Complementary Therapies in Clinical Practice 21 (2015) 181e187

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Complementary Therapies in Clinical Practice

journal homepage: www.elsevier.com/locate/ctcp

Efcacy and safety of topical Matricaria chamomilla L. (chamomile) oil

for knee osteoarthritis: A randomized controlled clinical trial
Ruhollah Shoara a, c, Mohammad Hashem Hashempur b, c, Alireza Ashraf d, e, *,
Alireza Salehi f, Shadab Dehshahri g, Zahra Habibagahi h
a

Department of Traditional Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
Essence of Parsiyan Wisdom Institute, Traditional Medicine and Medicinal Plant Incubator, Shiraz University of Medical Sciences, Shiraz, Iran
d
Shiraz Geriatric Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
e
Department of Physical Medicine and Rehabilitation, Shiraz University of Medical Sciences, Shiraz, Iran
f
Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
g
Department of Pharmacognosy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
h
Department of Internal Medicine, Division of Rheumatology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
b
c

a r t i c l e i n f o

a b s t r a c t

Article history:
Received 6 May 2015
Received in revised form
30 May 2015
Accepted 5 June 2015

Objective: To assess the efcacy and safety of topical Matricaria chamomilla (Chamomile) oil in patients
with knee osteoarthritis.
Method: Patients were randomized and treated with topical chamomile oil, diclofenac or placebo, 3
times/day for 3 weeks. They were allowed to use acetaminophen as analgesic. The patients were asked
about their total acetaminophen use. Moreover, they were assessed in the terms of pain, physical
function and stiffness by using Western Ontario and McMaster Universities Osteoarthritis Index
(WOMAC) questionnaire at the enrolling and weekly.
Results: Chamomile oil signicantly reduced the patients' need for acetaminophen (P 0.001) compared
with diclofenac and placebo. However, there were no signicant differences in WOMAC questionnaire
domains. The patients did not report any adverse events by using chamomile oil.
Conclusion: Chamomile oil decreased the analgesic demand of patients with knee osteoarthritis. In
addition, it may show some benecial effects on physical function, and stiffness of the patients.
2015 Elsevier Ltd. All rights reserved.

Keywords:
Osteoarthritis
Matricaria chamomilla
Chamomile oil
Traditional Persian Medicine
Herbal medicine
Phytotherapy

1. Introduction
Osteoarthritis (OA) also known as degenerative arthritis is a
progressive joint disease which affects joint cartilage, synovium,
subchondral bone and surrounding tendons and ligaments [1]. The
WHO Rheumatic Disease Panel made an estimation of 10% for OA in
the world's population aged 60 years and more [2].
Knee osteoarthritis is one of the leading causes of pain, physical
dependency and impaired mobility in the elderly [3,4]. According
to the severity of the disease, there are several therapeutic options
for knee OA, from non-pharmacologic modalities to pharmacologic
treatments and surgical procedures [5]. Non-pharmacologic treatments (e.g. educational programs, exercise, and physical therapy)

* Corresponding author. Department of Physical Medicine and Rehabilitation,

Shahid Faghihi Hospital, Zand Street, Shiraz 7134845794, Iran.
E-mail address: sbahar7@gmail.com (A. Ashraf).
http://dx.doi.org/10.1016/j.ctcp.2015.06.003
1744-3881/ 2015 Elsevier Ltd. All rights reserved.

are underestimated by many physicians and underutilized by patients [6]. In addition, surgery has remained as the last option and
rejected by many patients [7]. Therefore, medications (especially
analgesics) are the most prevalent prescriptions for the knee OA [8].
However, analgesic's adverse effects and patient's co-morbidities,
such as ischemic heart disease and gastric upset, are considered
as important limitations for this therapeutic option [9]. Thus, other
safe and efcient treatments are needed.
Today, Traditional Medicine (TM) is a medical system appreciated by general population and especially by patients who suffered
from chronic diseases [10]. Above the mentioned limitations for
treatment lines in knee OA, along with common reasons for use of
TM (e.g. easy accessibility, lower cost and its natural origination
[11]) directed these patients to use TM [12]. However, the efcacy
and safety of many of these modalities have not yet been elucidated
clearly.
According to the most famous Traditional Persian Medicine

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R. Shoara et al. / Complementary Therapies in Clinical Practice 21 (2015) 181e187

