Evaluation of broad-spectrum micronutrient (vitamins and minerals) treatment for childhood ADHD has been limited to open-label studies that highlight beneficial effects across many aspects of psychological functioning.
This is the first fully blinded randomized controlled trial of medication-free children (n = 93) with ADHD (7-12 years) assigned to either micronutrients (n = 47) or placebo (n = 46) in a 1:1 ratio, for 10 weeks. All children received standardized ADHD assessments. Data were collected from clinicians, parents, participants and teachers across a range of measures assessing ADHD symptoms, general functioning and impairment, mood, aggression and emotional regulation.
Intent-to-treat analyses showed significant between-group differences favouring micronutrient treatment on the Clinical Global Impression-Improvement (ES = 0.46), with 47% of those on micronutrients identified as 'much' to 'very much' improved versus 28% on placebo. No group differences were identified on clinician, parent and teacher ratings of overall ADHD symptoms (ES ranged 0.03-0.17). However, according to clinicians, 32% of those on micronutrients versus 9% of those on placebo showed a clinically meaningful improvement on inattentive (OR = 4.9; 95% CI: 1.5-16.3), but no group differences on improvement in hyperactive-impulsive symptoms (OR = 1.0; 95% CI: 0.4-2.5). Based on clinician, parent and teacher report, those on micronutrients showed greater improvements in emotional regulation, aggression and general functioning compared to placebo (ES ranged 0.35-0.66). There were two dropouts per group, no group differences in adverse events and no serious adverse events identified. Blinding was successful with guessing no better than chance.
Micronutrients improved overall function, reduced impairment and improved inattention, emotional regulation and aggression, but not hyperactive/impulsive symptoms, in this sample of children with ADHD. Although direct benefit for core ADHD symptoms was modest, with mixed findings across raters, the low rate of adverse effects and the benefits reported across multiple areas of functioning indicate micronutrients may be a favourable option for some children, particularly those with both ADHD and emotional dysregulation. Trial registered with the Australian New Zealand Clinical Trials Registry ACTRN12613000896774.
Vitamin-mineral treatment improves aggression and emotional regulation in children with ADHD: a fully blinded, randomized, placebo-controlled trial.
Rucklidge JJ, Eggleston MJF, Johnstone JM, Darling K, Frampton CM. J Child Psychol Psychiatry. 2017 Oct 2.
A micronutrient formulation co-developed† by Hardy Nutritionals® founder David Hardy, showed “statistically robust improvements” in the first-ever double-blind study to test the effectiveness and safety of a multivitamin-mineral treatment for adult ADHD. Researchers from the University of Canterbury and the University of Otago, New Zealand, randomized 80 adults diagnosed with ADHD to take either the micronutrient formulation or identical-looking placebo pills for 8 weeks. Most of the study participants had at least one psychiatric diagnosis in addition to ADHD. Additional diagnoses included multiple anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, reading disability, and alcohol/substance misuse or dependence. The nutrient group reported more than double the improvement in attention, hyperactivity, and impulsivity symptoms, compared with the placebo group. Clinical psychologists rated more than twice as many people in the nutrient group ‘very much’ or ‘much’ improved in overall symptoms. They also rated moderate and severely depressed participants in the nutrient group as having nearly double the improvement in depression symptoms. Researchers found that the micronutrients were completely safe; there were no differences in side effects between the two groups.
Vitamin–mineral treatment of attention-deficit hyperactivity disorder in adults: double-blind randomised placebo-controlled trial.
Rucklidge JJ, Frampton CMA, Gorman B, Boggis A. The British Journal of Psychiatry. 2014 Feb;204(2): doi: 10.1192/bjp.bp.113.132126 [Epub ahead of print]
A 7.1-magnitude earthquake in Christchurch, New Zealand created a natural experiment for measuring the protective effects of a micronutrient formulation co-developed† by Hardy Nutritionals® founder David Hardy on mood, anxiety and stress. Prior to the earthquake, researchers had assessed mood, anxiety and stress levels in a group of 33 adults diagnosed with attention deficit hyperactivity disorder, and they chose to repeat the same measures after the earthquake. Scores showed that the 16 participants taking micronutrients were more resilient to the effects of the earthquake than the 17 individuals not taking any supplement. This effect was particularly marked for depression scores.
