Skip to main content Accessibility help

Vitamin–mineral treatment of attention-deficit hyperactivity disorder in adults: double-blind randomised placebo-controlled trial

  • Julia J. Rucklidge (a1), Chris M. Frampton (a2), Brigette Gorman (a1) and Anna Boggis (a3)



The role of nutrition in the treatment of attention-deficit hyperactivity disorder (ADHD) is gaining international attention; however, treatments have generally focused only on diet restriction or supplementing with one nutrient at a time.


To investigate the efficacy and safety of a broad-based micronutrient formula consisting mainly of vitamins and minerals, without omega fatty acids, in the treatment of ADHD in adults.


This double-blind randomised controlled trial assigned 80 adults with ADHD in a 1:1 ratio to either micronutrients (n = 42) or placebo (n = 38) for 8 weeks (trial registered with the Australian New Zealand Clinical Trials Registry: ACTRN12609000308291).


Intent-to-treat analyses showed significant between-group differences favouring active treatment on self- and observer- but not clinician-ADHD rating scales. However, clinicians rated those receiving micronutrients as more improved than those on placebo both globally and on ADHD symptoms. Post hoc analyses showed that for those with moderate/severe depression at baseline, there was a greater change in mood favouring active treatment over placebo. There were no group differences in adverse events.


This study provides preliminary evidence of efficacy for micronutrients in the treatment of ADHD symptoms in adults, with a reassuring safety profile.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Vitamin–mineral treatment of attention-deficit hyperactivity disorder in adults: double-blind randomised placebo-controlled trial
      Available formats

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Vitamin–mineral treatment of attention-deficit hyperactivity disorder in adults: double-blind randomised placebo-controlled trial
      Available formats

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Vitamin–mineral treatment of attention-deficit hyperactivity disorder in adults: double-blind randomised placebo-controlled trial
      Available formats


Corresponding author

Julia Rucklidge, Department of Psychology, University of Canterbury, Private Bag 4800, Christchurch 8140, New Zealand. Email:


