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ASSOCIATION BETWEEN IRON DEFICIENCY AND HEARING LOSS

Article  in  Biochemical and Cellular Archives · June 2019

DOI: 10.35124/bca.2019.19.1.1019

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 DOI : 10.35124/bca.2019.19.1.1019
Biochem. Cell. Arch. Vol. 19, No. 1, pp. 1019-1024, 2019 www.connectjournals.com/bca ISSN 0972-5075

ASSOCIATION BETWEEN IRON DEFICIENCY AND HEARING LOSS

Sami R. Al-Katib1, Yasir L. Hasson1 and Rawaa H. Shareef2
1
College of Medicine, Kufa University, Iraq.
2
College of Pharmacy, Kufa University, Iraq.
e-mail : rawaa.noora@yahoo.com, rawaah.alsaabary@uokufa.edu.iq, sami.alkatib@uokufa.edu.iq,
yasir.almansoori@uokufa.edu.iq
(Accepted 10 March 2019)

ABSTRACT : Hearing loss is one of the most frequent sensory disorder and it is a chronic condition affect the adults
population. Iron is an important elements for almost living organisms, it has essential role in the DNA synthesis, respiration
of mitochondria and transporting of oxygen. To evaluate the association between iron deficiency and hearing loss and to
find out mechanisms that lead to this association. Three hundred persons included in this study, 150 as a patients group
which are suffering from hearing loss, while the other 150 participants selected randomly as controls group and they are
free from hearing loss. The ages of all participants were ranged between 18-70 years old and controls were matched
with patients by gender and age (within 5 years). Many parameters are measured in this study, such as blood parameters
(Hb, PCV, MCV, MCH,MCHC), iron, ferritin, TIBC, Tsat and IL-6 are measured in this study. Also, body mass index
(BMI) was measured for all participants in this study. Results of this study revealed that sensorineural was the most
common type of hearing loss (74%) followed by mixing type (26%). Also, it revealed that iron, ferritin and transferrin
saturation were significantly decreasing (P<0.05) in patients as compared with controls. In addition to that, the severity
of hearing loss increase significantly with deficiency of ironand it revealed a significant decrement in the level of blood
parameters such as (Hb, PCV, MCV, MCH and MCHC) were present in patients as compared with controls. While,
there was no significant differences between patients and controls in the levels of IL-6 and in BMI. The correlation
analyses showed a significant positive correlation between ferritin and IL-6. On the other hand, there was a negative
correlation between iron and IL-6. The results of the study showed that iron deficiency has a negative impact on hearing
sensation and there is a significant relationship between iron deficiency and severity of hearing loss.
Key words : Hearing loss, iron deficiency, ferritin, interleukin-6.

