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Introduction
In recent years, a number of clinical studies have appeared to
substantiate one of the traditional therapeutic uses of extracts of
bromelain, namely, in the treatment of inflammatory disorders
of the musculoskeletal system. This paper sets out to review the
clinical evidence for the use of bromelain in osteoarthritis.
Osteoarthritis is the most common form of arthritis in Western
countries; in the USA prevalence of osteoarthritis ranges from
3.2% to 33% dependent on the joint (1). Its prevalence increases
with age, and sex differences are evident (2). It can also create
substantial disability (2). The risk of disability attributable to
knee osteoarthritis alone is greater than any other medical disor-
der in the elderly (3), apart from cardiac diseases. Risk factors
associated with both the development (e.g. heredity, age, female
sex, obesity, trauma) and progression of the disease [e.g. obesity,
low bone density, non steroidal anti-inflammatory drug (NSAID)
use] have been identified (4); obesity is considered a major risk
factor for both the development and progression of osteoarthritis
(5,6). As allopathic medicine is unable to halt this progression
conventional medical treatment is aimed at decreasing pain
and improving function by the use of NSAIDs, other analgesics,
steroidal joint injections and, as a last resort, joint replacement.
Because the high incidence of adverse events, especially
gastrointestinal, associated with both non-selective and COX-2-
selective NSAID use is high (7–9), effective but safer alternative
treatments would be of benefit to osteoarthritis sufferers.
Bromelain
Bromelain is a food supplement that may provide an alterna-
tive treatment to NSAIDs for patients with osteoarthritis.
Bromelain is a crude, aqueous extract obtained from both the
stem and fruit of the pineapple plant, which contains a number
of proteolytic enzymes (10,11) and has shown potentially
beneficial effects due to its anti-inflammatory and analgesic
properties. Currently, bromelain is used for acute inflammation
and sports injuries. It is not a licensed medical product and is
freely available to the general public in health food stores and
pharmacies in the USA and Europe.
Mechanism of Action
The mechanisms of action have been reviewed (10–12).
Bromelain has been shown to have a number of beneficial
Advance Access Publication 6 October 2004 eCAM 2004;1(3)251–257
doi:10.1093/ecam/neh035
© 2004, the authors
Evidence-based Complementary and Alternative Medicine, Vol. 1, Issue 3 © Oxford University Press 2004; all rights reserved
Review
Bromelain as a Treatment for Osteoarthritis: a Review
of Clinical Studies
Sarah Brien
1
, George Lewith
1
, Ann Walker
2
, Stephen M. Hicks
2
and Dick Middleton
3
1
University of Southampton, Southampton,
2
University of Reading, Reading and
3
Medic Herb UK Ltd, UK
Bromelain, an extract from the pineapple plant, has been demonstrated to show anti-inflammatory and
analgesic properties and may provide a safer alternative or adjunctive treatment for osteoarthritis. All
previous trials, which have been uncontrolled or comparative studies, indicate its potential use for the
treatment of osteoarthritis. This paper reviews the mechanism of its putative therapeutic actions, those
clinical trials that have assessed its use in osteoarthritis to date, as well as considering the safety impli-
cations of this supplement for osteoarthritis and reviewing the evidence to date regarding the dosage for
treating this condition. The data available at present indicate the need for trials to establish the efficacy
and optimum dosage for bromelain and the need for adequate prospective adverse event monitoring in
such chronic conditions as osteoarthritis.
Keywords: bromelain – herbal – osteoarthritis – proteolytic enzymes – review
For reprints and all correspondence: Dr Sarah Brien, Complementary
Medicine Research, Primary Medical Care, Aldermoor Health Centre,
Aldermoor Close, Southampton, Hampshire, S016 5ST. Tel. 44 2380
241068; Fax: 44 2380 8070 1125; E-mail: sbb@soton.ac.uk
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access
version of this article provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original
place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a
derivative work this must be clearly indicated.
properties including anti-inflammatory and analgesic actions in
addition to its anti-oedematous, antithrombotic and fibrinolytic
effects (11). Experimental evidence suggests that bromelain’s
action as an anti-inflammatory is mediated via the following
factors: (i) by increasing serum fibrinolytic activity (13), reduc-
ing plasma fibrinogen levels (14) and decreasing bradykinin
levels (which results in reduced vascular permeability) and
hence reducing oedema and pain (15); (ii) by mediating
prostaglandin levels (by decreasing levels of PGE
2
and throm-
boxane A
2
); and (iii) through modulation of certain immune
cell surface adhesion molecules (16–20), which play a role in
the pathogenesis of arthritis (21). However, many of these stud-
ies are of poor quality and further data is needed to clarify
definitive mechanisms of its action.
