Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric disorder with increasing global prevalence and high heritability commonly diagnosed in childhood. Current pharmaceutical treatment options provide a poor long-term risk: benefit ratio. Nutrition has significant effects on neurological functioning, and increasing evidence exists to support the use of multinutrients as alternative treatment for ADHD. The goal of this study is to assess the efficacy and tolerability of a multinutrient supplement as an alternative treatment for ADHD and co-occurring mood dysregulation symptoms.
The Multinutrients in ADHD Youth study is a fully-funded, multi-site, randomized double-blinded clinical trial for adolescents ages 6–12 years (n = 135). The study is 16 weeks in total, with an 8-week randomized controlled trial (RCT) followed by an 8-week open label (OL) phase. During the RCT phase, participants are assigned to either the treatment or placebo group at a 3:2 ratio. Study outcomes of ADHD symptoms include child's inattention, hyperactivity and mood dysregulation, which are assessed using validated questionnaires. Outcome data for the OL phase of the study were analyzed using end of RCT phase as baseline given that the RCT component of the study is still blinded.
Preliminary findings based on the OL phase compared ADHD symptoms following 8 weeks of open label supplementation (n = 27 families). A significant decrease in symptom count was found for inattention (P ≤ 0.001), hyperactivity (P ≤ 0.001), ODD (P ≤ 0.001) and DMDD (P ≤ 0.001).
This study is the first adequately powered RCT in North America to investigate the effects of multinutrients supplements on ADHD symptoms among children. Preliminary findings indicate a trend in the improvements of ADHD symptoms of inattention, hyperactivity, ODD and DMDD in the OL phase of the study.
Foundation for the Center of Excellence in Mental Health, Canada; The Ohio State University Department of Human Sciences, College of Education and Human Ecology; The Ohio State University Wexner Medical Center, Clinical Research Center.
Multinutrients for ADHD Youth (MADDY) Trial: Preliminary Trends for Treatment
Madeline Stern, Leanna Perez, Jeanette Johnstone, Barbara Gracious, Brenda Leung, Eugene Arnold, Gabriella Tost, Irene Hatsu. Current Developments in Nutrition, Volume 3, Issue Supplement 1, June 2019, https://doi.org/10.1093/cdn/nzz050.P16-028-19
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.
Objective: This article presents 1-year follow-up of a randomized placebo-controlled trial with open-label extension evaluating the efficacy of a broad-spectrum micronutrient (vitamins and minerals) intervention. The object was to determine if dominant treatment at follow-up was associated with differential psychological outcomes.
Methods: Ninety percent of the original sample of 93 children with attention-deficit/hyperactivity disorder (ADHD) were followed 52 weeks postbaseline. Assessments included measures of ADHD, mood, anxiety, and general function based on parent/clinician report. Outcome was considered based on dominant therapy at 52 weeks (trial micronutrients [n = 19], medications [n = 21], and no treatment [n = 35]). Nine children were not categorized due to inconsistent therapies.
Results: Based on dominant treatment, more of those who stayed on trial micronutrients (84%) were identified as “Much” or “Very Much” improved overall relative to baseline functioning, compared to 50% of those who switched to psychiatric medications and only 21% of those who discontinued treatment [χ2(2) = 19.476, p < 0.001]. Fifteen (79%) of those still taking micronutrients, 8 (42%) of those using medications, and 7 (23%) of those who discontinued treatment were considered remitters based on parent-reported ADHD [χ2(2) = 15.3, p < 0.001]. Those who stayed on micronutrients were more likely to have failed medication treatment in the past. The micronutrient group also displayed better outcomes on measures of parent-rated hyperactivity and anxiety, and clinician-rated general function and mood, with moderate to large between-group effect sizes (micronutrients vs. medication: ES = 0.73–1.01; micronutrients vs. no treatment: ES = 0.54–1.01). Most common reasons for stopping trial micronutrients were cost and number of pills to swallow. No continued side effects were associated with micronutrients.
Conclusions: Children who benefitted from micronutrients in the short term maintained changes at follow-up, without side effects. While both those who continued micronutrients and those who switched to medication showed improved ADHD symptoms, psychiatric medication use was associated with deterioration in mood and anxiety. Inherent selection bias limits generalizability.