INTRODUCTION bones of middle ear (ASHA, 2011). Sensorineural hearing

Hearing loss or hearing impairment define as inability
to hear and may be happen in one of the ears or both. As
indicated by the world health organization more than 5%
of the world population (360 millions) individuals have
disabling hearing loss (WHO, 2015). Loss of hearing
causing impairing in the communication and it has a
negative effect on social interaction and the life quality
(Agrawal, 2008) and it affecting around 10% of the
general population (Tucci et al, 2010), while in those
over 60 years of age the percent is increase to more than
40% (Argawal et al, 2008). The severity of hearing loss
was categorized into five grades, extended from mild
degree of impairment, moderate, moderately sever, sever
to profound degree of impairment according to the
threshold (De Bonis and Donohue, 2008).
As indicated by the National Institute Health (NIH,
2012) hearing loss can be classified upon which part of
ear was influenced into: Conductive hearing loss and this
occur when the direction of the sound is not efficient
throughout the outer canal to the ear drum and to the tiny
loss and this type occur by a disruption of sound
conduction to the inner ear, the sound not percept by
cochlea sensory cells or the sound not processed in the
cochlear nerve, auditory pathway or auditory cortical
centers (Thomas and Zahnert, 2011). Mixed hearing loss
and this kind contain both types of hearing loss (conductive
and sensorineural hearing loss).
There are many causes or factorsfor hearing loss,these
factors may be external, which are related to the
environment such as, loud noise, exposure to infection
and use of ototoxic drugs or internal which are related to
genetic cause. But, the recent researches found there is
other causes or factors that can lead to this disease such
as, iron deficiency, which is recently may be consider as
one of these factors. Iron is the one of the most essential
micronutrient for human population, it has importance in
the most of the biological function or process like
production of energy, generation of cells, respiration and
synthesis of DNA (Hentz et al, 2010; Ward and Kaplen,
2012). Deficiency of iron is one of the most widespread
1020 Sami R. Al-Katib et al
nutritional deficiency and it occur in the developing
countries and considered as the main popular health
problem and is one of the most common cause of anemia
around world (Kassebaum et al, 2014). Reduction of the
concentration of iron in total body known as iron
deficiency and may occur as a result of either excessive
loss of iron or decrease absorption of iron (Gorddard et
al, 2000).
In human body iron found in different forms, it may
be found in the heme compounds such as hemoglobin and
myoglobin (Knovich et al, 2009) and in the heme enzymes
or in non heme compounds (Dowell, 2003). In the blood,
hemoglobin is contained around 65-80% of iron,
hemoglobin is found in the red blood cells and function
of itis transfer oxygen to the tissues, while around 20-
30% of iron is found in the form of iron-storage proteins
(ferritin and hemosiderin). Ferritin is a protein for storage
iron intracellulary, the main job of ferritin is to supply
stores of iron which may be utilized in the production of
heme and ferritin is present in most tissues as cytosolic
protein but little part of it also present in the many of
nucleus of cells. The function of ferritin in the nucleus is
transfer iron to the enzymes of iron-dependent or
activation of some transcription factors in addition to its
function in the scavenge of free iron because iron may be
caused oxidative damage to the DNA (AL-khateeb et al,
2010). Serum ferritin also known as acute phase reactant
and it indicated in the acute and chronic inflammation
and it is non-specifically rise in wide proportion of
inflammatory diseases, include chronic disease of kidney
(Kalantar et al, 2006), rheumatoidarthritis, acute
infection, malignancy and otherdisease related to
autoimmunity (Zandman et al, 2007). Acute phase
response include changes in the concentration of many
proteins, which are known as the acute phase proteins.
IL-6 is not only serve as an inducer of acute phase reaction
but also it is an important player in eliciting cellular
humoral response directed against infection (Gabay,
2006). IL-6 has many of the biological activities, it is a
cytokine and a mediator for immunoglobulin class
substituting, regulator for the acute phase response and
indicator for inflammation within body (Fuster, 2014).
MATERIALS AND METHODS
Study groups
This study was a case-control study carried out at
Al-Sader Teaching Hospital at Al-Najaf city, Iraq through
a period which extend from October 2017 to March 2018.
It included one hundred fifty patients (97 males and 53
females) and one hundred fifty controls (92 males and 58
females). The study included the patients who attended
the ENT (ear-nose-throat) consultation clinic suffering
from hearing loss matched by the controls who were
selected randomly and these controls must had the same
criteria of cases except they were free from hearing loss.
The ages of the studied groups were ranged between 18-
70 years old and the controls were matched with patients
by gender and age (within 5 years). The knowledgeable
agreement was achieved from the participants before
recruiting them in the study.
Exclusion criteria
Participants who were excluded from this study
include :
- Those with temporary and known causes of hearing
loss. - Those with genetic cause (family history of hearing
loss). - Noise exposure. - Participants with comorbidities
(hypertension, diabetic, heart disease, renal disease,
thyroid disease).
- Smoker participants.
Many information were taken from every participant
in this study such as, age, sex, height, weight, history of
disease and drugs in addition to pure tone audiometry
test was don for patients.
Determination of blood parameters
Blood parameters such as, hemoglobin (Hb),
hematocrit, mean corpuscular hemoglobin (MCH), mean
corpuscular volume (MCV), mean corpuscular
hemoglobin concentration (MCHC) are measured by
hematology analyzer (Abbott, USA).
Determination of iron
It is colorimetric technique and we has been used same
procedure, which recommended by the manufacture to
detect it (Cypress, Toronto).
Determination of total iron binding capacity (TIBC)
It is another colorimetric technique, which has been
used to detect the TIBC in the serum and this method
depend on saturation of the transferrin with excess of Fe+³,
and then used the same procedure, which recommended
by the manufacture (Linear, Spain).
Determination of transferrin saturation(Tsat %):
Transferrin saturation can be determined as the
follow:
Tsat = serum iron × 100/ TIBC
Determination of human serum ferritin
This kit used for quantitative determination of human
ferritin in the serum. The main procedure used is enzyme
linked immunosorbent assay. The micro ELISA plate was
previous coated with special human ferritin antibody. Then
 Association between iron deficiency and hearing loss
we used the same procedure which recommended by the
manufacture (Elabscience, China).
Determination of interleukin-6 (IL-6)
This kit measure the quantity of IL-6 in the human
serum by applied the Sandwich-ELISA as the major
procedure. The micro-plate used in this kit had previous
coated with special antibody for human IL-6, and we used
then the same procedure, which recommended by the
manufacture (Elabscience, China).
Body Mass Index Calculation (BMI)
For all participants (cases and controls) weight and
height were calculated by using sensitive balance after
removing excessive things (e.g. shoes, bags, coats and
jackets), then the height in meters(m) and weight in
kilograms (Kg) were recorded. BMI was calculated by
divided the weight on the square of height
BMI = weight(kg) / height (m2).
RESULTS
Distribution of the patients according to the types of
hearing loss
The result of this study showed that the highest percent
of hearing loss was sensorineural type (74%), while the
remaining is mixed hearing loss (26%).
The differences ofiron parameters in the patients and
controls
Table 2 showing that the iron parameters have a
significant differences (P<0.05) in the patients group when
comparing it with controls.
Table 1 : Distribution of the patients according to the types of
hearing loss.
Type of hearing loss Number of patients Percentage
Sensorineural hearing loss 111 74%
Mixed hearing loss 39 26%
1021
Blood parameters differences in the patients and
controls
Results of the study showing that there was a
significant differences (P <0.05) in the levels of all blood
parameters of patients as compared them with the controls.
Level of interleukin-6 in the patients and controls
The result of the study showing that there was no
significant differences (P > 0.05) in the level of (IL-6)
between the cases and the controls.
Body mass index (BMI) difference in patients and
controls
Table 5 showed that there is no statistically significant
difference between the patients and controls according to
their BMI.
Relationship between iron level and severity of hearing
loss (H.L.)
Result of study shows that there was a significant
relation between level of iron and severity of H.L.
Correlation between iron and interleukin-6 (IL-6)
The result of Fig. 1 shows that there was a significant
negative correlation between the level of iron and
interleukin-6 level in the patients group. r=-0.688, P<0.01
Correlation between ferritin and interleukin-6 (IL-6)
Result of the study shows that there was a positively
significant correlation between the level of ferritin and
IL-6 in the patients group. r = 0.320, P < 0.01.
DISCUSSION
Analyzing the data of this study showed that the
sensorineural hearing loss was the most common type
(74%) followed by the mixed type (26%) and this result
may be related to the exclusion of temporary hearing loss
and hearing loss with a known causes such as conductive