Data have also indicated that bromelain has analgesic prop-
erties, for example in inflammatory pain in humans (22),
human urogenital inflammation (23), and in various animal
inflammatory models (13,23). Its analgesic properties are
thought to be a result of its direct influence on pain mediators
such as bradykinin (15), as well as its indirect effects through
its anti-inflammatory actions (e.g. reduction in oedema, debris
and immune complexes), which reduce pain.
Clinical Studies
Bromelain was first reported to be of value as an analgesic/
anti-inflammatory for use in both rheumatoid arthritis and
osteoarthritic patients in 1964 (24). Clinical trials have
assessed the effectiveness of bromelain most frequently using
preparations containing differing complexes of proteolytic
enzymes and differing concentrations of bromelain. Three
complexes have been used: (i) Phlogenzyme
TM
(PHL), which
contains the proteolytic enzymes bromelain (90 mg/tab),
trypsin and rutin; (ii) Wobenzyme
TM
(WOB) which contains
bromelain (45 mg/tab), papain, trypsin, chymotrypsin,
pancreatin, lipase and amylase; and (iii) Wobenzym N
TM
(WOB-N) which contains bromelain (45 mg/tab), trypsin,
papain, chymotrypsin, pancreatin and rutin. Bromelain has
been assessed in the treatment of osteoarthritis of two joints,
i.e. the knee (24–30) and the shoulder (as assessed under the
global term periarthritis humeroscapularis) (31,32). Tables 1
and 2 summarise those studies that have investigated the effect
of bromelain in knee and shoulder osteoarthritis, respectively.
The majority of studies assessing bromelain for osteoarthritis
have been either open studies (24,30) or equivalence studies
designed to assess comparative effectiveness and safety against
standard NSAIDs treatment (25–29, Klein, 1994, unpublished
data.). A number of these studies are unpublished [as reviewed
by Leipner et al. (25)], including two placebo controlled studies
designed to assess the efficacy of bromelain in knee osteoarthri-
tis. The following sections will review the studies that have been
carried out to date. Direct comparison between these trials is dif-
ficult as different dosages or preparations of bromelain have
been administered. The majority of the studies have method-
ological issues that make it difficult to draw definite conclusions.
Bromelain for Knee Osteoarthritis
Ten studies have been identified that have assessed bromelain
in osteoarthritis of the knee (Table 1). The earliest reported
studies investigating bromelain were a series of case reports on
28 patients, with moderate or severe rheumatoid or osteoarthri-
tis, described by Cohen and Goldman (24). The studies
reported indicated that the use of bromelain, at varying doses
(these doses were relatively low as compared to subsequent
studies) and differing duration, had positive clinical effects in
18 patients (as measured by assessment of reduction in soft
tissue swelling, pain and/or joint stiffness) and no adverse
events associated with the medication were reported in any of
these case reports. This data therefore provided a plausible
basis for the further assessment of bromelain in musculoskeletal
disorders.
Four unpublished studies: two placebo-controlled, random-
ised trials and two controlled and randomised studies were
reported in the review by Leipner et al. (25). These studies
were designed to assess the comparative effectiveness of
bromelain with a standard treatment, the NSAID diclofenac
(DF). No significant improvement in outcome was observed in
either of the two placebo-controlled trials but both are of poor
methodological quality. The outcome measure for one of the
unpublished trials may have been inappropriate and both studies
may have been inadequately powered (sample size in both
studies was n 60). In addition, in common with the majority
of studies assessing bromelain for this indication, the treatment
period was short (3 weeks duration) as compared to normal
herbal practice where this preparation may be prescribed for
2–3 months in the first instance. Definitive conclusions cannot
therefore be drawn from these two efficacy studies. However
the safety and tolerability in both these studies appeared ade-
quate as only minor (mainly gastrointestinal) adverse events
were reported and dropout rates were low (5% in both studies).
