Impact of 1% malic acid spray on the oral health-related quality of life of patients with xerostomia

Abstract

Dry mouth sensation, also known as xerostomia, is a common clinical problem with an increasing prevalence. Although recent studies have reported promissory results of malic acid, none have evaluated the impact of malic acid on the oral health-related quality of life (OHRQoL) of patients with xerostomia. Thus, this study aimed to evaluate the impact of 1% malic acid, combined with fluoride and xylitol, on the OHRQoL of patients with xerostomia. We enrolled 70 patients and randomly allocated them into two groups: the intervention group (applied topical sialogogue with 1% malic acid) and the control group (applied a placebo). We assessed the OHRQoL and severity of xerostomia before and after treatment with the Spanish version of the Oral Health Impact Profile-14 questionnaire (OHIP-14sp) and a visual analogue scale (VAS), respectively. In addition, stimulated and non-stimulated salivary flow rates before and after treatments were also measured. In total, 60 patients completed the study. According to the VAS, both sprays significantly improved dry mouth sensation (P < 0.001). However, OHIP-14sp total scores decreased significantly in the intervention group from 20.8 ± 10.4 to 16.5 ± 9.5 (P < 0.001), indicating an improvement in the OHRQoL. No significant differences were observed in the control group (P > 0.05). Furthermore, non-stimulated salivary flow rates significantly increased in the intervention group from 0.25 ± 0.22 to 0.33 ± 0.33 mL/min (P < 0.001). Overall, this study demonstrated that malic acid improves the OHRQoL and dry mouth sensation in patients with xerostomia.

Full text

278
Abstract: Dry mouth sensation, also known as
xerostomia, is a common clinical problem with an
increasing prevalence. Although recent studies have
reported promissory results of malic acid, none have
evaluated the impact of malic acid on the oral health-
related quality of life (OHRQoL) of patients with
xerostomia. Thus, this study aimed to evaluate the
impact of 1% malic acid, combined with uoride and
xylitol, on the OHRQoL of patients with xerostomia.
We enrolled 70 patients and randomly allocated them
into two groups: the intervention group (applied
topical sialogogue with 1% malic acid) and the control
group (applied a placebo). We assessed the OHRQoL
and severity of xerostomia before and after treatment
with the Spanish version of the Oral Health Impact
Prole-14 questionnaire (OHIP-14sp) and a visual
analogue scale (VAS), respectively. In addition, stimu-
lated and non-stimulated salivary ow rates before
and after treatments were also measured. In total, 60
patients completed the study. According to the VAS,
both sprays signicantly improved dry mouth sensa-
tion (P < 0.001). However, OHIP-14sp total scores
decreased signicantly in the intervention group from
20.8 ± 10.4 to 16.5 ± 9.5 (P < 0.001), indicating an
improvement in the OHRQoL. No signicant differ-
ences were observed in the control group (P > 0.05).
Furthermore, non-stimulated salivary ow rates
signicantly increased in the intervention group from
0.25 ± 0.22 to 0.33 ± 0.33 mL/min (P < 0.001). Overall,
this study demonstrated that malic acid improves the
OHRQoL and dry mouth sensation in patients with
xerostomia.
Keywords: xerostomia; dry mouth; malic acid; oral
health-related quality of life.
Introduction
Saliva is an essential uid in the human body for the
maintenance of oral tissues and oral health. Alterations in
the amount or quality of saliva induce several changes in
the oral cavity, including predisposition to caries, infec-
tions, altered taste, halitosis, dysphagia, dysarthria, lack
of retention of dentures, and dry mouth sensation (1,2).