Mineral-Vitamin Treatment Associated with Remission in Attention-Deficit/Hyperactivity Disorder Symptoms and Related Problems: 1-Year Naturalistic Outcomes of a 10-Week Randomized Placebo-Controlled Trial
Kathryn A. Darling, Matthew J.F. Eggleston, Hannah Retallick-Brown, and Julia J. Rucklidge. Journal of Child and Adolescent Psychopharmacology 25 Jul 2019 doi.org/10.1089/cap.2019.0036
It has been widely hypothesized that both diet and the microbiome play a role in the regulation of attention-deficit/hyperactivity disorder (ADHD) behaviour. However, there has been very limited scientific investigation into the potential biological connection. We performed a 10-week pilot study investigating the effects of a broad spectrum micronutrient administration on faecal microbiome content, using 16S rRNA gene sequencing.
The study consisted of 17 children (seven in the placebo and ten in the treatment group) between the ages of seven and 12 years, who were diagnosed with ADHD. We found that micronutrient treatment did not drive large-scale changes in composition or structure of the microbiome.
However, observed OTUs significantly increased in the treatment group, and showed no mean change in the placebo group. The differential abundance and relative frequency of Actinobacteria significantly decreased post- micronutrient treatment, and this was largely attributed to species from the genus Bifidobacterium. This was compensated by an increase in the relative frequency of species from the genus Collinsella.
Further research is required to establish the role that Bifidobacterium contribute towards neuropsychiatric disorders; however, these findings suggest that micronutrient administration could be used as a safe, therapeutic method to modulate Bifidobacterium abundance, which could have potential implications for modulating and regulating ADHD behaviour.
Our pilot study provides an initial observation into this area of research, and highlights an interesting avenue for further investigation in a larger cohort. Furthermore, these novel results provide a basis for future research on the biological connection between ADHD, diet and the microbiome.
Human gut microbiome changes during a 10 week Randomised Control Trial for micronutrient supplementation in children with attention deficit hyperactivity disorder
Aaron J. Stevens, Rachel V. Purcell, Kathryn A. Darling, Matthew J. F. Eggleston, Martin A. Kennedy & Julia J. Rucklidge. Scientific Reportsvolume 9, Article number: 10128, 2019
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]
Many smokers do not achieve abstinence using current smoking cessation options. This randomized controlled trial (RCT) investigated a novel nutritional supplement to assist with quitting smoking.
Following a baseline phase where cigarettes per day and nicotine dependence were measured, participants (n = 107) were randomized to placebo (n = 50) or micronutrient conditions (n = 57). A 4-week pre-quit phase permitted titration up to 12 capsules/day. During the quit phase (12 weeks), participants were registered with a public Quitline while consuming micronutrients or placebo. Carbon monoxide levels were measured to confirm smoking cessation.
Forty-five (42%) participants completed the trial. Treatment and placebo groups did not differ on the primary outcome of continuous abstinence at 12 weeks using intention-to-treat analysis; however, 28% of the micronutrient-treated group had quit versus 18% for placebo (odds ratio [OR] = 1.78, 95% confidence interval [CI] = 0.71 to 4.48), with number needed to treat = 10. Comparison of cigarette consumption (cigarettes per day) between micronutrient and placebo groups showed that those taking micronutrients reported reduced consumption throughout the trial, notably at pre-quit weeks 1 and 4, and at quit phase week 4. There were no serious adverse events, blinding was successful, and there were no substantive group differences in side effects or dropout rate.
This is the first RCT investigating the impact of micronutrients on smoking reduction, finding that micronutrients reduced harm through reduction in number of cigarettes smoked relative to placebo. The small sample and high dropout rate limit confidence in the conclusions and generalizability of the study; however, assessed by number needed to treat, micronutrients are comparable to other smoking cessation treatments but with fewer side effects. Future research using larger and longer trials including cost-effectiveness and biomarker measures is encouraged.
Micronutrients are being increasingly studied for the treatment of psychiatric conditions, but direct application of micronutrients as a treatment for addictions is novel. There is extensive evidence that micronutrients alleviate stress. Given that tobacco smoking is often used to cope with stress, taking micronutrients may moderate the stress of withdrawal and increase the chance of a successful quit attempt. This study is the first known RCT to investigate the use of micronutrients to support smoking cessation. Treatments that are safe, effective, relatively inexpensive, and readily available are needed and micronutrient supplements offer one such possible alternative.
