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ORIGINAL ARTICLE
Magnesium supplementation in children
with attention deficit hyperactivity disorder
Farida El Baza, Heba Ahmed AlShahawi, Sally Zahra
*
, Rana Ahmed AbdelHakim
Ain Shams University, Cairo, Egypt
Received 20 May 2015; accepted 27 May 2015
Available online 7 July 2015
KEYWORDS
ADHD;
Magnesium;
Supplementation;
Treatment
Abstract Background: Attention deficit hyperactivity disorder (ADHD) is a common neurodevel-
opmental disorder with associated mineral deficiency.
Aim: To assess magnesium level in ADHD children and compare it to the normal levels in
children. Then, to detect the effect of magnesium supplementation as an add on therapy, on
magnesium deficient patients.
Methods: The study was conducted on 25 patients with ADHD and 25 controls. All subjects had
magnesium estimation in serum and hair. ADHD children were further assessed by Wechsler
intelligence scale for children, Conners’ parent rating scale, and Wisconsin card sorting test.
Then magnesium deficient patients were assigned into 2 groups, those who received magnesium,
and those who did not. The difference between the studied groups was assessed by Conners’ parents
rating scale and Wisconsin card sorting test.
Results: Magnesium deficiency was found in 18 (72%) of ADHD children. The magnesium
supplemented group improved as regards cognitive functions as measured by the Wisconsin card
sorting test and Conners’ rating scale. The patients reported minor side effects from magnesium
supplementation.
Conclusion: Magnesium supplementation in ADHD, proves its value and safety.
Ó2015 The Authors. Production and hosting by Elsevier B.V. on behalf of Ain Shams University. This is
an open access article underthe CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
1. Introduction
Attention-deficit/hyperactivity disorder (ADHD) is a com-
mon, early-onset and enduring neuropsychiatric disorder
characterized by developmentally inappropriate deficits in
attention, hyperactivity, increased impulsivity and emotional
deregulation, resulting in impairments in multiple domains of
personal and professional life [1].
Evidence for dietary/nutritional treatments of attention-def
icit/hyperactivity disorder (ADHD) varies widely; however
recommended daily allowance of minerals and essential fatty
acids is an ADHD-specific intervention [2].
Magnesium is the fourth most abundant mineral in the
body and is essential for good health [3]. Its biological
importance evolves from being an essential trace mineral
involved in over 300 metabolic reactions including cellular
*Corresponding author.
E-mail addresses: faridabaz@hotmail.com (F. El Baza), hebaelshahawi
@yahoo.com (H.A. AlShahawi), sallyzahra@yahoo.com (S. Zahra),
ranahak@hotmail.com (R.A. AbdelHakim).
Peer review under responsibility of Ain Shams University.
The Egyptian Journal of Medical Human Genetics (2016) 17, 63–70
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Ain Shams University
The Egyptian Journal of Medical Human Genetics
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http://dx.doi.org/10.1016/j.ejmhg.2015.05.008
1110-8630 Ó2015 The Authors. Production and hosting by Elsevier B.V. on behalf of Ain Shams University.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
energy generation, nucleic acid production (DNA, RNA), and
protein synthesis. Magnesium (Mg
+2
) is, also, the most abun-
dant intracellular divalent cation [4].
The mineral magnesium is necessary for sufficient brain
energy and aids smooth transmission of communications
through the central nervous system, calms the central nervous
system and is an important component in the making of
serotonin [5].
Magnesium deficiency is typified by a number of reductions
in cognitive ability and processes, and in particular a reduced
attention span along with increased instances of aggression,
fatigue and lack of concentration [6]. Other common symp-
toms of magnesium deficiency include becoming easily
irritated, nervousness, fatigue and mood swings [6].
Given the nature of these symptoms and the significant
amount of overlap that they share with ADHD, this led
many experts involved in the treatment and care of ADHD
to hypothesize that children who suffer from ADHD also have
magnesium deficiency as well.
In the current study, magnesium level in children with
attention deficit hyperactivity disorder (ADHD) will be
compared to normal children, in both serum and hair. Then,
the effects of magnesium supplementation in magnesium
deficient patients will be assessed.
2. Subjects and methods
This study is a case-control prospective interventional compar-
ative study. It was conducted on 25 patients with ADHD and
25 age and sex matched controls.
