ORIGINAL ARTICLE
Salivary α-amylase levels in vertigo:
Can it be an autonomic dysfunction?
Tanzer Korkmaz, MD; Yusuf Ozgur Bicer, MD; Erdinc Serin, MD; Sinan Seyhan, MD;
Serap Koybasi Sanal, MD
Abstract
We aim to demonstrate possible autonomic dysfunction
based on salivary α-amylase measurements during and
after the vertigo attacks associated with Ménière dis-
ease (MD) and benign paroxysmal positional vertigo
(BPPV). Patients admitted to the emergency room with
a diagnosis of vertigo attacks caused by either MD (n =
15) or BPPV (n = 9) constituted the study groups. The
control group (n = 10) consisted of volunteer patients ad-
mitted to the emergency department with minor soft-tis-
sue trauma. The first saliva samples were obtained im-
mediately during the attacks and the second and third
samples were obtained on the third and fifteenth days
of the attack, respectively. In the controls, the first sam-
ple was obtained after admission to the hospital and the
second sample was obtained on the third day. Salivary
α-amylase levels were evaluated. The difference between
salivary α-amylase levels in patients with MD and
BPPV was not significant. The amylase value measured
early after the BPPV attack was significantly lower than
that of the controls (p = 0.008). Although not significant,
an undulating pattern of salivary α-amylase levels was
observed with both diseases. An autonomic imbalance
could be partly demonstrated by salivary α-amylase
measurement early after the attack in patients with
BPPV. Therefore, amylase may be a promising marker
that is worth further investigation.
Introduction
Vertigo is a common symptom encountered in the
emergency department (ED). It adversely affects many
quality-of-life aspects. Benign paroxysmal positional
vertigo (BPPV) and, to a lesser extent, Ménière disease
From the Department of Emergency, Izmir Medicalpark Hospital, Izmir,
Turkey (Dr. Korkmaz); Department of Otolaryngology, Abant İzzet
Baysal University, Faculty of Medicine, Bolu, Turkey (Dr. Bicer, Dr.
Seyhan, and Dr. Sanal); and Department of Biochemistry, Ministry
of Health, İstanbul Training and Research Hospital, İstanbul,
Turkey (Dr. Serin). The study was conducted at Abant İzzet Baysal
University, Faculty of Medicine, Bolu.
Corresponding author: Tanzer Korkmaz, MD, Department of
Emergency, Izmir Medicalpark Hospital, Izmir, Turkey. Email:
tanzerkorkmaz@gmail.com
278 www.entjournal.com
(MD) account for a considerable number of patients
seeking medical help in EDs.
BPPV is characterized by brief, recurrent attacks of
vertigo triggered by changes in head position. The attacks
may be followed by residual dizziness in some patients.
With the use of canalith repositioning maneuvers,
management of BPPV is usually easy for most patients.1
MD is a disease of the peripheral vestibular system
characterized by repetitive attacks of vertigo, tinnitus,
and low-frequency hearing loss. Although many factors
such as genetics, allergy, autoimmunity, and stress are
presumed to have a role in the etiology of MD, the exact
pathophysiologic changes have not been elucidated.2,3
The hypothalamic pituitary adrenal axis, autonomic
nervous system, and immune system are interrelated
components of the stress response. The role of stress
has been documented in inner ear diseases in many
studies.4,5 Studies showed the vestibular system and the
autonomic system to be closely related since vestibular
activity influences the cardiovascular system. Central
anatomic connections between vestibular nuclei and the
autonomic pathways have been identified.6 In addition,
stress hormones have been reported to modify inner ear
functions such as threshold shifts.7
Horner reported prolactin to have a role in MD by its
effect on osmoregulatory mechanisms.6 Together with
growth hormone, prolactin is now considered a major
stress-induced hormone.8 Yildiz et al showed a marked
asymmetric sympathetic hypofunction in the area of the
postauricular region of the involved ear in patients with
MD.9 The hypofunction was demonstrated with the use
of sympathetic skin responses in the postauricular area.
Yamada et al reported autonomic nervous dysfunction
to be a predisposing factor in MD using heart rate vari-
ability.10 However, the question of whether it occurs as
a triggering factor or a consequence of vertigo in MD
was not determined in that study.