Hide All

Declaration of interest




Hide All
1 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (4th edn, text revision) (DSM-IV-TR). APA, 2000.
2 Kessler, RC Adler, L Barkley, R Biederman, J Conners, CK Demler, O, et al. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry 2006; 163: 716–23.
3 Molina, BSG Hinshaw, SP Swanson, JM Arnold, LE Vitiello, B Jensen, PS, et al. The MTA at 8 years: prospective follow-up of children treated for combined-type ADHD in a multisite study. J Am Acad Child Adolesc Psychiatry 2009; 48: 484500.
4 Klein, RG Mannuzza, S Olazagasti, MA Roizen, E Hutchison, JA Lashau, EC, et al. Clinical and functional outcome of childhood attention-deficit/hyperactivity disorder 33 years later. Arch Gen Psychiatry 2012; 69: 1295–303.
5 Torgersen, T Gjervan, B Rasmussen, K Treatment of adult ADHD: is current knowledge useful for clinicians? J Neuropsychiatric Dis Treat 2008; 4: 177–86.
6 Baumgaertel, A. Alternative and controversial treatments for attention-deficit/hyperactivity disorder. Pediatr Clin North Am 1999; 46: 977–92.
7 Nigg, JT. Where to with treatment for ADHD? Curr Med Res Opin 2011; 27 (suppl 2): 13.
8 Mattes, JA Gittelman, R. Effects of artificial food colorings in children with hyperactive symptoms: a critical review and results of a controlled study. Arch Gen Psychiatry 1981; 38: 714–8.
9 Arnold, LE Christopher, J Huestis, RD Smeltzer, DJ Megavitamins for minimal brain dysfunction: a placebo-controlled study. JAMA 1978; 240: 2642–3.
10 Nigg, JT Lewis, K Edinger, T Falk, M Meta-analysis of attention-deficit/hyperactivity disorder or attention-deficit/hyperactivity disorder symptoms, restriction diet, and synthetic food color additives. J Am Acad Child Adolesc Psychiatry 2012; 51: 8697.e8.
11 Howard, AL Robinson, M Smith, GJ Ambrosini, GL Piek, JP, Oddy, WH ADHD is associated with a ‘Western’ dietary pattern in adolescents. J Atten Disord 2011; 15: 403–11.
12 Pelsser, LM Frankena, K Toorman, J Savelkoul, HF Dubois, AE 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.
13 Arnold, LE Lofthouse, N Hurt, E Artificial food colors and attention-deficit/hyperactivity symptoms: conclusions to dye for. Neurotherapeutics 2012; 9: 599609.
14 Milte, CM Parletta, N Buckley, JD Coates, AM Young, RM, Howe, PRC Eicosapentaenoic and docosahexaenoic acids, cognition, and behavior in children with attention-deficit/hyperactivity disorder: a randomized controlled trial. Nutrition 2012; 28: 670–7.
15 Galler, JR Bryce, CP Zichlin, ML Fitzmaurice, G Eaglesfield, GD, Waber, DP Infant malnutrition is associated with persisting attention deficits in middle adulthood. J Nutr 2012; 142: 788–94.
16 Rucklidge, JJ Johnstone, J Kaplan, BJ Nutrient supplementation approaches in the treatment of ADHD. Expert Rev Neurother 2009; 9: 461–76.
17 Gately, D Kaplan, BJ. Database analysis of adults with bipolar disorder consuming a multinutrient formula. Clin Med Psychiatry 2009; 4: 316.
18 Kennedy, DO Veasey, R Watson, A Dodd, F Jones, E Maggini, S, et al. Effects of high-dose B vitamin complex with vitamin C and minerals on subjective mood and performance in healthy males. Psychopharmacology (Berl) 2010; 211: 5568.
19 Adams, J Audhya, T McDonough-Means, S Rubin, R Quig, D Geis, E et al. Effect of a vitamin/mineral supplement on children and adults with autism. BMC Pediatr 2011; 11: 111.
20 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.
21 Kaplan, BJ Crawford, SG Field, CJ Simpson, JS Vitamins, minerals, and mood. Psychol Bull 2007; 133: 747–60.
22 Gardner, A Boles, RG. Is a “Mitochondrial Psychiatry” in the future? A review. Cur Psychiatry Rev 2005; 1: 255–71.
23 Jackson, J Eaton, W Cascella, N Fasano, A, Kelly, D Neurologic and psychiatric manifestations of Celiac disease and gluten sensitivity. Psychiatr Q 2012; 83: 91102.
24 Bilici, M Yildirim, F Kandil, S Bekaroglu, M Yildirmis, S Deger, 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.
25 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.
26 Arnold, LE Disilvestro, RA Bozzolo, D Bozzolo, H Crowl, L Fernandez, S, 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: 119.
27 Katz, M Adar Levine, A Kol-Degani, H Kav-Venaki, L A compound herbal preparation (CHP) in the treatment of children with ADHD: a randomized controlled trial. J Atten Disord 2010; 14: 281–91.
28 Patel, K Curtis, LT. Comprehensive approach to treating autism and attention-deficit hyperactivity disorder: a prepilot study. J Altern Complement Med 2007; 13: 1091–7.
29 Kaplan, BJ Fisher, JE Crawford, SG Field, CJ, Kolb, B Improved mood and behavior during treatment with a mineral-vitamin supplement: an open-label case series of children. J Child Adolesc Psychopharmacol 2004; 14: 115–22.
30 Rucklidge, JJ Taylor, M Whitehead, K Effect of micronutrients on behavior and mood in adults with ADHD: evidence from an 8-week open label trial with natural extension. J Atten Disord 2011; 15: 7991.
