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EFFECT OF PYCNOGENOL ON OSTEOATHRITIS 1087
Copyright © 2008 John Wiley & Sons, Ltd. Phytother. Res. 22, 1087–1092 (2008)
DOI: 10.1002/ptr
Copyright © 2008 John Wiley & Sons, Ltd.
PHYTOTHERAPY RESEARCH
Phytother. Res. 22, 1087–1092 (2008)
Published online 20 June 2008 in Wiley InterScience
(www.interscience.wiley.com) DOI: 10.1002/ptr.2461
Effect of Pine Bark Extract (Pycnogenol®)
on Symptoms of Knee Osteoarthritis
Peter Cisár1, Richard Jány1, Iweta Waczulíková3, Katarína Sumegová2, Jana Muchová2,
Jozef VojtaSSák1, Zdenka DuraÇková2, Miroslav Lisy1 and Peter Rohdewald4*
12nd Department of Orthopaedics of the Comenius University School of Medicine, University Hospital Ruzinov, Ruzinovská 6,
82606 Bratislava, Slovakia
2Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, School of Medicine, Comenius University, Sasinkova 2,
Bratislava, Slovakia
3Department of Nuclear Physics and Biophysics, Division of Biomedical Physics, Faculty of Mathematics, Physics and
Informatics, Comenius University, Mlynska dolina F1, Bratislava, Slovakia
4Institute of Pharmaceutical Chemistry, University of Münster, Germany
Objective. The safe and efficacious use of Pycnogenol® (French maritime pine bark extract) in other inflam-
matory diseases prompted this study of its antiinflammatory effects in patients with osteoarthritis (OA).
The aim of the study was to evaluate whether Pycnogenol® reduces the symptoms of OA in a double-blind,
placebo-controlled, randomly allocated trial with patients suffering from knee osteoarthritis stages I and II.
Methods. 100 patients were treated for 3 months either by 150 mg Pycnogenol® per day at meals or by
placebo. Patients had to report any change of use of previously prescribed antiinflammatory medication during
the study period. Patients filled the Western Ontario and Mc Masters University (WOMAC) questionnaire
for osteoarthritis every 2 weeks and evaluated weekly pain symptoms using a visual analogue scale for pain
intensity.
Results. Following treatment with Pycnogenol® patients reported an improvement of WOMAC index
(p <<
<<
< 0.05), and a significant alleviation of pain by visual analogue scale (p <<
<<
< 0.04), the placebo had no effect.
The use of analgesics diminished in the verum group but increased under the placebo. Treatment with
Pycnogenol® was well tolerated.
Conclusion. Results show that Pycnogenol® in patients with mild to moderate OA improves symptoms and
is able to spare NSAIDs. Copyright © 2008 John Wiley & Sons, Ltd.
Keywords: osteoarthritis; Pycnogenol®; pine bark extract; WOMAC.
Received 18 October 2007
Accepted 7 November 2007
* Correspondence to: Peter Rohdewald, Twenteweg 15, 48161 Münster,
Germany.
E-mail: rohdewa@uni-muenster.de
Contract/grant sponsor: Horphag Research Ltd; VEGA of Ministry of
Education of Slovakia and Mind and Health, civil association; contract/
grant number: 1/2294/05, 1/1157/04, 1/3037/06.
INTRODUCTION
Osteoarthritis (OA) is a chronic, progressive disease
that particularly affects weight-bearing joints such as
hips and knees. The risk increases with aging. The
severity of OA varies from person to person, but the
consonant clinical signs include pain, reduced range of
motion, inflammation and deformity (Malemud et al.,
2003). The entire joint is affected by a complex com-
bination of degradative and reparative processes, which
alter the anatomy and function of articular cartilage,
subchondral bone and other joint tissues. Symptoms of
local inflammation and synovitis are present in many
patients with OA and are also seen in animal models
of OA (Goldring, 1999). Of the joints affected, knee
OA in particular is a major cause of morbidity, often
resulting in knee replacement (Dixon et al., 2004; Melzer
et al., 2003). The costs associated with OA are high – in
the USA alone in 1991, the annual cost of knee re-
placements was estimated to be more than one billion
dollars (Quam et al., 1991).
At the molecular level, OA is characterized by an
imbalance between anabolic (i.e. extracellular matrix
biosynthesis) and catabolic (i.e. extracellular matrix
degradation) pathways in which articular cartilage is
the principal site of tissue injury responses (Malemud
et al., 2003). Interleukin-1 (IL-1)-induced inflammatory
response in arthritic joints include the enhanced expres-
sion and activity of matrix metalloproteinases (MMPs).
