ARTICLE IN PRESS

The Effects of Caffeine on Voice: A Systematic Review

*

n Kenny, *yDublin, Ireland
Vasilis L. Georgalas, *Niki Kalantzi, †Isolde Harpur, and *Ciara

Summary: Background. Caffeine is considered a dehydrating agent due to its diuretic effects and influences
the body’s fluid balance. The relationship between voice and hydration has been widely investigated and it is
accepted that inadequate hydration has detrimental effects on phonation. Since dehydration negatively affects
the vocal folds and caffeine is considered a dehydrating agent, it can be hypothesized that voice might be nega-
tively affected by caffeine intake. This systematic review aims to summarize and appraise the available evidence
regarding the effects of caffeine on voice.
Methods. Randomized and non-randomized experimental studies of healthy participants were retrieved follow-
ing an electronic searching of six databases in June 2020. No publication, language or date restrictions were
applied. Data extraction of relevant data and risk of bias assessment was conducted independently by two
reviewers.
Results. Five non-randomized experimental studies were deemed eligible for inclusion. The format of the
administered interventions in the included studies was either liquid (coffee) or solid (caffeine tablets). Reported
outcome measures used to examine the effects of caffeine on phonation consisted of acoustic, aerodynamic and
(auditory & self-) perceptual. No measures were adversely affected by caffeine consumption.
Conclusion. Clinicians commonly advise patients to refrain from caffeine, as caffeine intake increases diuresis
with subsequent effects on fluid balance. Such imbalances can potentially induce dehydration which can be detri-
mental to phonation. This notion cannot be supported empirically, as the evidence is deemed unreliable and no
firm conclusions can be elicited to guide clinical practice. The results of this review demonstrate the lack of
research in the field and the necessity for future investigations in order to inform evidence-based practice through
reliable and valid outcomes.
Key Words: Caffeine−Voice− Hydration− Voice quality−Phonation− Systematic review.

INTRODUCTION Conversely, two studies reported to hydration status altera-

Caffeine tions were not noticed following consumption of moderate
Caffeine is one of the most consumed substances in the dosage of caffeine (244 mg-370 mg).12,13
world1. It consists of three central nervous system (CNS) Side-effects of caffeine include diuresis, increased alert-
stimulants; paraxanthine (84%), theobromine (12%) and ness and sleep deprivation, individuals can develop toler-
theophylline (4%).2,3 ance to these. The degree of tolerance varies amongst
Caffeine consumption has been linked with a lower risk of individuals and depends on an individual age and sex14.
particular types of cancer, minimized risk of Type II diabe- According to a review by Nehlig,15 the metabolic, pharma-
tes and a reduced risk of developing Parkinson’s disease, cokinetic, functional and physiological effects of caffeine
Alzheimer’s disease and depression.4 In spite of its beneficial may vary due to age, sex, diet, lifestyle and genetic factors.
effects, consumption has also been associated with bone Caffeine consumption is noted to be increasing world-
loss, reduced bone density, increased pregnancy risks, wide, since caffeine is contained in numerous sources such
behavioural changes and sleep deprivation.5,6 The impact of as coffee, tea, chocolate, sodas, energy drinks and medica-
caffeine on the body’s fluid balance as a result of increased tions.16 Despite a lack of consensus regarding safe levels of
diuresis has been investigated. A review by Maughan & intake, Health Canada (HC) provide advice about the
Griffin7 reported that 300mg of caffeine can induce diuresis, amount of caffeine that is considered safe to be consumed17
while a more recent meta-analysis suggested that 300mg of with values based on the review by Nawrot et al.18 (Table 1).
caffeine intake does not influence diuresis.8 Three studies
have demonstrated that higher dosages (>450 mg) of caf-
feine intake have subsequent effects on total body water Hydration and voice
(TBW) volume, fluid balance and urine output volume.9-11 Hydration refers to the TBW concentrations in the human
body. Hydration status is described with the following
terms: euhydration, dehydration and hyperhydration. Euhy-
Accepted for publication February 15, 2021.
From the *Department of Clinical Speech and Language studies, Trinity College
dration is the presence of fluid equilibrium and refers to ade-
Dublin, Dublin, Ireland; and the yThe Library of Trinity College, Dublin, Ireland. quate hydration levels within the human body.19 Research
Address correspondence & reprint requests: Vasilis L. Georgalas, Trinity College
Dublin, Phoenix House, 7-9 Leinster Street, Dublin 2, Dublin, Ireland. E-mail:
has shown that age, sex, adiposity levels and population
[email protected] characteristics (eg, occupation, ethnicity) are some of the
Journal of Voice, Vol. &&, No. &&, pp. &&−&&
0892-1997
factors contributing to different TBW volumes.20,21 On
© 2021 The Authors. Published by Elsevier Inc. on behalf of The Voice Founda- average, the TBW volume comprises approximately 63.3%
tion. This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/)
of total body weight (0.5-0.6L per kg), of which 24.9% is
https://doi.org/10.1016/j.jvoice.2021.02.025 located extracellularly and 38.4% intracellularly.22 More
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2 Journal of Voice, Vol. &&, No. &&, 2021