Novel Mineral–Vitamin Treatment for Reduction in Cigarette Smoking: A Fully Blinded Randomized Placebo-Controlled Trial
Phillipa K Reihana, Neville M Blampied, Julia J Rucklidge, Nicotine & Tobacco Research, , nty168
Objectives: There is an increasing body of literature documenting the efficacy of micronutrients (vitamins and minerals) interventions for the treatment of psychiatric problems in the short term; however, long-term safety is largely unexplored. The goal of this observational study was to investigate the safety of two commercially available broad-spectrum micronutrient formulas (EMPowerplus and Daily Essential Nutrients) given at doses above the Recommended Dietary Allowances for the long-term treatment of individuals with psychiatric symptoms.
Design:Participants on long-term treatment with micronutrients (medication-free) for psychiatric problems (attention-deficit hyperactivity disorder [ADHD, n = 21], anxiety/depression [n = 13]) were identified from ongoing research studies and the community through purchasing records. Seventeen children and 17 adults had blood tests to assess their full blood count, coagulation profile, liver and kidney function, fasting glucose, iron studies, key nutrients, and prolactin. Questionnaires assessed psychological/psychiatric functioning. Seventeen of the participants had completed the same measures pretreatment.
Results: The average length of consuming micronutrients was 2.66 years (standard deviation = 2.86). Excluding B12 (which was elevated for almost all participants), 94.6% of all blood test results were within the test reference ranges. One participant was diagnosed with hemochromatosis based on iron studies. No other clinically relevant adverse changes in blood results were identified pre- and post-treatment. No clinically significant adverse effects were reported. Post-treatment psychometrics identified that 85% of the participants were in nonclinical ranges for measures of ADHD, depression, anxiety, and stress.
Conclusions: We report preliminary evidence for the safety of long-term commercially available micronutrients, although questions remain. Overall, the substantial psychiatric benefits observed appear to outweigh the minimal observed risks in these participants. Screening for potential medical problems is recommended before initiating treatment. Long-term pharmacovigilance monitoring is required to ascertain any rare but significant adverse events.
An Observational Preliminary Study on the Safety of Long-Term Consumption of Micronutrients for the Treatment of Psychiatric Symptoms
Julia J. Rucklidge, PhD, Matthew J. F. Eggleston, MD, Breanne Ealam, BA (Hons), Ben Beaglehole, MD, and Roger T. Mulder, MD. J Altern Complement Med. 2019 Jun;25(6):613-622. doi: 10.1089/acm.2018.0352. Epub 2019 May 13.
Shaken but unstirred? Effects of micronutrients on stress and trauma after an earthquake: RCT evidence comparing formulas and doses.
Rucklidge JJ, Andridge R, Gorman B, Blampied N, Gordon H, Boggis A. Human Psychopharmacology. 2012 Sep;27(5):440-54.
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.
Database analysis of adults with bipolar disorder consuming a micronutrient formula.
Gately D, Kaplan BJ. Clinical Medicine Insights: Psychiatry. 2009 Apr;4:3-16.
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.
Micronutrients versus standard medication management in autism: a naturalistic case-control study.
Mehl-Madrona L, Leung B, Kennedy C, Paul S, Kaplan BJ. Journal of Child and Adolescent Psychopharmacology. 2010 Apr;20(2):95-103.
Do vitamins or minerals (apart from lithium) have mood-stabilizing effects?
Popper CW. The Journal of Clinical Psychiatry. 2001 Dec;62(12):933-5.
Nutritional approach to bipolar disorder.
Simmons M. The Journal of Clinical Psychiatry. 2003 Mar;64(3):338; author reply 338-9.
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.
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.
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.
Systematic review of safety and tolerability of a complex micronutrient formula used in mental health.
Simpson JS, Crawford SG, Goldstein ET, Field C, Burgess E, Kaplan BJ. BioMed Central Psychiatry. 2011 Apr 18;11:62.
Factors influencing frontal cortex development and recovery from early frontal injury.
Halliwell C, Comeau W, Gibb R, Frost DO, Kolb B. Developmental Neurorehabilitation. 2009;12(5):269-78.
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.
Successful treatment of OCD with a micronutrient formula following partial response to Cognitive Behavioral Therapy (CBT): a case study.
Rucklidge JJ. Journal of Anxiety Disorders. 2009 Aug;23(6):836-40.
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.
Multinutrient supplement as treatment: literature review and case report of a 12-year-old boy with bipolar disorder.
Frazier EA, Fristad MA, Arnold LE. Journal of Child and Adolescent Psychopharmacology. 2009 Aug;19(4):453-60.
Efficacy and cost of micronutrient treatment of childhood psychosis.
Rodway M, Vance A, Watters A, Lee H, Bos E, Kaplan BJ. BMJ Case Reports. 2012 Nov 9;2012.
