Alghadir et al. BMC Molecular and Cell Biology
https://doi.org/10.1186/s12860-023-00490-5(2023) 24:29

BMC Molecular andCell Biology

Open Access

RESEARCH

Mineral elements and adiposity‑relatedconsequences in adolescents with intellectual
disabilities
Ahmad H. Alghadir1, Sami A. Gabr1 and Amir Iqbal1*

Abstract
Background Patients with intellectual disabilities are shown to have a limited capacity for cooperation,communication,and other biological consequences, which significantly require a specialized interest in healthcare
professionals worldwide.
Aim In this respect, the present study was designed to evaluate the levels mineral elements, and their correlation
with oxidative stress markers and adiposity markers; leptin (L), adiponectin (A), and L/A ratio in adolescents withintellectual disabilities.
Methods A total of 350 schoolchildren aged (12–18 years) were randomly invited to participate in this prospective,
observational study. Only 300 participants agreed to participate in this study. According to Intelligence quotientsscores (IQ) measured by WISC-III, the participants were classified into two groups; the healthy control group (no = 180;
IQ = 90–114); and the moderate intellectual disability (MID) group (no = 120; IQ = 35–49). Adiposity markers; body massindex (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), physical activity scores, adipokines biomarkers;
leptin, adiponectin, L/A ratio, oxidative stress, and plasma mineral elements were evaluated by prevalidated questionnaires,
inductively coupled plasma-mass spectrometry (ICP-MS), colorimetric, and immunoassay techniques.
Results Intellectual disability of moderate type was reported in 40% of the studied populations most of them aremen aged 12–18 years (66.6% for men vs. 33.3 for females). Obesity was shown to be associated with the degreeof intellectual disability of the students. There was a significant (P = 0.001) increase in the BMI, WHR, and WHtR
scores as obesity markers with poor physical activity (P = 0.01) in students with poor disability compared to healthy
controls (HC). The levels of leptin (P = 0.001), adiponectin (P = 0.01), and L/A ratio (P = 0.01) as adiposity biomarkers
were significantly increased in students with MID compared to healthy controls. Also, oxidative stress measured
by malondialdehyde (MDA) (P = 0.01) and total antioxidant capacity (TAC) (P = 0.01) were significantly increased
in students with MID compared to healthy control subjects. In addition, mineral elements were shown to be linked
with intellectual disability. The data showed that the levels of Fe, Mn, Zn, Hg, Pb, Ca, Cr, Mg, and Ni significantly(P = 0.001) increased, and the levels of Al, Na, K, Cu, and Zn/Cu ratio significantly (P = 0.001) decreased in subjects
with MID*Correspondence:Amir Iqbal
physioamir@gmail.com; ajamaluddin@ksu.edu.sa
Full list of author information is available at the end of the article© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to theoriginal author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images orother third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit
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to the data.

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compared to healthy controls. Correlation analysis concluded that changes in mineral elements significantly correlatedwith adiposity markers, oxidative stress, and the scores of intellectual disability (WISC III-IQ score).
Conclusion The intellectual disability of moderate type (MID) was associated with abnormal changes in the levelsof essential mineral elements and adipokines and increased levels of cellular oxidative stress. Thus, evaluatingplasma mineral elements and adipokines levels could bea potential diagnostic parameter for diagnosing MID.
Keywords Oxidative stress, Mineral elements, Adipokines,Intellectual disability, Adolescence

