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ARTICLE IN PRESS

The Prevalence of Dysphonia and Dysphagia in Patients with


Vitamin D Deficiency
*Abdul-Latif Hamdan, *Elie Khalifee, *Nader Al Souky, *Bakr Saridar, *Pierre Richard Abi Akl,
*Anthony Ghanem, and †Sami Azar, *yLebanon

Abstract: Objective. To investigate the prevalence of phonatory and swallowing symptoms in patients with
hypovitaminosis D.
Methods/Design. All patients presenting to the endocrinology clinic and investigated for vitamin D deficiency
between January 2018 and April 2018 were asked to participate in this study. Demographic data included age,
gender, allergy, and history of smoking. Patients filled Voice handicap Index (VHI-10) and Eating Assessment
Tool (EAT-10).
Results. A total of 136 consecutive subjects presenting to the endocrinology clinic for vitamin D testing were
included: 60 with hypovitaminosis D and 76 with no hypovitaminosis D. The mean vitamin D level in the study
group and controls was 13.25 ng/mL and 31.91 ng/mL, respectively. There was no significant difference in the
mean score of VHI-10, nor in the mean score of EAT-10 in patients with hypovitaminosis D versus those with no
hypovitaminosis D (P value >0.05).
Conclusion. There was no significant difference in the prevalence of phonatory and dysphagia symptoms using
VHI-10 and EAT-10 questionnaires between subjects with hypovitaminosis D and those with normal serum vita-
min D levels.
Keywords: Vitamin D deficiency−Dysphonia−Dysphagia−EAT-10−VHI-10.

INTRODUCTION associated with pain in the musculoskeletal structures.


Vitamin D deficiency, also referred to as hypovitaminosis Based on the investigation by Gerwin, 89% of patients with
D, is defined as inadequate blood level of 25-hydroxy vita- chronic musculoskeletal pain had low vitamin D levels.13
min D of less than 20 ng/mL.1,2 It is a common health prob- Another study by Heath and Elovic on the implications of
lem in the world affecting millions of subjects of various vitamin D deficiency in the rehabilitation setting showed
ethnicity.2 The predictors of this clinical condition have that 93% of patients presenting with musculoskeletal pain
been related to many factors such as older age, female gen- were deficient in vitamin D.14 The musculoskeletal symp-
der, multi-parity, low socioeconomic status, inadequate toms and the decrease in physical activity in affected sub-
vitamin D intake, and insufficient exposure to the sun due jects have been linked to a decrease in muscle tissue vitamin
to conservative clothing.3,4 D receptors (VDRs).15
Hypovitaminosis D has been associated with numerous Despite the numerous studies ascertaining Vitamin D
diseases such as hypertension, cardiovascular diseases, oste- deficiency-induced muscular dysfunction and the well-estab-
omalacia, osteoporosis in adults, and rickets in children.2,5 lished similarity between the laryngopharyngeal complex
It has also been related to dysfunction in the muscular sys- and other musculoskeletal structures in the body, the litera-
tem with symptoms of weakness, decreased activity, and ture is sparse on the effect of vitamin D deficiency on swal-
hypotonia often reported by affected patients.6−8 To that lowing and phonation. Based on a literature review, only
end, several investigators examined the correlation between one study on the association between vitamin D deficiency
Vitamin D deficiency and muscle strength and function.9−12 and voice has been reported.16 This study carried out on
A cross-sectional study by Gschwind et al looking at the 19 patients with vitamin D deficiency in comparison to
association between vitamin D level and functional mobil- 19 controls with no vitamin D deficiency revealed no signifi-
ity, showed a decrease in physical performance in subjects cant difference in the mean or frequency of any of the pho-
with hypovitaminosis D.11 Likewise, Wicherts et al reported natory symptoms between the two groups. Moreover, there
a decline in physical activity and a poor performance was no statistically significant difference in the mean of the
with age in patients with low vitamin D.12 In keeping with Voice Handicap Index (VHI-10) or any of the acoustic vari-
the aforementioned, hypovitaminosis D has also been ables analyzed in patients with vitamin D deficiency in com-
parison to controls. One main limitation of that study was
Accepted for publication March 14, 2019. the sample size which could have masked any significant dif-
(There is no conflict of Interest or financial support in relation to this paper).
From the *Department of Otolaryngology Head & Neck Surgery, American Uni- ference in the phonatory symptoms between patients with
versity of Beirut Medical Center, Beirut, Lebanon; and the yDepartment of Internal vitamin D deficiency versus those with no vitamin D defi-
Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
Correspondence and reprint requests to Sami Azar, MD, American University of ciency. Careful examination of the data shows that both
Beirut Internal Medicine Department, P.O.Box: 11-0236, Beirut Lebanon E-mail: the mean score as well as the frequency of vocal fatigue and
sazar@aub.edu.lb
Journal of Voice, Vol. &&, No. &&, pp. &&−&& phonatory effort were higher in the group with vitamin
0892-1997 D deficiency in comparison to those with no deficiency.
© 2019 The Voice Foundation. Published by Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.jvoice.2019.03.007 Moreover, the lack of significant difference in the acoustic
ARTICLE IN PRESS
2 Journal of Voice, Vol. &&, No. &&, 2019

