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14 Urology Annals | Jan - Apr 2011 | Vol 3 | Issue 1
Objectives: To evaluate the effect of caffeine at the dose of 4.5 mg/kg on bladder function in overactive
bladder (OAB) adults.
Materials and Methods: Nine women and three men aged 21–40 years with OAB symptoms were included.
Each subject drank 8 ml/kg of water with and without caffeine at two separate sessions. Cystometry and
uroflowmetry were performed 30 minutes after each drink. The effects of caffeine on urodynamic parameters
were compared.
Results: After caffeine ingestion, the mean volume at bladder filling phase decreased at first desire to void
and normal desire to void (P<0.05), compared to the mean volume after taking water (control) drink. The
mean volume at strong desire to void, urgency and maximum cystometric capacity also tended to decrease.
No change in the detrusor pressure at filling phase was found. At voiding phase, the maximal flow rate,
average flow rate and voided volume were increased (P<0.05). The urine flow time and time to maximal
flow rate were not changed.
Conclusion: Caffeine at 4.5 mg/kg caused diuresis and decreased the threshold of sensation at filling phase,
with an increase in flow rate and voided volume. So, caffeine can promote early urgency and frequency of
urination. Individuals with lower urinary tract symptom should avoid or be cautious in consuming caffeine
containing foodstuffs.
Key Words: Caffeine, overactive bladder, uroflowmetry
Abstract
Address for correspondence:
Dr. Supatra Lohsiriwat, Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Prannok Rd, Bangkoknoi, Bangkok 10700,
Thailand. E-mail: sislr@mahidol.ac.th
Received: 18.06.2010, Accepted: 01.10.2010
Effect of caffeine on bladder function in patients with
overactive bladder symptoms
Supatra Lohsiriwat, Muthita Hirunsai, Bansithi Chaiyaprasithi1
Departments of Physiology and 1Surgery, Division of Urology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Original Article
INTRODUCTION
Overactive bladder (OAB) is a common syndrome described
by the International Continence Society (ICS) in 2002 as
“urgency, with or without urge incontinence, usually with
frequency and nocturia,” in the absence of infection or other
proven pathology.[1] Quality of life is significantly impaired in
OAB patients, especially in women.[2] Management includes
excluding pathology and implementing behavioral changes
such as caffeine reduction, bladder and pelvic floor training,
as well as antimuscarinic drug therapy.[3] As the etiology in
most cases is unknown, the treatment outcomes have until
recently been unsatisfactory.[3] Treatment compliance, either
in pharmacologic or nonpharmacologic therapy, is often
problematic. Caffeine is often blamed to exacerbate OAB
symptoms, so patients are usually advised to avoid caffeine
consumption.[3-5] For those OAB patients who are coffee
lovers, avoiding coffee and coffee products can equally hurt
their quality of life, and they may wonder if caffeine actually
has anything to do with their OAB symptoms at all.
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DOI:
10.4103/0974-7796.75862
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Urology Annals | Jan - Apr 2011 | Vol 3 | Issue 1 15
Lohsiriwat,
et al
.: Caffeine and OAB
This study aimed to evaluate the effect of caffeine at the dose
of 4.5 mg/kg on bladder function in OAB adults.
MATERIALS AND METHODS
This study was reviewed and approved by the Siriraj
Ethics Committee on Research Involving Human Subjects
(No.114/2004). Twelve OAB patients (nine females and
three males) were studied at the Urodynamic Laboratory,
Division of Urology, Department of Surgery, Faculty of
Medicine Siriraj Hospital, Mahidol University, Bangkok,
Thailand. They fulfilled the inclusion criteria that they were
OAB patients (urgency, with or without urge incontinence,
usually with frequency and nocturia), aged 18–40 years,
regular caffeine consumers (more than three cups of coffee
per week or equivalent), and routine urinalysis revealed no
abnormalities (negative result for sugar, protein, bile and
microscopic examination).
The exclusion criteria included diseases affecting urinary system
such as diabetes mellitus, hypertension, neurological diseases,
any urinary tract disorders such as benign prostatic hyperplasia
(BPH), prostate or bladder cancer, urethral stricture, urinary
tract stone, urinary retention, urinary tract infection (within
2 weeks before study), history of urinary tract surgery and
females during menstrual period or pregnancy.
Each subject completed a previously validated, self-
administered questionnaire to assess medical history and
urinary symptoms. The questionnaire consisted of 11
questions covering frequency, nocturia, weak urinary stream,
urgency, incomplete emptying, intermittency, hesitancy and
straining modified from American Urological Association
(AUA) symptom index to suit Thai cultures and used in
Division of Urology, Siriraj Hospital.
Voiding diary and water intake were recorded. Subjects were asked
to self-record 48-hour voiding diary and water intake. From
this record, the total 24-hour urinary output, number of voids,
voiding interval, diurnal distribution, timing and triggers for
incontinence, and functional bladder capacity were determined.