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.
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.
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.
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.
After devastating flooding in southern Alberta in June 2013, we attempted to replicate a New Zealand randomised trial that showed that micronutrient (minerals, vitamins) consumption after the earthquakes of 2010-11 resulted in improved mental health. Residents of southern Alberta were invited to participate in a study on the potential benefit of nutrient supplements following a natural disaster. Fifty-six adults aged 23-66 were randomised to receive a single nutrient (vitamin D, n=17), a few-nutrients formula (B-Complex, n=21), or a broad-spectrum mineral/vitamin formula (BSMV, n=18). Self-reported changes in depression, anxiety and stress were monitored for six weeks. Although all groups showed substantial decreases on all measures, those consuming the B-Complex and the BSMV formulas showed significantly greater improvement in stress and anxiety compared with those consuming the single nutrient, with large effect sizes (Cohen's d range 0.76-1.08). There were no group differences between those consuming the B-Complex and BSMV. The use of nutrient formulas with multiple minerals and/or vitamins to minimise stress associated with natural disasters is now supported by three studies. Further research should be carried out to evaluate the potential population benefit that might accrue if such formulas were distributed as a post-disaster public health measure.
A randomised trial of nutrient supplements to minimise psychological stress after a natural disaster
Kaplan BJ, Rucklidge JJ, Romijn AR, Dolph M. Psychiatry Res. 2015 Aug 30;228(3):373-9.
Following the devastating New Zealand earthquake of February 22, 2011, Dr. Rucklidge et al. conducted a 4 week randomized trial in which anxiety and stress were significantly reduced in adults given various doses of micronutrients when compared to untreated individuals. One year later Dr. Rucklidge followed up with the study participants to evaluate long-term outcomes.
Of the original 91 participants who took micronutrients in the original trial, 64 (70.3%) completed the follow-up questionnaires, as did 21 (72.4%) of the original control group. Both groups improved over their post-earthquake baseline scores, and the risk of PTSD declined drastically for both groups. However, the nutrient-treated group reported significantly lower stress and greater improvements in mood and energy than the control group one year later, even after adjusting for baseline differences (p<0.001).
Those who stayed on micronutrients through to follow-up or who stopped all treatment reported better psychological functioning than those who switched to other treatments, including medications (p<0.023). The researchers concluded that, while disaster survivors improve psychologically over time regardless of whether or not they receive an intervention, taking micronutrients during the acute phase immediately following a disaster might result in significantly better short and long-term outcomes.
Psychological functioning 1 year after a brief intervention using micronutrients to treat stress and anxiety related to the 2011 Christchurch earthquakes: a naturalistic follow-up
Rucklidge JJ, Blampied N, Gorman B, Gordon HA, Sole E. Hum Psychopharmacol. 2014 May;29(3):230-43. doi: 10.1002/hup.2392. Epub 2014 Feb 19. PubMed PMID: 24554519.
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.
Researchers collected safety, tolerability, and serum micronutrient concentration data s and their correlations with mood changes from an 8-week pilot feasibility study of a broad spectrum micronutrient formula.
Adverse effects were mild and transient, and chiefly initial insomnia or GI upset. No differences occurred in BMI (p = 0.310) or waist-hip ratio (WHR; p = 0.674) pre- to post-supplementation.
In this open prospective study, short-term use of the micronutrient formula in children with BPSD appeared safe and well-tolerated, with a side effect profile preferable to first-line psychotropic drugs for pediatric bipolar spectrum disorders. A double-blind, randomized clinical trial is feasible, appears safe, and is warranted by open-label clinical outcomes and plausible mechanisms of action combined with documentation of increased serum concentrations of specific micronutrients.
Nutritional and Safety Outcomes from an Open-Label Micronutrient Intervention for Pediatric Bipolar Spectrum Disorders
Frazier EA, Gracious B, Arnold LE, Failla M, Chitchumroonchokchai C, Habash D, Fristad MA. J Child Adolesc Psychopharmacol. 2013 Oct;23(8):558-67. doi: 10.1089/cap.2012.0098.
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.