measures was attributed to the limited vocal sample ana- TABLE 1.


lyzed, namely the sustained vowel /a/ and the lack of a read- Demographic Data
ing passage.
Given the scarcity of studies on the association between Study group Control group
(n = 60) (n = 76)
vitamin D deficiency and symptoms related to the laryngo-
pharyngeal complex, and in view of the aforementioned lim- Age (y)
itations of the study previously published by the same Mean §SD 45.9 § 12.1 49.5 § 12.2
authors, this investigation is intended to cast further infor- Gender, N (%)
mation on this topic using self-reported questionnaires in a Male 22 (36.6) 19 (25)
Female 38(63.3) 57 (75)
larger group of patients with vitamin D deficiency present-
Social history, N (%)
ing to the endocrinology clinic in a tertiary referral center. Smoking 25(41.6) 32 (42)
The prevalence of phonatory and swallowing symptoms as Allergy 13 (21.6) 24 (32)
reported by the patients will be reported.

METHODOLOGY
45.9 years with a SD of 12.1 years, while that of the control
Participants group was 49.5 years with a SD of 12.2 years. The preva-
After obtaining Institutional Review Board approval, all lence of smoking history was 41.6% and 42%, in the study
patients presenting to the endocrinology clinic at a tertiary and control group respectively. In regard to other comor-
medical referral center between January 2018 and April bidities, refer to Table 1.
2018, and who have been investigated for vitamin D defi-
ciency were asked to participate in this study. Exclusion cri-
teria included age below 18 years, recent onset of upper Level of vitamin D in the study group and controls
respiratory tract infection, and history of neurogenic disor- In the study group, the mean vitamin D level was
ders or laryngeal manipulation. 13.25 ng/mL with a SD of 4.02 ng/mL, whereas in the con-
A total of 136 subjects were included in this study. These trol group, the mean vitamin D level was 31.91 ng/mL with
were divided into two groups, those with vitamin D defi- a SD of 11.20 ng/mL. It is worth noting that 26.66% and
ciency or insufficiency (n = 60) referred to as hypovitamino- 61.8% of the study and control groups were on treatment.
sis D and those with no vitamin D deficiency (n = 76).
Vitamin D deficiency or insufficiency was defined as a blood Means and frequencies of VHI-10
level of 25-OH <20 ng/dL.1,2 Demographic data included There was no significant difference in the mean score of
age, gender, smoking, and history of allergy. All patients VHI-10 in patients with hypovitaminosis D versus those
were asked to fill the VHI-10 and the Eating Assessment with no vitamin D deficiency (Mean VHI-10 1.2 vs 1.68, P
Tool (EAT-10). The VHI-10 is a self-reported questionnaire value >0.05). Similarly, there was no statistically significant
on the impact of dysphonia on quality of life with a score difference in the frequency of subjects with VHI-10 > 11
above 11 being significant.5 Similarly, EAT-10 is a self- between the study and control groups (1.66% vs 3.94%
administered questionnaire for assessment of dysphagia respectively; P-value >0.05). See Table 2.
with a score above three being significant.17