31 Rucklidge, JJ Gately, D Kaplan, BJ Database analysis of children and adolescents with bipolar disorder consuming a multinutrient formula. BMC Psychiatry 2010; 10: 74.
32 Rucklidge, JJ Harrison, R. Successful treatment of bipolar disorder II and ADHD with a micronutrient formula: a case study. CNS Spectrums 2010; 15: 289–95.
33 Harding, KL Judah, RD Gant, C Outcome-based comparison of Ritalin versus food-supplement treated children with AD/HD. Altern Med Rev 2003; 8: 319–30.
34 Simpson, JSA Crawford, SG Goldstein, ET Field, C Burgess, E, Kaplan, BJ Systematic review of safety and tolerability of a complex micronutrient formula used in mental health. BMC Psychiatry 2011; 11: 62.
35 Rucklidge, JJ Kaplan, BJ. Broad spectrum micronutrient formulas for the treatment of psychiatric symptoms: a systematic review. Expert Rev Neurother 2013; 13: 4973.
36 Epstein, J Johnson, D Conners, C Conners' Adult ADHD Diagnostic Interview for DSM-IV (CAADID): Technical Manual. MHS, 2002.
37 Kaufman, J Birmaher, B Brent, D Rao, U Flynn, C Moreci, P, et al. Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry 1997; 36: 980–7.
38 Conners, CK Erhardt, D Sparrow, MA Conners' Adult ADHD Rating Scales (CAARS). Arch Clin Neuropsychol 2003; 18: 431–7.
39 Conners, CK. Conners' Rating Scales – Revised: Technical Manual. Multi-Health Systems, 1997.
40 First, MB Spitzer, RL Gibbon, M Williams, JBW Structured Clinical Interview for DSM–IV–TR Axis I Disorders: Research Version, Patient Edition (SCID–I/P). Biometrics Research Department, New York State Psychiatric Institute, 2002.
41 Guy, W. ECDEU Assessment Manual for Psychopharmacology. Revised DHEW Pub. (ADM). National Institute for Mental Health, 1976.
42 Montgomery, SA Åsberg, M A new depression scale designed to be sensitive to change. Br J Psychiatry 1979; 134: 382–9.
43 Conners, CK Erhardt, D Sparrow, E Conners Adult ADHD Rating Scales (CAARS). Technical Manual. Multi-Health Systems, 1999.
44 Leon, AC Solomon, DA Mueller, TI Endicott, J Posternak, M Judd, LL, et al. A brief assessment of psychosocial functioning of subjects with bipolar I disorder: the LIFE-RIFT. Longitudinal Interval Follow-up Evaluation-Range Impaired Functioning Tool. J Nerv Ment Dis 2000; 188: 805–12.
45 Baker, CW Little, TD Brownell, KD Predicting adolescent eating and activity behaviors. The role of social norms and personal agency. Health Psychol 2003; 22: 189–98.
46 Alexander, LB Luborsky, L. The Penn Helping Alliance Scales. In The Psychotherapeutic Process: A Research Handbook (eds Greenberg, LS Pinsof, WM): 325–66. Guilford Press 1986.
47 Wilens, TE Haight, BR Horrigan, JP Hudziak, JJ Rosenthal, NE Connor, DF, et al. Bupropion XL in adults with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled study. Biol Psychiatry 2005; 57: 793801.
48 Wechsler, D. Manual for the WAIS-III. Psychological Corporation, 1997.
49 Davis, P McLeod, K Ransom, M, Ongley, P The New Zealand Socioeconomic Index of Occupational Status (NZSEI). Statistics New Zealand, 1997.
50 Wilkinson, GS. WRAT3 Administration Manual. Wide Range, 1993.
51 Snaith, RP Harrop, FM Newby, DA Teale, C Grade scores of the Montgomery–Åsberg Depression and the Clinical Anxiety Scales. Br J Psychiatry 1986; 148: 599601.
52 Koesters, M Becker, T Kilian, R Fegert, JM, Weinmann, S Limits of meta-analysis: Methylphenidate in the treatment of adult attention-deficit hyperactivity disorder. J Psychopharmacol (Oxf) 2009; 23: 733–44.
53 Popper, CW. Do vitamins or minerals (apart from lithium) have mood-stabilising effects? J Clin Psychiatry 2001; 62: 933–5.
54 Kaplan, BJ Simpson, JSA Ferre, RC Gorman, CP McMullen, DM, Crawford, SG Effective mood stabilization with a chelated mineral supplement: an open-label trial in bipolar disorder. J Clin Psychiatry 2001; 62: 936–44.
55 Mehl-Madrona, L Leung, B Kennedy, C Paul, S, Kaplan, BJ A naturalistic case-control study of micronutrients versus standard medication management in autism. J Child Adolesc Psychopharmacol 2010; 20: 95103.
56 Frazier, EA Fristad, MA Arnold, LE Feasibility of a nutritional supplement as treatment for pediatric bipolar spectrum disorders. J Altern Complement Med 2012; 18: 678–85.
57 Rucklidge, JJ Andridge, R Gorman, B Blampied, N Gordon, H, Boggis, A Shaken but unstirred? Effects of micronutrients on stress and trauma after an earthquake: RCT evidence comparing formulas and doses. Hum Psychopharmacol Clin Exp 2012; 27: 440–54.
58 Perlis, RH Ostacher, M Fava, M Nierenberg, AA Sachs, GS, Rosenbaum, JF Assuring that double-blind is blind. Am J Psychiatry 2010; 167: 250–2.
59 Harris, E Kirk, J Rowsell, R Vitetta, L Sali, A Scholey, AB, et al. The effect of multivitamin supplementation on mood and stress in healthy older men. Hum Psychopharmacol 2011; 26: 560–7.
