The Efficacy and Safety of

Curcuma domestica Extracts

in Patients with Knee
Osteoarthritis
Vilai Kuptniratsaikul, M.D.*
Visanu Thamlikitkul, M.D.**
Sunee Thanakhumtorn, B.Sc., M.Ed.***
Pornsiri Chinswangwatanakul, B.Sc.,M.Ns. ***
Luksamee Watanamongkolsil, B.Sc., M.Sc.***
* Department of Rehabilitation Medicine,
** Department of Medicine,
*** Office for Research and Development,
Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok,
Thailand
 Background
OA knee: the most common degenerative
joint disorder and a major public health
problem

Causes pain and dysfunction in 20% of

elderly
Reduces the quality of life
Increases the risks of morbidity and mortality

NSAIDs : the commonest treatment to

relieve pain for OA , but most of them can
 Curcumin
Had an anti-inflammatory effect through inhibition
of
Lipo-oxygenase
Cyclo-oxygenase
Phospholipase
Collagenase, elastase and hyaluronidase
Free radical activated transcription factors such as
AP-1 , nuclear factor kappa B (NFkappaB)
Proinflammatory cytokines: tumor necrosis factor
alpha (TNF ), interleukin-1 beta (IL-1 ) and IL-8
Anti-oxidant : nitric oxide synthase
Collagenase and stromelysin expression
 Safety profile of Curcumin
1 trial with 25 subjects using curcumin up to
8000 mg of curcumin per day for 3 months

5 trials using 1,125-2,500 mg of curcumin per

day

No serious AE
 Objectives
To determine the efficacy and safety of
C.domestica extracts in pain reduction and
functional improvement in patients with
knee osteoarthritis
 Design study
RCT

The study was conducted from April 2005

to May 2006
 Inclusion criteria
Adult with primary knee OA according to the
criteria proposed by the American
Rheumatism
Association
Knee pain and radiographic osteophytes
and at least 1 of the following features:
1) age > 50 years,
2) morning less than 30 min,
3) crepitus on motion
Patients with a pain score of 5 out of 10
 Exclusion criteria
Any patient who had
Peptic ulcer
Hepato-biliary tract disease
Pregnant mother
Known allergy to curcumin or ibuprofen
 Methods
Discontinue the medications 1 week before
randomization
Unblind the patients, only the assessor was blinded

C.domestica extracts: produced by Thai Government

Pharmaceutical Organization under GMP standard

Dried rhizomes of C. domestica were grounded into

powder. The turmeric powder was extracted with
ethanol and then evaporated at low pressure to obtain
ethanolic extracts containing oil and curcuminiods.
The oil part was then removed in order to have
curcuminoids extracts
 Assessed for
eligibility
Flow of
Randomized
Study

C. Domestica Ibuprofen
2X4 per day 2,000 mg/d 800 mg/d 1X2 per day

Follow-up Follow-up
week 2 week 2

Follow-up Follow-up
week 4 week 4

Follow-up Follow-up
week 6 week 6
 Main Outcomes
Pain
Pain on level walking,
Pain on stairs

Functions of knee assessed by

Time spent during 100-meter walk
Time going up and down a flight of stairs

Adverse events
 Statistical Analysis
Main outcomes: Repeated-measures
ANOVA

Differences in mean value of pain and time

spent on a 100-meter walk and going up and
down a flight of stairs at week 6 between
groups : independent t-test

Adverse events and satisfaction level: chi-

square
Compliance of drug intake: Student t-test
Non inferiority trial: Per protocol analysis
 Results
Fifty-two and 55 patients were randomized
to C.domestica extracts and ibuprofen
groups, respectively.
Baseline characteristics of the patients in
both groups were not different
The mean scores of the aforementioned
outcomes at week 0, 2, 4, and 6 were
significantly improved when compared
with the baseline values in both groups.
 Assessed for
eligibility
(N=190) Fig 1.
Randomized Flow of
(N=107)
Study
2,000 mg/d C. Domestica Ibuprofen 800 mg/d
(N=52) (N=55)

week 2 week 2
(N=48) (N=52)

week 4 week 4
(N=46) (N=48)

week 6 week 6
(N=45) (N=46)
Fig 2. Mean pain scores on level walking, pain
on stairs, time spent on a 100-meter walk and
going up and down a flight of stairs at week 0,
2, 4, and 6
5.5 7