2. Materials and methods

extremities were included in the trial. The patients were eligible for
inclusion if they had knee OA according to suggested criteria by
American College of Rheumatology [23] and had OA grade 1 to 3
according to Kellgren-Lawrence Grading Scale [24].
The exclusion criteria were: serious comorbidities such as liver
disorders and renal failure, history of peptic ulcer disease, and
dermatologic disorder which affected the surrounding skin of the
knees. In addition, the patients were excluded if they had previous
surgery for knee replacement or intra-articular steroid injections
within 3 months before inclusion in the study or intramuscular
steroid injection within the previous month prior. Moreover, the
patients who had positive history of hypersensitivity to diclofenac
gel, chamomile derived products, were unable to complete data
gathering forms (such as cognitive impairment or language problem) and pregnant women were excluded from our study. Patients
with coexisting musculoskeletal diseases (including rheumatoid
arthritis, septic arthritis, metabolic arthritis, gout and pseudogout,
traumatic arthritis and bromyalgia) were also excluded from the
study. In addition, the patients were excluded if they had to use
more than 2 g acetaminophen/day or use other analgesics,
including injection drugs or other medications such as glucosamine
and chondroitin sulfate, during the study period.

2.1. Study design

2.5. Intervention

The study was designed as a three-arm, blinded, randomized,

placebo-controlled clinical trial using a parallel design. In addition,
the design and methods have not been changed after the trial's
commencement.

The patients were instructed to use their prescribed medication

(i.e. chamomile oil, parafn and diclofenac gel) three times per day,
for a period of 3 weeks. They were trained to use the medications
on their knee and the surrounding tissues so that it fully covered of
skin by the drugs (i.e. 1.5 cc of chamomile oil and parafn, and a pea
size diclofenac). In addition, the patients were advised not to
massage the mentioned zone. Patients who affected by knee OA
bilaterally, were evaluated, and more severe affected knee included
in the study.
All of the participants were allowed to use acetaminophen
tablet (500 mg) as the rescue drug, during the trial period. The
tablets were supplied for them by the researchers.

(TPM) textbooks, chamomile, which is known as Matricaria chamomilla L. (Asteraceae or Compositae) oil can demonstrate several
therapeutic effects. For example, in The Canon of Medicine, which
was written by Ibn-e-Sina or Avicenna (980e1037 AD) [13],
chamomile oil has been highlighted as a tonic for the nervous
system [14]. Also, chamomile oil was being prescribed for different
joint pains such as knee pain [15]. In addition, chamomile has been
used for alleviating rheumatic and arthritis pain by different TMs
[16]. Chamomile is a rich source of terpenoids and avonoids [17]
and can possess anti-inammatory, antioxidant [18] and antinociceptive [19] effects.
In addition, chamomile is a safe medicinal herb, and especially
there were several reports on its external use for a variety of diseases on different sites of the human body [20]. In addition,
Chamomile is listed on the FDA's generally recognized as safe
herbs [21].
Therefore, according to the aforementioned effects of the
chamomile in TPM and the current literature, this study was
designed to assess the efcacy and safety of topical chamomile oil
in knee OA.

2.2. Ethical issues

The study protocol was in compliance with the Declaration of
Helsinki (1989 revision) and approved by the Local Medical Ethics
Committee of Shiraz University of Medical Sciences (SUMS) with
reference number: CT-9376-7366. The trial protocol was registered
in Iranian Registry of Clinical Trials database under registration ID:
IRCT2015013120885N1. All of the enrolled participants returned
their signed informed consent forms.
2.3. Preparation of test drug, placebo and standard drug
Dried M. chamomilla owers were purchased from a local market in Shiraz, southern Iran. The plant sample was identied by a
herbalist and a voucher sample (No. 790) has been kept in faculty of
pharmacy of SUMS.
Chamomile oil was prepared via traditional direct heat method.
At rst, 600 gr. of dried owers was boiled in 3.6 L of water till 1/4 of
water remained. Then, powder was removed and the remained
water (i.e. aqueous extract of chamomile) was boiled with equal
amount of sesame oil. The boiling process continued until all the
water was vaporized and oily part remained. The detailed instruction of oil preparation was described earlier [22]. The chamomile oil was poured in 30 ml dark bottles. We used pharmaceutical
graded parafn as placebo, and chamomile oil and placebo were
placed in the same containers. Diclofenac gel 1% (BEHVAZAN) in
plastic containers was supplied as the positive control medication
which was prescribed for the third arm of the study.
2.4. Inclusion and exclusion criteria
Patients (from the Shahid Motahhari Outpatient Clinic, an academic center, afliated with SUMS) of both sexes, aged between 38
and 65 years old, willing to sign the informed consent form and had
no congenital disorders or abnormalities related to their lower