Klein and Kullich’s (27) double blind, randomised, controlled
trial of 73 patients with osteoarthritis of the knee compared a
commercial proteolytic enzyme preparation (Phlogenzym®)
containing bromelain (among other proteolytic enzymes) with
a dose of DF (100–150 mg/day) (24). They report an equivalent
reduction in pain indices of 80% for the two treatments during
3 weeks of therapy and 4 weeks of follow-up with few adverse
reactions to either treatment. The two unpublished compara-
tive trials identified that treatment with bromelain (540 mg/day
as part of the complexes PHL or WOB) reduced osteoarthritis
symptoms and that the reduction was comparable to standard
treatment. However, again the treatment period in both these
studies was short and it is not possible to identify if the study
was adequately powered as no sample size calculations are
available. Tolerability was good with both PHL and WOB;
however, a high rate of adverse drug reactions (none serious)
was reported in the WOB study, with a rate of reporting of 50%
of subjects in the WOB and the DF treatment groups. These
unpublished reports therefore show equivocal evidence in
support of bromelain in osteoarthritis, but highlight the potential
safety issue.
252 Bromelain for osteoarthritis review
eCAM 2004;1(3) 253
Table 1. Summary of studies assessing the effectiveness of bromelain as a treatment for osteoarthritis of the knee
Authors Study design n
Dosage Condition Treatment Follow up Adverse events Primary outcome Conclusion
period
Cohen & Uncontrolled 29 60–160 mg/day Moderate to 3 weeks to When soft None reported Soft tissue Reduction in soft
Goldman (24) series of case bromelain severe arthritis 13 months tissue swelling and pain tissue swelling
reports (25 RA; 2 OA; swelling in 72.4%
10 A and RA;
and 1 gout)
Leipner et al. (25). (i) placebo (ii) 60 PHL 3 2 tabs/ Arthrosis of 3 weeks NK No SAE reported. Sum score of various Similar reduction in
Series of unpublished controlled DB (ref. 31) day (540 mg/ the knee Two ADR reported pain (active, pressure, primary outcome for
studies in OA involving RCT day bromelain) (57%) or in PHL group rest, night) and both groups. NS group
Phlogenzym
TM
(PHL), versus placebo hip (43%) dysfunction (four differences. Drop
Wobenzym
TM
(WOB), point category scale) out n (1 PHL)
Wobenzym N
TM
(WOB-N). measures
Studies investigating OA (ii) placebo (ii) 60 PHL 3 2 OA of the 3 weeks NK No SAE reported. Lequesne index Reduction in primary
of knee are reported controlled (ref 32) tabs/day knee joint Two ADR reported outcome for both groups;
DB RCT (540 mg/day in PHL group NS group differences.
bromelain) Drop out n 3 (1 PHL)
versus placebo
(iii) Comparative (ii) 60 PHL 3 2 OA of the 3 weeks NK No SAE reported. Lequesne index Similar reduction in primary
DB, RCT (ref 38) tabs/day (540 knee joint One ADR outcome for both groups. NS
mg/day (0 PHL; 1 DF) group differences.
bromelain) Drop out n 1 (0 PHL)
versus DF
(100–150 mg/day)
(iv) Comparative (iv) 60 WOB 3 4 OA of the 3 weeks NK No SAE reported Lequesne index Similar reduction in primary
DB, RCT (ref 45) tabs/day (540 knee joint but 30 ADR outcome for both groups. NS
mg/day bromelain) (15 WOB; 15 DF) group differences. Drop
versus DF out n 2 (1 WOB)
(100–150 mg/day)
Singer and Comparative 80 WOB 4 7 OA of the 4 weeks 4 weeks No SAE reported. Mobility and pain Equivalence not tested but
Oberleitner (26) DB, RCT tabs/day (945 mg/ knee joint 22 ADR (13 WOB) (five point scale) similar reductions in primary
day bromelain) Mainly GI but allergic in morning outcome for both groups. NS
versus DF skin reaction in n 1 group differences. Drop outs
(100 mg) n 12 (8 WOB; 4 DF)
Klein & Comparative 73 PHL 3 2 tabs/ Knee OA 3 weeks 4 weeks 1 in 36 (2.8%) Lequesne index Reduction in pain indices by
Kullich (27) DB, RCT day (540 mg/day (headache probably (pain and function) 80% sustained at 4 weeks post
bromelain) not related) treatment. Equivalence was
versus DF identified at week 3 (Mann
(100–150 mg/day) Whitney 0.47) and week 7
(Mann Whitney 0.55)
Singer et al. (28) Comparative 68 PHL 3 2 tabs/ OA of the knee 3 weeks 4 weeks No SAE reported. Lequesne index and PHL group showed significant
DB, RCT (ref 37) day (540 mg/day joint 14 ADR (7 PHL; sum of pain scores reduction compared to DF
bromelain) versus 7 DF) for both Lequesne (P 0.017)
DF (100–150 mg/ and sum of pain scores
day) (P 0.047). Drop out
n 5 (3 PHL)
254 Bromelain for osteoarthritis review
Table 1. Continued
Authors Study design n
Dosage Condition Treatment Follow up Adverse events Primary outcome Conclusion
period
Tilwe et al. 2001 (29) Comparative 50 PHL 4 7 tabs/ Arthritis of 3 weeks 4 weeks ‘well tolerated’; Likert scale to Equivalence not tested.