Dry mouth sensation, or xerostomia, is a subjective
symptom characterized by a decline in the salivary
ow rate or alteration in the chemical composition of
saliva (3). Xerostomia is a common clinical problem,
with an increasing prevalence; the estimated prevalence
is 0.9-64.8% (4,5). Xerostomia can be a symptom of
various disorders and can be attributed to several causes
such as medications, head and neck radiotherapy, chemo-
therapy, Sjögren’s syndrome, and psychological illness
(5-8). Despite its cause, xerostomia has been reported
to adversely affect the oral health-related quality of
life (OHRQoL) (5,9-11). Willumsen et al. reported that
xerostomia affects the quality of life by interfering with
speech, taste, and mood (12). Moreover, patients with
dry mouth are prone to having dental caries, periodontal
Journal of Oral Science, Vol. 60, No. 2, 278-284, 2018
Original
Impact of 1% malic acid spray on the oral health-related
quality of life of patients with xerostomia
Sven Niklander, Flavio Fuentes, Daniela Sanchez, Verónica Araya, Giuliana Chiappini,
René Martinez, and Maureen Marshall
Department of Oral Pathology and Oral Surgery, Dentistry Faculty, Andres Bello University,
Viña del Mar, Chile
(Received April 20, 2017; Accepted September 14, 2017)
Correspondence to Dr. Sven Niklander, Department of Oral
Pathology and Oral Surgery, Dentistry Faculty, Andres Bello
University, Av. Valparaiso #1560, Viña del Mar, Chile
E-mail: sven.niklander@unab.cl
Color gures can be viewed in the online issue at J-STAGE.
doi.org/10.2334/josnusd.17-0164
DN/JST.JSTAGE/josnusd/17-0164

279
disease, and burning sensation, also contributing to the
deterioration of the OHRQoL (13).
Because therapies for xerostomia are highly variable,
treatment must be selected according to the cause and
severity of dry mouth. Although topical agents are the
most prevalent treatment options, as they relieve symp-
toms with no or little side effects, no substantial evidence
proves their efcacy in relieving the dry mouth sensation
(14). Acidic substances, such as malic and citric acid,
have been used as salivary stimulants, but their use has
been discontinued because of their demineralizing effect
(13). Several studies have demonstrated that 1% malic
acid, in combination with xylitol and uoride, exerts no
or little effect on tooth demineralization and maintains
its properties as a salivary stimulant (15). In fact, recent
studies have demonstrated promissory results of 1%
malic acid; they have reported an increase in salivary
ow and a reduction in dry mouth sensation (16-18).
Nevertheless, none of these studies have evaluated the
impact of 1% malic acid on the OHRQoL in patients with
xerostomia.
The present study aimed to investigate the impact of
a topical sialogogue spray containing 1% malic acid,
combined with uoride and xylitol (Xeros Dentaid
Spray; Dentaid, Barcelona, Spain), on the OHRQoL of
patients with xerostomia.
Materials and Methods
Participants and study design
In this study, we enrolled 70 patients with xerostomia
who attended a dental clinic of the Dentistry Faculty of
Andres Bello University (Viña del Mar, Chile) between
2014 and 2015. This study was approved by the Ethical
and Scientic Committee of the Dentistry Faculty of
Andres Bello University (approval number 026, 2014).
This research was conducted in full accordance with the
World Medical Association Declaration of Helsinki. The
study was designed as a double-blind randomized clinical
trial according to the guidelines established by The
CONSORT Statement (http://www.consort-statement.
org/consort-statement/).
We randomly distributed patients with xerostomia into
two groups of 35 and 35 individuals (treatment and control
group, respectively), which were balanced in terms of
age and salivary ow rates (Fig. 1). Randomization was
performed by an investigator not involved in this study
through a specic webpage (http://www.randomization.
com/) using the method of randomly permuted blocks,
setting 35 subjects per block and two labels, A and B, for
the intervention and control group, respectively. More-
over, randomization was kept in a sealed envelope in an
unknown place for examiners till the end of the study.