2.1. Participants
Patients were considered ineligible for the study, if they
fulfilled criteria of ADHD according to DSMIV, their age
range was between 6 and 16 years and their IQ above 70.
Ineligibility for the study included presence of other medical
conditions as significant anemia, chronic illness, hearing or
vision impairment, medication side effects which may result
in hyperactivity and impaired sleep rhythm.
Twenty five healthy children recruited from the sibs of the
ADHD group were included in the study as a control group.
Both patients and healthy controls were recruited from
Children’s hospital and institute of psychiatry, Ain Shams
University, Cairo, Egypt. The work has been carried out in
accordance with the code of Ethics of the World Medical
Association (Declaration of Helsinki) for experiments involv-
ing humans.
2.2. Study design
Patients were recruited from the clinic randomly. After
explaining the purpose of the study, written consents from
parents and the acceptance of the ethics committee of Ain
Shams University were obtained. Data were collected through
the administration of the predesigned questionnaires to the
parents.
Each patient in this study was subjected to the following;
Full detailed medical history including presence of organic or
psychological diseases, perinatal and developmental history,
family history of similar cases, and the previous treatment
which was received.
Clinical Examination included; body measurements,
physical examination and neurological examination.
2.3. Investigations
Serum magnesium level was assayed by auto analyzer [7].
Hair magnesium level (Fresh, clean hair sample) was sub-
jected to Inductively Coupled Mass Spectroscopy (ICP-MS)
which has been cited as currently the most sensitive and com-
prehensive technique available for multi-element analysis of
trace elements to measure hair magnesium in both cases and
controls [8].
2.4. Scales
DSM (IV) to confirm the diagnosis of ADHD in cases and to
exclude concomitant psychiatric disease [9].
Conners’ parent rating scales using an Arabic version for
detection of the severity of ADHD [10]. Items are scored on
14 subscales but in our study we used only the hyperactivity,
inattention, oppositional and impulsivity scores.
Wisconsin’s card sorting test (WCST) is a neuropsycholog-
ical test of ‘‘set-shifting’’, i.e. the ability to display flexibility in
the face of changing schedules of reinforcement. It’s a measure
of executive function.We used computerized versions of the
task (Microsoft Windows-compatible version 4.0). It has the
advantage of automatically scoring the test, which was quite
complex in the manual version [11].
Wechsler intelligence scale for children (WISC) using the
Arabic version for IQ assessment [11].
We compared the ADHD group (25 patients) with the
matched control group (25 children) as regards different
variables mainly the hair and serum magnesium. The ROC
Curve (Receiver Operating Characteristics) was used for the
diagnosis of decreased magnesium level in hair among
ADHD children as there is no available reference in Egypt
for hair Magnesium in this age group. Using ROC Curve,
0
0.2
0.4
0.6
0.8
1
1.2
4
14.5
24.5
32.5
38
40.5
44
48.5
52.5
60
66
90.5
98
140
Magnesium in hair
Percent
Sensitivity Specificity
Figure 1 Using ROC Curve the cut off value for deficient
magnesium level in hair was equal or less than 60.
64 F. El Baza et al.
the cut off value for deficient Magnesium level in hair was
equal or less than 60 as shown in Fig. 1. And according to this
cut off value; the magnesium deficient ADHD patients were
found to be 18 (group B) and the ADHD cases with normal
hair magnesium were 7 cases (group A).
The magnesium deficient children were randomly assigned
into 2 equal groups. The first group received magnesium sup-
plementation in a dose of 200 mg/day as an add on therapy to
the standard medical treatment. The second group received
standard medical therapy alone. After 8 weeks the 2 groups
will be compared with Conners’ parent rating scale and
Wisconsin card sorting test.
2.5. Statistical analysis
The collected data were revised, coded, tabulated and intro-
duced to a PC using Statistical package for Social Science.
Data were presented and suitable analysis was done according
to the type of data obtained for each parameter.
I. Descriptive statistics: mean, standard deviation (±SD),
minimum and maximum values (range) for numerical
data and frequency and percentage of non-numerical
data were applied.
