COMPARING THE EFFECTS OF GINGER (ZINGIBER OFFICINALE) EXTRACT AND IBUPROFEN ON PATIENTS WITH OSTEOARTHRITIS

Arch Iranian Med 2005; 8 (4): 267 – 271


Original Article




COMPARING THE EFFECTS OF GINGER (ZINGIBER
OFFICINALE) EXTRACT AND IBUPROFEN ON PATIENTS
WITH OSTEOARTHRITIS

•
Masoud Haghighi PhD *, Ali Khalvat MD**, Tayebeh Toliat PhD***, Shohreh Jallaei MSc†


Background: Ginger (Zingiber officinale) extract supplementation has been shown to improve
the severity of symptoms and decrease the nonsteroidal antiinflammatory drug (NSAID)
requirements in patients with osteoarthritis (OA).
Objective: To assess the effects of ginger extract as an alternative to NSAIDs and as a
supplement drug in the symptomatic treatment of OA.
Methods: Between April and October 2002, 120 outpatients with OA of moderate to severe
pain, requiring only the use of NSAIDs, were enrolled into a double-blind, randomized, placebo-
controlled clinical trial. These patients were randomized into three groups of 40, including the
placebo (PL), ginger extract (GE), and ibuprofen (IBP) groups. After a washout period of one week
(week 0), patients received either 30 mg ginger extract in two 500 mg capsules, placebo, or three
400 mg ibuprofen tablets daily for one month. Acetaminophen tablet was prescribed as a rescue
analgesic during the study. The clinical assessments included a visual analog scale (VAS) for pain,
gelling pain, joint swelling measurement, and joint motion slope measurement. Joint motion slope
was measured by goniometry (normal = 130°, limited = 120°, and very limited = 110°).
Results: The improvement of symptoms (defined as reduction in the mean change) was
superior in the ginger extract and ibuprofen groups than the placebo group. VAS scores and
gelling or regressive pain after rising the scores were significantly higher in the PL group than
both the GE and IBP groups, a month after the treatment (P < 0.0001). However, there was no
significant difference in VAS and gelling pain scores between the ginger extract and the ibuprofen
groups.
Conclusion: Ginger extract and ibuprofen were significantly more effective than the placebo in
the symptomatic treatment of OA, while there was no significant difference between the ginger
extract and ibuprofen groups in a test for multiple comparison.

Archives of Iranian Medicine, Volume 8, Number 4, 2005: 267 – 271.

Keywords: Ginger extracts • ibuprofen • inflammation • osteoarthritis • pain

Introduction
popular herbal medications for rheumatic diseases.

Ginger (Zingiber officinale) has been used for
here is an increasing awareness, both in
medicinal purposes since antiquity. In particular, it
the medical community and among public,
has been an important plant for the traditional
T for the use of unconventional or alternative Chinese and Indian medicines. Although one of its
treatment modalities by patients.1, 2 Patients with
indications has been historically to treat rheumatic
chronic painful disease often seek alternative
disorders, and although ginger extracts have shown
therapy,3 and currently ginger is one of the most
the ability to inhibit arachidonic acid metabolism
and have antiinflammatory action and/or anti-
rheumatic properties,4, 5 there are very limited
Authors’ affiliations: *Ecological Institute of Caspian Sea, Sari,
**Department of Rheumatology, Imam Khomeini Hospital,
published reports on the efficacy of this herb.4, 6 – 8
***Faculty of Pharmacy, and †Faculty of Rehabilitation, Tehran
The currently available treatment for osteoarthritis
University of Medical Sciences, Tehran, Iran.
•Corresponding author and reprints: Masoud Haghighi PhD,
(OA) afford only palliative care. The prescription
Ecological Institute of Caspian Sea, Sari 961, Iran.
of simple analgesics, such as acetaminophen to
Tel: +98-152-3462495, E-mail: masoud126@yahoo.com.
Archives of Iranian Medicine, Volume 8, Number 4, October 2005 267