Introduction
Obesity is considered one of the most problematic issuesof health worldwide. It affects all populations at different ages and socio-economic levels. Most studies reveal
the contribution of obesity to human diseases, including
diabetes mellitus [1, 2]. It becomes significantly associated with food containing high calories and poor physical activity. Several research studies linked obesity witheconomic, social, and lifestyle changes that lead to major
public health problems [2–4]. In childhood, obesity
is shown to be linked with several genetic and environmental factors. Lifestyle, social culture, and genealogy
play a potential role in the spreading rates of obesity
worldwide [4–8].
On biochemical and cellular levels, obesity is controlled
by some proteins expressed from adipocytes, especially
leptin. Leptin is a neurohormone (16 kDa) expressed byadipocytic cells and predominantly released into blood
circulations. Physiologically, the release of leptin acts asa signal to the brain to control the storage of energy by
the human body [9]. Thus, it was reported that leptin significantly controls food intake by inhibiting the releaseof Neuropeptide Y (NPY) through its hypothalamic
receptors, reducing food intake with increased body
thermogenesis [9].
Essential menirals and trace elements are cofactors
essential for several cellular processes in human bodies.
It plays potential roles in normal and diseased cells as
regulatory, immunologic, or antioxidant factors, particularly as cofactors or essential components in the structures of cellular enzymes [10]. In obesity, trace elements
are shown to be associated with the severity of the disease and its associated complications, such as peroxidation, inflammation, and metabolic disturbances [11, 12].
Previously, the deficiency in the levels of cellular
micronutrients was reported to be significantly associated with fat deposition and chronic inflammation[13–15]. In addition, low levels of iron, zinc, and a deficiency in the levels of essential vitamins (A, E, and C)
were estimated in children and adolescents with obesity compared to non obese controls of the same age[16–19]. These micronutrients, especially vitamins (A,E, and C), are essential for inhibiting or suppressing
leptin expression [13, 20–22].
Several research studies reported a significant association between obesity levels and youth with intellectualand developmental disabilities. Obesity was significantly
reported in children or adolescents with intellectual disabilities (ID). It was nearly twice the prevalence for those
without ID (28.9% vs. 15.5%) [23, 24]. This may be related
to poor physical activity and longer time spent sitting infront of screen-based media [25–30]. In childhood andadolescence, cognitive, behavioral, and neuropsychological defects; particularly ID, showed to be associated respectively with exposure to heavy metals such asarsenic (As), cadmium (Cd), manganese (Mn), mercury(Hg), and Lead (Pb) [31–33]. Reduced IQ and cognitive
functions, learning difficulties, and impaired growth
were reported in children with Pb blood levels above 10
μg·dL − 1 [34–37]. The pathophysiology of metal intoxication and producing intellectual or developmental
defects may proceed with cellular free radical oxidative
stress mechanisms [38, 39]. Higher malondialdehyde(MDA) and lower total antioxidant capacity (TAC) werereported as an indicator of cell membrane injury [38, 39].
In this respect, the present study was designed to evaluate the levels of mineral elements, and their correlation
with oxidative stress markers and adiposity markers; leptin (L), adiponectin (A), and L/A ratio in adolescents withintellectual disabilities.

Materials and methods
Subjects

A total of 350 Saudi school students aged (12–18 years)
attending various schools in Riyadh were randomly
invited to participate in this study. Firstly, the school
administration was notified about the need and importance of the study. Once necessary permission was
obtained, they connected us with the students and theirparents. Only 300 participants agreed to participate inthis study. None of the selected participants have any
physical disabilities, genetic disorders, or acute infections or received medical therapy for ID or obesity that
had affected the data. Based on the intelligence quotients(IQ), the participants were classified into two groups; thenormal healthy group (no = 180; IQ = 90–114); and theAlghadir et al. BMC Molecular and Cell Biology(2023) 24:29

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Table 1 Baseline of clinical and laboratory characteristics of thestudy groups. Healthy control (HC) and adolescents subjects
suffering from moderate intellectual disabilities (MID) (n = 300;
mean ± SD)

Moderate intellectual disability (IQ 40–54), below normal (IQ 70–84), normal (IQ 85–114), Above normal (IQ
115–129), Gifted (IQ 130–144), and Highly Gifted (IQ
145–160). In this study, IQ measurements of the participants were in the range of normal (IQ = 85–114; n = 180)and moderate (IQ = 40–54, n = 120), respectively.

Parameters

HC (n = 180; 60%)
(IQ = 85–114)

MID (n = 120;40%)
(IQ = 40–54)

P-value

Age in years

14.86 ± 2.5

14.9 ± 1.5

0.123

Anthropometric measurements

Genders (B/G)

120/60

80/40

0.13

All participants’ height and weight were estimatedusing standardized procedures such as a tape measure
and calibrated Salter Electronic Scales (Digital Pearson
Scale; ADAM Equipment Inc., Columbia, MD, USA),
respectively. Validated universal cutoff values [42, 43]
were used to calculate adiposity parameters, such as
BMI and Waist-to-height ratio (WHtR), respectively.