The inclusion criteria in this study were that participants
had to be over 18 years and have dry mouth according to
Assessed for eligibility (n= 96)
Excluded (n= 26)
- Not meeting inclusion criteria (n= 26)
- Declined to participate (n= 0)
- Other reasons (n= 0)
Analyzed (n= 31)
- Excluded from the analysis (n= 0)
Lost to follow-up (n= 4)
Lack of time and commitment with the study
Discontinued intervention (n= 0)
Allocated to the intervention group (n= 35)
- Received allocated intervention (n= 35)
- Did not receive allocated intervention (n= 0)
Lost to follow-up (n= 5)
Lack of time and commitment with the study
Discontinued intervention (n= 1)
Rise in blood pressure associated with the spray
Allocated to the control group (n= 35)
- Received allocated intervention (n=35)
- Did not receive allocated intervention (n= 0)
Analyzed (n= 29)
- Excluded from the analysis (n= 0)
Allocation
Analysis
Follow-up
Randomized (n= 70)
Enrollment
Fig. 1 Study CONSORT owchart.

280
a previously established question (see measurements). In
contrast, patients who have had topical or systemic treat-
ment for xerostomia in the last 3 months or had history
of head and neck radiotherapy, chemotherapy, and/or
any systemic disease reported to produce hyposaliva-
tion (Sjögren’s syndrome, scleroderma, hepatitis C,
HIV, sarcoidosis, rheumatoid arthritis, polyarteritis
nodosa, systemic sclerosis, or lupus erythematosus) were
excluded from this study.
We obtained written informed consent from all eligible
individuals who agreed to participate in this study.
Furthermore, data were collected by personal interviews
and clinical examination, which were conducted at the
dental clinic and were recorded in a specially designed
questionnaire.
Sample size calculation
We calculated the sample size using Stata software v11.2
and the sample size tool (StataCorp LP, College Station,
TX, USA). We set the signicance level and power
of the study at 5% and 95%, respectively. Proportions
were obtained per Gomez et al. (17,18). Based on these
settings, the minimum sample size required was 15
patients for each group.
Interventions
In the intervention group, patients received a topical
spray comprising 1% malic acid, 10% xylitol, and 0.05%
sodium uoride (Xeros Dentaid Spray; Dentaid). In the
control group, patients received a placebo topical spray
comprising 10% xylitol and 0.05% sodium uoride.
Each formulation was placed into identical opaque asks
and labeled according to randomization by personnel
unrelated to this study. Patients in both groups were
instructed to use the spray on demand for 2 weeks, with
a maximum of eight applications per day and record the
daily number of applications in a diary. We controlled
patients during that period to ensure correct use and
resolve possible problems with the sprays. Furthermore,
patients were advised to interrupt the treatment and call
investigators in case they felt insecure or experienced
unpleasant symptoms upon the use of the solutions.
Measurements
Xerostomia
We assessed the presence of xerostomia with the following
question, as reported elsewhere (19): “How often do you
feel that your mouth is dry?”. Participants could select
from the following answers: “never”, “sometimes”,
“usually”, or “always”. Those who answered “usually”
or “always” were considered to have xerostomia (19).
The severity of xerostomia was assessed using the
visual analogue scale (VAS), which comprised a 10-cm
horizontal line with a “0” and “10” marked on each
extreme. A score of 0 indicated “no xerostomia” and 10
indicated the “worst imaginable xerostomia”. All patients
were asked to draw a vertical line perpendicular to this
horizontal line to reect their symptom severity. We
evaluated and recorded the distance between the vertical
line and the zero extreme to obtain the VAS score for
each patient (20).
Evaluation of impact on the quality of life
The OHRQoL was assessed using the Spanish version
of the Oral Health Impact Prole-14 questionnaire
(OHIP-14sp) before and after the treatment. OHIP-14 is
a 14-item questionnaire designed to assess self-reported
functional limitation, discomfort, and disability attributed
to oral conditions. Despite being a short questionnaire,
the OHIP-14sp has been proven to be reliable, sensitive
to changes, and have adequate cross-cultural consistency
(21). We evaluated the OHIP-14sp according to the
following dimensions: functional limitation, physical
pain, psychological discomfort, physical incapacity,
psychological incapacity, social incapacity, and social
disadvantage. The answers were assessed using a Likert-
type evaluation scale with ve points as follows: never =
0; rarely = 1; sometimes = 2; repeatedly = 3; and always
= 4. Of note, the OHIP-14sp scale ranges from 0 to 56.