Table 2 : The differences ofiron parameters in the patients and controls.

Parameter Mean±S.D of cases Mean±S.D of controls (P) (OR) (95% CI)
Iron µg/dL (71.045±27.115) (82.604±23.445) 0.0001 0.871 0.817-0.92
Ferritinng/ml ( 17.1±9.47) (22.05± 7.41) 0.0001 0.933 o.88-0.98
Tsat % (24.054± 12.97) ( 28.38± 10.1) 0.001 1.445 1.206-1.73
TIBCµg/dL (324.424±68.06) ( 300.923± 45.5) 0.001 1.31 1.1-1.5

Table 3 : Blood parameters differences in the patients and controls.

Parameter Mean±S.D Mean±S.D (P) (OR) (95% CI)
of cases of controls
Hb g/dL 12.380±2.125 13.403±1.710 0.0001 0.597 0.396-0.901
PCV 37.183±5.7516 39.076±4.5761 0.002 1.12 0.987-1.283
MCV fL 81.263±6.9165 84.227±5.1164 0.001 0.981 0.89-1.07
MCH pg 27.945±3.2136 29.177±2.5362 0.0001 1.10 0.789-1.23
MCHC g/dL 33.266±2.6361 34.002±2.4144 0.012 1.1 0.89-1.36
1022 Sami R. Al-Katib et al
degradation of the lipid saturase and desaturase and this
leading to the impairing in the production of energy in
addition to impairing the production of myelin (Todorich
et al, 2009). The myelination of axon is provide a mean
to regulate the velocity of conduction which is important
for sensory processing and highly integrative function
(Seidl, 2013). So, the reduction of myelin production or
damage of this myelin that surrounding auditory nerve
by iron deficiency result in impairing of the conduction
velocity (Tagoe et al, 2014). Also, the iron has central
job in the maturation of proper axonal (Lee et al, 2012),
preserving of the blood labyrinth barrier integrity and
cochlea homeostasis (Liu et al, 2013). Moreever, there
was old study by Sun et al (1987), who first reported
evidence of cochlear damage with iron deficiency in animal
Fig. 1 : Correlation between iron level and interleukin-6. rat model, and it found that deficiency of iron result in
many defects in the cochlea including, atrophy of strial
and reducing in the spiral ganglion cells with effect on
the sterocilia of inner and outer hair cells among affected
rats (Sun et al, 1992). In addition to iron, the ferritin
,transferrin saturation and total iron binding capacity all
these factors are significantly different between patients
and controls and this differences in the levels of them
related to the reduction of iron. Furthermore, the result
of Table 3 shows that blood parameters decrease
significantly in patients with hearing loss as compared
with controls. Deficiency of iron result in decreasing the
formation of hemoglobin, hemoglobin is an iron-
containing metalloproteins responsible for physiologic
transporting of oxygen inside red blood cells throughout
human body (Shandr et al, 2014). A lack of oxygen is
known to be fatal for human organ and may cause
malfunction and persisting of it may causing organ failure
Fig. 2 : Correlation between ferritin level and interleukin-6.
Table 4 : Level ofinterleukin-6 (IL-6) in the patients and controls.
Parameter Mean±S.D Mean±S.D (P) (OR) (95% CI)
of cases of controls
IL-6 pg/ml (19.15±17.44) (15.86±13.90) 0.072 1.022 0.996-1.049