Insomnia is a debilitating condition causing psychological distress and frequently comorbid with other mental health conditions. This study examined the effect of 8 weeks of treatment by broad spectrum micronutrients (Hardy Nutritionals® Daily Self Defense™) on insomnia using a multiple-baseline-across-participants open-label trial design. Seventeen adults were randomized to 1-, 2-, or 3-week baseline periods (14 completed). Self-report measures were the Consensus Sleep Diary–Morning (CSD-M), the Pittsburgh Insomnia Rating Scale (PIRS), and the Depression, Anxiety, Stress Scale (DASS). Baselines were generally stable. Treatment completers reported reliable and clinically significant change in insomnia severity (PIRS), in depression, stress, and anxiety (DASS), and on at least two aspects of sleep measured by the CDS-M. All completers were treatment-compliant, and side effects were minimal. Nutritional supplementation is shown to be a novel, beneficial treatment for insomnia in adults. Follow-up research using placebo-controlled designs as well as comparisons to cognitive-behavioral and other treatments is recommended.
Effect of Micronutrients on Insomnia in Adults: A Multiple-Baseline Study
Joanna Lothian, Neville M. Blampied, Julia J. Rucklidge. Clinical Psychological Science. May 23, 2016.doi:10.1177/2167702616631740
Vitamin-Mineral Treatment of ADHD in Adults: A 1-Year Naturalistic Follow-Up of a Randomized Controlled Trial
Rucklidge JJ, Frampton CM, Gorman B, Boggis A. J Atten Disord. 2014.
Emotional dyscontrol following traumatic brain injury (TBI) impairs social relationships and employability. Micronutrients (minerals, vitamins) stabilize emotional lability in psychiatric patients, and various individual nutrients have been used to treat experimental brain injury in laboratory animals in the acute phase. However, the current case report appears to be the first documentation of micronutrients resulting in normalization of emotion regulation in a long-standing brain injury in a human.
Case presentation: A broad-spectrum formula of micronutrients was evaluated in a 35-year-old male who had incurred a severe TBI eight years previously. Resolution of most post-TBI symptoms was achieved during those eight years, but not his episodic loss of emotional control, which psychiatrists evaluated as being permanent. The trial of micronutrients began after five weeks of baseline symptom monitoring with a mood stability scale. By three months mood stability had improved markedly according to data submitted by two raters (the patient and his clinician) who were blind to each other’s evaluations. Data collection continued for one year, showing significant improvement (p<.0001), at which time the patient reported that his emotional control had returned to his pre-TBI level. The improvements led to his establishing his own business and improving his family relationships.
Micronutrient treatment resulted in resolution of this patient’s longstanding post-TBI emotional dyscontrol. Broad-spectrum micronutrient formulas are showing benefit for the treatment of mood lability in various types of psychiatric patients; this report indicates there is also potential value in using them for the emotional dyscontrol found in post-TBI patients.
Micronutrient Treatment of Emotional Dyscontrol Following Traumatic Brain Injury
Kaplan, B. J., Leaney, C., Tsatsko, E. Annals of Psychiatry and Mental Health. 29 August 2016.
Background: Healthcare costs are skyrocketing, with mental health treatment amongst the most expensive, especially when hospitalization is involved. According to the Mental Health Commission of Canada, one in five Canadians is living with a mental disorder in any given year, at an annual cost of $50 billion. In light of this societal burden, alternative approaches are being evaluated, such as brief psychotherapy by phone, peer support, and, as part of the emerging field of nutritional mental health, treatment with micronutrients (minerals and vitamins). Effectiveness of micronutrients has been demonstrated for many types of psychiatric symptoms, in about 45 studies of formulas that are either multinutrient (e.g., several B vitamins) or broad-spectrum (usually over 20 minerals and vitamins). Although this literature demonstrates therapeutic benefits, the potential economic impact of micronutrient treatment has been evaluated in only one case study of childhood psychosis.
Methods: The current case study was initiated to evaluate mental health-related hospitalization costs from 1997 to 2003 for a female adult diagnosed with various mood and psychotic symptoms. She was treated for the first 5 years with conventional methods and then subsequently with a broad-spectrum micronutrient formula.Results: The patient’s annual mental health hospitalization costs during conventional treatment averaged $59,864 across 5 years (1997–2001), with a peak annual cost of about $140,000. Since transitioning to broad-spectrum micronutrients, she has incurred no provincial hospitalization costs for mental health care, though her self-funded costs are currently $720/year for the micronutrients.
Conclusion: Further exploration of the treatment of mental health problems with broad-spectrum micronutrient formulas has the potential to make two significant contributions: improved mental health, and decreased costs for governments.
Hospitalization cost of conventional psychiatric care compared to broad‑spectrum micronutrient treatment: literature review and case study of adult psychosis
Kaplan BJ, Isaranuwatchai W, Hoch JS. Int J Ment Health Syst. 2017 Jan 31;11:14.