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Comparing the effects of ginger (Zingiber officinale) extract and ibuprofen on
patients with osteoarthritis

reduce pain, generally precedes the treatment with
controlled clinical trial. Exclusion criteria were
nonsteroidal antiinflammatory drugs (NSAIDs).
rheumatoid arthritis, metabolic disorders
NSAIDs use is limited by the risk of adverse
(diabetes), gastrointestinal disorders (gastritis or
effects, particularly gastrointestinal and renal
duodenum ulcer), neurological disorders, and
toxicity.
dementia. The patients were then randomized into
The purpose of this study was to assess the
three treatment groups of 40, receiving either 30
effects of ginger extract as an alternative to
mg ginger extract in two 500 mg tablets; placebo
NSAIDs and as a supplement drug in the symp-
daily, or three 400-mg ibuprofen capsules daily for
tomatic treatment of OA.
one month. Acetaminophen was used as a rescue

medication throughout the study (1 to 3 tablets
Patients and Methods
daily). Treatment with analgesics and NSAIDs was

discontinued during the one-week wash-out period.
Plant material and preparation of extract
The following measurements were taken from
Fresh rhizome of ginger (Zingiber officinale
the above-mentioned agents:
Rosce) was purchased from a local market in India
•
One hundred-mm VAS for assessing the
and authenticated by a botanist (Institute of
severity of pain;
Medicinal Plants, Jahad-e-Daneshgahi). The plant
was dried in the shade. The dried rhizome was •
Gelling pain;
powdered mechanically and extracted by cold
percolation with 95% ethanol for 24 hr. The extract
•
Joint swelling measurements; and
was recovered and 95% ethanol was further added
to the plant material and the extraction continued.
•
Joint motion slope measurements.
The process was repeated three times. The three

extracts were pooled together and the combined
Statistical analysis
extract was concentrated under reduced pressure
The data expressed as mean±SEM were
(22 – 26 mm Hg) at 45 – 60?C. Thirty gram of
statistically analyzed by the analysis of variance
solvent-free extract was equivalent to one kilogram
(ANOVA) followed by the Kruskal-Wallis non-
of the dried ginger (W/W) powder. The
parametric test for between-group differences and
concentrate was weighed and combined with the
Dunn’s correction of the significance level for
necessary exipients, and then filled into 500-mg
multiple comparison. The level of significance
capsules, each containing 15 mg of the ginger
adopted was P < 0.05. Calculations were
extract. Lactose (placebo) was also capsulated
performed on a personal computer, using the Instat
similarly (all of the above-mentioned procedures
program, before breaking the code.
were undertaken in the industrial pharmacy

department of the Faculty of Pharmacy, Tehran
Results
University of Medical Sciences).


Characteristics
Patient selection and study design
A total of 120 patients with OA were enrolled
This study was approved by the local
in three treatment groups: ginger extract, placebo,
committee for medical ethics and prior written
and ibuprofen group. Table 1 shows a brief
informed consent was obtained from all patients.
characteristical comparison of the study groups
One hundred and twenty outpatients with OA (89
before the start of the treatment (baseline). There
men, and 31 women), aged 52 to 64 years (mean:
was no significant difference between the groups
58.5 years) were recruited for this study, which
for mean age, pain, joint swelling measurement,
was carried out in the rheumatology clinic of Imam
joint motion slope measurement (one-way
Khomeini Hospital. All the patients had complaints
ANOVA), and sex (Chi-square).
of clinical dysfunction and pain due to OA. Radio-

logically, it was verified that they had OA in the
Efficacy
hip or knee with pain on movement of >30 mm on
During the treatment period, no patient was
a 100-mm visual analog pain scale9 (VAS, mean 69
excluded from this study. At the end of one month
mm) on their first visit for this study. The study
of treatment, VAS and gelling or regressive pain
was a double-blinded randomized placebo-
after rising changed in comparison to the baseline
268 Archives of Iranian Medicine, Volume 8, Number 4, October 2005

