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CASE REPORT Open Access
Micronutrient treatment for children with
emotional and behavioral dysregulation:
a case series
Bonnie J. Kaplan1*
, Paula Hilbert2
and Ekaterina Tsatsko3
Abstract
Introduction: In clinical studies of adults and children, broad-spectrum micronutrients (minerals and vitamins) have
proven beneficial for improving mood regulation and attention. We report here pilot work whose primary objective
was to evaluate the feasibility of studying micronutrient treatment in school-aged children with emotional and
behavioral problems. Issues examined included feasibility of participant recruitment from a culturally diverse
population, probability of sample retention for a 12-week trial, acceptability of the outcome measures, supplement
adherence, as well as trends in treatment benefit.
Case presentation: The families of two boys (ages 5 and 6) and one girl (age 14) were invited to participate in a
12-week pilot trial of micronutrients carried out during the summer months. All children were enrolled in the
private school at which future research was being considered. During the previous school year, all three had been
extremely difficult to educate due to their inability to pay attention and learn, as well as their behavior problems.
Although the two younger children had not been formally diagnosed, parents and teachers provided reports of
hyperactivity and inability to focus on education in the classroom. The oldest child was often aggressive, and had
been diagnosed with bipolar disorder, attention deficit hyperactivity disorder, and oppositional defiant disorder.
All three children were Hispanic and spoke both Spanish and English. For 12 weeks, after signing consent
forms, the children’s parents provided weekly ratings on the parent-report Child Mania Rating Scale; the
children consumed the micronutrient formula daily and provided a daily rating of how they felt. The parent
ratings revealed significantly improved behavior, p = .002. Children’s ratings approached the ideal level of 7,
indicating “happy”
self-reports. Parent interviews confirmed the weekly scores. Several feasibility questions were answered: all
three children completed the 12-week trial, all scores were completed by parents and children, adherence
to the protocol was excellent, and no adverse reactions emerged.
Conclusions: Family physicians and pediatricians are often confronted with the challenge of improving the
lives of families whose children experience school crises due to emotional and behavioral dysregulation. Three
children, who participated in pilot work to determine the feasibility of further investigations, experienced
impressive changes that clearly warrant both research and clinical exploration.
Keywords: Micronutrients, Treatment outcome, ADHD, Child behavior disorders
* Correspondence: Kaplan@ucalgary.ca
1
Faculty of Medicine, University of Calgary, The Child Development Centre,
3820 - 24 Avenue NW, Calgary, AB T3B 2X9, Canada
Full list of author information is available at the end of the article
JOURNAL OF MEDICAL
CASE REPORTS
© 2015 Kaplan et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Kaplan et al. Journal of Medical Case Reports (2015) 9:240
DOI 10.1186/s13256-015-0735-0
Introduction
Success in the classroom is a function of many variables,
not the least of which is children’s ability to regulate
emotions, attention and behavior. Even very intelligent
children who lack this self-regulation may struggle in
school, and may be faced with multiple disciplinary inci-
dents or even expulsion.
The Learning Curve Academy in north central Florida
is an independent school established in 2007. It is an in-
clusion school and serves typically developing children
as well as disabled children and children diagnosed with
learning and behavioral problems. Approximately 50
children are enrolled in grades kindergarten to grade 12
in this private school, and many of them receive special-
ized services. Some of the children have been diagnosed
with a behavioral/mental disorder, most frequently atten-
tion deficit hyperactivity disorder (ADHD) and bipolar
disorder. Most had previously failed in the public school
system, where assessments by social workers and
psychologists resulted in Individual Educational Plans
(IEPs). The tuition fees for all three children were heav-
ily subsidized by the state government because of the
severity of their learning and behavioral problems, or
because their families live at or below poverty level.
Although school staff members focus primarily on edu-
cation and fulfillment of IEP goals, the significant emo-
tional and behavioral problems in the classroom often
prevent successful achievement.
In the last 15 years, several studies have demonstrated
that nutrient supplementation for school-aged children
can improve their attention and emotional self-regulation,
as well as decrease behavioral problems and disciplinary
events. Schoenthaler showed that giving 40 schoolchildren
aged 6–12 years a broad spectrum of nutrients resulted in
47 % fewer antisocial acts requiring discipline than the
40 children who received a placebo [1]. Outside the
classroom, research by Harding and colleagues showed
improved self-regulation in children diagnosed with
ADHD or bipolar disorder who were treated with min-
erals and vitamins [2]. In fact, the improvements in
ADHD symptomatology in 20 children given a range of
dietary nutrients over a 4-week period were similar in
magnitude to the changes obtained from methylphenid-
ate. A randomized, placebo-controlled trial (RCT) by
Katz et al. evaluated children diagnosed with ADHD:
half received an herbal compound with essential nutri-
ents, including essential fatty acids, phospholipids, es-
sential amino acids, B vitamins, vitamins E and C, and
minerals, and half received a placebo [3]. Change over
the 4-month trial period was assessed with the Test of
Variables of Attention (TOVA) [3]. The children taking
the active ingredients exhibited significant improve-
ments on all TOVA subscales whereas those taking the
placebo did not change.
