Treatment of Mood Lability and
Explosive Rage with Minerals and Vitamins:
Two Case Studies in Children
 

Journal of Child and Adolescent Psychopharmacology
Volume 12, Number 3, 2002

Read the abstract on the National Library of Medicine website or read the editorial review of the actual Journal article below.

Summary of Journal Article

The theory linking mood disorder and vitamin deficiency is not by any means new. In fact, as early as 1928, clinicians noted positive results in patients treated with essential trace minerals. In the years since, subsequent studies have reinforced and supported the belief that dietary nutrients, specifically minerals such as calcium, zinc, iron, magnesium, selenium and chromium, hold sway over mood disorders.

Calcium has been found to influence mood; zinc is known to play a role in brain function and development and its deficiency may play a role in the expression of psychiatric conditions such as unipolar depression in adults and attention deficit hyperactivity disorder in children. Aggressive behaviour in prison inmates has also been tied to zinc deficiency.

These findings are noted by Dr. Bonnie Kaplan, Alberta Children's Hospital in Calgary , Alberta , Canada , in the preface to her abstract published in the Journal of Child and Adolescent Pschopharmacology in 2002 detailing findings from a study she and three colleagues conducted on Empowerplus.

Kaplan's preface also noted:

• A 60-day, randomized, double-blind, placebo-controlled study of 120 women found increased dosages of thiamine improved cognitive function and reaction time.
• Another randomized, double-blind, placebo-controlled study in 50 adults showed significant relation between selenium intake and improved mood.
• Improved behaviour was noted in 14 boys with ADHD when their iron intake was increased.
• Improved response to stimulant medication was noted in 18 boys with ADHD whose zinc level, was raised.

In her own study, Kaplan noted most of this research focused on the effects of a single nutrient rather than on a broad spectrum of elements. One year-long controlled study, however, found that a high daily dose of multivitamins in 129 healthy young volunteers found better mood in those receiving the treatment. Improved task performance and physical growth were similarly reported in a broad-spectrum study of 740 children in China .

In a test in 2000, subjects were found to exhibit significant improvement on all psychometric measures of stress compared to a control group, while another study indicated a multi-vitamin and mineral supplement significantly lowered anxiety and perceived stress.

“In general, the strategy of studying several nutrients together is unusual, especially given the standard scientific approach of examining the effects of one pharmacologic agent at a time,” wrote Kaplan.

But Kaplan and her team were intent on studying the effects of a multi-nutritional supplement derived from studies by David Hardy and Anthony Stephan in their work with the forerunner of Empowerplus in swine and, later, two of Stephan's children. Her findings were immediate.

“In an unselected case series of 14 adults with bipolar disorder, the micronutrient supplement resulted in clinically and statistically significant improvements as measured by the Hamilton Depression Scale, the Brief Psychiatric Rating Scale and the Young Mania Rating Scale,” wrote Kaplan. “In addition, the need for psychotropic medication decreased by more than 50 per cent.”

Two particular cases intrigued Kaplan's team: two boys, aged eight and 12, part of a larger number of children referred to the study by pediatricians and child psychiatrists in the Calgary area. “The fact this experimental intervention consisted of dietary nutrients appealed to families who felt uncomfortable using psychiatric medication or had previously experienced adverse medication effects,” she noted.

The children selected had to be at least eight years old, physically healthy, comfortable swallowing large capsules and to exhibit mood lability, irritability, uncontrolled temper outbursts or aggression. The Conjoint Health Research Ethics Board of the University of Calgary 's Faculty of Medicine gave its approval for the project.

The Empowerplus supplement, consisting of 36 ingredients was administered to the two children in doses of 32 capsules daily. Kaplan notes the individual ingredients, 33 of which are natural dietary minerals and vitamins, are all below the known toxicity levels. A previous study had already revealed normal heart rates, blood pressure and blood samples in Empowerplus subjects, and no evidence was shown of weight loss, muscle weakness, nausea, vomiting or anorexia.

In the case of the eight-year-old, tantrum behaviour had been a problem for two years. Although he had been a normal, affectionate child until four, by now he had been exhibiting significant angry outbursts at least twice a day for the previous year. His obsessions were severe and pervasive, including a preoccupation with weapons. He exhibited depressive withdrawal, irritability, anxiety, hyperactivity and hypertalkativeness.

His rage had begun to include aggression toward family and friends. “His family reported living in fear of his potential for violence,” wrote Kaplan. “He recognized his obsessions were not normal and he wished to be free of them.” He was started on the full Empowerplus dosage of 32 capsules taken in eight capsules four times a day.

“By Day 15, the family reported a reduction in the frequency and especially the duration of rage attacks,” said Kaplan. “He was noted to have a generally calmer mood.”

The boy suffered a relapse in treatment two weeks later which his parents believed was linked to a decision to move him to a school specializing in behavioural problems.

But by the end of Week 9, his parents observed a decrease in obsessions and, three weeks later, he and his parents noted his tantrums, moods and obsessive symptoms had all improved to some extent. By the end of Week 16, his mother described him as “wonderful.” He explained he could go all day without thinking about guns.

After several weeks, his parents made a decision to take him off the supplement, but continued monitoring the boy's behaviour.