TABLE 1. MATERIALS AND METHODS

Caffeine Consumption Safe Levels as Proposed by Preferred Reporting Items for Systematic Reviews and
Health Canada Meta-Analysis (PRISMA) guidelines were used in this sys-
tematic review.38 A protocol was developed to reduce
Age group/Condition Amount of caffeine
author bias and increase methodological quality.39 The pro-
Adults ≤400mg tocol was registered in the PROSPERO database40 (PROS-
Children (6-12years) 45-85mg PERO ID: CRD42020196488).
Adolescents (≥12years) 2.5mg per kg
Pregnant Women <300mg
Search strategy
Prior to search strategy development, scoping (preliminary)
searches were utilized, using simple terms, in order to exclude
the possibility of an existing SR in the same topic and to locate
specifically, the extracellular volume contains 5% of plasma essential studies.41 Next, a search strategy was developed in
water and about 20% interstitial fluid.22 collaboration with a subject librarian (IH). This search was
Voice-related studies of hydration have been concerned piloted and refined to minimize irrelevant results. The search
with systemic and superficial hydration. Systemic hydration was devised to search for synonyms and related terms for:
refers to adequate fluid located within body tissues and is “healthy adults AND caffeine AND decaffeinated AND
predominantly achieved through water intake23. Con- voice outcome measures”. To ensure the search strategy’s
versely, superficial (or surface) hydration is defined as the accuracy, the Peer Review of Electronic Search Strategy
hydration of the surface of laryngeal mucosa that keeps the (PRESS) guidelines were used by the second reviewer (NK) to
epithelial cells moisturized and lubricated, and is achieved appraise the quality of the search and offer recommendations
via steam inhalation or increased environmental humidity.24 for change.42 Overall, the search strategy was deemed appro-
Inadequate hydration can adversely affect vocal fold visco- priate and no revisions were proposed. Six databases
elasticity, oscillation threshold and voice quality, since vocal (PubMed, Cinahl Complete, Web of Science Core Collection,
folds are covered with a thin mucosal surface layer that has EMBASE, Cochrane Central, ProQuest Dissertation and
biomechanical and protective properties.24 Theses A&I) were searched for eligible studies in June 2020.
In vivo studies on excised animal larynges examined the The finalized search strategy consisted of 9 thesaurus (or sub-
physiology and biomechanics of the vocal folds after ject heading) terms and 24 title & abstract terms. The ‘human’
induced dehydration and rehydration challenges. The desic- filter option was used across databases to exclude animal stud-
cation challenges utilized to dehydrate the excised animal ies. Otherwise, no filters or restrictions were used. A sample
larynges resulted in increased tissue stiffness with conse- search strategy for the PubMed database is in Appendix.
quent increased phonation threshold pressure (PTP), vocal Backward citation chaining was also used. This refers to a sys-
fold tension and viscosity alterations.25-30 tem of identifying important articles through scanning the ref-
Human studies have demonstrated that both systemic and erence list of included studies.43
superficial dehydration adversely affects phonation.
Reduced hydration over a fasting period greatly affected Eligibility criteria
maximum phonation time (MPT) and perceived phonatory The PICOS framework44 was used to guide study eligibility.
effort (PPE) in males and females.30,31 Inadequate hydra- Participants had to be vocally healthy without diagnosed
tion also negatively impacted acoustic, perceptual and aero- voice disorders. No age or sex restrictions applied. Studies
dynamic measures in professional singers following a 2- were eligible for inclusion only if the substance type (e.g. cof-
hour rehearsal.32 Three studies demonstrated that superfi- fee, caffeine tablets, energy drinks) and dosage of caffeine con-
cial dehydration due to low relative humidity (RH) sumed were reported. Although comparators were not a
adversely influenced PPE, PTP and other acoustic measures prerequisite for inclusion, if the study had a control group, the
compared to moderate or high RH.33-35 Two more studies comparator could be a decaffeinated beverage, placebo or
investigated the effects of oral breathing combined with var- water. Outcomes of interest were any acoustic, aerodynamic,
ious levels of RH and the results indicated that PPE and auditory-perceptual or self-perceptual voice measures.
PTP measures were negatively affected, however the influ- Randomized control trials (RCTs) and non-randomized
ence of low RH exacerbate the outcomes.36,37 studies (NRS) were eligible irrespective of publication, date
While increased water intake is a common recommenda- or language status.
tion by clinicians, especially if caffeinated beverages are
consumed, the available evidence on the effects of caffeine
on the body’s hydration levels has yielded inconsistent Study selection
results. Clinical advice is based on the anecdotal notion that All retrieved studies were imported into Covidence and were
caffeine increases diuresis, hence fluid balance within the automatically de-duplicated. The software de-duplicates the
body is affected. This systematic review seeks to summarize articles on the basis of author, title, year and volume of pub-
the available evidence about the effects of caffeine on voice- lication. Title and abstract, as well as full text screening were
related measures in healthy participants. conducted independently by two reviewers (VG & NK) in
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Vasilis L. Georgalas, et al Effects of Caffeine on Voice 3