These studies are intriguing, but it is difficult to
generalize from any of them as the nutrient treatments
have varied so much across investigations. However, there
are now several reports using a single broad-spectrum
formula of minerals and vitamins (EMPowerplus1
) in chil-
dren with emotional and behavioral dysregulation. Kaplan
and colleagues conducted an open-label trial of this for-
mula with children with a variety of psychiatric disorders,
including ADHD, bipolar disorder, anxiety, and oppos-
itional defiant disorder [4]. Six of the 11 children in the
trial met criteria for ADHD, one of whom dropped out.
After 16 weeks of taking the nutrient formula, and being
monitored with the Child Behavior Checklist (CBCL), the
ten remaining children were significantly improved on
seven CBCL scales: withdrawn behavior, anxious/de-
pressed mood, social problems, thought problems, at-
tention problems, delinquent behavior, and aggressive
behavior. Later, Rucklidge et al. published a database
analysis of 41 children with ADHD taking this same
formula, finding a significant improvement in ADHD
symptoms [5]. The improvement in behavior ratings
was 47 % and was sustained over a 6-month period.
Frazier et al. used the same broad-spectrum formula
in a small group of children who met criteria for
pediatric bipolar disorder, most of whom also had
ADHD [6]. This 8-week trial resulted in significant
improvements in emotion regulation. Finally, in
adults, Rucklidge and colleagues reported a positive
RCT in those with ADHD treated for 8 weeks with
the same micronutrient formula [7]. This study in-
cluded 80 adults with ADHD, half randomized to
micronutrients and half to placebo. Those who re-
ceived the micronutrient treatment reported greater
change in the key areas of ADHD symptoms (atten-
tion, hyperactivity and impulsivity) than those who re-
ceived the placebo. Of the approximately 25 % of the
participants who entered the trial depressed, greater
benefit was found in those treated with the micronu-
trients compared to placebo.
As there is now an increasing body of literature on
this one micronutrient formula, enabling comparisons
and generalizations across studies, we decided to revisit
the classroom environment studied by Schoenthaler
over 15 years ago, and determine whether this formula
should be studied systematically for its potential benefit
for self-regulation in schoolchildren. Prior to doing so,
it was important to evaluate several issues related to
feasibility of pursuing this line of research, including
feasibility of participant recruitment from a culturally
diverse population, probability of sample retention for a
12-week trial, acceptability of the outcome measures,
and supplement adherence. The results of this feasibil-
ity pilot study are reported here, including the trends in
treatment response.
Kaplan et al. Journal of Medical Case Reports (2015) 9:240 Page 2 of 6
Case presentation
Participants
The three children who participated in this pilot study
were ones who had had extremely challenging problems
with classroom attention and behavior during the previ-
ous school year, happened to be available during the
summer months, and were willing to participate. None
was receiving any other treatments or interventions dur-
ing their participation in this pilot study.
At the time of the trial, the three children were aged 5
(male), 6 (male), and 14 (female) years. All three were
Hispanic (which is the majority of this school’s popula-
tion) and spoke both Spanish and English. All materials
were translated for their parents, who were not always
fluent in English. None of the three children had any
known physical health problems, and none were taking
medications. The two younger children had not been
formally diagnosed, in both cases their classroom dif-
ficulties with attention and behavior regulation had
been significant challenges during the previous school
year. The 14-year-old girl had been diagnosed with
bipolar disorder, ADHD, oppositional defiant disorder,
and aggressive behavior but was not taking psychiatric
medication.
Measures
Two measures were used to monitor symptoms over the
12 weeks. Parents were asked to complete a weekly
checklist consisting of the 21 items from the parent-
report Child Mania Rating Scale [8]. This form was la-
beled the “Parent Weekly Form” for current purposes,
and covered topics such as irritability, sleep, energy
levels, risky behavior, and rapid mood changes. Each
item is scored from 0 (not at all) to 3 (very often), yield-
ing a maximum weekly score of 63.
For the children, a short checklist was developed and
was used daily. They were asked to rate the entire day
on a nominal categorical scale: 1 (happy), 2 (sleepy), 3
(sad), or 4 (mad). A verbal version was used for the older
child; a version that used happy and angry faces was
employed for the two younger children. Since it was a
daily score, the checklists were simply summed for a
total weekly score.
In addition, the study coordinator met with each fam-
ily every 2 weeks to ensure compliance with capsule
consumption, as well as questionnaire completion. In
that interview, she also questioned families about any
adverse events.