Post-earthquake psychological functioning in adults with attention-deficit/hyperactivity disorder: positive effects of micronutrients on resilience.
Rucklidge JJ, Blampied, NM. New Zealand Journal of Psychology. 2011;40(4):51.
Scientists analyzed data from 120 children with pediatric bipolar disorder who were treated with a micronutrient formulation co-developed† by Hardy Nutritionals® founder David Hardy for at least 6 months. 24% of these children also had a diagnosis of attention deficit hyperactivity disorder (ADHD). Their results were compared with an additional 41 children who were diagnosed with ADHD alone. Children with a bipolar diagnosis showed a 59% decline in symptoms, whereas children with ADHD showed a 40% decrease in symptoms. The duration of symptom reduction suggests that benefits of micronutrient treatment were not attributable to placebo or expectancy effects. Of those taking psychiatric medications, more than half were able to completely discontinue them over a 6-month period. Medication use by the remainder of children was reduced by 74% during the same time period.
Database analysis of children and adolescents with bipolar disorder consuming a micronutrient formula.
Rucklidge JJ, Gately D, Kaplan BJ. BioMed Central Psychiatry. 2010 Sep 28;10:74.
Researchers documented the impact of a micronutrient formulation co-developed† by Hardy Nutritionals® founder David Hardy in the treatment of 14 medication-free adults with attention deficit hyperactivity disorder. The adults’ additional psychiatric diagnoses included major depressive disorder, bipolar disorder II, generalized anxiety disorder, social phobia, obsessive compulsive disorder, post-traumatic stress disorder, panic disorder with agoraphobia, and psychotic disorder not otherwise specified. During 8 weeks of micronutrient treatment, mood and hyperactivity/impulsivity symptoms normalized. Researchers also noted significant improvements on measures of anxiety, attention, stress, and quality of life. In follow-up, those who continued to take the micronutrients for 2-6 months experienced sustained or improved symptom relief.
Effect of micronutrients on behavior and mood in adults with ADHD: evidence from an 8-week open label trial with natural extension.
Rucklidge J, Taylor M, Whitehead K. Journal of Attention Disorders. 2011 Jan;15(1):79-91.
Researchers treated 11 adults diagnosed with various types of bipolar disorder for an average of 44 weeks with a micronutrient formulation co-developed† by Hardy Nutritionals® founder David Hardy. The adults’ additional diagnoses included attention deficit hyperactivity disorder, dysthymic disorder, and obsessive-compulsive disorder. The adults experienced a 55% reduction in depression symptoms, a 60% reduction in mania symptoms, and a 66% reduction in general psychiatric symptoms. Their psychiatric medication use decreased by more than 50%. The only reported side effect, nausea, was infrequent, minor, and transitory.
Effective mood stabilization with a chelated mineral supplement: an open-label trial in bipolar disorder.
Kaplan BJ, Simpson JS, Ferre RC, Gorman CP, McMullen DM, Crawford SG. The Journal of Clinical Psychiatry. 2001 Dec;62(12):936-44.
Researchers treated nine unselected children with mood and behavioral problems with a micronutrient formulation co-developed† by Hardy Nutritionals® founder David Hardy. The children’s psychiatric diagnoses included attention deficit hyperactivity disorder, bipolar disorder, depression, oppositional defiant disorder, obsessive-compulsive disorder, generalized anxiety disorder, Asperger syndrome, and Prader-Willi syndrome. After a minimum of 8 weeks of micronutrient treatment, the children’s behavior improved significantly in the following areas: anxious and depressed mood, thought problems, interpersonal relationship problems, attention problems, social problems, withdrawn behavior, disruptive behavior, delinquent behavior, aggressive behavior, and self-harm behavior.
Improved mood and behavior during treatment with a mineral-vitamin supplement: an open-label case series of children.
Kaplan BJ, Fisher JE, Crawford SG, Field CJ, Kolb B. Journal of Child and Adolescent Psychopharmacology. 2004 Spring;14(1):115-22.