MD and BPPV are different entities. Although idio-
pathic in most cases, BPPV can be observed after MD
attacks. BPPV that occurs after inner ear diseases, includ-
ing MD, has been shown to have a higher recurrence rate
and a longer recovery period.11,12 Kim and Lee showed
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 Korkmaz, Bicer, Serin, Seyhan, Sanal
an association between residual dizziness in BPPV and
sympathoneural autonomic dysfunction.13 Pezzoli et al
also hypothesized autonomic dysfunction to have a role
in orthostatic dizziness after recovery of BPPV attacks.14
However, they failed to show any significant relation
between BPPV and orthostatic dizziness through the
use of the head-up tilt test.
Salivary α-amylase is a peptide with sympathetic
activity and so affects the autonomic nervous system.
Many studies in the literature use salivary α-amylase as a
marker of sympathetic activity.15-17 Instead of employing
venous puncture, obtaining saliva is a noninvasive and
cost-effective method to measure α-amylase.
Our objective in this study was to demonstrate pos-
sible autonomic dysfunction with the use of salivary
α-amylase measurements during and after the vertigo
attacks of MD and BPPV.
Patients and methods
This study was approved by the Ministry of Health, İstan-
bul Training and Research Hospital Ethical Committee
for Clinical Research with approval number of 2014/459.
Informed consent was obtained from each participant.
Patients. Patients with a diagnosis of MD attacks or
BPPV were recruited from EDs. Patients 18 to 65 years
old who agreed to participate were included in the study.
A bedside confirmation of the attacks was performed by
the otolaryngologists according to the criteria recom-
mended by the Committee on Hearing and Equilibrium
of the American Academy of Otolaryngology–Head and
Neck Surgery.18 The control group consisted of patients
presenting to the ED with acute, minor soft-tissue injuries
(i.e., bruises) who were willing to participate in the study.
The routine workup was performed for these patients
together with the saliva sampling.
Exclusion criteria included use of medications with an
effect on the central nervous system, drinking alcohol
or acidic beverages, or doing physical exercise within
the preceding 1 hour.
Saliva collection and amylase analysis. Saliva was
collected three times from all patients with MD and
BPPV and two times from participants in the control
group. The first sample was obtained shortly after
the patients arrived. For patients with MD, the first
sample was obtained during the attack (before any
medication use). The second sample was obtained on
the third day, and the third sample was obtained on
the fifteenth day.
Saliva collection was performed as follows: the patients
were asked to collect their saliva for 5 minutes. After its
collection, the sample was frozen at -20°C. All samples
were unfrozen at 4 to 8°C on the same day. A supernatant
was prepared by centrifuging the samples at 1,500 rpm
for 10 minutes. Salivary α-amylase analysis of these
280 www.entjournal.com
supernatants was performed after adequate dilution
using Siemens Advia 2400 kits (Erlangen, Germany).
Statistical analysis. SPSS for Windows (version
17.0, IBM; Armonk, New York) was used for statistical
analysis. All data are presented as the mean ± standard
deviation. Associations between salivary α-amylase
measures were evaluated using the Wilcoxon signed rank
test. Comparison between group means was carried out
using the Kruskal-Wallis test at the significance level of
p < 0.05. Multiple comparisons were performed using
the post hoc Mann-Whitney U test with Bonferroni
correction. Bonferroni correction was conducted manu-
ally, and values at the level of p < 0.016 were considered
significant for post hoc analysis.
Results
Patients who did not come for the repeated saliva mea-
surements were excluded from the study. Also, if it was
determined that patients did not have MD or there was a
residual vertiginous symptom at the time of the second or
third measurement, they were excluded from the study.
Overall, 15 patients in the MD group, 9 patients in
the BPPV, and 10 participants in the control group
were included in the study. The MD group consisted
of 10 men and 5 women aged 18 to 62 years (mean:
39 years). The BPPV group consisted of 2 men and 7
women aged 21 to 65 years (mean: 38 years), and the
control group included 6 men and 4 women aged 24 to
62 years (mean: 46 years).
Patients in the MD group had experienced at least two
attacks of vertigo previously. Five of the 15 patients had
experienced at least 10 attacks. All patients with BPPV
were diagnosed with posterior canal BPPV.
In patients with MD, the mean level of salivary α-amy-
lase on first, second, and third measurements were 2,676
± 4,110 U/l, 1,106 ± 1,411 U/l, and 1,811 ± 2,338 U/l,
respectively. Values were 2,087 ± 1,357 U/l, 236 ± 237 U/l,
and 813 ± 1,169 U/l in sequential order in patients with
BPPV, and 1,020 ± 2,089 U/l and 2,210 ± 8,736 U/l on
the first and second measurements of the control group.