Procedure
Dose was titrated according to the following schedule:
one capsule/day for the first week, two/day for the
second week, three/day for the third day, and then
four/day from week 4 until the end of the study
(week 12). Beginning in the second week, the doses
were divided into morning and afternoon, so for most
of the 12-week trial each child consumed two cap-
sules twice a day.
Results
A paired sample t test evaluated change in parent-
reported scores from baseline to week 12. The behavior
changes were significant (see Fig. 1), t(2) = 23.00, p =
.002, with a large effect size (d = 5.95).
There were no separate baseline data points for the
children’s data, as the checklist began the same day
the children began the nutrient formula, albeit at the
initial low dose of only one capsule/day. Statistical
testing of this scale was not appropriate, as it was a
repeated measures nominal scale. Figure 2 should be
interpreted as simply showing a trend toward the
ideal score of 7 (which would reflect “happy” for all 7
days in a week).
On the parent questionnaire submitted weekly,
there was no evidence of adverse events such as irrit-
ability or fatigue. The study coordinator’s biweekly in-
person interview also did not uncover any reports of
adverse events.
Discussion
The primary purpose of this pilot work was to determine
the feasibility of conducting a future, school-based
evaluation of micronutrient treatment in children with
emotional dysregulation and behavior problems. Feasi-
bility was examined from several perspectives, and the
result for each was quite positive: all three children
remained in the trial throughout the 12 weeks, indicat-
ing that sample retention was not a problem; supple-
ment adherence was excellent as all three families
reported that they ensured their child took the daily
doses; and the rating forms appeared to be easy for both
parents and children to complete. As reported in many
other studies, as well as in an article on safety and tox-
icity of this formula [9], no adverse reactions emerged.
The measures used to monitor symptoms seemed to be
sensitive to the changes reported verbally by parents in
one-to-one interviews (reported below as “Parental
perspectives”).
Although evaluating the actual treatment impact of
this micronutrient formula on behavior was not the pri-
mary focus of this pilot feasibility work, the changes that
emerged were very positive, as shown in Figs. 1 and 2.
However, interpretation of those changes must be tem-
pered by several limitations. The study employed no
placebo and no teacher evaluations (as it was carried
out during summer holidays). One could assume that
a large positive expectancy effect would be possible,
given this design.
Kaplan et al. Journal of Medical Case Reports (2015) 9:240 Page 3 of 6
Conclusions
The primary conclusion of this pilot study is that further
evaluation of micronutrient treatment in school-aged
children with significant emotional and behavioral chal-
lenges is warranted and feasible. Such evaluations could
be carried out both in the context of research as well as
clinical use. Children with learning challenges warranting
special settings such as the Learning Curve Academy have
many obstacles to achievement; finding out whether just
one set of obstacles (attention and behavior problems) can
be ameliorated to enhance their educational experience is
inherently worthwhile. It is this set of challenges which
make it imperative that research be carried out in natural-
istic, educational settings.
Health care personnel often struggle to help families
cope with children’s emotional and attentional problems
in school. Family physicians and pediatricians, in par-
ticular, are often confronted with the challenge of im-
proving the lives of families who are burdened by school
crises due to children’s emotional and behavioral dysreg-
ulation. The burden of these crises affects many people:
the children themselves, their families, fellow classmates,
Fig. 1 Parent-reported scores. Each weekly score could range from 0 to 63, with 0 representing virtually no behavioral or emotional problems
Fig. 2 Child-reported scores. Each weekly data point is the sum of seven daily ratings, each of which could range from 1 to 4. Hence, a weekly
score could range from 7 to 28, with 7 indicating that the child consistently reported feeling happy every day that week
Kaplan et al. Journal of Medical Case Reports (2015) 9:240 Page 4 of 6
and school personnel. The children described here,
whose families volunteered to help determine the feasi-
bility of further research at their school, experienced im-
pressive changes that clearly warrant both research and
clinical exploration. Currently, children’s weaknesses in
attention and behavior control often result in medical
interventions that may or may not be the ideal choice.
There is significant potential for improved educational
experiences of school-aged children who receive en-
hanced nutrition, which is a compelling reason to en-
courage further research.
Parental perspectives
Language and cultural differences were barriers to
obtaining written parental descriptions of their per-
spectives. Hence, information was obtained from per-
sonal interviews carried out by PH with the assistance
of a translator who attended each meeting:
From the mother of child 1 (a 5-year-old boy):
 After 4 weeks: She no longer has to spank him; she
can now communicate with him. As soon as she
started giving him four capsules/day (week 4), she
saw big changes. He goes to sleep quicker without
a fight; he calms down quicker; his social and family
time is improved because he is behaving now; more
loving with his mother; used to annoy family
members and is now caring; more independent and
compassionate and sentimental.