Their matrix degrading activity contribute to the irre-
versible loss of cartilage and may also be associated
with sustained chronic inflammation (Ahmed et al., 2004).
Current treatment modalities for OA are mostly
symptomatic and include awide range of analgesics (e.g.
nonsteroidal antiinflammatory drugs (NSAIDs) and
specific cyclooxygenase-2 (COX-2) inhibitors. The ma-
jor side effects of NSAIDs are their propensity to cause
stomach ulcers, GI bleeding and perforations. Although
a new class of NSAIDs – the specific inhibitors of COX-
2 – was developed, these drugs have similar efficacy
to the general NSAIDs, but fewer gastrointestinal trou-
bles. However, some of these COX-2 inhibitors were
recently withdrawn from the market or ordered by the
United States Food and Drug Administration (FDA)
to have a black box warning on the label because of
concerns that their long-term use may increase the risk
Copyright © 2008 John Wiley & Sons, Ltd. Phytother. Res. 22, 1087–1092 (2008)
DOI: 10.1002/ptr
1088 P. CISAR ET AL.
of stroke and heart attack (Ahmed et al., 2005). The
group of drugs known as SYSADOA (Symptomatic Slow
Acting Drugs of Osteoarhritis), or chondroprotectives,
act differently. The onset of effect is slow, but can
remain for a longer period. They can be applied locally
– intraarticularly (derivates of hyaluronic acid), or
systemically (glucosamine sulfate, chondroitine sulfate).
It is believed that SYSADOA bind to chondrocyte
receptors and influence the cell metabolism, stimulat-
ing chondrocytes to synthesize matrix elements and
inhibit MMPs.
Pycnogenol is aspecial standardized extract from the
bark of the French maritime pine (Pinus pinaster) (Roh-
dewald, 2005). This extract represents aconcentrate
of polyphenols, composed of several phenolic acids,
catechin, taxifolin and procyanidins with diverse bio-
logical and clinical effects (Rohdewald, 2005). In the con-
text of the treatment of OA, the interaction of Pycnogenol
with MMPs is of great interest. In vitro, Pycnogenol
inhibits selectively MMPs (Grimm et al., 2004). After
intake of Pycnogenol, the plasma from volunteers
inhibited the release of MMP-9 from activated macro-
phages (Grimm et al., 2006) thus demonstrating the
bioavailabilty of the inhibitor of MMP-9. These findings
led to the assumption that Pycnogenol could be helpful
in OA by blocking the deleterious actions of MMPs
on cartilage.
The transcription factor NF
κ
B is a key element in
inflammation as its activation starts the synthesis of
cytokines and adhesion factors. It could be shown
in vitro that Pycnogenol inhibits the activation of NF
κ
B
(Peng et al., 2000; Saliou et al., 2001; Cho et al., 2001).
Recently, it could be proven that after intake of
Pycnogenol plasma contains enough activity to inhibit
significantly the activation of NF
κ
B in inflammatory
cells (Grimm et al., 2004). This inhibition, down-
regulating the subsequent steps of inflammation, ex-
plains the antiinflammatory activity of Pycnogenol which
had been observed in many studies (Rohdewald, 2005).
As cyclooxygenases are the enzymes driving the pro-
duction of pain-producing prostaglandins, it is impor-
tant for the treatment of OA that Pycnogenol inhibits
unspecifically COX1 and COX2 (Schäfer et al., 2006).
Also this effect was found ex vivo in plasma of human
volunteers after supplementation with Pycnogenol. The
sum of these antiinflammatory effects encouraged us
to initiate acontrolled clinical trial to investigate the
effect of Pycnogenol on OA.
MATERIALS AND METHODS
Study design and selection of patients. This study was
conducted as a 3-month prospective, double-blind,
placebo-controlled, single centre study at 2nd Depart-
ment of Orthopaedics of the Comenius University
School of Medicine, University Hospital Ruzinov,
Bratislava, Slovakia.
One hundred outpatients with mild OA stages and
corresponding clinical symptoms were enrolled into the
study.
Inclusion criteria were mild primary OA (stage I or
II, according to Kellgren-Lawrence in standard AP view
radiographs) in at least one target knee, mild to mod-
erate pain in the target knee for at least 3 months pre-
ceding the study, and/or morning knee stiffness and/or
knee crepitus and age of more than 25 years. At baseline,
female subjects of childbearing potential must have
confirmed that they were not pregnant at the time of
enrolment and that they did not plan to get pregnant
for at least 1 year after the end of the trial. Postmenopausal
female subjects must have been amenorrhoic for at least
1 year, in this case the confirmation was not required.