hearing loss and this result is compatible with the results (Ince and Mike, 2016). The cochlea is highly susceptible
of studies done by Lohi et al (2017) and Ravi et al (2017), to ischemic damage that occur by decreasing blood flow
who found that the sensorineural hearing loss type was to this area (Nakashima et al, 2003). The results of Table
more common than conductive hearing loss and mixed. 4 showed that interleukin-6 was not significantly
After control of age, sex, smoking state and noise associated with hearing loss, while other studies found a
exposure, the result showed that patients have low level different results. A study by So et al (2007) found
of iron, ferritin, transferrin saturation in comparism with interleukin-6 act as inducer for acute cochlear damage.
controls. Additionally, the result of Table 6 showed that The releasing of IL-6 by cochlear spiral ligament,
iron deficiency was significantly correlated with severity
Table 5 : BMI differences in patients and controls.
of hearing loss and many of studies found a significant
relation between iron deficiency and hearing loss, like Parameter Mean±S.D Mean±S.D (P)
of cases of controls
Chung et al (2014) and Schiffer (2016). So, this results
may be occur because in iron deficiency there is a BMI (Kg/m²) 24.7±3.02 23.8±3.1 0.07
 Association between iron deficiency and hearing loss
Table 6 : Relationship between iron (µg/dL) and severity of hearing loss (H.L).
Parameter Mean ± S.D of Mean ± S.D of
mild cases moderate cases
no.= 48 no.=38
Iron µg/dL (97.7±22.6) (73.3±15.4 )
P1(comparison between mild and moderate), P2(comparison between mild and severe), P3(comparison
between moderate and severe).
fibrocytes and peripheral immune cells can started the
cell death programmers in the auditory hair cells
(Wakabayashi et al, 2010). Also, IL-6 can cause
inflammation of inner ear and mobilization of circulating
white blood cells to the infection site. So, the infiltrating
immune cells and their cytokines in addition to the
cytokines generated by resident cochlear cells lead to
irreparable damage of hair cells and neurons (Wood and
Zuo, 2017). Also, results of this study found there is no
significant differences in the body mass index between
the patients and controls and this result may be related to
the socioeconomic factors and feeding habits and these
results is agree with other results by Yikawe et al (2017)
and Lee et al (2018) found that obesity is not associated
with hearing loss. While, other studies by Rigters et al
(2016) and Tan et al (2018) found that obesity was
correlated with the loss of hearing. In correlation analyses,
the study showed that there was a significant negative
correlation between iron and IL-6 and this study was
agreed with other studies by Kuo et al (2012); Nakagawa
et al (2014) and Gupta et al (2018). IL-6 stimulates
hepcidin expression (Peeling et al, 2008), hepcidin form
a complex with ferroportin and it induce ferroportin
degradation in the cytoplasm of cells lead to decrease
ferroportin content in cell membrane and block iron output
from intestinal mucosal cells and increase intracellular
iron content (Xu et al, 2015) and this lead to decrease the
amount of available iron in serum (Weiss and Goodnough,
2005). Also, the result of Fig. 2 showed that IL-6 is
correlated significantly with ferritin and these finding is
agreed with other results by Victor et al (2017) and Gupta
et al (2018). During inflammation, iron is withdrawn and
redirected from the circulation to the hepatocyte cells and
macrophages and this result in decreasing the availability
of this important element in the serum (Weiss, 2005), this
causes overload of iron in the hepatocyte cells and
macrophages and this leads to the enhancement of ferritin
translation throughout iron response protein (Thompson
et al, 1999), fraction of this elevated ferritin is loaded in
the macrophages and then translocate to the compartment
of lysosome to protect it from reactive iron then the
secretion of ferritin occur by secretory lysosomal pathway
(Cohen et al, 2010).
1023
Mean ± S.D of (P1) (P2) (P3)
severe cases
no.=64
(49.7±14.4) 0.0001 0.0001 0.0001
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