 After 6 weeks: She said her son was never diagnosed
with a mental disorder, but she had a referral to see
a psychologist when she was introduced to [the
nutrient formula]. Now she does not believe he
needs to see the psychologist.
 At the end of the trial: The mother reported
significantly improved behavior at home. She
said he became calmer and slowed down. She
said he was less hyper, more focused.
From the mother of child 2 (a 6-year-old boy).
 After 4 weeks: She reports that her son has become
so relaxed, they often have to wake him up; he is
sleeping much better and sleeping longer; much
calmer; drinking more water; would rather drink
water than Hawaiian Punch; less accident prone;
sharing with his sister; seeks approval from his
mother for good behavior; more sociable; family
atmosphere improved because of better behavior.
 At the end of the trial: During the previous year this
child lived in his own world. He chose not to
communicate with his family and he had no friends.
At around week 3 on the micronutrient formula, he
started making friends and started being nicer to his
sister. This child had also never shown emotion
prior to the nutrient trial, but after 4 weeks on the
micronutrients, his mother reported that she was
crying one day, and her son came to her, put his
arm around her, and said, “It’s OK Mommy, don’t
cry.” This amount of compassion had not been
exhibited by him prior to this time.
From the father of child 3 (a 14-year-old girl):
 After 6 weeks: The father reported she is sleeping so
much better. She used to suffer from insomnia for
2–3 days straight. She was hyperactive 24 hours a day,
7 days a week. She talked really fast and changed
subjects too quickly. She used to fight with everybody.
Dad could not trust her; could never leave her alone.
The father said his child herself does not remember
back to before she was taking the nutrients; she does
not remember how bad she was and shrieks in horror
when she listens to her father describe how bad she
was compared to how good she is now.
 After 9 weeks: They just moved again (during week 9)
for the second time this summer, and life has been
very hectic. By the third week, she was sleeping better
and her behavior was improving. He told us that his
daughter had been wanting an iPad for a long time,
and he had continued to tell her “no” because her
behavior was so bad. At the end of the trial he was
pleased to report that he was able to buy her one.
He also reported that her improved behavior had
given him a lot of peace. The other people around this
girl who knew her well (for example, the interpreter
and the school principal) reported that it was a
miracle how this child’s behavior had improved.
Consent
Written informed consent was obtained from the patients’
legal guardians for publication of these three cases and
any accompanying data. Copies of the written consents
are available for review by the Editor-in-Chief of this
journal.
Endnotes
1
There are several variants of EMPowerplus Advanced
with similar formulas, such as Truehope EMP, EMPow-
erplus, Q96, and Daily Essential Nutrients. The ingredi-
ents of the one used in these case reports can be found
on the following website: www.Truehope.com
Competing interests
BJK and ET declare they have no competing interests. PH is commercially
affiliated with the company that provided the micronutrient formula, but the
company placed no obligation on any author to conduct this research in any
particular manner, nor to permit them to review the data or results. This work
contributed to the class assignments completed by PH for her Master’s degree
in Health Education.
Kaplan et al. Journal of Medical Case Reports (2015) 9:240 Page 5 of 6
Authors’ contributions
PH and BJK planned the intervention and method of data collection
together. PH provided the interface to the school and families. ET and BJK
analyzed and interpreted the patient data. BJK drafted the manuscript, and
all three authors read and approved the final manuscript.
Acknowledgements
We thank the board and staff of the Learning Curve Academy, as well as
the three families who participated. We also thank the company Truehope
Nutritional Support Ltd. for providing their formula EMPowerplus Advanced
at no cost for this trial. Finally, we thank Prof. Dermot Gately for his
assistance in generating the figures.
Author details
1
Faculty of Medicine, University of Calgary, The Child Development Centre,
3820 - 24 Avenue NW, Calgary, AB T3B 2X9, Canada. 2
59 Dogwood Trail,
Ocala, FL 34472, USA. 3
1501, 1410 1 St SE, Calgary, AB T2G 5 T7, Canada.
Received: 29 April 2015 Accepted: 13 October 2015
References
1. Schoenthaler SJ, Bier ID. The effect of vitamin-mineral supplementation on
juvenile delinquency among American schoolchildren: a randomized,
double-blind placebo-controlled trial. J Altern Complement Med.
2000;6:7–17.
2. 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.
3. Katz M, Levine AA, 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.
4. 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.
5. Rucklidge JJ, Gately D, Kaplan BJ. Database analysis of children and
adolescents with bipolar disorder consuming a multinutrient formula. BMC
Psychiatry. 2010;10:74.
6. 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.
7. Rucklidge JJ, Frampton CM, Gorman B, Boggis A. Vitamin-mineral treatment
of attention-deficit hyperactivity disorder in adults: double-blind
randomised placebo-controlled trial. Br J Psychiatry. 2014;204:306–15.