Exclusion criteria were participation in another study,
less than 30 days before the start of this study, moder-
ate or severe stage OA (stage III and IV according to
Kellgren-Lawrence), rheumatoid arthritis (RA) or other
chronic inflammatory process in the target joint, any
other secondary OA, arthroscopic surgery or other major
surgery of the target knee, major trauma of the target
joint, intra-articular injection of corticosteroids or
SYSADOA drugs in the target joint in the past 3 months
preceding study entry. Acute infection of the target joint
in the last 6 months or if subject has started any form
of physiotherapy in the 3 weeks preceding study entry.
Excluded were subjects with a significant psychiatric
disorder (including depression), or subjects receiving
antipsychotic medication. Breastfeeding female subjects
were also excluded.
Subjects were withdrawn in the case of serious
adverse event (SAE), if the subjects revoked the con-
sent or if the investigator considered that for safety
reasons it was in the best interest of the subject to be
withdrawn.
The study was approved by Local Ethical Committee
of the University Hospital in Bratislava.
Main outcome criteria. The main outcome criteria were:
(1) reduction of symptoms of OA using WOMAC sores;
(2) reduction of pain using visual analogue scale (VAS).
The secondary outcome criterion was a decrease of the
use of analgesics.
Treatment assignment. The subjects were randomly
allocated to Pycnogenol®, product of Horphag Research
Ltd, UK, or the placebo group by the principal investi-
gator responsible for the biochemical, but not for the
clinical part.
Sample size. The sample size was estimated assuming
the power of 90% (beta of 10%), the type-one error
(alpha) of 5% and the number of controls per subject
of 1. The recommended number of patients to study
was calculated as 35 per group. To compensate a priori
for dropouts, 50 patients were included in each arm.
Medication. Patients were allowed to continue with
their medication with NSAIDs or analgesics prescribed
before the start of the study. Patients were allowed
to change medication on demand but were instructed
to report at each visit whether dosage or frequency of
intake was lowered or increased.
The patients received 150 mg Pycnogenol per day,
taken as 50 mg t.i.d. with the meals, or identically look-
ing coated placebo pills, produced by the same manu-
facturer (Manhattan Drug Co, N.Y., USA)
Study design. Patients were examined at enrolment to
fulfil inclusion criteria. After signing informed consent,
patients received medication for 4 weeks. The WOMAC
questionnaire, translated into Slovakian language, and
EFFECT OF PYCNOGENOL ON OSTEOATHRITIS 1089
Copyright © 2008 John Wiley & Sons, Ltd. Phytother. Res. 22, 1087–1092 (2008)
DOI: 10.1002/ptr
the visual analogue scale (VAS) were given to the
patients every 2 weeks. VAS was used to rate pain by
the patient on a scale of 0, no pain, to 100, very severe
pain at weekly intervals. Patients received new medica-
tion every month.
Patients were investigated at the start, at 3 months
and 4 weeks after finishing treatment. Patients visited
the center at the start and each 4 weeks.
The WOMAC questionnaire (Bellamy, 1995) (5-point
Likert format in Slovak version) for pain, stiffness and
daily activities was filled in by the patients every 2 weeks
during the whole study (14 weeks).
The VAS (visual analogue scale) for pain was filled
in by the patients each week during the whole study
(14 weeks).
The patients were asked whether analgesics consump-
tion had changed at each visit.
Determination of biochemical parameters. Blood samples
for biochemical analyses were taken from fasting venous
blood in the morning at the start, after 3 months
of treatment and after the washout period into com-
mercial tubes without anticoagulant for determination
of biochemical parameters. Basic biochemical para-
meters (glucose, uric acid, lipid profile, total cholesterol,
HDL-, LDL-cholesterol, TAG, hSCRP, gamma-glutamyl
transferase, alkaline phosphatase, aspartate aminotrans-
ferase and alanine aminotransferase) were analysed
in the serum by standard biochemical procedures using
the Hitachi 911 automatic analyser and kits, Roche,
Switzerland.
Unwanted effects. Patients were asked every 2 weeks
to report any unwanted or unusual effects.