Means and frequencies of EAT-10


Statistical analysis There was no significant difference in the mean score of
Means (§standard deviation) and frequencies were calcu- EAT-10 in patients with hypovitaminosis D versus controls
lated to describe continuous and categorical variables, (Mean EAT-10 1.16 vs 1.71, P value >0.05). Similarly, there
respectively. The dependent variable was if the patient had was no statistically significant difference in the frequency of
normal serum vitamin D levels or vitamin D deficiency, subjects having an EAT-10 score ≥3 between the study and
whereas the independent variables were the phonatory and control groups (16.66% vs 22.36% respectively; P value
dysphagia scores reported by the patients. Mann-Whitney >0.05). See Table 2.
U test was used to compare the means of the continuous
variables between patients and controls. Data was analyzed
using SPSS version 23 (SPSS Inc, Chicago, Ill). DISCUSSION
Vitamin D is essential to one's well-being. It is known to
stimulate the immune system, contribute to cardiovascular
RESULTS health, and to improve physical performance.18 The pan-
Demographic data demic increase in the prevalence of vitamin D deficiency
A total of 136 patients were enrolled in the study. These over the last few decades has led to the emergence and
were divided into 60 subjects with hypovitaminosis D (study perpetuation of numerous diseases.19 Among the various
group) and 76 subjects with normal serum vitamin D level systems affected, the musculoskeletal system has been thor-
(control group). The mean age of the study group was oughly investigated with numerous studies on the impact of
ARTICLE IN PRESS
Abdul-Latif Hamdan, et al Prevalence of Dysphonia and Dysphagia in Patients with Vitamin D Deficiency 3