BMI (kg/m2)

18.6 ± 2.3

32.8 ± 6.3

0.001

Waist (cm)79.3 ± 5.1

116.3 ± 8.3

0.001

Hips (cm)

92.5 ± 2.6

78.9 ± 11.8

0.001

WHR

0.79 ± 0.029

1.47 ± 0.16

0.001

WHtR

0.46 ± 0.05

0.89 ± 0.09

0.001

32.6 ± 4.31

21.3 ± 2.1

BMR (kcal/day)

3.6 ± 2.5

1.36 ± 1.4

TEE (kcal/day)

6.7 ± 5.3

2.9 ± 1.6

PA scores

4.9 ± 3.1

1.9 ± 1.25

WISC- IQ test scores 93.8 ± 2.6

39.2 ± 3.1

Physical activity (PA): ­VO2 max
(ml/kg*min)

0.01

Assessment of adiposity markers

0.001

Values are expressed as mean ± SD; Kruskal–Wallis one-way ANOVA and posthoc (Tukey HSD) test were used to compare the mean values of the studied
variables. Variables were considered significantly different at P < 0.05
Abbreviation: HC Healthy control, BMI Body mass index, WHR Waist to hip ratio,
WHtR Waist to height ratio, PA Physical activity, VO2 max maximal oxygen uptake,
BMR Basal metabolic rate (kcal/day), TEE Total energy expenditure (kcal/day),
WISC- IQ Wechsler Intelligence Scale test

moderate ID group (no = 120; IQ = 35–49). Whole blood
samples were collected from all participants and centrifuged ( 1 min at 1400 rpm), and the resulting plasma samples were kept frozen at—20°C until reused. Demographic
and clinical data of the participants are in Table 1.
Ethical considerations

The current protocol was prepared according to the
ethical guidelines of the 1975 Declaration of Helsinki
and finally reviewed and approved by the ethics subcommittee of King Saud University, Kingdom of Saudi
Arabia, under file number ID: RRC-2015–089. All participating schoolchildren were informed of the steps
and all protocol details. The participants’ parents wereassigned to return written informed consent before
data collection.
Intelligence assessment

The participants’ intelligence quotients (IQ) were evaluated using a pre-validated Wechsler Intelligence Scale
for Children (WISC-III), as previously reported [40, 41].
The results of IQ measured by WISC-III are categorized
into seven scores; Mild intellectual disability (IQ 55–69),

Adiponectin and leptin levels as adiposity biomarkers were estimated in all participants’ plasma samples
using a specific ELISA kit (R&D Systems®, Minneapolis, USA). All samples were estimated in duplicate
according to the manufacturer’s instructions to avoid
inter-assay variation, as previously reported [44]. In
contrast, the detection limits for adiponectin and leptin
were 5 pg/mL, respectively [44].
Assessment of essential mineral elements concentrations

In this experiment, plasma samples of all participants
were subjected to estimate mineral elements concentrations by using a Thermo Fisher Scientific (Waltham,
MA, USA) iCAP— Q instrument, equipped with standard components and accessories: a MicroMist™ nebulizer (Glass Expansion, Port Melbourne, Australia) as
previously reported [45]. This method used multi-element standard solutions (Plasma CAL, SCP Science,
Baie D’Urfé, Canada) to prepare calibration standards.
In addition, an iso standard solution (Madrid, Spain)
was used to prepare the internal standard solution. Ten
replicate measurements of the blank solution (2% v/v
HNO3) were performed to calculate the limits of detection (LoD) as previously reported [45].
Assessment of oxidative stress

As a quantitative measure of lipid peroxidation,
Malondialdehyde was estimated in the plasma samples
using high-performance liquid chromatography, as
mentioned previously [46–48]. In addition, a total
antioxidant capacity (TAC), a measure of oxidative
stress, was estimated in the plasma samples using acolorimetric assay kit (K274-100; BioVision, Milpitas,
CA, USA). The antioxidant activity was measured as a