II. Analytical statistics: included The ROC Curve (receiver
operating characteristic) which provides a useful way
to evaluate the sensitivity and specificity for quantitative
diagnostic measures that categorize cases into one of
two groups. Student t test was used to assess the statisti-
cal significance of the difference between the two study
group means. Correlation analysis (using Pearson’s
method): To assess the strength of association between
two quantitative variables. The correlation coefficient
denoted symbolically by ‘‘r’’ defines the strength and
direction of the linear relationship between two
variables. Chi square test: was used to examine the
relationship between two qualitative variables. Fisher’s
exact test: was used to examine the relationship between
two qualitative variables when the expected count was
less than 5 more than 20% of cells. Paired t-test was
used to assess the statistical significance of the difference
between two means measured twice for the same study
group.
3. Results
In the current study, there was no significant difference regard-
ing the age and gender among normal children (control) and
ADHD patients Table 1. i.e the two samples were homogenous
(Pvalue > 0.05).
There was a significant difference between cases and con-
trols as regards hair magnesium level but there was no signif-
icant difference as regards serum magnesium level Table 2.
Magnesium deficiency was more common in males than in
females, otherwise the other characteristics showed no signifi-
cant difference (Table 3).
Also, there was no statistically significant difference as
regards attention, memory loss, fear, restlessness, insomnia,
tics, cramps and dizziness between the two groups.
At the beginning of the study there was no statistically
significant difference between the two groups as regards the
different psychiatric scales Table 4.
However, when we correlated hair magnesium level to the
different psychiatric scales among children with ADHD we
found a significant correlation between hair magnesium and
total IQ and an indirect significant correlation between hair
magnesium and the hyperactivity components of Conners’
scale Table 5.
The magnesium deficient patients (18 patients) were then
randomly divided into two groups; Group B 1 (9 patients)
received magnesium supplementation, Group B 2 (9 patients)
received their standard medical treatment without magnesium
supplementation.
Comparison between the psychiatric scales at baseline and
at follow up among magnesium treated ADHD cases who
had low hair magnesium level (group B1) showed that there
was a highly significant improvement in hyperactivity and
impulsivity, and also a significant improvement in inattention,
opposition and conceptual level Table 6.
While, comparison between the psychiatric scales at base-
line and at follow up among untreated low hair Magnesium
ADHD cases showed that there was no such improvement
Table 7.
Percentage of improvement of the psychiatric scales at fol-
low up among magnesium treated (group B1) and untreated
(group B2) Fig. 2.
Percentage of change in Categories completion, Conceptual
level, Oppositional and impulsivity components of Conners’
scale although showed improvement at follow up in
Table 1 Comparison between cases and controls regarding
personal characteristics.
Type P
*
Sig
Cases
N=25
Controls
N=25
%%
Sex Male 20 80.0 19 76.0 0.107 NS
Female 5 20.0 6 24.0
Age Mean ± SD 7.74 ± 1.48 7.40 ± 1.35 0.534
**
NS
NS = non significant; Sig = significance.
*
Chi square test.
**
Student’s ttest.
Table 2 Comparison between cases and control as regards
serum and hair magnesium level.
Type PSig
Cases N= 25 Controls
N=25
Mean ±SD Mean ±SD
Serum Mg (mg/dl) 2.23 0.13 2.32 0.28 0.366 NS
Hair Mg (mg/kg) 54.48 16.65 109.20 26.34 0.0001 HS
SD = standard deviation; NS = non significant; HS = highly
significant; Sig = significance.
Magnesium in ADHD 65
magnesium treated patients of group B1 rather than untreated
patients of group B2. However these changes were not statisti-
cally significant (60%, 60%, 55.6% and respectively).
However, the percentage of change in the inattention as
well as hyperactivity components of Conners’ scale showed
a statistically significant improvement (77.7% and 88.9%
respectively).
As regards the side effects of magnesium supplementation
in our patients (group B1) 22.2% experienced adverse effects
in the form of mild abdominal pain and diarrhea Table 8.
4. Discussion
In the current study, there is a robust finding of decreased hair
magnesium in 18 (72%) of children with ADHD, while serum
hair magnesium is normal. This could be explained on genetic
and metabolic basis. Metabolically, Mg
2+
transport may be
reduced without change in serum MG
2+
concentrations.
This supports the finding of low hair follicle Mg
+2
, while
serum Mg
2+
is normal. Furthermore, abnormalities in
TRPM6 genes, which regulates the entry of magnesium into
Table 3 Comparison between cases with normal (group A) and low hair magnesium (group B) as regards personal and medical
characteristics.