The lowest scores represent a satisfactory perception of
an individual’s oral conditions and, therefore, a higher
satisfaction and better quality of life.
Salivary ow rate
We assessed stimulated and non-stimulated salivary
ow rates before and after treatment using the spitting
method. All patients were instructed to refrain from
eating, drinking, smoking, and oral hygiene procedures
for a minimum of 60 min before the procedure. Samples
were collected in the morning hours, between 9:30 and
11:30 am, always in the same room under similar room
temperatures. The collection time for stimulated and
non-stimulated whole salivary ow was 5 min. First,
non-stimulated whole saliva was collected. Patients were
instructed to spit into a tube for 5 min, and the amount
of saliva was measured using a graduated syringe. Then,
stimulated whole saliva was collected after a break of 3
min using the mastication method. Patients were asked to
chew a wax cube of 15 × 10 mm for 1 min at their own
pace and then to spit into a tube for 5 min. Wax residues
were eliminated using a lter paper before quantication
using a graduated syringe.

281
All saliva collections and further measurements in
this study were performed by three different exam-
iners. Thereafter, standardization and calibration were
performed among the examiners. Of note, Lin’s concor-
dance agreement was 0.97.
Outcomes
In this study, the primary outcome was to assess the
effect of 1% malic acid on the OHRQoL, dened as the
difference between the baseline total OHIP-14sp scores
and post-treatment total OHIP-14sp scores. Results were
expressed as mean ± standard deviations.
The secondary outcome was salivary ow stimulation,
dened as the difference between the stimulated and
non-stimulated salivary ows before and after treatment,
expressed as mL/min. Both primary and secondary
outcomes were measured 2 days after patients nished
the 2-week treatment, whether with the placebo or malic
acid spray (Xeros Dentaid Spray).
Statistical analysis
The data were analyzed using Microsoft Excel v.2007
(Microsoft Corporation, Redmond, WA, USA) and
R-Cran 3.1.1. (The R Foundation, Vienna, Austria).
For independent and related samples, we used the
Kolmogorov-Smirnov and Wilcoxon signed-rank test,
respectively. P < 0.05 was considered statistically
signicant. Patients who did not complete the study were
excluded from the statistical analysis.
Results
We enrolled 70 patients in this study who were randomly
allocated to the intervention and control groups. Ten
patients (control group, 6; intervention group, 4) did
not complete the study and were thus excluded from the
statistical analysis. Of these 10 patients, nine were lost to
follow-up because of the lack of time and commitment to
the study. The remaining patient (from the control group)
discontinued the intervention because he associated one
application of the placebo with a rise in blood pressure.
Hence, 60 patients completed this study (control group,
29; intervention group, 31; Fig. 1). No patient reported
any adverse effect. No signicant differences were
observed between the mean ages and group (P > 0.05) or
between gender and group (P > 0.05).
While xerostomia was correlated with drug use in
47 patients (78.3%), it was associated with idiopathic
causes in the remaining 13 patients (21.7%). The most
commonly used medications in this study were antihy-
pertensives, followed by antidepressants, anxiolytics,
antihistaminics, and hypoglycemic agents. Furthermore,
the average number of drugs consumed by patients with
drug-related xerostomia was 2.5.