Alghadir et al. BMC Molecular and Cell Biology(2023) 24:29

function of Trolox concentration at a wavelength of (λ;570 nm) as previously reported [47, 48].
Assessment of physical activity

Physical fitness score is measured as maximum oxygen uptake (VO2 max) and total energy expenditure(TEE), as previously reported [29, 47–49]. Total energy
expenditure (TEE) was evaluated by calculating basal
metabolic rates (BMR) from body mass, height, age,sex, and type of physical activity of all participants
using a pre-validated equation as previously reported[29, 47, 48].
Statistical analysis

In this study, the statistical software SPSS version 18 wasused. The results obtained were expressed as Mean, andstandard deviation among groups, Kruskal–Wallis oneway ANOVA and post-hoc (Tukey HSD) test were used
to compare the mean values of the studied variables [45].
Additionally, post hoc pairwise multiple comparisonsusing Bonferroni correction and the one-way analysis of covariance were performed to evaluate significant
differences in trace elements hair contents between the
study groups. The relationship between various study
parameters was performed in steps by Spearman rankcorrelation analysis. The data obtained were consideredsignificant at P < 0.05 [45].

Results
The clinical and baseline characteristics of 300 adolescents with a mean range of age 14.9 ± 1.5 years who participated in this prospective study are shown in Table 1.
In this study, intellectual disability of moderate type(MID; WISC-IR score:39.2 ± 3.1) was reported in 40%of the study population, most of whom are men (66.6%
for men vs. 33.3 for females) (Table 1). Compared tohealthy control subjects, adiposity markers; BMI, waist,
hips, WHR, and WHtR significantly increased (P = 0.001)
in adolescents with MID (Table 1). In addition, physicalactivity scores measured in terms of VO2 max, BMR, andTEE significantly decreased (P = 0.01) in adolescents with(MID) compared to those of healthy controls (HC), as
shown in Table 1 and Fig. 1. Also, IQ-score was lower inadolescents with MID compared to healthy controls, as
shown in Table 1 and Fig. 1.
In this study, plasma mineral elements were significantly estimated in all participants (Table 2). Adolescentswith MID showed a significant increase in the levels of
Fe, Mn, Zn, Hg, Pb, Ca, Cr, Mg, and Ni, and they significantly decreased in Al, Na, K, Cu, and Zn/Cu ratio levels
compared to healthy controls (Table 2).

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The physiological changes in the plasma levels of mineral elements correlated positively with the WISC-IQ
score, estimating the potential role of these elements inthe pathogenesis of intellectual disability among younger
ages with MID (Table 3). Moreover, the results showedthat the increase in the levels of Fe, Mn, Zn, Hg, Pb, Ca,
Cr, Mg, and Ni, and the decrease in the levels Al, Na, K,
Cu, and Zn/Cu ratiocorrelated positively with the cellularoxidative stress parameters; MDA, TAC, and negatively
with adiposity parameters; BMI, WHR, and WHtR as
shown in (Table 4).
However, increased or decreased levels of mineral elements showed no statistical significance with gendereffect (Table 4). The increment of Fe, Mn, Zn, Hg, Pb, Ca,
Cr, Mg, Ni, and decrement in the levels of Al, Na, K, Cu,
and Zn/Cu ratio showed no significant effect with genderin subjects with ID (Table 4).
Also, leptin, adiponectin, and L/A ratio as adipokines
biomarkers were estimated in all studied populations.
Higher plasma levels of leptin and L/A ratio and lower
adiponectin concentrations were reported in adolescentswith MID (P = 0.001) compared with healthy controls(Fig. 1). In addition, MDA and TAC as parameters of oxidative stress were significantly evaluated in this study.
The levels of MDA significantly increased, and TAC significantly decreased in adolescents with MID (P = 0.001)
compared to healthy controls (Fig. 1).
In subjects with MID, the correlation between serum
levels of adipokines and plasma mineral elements
and clinically studied adiposity variables are shownin (Table 4). Leptin, adiponectin, and L/A as adiposity markers correlated negatively with BMI, WHtR, PA
scores, and TAC and positively with gender, WISC-IQ
score, MDA, and plasma trace elements (Table 5).
Regarding gender effect on physical activity, adipokines
levels, and oxidative stress, girls with MID had lower
physical activity scores than males in the same group(Fig. 2A). Also, higher leptin and L/A ratios with lower
plasma adiponectin levels were reported in girls withMID compared to males of the same group (Fig. 2B,
C and D). However, in normal control subjects, there
were comparable levels of the studied parameters;
leptin (p = 0.001), adiponectin (p = 0.001), and L/A ratio(p = 0.001) in boys compared to healthy girls as shown in
Fig. 2B, C and D). In addition, a significant increase in thelevels of MDA and a decrease in the levels of TAC activity
were reported in girls (P = 0.001) compared to men of thesame group ( Fig. 3A and B).