Mg in hair diagnosis PSig
Normal Mg (group A) N= 7 Decreased Mg (group B) N=18
N% N %
Sex Male 3 42.9% 17 94.4% 0.012 S
Female 4 57.1% 1 5.6%
Age Mean ± SD 7.8 ± 1.2 7.7 ± 1.6 0.917 NS
Maternal age at conception Mean ± SD 25.7 ± 3.3 25.3 ± 5.1 0.836 NS
Number of sibling Mean ± SD 1.6 ± 1.3 1.7 ± 0.7 0.700 NS
Order of birth Mean ± SD 1.9 ± 0.9 1.8 ± 0.9 0.840 NS
Consanguinity Negative 6 85.7% 14 77.8% 0.999 NS
Positive 1 14.3% 4 22.2%
Socioeconomic Unprivileged 6 85.7% 11 61.1% 0.362 NS
Privileged 1 14.3% 7 38.9%
Family history Non 4 57.1% 12 66.7% 0.434 NS
ADHD 0 0.0% 3 16.7%
Mother’s occupation Negative 5 71.4% 14 77.8% 0.739 NS
Positive 2 28.6% 4 22.2%
Perinatal asphyxia Negative 3 42.9% 15 83.3% 0.066 NS
Positive 4 57.1% 3 16.7%
Development Delayed 1 14.3% 7 38.9% 0.362 NS
Normal 6 85.7% 11 61.1%
Medical treatment Ritalin 6 85.7% 12 66.7% 0.341 NS
Atomoxetine 1 14.3% 6 33.3%
Serum Mg (mg/dl) Mean ± SD 2.2 ± 0.1 2.3 ± 0.1 0.081 NS
Table 4 Comparison between cases with normal (group A) and low hair magnesium (group B) as regards different psychiatric scales.
Mg in hair PSig
Normal Mg (group A)
N=7
Decreased Mg (group B)
N=18
Mean ±SD Mean ±SD
Wechesler scale Verbal skills Comprehension 9.6 1.5 9.9 2.8 0.676 NS
Arithmetic 7.7 2.5 8.7 3.7 0.541 NS
Similarities 11.1 2.5 10.2 3.7 0.490 NS
Digit span 5.9 2.0 7.6 2.9 0.158 NS
Performance skills Picture completion 8.9 2.5 8.7 2.7 0.908 NS
Block design 9.0 2.1 8.6 2.5 0.677 NS
Digit symbol 8.0 3.6 8.9 3.0 0.577 NS
Total IQ Verbal IQ 96.6 8.6 99.2 17.4 0.712 NS
Performance IQ 95.1 13.5 96.9 14.1 0.779 NS
Total IQ 95.9 10.5 97.7 15.6 0.775 NS
Wisconson’s card sorting test Categories completion 3.5 2.1 2.9 2.0 0.643 NS
Conceptual level 48.8 33.0 41.4 27.0 0.672 NS
Connors’ Oppositional 67.7 8.4 67.8 11.8 0.978 NS
Inattention 75.9 9.1 71.2 12.4 0.381 NS
Hyperactivity 78.6 11.3 79.4 9.0 0.859 NS
Impulsivity 82.7 11.4 78.2 9.2 0.308 NS
66 F. El Baza et al.
epithelial cells and controls Mg
2+
urinary excretion could be a
putative factor in the previous finding [12].
The results gives us the clue that the total serum magnesium
concentration is not the best method to evaluate the magne-
sium status; as changes in serum protein concentrations may
affect the total concentration without necessarily affecting
the ionized fraction or total body magnesium status, since
about 30% of serum magnesium is bound to proteins [13].
For this reason, we used both serum and hair magnesium to
assess magnesium status.
Magnesium interacts with noradrenergic and dopaminergic
system [14]. The role of noradrenergic and dopaminergic sys-
tem in the pathophysiology of ADHD has been extensively
studied. In addition, stimulants and atomoxetine act through
adrenergic and dopaminergic receptors [15]. Thus, magnesium
deficiency could be related to the pathophysiology of ADHD.