On arrival in our urodynamics unit, the patients were asked
to void in uroflowmetry machine (Dantec Urodyn 1000).
The parameters recorded were voided volume (
V
comp), total
voiding time (
T
100), time to maximum flowrate (
TQ
max), time
of descending (
T
desc), voiding time for 90% voided volume,
peak flow rate (
Q
max), mean flow rate
(Q
ave), maximum rate of
increase of flow rate (d
Q
/d
T
).
Cystometry was performed with Dantec Manuet Multichannel
clinical urodynamics investigation System (Dantec Electrons,
Skovlunde, Danmark). It was set up and the method was
performed according to “Good Urodynamics practice” as
recommended by the International Continence Society.[6] A
10-Fr double lumen catheter was inserted into the bladder.
The bladder was filled with 0.9% sodium chloride at room
temperature at a rate of 50 ml/minute in sitting position. Intra-
abdominal pressure was measured by inserting 8 Fr single lumen
catheter into the rectum. Bladder sensations of first desire to
void (FDV), normal desire to void (NDV), strong desire to
void (SDV) and urgency were recorded toward the increase
infiltrate volume. Maximum cystometric capacity (MCC)
was recorded when the patients felt that they could no longer
delay micturition. The following pressure parameters were
recorded: abdominal pressure (Pabd), intravesical pressure (Pves),
detrusor pressure (Pdet = Pves –Pabd), compliance (δ V/δ P) and
involuntary bladder contraction during filling the bladder.[7]
Two series of urodynamic study were performed on each
subject at two different occasions by random, with at least
1 week interval. In one occasion, a control drink (8 ml/kg
body weight of boiled water) was taken. In another occasion,
a caffeine drink (caffeine 4.5 mg/kg of body weight in 8 ml/
kg body weight of boiled water) was taken. According to many
articles, caffeine content of beverages in the market ranges from
a modest 50 mg to an alarming 505 mg per can or bottle. So,
we aimed to test for caffeine effect at the dose of 200–250
mg or about 4.5 mg/kg.
All data were calculated in the computer using SPSS program
version 12.0. All basic parameters including dPdet were presented
as mean and standard error of mean (SEM). Kolmogorov-
Smirnor test was used to test the data distribution. Wilcoxon’s
signed-rank test was used to test the difference in variables that
were not normal distribution. Two-sided
P
value of less than
0.05 was considered statistically significant.
RESULTS
The effects of caffeine on bladder functions were studied in 12
OAB subjects using cystometric and uroflowmetric techniques.
The subjects’ characteristics are shown in Table 1.
The temperature of the control and the caffeine drinks was
about 24°C. The total amounts of water and caffeine consumed
by the subjects are shown in Table 1.
Table 1: Subject characteristics and the amount of water and
caffeine consumed (mean±SEM)
Female:male 9:3
Age (yr) 31.4±1.7 (range 21-40)
Body weight (kg) 53.8±3.1 (range 43-75)
Total dose of caffeine consumed (mg) 242.1±14.0 (range 193.5-337.5)
Total volume of water consumed (ml) 433.3±23.5 (range 344-600)
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16 Urology Annals | Jan - Apr 2011 | Vol 3 | Issue 1
Lohsiriwat,
et al
.: Caffeine and OAB
The baseline data on bladder functions were obtained from
the voiding diary. The mean frequency of urine voiding was
9.8±0.7 (range 6–16) times during the day and 3.0±0.6 (range
1–8) times during the night. Five subjects had incontinence
episodes and nine subjects had urgency symptom.
The results of the control and the caffeine drinks on bladder
sensation are shown in Figure 1. After caffeine drink, volumes
of FDV and NDV decreased significantly compared to the
volumes at control day. The filling volume at FDV after
caffeine drink decreased in 10 subjects and increased in 2
subjects, while the filling volume at NDV after caffeine drink
decreased in 9 subjects and increased in 3 subjects. The volumes
of bladder filling at the SDV, urgency and MCC were all
decreased slightly without statistical significance (
P
>0.05).
After caffeine ingestion, the desire to void (FDV, NDV, and
SDV) came earlier at lower Pdet compared to that found in
those after drinking water, though no statistical significance
was reached. This finding indicates a tendency to an increase
in bladder sensitivity after caffeine ingestion.
The Pdet at urgency and MCC were higher after caffeine intake,
though not statistically significant. This indicates a tendency
to stronger detrusor contractions at urgency and MCC after
caffeine ingestion. No involuntary detrusor contractions were
found. The Pdet values are shown in Figure 2.
The uroflowmetric parameters examined were
V
comp,
T
100,
TQ
max,
Q
max and
Q
ave as presented in Figure 3.
After caffeine consumption, the mean
V
comp increased
significantly compared to that after water ingestion. The mean
T
100 tended to decrease after caffeine ingestion, though not
significantly.
T
100 decreased in 10 subjects and increased
in 2 subjects.