The statistical analysis revealed no significant difference
among the three groups with respect to the first salivary
α-amylase measurements (p > 0.05). The second salivary
α-amylase measurement on the third day of the vertigo attack
(defined as early after the attack) was significantly different
in the BPPV group compared with controls (p = 0.024).
No significant difference was detected in salivary α-am-
ylase levels between the patients with MD and those with
BPPV (p = 0.055); however, a significant difference between
the BPPV and control groups was found (p = 0.008). No
significant difference was found in salivary α-amylase
measurements between the MD and control groups. In
the BPPV group, however, a significant difference was
observed between the first and second salivary α-amylase
ENT-Ear, Nose & Throat Journal September 2018
 SALIVARY α-AMYLASE LEVELS IN VERTIGO: CAN IT BE AN AUTONOMIC DYSFUNCTION?
measurements (p = 0.038) and between the second and
third salivary α-amylase measurements (p = 0.008).
The second measurements in the control group could
be considered normal values since those patients had only
minor soft-tissue injuries. A comparison of those values
to the first measurements taken in the MD and BPPV
groups revealed no significant difference between groups.
Discussion
Salivary α-amylase is a member of glucosyl hydrolases
and is produced mainly in the parotid glands. Its main
role is degradation of carbohydrates. Numerous in-
vestigators have proposed salivary α-amylase to be a
marker of the adrenergic system. It was shown to be
secreted from the salivary glands mainly in response to
beta adrenergic and partly to alpha adrenergic stimuli.
Salivary α-amylase has been advocated as a biologic
marker of physiologic and psychological stress. The
interaction between the autonomic nervous system and
stress is well known. Many studies have demonstrated a
marked increase in salivary α-amylase in anxiety-related
diseases, post-traumatic stress, and mental disorders.15,17-19
Sympathetic innervation and the presence of stress
hormone receptors in the inner ear tissue are evident.20
Steroid hormones are shown to slowly modify the
inner ear physiology via changing gene expressions or
nongenomic pathways. Possible multiple interactions
between the sympathetic and the complex feedback
neuroendocrine systems have been proposed. Via in-
teracting with the immune system, these interactions
and the cytokines contribute to inner ear pathologies
such as tinnitus, hearing loss, and vertigo.21 In noise
trauma, for example, even though glucocorticoids are
not the sole actors, a more rapid recovery has been
observed in adrenalectomized animals.22
Vasopressin, also known as antidiuretic hormone, is
secreted in the hypothalamus and is associated with
corticotrophin-releasing hormone. It stimulates ade-
nylate cyclase activity both in the stria vascularis and
semicircular canal epithelium and has been reported to
be elevated under psychological stress conditions.23-25
Vasopressin levels are increased with endolymphatic hy-
dropic states and are associated with vertigo attacks.26,27
Takeda et al demonstrated that the administration of
vasopressin, which increases the activity of aquaporin 2,
to guinea pigs over 1 week resulted in the development
of hydrops.26
Because evidence supports stress-related inner ear pa-
thologies, we aimed to demonstrate possible autonomic
dysfunction in MD and BPPV with salivary α-amylase
measurements. The first salivary α-amylase measure-
ments (during the vertigo episode) in all the groups were
highest compared with subsequent measurements. This
finding may be attributed to sympathetic over-reactivity
Volume 97, Number 9
caused by the stress of the attack itself in addition to the
stress provoked by the atmosphere of the ED.
Patients with MD demonstrated the highest levels of
salivary α-amylase during their attacks. Our statistical
analysis supports our hypothesis of increased sympa-
thetic activity during the vertigo attacks, although the
difference was not significant. However, a noteworthy
finding was the undulating pattern of the salivary
α-amylase measurements; salivary α-amylase levels
decreased initially at the second measurement and
increased again in the following days. We therefore
believe that repeating such types of studies with a bigger
sample size may reveal more striking results.
The results of the second amylase measurements pro-
vide a clue about the role of the autonomic nervous system
in these diseases. The difference between the second
measurements of salivary α-amylase was significantly
lower in BPPV patients than in the MD and control
patients. Therefore, a depression in sympathetic tone or
a parasympathetic overactivation might be responsible.