order to minimize the possibility of human error and bias.39 the Downs & Black (D&B) checklist was selected an appropri-
Disagreements were resolved by consensus. In cases where ate tool that can be implemented in an array of study method-
potential disagreements could not be resolved, a third reviewer ologies.45 A modified version of D&B checklist was utilized.46
(CK) acted as an arbitrator by providing a casting vote. This adapted version of D&B that was implemented in this
SR consists of a 28-point scale compared to the original 32-
point scale. The variation of the total score is a result of the
Data analysis and synthesis altered scoring system of the last domain Power. In the origi-
A data extraction form was designed to capture information nal version by D&B the score in the domain Power ranges
about participants, study methods, outcome measures and from 0 to 5 depending on the number of subjects allocated to
results. Each section was revised and tailored to the review’s each group. Conversely, in this adapted version the last ques-
needs by the principal investigator (VG). Prior to data tion in the domain Power was scored on the basis of whether
extraction, the form was piloted on three randomly chosen the study reported a power analysis or not. Thus, the score in
included studies. Since the data and methodology of each this domain ranges from 0 to 1 (refer to Table 2 for a detailed
study may vary, piloting was necessary in order to ensure description of the tool).
that the data collection form could meet each study’s
requirements.39 After piloting, the final data collection form
included the following domains: population and setting,
study methodology, participant information, study charac-
Levels of evidence
teristics and experimental procedures, outcome measures.
The Oxford Centre of Evidence Based Medicine (OCEBM)
Data were extracted independently by two reviewers (VG,
guide appraises the evidence level of a study based on type of
NK). Missing data was addressed by the principal investiga-
evidence and study methodology.47 This guide consists of
tor (VG), who contacted authors in order to request infor-
seven questions. Each is a typical question a clinician might
mation essential for this review. The extracted data were
encounter when providing advice. For this review the question
tabulated and summarized narratively, since a meta-analy-
What are the COMMON harms? was chosen on the basis that
sis was not possible due to heterogeneity across studies.
caffeine is considered to be potentially harmful to the voice
(Table 3). Other questions from the guide were not included
Quality assessment as they were irrelevant. It was agreed by the review team to
Risk of bias include pilot studies at Level 5 of evidence, as pilot studies,
Risk of bias was independently appraised by two reviewers much like “mechanism-based reasoning” studies, explore the
(VG, NK). The Risk of Bias (RoB) tool by Cochrane Collab- feasibility of larger scale RCTs and summarize information
oration was selected in for RCTs. For NRS methodologies, for future hypothesis testing.48

TABLE 2.
Downs and Black Risk of Bias Tool With Adaptations by Hooper et al. (2008)
Domains Scoring System Score Range Quality appraisal based
on the overall score
Reporting Yes=1, No=0, 0−28 Excellent ! 26−28
External Validity Unable to determine=0, Good ! 20−25
Internal Validity (Bias) [Yes=2, Partially=1, Fair ! 15−19
Internal Validity (Confounding) No=0 − used only in one item] Poor ! ≤ 14
Power

TABLE 3.
OCEBM Treatment Harms Domain
What are the COMMON harms? (Treatment Harms)
Level 1 Systematic review of randomized trials, systematic review of nested case-control studies, n-of-1 trial
with the patient you are raising the question about, or observational study with dramatic effect
Level 2 Individual randomized trial or (exceptionally) observational study with dramatic effect
Level 3 Non-randomized controlled cohort/follow-up study (post-marketing surveillance) provided there
are sufficient numbers to rule out a common harm. (For long-term harms the duration of follow-up
must be sufficient.)
Level 4 Case-series, case-control, or historically controlled studies
Level 5 Mechanism-based reasoning & pilot studiesa
a
Pilot study designs were added by the review team.
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RESULTS Study characteristics