60 Gosney, MA Hammond, MF Shenkin, A Allsup, S Effect of micronutrient supplementation on mood in nursing home residents. Gerontology 2008; 54: 292–9.
61 Ardagh, MW Richardson, SK Robinson, V Than, M Gee, P Henderson, S, et al. The initial health-system response to the earthquake in Christchurch, New Zealand, in February, 2011. Lancet 2012; 379: 2109–15.
62 Helton, WS Head, J. Earthquakes on the mind. Hum Factors 2012; 54: 189–94.
63 Mertz, W. A balanced approach to nutrition for health: the need for biologically essential minerals and vitamins. J Am Diet Assoc 1994; 94: 1259–62.
64 Rucklidge, JJ Johnstone, J Kaplan, BJ Single bullet madness – why do we continue to perpetuate this fallacy? Br J Psychiatry 2013; 203: 154–5.
65 Head, KA Kelly, GS. Nutrients and botanicals for treatment of stress: adrenal fatigue, neurotransmitter imbalance, anxiety, and restless sleep. Altern Med Rev 2009; 14: 114–40.
66 Maguire, GA. Prolactin elevation with antipsychotic medications: mechanisms of action and clinical consequences. J Clin Psychiatry 2002; 63 (suppl 4): 5662.
67 Shaw, I Rucklidge, JJ Hughes, RN A possible biological mechanism for the B Vitamins altering behaviour in ADHD. Pharm Med 2010; 24: 16.
68 Oner, O Oner, P Bozkurt, OH Odabas, E Keser, N Karadag, H, et al. Effects of zinc and ferritin levels on parent and teacher reported symptom scores in attention deficit hyperactivity disorder. Child Psychiatry Hum Dev 2010; 41: 441–7.
69 Australian Government. Nutrient Reference Values for Australia and New Zealand: Including Recommended Dietary Intakes. National Health and Medical Research Council, 2006.
70 Huskisson, E Maggini, S Ruf, M The influence of micronutrients on cognitive function and performance. J Int Med Res 2007; 35: 119.
71 Wilkins, CH Sheline, YI Roe, CM Birge, SJ, Morris, JC Vitamin D deficiency is associated with low mood and worse cognitive performance in older adults. Am J Geriatr Psychiatry 2006; 14: 1032–40.
72 Taylor, MJ Carney, SM Goodwin, GM Geddes, JR Folate for depressive disorders: systematic review and meta-analysis of randomized controlled trials. J Psychopharmacol 2004; 18: 251–6.
73 Bottiglieri, T Laundy, M Crellin, R Toone, BK Carney, MWP, Reynolds, EH Homocysteine, folate, methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry 2000; 69: 228–32.
74 Sobanski, E Bruggemann, D Alm, B Kern, S Deschner, M Schubert, T, et al. Psychiatric comorbidity and functional impairment in a clinically referred sample of adults with attention-deficit/hyperactivity disorder (ADHD). Eur Arch Psychiatry Clin Neurosci 2007; 257: 371–7.
75 Amiri, S Farhang, S Ghoreishizadeh, MA Malek, A, Mohammadzadeh, S Double-blind controlled trial of venlafaxine for treatment of adults with attention deficit/hyperactivity disorder. Hum Psychopharmacol Clin Exp 2012; 27: 7681.
76 Spencer, T Biederman, J Wilens, T Faraone, S Prince, J Gerard, K, et al. Efficacy of a mixed amphetamine salts compound in adults with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 2001; 58: 775–82.
77 Emilsson, B Gudjonsson, G Sigurdsson, JF Baldursson, G Einarsson, E Olafsdottir, H, et al. Cognitive behaviour therapy in medication-treated adults with ADHD and persistent symptoms: a randomized controlled trial. BMC Psychiatry 2011; 11; 116.
78 Sonuga-Barke, EJ Brandeis, D Cortese, S Daley, D Ferrin, M Holtmann, M, 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.
79 Gesch, CB Hammond, SM Hampson, SE Eves, A, Crowder, MJ Influence of supplementary vitamins, minerals and essential fatty acids on the antisocial behaviour of young adult prisoners. Randomised, placebo-controlled trial. Br J Psychiatry 2002; 181: 22–8.
80 Whitaker, R. The case against antipsychotic drugs: a 50-year record of doing more harm than good. Med Hypotheses 2004; 62: 513.
81 Fava, GA. Long-term treatment with antidepressant drugs: the spectacular achievements of propaganda. Psychother Psychosom 2002; 71: 127–32.
82 Offidani, E Fava, GA Tomba, E Baldessarini, RJ Excessive mood elevation and behavioral activation with antidepressant treatment of juvenile depressive and anxiety disorders: a systematic review. Psychother Psychosom 2013; 82: 132–41.
83 Advokat, C. What are the cognitive effects of stimulant medications? Emphasis on adults with attention-deficit/hyperactivity disorder (ADHD). Neurosci Biobehav Rev 2010; 34: 1256–66.
84 Kleinman, A. Rebalancing academic psychiatry: why it needs to happen – and soon. Br J Psychiatry 2012; 201: 421–2.

Related content

Powered by UNSILO
Type Description Title
Supplementary materials

Rucklidge et al. supplementary material
Supplementary Table S1-S2

 PDF (33 KB)
33 KB

Vitamin–mineral treatment of attention-deficit hyperactivity disorder in adults: double-blind randomised placebo-controlled trial

  • Julia J. Rucklidge (a1), Chris M. Frampton (a2), Brigette Gorman (a1) and Anna Boggis (a3)


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.