Researchers documented the effects of a micronutrient formulation co-developed† by Hardy Nutritionals® founder David Hardy on psychiatric and neurocognitive functioning in a naturalistic off-on-off-on design. A 21-year old female with bipolar II disorder, attention deficit hyperactivity disorder (ADHD), social anxiety, and panic disorder began taking a vitamin-mineral formulation following a documented 8-year history of ongoing psychiatric symptoms that were not well managed by medications. After 8 weeks on the formula, she showed significant improvements in mood, anxiety, and hyperactivity/impulsivity. She then chose to come off the formula. After 8 weeks, her depression scores returned to pre-treatment levels, and anxiety and ADHD symptoms worsened dramatically. When the formula was reintroduced, all psychiatric symptoms showed gradual improvements. After one year, she was in remission of all mental illness diagnoses. Her neurocognitive changes mirrored behavioral changes, showing improved processing speed, variability in response, and verbal memory.
Successful treatment of bipolar disorder II and ADHD with a micronutrient formula: a case study.
Rucklidge JJ, Harrison R. CNS Spectrums. 2010 May;15(5):289-95.
Researchers describe two medication-free boys with unstable mood and explosive rage who took a micronutrient formulation co-developed† by Hardy Nutritionals® founder David Hardy followed by reversal and re-treatment. The boys’ diagnoses included pervasive developmental disorder with Asperger characteristics, attention deficit hyperactivity disorder, obsessive-compulsive disorder, and autism. Both boys benefited significantly from the micronutrient formula: mood, angry outbursts, delinquent behavior, social and attention problems, and anxious/obsessional symptoms improved when initially treated, returned when they discontinued treatment, and remitted when the micronutrient treatment was reintroduced. During a follow-up of over 2 years, both boys continued to be stable while taking the micronutrient treatment.
Treatment of mood lability and explosive rage with minerals and vitamins: two case studies in children.
Kaplan BJ, Crawford SG, Gardner B, Farrelly G. Journal of Child and Adolescent Psychopharmacology. 2002 Fall;12(3):205-19.
Researchers investigated the therapeutic effects of a micronutrient formulation co-developed† by Hardy Nutritionals® founder David Hardy in 7 children with bipolar disorder. The children’s additional psychiatric diagnoses included attention deficit hyperactivity disorder, oppositional defiant disorder, major depressive disorder, generalized anxiety disorder, conduct disorder, and obsessive-compulsive disorder. The children experienced a 37% decrease in depression scores and a 45% decrease in mania scores over 8 weeks. Side effects were minor and transient—mostly temporary gastric discomfort.
Feasibility of a nutritional supplement as treatment for pediatric bipolar spectrum disorders.
Frazier EA, Fristad MA, Arnold LE. Journal of Alternative and Complementary Medicine. 2012 Jul;18(7):678-85.
Researchers studied the impact of a micronutrient formulation co-developed† by Hardy Nutritionals® founder David Hardy on neurocognitive functioning in 14 adults with attention deficit hyperactivity disorder (ADHD) and severe mood dysregulation over an 8-week period. Significant improvement was observed in the ADHD-micronutrient group, but not the control group, across a range of verbal abilities, including verbal learning, verbal cognitive flexibility and fluency, and verbal inhibition. These neurocognitive improvements were large and consistent with improved psychiatric functioning.
Can micronutrients improve neurocognitive functioning in adults with ADHD and severe mood dysregulation? A pilot study.
Rucklidge JJ, Harrison R, Johnstone J. Journal of Alternative and Complementary Medicine. 2011 Dec;17(12):1125-31.
A 24-year-old woman who experienced dramatic improvement in her ADHD and depression symptoms for more than 2 years while taking a micronutrient formulation co-developed† by Hardy Nutritionals® founder David Hardy later experienced a recurrence of her former psychiatric symptoms as a result of a severe yeast infection. Her physical symptoms included an overall flu-like feeling; a chronic sore throat and runny nose; cravings for sugary and starchy foods; gastrointestinal cramps; and rashes and itching on her legs, groin, genital and rectal areas. Psychiatric symptoms included severe moodiness, inability to experience pleasure, and chronic irritability. These physical and psychiatric symptoms persisted for several months despite her ongoing use of a prescription antifungal cream. The woman began taking four capsules of olive leaf extract (identical to our Hardy Nutritionals™ Olive Leaf Extract) as well as two capsules of probiotics (identical to our Hardy Nutritionals™ Greens & Probiotics) daily to treat the yeast infection, in addition to her regular therapeutic dose of the micronutrients. After a week and a half, the woman’s physical and psychiatric symptoms both improved, including disappearance of her rashes, cessation of the chronic itching, elimination of her runny nose, and improved mood and energy levels. After 2 months, she had returned to her previous level of function. During a year of follow-up, researchers found that the woman continued to enjoy relief from the physical and psychiatric symptoms caused by the yeast infection as long as she continued to take the Olive Leaf Extract.