Database search results All eligible studies had non-randomized study designs.50-54 Three
The total search results retrieved from all databases was of five were pilot studies,50,51,53 while the remaining two were
n=1818. Following de-duplication, n = 1443 title and true experimental studies.52,54 The findings of the pilot study by
abstracts were screened and n = 1435 of them were rejected Ahmed et al.50 were published as a “Letter to the Editor”.
based on inclusion/exclusion criteria. A total of n=8 studies
were deemed eligible for full-text screening. The full text of
one study was not available online,49 thus the primary inves- Sample size and participant characteristics
tigator (VG) corresponded with the primary author. This A total of n=155 healthy participants were recruited
study was excluded due to lack of response, therefore n = 7 amongst the included studies. The age range was reported
studies were included for full-text review. During full-text in four out of five studies and the overall range was 18 to 55
review, two further studies were removed as they did not years,51-54 with the most common age range between 18-
meet eligibility criteria. No disagreements between the 35 years. Mean participant age was reported in only one
reviewers occurred. A total of n = 5 studies were included study53 and was 23. In another paper raw data were avail-
for data extraction. The citation chaining method did not able, so mean age and standard deviation were computed as
identify additional articles. The PRISMA flow diagram 22.7§3.86.52 Participant sex was reported in only four out
(Figure 1) illustrates the review phases. of five studies and was 91% female, 9% male51-54 (Table 4).

FIGURE 1. PRISMA flow-chart. Adapted from Moher et al. (2009)

 Vasilis L. Georgalas, et al
TABLE 4.
Summary of Study and Participant Characteristics per Study
Reference Study design Participants Sampling Eligibility criteria
method
N of participants Gender ratio % Age Inclusion Exclusion
a

Effects of Caffeine on Voice

Ahmed et al. 2012 Pilot, repeated measures, N=25 N/R N/R N/R No diagnosis of Recent upper respiratory tract
sham-controlled, voice disorder, no infection, hypothyroidism,
experimental study oral cavity renal or blood pressure
disorders problems

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Akhtar et al. 1999 Pilot, repeated measures, N=8 Male: Mean: N/R N/R No recent diagnosis Diagnosis of systemic
one group study 50% Median: N/R of voice disorders illnesses especially
Female: Range: 27-55 respiratory or
50% cardiovascular
Erickson-Levendoski Prospective, N=16 Male: Mean: 22.7 N/R Perceptually normal Respiratory disease, reflux,
& Sivansankar, double-blinded, sham- 50% Median: 20 speech and voice, smoking, prescription
2011 controlled repeated Female: Range: 18-32 no hearing medication except oral
measures experimental 50% problems contraceptives
study
Franca & Simpson, Pilot, repeated measures, N=48 Male: Mean: 23 N/R Self-reported normal High blood pressure,
2013 experimental 0% Median: - voice coronary disease,
study Female: Range: 18-35 self-reported discomfort
100% while consuming caffeine
Franca et al., 2013 Prospective, repeated N=58 Male: Mean: N/R N/R Self-reported normal High blood pressure,
measures, experimental 0% Median: - voice, general coronary disease
design Female: Range: 18-35 good health
100%
a
N/R= Not reported