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M. Haghighi, A. Khalvat, T. Toliat, et al
Table 1. Baseline characteristics of patients evaluated at the end of the washout period.
Treatment groups
Characteristic
Ginger extract
Placebo
Ibuprofen
P Value
n = 40
n = 40
n = 40
Mean age (years)
58.3 ± 0.33
58.4 ± 0.36
58.8 ± 0.35
P > 0.05
Range
(55 – 64)
(52 – 62)

Sex (man : woman)
29 : 11
28 : 12
32 : 8
P > 0.05
VAS
71.7 ± 3.5
64.2 ± 2.8
71.2 ± 2.4
P > 0.05
Gelling or regressive pain after rising score
3.65 ± 0.18
3.22 ± 0.27
3 ± 0.20
P > 0.05
Joint swelling scores
1.25 ± 0.06
1.07 ± 0.04
1.15 ± 0.05
P > 0.05
Joint motion slope scores
1.62 ± 0.07
1.37 ± 0.07
1.45 ± 0.07
P > 0.05
values (before treatment), but not in the remaining
< 0.001), but not between the ginger extract and
outcome parameters, including joint swelling
ibuprofen (P > 0.05) at the end of one month of
measurement and joint motion slope measurement
treatment (Figure 2).
(Table 2). There was no significant difference
These results also showed a significant
between the three groups in terms of the pain level
difference between both the ginger extract and
at study entry (P > 0.05), as examined by the
ibuprofen groups with the placebo group, but not
Kruskal-Wallis nonparametric test. VAS changed
between the ginger extract and ibuprofen group.
from the entry median value of 64.2 ± 2.8 mm to
The number of acetaminophen used in these
56.5 ± 3.6 mm in the placebo group, 71.7 ± 3.5
treatment groups could not be assessed, because
mm to 30 ± 3.7 mm in the ginger extract group,
the majority of the patients did not fill in this form
and 71.2 ± 2.48 mm to 28 ± 3 mm in the ibuprofen
correctly.
group (Figure 1). There was a significant

difference between the three groups in VAS at the
Discussion
end of one month treatment (P < 0.0001), as

examined by the Kruskal-Wallis nonparametric
The findings of this study demonstrate a
test. The Dunn’s test for multiple comparisons
ranking of efficacy in pain level in patients with
showed a significant difference in these tests
osteoarthritis, with ginger extract and ibuprofen
between the ginger extract and placebo (P <
being more effective than placebo. Nonetheless,
0.001), as well as ibuprofen and placebo (P <
there is an identical efficacy between the ginger
0.001), but not between the ginger extract and
extract and ibuprofen.
ibuprofen (P > 0.05) at the end of one month of
Although the use of NSAIDs in osteoarthritis is
treatment (Figure 1). Also gelling or regressive
highly controversial,10 the fact is that many
pain after rising the scores changed from the entry
physicians and patients favor these agents for
median values of 3.22 ± 0.27 to 1.77 ± 0.11 in the
short- and long-term use. However, the therapeutic
placebo group, to 3.65 ± 0.18 to 1.3 ± 0.13 in the
utility of these agents is frequently limited by the
ginger extract group, and 3.0 ± 0.2 to 0.97 ± 0.1 in
development of side effects, especially
the ibuprofen group (Figure 2). There was a
gastrointestinal ulceration and ulcer complications.
significant difference between the three groups in
Ulcer complications, such as bleeding and
the gelling pain at the end of one month treatment
perforation, associated with NSAID therapy often
(P < 0.0001), as examined by the Kruskal-Wallis
occur without warning and could be life
nonparametric test. The Dunn’s test for multiple
threatening.
comparison showed a significant difference in
The active components of ginger are not known
these tests, between the ginger extract and placebo
with certainty, but studies of the lipophilic rhizome
(P < 0.05) as well as the ibuprofen and placebo (P
extracts have yielded the potentially active
Table 2. The change in outcome parameters after a month of treatment.
Treatment groups
Parameters
Ginger extract
Placebo
Ibuprofen
P Value
n = 40
n = 40
n = 40
VAS
30 ± 3.7
56.5 ± 3.6
28 ± 3.4
P < 0.0001
Gelling pain score
1.30 ± 0.13
1.77 ± 0.11
0.97 ± 0.11
P < 0.0001
Joint swelling scores
1.12 ± 0.52
1.02 ± 0.02
1.10 ± 0.04
P > 0.05
Joint motion slope scores
1.55 ± 0.07
1.30 ± 0.07
1.40 ± 0.07
P > 0.05
Archives of Iranian Medicine, Volume 8, Number 4, October 2005 269