Table 1 summarizes the mean ages, gender distribu-
tion, OHIP-14 score before and after treatment, VAS
score before and after treatment, and mean number of
applications in both groups. According to the VAS, both
sprays signicantly improved xerostomia (P < 0.001),
but only the spray containing 1% malic acid (Xeros
Dentaid Spray) signicantly improved the OHRQoL (P
< 0.001). The difference in the OHIP-14sp total score
pre-post treatment between the groups was statistically
signicant (P < 0.05). Patients in the intervention group
reported a decrease in all seven dimensions from the
OHIP-14sp after the treatment, with statistically signi-
cant differences for physical pain (P < 0.001), physical
incapacity (P < 0.05), and social disadvantage (P < 0.05;
Fig. 2). Conversely, patients in the control group had
no statistically signicant decrease in any of the dimen-
sions; in fact, three dimensions (physical pain, physical
Table 1 Age, gender, OHIP-14sp total score, VAS score and the mean number of applications
of both groups at baseline and 2 weeks after treatment
Variables Intervention group Control group
Sample size 31 29
Age (years) 54.6 ± 14.9 49.2 ± 14.9
Gender
Male 5 3
Female 26 26
OHIP-14sp total score
Baseline 20.8 ± 10.4 22.3 ± 12.2
Final (2 weeks after treatment) 16.5 ± 9.5* 22.6 ± 12.2
OHIP-14 difference 4.4 ± 8.2* − 0.2 ± 9.8
VAS score
Baseline 56.6 ± 20.3 58.2 ± 21.5
Final 28.5 ± 22.0* 33.7 ± 18.3*
No. of daily applications 2.47 ± 1.54* 3.55 ± 1.72
*Statistically signicant results with P < 0.05.

282
discomfort, and physiological incapacity) registered an
increase, which was not statistically signicant (P > 0.05;
Fig. 3).
Furthermore, non-stimulated salivary ow rates
signicantly increased after the 2-week treatment in
the intervention group (P < 0.001). The control group,
however, revealed a small increase, which was not
statistically signicant (P > 0.05; Table 2). Although the
intervention group reported an increase in stimulated
salivary ow rates after the treatment, the difference was
not statistically signicant (P > 0.05; Table 2).
Discussion
The most commonly used agents for the treatment of dry
mouth are salivary stimulants and/or substitutes. Never-
theless, not much evidence supports any treatment to be
more effective than the other (14,22). Hence, the selection
of the agent is primarily based on the clinical experi-
ence or by allowing patients to decide which one works
the best for them, which could be both expensive and
frustrating. Usually, topical treatments are preferred over
systemic treatments because of their fewer side effects,
easy administration, and acceptance by patients. The use
of topical salivary stimulants based on acidic substances,
such as citric, tartaric, or phosphoric acid, is not new;
however, their use has been questioned because of their
intrinsic erosive potential, which is contra-productive
in patients with reduced salivary ow (23,24), thereby
increasing the risk of caries (25). In contrast, the use of
weaker acid-based salivary stimulants, such as malic
acid, combined with uoride and xylitol, has been shown
to reduce the risk of lowering the salivary pH under the
hydroxyapatite critical level (5.5) when compared with
stronger acids (citric acid) having no impact on tooth
demineralization, even with relatively high concentra-
tions (4.7%) (15). Malic acid is an organic acid found
in fruits, such as pears and apples, and can be obtained
for commercial use by chemical synthesis (26). Malic
acid stimulates salivary ow by dissociating into H+
ions when mixed with water and becoming hydronium
ions (H3O+), leading to saliva secretion to neutralize the
acid formation (17). Recently, a new spray formula-
tion containing 1% malic acid, 10% xylitol, and 0.05%
uoride (Xeros Dentaid Spray) has been proven to be
clinically safe and efcient in reducing xerostomia and
increasing salivary ow rates in patients with dry mouth
secondary to drugs (16-18,27). Nevertheless, its ability
to improve the OHRQoL has not been investigated, and
Table 2 Stimulated and non-stimulated salivary ow rates at baseline and 2 weeks after
treatment
Intervention group Control group
Stimulated salivary ow rate
Baseline 1.30 ± 0.79 mL/min 1.45 ± 1.11 mL/min
Final (2 weeks after treatment) 1.48 ± 0.81 mL/min 1.36 ± 1.11 mL/min
Unstimulated salivary ow rate
Baseline 0.25 ± 0.22 mL/min 0.28 ± 0.28 mL/min
Final 0.33 ± 0.33 mL/min* 0.31 ± 0.30 mL/min
*Statistically signicant results with P < 0.05.