Discussion
Intellectual and developmental disabilities are broadly
conceptualized to include a range of physical, mental, andbehavioral impairments [26]. Patients with intellectual

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Fig. 1 Plasma levels of adiponectin, leptin (L), and L/A ratio (pg/mL) (A), MDA and TAC (B), along with physical activity (C), and IQ-score (D) in HC(n = 180) and MID (n = 120). **p < 0.01 (KruskaleWalis, Dunn’s post hoc test). ***p < 0.001 (KruskaleWalis, Dunn’s post hoc test). HC: healthy controls,
MID: moderate intellectual disability; IQ: Intelligence quotients; MDA: malondialdehyde, TAC: total antioxidant capacity

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Table 2 Mineral elements levels (µg/g) in plasma samples of thestudy participants, reported as mean ± SD and (range) according
to the intellectual disability status measured by the Wechsler
Intelligence Scale test. (HC = healthy control; MID = moderateintellectual disabilities
Element (µg/g)

HC (n = 180; 60%)
(IQ = 85–114)

MID (n = 120; 40%)
( IQ = 40–54)

P-value

Table 4 Correlation between plasma mineral elements andadiposity parameters, WISC- IQ score,oxidative stress, and genderin adolescents with MID
Variables

Elemental decrease (⬇)
Al

4.5 ± 2.8

2.9 ± 1.8

0.001

Na

31.7 ± 4.7

18.2 ± 2.8

0.001

K

6.8 ± 4.6

4.7 ± 2.5

0.001

Zn/Cu ratio

0.69 ± 0.11

0.41 ± 0.18

0.001

Cu

116.3 ± 8.3

89.3 ± 12.8

0.001

Elemental increase (⬆)
Zn

25.7 ± 3.1

36.5 ± 9.7

0.001

Fe

3.75 ± 2.8

8.7 ± 4.3

0.001

Hg

0.85 ± 0.89

1.7 ± 0.42

0.001

Pb

0.21 ± 0.12

0.42 ± 0.13

0.001

Ca

6.2 ± 1.5

8.7 ± 1.3

0.001

Cr

22.3 ± 4.6

31.1 ± 2.4

0.001

Mg

1.5 ± 1.1

2.9 ± 0.86

0.001

Ni

2.7 ± 0.25

4.2 ± 1.5

0.001

Mn

0.18 ± 0.120

0.95 ± 1.14

0.001

Data expressed as mean ± SD. Post hoc analysis using the Bonferroni method;
The data obtained were deemed significant at P < 0.05 (HC vs. Moderate ID)

Table 3 Correlation between plasma mineral elements with
WISC-IQ score as a measure of ID in healthy control (HC) andadolescents with MID
HC (n = 180; 60%)
(IQ = 85–114)

MID (n = 120; 40%)
( IQ = 40–54)

R

P

R

P

Al

0.012

0.01

0.015

0.05

Na

0.015

0.05

0.025

0.05

K

0.036

0.05

0.039

0.05

Zn/Cu ratio

0.056

0.01

0.058

0.01

Cu

0.035

0.01

0.49

0.02

Zn

0.4051

0.001

0.057

0.001

Fe

0.038

0.006

0.046

0.008

Hg

0.035

0.01

0.037

0.05

Pb

0.036

0.01

0.048

0.02

Ca

0.038

0.001

0.042

0.002

Cr

0.012

0.001

0.048

0.003

Mg

0.024

0.001

0.052

0.003

Ni

0.021

0.001

0.058

0.002

Mn

0.035

0.001

0.065

0.001

Element (µg/g)