The autonomic nervous system with its sympathetic
and parasympathetic subdivisions should be in balance
to avoid disease states. Disruption of this balance in either
hyperadrenergic or hypervagal mixed states can result
in a variety of symptoms such as dizziness, palpitations,
anxiety, fatigue, syncope, and gastrointestinal symptoms.28
Although autonomic dizziness is generally con-
sidered to be lightheadedness, vertigo in association
with autonomic dysfunction is being reported more
frequently.28-30 Low et al reported vertigo as a symptom
of orthostatic hypotension in 37% of cases.29 Although
the lightheadedness is believed to occur as a result of
a transient acute decrease in cerebral blood flow, the
mechanism of vertigo is still poorly understood.28
The underlying mechanisms of BPPV have been
better elucidated than those of MD or other hydropic
states. Residual dizziness is a commonly encountered
condition after BPPV.14 Kim and Lee reported a 43%
rate of dizziness after successful canalith repositioning
maneuvers.13 This by itself points to a connection of
some type between BPPV and the autonomic nervous
system. The mentioned reports demonstrated autonomic
dysfunction by means of the head-up tilt test. Our aim
in this study was to determine whether this autonomic
dysfunction was also possible during vertigo attacks
by using a relatively simple method—measurement of
salivary α-amylase levels during the attacks.
In BPPV, salivary α-amylase levels were lowest on
the third day and then rose again on the 15th day. This
result points to a possible imbalance in the autonomic
nervous system in BPPV. This possibility is important
during follow-up; the clinician should keep in mind
that an autonomic dysfunction is possible and should
evaluate patients by repeating the maneuvers.
www.entjournal.com 281
 Korkmaz, Bicer, Serin, Seyhan, Sanal

10. Yamada M, Mizuta K, Ito Y, et al. Autonomic nervous function in

Salivary α-amylase is accepted to reflect sympathetic patients with Ménière’s disease evaluated by power spectral analysis
tone. A possible autonomic imbalance in peripheral of heart rate variability. Auris Nasus Larynx 1999;26(4):419-26.
vertigo might be due to a change in parasympathetic 11. Su P, Liu YC, Lin HC. Risk factors for the recurrence of post-
tone. This possibility needs further studies. semicircular canal benign paroxysmal positional vertigo after
The timing of the second and third measurements of canalith repositioning. J Neurol 2016;263(1):45-51.
12. Lee NH, Ban JH, Lee KC, Kim SM. Benign paroxysmal positional
salivary α-amylase in our study can be criticized. As no vertigo secondary to inner ear disease. Otolaryngol Head Neck
globally accepted normal range of salivary α-amylase Surg 2010;143(3):413-7.
currently exists, we compared its levels in patients with 13. Kim HA, Lee H. Autonomic dysfunction as a possible cause of
different diseases and in patients presenting to the ED residual dizziness after successful treatment in benign paroxysmal
with minor soft-tissue trauma and no history of vertigo. positional vertigo. Clin Neurophysiol 2014;125(3):608-14.
14. Pezzoli M, Garzaro M, Pecorari G, et al. Benign paroxysmal
The second measurements in the control group can be positional vertigo and orthostatic hypotension. Clin Auton Res
considered normal values. 2010;20(1):27-31.
Cochleovestibular physiology is affected by the 15. Schumacher S, Kirschbaum C, Fydrich T, Ströhle A. Is
autonomic nervous system. Many mechanisms in the salivary alpha-amylase an indicator of autonomic nervous
etiology of MD and BPPV have been proposed. The system dysregulations in mental disorders? A review of
preliminary findings and the interactions with cortisol.
results of our study related to salivary α-amylase levels Psychoneuroendocrinology 2013;38(6):729-43.
suggest an autonomic imbalance early after the canalith 16. Rohleder N, Nater UM, Wolf JM, et al. Psychosocial stress-
repositioning maneuvers in BPPV but do not support induced activation of salivary alpha‐amylase: An indicator of
autonomic dysfunction in MD. sympathetic activity? Ann N Y Acad Sci 2004;1032:258-63.
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biomarker for the sympathetic nervous system: Current state of
to measure salivary α-amylase in patients with inner research. Psychoneuroendocrinology 2009;34(4):486-96
ear diseases. Further studies with a larger sample size 18. [No authors listed]. Committee on Hearing and Equilibrium
are required to identify salivary α-amylase as a possible guidelines for the diagnosis and evaluation of therapy in Ménière's
biomarker of autonomic imbalance in patients with ver- disease. American Academy of Otolaryngology-Head and Neck
tigo. Diagnosis of vertigo in the ED can be challenging, Foundation, Inc. Otolaryngol Head Neck Surg 1995;113(3):181-5.
19. Chatterton RT Jr, Vogelsong KM, Lu YC, et al. Salivary α‐amylase
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Acknowledgment corticoid receptor within the rat inner ear. Hear Res 1993;64(2):205-10.
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the inner ear: Current and future therapeutic strategies. Adv
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