Fig. 2 OHIP-14sp scores per dimension for the intervention
group at baseline and 2 weeks after treatment. *Statistically
signicant results with P < 0.05.
Fig. 3 OHIP-14sp scores per dimension for the control group at
baseline and 2 weeks after treatment.

283
patient-centered outcome measures, such as the quality
of life, are considered as vital outcome measures in the
evaluation of any treatment or health-related intervention
(28,29). Hence, the present study assessed the effect of
1% malic acid on the OHRQoL.
When indicating treatment for xerostomia, it is crucial
to identify the underlying cause. If xerostomia is caused
by a disease that is known to destroy the salivary gland
acini (such as advanced cases of Sjögren’s syndrome
or post-head and neck radiotherapy), it is unlikely that
patients will benet from a salivary stimulant; in fact,
they are more likely to benet from a salivary substi-
tute. In this study, we only included patients in whom
xerostomia was associated with a specic type of drug or
idiopathic causes. In both cases, xerostomia is considered
to be reversible, as there is no glandular damage. Hence,
patients are likely to benet from a topical stimulant,
such as malic acid.
Plenty of evidence conrms that xerostomia negatively
affects the OHRQoL (5,10,30). Patients using a spray
containing 1% malic acid, 10% xylitol, and 0.05% uo-
ride (Xeros Dentaid Spray) demonstrated a statistically
signicant increase in their OHRQoL compared with that
in patients using the placebo. All seven dimensions from
the OHIP-14sp revealed an improvement in the interven-
tion group, with statistically signicant differences for
physical pain, physical incapacity, and social disadvan-
tage. Gerdin et al. (9) and Thomson et al. (30) reported
that physical pain and physical incapacity dimensions
exert a signicant impact on the OHRQoL of patients
with xerostomia, which is in accordance with our results.
When analyzing xerostomia with the VAS, both groups
reported statistically signicant improvement, which is
in discordance with the studies of Gomez-Moreno et al.
(17,27) who reported a statistically signicant difference
just for the malic acid group. This discordance can be
attributed to several reasons. One could be that xylitol
in the placebo group could have some salivary stimulant
activity because of its sweetness, acting as an “active
placebo” (18), thereby decreasing the severity of xero-
stomia without improving the OHRQoL. Söderling et
al. revealed that chewing gums with xylitol signicantly
increased the salivary ow rate compared to chewing
gums without xylitol, suggesting an independent effect
of xylitol on salivary ow (31). Nevertheless, Giertsen
et al. established no effect of xylitol or uoride on the
salivary ow rate (32). However, none of these authors
assessed the effect of xylitol on xerostomia itself. Another
explanation could be that patients from the control group
used the spray more signicantly than patients from the
intervention group, which can increase the placebo effect
because of the willingness of patients to improve their
clinical condition by using the treatment more often (18).
As reported earlier, an increase was noted in the
non-stimulated salivary ow rates (which was statisti-
cally signicant) and the stimulated salivary ow rates
(which did not reach statistical signicance) in the malic
acid group. Our results correspond to those of previous
studies, with the primary difference being that these
studies reported statistically signicant differences in
both stimulated and non-stimulated salivary ow rates
(15,17,27). The signicant improvement in the OHRQoL
observed in the intervention group could be attributed to
an increase in both non-stimulated and stimulated sali-
vary ow rates. Only an increase in the non-stimulated
salivary ow rate was statistically signicant, and the
increase in the stimulated salivary ow rate almost
reached statistical signicance (P = 0.055). Hence, it is
likely that its increase also contributed to the improve-
ment in the OHRQoL, as reported in the literature
(15,17,27).