8. Pavuluri MN, Henry DB, Devineni B, Carbray JA, Birmaher B. Child mania
rating scale: development, reliability, and validity. J Am Acad Child Adolesc
Psychiatry. 2006;45:550–60.
9. 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.
Submit your next manuscript to BioMed Central
and take full advantage of:
• Convenient online submission
• Thorough peer review
• No space constraints or color figure charges
• Immediate publication on acceptance
• Inclusion in PubMed, CAS, Scopus and Google Scholar
• Research which is freely available for redistribution
Submit your manuscript at
www.biomedcentral.com/submit
Kaplan et al. Journal of Medical Case Reports (2015) 9:240 Page 6 of 6

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2015 Kaplan et al Tx of school children 3 cases (1)

  • 1. CASE REPORT Open Access Micronutrient treatment for children with emotional and behavioral dysregulation: a case series Bonnie J. Kaplan1* , Paula Hilbert2 and Ekaterina Tsatsko3 Abstract Introduction: In clinical studies of adults and children, broad-spectrum micronutrients (minerals and vitamins) have proven beneficial for improving mood regulation and attention. We report here pilot work whose primary objective was to evaluate the feasibility of studying micronutrient treatment in school-aged children with emotional and behavioral problems. Issues examined included feasibility of participant recruitment from a culturally diverse population, probability of sample retention for a 12-week trial, acceptability of the outcome measures, supplement adherence, as well as trends in treatment benefit. Case presentation: The families of two boys (ages 5 and 6) and one girl (age 14) were invited to participate in a 12-week pilot trial of micronutrients carried out during the summer months. All children were enrolled in the private school at which future research was being considered. During the previous school year, all three had been extremely difficult to educate due to their inability to pay attention and learn, as well as their behavior problems. Although the two younger children had not been formally diagnosed, parents and teachers provided reports of hyperactivity and inability to focus on education in the classroom. The oldest child was often aggressive, and had been diagnosed with bipolar disorder, attention deficit hyperactivity disorder, and oppositional defiant disorder. All three children were Hispanic and spoke both Spanish and English. For 12 weeks, after signing consent forms, the children’s parents provided weekly ratings on the parent-report Child Mania Rating Scale; the children consumed the micronutrient formula daily and provided a daily rating of how they felt. The parent ratings revealed significantly improved behavior, p = .002. Children’s ratings approached the ideal level of 7, indicating “happy” self-reports. Parent interviews confirmed the weekly scores. Several feasibility questions were answered: all three children completed the 12-week trial, all scores were completed by parents and children, adherence to the protocol was excellent, and no adverse reactions emerged. Conclusions: Family physicians and pediatricians are often confronted with the challenge of improving the lives of families whose children experience school crises due to emotional and behavioral dysregulation. Three children, who participated in pilot work to determine the feasibility of further investigations, experienced impressive changes that clearly warrant both research and clinical exploration. Keywords: Micronutrients, Treatment outcome, ADHD, Child behavior disorders * Correspondence: Kaplan@ucalgary.ca 1 Faculty of Medicine, University of Calgary, The Child Development Centre, 3820 - 24 Avenue NW, Calgary, AB T3B 2X9, Canada Full list of author information is available at the end of the article JOURNAL OF MEDICAL CASE REPORTS © 2015 Kaplan et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Kaplan et al. Journal of Medical Case Reports (2015) 9:240 DOI 10.1186/s13256-015-0735-0
  • 2. Introduction Success in the classroom is a function of many variables, not the least of which is children’s ability to regulate emotions, attention and behavior. Even very intelligent children who lack this self-regulation may struggle in school, and may be faced with multiple disciplinary inci- dents or even expulsion. The Learning Curve Academy in north central Florida is an independent school established in 2007. It is an in- clusion school and serves typically developing children as well as disabled children and children diagnosed with learning and behavioral problems. Approximately 50 children are enrolled in grades kindergarten to grade 12 in this private school, and many of them receive special- ized services. Some of the children have been diagnosed with a behavioral/mental disorder, most frequently atten- tion deficit hyperactivity disorder (ADHD) and bipolar disorder. Most had previously failed in the public school system, where assessments by social workers and psychologists resulted in Individual Educational Plans (IEPs). The tuition fees for all three children were heav- ily subsidized by the state government because of the severity of their learning and behavioral problems, or because their families live at or below poverty level. Although school staff members focus primarily on edu- cation and fulfillment of IEP goals, the significant emo- tional and behavioral problems in the classroom often prevent successful achievement. In the last 15 years, several studies have demonstrated that nutrient supplementation for school-aged children can improve their attention and emotional self-regulation, as well as decrease behavioral problems and disciplinary events. Schoenthaler showed that giving 40 schoolchildren aged 6–12 years a broad spectrum of nutrients resulted in 47 % fewer antisocial acts requiring discipline than the 40 children who received a placebo [1]. Outside