5
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With regards to participant eligibility, perceptual or self- ‘Excellent’ quality (Table 7). Three of the studies were rated
reported normal voice with absence of voice pathology was as ‘Fair’ and the remaining two as ‘Poor’ quality. Power,
the main inclusion criterion in every study. In the majority External Validity and Internal Validity-Confounding
of the studies, subjects were excluded if high blood pressure domains presented the highest risk of bias between domains
and coronary disease were reported.50,51,53,54 Reflux symp- in all studies. Conversely, low risk of bias was noted in the
toms, smoking and medication (except oral contraceptives) Reporting domain in three studies, however in the rest of the
were exclusion criteria in one study.52 Lastly, three studies studies the risk of bias in the same domain was unclear.
deemed participants ineligible for inclusion on the basis of External Validity was at high risk due to lack of informa-
self-reported or diagnosed respiratory disorders.50-52 tion regarding the sampling method, nonrepresentative pop-
(Table 4) ulation and non-representative experimental conditions.
Random allocation of participants into intervention or con-
trol groups was not performed in any of the experiments
Experimental procedures and potential confounders were not provided, thus high risk
Variation was noted in the experimental procedures of bias was observed in the Internal Validity-Confounding
employed in each study (Table 5). With regards to the inter- domain. Lastly, none of the studies presented evidence of
vention, the type and dose of the caffeine varied amongst power analysis. Despite the fact that a power analysis was
the studies. The participants in three of the studies con- not conducted, it can be deduced that the power level was
sumed caffeine tablets51,53,54 while in the rest of the studies reduced as it was influenced by small sample sizes, which
subjects ingested coffee.50,52 The milligrams (mg) of caffeine may have increased the chance for a Type II error.
ingested by participants in included studies ranged from Using the OCEBM Levels of Evidence, the two experi-
100mg to 480mg. The comparator intervention consisted of mental studies were placed at Level 3 of evidence, since they
placebo, water, decaffeinated coffee and no intervention at were non-randomized experimental studies. Pilot studies
all. While all studies had pre-caffeine baseline measures, were automatically assigned in the Level 5 of evidence,
only four of them collected voice measures on the same day. as their study design explores the feasibility of a larger
The duration of the study procedures varied from two hours scale studies and do not provide substantial evidential
to two days, though duration was not reported in two stud- information.
ies53,54. Abstention from caffeine to better control experi-
mental procedures was used in four out of five studies, but
with varying instructions. DISCUSSION
The aim of this study was to identify and critically appraise
the available evidence regarding the potential effects of caf-
Outcome measures feine on voice-related measures. Due to small number of
The primary outcome measures utilized in the included included studies, lack of methodological integrity and high
studies were aerodynamic, acoustic and perceptual. Acous- risk of bias, the evidence regarding the effects of caffeine on
tic measures like jitter and shimmer were the most fre- phonation is unreliable. This review cannot therefore pro-
quently reported outcomes, while perceptual measures were vide robust advice about the effects of caffeine on voice.
utilized in only one study. Perceptual and acoustic measures
were obtained under different conditions, such as sustained
“ah” sound, singing, reading or speaking. PTP and aerody- Methodological considerations
namic airflow were the only aerodynamic measures col- Caffeine is known to have a potentially systemic dehydrat-
lected. PTP and airflow outcomes were obtained while the ing effect. The degree of localised dehydration within the
subjects repeatedly uttered the syllables /pi/ or /pa/ respec- vocal folds is however unknown. Vocal fold dehydration
tively. Secondary outcome measures were considered in one can lead to aberrant voice quality through mechanisms such
study, where the participants were requested to rate their as reduction in vocal fold lubrication, reduced oscillation
vocal effort using a visual analog scale52. Overall, all studies and increased risk of trauma through vocal fold collision.23
reported non-significant effects of caffeine on voice-related These findings have been confirmed in a canine model,
measures (P ≥ 0.05). To be noted, only two studies reported where dehydrated vocal folds were found to be stiffer and
the exact p values for each outcome measure53,54. One study more viscous.25 The studies in this systematic review are
reported subtle changes in irregularity of fundamental fre- thus based on the hypothesis that systemic dehydration may
quency, however the authors attributed these irregularities induce vocal fold dehydration, which would manifest as
to individual characteristics51. Detailed description of the abnormal voice production due to the factors above.
results is provided in Table 6. All included studies had a repeated measures experimen-
tal design in order to demonstrate the effects of caffeine
intake. This is considered acceptable to measure the cause-
Methodological quality assessment [Table 7 near this and-effect relationships between independent and dependent
section] variables between groups.55 Three of these however
Risk of bias appraisal was conducted using the D&B check- employed the pre-post design in a pilot study methodology.
list. Overall, none of the studies was deemed of ‘Good’ or Pilot studies provide non-evidential information, as they are
 Vasilis L. Georgalas, et al
TABLE 5.
Overview of experimental Procedures in Included Studies

Effects of Caffeine on Voice

Reference Intervention Comparator Duration Absorption of Hydration status Environmental
caffeine measurements parameters

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Ahmed et al. Type: Coffee Type: Decaffeinated 2 days N/R N/R N/R
2012 Dosage: 400mg coffee
Dosage: Not
clearly defined
Akhtar et al. Type: None Approximately N/R N/R N/R
1999 Caffeine tablets 2 hours Blood tests
Dosage: 250mg employed to
(5 £ 50mg ensure absorption
Erickson- Type: Coffee Type: Decaffeinated Approximately 2.5-3hours N/R Environmental
Levendoski & Dosage: 480mg coffee 5 hours humidity control
Sivansankar, 2011 (2 £ 240mg) Dose: 24mg during measure-
2 coffees consumed ments (70% § 6%)
(12 £ 2=24mg)
Franca & Simpson, Type: None N/R 30mins N/R N/R
2013 Caffeine tablet
Dosage: 200mg
Franca et al., 2013 Type: Type: Placebo N/R 30mins N/R N/R
Caffeine tablet (tablet)
Dosage: 100mg Dose: 0mg

7
 8
TABLE 6.
Overview of Outcome Measures and Statistical Findings
Reference Outcome measures Measurement Conditions Statistical Findings
Primaryoutcomes Secondary outcomes
Ahmed et al. 2012 Acoustic: - Acoustic: N/R
Jitter, Shimmer, f0 Sustained “ah” sound
Auditory-Perceptual: GRBAS:
GRBAS Grandfather Passage
Akhtar et al. 1999 F0 irregularity (using a - Free speech, reading, singing Effects of caffeine on f0
laryngograph) (“Happy Birthday”) non-significant (p ≥ 0.05)
Erickson-Levendoski Aerodynamic: Perceived phonatory PTP: Effects of caffeine on PTP