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Comparing the effects of ginger (Zingiber officinale) extract and ibuprofen on
patients with osteoarthritis

y
it 8
ns
e
Before treatment
in int 6
After treatment
lling pa 4

ge
e
h 2
in t
nge
a 0
h
C
Ginger extract group
Ibuprofen group
Placebo group
Figure 1. The effects of ginger extract, ibuprofen,

and placebo on the change in the mechanical pain
intensity. There was no significant difference between the groups before treatment (P > 0.05). There was a
significant difference between the ginger extract and placebo groups (P < 0.001) and also, between the
ibuprofen and placebo groups (P < 0.001) after treatment. There was no significant difference between the
ginger extract and ibuprofen groups (P > 0.05).
Before treatment:
Ginger extract group = 3.65 ± 0.18; ibuprofen group = 3 ± 0.2; placebo group = 3.22 ± 0.27.
After treatment:
Ginger extract group = 1.3 ± 0.13; ibuprofen group = 0.97 ± 0.1; placebo group = 1.77 ± 0.11.
components, gingerols and shogaols.11
dual inhibitors of eicosanoid synthesis, which
One of the mechanisms of inflammation is the
makes the substances even more interesting in the
increased oxygenation of arachidonic acid, which
field of rheumatology.15 – 17 Thus, antiinflammatory
is metabolized by cyclooxygenase and 5-
effect of ginger may be due to a decrease in the
lipoxygenase, leading to prostaglandin E2 and
formation of prostaglandins and leukotrienes.18 A
leukotriene B4, two potent mediators of
suppressive effect of ginger compounds in arthritic
inflammation.4 Ginger contains chemical
rats has been reported.19, 20 A retrospective case
substances with an antiinflammatory potential, and
series was reported on the use of ginger in 56
the effect might be attributed to the actions of
patients with rheumatoid arthritis, osteoarthritis,
gingerols, shogaols, diarylheptanoids, and
and muscle discomfort.4 The patients subjectively
dialdehyd diterpens, which may inhibit infla-
described symptom relief, with many reporting that
mmatory prostaglandins.12 – 14 These agents are
they were able to reduce their use of other

n
100
Before treatment
pai
90
cal
S)
80
After treatment
70
60
echani
mm VA
(
50
y
it
40
the m
ns
30
n
i
t
e
20
in
10
0
Change
Ginger extract group
Ibuprofen group
Placebo group
Figure 2. The effect of ginger extract, ibuprofen, and placebo

on the change in gelling pain intensity.
There was no significant differences between the groups before treatment (P > 0.05). There was a
significant difference between the ginger extract and placebo groups (P < 0.05) and also, between the
ibuprofen and placebo groups (P < 0.001) after treatment. There was no significant difference between the
ginger extract and ibuprofen groups (P > 0.05).
Before treatment:
Ginger extract group = 71.7 ± 3.50; ibuprofen group = 71.2 ± 2.48; placebo group = 64.2 ± 2.8.
After treatment:
Ginger extract group = 30 ± 3.7; ibuprofen group = 28 ± 3; placebo group = 56.5 ± 3.6.
270 Archives of Iranian Medicine, Volume 8, Number 4, October 2005

