dependent upon multiple co-enzymes (cofactors). A variety of vitamins and minerals are required as cofactors in most, if not all, of those steps. Some people may inherit an in-born error of metabolism that results in less than optimal use of nutrients that are present (3). Flooding the system with high doses of nutrients ensures the body receives what it requires for optimal brain functioning.

We also challenge the article's focus on serum nutrient levels, as they often fail to identity individual nutrient requirements unless a frank nutritional deficiency is present. Serum levels are simply too crudeto provide a complete picture of the metabolic needs of the brain. How accurately can peripheral metabolites and biomarkers predict change in a complex, multifactorial disorder such as ADHD and reflect what might be going on at a subcellular level in a metabolically active brain (4)? To date, no single biomarker for ADHD has achieved clinical utility as a diagnostic tool or a predictor of treatment outcome (5). We aren't convinced a single biological marker exists.

The one-disease, one-nutrient solution to mental disorders is outdated, and needs to be replaced by a model that is responsive to the broad spectrum of human nutritional needs. Perhaps the perpetuation of single-nutrient studies continues because this methodology fits comfortably within the pharmaceutical paradigm and traditional scientific methodology where drugs are typically single ingredient and independent variables are manipulated one at a time. However, shifting psychiatric research towards a consideration of multi-ingredient formulations requiresrethinking the scientific paradigm that has thus far shaped this field.

1.Rucklidge JJ, Johnstone J, Kaplan BJ. Nutrient supplementation approaches in the treatment of ADHD. Expert Rev Neurother 2009; 9(4): 461-76.

2.Rucklidge JJ, Kaplan BJ. Broad-spectrum micronutrient formulas forthe treatment of psychiatric symptoms: a systematic review. Expert Rev Neurother 2013; 13(1): 49-73.

3.Ames BN, Elson-Schwab I, Silver E. High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased Km): relevance to genetic disease and polymorphisms. Am J Clin Nutr 2002; 75: 616-58.4.Benton D. To establish the parameters of optimal nutrition do we need to consider psychological in addition to physiological parameters? Mol Nutr Food Res 2013; 57(1): 6-19.

5.Scassellati C, Bonvicini C, Faraone SV, Gennarelli M. Biomarkers and attention-deficit/hyperactivity disorder: A systematic review and meta-analyses. J Am Acad Child Adolesc Psychiatry 2012; 51(10): 1003-19.

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