2.6. Outcome measures

Need of the participants for supplied analgesic (i.e. acetaminophen tablet 500 mg) was chosen as one of the outcome measures.
The patients were evaluated in terms of the number of consumed
tablets at the end of the 3rd week.
Moreover, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire, as a self-administered and
validated tool [25] was chosen as the other outcome measure. The
patients were evaluated by WOMAC in terms of three domains
(pain score ranged from 0 (no pain) to 4 (extreme pain); physical
function score ranged from 0 (no difculty) to 4 (the most severe
difculty); also, stiffness score ranged 0 (no stiffness) to 4 (the
worst stiffness)). At the beginning of the enrollment and every
week during the intervention, the data related to the WOMAC
scores were obtained and recorded.
In addition, the patients were asked about any allergic or any
adverse reactions at weekly visits.
2.7. Randomization, blinding and concealment of allocation
Eighty four eligible patients were randomly allocated to three
parallel groups (i.e. the test drug, placebo and standard drug
groups), by the secretary of the clinic, who had been trained and
instructed to use a block-randomization list. The list was generated
by computer as a non-stratied list, with the same block lengths.
Parafn was chosen as a placebo which has been packed in the

R. Shoara et al. / Complementary Therapies in Clinical Practice 21 (2015) 181e187

same containers of opacity and darkened color which supported

the blinding of the design. Moreover, there was no similar choice
(an oily medication) as a standard positive control, and we selected
diclofenac gel which has the most similarity, either in topical
application or in liquidity of drug. The physicians, researchers, and
statisticians were kept blind to the allocation of patients.
2.8. Statistical analysis
The sample size was calculated by considering one-sided signicance level of 0.05, 0.80 power, and a probable 20% drop-out
rate of the enrolled patients. It was estimated to be 28 participants in each group.
Demographic and clinical characteristics of the included patients are shown as the mean standard deviation (SD) for
continuous variables. The statistical analyses included Chi-square,
repeated measure ANOVA, and one way ANOVA. P values less
than 0.05 were considered signicant. The Statistical Package for
the Social Sciences, version 18.0 (SPSS Inc., Chicago, IL, USA), was
used for all statistical analyses.

183

of the study regarding demographic and clinical parameters.

As shown in Table 2, the No. of acetaminophen tablets used by
patients was signicantly lower in the chamomile group as
compared with diclofenac and placebo groups (P 0.001).
The resulted values of three different domains of WOMAC
questionnaire were reported in Table 3, weekly. The result of
repeated measure ANOVA and post-hoc test showed signicant
differences in the elds of pain, physical function and stiffness in all
of the study groups, at follow up contacts when compared with
their baseline values (P < 0.001 for all of them). However, there
were no signicant between groups differences in the elds of pain,
physical function and stiffness of WOMAC questionnaire (P 0.53,
P 0.23, P 0.72, respectively).
3.1. Safety and tolerability
Chamomile oil was well tolerated by patients, and no adverse
effects, neither local nor systemic, were reported by them. Moreover, no abnormal physical examination was noted on the followup contacts.

3. Results

4. Discussion

From January 2015 to March 2015, a total of 130 patients were

assessed for eligibility and nally 99 patients, who were eligible
and returned their signed informed consent form, were randomized into the 3 arms of the trial (i.e. the trial drug, diclofenac or
placebo). Twenty eight patients in each group completed the study.
The patients' enrolment, randomization and outcomes are
demonstrated in Fig. 1.
The baseline properties of the patients are presented in Table 1
(age, sex, duration of disease, pain, physical function and stiffness).
On entry, there were no signicant differences between the 3 arms

The results of this study showed signicant benecial effect of a

traditional topical formulation of chamomile ower oil on the use
of analgesic by patients with knee OA. In addition, chamomile oil
showed some benecial effects on pain, stiffness and physical activity of the patients.
Chamomile is a rich source of avonoids; for example, apigenin
7-O-glucoside can play a strong inhibitory effect on prostaglandin
E2 level. Chamomile interferes with COX-2 pathway and possesses
anti-inammatory effect, similarly to NSAIDs [26]. Polyphenolic
compounds of chamomile can also have anti-inammatory effects

Fig. 1. Flowchart of the inclusion, allocation and outcomes of the trial.

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R. Shoara et al. / Complementary Therapies in Clinical Practice 21 (2015) 181e187

Table 1
Baseline characteristics (demographic and clinical) of the patients in the 3 arms of the study.

Age (years) S.D.