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& Sivansankar, 2011 Phonation threshold effort (PPE) Measures obtained in two (10th−80th) and PPE non-
pressure (PTP) different pitches: Sustained significant (p ≥ 0.05)
“ah” sound obtained at 10% Differences between caffeinated
and 80% of the participant’s and decaffeinated conditions
pitch range non-significant (p ≥ 0.05)
PPE:
Self-rated vocal effort after
singing (“Happy Birthday”)
using a visual analog scale
Franca & Simpson, Aerodynamic: - All measures: Effects of caffeine consumption
2013 Aerodynamic measure Sustained “ah” sound, with or without water on voice
of airflow x3 times repetition measures
Acoustic: “Pa” syllable produced
Jitter, Shimmer, x3 times
Sound Pressure

Journal of Voice, Vol. &&, No. &&, 2021

Level
Franca et al., 2013 Aerodynamic: - All measures: Effects of caffeine on voice
Aerodynamic measure Sustained “ah” sound, measures
of airflow x3 repetitions
Acoustic: “Pa” syllable produced
Jitter, Shimmer, x3 times
Sound Pressure
Level
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Vasilis L. Georgalas, et al Effects of Caffeine on Voice 9

TABLE 7.
Risk of Bias Overall Score per Domain for Each Study
Reference Reporting External Internal Internal Validity Power Overall
Validity Validity Confounding Score &
Bias Quality
Ahmed et al. 2012 7 0 3 1 0 11/28 ‘Poor’
Akhtar et al. 1999 7 0 2 1 0 10/28 ‘Poor’
Erickson-Levendoski & 9 0 7 2 0 18/28
Sivansankar, 2011 ‘Fair’
Franca & Simpson, 9 0 4 2 0 15/28
2013 ‘Fair’
Franca et al., 2013 9 0 4 2 0 15/28
‘Fair’