SB, RCT day (1890 mg/ the knee specific AE not assess pain Reduction in pain (NS),
day bromelain) reported. tenderness (P 0.05) and
versus DF swelling (NS) in both groups.
(100–150 mg/day) Joint tenderness was
significantly greater
(P 0.05) in PHL group
than DF group
Walker et al. (30) Open. 77 Bromelin
TM
Mild, acute 4 weeks 4 weeks No SAE. Minor WOMAC i.e. total Significant WOMAC total
Dose ranging 200 or knee pain AE (n 19) score, pain, stiffness score at both doses
400 mg/day mainly GI and function (P 0.0001 for 200 mg;
P 0.000001 for 400 mg).
Significant difference between
groups for total score
[(P 0.036), stiffness
(0.026), physical function
(0.021), well-being.]
Citations quoted in this column refer to references contained within publications listed in the first column.
PHL, Phlogenzym; WOB, Wobenzym; DF, diclofenac; DB, double blind; SB, single blind; RCT, randomised controlled trial; AE, adverse event; SAE, serious adverse event; ADR, adverse drug reaction; GI,
gastrointestinal; WOMAC, Western Ontario McMaster University Arthritis Index; NK, not known; NS, not significant.
Bromelin
TM
contains bromelain 200 mg per tablet. Phlogenzym
TM
each tablet contains proteolytic enzymes in the following doses: bromelain (90 mg), trypsin (48 mg), rutin (100 mg). Wobenzym
TM
, each
tablet contains: bromelain (45 mg), papain (60 mg) trypsin (24 mg), chymotrypsin (1 mg), pancreatin (100 mg), lipase (100 mg), amylase (100 mg), rutin (50 mg).
Four published studies reported trials to assess the effective-
ness of bromelain for knee osteoarthritis (26–29). These studies
used similar treatment periods (3 or 4 weeks) and similar daily
doses of a standard treatment, DF (150–100 mg/day); however,
different doses of bromelain were tested (range from 540 to
1890 mg/day). The first study reported by Singer and
Oberleitner (26) assessed bromelain at a dose of 945 mg/day
(which is higher than that used in most studies) versus DF after
4 weeks of treatment, and although assessment of equivalence
was not reported, both groups showed similar reductions in the
primary outcome. However, there were more adverse drug
reactions (mainly gastrointestinal: 13 in the WOB group
versus nine in the DF group) and drop-outs (20% WOB versus
10% DF) as compared to the standard treatment group, which
raises concerns about the safety and tolerability of bromelain
at this higher dose. These safety and tolerability issues were
not replicated in the study by Tilwe et al. (29) who adminis-
tered a daily bromelain dose of 1890 mg/day (in the form of
the complex PHL) against the DF comparative group.
Equivalence was not tested in this study, but both groups
showed reduced symptoms of pain and swelling (comparable
across groups), and also joint tenderness (the improvement
was significantly better in the PHL group). Tolerability was
deemed good (there were no drop-outs), and no significant
safety issues were raised in this study despite the high dose
employed. The final comparative study was reported by Singer
et al. (28) who compared bromelain (in the complex PHL) at a
dose of 540 mg/day against DF in 68 subjects. This study
demonstrated that bromelain showed significantly better
improvement in both the primary outcome (Lequesne index,
P 0.017) and summary pain scores (P 0.047) as compared
to DF. Tolerability and safety were acceptable and levels were
similar in both treatment groups. In summary, the four com-
parative trials indicate that bromelain appears to be as effective
as the standard treatment in osteoarthritis of the knee, but
higher doses may be associated with safety concerns.