Male/female (n)
Duration (months) S.D.
Pain (pts) S.D.
Stiffness (pts) S.D.
Physical function (pts) S.D.

Chamomile

Diclofenac

Placebo

P Value

50.57 7.15
2/26
37.93 62.54
10.96 4.77
4.21 1.50
28.07 14.18

52.68 7.44
7/21
46.07 47.35
11.29 4.80
4.50 2.10
30.36 13.96

52 8.94
4/24
47.18 47.96
11.32 4.20
4.32 2.09
27.11 12.83

0.59
0.17
0.77
0.95
0.85
0.66

In addition, there are several complementary and alternative

treatments which were evaluated for their possible effects on OA.
Herbal therapies for OA can be divided into 2 main domains of oral
and topical medicines, which were reviewed by The Cochrane
Collaboration [36,37]. In Iran, there is a special tendency toward the
use of herbal remedies [10,38], and several studies have evaluated
the efcacy of them for OA, both in vivo and in vitro [39e48].
For example, Comfrey root [49], Arnica [50], Capsaicin [51] and
Stinging nettle [52,53] in addition to Marhame-Mafasel (a TPM
compound medicine) [33,34] and 2 Chinese compound medicines,
Shangshi Jietong Gao, and Fufang Nanxing Zhitong Gao [54] are
some of the most popular topical herbal medicines that have been
shown to have benecial effects on OA. There are several described
mechanisms of action which are thought to be related to clinical
effectiveness of these formulations. For example, some of them act
as skin irritants and also may inhibit COX-1, COX-2 and proinammatory biomarkers. Inhibition of lipoxygenase and participating enzymes in destruction of cartilage may also explain the
efcacy of some of the topical herbal medicines for OA [55].
However, there are several limitations which can affect generalizability of the results of the mentioned studies. For example,
several studies had not a standard comparator (i.e. a standard
conventional medication for OA). Complexity of formulations, high
rate of adverse events, choosing subjective parameters as outcome
measures and small size of the study groups can be mentioned as
the other methodological limitations of some of these studies.

Table 2
Number of acetaminophen tablets (500 mg) used in each group of the study.

Acetaminophen tablets

Chamomile

Diclofenac

Placebo

P value

21.00 10.35

28.14 4.90

27.46 7.10

0.001

as potent as corticosteroids by inhibition of pro-inammatory

biomarkers [27e29]. This could be mentioned as an important
possible mechanism of chamomile oil in decreasing patients' demand for analgesic use. In fact, the reduction in demand for analgesic was because the pain was less following a reduction in
inammation by the chamomile. In addition, COX-2 inhibitors can
block the central neurons and show pain relief effect [30]. Moreover, it should be noted that avonoids and essential oils of
chamomile can penetrate the skin layers [31]; accordingly, topical
use of chamomile oil was proven to possess anti-inammatory and
analgesic effects [32].
Chamomile oil has been evaluated for knee OA in several previous studies as polyherbal formulations, but there was no previous
study on assessing the efcacy of chamomile oil itself [33e35].
These studies showed benecial effects of herbal mixtures, containing chamomile oil, on pain reduction of patients with knee OA.
One study showed also its benecial effect on knee function of
patients. The result of our study is consistent with the mentioned
trails. In fact, chamomile oil reduced analgesic need of our patients
and, therefore, it could logically be concluded that patients experienced less pain than the 2 other groups. Although the patients
were supplied with and allowed to use acetaminophen for pain
control, the patients in the 2 other arms of the study subsided their
pain by using more acetaminophen. Hence, there was no signicant
difference between WOMAC pain score of the patients in the
chamomile group and the other groups. It should be mentioned
that chamomile oil could improve WOMAC scores like diclofenac,
plus its lower costs for patients. Also, the cost-saving feature of
chamomile oil due to the diminished demand for the analgesic use,
should be mentioned.

4.1. Study limitations

At rst, we cannot attribute the resulted efcacy to chamomile,
only. We used sesame oil as an oily vehicle for active constituents of
chamomile ower. Sesame oil has demonstrated anti-oxidant, antiinammatory [56] and anaesthetic activity [57], and benecial effects in a compound herbal medicine for knee OA [43]. In addition,
sesamine as the major active constituent of sesame oil was evaluated and proved for its chondroprotective effects in OA model [58].