designed to explore the feasibility of larger-scale studies and caffeine to be detected in blood plasma, absorption and
not answer hypotheses or draw firm conclusions.48 metabolism of caffeine varies amongst subjects depending
The recruited subjects were not representative of the on individual characteristics like sex and pharmacokinet-
entire population, hence a higher risk of selection bias is ics.15 Since the presence of caffeine in blood was not objec-
noted. Indeed, the studies’ participants were predominantly tively measured, it is impossible to determine whether the
females, and the age range in three out of five studies was caffeine was completely absorbed within the 30 minutes
between 18 and 35 years old. Therefore, the demographic allotted. One study did however use blood tests for detection
characteristics of the subjects do not represent the true val- of caffeine plasma and the values of caffeine concentrations
ues of the population and differences based on sex could not in blood increased following caffeine consumption.51 Fol-
be drawn. lowing oral intake, caffeine’s distribution is completed
Sample size and power level are bidirectionally corre- within 20 minutes through the biological membranes.59
lated; the bigger the sample the greater the power level. However, regular consumption of higher caffeine dosages
Since the majority of the studies recruited a relatively small can increase the distribution and excretion rate of caf-
number of participants, the power of the studies was feine.59,60 Participants’ caffeine consumption habits were
reduced, as it is influenced by the sample size. Consequently, not reported in any of studies, thus differences in distribu-
the probability of detecting any effects is reduced and the tion and excretion rates may have been occurred. Caffeine’s
probability of a Type II error is increased.56 Another limita- metabolic rate is significantly increased for smokers, a factor
tion that adversely influenced the generalizability and appli- that was taken into account in only one study15,52.
cability of the evidence is the type of intervention Caffeine tolerance is another variable that could have
implemented in the studies. The participants of the interven- influenced outcomes. Information about the average daily
tion groups predominantly consumed caffeinated tablets, a caffeine intake of participants was not provided in any of
source of caffeine that does not reflect a realistic caffeine the studies. Various studies have examined the tolerance lev-
source, as the average populations’ source of caffeine is cof- els and the effects of caffeine on habitual and non-habitual
fee, tea and soft drinks.57 This disimproved the ecological coffee drinkers. It is reported that repeated caffeine con-
validity of the studies. sumption can induce tolerance, a factor that mitigates caf-
feine’s effects, such as diuresis, increased alertness, sleep
deprivation and reduced sense of fatigue2,7. Tolerance can
Experimental considerations be induced in approximately 10 days, however the degree of
The findings suggest that voice production was not tolerance varies amongst individuals, as it depends on indi-
adversely affected by caffeine consumption. This non-signif- vidual characteristics (eg, sex, age).14
icant outcome could be attributed to a variety of factors. Objective assessment of hydration status was not
The majority of the studies utilized moderate caffeine dos- employed in any of the studies (eg, bioelectrical impedance
ages, which are considered safe for the human body.17 analysis, urine samples). Assessment of hydration could
Another factor that should be taken into account is the caf- provide an insight on possible systemic hydration status fol-
feine absorption rate. Caffeine absorption is completed in lowing caffeine consumption, since hydration levels vary
approximately 50 minutes; however, caffeine can be amongst individuals. It should be noted though that the
detected in blood plasma within approximately 35 investigators in two of the studies instructed participants to
minutes.58 In two of the studies, voice measures were col- avoid liquids 12 hours prior to the experimental proce-
lected 30 minutes following caffeine consumption.53,54 dures,53,54 in an attempt to create equal baseline levels of
Although theoretically 30 minutes are sufficient for the hydration. Since an objective hydration assessment was not
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employed, it was impossible to determine whether the par- Five studies were deemed eligible for inclusion, but all
ticipants adhered to the investigators’ instructions or were characterized by methodological flaws and high
whether equal baseline hydration levels were achieved. The risk of bias rendering the results unreliable. The method-
effects of environmental humidity and its effects on superfi- ological limitations of the included studies that are
cial hydration of the vocal folds were acknowledged in one described in this review could however provide the basis
study where the investigators adjusted the RH to moderate for more robust investigations of the effects of caffeine
levels (70% RH).52 on phonation in the future.
Overall, a few potential confounders were taken into RCTs utilizing randomization (eg, allocation, sampling)
account (eg, menstrual cycle, smoking), however none of and blinding could ensure that cause-and-effect relation-
the experiments described comprehensive experimental con- ships may be attributed to the implemented intervention.
trol by listing and exhaustively controlling potential con- However, RCTs are not always feasible, so carefully
founders. designed true experimental studies can also yield evidence
that can be internally valid. Future investigations must
focus on controlling extraneous factors that potentially
Implications for clinical practice
influence the outcomes. Controlling for all potential con-
Physicians and speech and language therapists advise
founders might not be possible, thus it is essential to include
patients to refrain from caffeine consumption on the
an objective hydration assessment method in order to deter-
assumption that caffeine intake induces diuresis, which low-
mine whether caffeine has an influence on the hydration sta-
ers fluid balance. Such imbalances can induce dehydration
tus of the participants and to utilize blood or urine tests to
which can be detrimental to phonation. The implied transi-
measure caffeine absorption.
tive relationship must however be supported empirically.
A recent review by Wikoff et al.6 reviewed data for poten-
This systematic review focused on the impact of caffeine on
tial adverse effects of caffeine consumption and the results
voice in healthy adults and found inconclusive evidence
showed that low to moderate doses (up to 400mg) of caf-
about any deleterious effects. Due to lack of methodological
feine do not negatively affect the body. Thus, greater dos-
quality and risk of bias, the outcomes of this review do not
ages of caffeine (>400mg) should be used to increase the
provide robust evidence regarding the potential adverse
possibility of detecting effects on voice quality and to reflect
effects of caffeine on phonation. Thus, clinicians should be
the fact that some individuals consume caffeine above rec-
cautious when counselling patients to refrain from caffeine,
ommended amounts. Future research should examine caf-
as clinical recommendations cannot be supported. Health
feine concentrations in the medium in which they are
professionals could refer to published guidelines17 regarding
served. For instance, weaker coffee (higher water to caffeine
the safe values of caffeine consumption to advise patients to
ratio) might promote hydration and mitigate the dehydrat-
moderate caffeine intake if uncertain.
ing effects of caffeine as compared to another study that
This is not to say that counselling patients to reduce caf-
uses stronger coffee (lower water to caffeine ratio). In addi-
feine intake is totally without merit. Clinicians should con-
tion, control over environmental confounders such as
sider the other relationships between caffeine with voice.
humidity is advisable, as superficial hydration of the vocal
For instance, caffeine intake might exacerbate existing dis-
fold tissues is achieved through higher RH, a factor that
orders such as laryngopharyngeal reflux, making avoidance
might influence outcomes.
appropriate in some cases.61 In vivo studies62 have also
Prospective studies should recruit an adequate number of
demonstrated that caffeine can interfere with circadian
participants that will be representative of the entire popula-
rhythms, altering sleep and/or wake cycles. While a systemic
tion. A large sample size would ensure adequate power lev-
effect and not one isolated to the vocal folds, this may cause
els, so the probability of detecting potential effects would be
those with voice difficulties not to obtain refreshing sleep,
increased. Additionally, effects should be investigated
which could exacerbate feelings of stress. Despite the fact
amongst different age groups and sexes in order to render
that caffeine has been associated with lower risk of depres-
outcomes more generalizable and representative. Another
sion, caffeine consumption might adversely affect people
factor that could be taken into consideration is the long-
with mental health issues. Caffeine has been positively asso-
term effects of caffeine consumption on phonation. Future
ciated with an increased risk for deterioration of anxiety
prospective longitudinal studies could shed light to the long-
symptoms and higher risk of relapse episodes.63 SLTs work-
term effects of caffeine intake on phonation, rendering them
ing with patients with mental health issues should consider
more representative of real-life situations, where caffeine is
the effects of caffeine consumption on these patients, since
consumed regularly and not in isolation.
no specific guidelines have been published for safe dosages
It should be noted that no studies that investigated the
of caffeine consumption amongst people with mental and
effects of caffeine in children under-18 years of age were
psychiatric health issues.63
identified, highlighting the lack of research and evidence in
this area. In terms of occupation, future research should
Directions for future research also investigate the potentially adverse effects of caffeine on
The low quantity and quality of the studies that were identi- occupational and professional voice users, a population that
fied highlights the need for further, more robust research. is particularly prone to voice disorders.
 ARTICLE IN PRESS
Vasilis L. Georgalas, et al Effects of Caffeine on Voice 11