Elemental decrease (⬇)

Elemental increase (⬆)

Plasma Trace ­elementsc
Elements
with
Increased­valuesa

Elements with
Decreased­valuesb

R

R

P

P

Gender (M/F)

0.0125

0.12

0.034

0.18

WISC- IQ score

0.124

0.001

0.068

0.001

Adiposity paramters (BMI, WHR, WHtR)-0.5240.001-0.0890.001

Oxidative stress (MDA, TAC)

0.452

0.001

0.256

0.001

a
{ Fe, Mn, Zn, Hg, Pb, Ca, Cr, Mg, Ni}; b{ Al, Na, K, Cu, and Zn/Cu ratio}; cData are R(spearman)

disabilities have been shown to have a limited capacity
for cooperation, communication, and other biologicalconsequences, which significantly requires a specializedinterest from healthcare professionals worldwide [50, 51].
In this study, intellectual disability of moderate type(MID) was reported in 40% of the studied populations,most of whom are men aged 12–18 years (66.6% for men
vs. 33.3 for females). The incidence of MID among thestudied sample was linked with the release of adiposity
markers; BMI, WHR, and WHtR, and lower physicalactivity compared to healthy control subjects. Matchedwith our results, obesity was significantly reported inchildren or adolescents with intellectual disabilities (ID);it was nearly twice the prevalence for those without ID(28.9% vs. 15.5%) [23, 24]. This may be related to poor
physical activity and longer time spent sitting in front ofscreen-based media [26–30].
Supported data also recently reported that childhood
overweight or obesity is clearly very pervasive or problematic among healthy children and those with ID [23,52–55]. This is commonly attributed to poor physicalactivity and increased sedentary lifestyles, such as excess
food intake and screen-based media use for longer periods[23, 52–55]. In addition, an elevated weight status among
youth with ID is the leading risk for mental health problems and increased morbidity and mortality rates among
adults with ID [55]. Thus, increasing physical activity anda self-monitoring diet were recommended among younger
and older ages to yield clinically meaningful weight losses
among adults with ID, reducing the severity of ID-relatedconsequences [26, 56, 57].
Despite the prevalence of obesity increasing and prevailing among people with disabilities [58, 59], surprisingly, no or little attention has been paid to addressing
the profile or potential roles of adipokines as measuresof adiposity and metabolic disorders and oxidative stress(OS) among youth with disabilities [60].

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Table 5 Correlation between adipokines biomarkers with plasma mineral elements and clinically studied variables of adiposity inadolescents with MID
Variables

Adipokines (pg/ml) as markers of adiposity
Leptin (L)Adiponectin (A)L/A ratio

R

P

R

P

R

P

BMI

-0.2150.01-0.2380.01-0.3240.001

WHR-0.2580.01-0.3420.01-0.365

0.001

WHtR

-0.2350.01-0.3690.05-0.3420.01

PA score-0.2510.05-0.3920.01-0.2590.001

Gender

0.328

0.01

0.393

0.01

0.254

0.01

MDA

0.265

0.05

0.256

0.002

0.249

0.001

TAC​

-0.3680.001-0.2380.002-0.4560.001

Mineral elements

0.358

0.001

0.367

0.004

0.357

0.01

WISC- IQ score

0.325

0.002

0.213

0.01

0.256

0.001

In the present study, adiponectin and leptin, the mostessential adipokines associated with adiposity and metabolic disorders, were estimated among adolescents e with
ID disabilities. Changes in plasma levels of leptin, L/A
ratio, and adiponectin are significantly associated with theincidence of ID among adolescents. Higher plasma levelsof leptin and L/A ratio and lower adiponectin concentrations were significantly reported in adolescents with MID(P = 0.001) compared with the healthy controls.
In addition, MDA and TAC as parameters of oxidative
stress were significantly evaluated in this study. The levelsof MDA significantly increased, and TAC significantly
decreased in adolescents with MID (P = 0.001) comparedto the healthy controls.
In adolescents, obesity was associated with severe
health complications such as mental disorders, longterm vascular complications, oxidative stress, andhigher rates of severe metabolic syndrome [61, 62] previously. At younger ages, the lower levels of adiponectin
and the higher levels of leptin were shown to be associated with the risk for mental health problems, particularly ID [26, 23, 52–62]. Similarly, the levels of OS
measured by MDA were significantly higher, along witha reduction in TAC activity in persons with ID compared to the control group [38, 39, 46].
In this current study, leptin, adiponectin, and L/A were
measured as markers of adiposity in subjects with ID correlated negatively with BMI, WHtR, PA scores, and TAC
and positively with gender, WISC-IQ score, and MDA.
A cascade of events characterized by an asymptomatic
inflammatory process, including inflammatory cytokines
along with oxidative stress significantly associated withthe severity of intellectual disabilities (ID) among older
and younger ages [46, 62, 63]. Thus, monitoring the levels of oxidative and adipokine molecules could serve as