the classroom, research by Harding and colleagues showed improved self-regulation in children diagnosed with ADHD or bipolar disorder who were treated with min- erals and vitamins [2]. In fact, the improvements in ADHD symptomatology in 20 children given a range of dietary nutrients over a 4-week period were similar in magnitude to the changes obtained from methylphenid- ate. A randomized, placebo-controlled trial (RCT) by Katz et al. evaluated children diagnosed with ADHD: half received an herbal compound with essential nutri- ents, including essential fatty acids, phospholipids, es- sential amino acids, B vitamins, vitamins E and C, and minerals, and half received a placebo [3]. Change over the 4-month trial period was assessed with the Test of Variables of Attention (TOVA) [3]. The children taking the active ingredients exhibited significant improve- ments on all TOVA subscales whereas those taking the placebo did not change. These studies are intriguing, but it is difficult to generalize from any of them as the nutrient treatments have varied so much across investigations. However, there are now several reports using a single broad-spectrum formula of minerals and vitamins (EMPowerplus1 ) in chil- dren with emotional and behavioral dysregulation. Kaplan and colleagues conducted an open-label trial of this for- mula with children with a variety of psychiatric disorders, including ADHD, bipolar disorder, anxiety, and oppos- itional defiant disorder [4]. Six of the 11 children in the trial met criteria for ADHD, one of whom dropped out. After 16 weeks of taking the nutrient formula, and being monitored with the Child Behavior Checklist (CBCL), the ten remaining children were significantly improved on seven CBCL scales: withdrawn behavior, anxious/de- pressed mood, social problems, thought problems, at- tention problems, delinquent behavior, and aggressive behavior. Later, Rucklidge et al. published a database analysis of 41 children with ADHD taking this same formula, finding a significant improvement in ADHD symptoms [5]. The improvement in behavior ratings was 47 % and was sustained over a 6-month period. Frazier et al. used the same broad-spectrum formula in a small group of children who met criteria for pediatric bipolar disorder, most of whom also had ADHD [6]. This 8-week trial resulted in significant improvements in emotion regulation. Finally, in adults, Rucklidge and colleagues reported a positive RCT in those with ADHD treated for 8 weeks with the same micronutrient formula [7]. This study in- cluded 80 adults with ADHD, half randomized to micronutrients and half to placebo. Those who re- ceived the micronutrient treatment reported greater change in the key areas of ADHD symptoms (atten- tion, hyperactivity and impulsivity) than those who re- ceived the placebo. Of the approximately 25 % of the participants who entered the trial depressed, greater benefit was found in those treated with the micronu- trients compared to placebo. As there is now an increasing body of literature on this one micronutrient formula, enabling comparisons and generalizations across studies, we decided to revisit the classroom environment studied by Schoenthaler over 15 years ago, and determine whether this formula should be studied systematically for its potential benefit for self-regulation in schoolchildren. Prior to doing so, it was important to evaluate several issues related to feasibility of pursuing this line of research, including feasibility of participant recruitment from a culturally diverse population, probability of sample retention for a 12-week trial, acceptability of the outcome measures, and supplement adherence. The results of this feasibil- ity pilot study are reported here, including the trends in treatment response. Kaplan et al. Journal of Medical Case Reports (2015) 9:240 Page 2 of 6
  • 3. Case presentation Participants The three children who participated in this pilot study were ones who had had extremely challenging problems with classroom attention and behavior during the previ- ous school year, happened to be available during the summer months, and were willing to participate. None was receiving any other treatments or interventions dur- ing their participation in this pilot study. At the time of the trial, the three children were aged 5 (male), 6 (male), and 14 (female) years. All three were Hispanic (which is the majority of this school’s popula- tion) and spoke both Spanish and English. All materials were translated for their parents, who were not always fluent in English. None of the three children had any known physical health problems, and none were taking medications. The two younger children had not been formally diagnosed, in both cases their classroom dif- ficulties with attention and behavior regulation had been significant challenges during the previous school year. The 14-year-old girl had been diagnosed with bipolar disorder, ADHD, oppositional defiant disorder, and aggressive behavior but was not taking psychiatric medication. Measures Two measures were used to monitor symptoms over the 12 weeks. Parents were asked to complete a weekly checklist consisting of the 21 items from the parent- report Child Mania Rating Scale [8]. This form was la- beled the “Parent Weekly Form” for current purposes, and covered topics such as irritability, sleep, energy levels, risky behavior, and rapid mood changes. Each item is scored from 0 (not at all) to 3 (very often), yield- ing a maximum weekly score of 63. For the children, a short checklist was developed and was used daily. They were asked to rate the entire day on a nominal categorical scale: 1 (happy), 2 (sleepy), 3 (sad), or 4 (mad). A verbal version was used for the older child; a version that used happy and angry faces was employed for the two younger children. Since it was a daily score, the checklists were simply summed for a total weekly score. In addition, the