“At the end of six weeks of the discontinuation phase, the parents reported a significant clinical regression,” wrote Kaplan. “The boy was described as obstinate, argumentative, loud, provocative and constantly talking about guns. He was non-compliant at home and easily lost his temper.”

Again, the boy began taking Empowerplus. Two weeks later, his parents reported improvement in mood, temper and obsessions. About 40 days after restarting the supplements, he was reported using self-talk anger management. Anger recovery time had dropped to five minutes from half an hour. Even the boy commented: “The pills slow my brain down so I can think before I decide to punch the guy's lights out.”

“By Week 18, the school psychologist reported that behaviour and attention had both improved sufficiently that he was ready to be reintegrated back to a regular school,” wrote Kaplan. “One year later, he was successfully proceeding with his education in a regular classroom. There were no behavioural or attentional difficulties reported.”

A second termination of the supplement produced similar negative results and the parents quickly reinstated it. Now 11, the boy reports he no longer “flips out”, has more friends and is enjoying life. “ After 26 months of treatment, the child continues to do well on a maintenance dose that is 25 per cent of his initial full dose,” says Kaplan.

The second child had been diagnosed at two with autism and at four with pervasive development disorder. He exhibited severe ADHD, learning problems, an irritable temperment and explosive outbursts. These symptoms increased significantly with the onset of puberty. Although he exhibited no suicidal tendencies, he showed an intense focus on a narrow range of interests and an obsession with “germs.” He was negative, pessimistic, and worried about possible negative experiences in school the next day. But his explosive temper was the main concern.

He had been monitored all his life by the medical community and his mother was a psychologist with an interest in children with special needs. Although he had taken dextroamphetamine for 16 months prior to the Empowerplus trial to help him focus on school, his parents saw no change in his mood and irritability. At the time of his referral, his school situation had been deteriorating for months and his parents were searching for alternatives. He was described by teachers as loud, angry, disruptive, rude and unable to control his anger.

He was started on the full Empowerplus dosage. “After three weeks, the parents reported that both mood and behaviour were much improved, noting that his temper outbursts ceased much more quickly,” noted Kaplan. “His parents described a marked lifting of his general mood.

As with the first child, a marked regression was noted when he was taken off the supplement. The family noted every event, no matter how small, triggered an emotional reaction, and he returned to worrying about school and relationships. He was put back on the supplement and after six weeks showed marked improvement. “At follow-up, the child has been doing well emotionally after 32 months,” writes Kaplan.

The supplement was insufficient to treat his inattention; he has returned to taking 15 mg of dextroamphetamine to help him focus in school. “On the combination. . . he has been doing well in school both academically and socially,” notes Kaplan. “His parents report he works hard, studies conscientiously, copes with stresses comfortably and is able to quickly resolve his feelings when conflicts arise. He continues to experience no adverse affects.”

“Both children. . . showed clinically significant improvements while taking a nutritional supplement of minerals and vitamins,” says Kaplan. “In the first case, psychiatric medications were no longer needed. In the second case, a psychostimulant remained helpful for treating inattention.

“The clinical effectiveness of the nutrients was confirmed by treatment withdrawal and reinstatement, with routine outcome measures supporting changes in mood and behaviour.

“In both cases, (it was demonstrated) that mood lability increased when the supplement was removed and was ameliorated when it was reintroduced, thereby strengthening the evidence for the role of the supplement in the observed mood stabilization. For both boys, the supplementation resulted in fewer emotional outbursts, better temper control and more positive mood.”

Other findings by Kaplan's team showed, in both cases:

• a decrease in the duration of temper outbursts, followed by a decrease in frequency.
• a drop in obsessional thinking.
• mood stabilization
• no adverse effects from the supplement.

Kaplan agrees open-label trials like hers are open to observer bias. Double-blind trials were not possible and the allocation of treatment order was not random. The boys' parents served as observers and knew when their children were taking the supplements.

“However, the changes observed in moth children were maintained for more than two years, which ought to be sufficient time for a positive expectancy bias to habituate.”

She notes the improvements associated with the nutrient supplement were clinically significant, though not evidence of complete normalization of brain function. The younger boy still has significant deficit of social skills, while the older child suffers from Asperger's syndrome, learning problems and attentional symptoms requiring independent treatment. “Perhaps it should be emphasized that the results do not shed any meaningful light on whether this supplement has potential therapeutic benefit for ADHD.”

She also notes some patients have shown minimal adverse effects from the supplement, less likely to occur if it is taken with food and if the dose is increased slowly. Ongoing trials are collecting data on other health concerns to ensure the complete safety of the formula. Also, the size and number of capsules required daily is an obstacle for some children. That is being addressed with the development of a powdered version.

“This research joins the few studies that have demonstrated psychological effects following treatment with a complex nutrient formulation that includes vitamins and minerals. One question that emerges when evaluating research that employs a complex formula is: Which of the many ingredients are relevant?”

“Perhaps the most important unanswered question relates to mechanism: How can ordinary dietary minerals and vitamins have such a large impact on mental function?

In one sense the large impact. . . is exquisitely logical. . . it seems reasonable to speculate that a broader intervention might indeed have a larger effect.