This study has some limitations. First, most patients
included in this study were females; this indicates that
xerostomia is more common in females than in males
(5). Nevertheless, as groups were balanced regarding
gender and age, not many differences were present
between groups. Second, we recognized that it would
have been ideal to assess xerostomia using a specially
designed questionnaire, such as the xerostomia inven-
tory; however, a Spanish, validated version of such a
questionnaire was not available during this study period.
This clinical trial demonstrates that a topical sali-
vary stimulant containing 1% malic acid improves the
OHRQoL and dry mouth sensation in patients with drug-
induced or idiopathic xerostomia.
Acknowledgments
This research received nancial support from Andres Bello
University (grant: UNABDI-822-15/CB).
Conict of interest
The authors declare no conict of interest.
References
1. Suh KI, Lee JY, Chung JW, Kim YK, Kho HS (2007) Rela-
tionship between salivary ow rate and clinical symptoms
and behaviours in patients with dry mouth. J Oral Rehabil 34,
739-744.
2. Turner M, Ship J (2009) Dry mouth and its effects on the oral
health of elderly people. J Am Dent Assoc 138, 15s-20s.
3. Aliko A, Wolff A, Dawes C, Aframian D, Proctor G, Ekstrom
J et al. (2015) World Workshop on Oral Medicine VI: clinical

284
implications of medication-induced salivary gland dysfunc-
tion. Oral Surg Oral Med Oral Pathol Oral Radiol 120,
185-206.
4. Orellana MF, Lagravère MO, Boychuk DGJ, Major PW,
Flores-Mir C (2006) Prevalence of xerostomia in population-
based samples: a systematic review. J Public Health Dent 66,
152-158.
5. Niklander S, Veas L, Barrera C, Fuentes F, Chiappini G,
Marshall M (2017) Risk factors, hyposalivation and impact
of xerostomia on oral health-related quality of life. Braz Oral
Res 31, e14.
6. Schubert MM, Izutsu KT (1987) Iatrogenic causes of salivary
gland dysfunction. J Dent Res 66, 680-688.
7. Bergdahl M, Bergdahl J (2000) Low unstimulated salivary
ow and subjective oral dryness: association with medication,
anxiety, depression, and stress. J Dent Res 79, 1652-1658.
8. Gonzalez S, Sung H, Sepulveda D, Gonzalez M, Molina C
(2014) Oral manifestations and their treatment in Sjogren’s
syndrome. Oral Dis 20, 153-161.
9. Gerdin EW, Einarson S, Jonsson M, Aronsson K, Johansson I
(2005) Impact of dry mouth conditions on oral health-related
quality of life in older people. Gerodontology 22, 219-226.
10. Ikebe K, Matsuda K, Morii K, Wada M, Hazeyama T, Nokubi
T et al. (2007) Impact of dry mouth and hyposalivation on
oral health-related quality of life of elderly Japanese. Oral
Surg Oral Med Oral Pathol Oral Radiol Endod 103, 216-222.
11. Hahnel S, Schwarz S, Zeman F, Schafer L, Behr M (2014)
Prevalence of xerostomia and hyposalivation and their asso-
ciation with quality of life in elderly patients in dependence
on dental status and prosthetic rehabilitation: a pilot study. J
Dent 42, 664-670.
12. Willumsen T, Fjaera B, Eide H (2010) Oral health-related
quality of life in patients receiving home-care nursing:
associations with aspects of dental status and xerostomia.
Gerodontology 27, 251-257.
13. Hopcraft MS, Tan C (2010) Xerostomia: an update for clini-
cians. Aust Dent J 55, 238-244.
14. Furness S, Bryan G, Birchenough S, McMillan R (2013)
Interventions for the management of dry mouth: topical
therapies. Cochrane Database Syst Rev, CD008934.
15. da Mata AD, da Silva Marques DN, Silveira JM, Marques
JR, de Melo Campos ET et al. (2009) Effects of gustatory
stimulants of salivary secretion on salivary pH and ow: a
randomized controlled trial. Oral Dis 15, 220-228.