study coordinator met with each fam- ily every 2 weeks to ensure compliance with capsule consumption, as well as questionnaire completion. In that interview, she also questioned families about any adverse events. Procedure Dose was titrated according to the following schedule: one capsule/day for the first week, two/day for the second week, three/day for the third day, and then four/day from week 4 until the end of the study (week 12). Beginning in the second week, the doses were divided into morning and afternoon, so for most of the 12-week trial each child consumed two cap- sules twice a day. Results A paired sample t test evaluated change in parent- reported scores from baseline to week 12. The behavior changes were significant (see Fig. 1), t(2) = 23.00, p = .002, with a large effect size (d = 5.95). There were no separate baseline data points for the children’s data, as the checklist began the same day the children began the nutrient formula, albeit at the initial low dose of only one capsule/day. Statistical testing of this scale was not appropriate, as it was a repeated measures nominal scale. Figure 2 should be interpreted as simply showing a trend toward the ideal score of 7 (which would reflect “happy” for all 7 days in a week). On the parent questionnaire submitted weekly, there was no evidence of adverse events such as irrit- ability or fatigue. The study coordinator’s biweekly in- person interview also did not uncover any reports of adverse events. Discussion The primary purpose of this pilot work was to determine the feasibility of conducting a future, school-based evaluation of micronutrient treatment in children with emotional dysregulation and behavior problems. Feasi- bility was examined from several perspectives, and the result for each was quite positive: all three children remained in the trial throughout the 12 weeks, indicat- ing that sample retention was not a problem; supple- ment adherence was excellent as all three families reported that they ensured their child took the daily doses; and the rating forms appeared to be easy for both parents and children to complete. As reported in many other studies, as well as in an article on safety and tox- icity of this formula [9], no adverse reactions emerged. The measures used to monitor symptoms seemed to be sensitive to the changes reported verbally by parents in one-to-one interviews (reported below as “Parental perspectives”). Although evaluating the actual treatment impact of this micronutrient formula on behavior was not the pri- mary focus of this pilot feasibility work, the changes that emerged were very positive, as shown in Figs. 1 and 2. However, interpretation of those changes must be tem- pered by several limitations. The study employed no placebo and no teacher evaluations (as it was carried out during summer holidays). One could assume that a large positive expectancy effect would be possible, given this design. Kaplan et al. Journal of Medical Case Reports (2015) 9:240 Page 3 of 6
  • 4. Conclusions The primary conclusion of this pilot study is that further evaluation of micronutrient treatment in school-aged children with significant emotional and behavioral chal- lenges is warranted and feasible. Such evaluations could be carried out both in the context of research as well as clinical use. Children with learning challenges warranting special settings such as the Learning Curve Academy have many obstacles to achievement; finding out whether just one set of obstacles (attention and behavior problems) can be ameliorated to enhance their educational experience is inherently worthwhile. It is this set of challenges which make it imperative that research be carried out in natural- istic, educational settings. Health care personnel often struggle to help families cope with children’s emotional and attentional problems in school. Family physicians and pediatricians, in par- ticular, are often confronted with the challenge of im- proving the lives of families who are burdened by school crises due to children’s emotional and behavioral dysreg- ulation. The burden of these crises affects many people: the children themselves, their families, fellow classmates, Fig. 1 Parent-reported scores. Each weekly score could range from 0 to 63, with 0 representing virtually no behavioral or emotional problems Fig. 2 Child-reported scores. Each weekly data point is the sum of seven daily ratings, each of which could range from 1 to 4. Hence, a weekly score could range from 7 to 28, with 7 indicating that the child consistently reported feeling happy every day that week Kaplan et al. Journal of Medical Case Reports (2015) 9:240 Page 4 of 6
  • 5. and school personnel. The children described here, whose families volunteered to help determine the feasi- bility of further research at their school, experienced im- pressive changes that clearly warrant both research and clinical exploration. Currently, children’s weaknesses in attention and behavior control often result in medical interventions that may or may not be the ideal choice. There is significant potential for improved educational experiences of school-aged children who receive en- hanced nutrition, which is a compelling reason to en- courage further research. Parental perspectives Language and cultural differences were barriers to obtaining written parental descriptions of their per- spectives. Hence, information was obtained from per- sonal interviews carried out by PH with the assistance of a translator who attended each meeting: From the mother of child 1 (a 5-year-old boy): After 4 weeks: She no longer has to spank him; she can now communicate with him. As soon as she started giving him four capsules/day (week 4), she saw big changes. He goes to sleep quicker without a fight; he calms down quicker; his social and family time is improved because he is behaving now; more loving with his mother; used to annoy family