biomarkers of ID which may allow early diagnosis andintervention and improve the quality of care for persons
with ID.
In obese people, the metabolic disturbances aredecompensated. Although overweight is a preclinicalcondition, obesity is a clinically manifested metabolic
disorder, including mineral imbalances [12], which could
play a potential role in the pathogenesis of intellectual
disabilities (ID).
In this study, plasma mineral elements were estimatedin all participants. A significant increase in the levels of
Fe, Mn, Zn, Hg, Pb, Ca, Cr, Mg, and Ni, and a decrease in
the levels of Al, Na, K, Cu, and Zn/Cu ratio were reported
in cases with MID compared to healthy controls. Changes
in the levels of mineral elements correlated positively
with plasma levels of adipokines; leptin, adiponectin, L/A
ratio, MDA, TAC, and ID score (WISC-IQ score) andnegatively with adiposity parameters; BMI, WHR, andWHtR. In addition, the increment of Fe, Mn, Zn, Hg, Pb,
Ca, Cr, Mg, Ni, and decrement in the levels of Al, Na, K,
Cu, and Zn/Cu ratio showed no significant effect withgender in subjects with ID.
Mineral elements as essential nutrients showed
potential regulatory, immunologic, and antioxidant
functions in biological systems [10]. Their potential
action was significantly related to their incorporation
as essential components or cofactors of enzymes
throughout cellular metabolism [10]. Thus, it wasreported that trace elements and minerals interferewith the pathogenesis of obesity and its complications,such as mental diseases, mainly through theirinvolvement in the processes of peroxidation andinflammation [11]. Reduced IQ and cognitive
functions, learning difficulties, and impaired growth
were reported in children with Pb blood levels below

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Fig. 2 Effect of Gender on physical activity (A), plasma levels of adipokines (pg/mL); leptin (B), Adiponectin (C), and L/A ratio (D) in HC (n = 180)
and adloscence withMID (n = 120). HC: healthy controls, MID: moderate intellectual diability. **p < 0.01. ***p < 0.001 ManneWhitney testAlghadir et al. BMC Molecular and Cell Biology(2023) 24:29

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Fig. 3 Effect of Gender on oxidative stress plasma levels MDA (A) and TAC (B) in HC (n = 180) and adloscence withMID (n = 120). *p < 0.01.
**p < 0.001 Manne Whitney test. MDA: malondialdehyde, TAC: total antioxidant capcity, HC: healthy controls, MID: moderate intellectual diability

10 μg·dL − 1 [34–37]. Also, the pathophysiology
of mental intoxication and producing intellectualor developmental defects may proceed via cellular
free radical oxidative stress mechanisms [38, 39]. In
recent studies, the levels of iron, copper, and zinc
were lower in the plasma / serum of the children withintellectual disabilities compared to typically developing
controls [64–68]. However, the relationship between
physiological antagonists and intellectual activity isless clear. While some studies have suggested that
excess intake of certain minerals can interfere with theabsorption or utilization of other essential minerals[69–71], it is not clear how this affects cognitive
function, and intellectual abilities in children andadolescents.