In agreement with our results came a study done by
Kozielec [16] who observed low magnesium level in ADHD
children; where Magnesium deficiency was found in 95 percent
of ADHD patients examined, most frequently in hair (77.6
percent), in red blood cells (58.6 per cent) and in blood serum
(33.6 percent) indicating that magnesium deficiency in children
with ADHD occurs more frequently than in healthy children.
Mousain-Bosc et al. [17] reported that, intraerythrocytic
magnesium were lower in children with ADHD, while serum
magnesium was normal.
Similar results were obtained also from another Egyptian
study, where serum ferritin, zinc and magnesium levels were
lower in ADHD children than controls (p= 0.001) [18].
We can speculate that magnesium deficiency in ADHD due
to behavioral manifestation related to the core pathology of
ADHD [19]. Children with ADHD may suffer from feeding
problems owing to their stubbornness and unexpected reac-
tions to the parent’s orders [20]. They lack the attention
required to sit through a meal to obtain adequate levels of
nutrient intake, as well as the appetite suppressant effects of
treatment medication [21].
In the current study, magnesium deficiency was more
prevalent in males than in females. Also, no significant differ-
ence was observed regarding serum magnesium and sociode-
mographic data. This finding was supported by previous
study, where magnesium levels were higher in girls with
ADHD [22]. This gender difference seen in our studies, could
be partly due to the hormonal difference between males and
females where estrogen secretion is responsible for the better
magnesium utilization by young female adolescents (it may
slow the metabolic rate and hence increases the magnesium
level in hair) [23].
At the beginning of the study there was no significant dif-
ference among cases with normal (group A) and cases with
low hair magnesium (group B) as regards the different psychi-
atric scales. This could be explained by the fact that ADHD is
largely a heterogeneous disorder stemming from genetics and
environmental factors [24] and, small sample size in the current
study. For that reason also not all the patients who received
the magnesium supplementation improved at follow up.
However, there was a significant correlation between hair
magnesium and total IQ, and an indirect significant correlation
between hair magnesium and hyperactivity score. Previous
studies demonstrate that magnesium deficiency was associated
with deficient cognitive function and low academic achieve-
ment in adolescent girls. Moreover, familial hypomagnesemia
was related to inattention, mental retardation and speech
problems [25].
Table 5 Correlation between magnesium hair and serum levels and the psychiatric scales among children with ADHD.
Total IQ Categories completion Conceptual level Oppositional Inattention Hyperactivity Impulsivity
Hair Mg
Mg/kg
r0.749 0.028 0.105 0.173 0.311 0.663 0.086
P
*
0.0001 0.939 0.773 0.493 0.210 0.003 0.734
Sig HS NS NS NS NS S NS
Serum Mg
Mg/dl
r0.097 0.651 0.565 0.996 0.370 0.704 0.946
P
*
0.340 0.133 0.168 0.001 0.187 0.080 0.014
Sig NS NS NS NS NS NS NS
R= correlation coefficient; NS = non significant; HS = highly significant.
*
Pearson correlation test.
Table 6 Comparison between psychiatric scales at baseline
and at follow up among magnesium treated cases (group B1).
Mean N±SD PSig
Categories
completion
Before
treatment
3.40 5 2.074 0.061 NS
After
treatment
5.80 5 0.447
Conceptual level Before
treatment
49.20 5 30.376 0.038 S
After
treatment
81.00 5 10.173
Oppositional Before
treatment
64.44 9 12.022 0.024 S
After
treatment
52.78 9 10.022
Inattention Before
treatment
69.89 9 13.797 0.012 S
After
treatment
53.44 9 8.918
Hyperactivity Before
treatment
79.22 9 9.066 0.001 HS
After
treatment
55.33 9 10.380
Impulsivity Before
treatment
77.44 9 8.705 0.001 HS
After
treatment
56.44 9 10.608
SD = standard deviation; NS = non significant; HS = highly
significant; S = significant; Sig. = Significance.
*
Paired ttest.
Magnesium in ADHD 67
In phase 2 of the current study, magnesium deficient
patients were randomly assigned into two groups; those who
received magnesium supplementation and those who did not.