Statistical evaluation. The copies of all data obtained
from questionnaires and outputs from computerized
analysers were checked twice before their evaluation
and statistical analysis. The effect of Pycnogenol or
placebo was evaluated with two-way randomized block
analysis of variance. For multiple comparisons of treat-
ment periods with the baseline value Dunnett’s test
was used. For the statistical evaluation of the differ-
ences between the Pycnogenol and placebo group,
a non-parametric Mann-Whitney test was used. For
statistical analysis statistical programmes StatsDirect
2.3.7 (StatsDirect Sales, Sale, Cheshire M33 3UY, UK)
and Statistica 6.0 (StatSoft, Inc. 2000) were employed.
RESULTS
Patient’s characteristics
The demographic data of patients, given in Table 1, did
not differ significantly in age, male to female ratio
and BMI. From 100 patients included in the study,
90 patients completed the 12 weeks treatment period,
81 completed after 14 weeks the washout period. Ten
patients dropped out before the end of the treatment
period, nine more did not finish the wash-out period.
The group of 19 dropout patients consisted of 13 from
the placebo group and six from the Pycnogenol group.
Data of all patients were evaluated in the intention-
to-treat analysis.
WOMAC scores
The WOMAC-A score, summarizing the scores for pain,
improved sigificantly in Pycnogenol group (p = 0.0004)
with time (Fig. 1). The time dependence of pain reduc-
tion for placebo showed only a trend (p = 0.26). The
difference to baseline was statistically significant for the
Pycnogenol group after weeks 8, 12 and 14 (p < 0.001).
The difference between the Pycnogenol and placebo
groups was near to significance level at week 8 of the
investigation (p = 0.08).
Stiffness (WOMAC B score) improved in the Pycno-
genol group versus baseline after 8, 12 and 14 weeks
significantly (p = 0.01) (Fig. 2). Statistically significant
differences between the Pycnogenol and placebo groups
were observed at weeks 8 and 12 (p < 0.05).
The WOMAC score, characterizing the ability to
perform daily activities, improved significantly versus
Table 1. Basic characteristic of patients
Parameter Pycnogenol group Placebo group
Included patients 50 50
Patients finishing treatment period 48 42
Patients finishing the whole study 44 37
Age (average) 54 (25–65) 54 (30–65)
M/F number (M/F ratio) 14/36 (0,39/1) 18/32 (0,56/1)
BMI (average) 27,29 (16,9–35,4) 27,17 (20,7–37,2)
Drop-outs 6 13
Treatment period
Together 2 8
No compliance/No effect 0 4
Increased pain 0 3
Chest pain 1 0
Foetor from mouth 1 0
Gastric pain 0 1
Wash-out period
Together 4 5
No compliance/No effect 4 4
Illness 0 1
Copyright © 2008 John Wiley & Sons, Ltd. Phytother. Res. 22, 1087–1092 (2008)
DOI: 10.1002/ptr
1090 P. CISAR ET AL.
Figure 1. Reduction of pain according to WOMAC A score for
pain (median). *** Statistical significance of differences Pycno-
genol versus start after 8, 12 and 14 weeks:
p
= 0.001. ° Statis-
tical significance of difference Pycnogenol versus placebo after
week 8:
p
< 0.08.
Figure 3. Influence of treatment on daily activities according
to WOMAC C scores (median). *** Statistical significance of
differences Pycnogenol versus start after 8, 12 and 14 weeks:
p
= 0.01.
Figure 2. Reduction of stiffness according to WOMAC B score
(median). *** Statistical significance of differences Pycnogenol
versus start after 8, 12 and 14 weeks:
p
< 0.01. °° Statistical
significance of difference Pycnogenol versus placebo after 8
and 12 weeks:
p
< 0.05.
baseline at weeks 8, 12 and 14 (p < 0.01), the increase
was not significant under placebo (Fig. 3). However,
the difference between the Pycnogenol and placebo
groups was not significant.
The overall WOMAC score, summarizing pain, stiffness
and daily activities in one score, improved significantly
during the time of the treatment in the Pycnogenol
group (Fig. 4). Statistical significant differences between
Pycnogenol and placebo (p < 0.05) were observed at
weeks 6, 8 and 12 of investigation. The difference to
baseline was significantly (p < 0.05) different after week
8. Overall the WOMAC score of the placebo group
Figure 4. Reduction of symptoms of osteoarthritis. Medians of
overall WOMAC scores. * Statistical significance of differences
Pycnogenol versus start after 8 weeks:
p
= 0.032, 10 weeks:
p
= 0.06. ° Statistical significance of differences Pycnogenol versus
placebo after 6 weeks:
p
= 0.04, 8 weeks:
p
= 0.03, 12 weeks:
p
= 0.03. # Statistical significance of difference of placebo versus
start after 12 weeks:
p
= 0.02, 14 weeks:
p
= 0.01.