Finally, Walker et al. (30) recently described an open study
of one month treatment intervention of bromelain using two
dose regimes (200 and 400 mg) in otherwise healthy adults
(n 77) with acute knee pain with no medical diagnosis. The
data identified a significant clinical improvement compared to
baseline in both the primary outcome [symptoms assessed by
the Western Ontario McMaster University Arthritis Index,
WOMAC (32)] and in the secondary outcomes (overall
psychological wellbeing), at both doses. Furthermore, mean
improvements in total symptom score, stiffness and physical
function and psychological well-being were significantly
greater in the high-dose compared with the low-dose group.
However, definitive conclusions cannot be drawn from this
study since there are a number of methodological shortcomings.
These include the issue of power, which was not addressed:
there was no control group (and therefore bias cannot be
eliminated) and these patients did not have a formal diagnosis
of their knee pain.
In conclusion, bromelain appears to have potential for the
treatment of knee osteoarthritis. However it is important to
eCAM 2004;1(3) 255
note that there are a number of methodological issues that are
common to the studies reported, including the possibility of
inadequate power, inadequate treatment periods, inadequate or
non-existent follow-up to monitor possible adverse drug
reactions. Furthermore, the optimum dosage for this condition
remains unclear. A phase II clinical trial would be beneficial to
identify the optimal dosage and to systematically monitor
safety issues before a definitive efficacy study could be
completed.
Bromelain for Osteoarthritis of the Shoulder
Two studies have assessed the use of bromelain in osteoarthritis
of the shoulder (31, Klein, 1994, unpublished data) (Table 2).
Both studies have assessed the complex PHL, which has been
used at the same daily dose (equivalent of 540 mg bromelain
per day) and for the same treatment period of 3 weeks with no
follow-up. The first study (by Klein, 1994) is an unpublished
report of a double blind placebo controlled trial assessing PHL
in 60 patients. No significant difference in treatment groups
was observed after treatment. The level of adverse drug reac-
tions and rate of drop out was low. However, there are a num-
ber of methodological caveats. It is unclear if the study was
adequately powered to detect treatment group differences and,
as with the knee osteoarthritis studies, the treatment period and
lack of follow-up period are inadequate and the optimum
dosage is not clear. The second study by Klein et al. (31) was
designed to compare PHL against the standard DF treatment
(100 mg/day) in n 40 patients with this condition. No group
differences in the primary outcome measures (summary pain
score) were observed and safety and tolerability were adequate
at this dose. However, this study also suffers from possibly
being inadequately powered, a brief treatment period and lim-
ited follow up.
In conclusion the data from these two studies do not provide
support for the effectiveness and safety of bromelain in
osteoarthritis of the shoulder; further studies are needed that
are adequately powered to identify the optimal dose and
optimal treatment period for this condition.
Summary of Clinical Trials Assessing Bromelain for
Osteoarthritis
The use of bromelain for the treatment of osteoarthritis looks
promising. However, a number of methodological caveats
indicate that further studies are warranted, in particular phase II
clinical trials to identify the optimum dosage, followed by a
definitive randomised placebo-controlled trial to confirm its
efficacy in the treatment of osteoarthritis.
Bromelain and Adverse Events
Bromelain has been used as treatment for a number of disease
conditions, in addition to osteoarthritis of the knee and shoulder
joints (Table 1). No serious adverse events have been reported
with the consumption of either bromelain or pineapples in
these studies. Adverse events that have been reported are
mainly gastrointestinal (i.e. diarrhoea, nausea and flatulence),
but have also included headache, tiredness, dry mouth, skin
rash and allergic reactions (not specified).
The trials assessing bromelain in osteoarthritis have used
doses of bromelain in the range 540–1890 mg/day. Safety and
tolerability for bromelain at the lower dose appears good with
similar if not better safety profiles as compared to standard
treatment. However, the studies that have used a higher daily
dose of bromelain [945 mg/day (26); 1890 mg/day (29)]
appear to be conflicting. The authors employing the highest
dose reported that the medication was well tolerated; the dose
of 945 mg/day, however, showed a higher incidence of adverse
drug reactions and drop-outs as compared to the profiles from
the standard NSAID treatment group. A formal phase II study
is needed to identify safety and efficacy/effectiveness of
bromelain. In addition, it is conceivable that patients would
clinically receive bromelain for longer treatment periods than
have been assessed by the current osteoarthritis studies.