16. Martin-Piedra MA, Aguilar-Salvatierra A, Herrera D, Gomez-
Moreno G (2011) Effectiveness of a recent topical sialogogue
in the management of drug-induced xerostomia. J Clin Exp
Dent 3, e268-273.
17. Gomez-Moreno G, Aguilar-Salvatierra A, Guardia J, Uribe-
Marioni A, Cabrera-Ayala M, Delgado-Ruiz RA et al. (2013)
The efcacy of a topical sialogogue spray containing 1%
malic acid in patients with antidepressant-induced dry mouth:
a double-blind, randomized clinical trial. Depress Anxiety 30,
137-142.
18. Gomez-Moreno G, Cabrera-Ayala M, Aguilar-Salvatierra A,
Guardia J, Ramirez-Fernandez MP, Gonzalez-Jaranay M et al.
(2014) Evaluation of the efcacy of a topical sialogogue spray
containing malic acid 1% in elderly people with xerostomia:
a double-blind, randomized clinical trial. Gerodontology 31,
274-280.
19. Murray W, Poulton R, Broadbent M, Al-Kubaisy S (2006)
Xerostomia and medications among 32-year-olds. Acta
Odontol Scand 64, 249-254.
20. Davies AN, Daniels C, Pugh R, Sharma K (1998) A compar-
ison of articial saliva and pilocarpine in the management of
xerostomia in patients with advanced cancer. Palliat Med 12,
105-111.
21. Montero-Martin J, Bravo-Perez M, Albaladejo-Martinez A,
Hernandez-Martin LA, Rosel-Gallardo EM (2009) Validation
the Oral Health Impact Prole (OHIP-14sp) for adults in
Spain. Med Oral Patol Oral Cir Bucal 14, E44-50.
22. Furness S, McMillan R, Birchenough S, Worthington H
(2011) Interventions for the management of dry mouth: non-
pharmacological interventions. Cochrane Database Syst Rev,
CD009603.
23. Sreebny LM (2000) Saliva in health and disease: an appraisal
and update. Int Dent J 50, 140-161.
24. Visvanathan V, Nix P (2010) Managing the patient presenting
with xerostomia: a review. Int J Clin Pract 64, 404-407.
25. Gambon DL, Brand HS, Nieuw Amerongen AV (2009) The
erosive potential of candy sprays. Br Dent J 206, E20.
26. Russell IJ, Michalek JE, Flechas JD, Abraham GE (1995)
Treatment of bromyalgia syndrome with Super Malic: a
randomized, double blind, placebo controlled, crossover pilot
study. J Rheumatol 22, 953-958.
27. Gomez-Moreno G, Guardia J, Aguilar-Salvatierra A,
Cabrera-Ayala M, Mate-Sanchez de-Val JE, Calvo-Guirado
JL. (2013) Effectiveness of malic acid 1% in patients with
xerostomia induced by antihypertensive drugs. Med Oral
Patol Oral Cir Bucal 18, e49-55.
28. Skevington SM (1998) Investigating the relationship between
pain and discomfort and quality of life, using the WHOQOL.
Pain 76, 395-406.
29. Ni Riordain R, McCreary C (2010) The use of quality of life
measures in oral medicine: a review of the literature. Oral Dis
16, 419-430.
30. Thomson WM, Lawrence HP, Broadbent JM, Poulton R
(2006) The impact of xerostomia on oral-health-related
quality of life among younger adults. Health Qual Life
Outcomes 4, 86.
31. Söderling E, Rekola M, Mäkinen KK, Scheinin A (1976)
Turku sugar studies XXI. Xylitol, sorbitol-, fructose- and
sucrose-induced physico-chemical changes in saliva. Acta
Odontol Scand 34, 397-403.
32. Giertsen E, Emberland H, Scheie AA (1999) Effects of mouth
rinses with xylitol and uoride on dental plaque and saliva.
Caries Res 33, 23-31.