On follow up; in the magnesium supplemented group,
Conners’ parents rating scores sub items improved, with a
highly significant improvement in the hyperactivity
(p= 0.001) and the impulsivity domain (p= 0.001). Other
sub items improved, but the improvement was not statistically
significant. The highly significant improvement seen in hyper-
activity could be due to the fact that magnesium is needed for
relaxation at the neuromuscular junctions [26]. Similarly, fol-
low up of cognitive function using Wisconsin card sorting test,
showed significant improvement in the category completion
(p= 0.061) in the conceptual level (p= 0.038).
In the current study; despite the general improvement of
Conners’ scores in group B1 compared to group B2 after sup-
plementation, this improvement pushed the patient from one
category of the rating scale (obtained at beginning of the
study) to another only in the change in inattention
(p= 0.05), and the hyperactivity (p= 0.001) sub items of
Conners’ scale; otherwise the changes in the other components
were not statistically significant.
On the other hand, follow up of the magnesium unsupple-
mented group showed that the cognitive function and
Conners’ rating scale sub items did not improve, except for
Table 7 Comparison between the psychiatric scales at baseline and at follow up among untreated ADHD cases with magnesium who
had low hair magnesium levels (group B2).
Mean N±SD PSig
Categories completion Baseline 2.40 5 2.074 0.063 NS
Follow up 3.60 5 1.517
Conceptual level Baseline 33.60 5 23.891 0.066 NS
Follow up 43.00 5 21.966
Oppositional Baseline 71.22 9 11.300 0.018 S
Follow up 66.89 9 10.994
Inattention Baseline 72.56 9 11.588 0.237 NS
Follow up 70.56 9 11.970
Hyperactivity Baseline 79.67 9 9.500 0.201 NS
Follow up 76.44 9 8.805
Impulsivity Baseline 78.89 9 10.093 0.062 NS
Follow up 71.78 9 8.941
SD = standard deviation; NS = non significant; S = significant; Sig. = Significance.
*
Paired ttest.
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Percent
Categories completion
Conceptual level
Oppositional
Inattention
Hyperactivity
Improvement at follow up
Treated with Mg
Untreated
0%
88.9%
11.1%
77.7%
22.2%
55.6%
20%
0%
60% 60%
Figure 2 Improvement of psychiatric scales at follow up among treated (group B1) and untreated group (group B2).
Table 8 Adverse effects among magnesium treated cases
(group B1).
Adverse effect (Group B1) N=9 %
Negative 7 77.8
Positive 2 22.2
68 F. El Baza et al.
the oppositional scale, as parents of this group were assigned
to behavioral therapy.
Our results match with those obtained by Nogovitsina [27]
where analysis was done after 30 days of magnesium supple-
mentation to ADHD patients and showed improvement in
the form of significant decrease in the total point scores on
all scales (p< 0.05; p< 0.001) There was also a significant
decrease in point scores on the ‘‘anxiety’’ and ‘‘impairment
of attention and hyperactivity’’ scales.In another study, sup-
plementation of ADHD patients with Mg-B6 regimen for at
least 2 months significantly modified the clinical symptoms of
the disease: namely, hyperactivity and aggressiveness were
reduced, school attention was improved. When the Mg-B6
treatment was stopped, clinical symptoms of the disease reap-
peared in few weeks [17]. Similar results were obtained by
other studies [27,28].
These results suggest that magnesium supplementation, or
at least proper amounts of magnesium in the diet, may prove
to be beneficial for children with ADHD. Further research is
needed to help to identify the etiology, impact, and possible
therapeutic implications of low micronutrient status in
ADHD, given the essential nature of these micronutrients in
the production of the neurotransmitters involved in ADHD.
Regarding the side effects of supplementation, we found
that 22% of the cases given the treatment suffered from mild
attacks of abdominal pain or diarrhea. This is consistent with
Jaing [29] who reported that oral magnesium supplementation
can cause mild side effects, such as diarrhea and abdominal
cramps.
Although, our study is limited by small number of cases,
but it has an advantage on other studies in that we used mag-
nesium without B6 in treatment of ADHD, the use of sibs as a
control group and the use of objective scales (Wisconsin card
sorting test) in the assessment of response to magnesium
treatment.
5. Conclusion
Mg supplementation for few weeks significantly reduced the
clinical symptoms of ADHD. Further studies on larger sam-
ples and over longer periods of time are needed to generalize
the study.
Conflict of interest
The authors declare no conflict of interest. There is no finan-
cial and personal relationship with other people or organiza-
tions that could inappropriately influence their work.
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