5.0
6

4.5

4.0
Pain on 5 Pain on
walking stairs
Mean of pain on level walking

3.5
4

Mean of pain on stairs

3.0
GROUP GROUP
3
2.5
control (Ibuprofen) control (Ibuprofen)

2.0 study (Curcumin) 2 study (Curcumin)

0 2 4 6 0 2 4 6

Weeks Weeks

108 32
Mean of time spent during 100-meter walk (sec)

Mean of time spent going up & downstairs (sec)

31
106

30

104
29

102 Time spent 28 Time spent

100 100 m. walk 27
up & down
98
GROUP
(sec) 26
GROUP stairs
(sec)
control (Ibuprofen) 25 control (Ibuprofen)

96 study (Curcumin) 24 study (Curcumin)

0 2 4 6 0 2 4 6

Weeks Weeks
 Table 1 Mean value of pain on level walking, pain on stairs, time spent on
100-meter walk and going up and down a flight of stairs between two groups
at week 6 adjusted by week 0
Mean SD at week 6 Difference in mean p-

Ibuprofen Curcumin (95% CI) at week 6 value

(n=45)
(n=46) adjusted by wk 0 # *

Pain level walking 3.1 2.3 2.5 1.6 0.65 (-0.14 to 1.43) 0.10

Pain on stairs 3.9 2.4 3.1 1.5 0.55 (-0.26 to 1.35) 0.18

Time on 100- 97.0 25.7 96.7 17.0 3.54 (-2.93 to 10.0) 0.28

meter walk (sec)

Time on going up 25.9 12.3 24.8 10.2 2.28 (-0.57 to 5.13) 0.11

and down stairs

# Difference = mean of Ibuprofen mean of C.domestica, * Regression Analysis
 C.domestica Ibuprofen p-value*
Adverse Events
(n=48) (n=52)

Total no. of patients with an AE 16 (33.3%) 23 (44.2%) 0.36

Adverse events

Dyspepsia 10 (20.8%) 14 (26.9%)

Dizziness 5 (10.4%) 2 (3.8%)

Nausea / vomiting 3 (6.3%) 3 (5.8%)

Loose stool 2 (4.2%) 1 (1.9%)

Constipation 0 2 (3.8%)

Dry mouth 0 2 (3.8%)

Rash 0 1 (1.9%)

Fatigue 0 1 (1.9%)

GI bleeding 0 1 (1.9%)

Feeling of drug obstructed 1 (2.1%) 0


2548 : 2,000 .
800 .
100 6

100


C domestica extracts seem to be efficacious and
safe for the treatment of knee OA similar to
ibuprofen
 Curcumin Multicenter
1. (Dosage) :

(Therapeutic dose = 1,200-2,400 mg/d)
2,000 .

1,200-1,500 mg

2. :
single blind (blind
assessor)
3. :
6 (
) 4
4
5.5 7

5.0
6

4.5

5
4.0
Mean of pain on level walking

3.5 4

Pain on

Mean of pain on stairs

Pain on
stairs
3.0
GROUP

walking
GROUP 3

2.5 control (Ibuprofen)

control (Ibuprofen)
2 study (Curcumin)
2.0 study (Curcumin) 0 2 4 6
0 2 4 6

Weeks
Weeks
32
108

Mean of time spent going up & downstairs (sec)

31
Mean of time spent during 100-meter walk (sec)

106 30

29
104

28

102

Time spent Time spent up

27

100 26
GROUP

98
GROUP

control (Ibuprofen)
100 m. walk 25

24
control (Ibuprofen)

study (Curcumin)
& down stairs
96
0 2 4 6
study (Curcumin)
(sec) 0 2

Weeks
4 6

(sec)
Weeks
 Assessed for
eligibility

Curcumin
Randomized
Multicenter

C. Domestica Ibuprofen Dosage

1,500 mg/d 1,200
1,2 mg/d 2x3 per day

Follow-up Follow-up Short duration

week 2 week 2 4 weeks

Follow-up Follow-up Blindness

week 4 week 4 Doule blinded

Follow-up Follow-up Add QoL

week 6 week 6
SF-36