members and is now caring; more independent and compassionate and sentimental. After 6 weeks: She said her son was never diagnosed with a mental disorder, but she had a referral to see a psychologist when she was introduced to [the nutrient formula]. Now she does not believe he needs to see the psychologist. At the end of the trial: The mother reported significantly improved behavior at home. She said he became calmer and slowed down. She said he was less hyper, more focused. From the mother of child 2 (a 6-year-old boy). After 4 weeks: She reports that her son has become so relaxed, they often have to wake him up; he is sleeping much better and sleeping longer; much calmer; drinking more water; would rather drink water than Hawaiian Punch; less accident prone; sharing with his sister; seeks approval from his mother for good behavior; more sociable; family atmosphere improved because of better behavior. At the end of the trial: During the previous year this child lived in his own world. He chose not to communicate with his family and he had no friends. At around week 3 on the micronutrient formula, he started making friends and started being nicer to his sister. This child had also never shown emotion prior to the nutrient trial, but after 4 weeks on the micronutrients, his mother reported that she was crying one day, and her son came to her, put his arm around her, and said, “It’s OK Mommy, don’t cry.” This amount of compassion had not been exhibited by him prior to this time. From the father of child 3 (a 14-year-old girl): After 6 weeks: The father reported she is sleeping so much better. She used to suffer from insomnia for 2–3 days straight. She was hyperactive 24 hours a day, 7 days a week. She talked really fast and changed subjects too quickly. She used to fight with everybody. Dad could not trust her; could never leave her alone. The father said his child herself does not remember back to before she was taking the nutrients; she does not remember how bad she was and shrieks in horror when she listens to her father describe how bad she was compared to how good she is now. After 9 weeks: They just moved again (during week 9) for the second time this summer, and life has been very hectic. By the third week, she was sleeping better and her behavior was improving. He told us that his daughter had been wanting an iPad for a long time, and he had continued to tell her “no” because her behavior was so bad. At the end of the trial he was pleased to report that he was able to buy her one. He also reported that her improved behavior had given him a lot of peace. The other people around this girl who knew her well (for example, the interpreter and the school principal) reported that it was a miracle how this child’s behavior had improved. Consent Written informed consent was obtained from the patients’ legal guardians for publication of these three cases and any accompanying data. Copies of the written consents are available for review by the Editor-in-Chief of this journal. Endnotes 1 There are several variants of EMPowerplus Advanced with similar formulas, such as Truehope EMP, EMPow- erplus, Q96, and Daily Essential Nutrients. The ingredi- ents of the one used in these case reports can be found on the following website: www.Truehope.com Competing interests BJK and ET declare they have no competing interests. PH is commercially affiliated with the company that provided the micronutrient formula, but the company placed no obligation on any author to conduct this research in any particular manner, nor to permit them to review the data or results. This work contributed to the class assignments completed by PH for her Master’s degree in Health Education. Kaplan et al. Journal of Medical Case Reports (2015) 9:240 Page 5 of 6
  • 6. Authors’ contributions PH and BJK planned the intervention and method of data collection together. PH provided the interface to the school and families. ET and BJK analyzed and interpreted the patient data. BJK drafted the manuscript, and all three authors read and approved the final manuscript. Acknowledgements We thank the board and staff of the Learning Curve Academy, as well as the three families who participated. We also thank the company Truehope Nutritional Support Ltd. for providing their formula EMPowerplus Advanced at no cost for this trial. Finally, we thank Prof. Dermot Gately for his assistance in generating the figures. Author details 1 Faculty of Medicine, University of Calgary, The Child Development Centre, 3820 - 24 Avenue NW, Calgary, AB T3B 2X9, Canada. 2 59 Dogwood Trail, Ocala, FL 34472, USA. 3 1501, 1410 1 St SE, Calgary, AB T2G 5 T7, Canada. Received: 29 April 2015 Accepted: 13 October 2015 References 1. Schoenthaler SJ, Bier ID. The effect of vitamin-mineral supplementation on juvenile delinquency among American schoolchildren: a randomized, double-blind placebo-controlled trial. J Altern Complement Med. 2000;6:7–17. 2. 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. 3. Katz M, Levine AA, 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. 4. 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. 5. Rucklidge JJ, Gately D, Kaplan BJ. Database analysis of children and adolescents with bipolar disorder consuming a multinutrient formula. BMC Psychiatry. 2010;10:74. 6. 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. 7. Rucklidge JJ, Frampton CM, Gorman B, Boggis A. Vitamin-mineral treatment of attention-deficit hyperactivity disorder in adults: double-blind randomised placebo-controlled trial. Br J Psychiatry. 2014;204:306–15. 8. Pavuluri MN, Henry DB, Devineni B, Carbray JA, Birmaher B. Child mania rating scale: development, reliability, and validity. J Am Acad Child Adolesc Psychiatry. 2006;45:550–60. 9. 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. Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit Kaplan et al. Journal of Medical Case Reports (2015) 9:240 Page 6 of 6