TABLE 2. D are more likely to exhibit symptoms of laryngopharyng-


Mean Score and Frequencies of VHI-10 and EAT-10 in the eal dysfunction. Indeed, the intricate anatomy of the larynx
Study Group and Control and the cross-cutting in its performance of various tasks,
puts it at high risk for laryngeal muscle dysfunction
Study group Control group
in patients with hypovitaminosis D, at least hypothetically.
(N = 60) (N = 76) P value
As phonation is governed by a complex interplay of neuro-
VHI-10 muscular processes32,33 any alteration in laryngeal muscle
Mean §SD 1.20 § 2.69 1.68 § 3.85 0.655 performance, particularly at the level of the vocal folds,
No (%) with 1(1.66) 3 (3.94) may lead to dysphonia and voice related complaints. Simi-
VHI-10 > 11
larly, any dysfunction of the pharyngeal muscles may
EAT-10
Mean §SD 1.16 § 2.60 1.71 § 3.01
impair the pharyngeal phase of swallowing and lead to dys-
No (%) with 10 (16.66) 17 (22.36) 0.703 phagia and throat related symptoms. Contrary to the
EAT-10 ≥ 3 hypothesis set forth in the introduction, the results of this
investigation showed no significant difference in the preva-
lence of phonatory and swallowing symptoms in patients
with hypovitaminosis D in comparison to those with no
vitamin D deficiency on muscle function, exercise capacity, hypovitaminosis D, as evidenced by the mean score of
and morphology being reported.6,20−22 Hypotonia, muscle VHI-10 and EAT-10. A possible explanation for the lack of
weakness, and fatigability have been described as the most laryngopharyngeal symptoms in the affected group is the
common musculoskeletal symptoms in affected sub- histologic difference between the intrinsic muscles of the lar-
jects.11,12,23 The molecular mechanism of vitamin D action yngopharyngeal complex and muscles of the extremities.
on muscle tissue is complex. Several mechanisms have been Skeletal muscle fibers in adults can be classified, using histo-
suggested, among which are the genomic and nongenomic chemical techniques of staining for myofibrillar ATPase,
pathways. The genomic pathway starts with the activation into three fiber types with different mechanical properties,
of nuclear VDR, which is a transcription factor, via 1,25 namely type I, type IIa, and type IIb fibers.34 In a study by
(OH)2D. As a result, synthesis of muscular cytoskeletal pro- Rosenfield et al, laryngeal muscles were found to be com-
teins important for muscle function, such as insulin-like posed of a higher percentage of type 1 fibers which are
growth factor binding protein and calmodulin, is slow-twitch capable of generating low forces and are highly
increased.24−27 Activation of nuclear VDR is also thought resistant to fatigue.35 The thyroarytenoid muscle, made of
to affect phospholipids’ metabolism which is likely to type I, type IIa, and hybrid fibers, has a distinguished histo-
impact muscle contraction.21,28 On the other hand, the non- logic architecture in terms of fiber arrangement (fast fibers
genomic pathway consists of 1,25 (OH)2D activating located medially) which makes it more fatigue-resistant.36
plasma-membrane VDR's, which involve invaginations of Similarly, Malmgren and Gacek found that a normally
the plasma membrane, referred to as caveolae. This allows innervated human posterior cricoarytenoid muscle con-
for a rapid cascade of signaling pathways, taking seconds to tained more slow-twitch type I fibers than fast-twitch type
minutes for a response as compared to hours for protein II fibers.37 To add, Rosenfield et al demonstrated unique
synthesis in the genomic pathway.29−31 Both pathways stim- morphologic and histochemical features in normal laryn-
ulate muscle proliferation and differentiation. Another pro- geal muscles not present in limb skeletal muscles such as
posed mechanism of the action of Vitamin D on muscle smaller fiber size, higher size variability, basophilia, and
cells, is through the activation of mitogen-activated protein increased concentration of mitochondria and fibrous tis-
kinase signaling pathway.19 In humans, mitogen-activated sue.35 These differences in comparison to limb muscles,
protein kinase pathways control cellular processes such as namely the fiber size, type, distribution as well as the mito-
cell proliferation, apoptosis, myogenesis, and differentia- chondrial content, are suitable for the intricate role of laryn-
tion. As such, vitamin D sufficiency is thought to stimulate geal muscles in regard to respiration, phonation, and
cellular growth and proliferation whereas vitamin D defi- swallowing. Another potential explanation for the lack of
ciency has been associated with fatty infiltration, type II significant difference in the prevalence of phonatory and
fiber atrophy, fibrosis, and increased inter fibrillar spaces as swallowing symptoms between the study and control groups
reported by Pfiefer et al6,21 These noted histologic findings is the fact that the questionnaires used in this study were not
lead to prolonged time for muscle relaxation and for peak filled following vocal fatiguing tasks. Vocal loading may
muscle contraction resulting in decreased physical perfor- precipitate a muscular functional impairment as commonly
mance and fatigability. reported in patients with impaired mobility of the vocal
Given all the aforementioned evidence on the impact of folds.38,39
vitamin D deficiency on the musculoskeletal system, and The results of this investigation, though do not show a
given that the laryngopharyngeal complex is a musculoskel- significant difference in the self-reported prevalence of vocal
etal structure potentially equally prone to vitamin D defi- complaints in patients with hypovitaminosis D in compari-
ciency induced muscle dysfunction, the authors of this son to normal subjects, do not preclude the presence of
manuscript hypothesized that patients with hypovitaminosis objective phonatory changes. Vitamin D deficiency induced
ARTICLE IN PRESS
4 Journal of Voice, Vol. &&, No. &&, 2019

myopathy can hypothetically affect any musculoskeletal based on the laboratory result whereas the deficiency could
structure including the laryngeal muscles, leading to have been long standing prior to the laboratory testing.
decrease in muscle endurance and vocal fatigue in various
degrees. Based on the report by Welham and Maclagan,
neuromuscular dysfunction in addition to increased vocal CONCLUSION
fold viscosity and respiratory dysfunction, is one of the Several studies concur that vitamin D deficiency impairs
most plausible causes of vocal fatigue.40 Affected patients muscular function and strength. The results of this investiga-
can display stroboscopic changes such as incomplete glottic tion showed no significant difference in the prevalence of
closure and decrease in mucosal waves and amplitude phonatory and dysphagia symptoms between subjects with
excursion as reported by Mann et al in a group of 42 sub- hypovitaminosis D and those with normal serum vitamin D
jects 5 days following vocally loading exercises.41 In parallel levels. A larger study using a comprehensive voice evalua-
with these endoscopic findings, there is an increase in the tion, subjective, acoustic, and aerodynamic will elucidate fur-
perturbation parameters, namely in cycle to cycle variation ther the association between hypovitaminosis D and voice.
in intensity and frequency. Airflow measurements often
reveal an increase in the mean flow rate and a decrease in
glottal resistance and maximum phonation time. To that REFERENCES
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