Table 3
Comparison of secondary outcome measures among the 3 groups of the study.
Chamomile
Pain
Baseline
Week 1
Week 2
Week 3
Stiffness
Baseline
Week 1
Week 2
Week 3
Physical function
Baseline
Week 1
Week 2
Week 3

10.96 4.77
8.75 4.59
8.96 4.58
8.18 4.60
4.21
3.32
3.54
3.50

28.07
25.50
27.21
25.25

1.50
2.02
2.13
2.19

14.18
13.80
13.47
13.1

Diclofenac
11.29 4.80
8.75 4.36
7.82 4.02
8.25 4.77
4.50
3.21
3.50
3.29

30.36
26.21
25.79
24.04

2.10
2.38
2.40
2.34

13.96
13.41
13.90
12.95

Placebo

P value (within groups)

P value (between groups)

<0.001

0.53

<0.001

0.72

<0.001

0.23

11.32 4.20
9.96 5.73
9.89 5.68
9.68 5.50
4.32
3.68
3.68
3.64

27.11
26.43
26.36
24.82

2.09
2.48
2.63
2.41

12.83
15.97
17.14
17.2

R. Shoara et al. / Complementary Therapies in Clinical Practice 21 (2015) 181e187

However, the aim of our study was to evaluate the efcacy of

traditional topical formulation of chamomile oil, which had been
advised in TPM resources and is being marketed in Iran, on knee
OA. Therefore, we used sesame oil as a popular oily vehicle for
medicinal oils [59] which has been recommended for chamomile
oil formulation in TPM.
Duration of follow-up is another issue that should be mentioned
as a limitation. In fact, OA is a chronic disease and we have tested
short-term effect of chamomile oil. However, our study aimed to
assess the efcacy of this topical formulation on knee OA for the
rst time. In addition, another limitation was relatively small size of
the study population. However, according to the mentioned aim,
we chose a logical and statistically acceptable sample size.
Finally, inappropriate proportion of the included male patients
should be mentioned as another limitation. In fact, about 15.5% of
the patients were male and this can limit the generalizability of our
results for male patients with knee OA.

[9]

[10]

[11]

[12]

[13]

[14]

5. Conclusion
According to the results of this randomized controlled clinical
trial, topical use of traditional formulation of chamomile oil can
decrease the analgesic demand of patients with knee OA. In addition, it may show some benecial effects on pain, physical function
and stiffness of the patients. It is, therefore, suggested that its efcacy on knee OA should be evaluated in future studies with larger
sample size and of longer duration of follow-up. Finally, the potential effects of chamomile oil on other joint pains (as recommended by TPM resources) could be an interesting topic for further
researches.

[15]
[16]

[17]

[18]
[19]

[20]
[21]
[22]

Acknowledgments
This study was a part of a PhD thesis by Dr. Ruhollah Shoara that
was supported by Shiraz University of Medical Sciences (grant
number: 93-7366). The authors would like to thank the Vice
Chancellery of Technology and Research of the University, all the
study participants for their participation, the University's Research
Consultation Center for editing the nal manuscript and statistical
analysis, Dr. Ali Soleymani for his assistance in statistical analysis,
and Dr. Seyed Taghi Heydari for his useful comments.
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Ruhollah Shoara M.D. & Ph.D. student of traditional Iranian medicine, born on 1979 in Shiraz. He is interested in
traditional Iranian medicine and Medical doctrine of
divine religions.

Mohammad Hashem Hashempur is Assistant Professor in

traditional Iranian medicine at Fasa University of Medical
Sciences. He was graduated in medicine (M.D.) and then
was graduated in Ph.D of traditional Iranian medicine. He
published 16 articles and managed several graduate thesis.

Alireza Ashraf: I was born on June 4, 1973 in Tehran,

capital of Iran. I was graduated from Physical Medicine and
Rehabilitation (PM&R) specialty with 1st rank of national
board in 2003. After that, I have been in PM&R ward as an
academic staff at Shiraz medical school.

Alireza Salehi is Dean of Traditional Medicine School in

Shiraz University of Medical Sciences. He is Director of
Research Center for Traditional Medicine and History of
Medicine. He published 3 books and 12 articles in eld of
Traditional Medicine, Complementary, and Alternative
Medicine.

R. Shoara et al. / Complementary Therapies in Clinical Practice 21 (2015) 181e187

Shadab Dehshahri is assistant professor in pharmacognosy department of pharmacy school, Shiraz University of
Medical Sciences. She graduated in pharmacy and then
took her Ph.D degree in pharmacognosy. She interested in
bioactivity of medicinal plants and also traditional
medicine.

187

Zahra Habibagahi: 2002 e Present: Assistant Professor of

Rheumatology, Department of Internal Medicine, Shiraz
University of Medical Sciences, Iran.