TQ
max after the caffeine ingestion was slightly
decreased.
Q
max and the
Q
ave increased significantly.
DISCUSSION
This study, using cystometric and uroflowmetric techniques,
demonstrated that drinking caffeine at the dose of 4.5 mg/kg
Figure 1: Sensation and volumes at bladder lling phases (mean±SE)
in milliliters after water and caffeine ingestions (n=12) (FD=first
desire to void, ND=normal desire to void, SD=strong desire to void,
MCC=maximal cystometric capacity); *P≤0.05 on comparing the
volumes after water and caffeine ingestions
Figure 2: Detrusor pressure at lling phase (mean±SE) in mmHg after
water and caffeine ingestions (FD=rst desire to void, ND=normal
desire to void, SD=strong desire to void, MCC=maximal cystometric
capacity)
Figure 3: Uroowmetric parameters (mean±SE) after water and caffeine
ingestions (Q100=ow time, TQmax=time to max ow rate, Qmax=maximal
ow rate, QM90=average ow rate, Vcomp=voided volume); *P≤0.05 on
comparing the values after water and caffeine ingestions
400
Volume (ml) Water
Caffeine
0
FD ND SD
Sensations
Urgency MCC
100
200
300
Detrusor Pressure
(mmHg)
Water
Caffeine
0
FD ND SD
Sensations
Urgency MCC
4
8
12
Water Caffeine
Qm
ax
QM
90
Q TQ
max
Water
Cafferine
0
0
0
20
40
60
Time (Sec)
10
15
20
25
100
300
500
Vcomp (ml)
Flow Rate (ml/sec)
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Urology Annals | Jan - Apr 2011 | Vol 3 | Issue 1 17
affected urinary bladder function in patients with OAB
symptoms when compared to drinking plain water. The
cardiovascular parameters recorded in this present study also
indicated that caffeine at 4.5 mg/kg caused an increase in the
systolic blood pressure and the diastolic blood pressure. This
is most likely due to the action of caffeine in increasing cardiac
contractility, and the slight decrease in heart rate is most likely
due to the baroreceptor reflex.
Caffeine (chemical name 3,7-dihydro-1,3,7-trimethyl-1H-
purine-2,6-dione) has four identifiable cellular actions
in vitro.
[8] Firstly, caffeine is able to significantly block adenosine
effects on A2A and A1 receptors at the low concentrations
achieved after a single cup of coffee. Secondly, caffeine
inhibits cyclic nucleotide breakdown via inhibition of
phosphodiesterase, for which 20 times higher concentrations
are required. Thirdly, caffeine blocks GABAA receptors at 40
times higher concentrations. Fourthly, at 100 times higher
concentrations, caffeine mobilizes intracellular calcium depots.
Based on these cellular actions, caffeine affects various organ
functions in the human body, including the urinary system. In
the present study, the urine volume was increased in the caffeine
group, confirming the diuretic effect of caffeine. Nocturia was
found to associate with caffeine consumption.[5]
The present study showed that
Q
max and
Q
ave were significantly
increased in the caffeine group. Yi
et al
., in 2006, studied the effects
of caffeine in streptozotocin-induced diabetic rats and found that
caffeine improved the detrusor contractility.[9] Creighton
et al.
reported that after consuming 200 mg of caffeine, patients
with detrusor instability showed an increase in detrusor pressure
on bladder filling, while normal women showed no change in
cystometric parameters.[10]
Caffeine at a high concentration is a calcium releaser, releasing
calcium from its intracellular store.[11] This results in stronger
muscular contraction. Caffeine at a high concentration also
improves reaction time, increases tense arousal, including
anxiety, nervousness and jitteriness.[12] This may result in an
increase in perception of visceral sensation and interpretation.
Since the pathophysiology of OAB is quite complex and still
not so clear,[13] the treatment is sometimes not satisfactory. It
is suggested that various stimulations release many substances,
including adenosine triphosphate, prostaglandins, nitric oxide,
and acetylcholine, from urothelium, which contributes to
pathophysiology of the increased bladder sensation, OAB
symptoms, and detrusor overactivity.[14] The bladder sensory
profiles displayed a more sensitive bladder in OAB patients
compared with non-OAB subjects. OAB patients may have
bladders that are not only overactive but also hypersensitive.[15]
This study demonstrated that caffeine decreased the bladder
volumes at the FDV and NDV, thereby making the bladder
more sensitive to bladder filling. This finding agrees with the
concept that coffee or caffeine aggravates the OAB symptoms
and caffeine restriction can be beneficial.[16-20]
CONCLUSIONS
This study showed that caffeine at a dose of 4.5 mg/kg caused
diuresis and decreased threshold of sensation at filling phase,
with an increase in flow rate and voided volume. So, caffeine
can promote early urgency and frequency of urination as well
as nocturia symptoms. Individuals with lower urinary tract
symptom should avoid or be cautious in consuming caffeine
containing foodstuffs.
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