This systematic review focused on the impact of caffeine dehydrat* [Title/Abstract] OR de-hydrat* [Title/
on voice in healthy adults and found inconclusive evidence Abstract] OR de hydrat*[Title/Abstract]
about any deleterious effects. Clinicians working with those 3. 1 OR 2
who have voice disorders may be interested in how caffeine 4. Phonation [MeSH] OR Larynx [MeSH] OR Voice
affects those with dysphonia, since dysphonic individuals [MeSH] OR Voice Disorders [MeSH] OR Speech
could be at increased risk of harm due to their underlying Acoustics [MeSH]
pathology. Even modest dehydration of the vocal folds in 5. “speech acoustic*” [Title/Abstract] OR “perturbation
such individuals could exacerbate voice difficulties and it measure*” [Title/Abstract] OR “aerodynamic mea-
would be illuminating to identify whether caffeine might sure*” [Title/Abstract] OR “acoustic measure*” [Title/
contribute to this. Any researchers engaging in such studies Abstract] OR “perceived phonatory effort” [Title/
would however need to carefully consider the ethical diffi- Abstract] OR voice [Title/Abstract] OR phonation
culties of potentially exposing participants to further vocal [Title/Abstract] OR larynx [Title/Abstract] OR laryn-
harm, in addition to controlling for anatomical, physiologi- ges [Title/Abstract] OR laryngeal [Title/Abstract] OR
cal and biomechanical variation between different voice dis- vocal [Title/Abstract]
orders. 6. 4 OR 5
7. 3 AND 6
Limitations
(phonation[MeSH Terms] OR larynx[MeSH Terms] OR
Due to small number of studies, poor quality of data and
voice disorders[MeSH Terms] OR voice[MeSH Terms] OR
lack of homogeneity amongst the studies a meta-analysis
speech acoustics[MeSH Terms] OR speech acoustic*[Title/
was not conducted, hence a quantitative analysis and pre-
Abstract] OR perturbation measure*[Title/Abstract] OR
sentation of the findings was not possible.
aerodynamic measure*[Title/Abstract] OR acoustic mea-
Although sample sizes were small in a few studies, and
sure*[Title/Abstract] OR perceived phonatory effort[Title/
although this most likely had a detrimental effect on statisti-
Abstract] OR voice[Title/Abstract] OR phonation[Title/
cal power, two of the studies utilized relatively high sample
Abstract] OR larynx[Title/Abstract] OR larynges[Title/
sizes. Since a power analysis was not computed, a precise
Abstract] OR laryngeal[Title/Abstract] OR vocal[Title/
estimation of the ability of the included studies to establish
Abstract]) AND (dehydration[MeSH Terms] OR beverage
an effect could not be determined.
[MeSH Terms] OR caffeine[MeSH Terms] OR coffee
[MeSH Terms] OR coffee[Title/Abstract] OR caffein*[Title/
CONCLUSION Abstract] OR decaffein*[Title/Abstract] OR de-caffein*
The findings of the present review cannot provide robust [Title/Abstract] OR de caffein* [Title/Abstract] OR bever-
evidence regarding the effects of caffeine on voice-related age*[Title/Abstract] OR hydrat*[Title/Abstract] OR rehy-
measures. Since no firm conclusions can be elicited to guide drat*[Title/Abstract] OR re-hydrat*[Title/Abstract] OR re
clinical practice, clinicians should be cautious when recom- hydrat* [Title/Abstract] OR dehydrat*[Title/Abstract] OR
mending caffeine abstinence to patients. de-hydrat*[Title/Abstract] OR de hydrat*[Title/Abstract]
The results of this review demonstrate the lack of research
in the field and the necessity to inform evidence-based prac-
tice through reliable and valid outcomes. Future research
should recruit a more representative sample and employ
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