Further work is therefore needed to evaluate the long-term
safety of this supplement. Finally, there are also a number of
other potential safety issues that need to be addressed. These
include investigating the possibility of renal effects (because of
modulation of biosynthesis of prostaglandins), potentiating
effects on the action of anticoagulants [e.g. warfarin (33)] and
enhanced absorption of antibiotics (11).
Dosage in human studies
The review by Maurer (11) identified that bromelain has been
used in the daily dosage range of 200–2000 mg, with therapeu-
tic action shown at 160 mg/day. The trials assessing bromelain
in osteoarthritis have used bromelain at a higher therapeutic
dose, in the range of 540–1890 mg/day. Safety and tolerability at
the lower dose appears to be good; the data indicates that brome-
lain at this dose appears to be as effective as standard treatment
with at least similar safety and tolerability profiles. The two
studies employing a higher daily dose [945 mg/day (26) and
1890 mg/day (29), both comparative trials] showed that the dose
of 945 mg/day showed similar outcomes to DF, whereas 1890
mg/day appeared to be superior to DF in one of the primary out-
come measures (joint swelling). As yet there have been no for-
mal phase II studies to assess the optimal dose. However, the
recent study by Walker et al. (30) in acute knee pain showed a
significant dose-dependent effect between the two doses of 200
and 400 mg per day, over a period of one-month therapy. Further
study is needed to identify the optimal dose for the treatment of
chronic joint inflammation over longer periods of time (e.g. 3–4
months) within a blinded and randomised trial.
Summary
The currently available data do indicates the potential of
bromelain in treating osteoarthritis. However, further studies
are needed before a definitive conclusion can be drawn.
Specifically, there is a need for trials to establish efficacy, and
dose ranging studies to identify the optimum dosage (with
256 Bromelain for osteoarthritis review
Table 2. Summary of studies assessing the effectiveness of bromelain as a treatment for osteoarthritis of the shoulder (periarthritis humero scapularis)
Authors Study design n Dosage Condition Treatment period Follow up Adverse events Primary outcome Conclusion
Klein et al. DB, placebo 60 PHL 3 2 Peri arthritis 3 weeks N/A No SAE reported. Sum score of various No significant group
(33) Unpublished controlled RCT tabs/day (540 humero Three ADR pain (active, pressure, difference in primary
mg/day bromelain) scapularis (1 PHL) rest, night) and dysfunction outcome after 3 weeks
versus placebo (four point category treatment. n 4 drop
scale) measures outs (2 PHL)
Klein et al. (31) Comparative 40 PHL 3 2 tabs/day Peri arthritis 3 weeks N/A No SAE reported. Sum score of various No significant group
DB, RCT (540 mg/day humero Three ADR pain (active, pressure, difference at outcome
bromelain) scapularis (2 PHL) rest, night) and dysfunction after 3 weeks treatment
DF (100 mg/day) tendopathica (four point category scale) (P 0.14). n 5 drop
measures outs (3 PHL)
PHL, Phlogenzym; DF, diclofenac; DB, double blind; RCT, randomised controlled trial; SAE, serious adverse event; ADR, adverse drug reaction; N/A, not applicable.
Phlogenzym
TM
each tablet contains proteolytic enzymes in the following doses: bromelain (90 mg), trypsin (48 mg), rutin (100 mg).
eCAM 2004;1(3) 257
adequate prospective adverse event monitoring). Finally,
future work should focus on the dose–response parameters and
efficacy of long-term bromelain use in chronic conditions such
as osteoarthritis.
Conflict of Interest
Dick Middleton is consultant to Lichtwer Pharma UK Ltd who
manufacture bromelain. Steven Hicks was funded by Lichtwer
for a post-graduate fellowship from 1998 to 2002.
Acknowledgements
S.B. is funded by a grant from the Hospital Savings Association.
G.L. is funded by a grant from the Maurice Laing Foundation.
A.W. and S.M.H. are funded by The University of Reading.
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Received February 9, 2004; accepted July 29, 2004