Could yeast infections impair recovery from mental illness? A case study using micronutrients and olive leaf extract for the treatment of ADHD and depression.
Rucklidge JJ. Advances in Mind-Body Medicine. 2013 Summer;27(3):14-8.
Scientists observed while conducting previous studies that many study participants whose psychiatric symptoms were treated successfully with a micronutrient formulation co-developed† by Hardy Nutritionals® founder David Hardy tended to reduce or eliminate use of alcohol, cigarettes and cannabis on their own. This study details one case in which on-off micronutrient use resulted in off-on cigarette and cannabis smoking as well as off-on psychiatric symptoms. Micronutrients provide the necessary precursors and cofactors for adequate neurotransmitter production and regulation. In this way, micronutrients assist with mood regulation, help reduce anxiety, and directly affect brain reward circuitry, all of which can help individuals to successfully stop drug use.
Use of micronutrients attenuates cannabis and nicotine abuse as evidenced from a reversal design: a case study.
Harrison R, Rucklidge JJ, Blampied N. Journal of Psychoactive Drugs. 2013 Jun;45(2):168-178.
Dr. Julia Rucklidge conducted nutrient assays on study participants in her 8 week double-blind RCT using micronutrient treatment for adult ADHD. Using this extensive data set, she performed a post-hoc analysis of the original study in an attempt to determine if blood levels of nutrients in adult ADHD patients could be used to predict whether or not they would respond to micronutrient treatment. The blood markers measured were Vitamin D, Vitamin B12, Folate, Iron, Zinc, Copper, and Ferritin.
With the exception of Vitamin d (27% of participants deficient), nutrient deficiencies were slight or non-existent for the majority of participants at the beginning of the trial. In spite of the fact that only one participant exhibited iron deficiency, low iron levels were associated with higher baseline depression scores (p=0.009). No other nutrient significantly correlated with baseline psychiatric scores.
Throughout the course of the trial, micronutrient treatment was associated with significant increases in blood Vitamin D, Vitamin B12, and Folate (all p<0.001), but only Vitamin D was also identified as one of the nutrient markers that showed a statistically significant effect on treatment response.
The nutrient markers affecting treatment response were: ferritin, vitamin D, and copper. Greater ferritin at baseline correlated with being an ADHD responder (p=0.027). (ADHD response was defined as ≥30% decrease in symptom scores for a comprehensive combination of outcome measures. Of the 64 original study participants with complete nutrient assays, 39 (60.9%) were identified as ADHD responders.) Lower baseline vitamin D was predictive of greater improvements in depression (p=0.011) and global functioning (p=0.045) scores, and lower baseline copper levels predicted greater response in the depression (p=0.002) and clinical global improvement (p=0.007) outcome measures.
From among the non-nutrient variables measured, the researchers identified developmental history as the only noticeable predictor of response. This means that people with a history of developmental risk factors (e.g., slow to talk, walk, read, toilet train) may benefit even more from micronutrient treatment than those who developed normally as a child. It is also worth noting that several participants who reported alcohol or drug use at baseline later reported a reduction or cessation of these behaviours during micronutrient treatment, suggesting the possible value of nutrients in addiction therapy.Only a few significant associations were identified between baseline biomarkers and outcomes, but, despite the difficulty in predicting the outcome for any given person, micronutrient treatment proved very effective – providing substantial ADHD symptom reduction for over half of the adults in this study.
Moderators of treatment response in adults with ADHD treated with a vitamin-mineral supplement
Rucklidge JJ, Johnstone J, Gorman B, Boggis A, Frampton CM. Prog Neuropsychopharmacol Biol Psychiatry. 2014 Apr 3;50:163-71. doi:10.1016/j.pnpbp.2013.12.014. Epub 2013 Dec 26. PubMed PMID: 24374068.