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M. Haghighi, A. Khalvat, T. Toliat, et al
antiarthritis drugs. Not long ago, in various
ginger extracts and ibuprofen in osteoarthritis.
randomized, double-blind, placebo-controlled trials
Osteoarthritis Cartilage. 2000; 8: 9 – 12.
8
Altman RD, Marcussen KC. Effects of a ginger extract
ginger was shown to reduce symptoms of
on knee pain in patients with osteoarthritis. Arthritis
osteoarthritis.7, 8
Rheum. 2001; 44: 2531 – 2538.
A one-month period of therapy with only one
9
Huskisson EC. Measurement of pain. J Rheumatol. 1982;
dose of ginger extract applied in this study might
9: 768 – 769.
not have been adequate for all the effects of ginger
10 Doherty M, Jones A. Indomethacin hastens large joint
osteoarthritis in humans-how strong is the evidence. J
extract to be detected. Future studies might look
Rheumatol. 1995; 22: 2013 – 2016.
into the dose-response and duration of therapy of a
11 Bisset NG. Herbal Drugs and Phytopharmaceuticals: a
standardized and highly concentrated ginger
Handbook for Practice on a Scientific Basis. Boca Raton,
extract in patients with osteoarthritis.
FL: CRC Press; 1994.
12 Kiuchi F, Iwakami S, Shibuya M, Hanaoka F, Sankawa
In conclusion, the results of our study indicated
U. Inhibition of prostaglandin and leukotriene bio-
that ginger extract could be used as an alternative
synthesis by gingerol and diaryheptanoids. Chem Pharm
to the NSAID and as a supplement drug in patients
Bull. 1992; 40: 387 – 391.
with osteoarthritis.
13 Kawakishi S, Morimitsu Y, Osawa T. Chemistry of
ginger compounds and inhibitory of arachidonic acid

cascade. Am Chem Soc Symp Ser. 1994; 547: 244 – 250.
References
14 Suekawa M, Yuasa K, Isono M. Pharmacological studies

on ginger. IV. Effect of (6)-shogaol on the arachidonic
1
Eisenberg DM, Kessler RC, Foster C, Norlock FE,
cascade [in Japanese]. Nippon Yakurigaku Zasshi.
Calkins DR, Delbanco TL. Unconventional medicine in
1986; 88: 263 – 269.
the United States. Prevalence, costs, and patterns of use.
15 Backon J. Ginger: inhibition of thromboxane synthetase
N Engl J Med. 1993; 328: 246 – 252.
and stimulation of prostacyclin: relevance for medicine
2
Murray RH, Rubel AJ. Physicians and healers-unwitting
and psychiarty. Med Hypotheses. 1986; 20: 271 – 278.
partners in health-care. N Engl J Med. 1992;

16 Weidner MS. HMP-33 ginger extract-a new
326 (suppl 1): 61 – 64.
antiinflammatory compound. Osteoarthritis Cartilage.
3
Visser GJ, Peters L, Rasker JJ. Rheumatologists and their
1997; 5 (suppl A): 42.
patients who seek alternative care: an agreement to
17 Srivastava KC. Aqueous extracts of onion, garlic and
disagree. Br J Rheumatol. 1992; 31: 485 – 489.
ginger inhibit platelet aggregation and alter arachidonic
4
Srivastava KC, Mustafa T. Ginger (Zingiber officinale) in
acid metabolism. Biomed Biochem Acta. 1984; 43:
rheumatism and musculoskeletal disorders. Med
S335 – 346.
Hypotheses. 1992; 39: 342 – 348.
18 Mustafa T, Srivastava KC, Jeusen KB. Drug
5
Sharma JN, Srivastava KC, Gan EK. Suppressive effects
development reports. Pharmacology of ginger (Zingiber
of eugenol and ginger oil on arthritic rats. Pharmacology.
officinale). J Drug Dev. 1993; 6: 25 – 39.
1994; 49: 314 – 318.
19 Mascolo N, Jain R, Jain S, Capasso, F.
6
Srivastava KC, Mustafa T. Ginger (Zingiber officinale)
Ethnopharmacologic investigation of ginger (Zingiber
and rheumatic disorders. Med Hypotheses. 1989; 29:
officinale). J Ethnopharmacol. 1989; 27: 129 – 140.
25 – 28.
20 Sharma JN, Srivastava KC. Suppressive effects of
7
Biddal H, Rosetzsky A, Schlichting P, et al. A
eugenol and ginger oil on arthritic rats. Pharmacology.
randomized, placebo-controlled, cross-over study of
1994; 49: 314 – 318.














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