The usual normal human health needs adequate
amounts of essential and trace elements with optimum
levels either increasing or decreasing according to
the vital cellular processes [72–76]. It was reviewed
previously that the administration of selective
antioxidants along with essential trace elements andminerals were required efficiently to reduce the extent ofoxidative damage and related complications and to avoid
serious diseases such as beta-thalassemia major andother brain-related disorders [76]. Elements and minerals
should be present in the body in appropriate amounts
and must be available for reacting with other elements toform critical molecules as well as to participate in various
important chemical reactions [77].
According to the effect of gender, a clinical change inthe levels of adipokines; leptin, adiponectin, L/A-ratio,

Alghadir et al. BMC Molecular and Cell Biology(2023) 24:29

Page 10 of 12

oxidative stress; MDA, TAC, and detrimental changes
in the levels of essential trace elements were reported ingirls with MID compared to men of the same category.
In addition to that, the levels of adipokines and traceelements were clinically associated with adiposity parameters; BMI, WHR, WHtR, and the severity score (WISCIQ score) of the severity of intellectual disabilities (ID).
It was suggested previously that the inadequate ingressof trace elements into the biological cells may provide
deleterious effects on different tissue functions and maylead to disease [78]. For this reason, analyzing changes tooligo-element concentrations in patients with MID could
lead to a better understanding of any functional abnormalities associated with MID [78–80].
Finally, significant changes in plasma concentrationsof plasma mineral elements were reported in obese adolescents with MID, which correlated positively with oxidative stress parameters; MDA, TAC, and adipokines;
leptin, adiponectin, L/A ratios, and other related biomarkers of adiposity.

trace elements, and adipokines levels is used as a potential diagnostic parameter in diagnosing MID.

Strengthen and limitations

Declarations

Our study had several limitations. Although our study
generally showed the importance of identifying the levels of mineral elements and their association with obesity
and intellectual disability scores among younger aged
12–18 individuals, the lack of association between compromised nutritional status due to factors such as feeding difficulties, limited food choices, and medicationside effects should be addressed to evaluate long-lastingchanges of mineral elements and their essential roles in
the pathogenesis of intellectual disability among younger
ages. Our results can be interpreted as preliminary findings. Thus, further studies based on long follow-ups arerecommended to understand the potential associationof mineral elements with intellectual activities.Therefore, individualized assessments of nutritional status andmineral intake are important for guiding appropriate
interventions and monitoring the progress of intellectual
abilities among children and adolescents. In addition,
our study recommended that it is important for students
with moderate intellectual disabilities to receive adequatelevels of essential minerals in their diet to support theiroverall health and well-being. A balanced and varied dietthat includes a variety of nutrient-dense foods can help
ensure adequate mineral intake.

Conclusions
Moderate intellectual disability (MID) was associatedwith abnormal changes in essential mineral elements andadipokines levels and increased levels of cellular oxidative stress. Thus, evaluation of the plasma mineral andAcknowledgements
The authors are grateful to the Researchers Supporting Project number(RSP2023R382), King Saud University, Riyadh, Saudi Arabia for funding thisresearch.
Authors’ contributions
G.S.A. A.H.A. and A.I. proposed the study conception and design. G.S.A.
completed the practical work. G.S.A. collected data. G.S.A. and A.I. contributed
to the data analysis. A.H.A. G.S.A. and A.I. contributed to data interpretation.
A.H.A. G.S.A. and A.I. prepared the manuscript’s initial draft. A.H.A. criticallyreviewed and edited the intellectual content of the manuscript. All authors
read, understood, reviewed, and approved the manuscript’s final version to besubmitted/published and took responsibility for the intellectual content of thesame manuscript.
Funding
The study was funded by the Researchers Supporting Project number(RSP2023R382), King Saud University, Riyadh, Saudi Arabia.
Availability of data and materials
All data generated or analyzed during this study are presented in the
manuscript. Please contact the corresponding author for access to the data
presented in this study.

Ethics approval and consent to participate
The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki. It was reviewed and approved by the Ethics Sub-Committeeof King Saud University, Saudi Arabia, under file number ID: RRC-2015–089.
The study’s aims and risks were explained to all participants, and their written
informed consent was obtained before starting the study.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests, either financial or
non-financial.
Author details
1
Department of Rehabilitation Sciences, College of Applied Medical Sciences,King Saud University, P.O. Box 10219, Riyadh 11433, Saudi Arabia.
Received: 14 June 2023 Accepted: 12 September 2023

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