The role of good nutrition for resilience in the face of stress is a topic of interest, but difficult to study. A 7.1 earthquake took place in the midst of research on a micronutrient treatment for Attention-Deficit/Hyperactivity Disorder (ADHD), providing a unique opportunity to examine whether individuals with ADHD taking micronutrients demonstrated more emotional resilience post-earthquake than individuals with ADHD not taking micronutrients. Thirty-three adults with ADHD were assessed twice following the earthquake using a measure of depression, anxiety and stress also completed at some point pre-earthquake (baseline). Seventeen were not taking micronutrients at the time of the earthquake (control group), 16 were (micronutrient group). While there were no between-group differences one week post-quake (Time 1), at two weeks post-quake (Time 2), the micronutrient group reported significantly less anxiety and stress than the controls (effect size 0.69). These between group differences could not be explained by other variables, such as pre-earthquake measures of emotions, demographics, psychiatric status, and personal loss or damage following the earthquake. The results suggest micronutrients may increase resilience to ongoing stress and anxiety associated with a highly stressful event in individuals with ADHD and are consistent with controlled studies showing benefit of micronutrients for mental health.
Micronutrients reduce stress and anxiety following a 7.1 earthquake in adults with Attention-Deficit/Hyperactivity Disorder
Rucklidge JJ, Johnstone J, Harrison R, Boggis A. 2011. Psychiatry Research, 189:281-87.
In January 2014, The British Journal of Psychiatry published the results of a double-blind controlled trial which provided evidence of efficacy for micronutrients† (vitamins and minerals) in the treatment of ADHD symptoms in adults, with a reassuring safety profile.
As a follow-up to the adult trial, and pilot study for a RCT in childhood ADHD, the Journal of Child and Adolescent Psychopharmacology recently published the results of a study which treated 14 children with Attention-Deficit/Hyperactivity Disorder (ADHD) using micronutrients† instead of medication.
The study demonstrated the clinical benefit, feasibility, and safety of broad-spectrum micronutrients in the treatment of childhood ADHD.
In the recently published study, medication-free children were treated with a micronutrient formula† for eight weeks and then taken off it for four weeks—with the on-off cycle repeating itself over a six-month period.
Modified Brinley plots revealed a reduction in ADHD symptoms, improved mood, and improved overall functioning during intervention phases, and deterioration in ADHD symptoms, mood, and overall functioning during the withdrawal phases. Reliable change analyses, Cohen's d and percent superiority effect sizes, 95% confidence intervals and t tests confirmed clinically and statistically significant change between the intervention and withdrawal phases, with large effect sizes observed pre- to post-exposure of micronutrients (d = 1.2–2.2) on ADHD symptoms during intervention phases. Seventy-one percent of participants showed at least a 30% decrease in ADHD symptoms by the end of the second treatment phase, and 79% were identified as “much improved” or “very much improved” at the end of the second phase (5 months) based on the clinician-rated CGI when considering functioning generally. The SDQ showed that these benefits occurred across other areas of functioning including emotional symptoms, conduct problems, and prosocial behaviours. The children's self-reports confirmed the improvements. Excellent adherence to treatment occurred throughout, side effects were mild and transitory, and no safety issues were identified through blood analyses.The researchers said the results were so effective that some parents were reluctant to take their children off the micronutrients† for the full four weeks. They noted “When they came off the micronutrients†, some children’s symptoms returned within days, which was a good indication of their effectiveness.”
Clinically Significant Symptom Reduction in Children with Attention-Deficit/Hyperactivity Disorder Treated with Micronutrients: An Open-Label Reversal Design Study
Gordon HA, Rucklidge JJ, Blampied NM, Johnstone JM. J Child Adolesc Psychopharmacol. 2015 Dec;25(10):783-98. doi: 10.1089/cap.2015.0105. PubMed PMID: 26682999; PubMed Central PMCID: PMC4702182.
†The micronutrient formulation studied was a pre-2013 version of Truehope EMPowerplus which was co-formulated by David Hardy and Anthony Stephan. Truehope EMPowerplus is a registered trademark of The Synergy Group of Canada Inc., which was co-founded by David Hardy and Anthony Stephan in 1999. David Hardy officially resigned as a shareholder of The Synergy Group of Canada Inc. and director of Truehope Nutritional Support Ltd. in 2013 to focus his efforts exclusively on Hardy Nutritionals®.