Figure 5. Alleviation of pain scored by the visual analogue
scale (VAS), medians. * Statistical significance of differences
Pycnogenol versus start after 8 weeks:
p
= 0.054, 12 weeks:
p
= 0.058, 14 weeks:
p
= 0.032. ° Statistical significance of dif-
ferences Pycnogenol versus placebo after 4 weeks:
p
= 0.08,
8 weeks:
p
= 0.07.
was significantly different from start (p < 0.05) after
weeks 12 and 14.
Pain scores by VAS
At the start, the pain caused by OA scored by VAS
was somewhat higher in the placebo group compared
with the Pycnogenol group (Fig. 5), however, the dif-
ference between groups was not significant. Following
treatment for 4 weeks, the verum group reported
less pain relative to the placebo, pain diminished suc-
cessively over the study period until month 3. The VAS
scores increased slightly, but not significantly after the
washout period, but remained significantly lower com-
pared with the start of treatment. The same trend, but
not significant, was reported for the placebo group.
The correlation of pain attenuation with the time of
treatment was statistically significant (p < 0.04) for the
Pycnogenol group, whereas this correlation was poor
for placebo (p < 0.17)
A marginal statistical significance for comparisons of
the effect of Pycnogenol versus placebo was seen at
weeks 4 (p = 0.08) and 8 (p = 0.07) of treatment (Fig. 5).
EFFECT OF PYCNOGENOL ON OSTEOATHRITIS 1091
Copyright © 2008 John Wiley & Sons, Ltd. Phytother. Res. 22, 1087–1092 (2008)
DOI: 10.1002/ptr
DISCUSSION
The results demonstrate an onset of action of Pycnogenol
following the first month of treatment, reaching bor-
derline level of significance. WOMAC scores as well
as VAS signalize the maximum effect after the second
month of treatment. Thereafter values declined until
the end of washout period, but remained at higher scores
compared with the start.
The results cannot be evaluated without taking into
consideration the concomitant medication with anal-
gesics and NSAIDs in both groups. Patients con-
sumed different types of drugs, brands and dosages
of analgesics and NSAIDs at inclusion prescribed by
practitioners. Therefore, only a qualitative evaluation
of use of medication could be done. As consumption
of analgesics disminished in the Pycnogenol group,
Pycnogenol’s effect had to compensate first of all for
the lower dose of analgesics. The results demonstrate
that Pycnogenol lowered pain and WOMAC scores to
a greater extent compared with the placebo group,
despite the fact that the mean intake of analgesics
was increased under placebo during the study period.
It is reasonable to assume that patients in the placebo
group compensated for the lack of effect of placebo
by taking more analgesics, especially after alonger
period of treatment. The higher dropout rate in the
placebo group due to a lack of pain relief demonstrates
that the placebo effect was not sufficient to satisfy
the needs of the patients. These findings point to a
reasonable antiinflammatory action of Pycnogenol in
patients with OA.
The basis for the observed positive effects in OA
delivers the cascade of inhibitory actions by Pycnogenol
on inflammation, starting from inhibition of free radi-
cals to inhibition of transcription factors and proteases,
ending with inhibition of cytokines, adhesion factors
and of COX1 and COX2 (Rohdewald, 2005). After oral
administration of Pycnogenol two major metabolites are
formed in vivo (Grimm et al., 2004). Both metabolites
exhibit antioxidant activities and strong inhibitory effects
towards the activity of proteases.
The treatment with Pycnogenol was well tolerated.
The two drop-outs during treatment period, caused
by bad breath or chest pain were not attributed to
Pycnogenol treatment.
Unexpectedly, patients in the verum group reported
spontaneously anumber of positive side effects. The
findings of reduced high blood pressure in hyperten-
sive patients are in agreement with the antihypertensive
effects of Pycnogenol in hypertensive patients (Hosseini
et al., 2001; Liu et al., 2004). The lowering of blood
pressure is caused by the beneficial effects of Pycnogenol
on endothelial health. Pycnogenol stimulates e-NOS
activity which leads to enhanced NO production, caus-
ing vasodilatation. Simultaneously, vasodilatation is
stimulated by enhanced prostacyclin levels in plasma
and lower levels of endothelin-1 and thromboxan, which
act as vasoconstrictory agents (Rohdewald, 2005).
Interestingly, Pycnogenol had no effect on blood pres-
sure in clinical trials with normotensive persons, but
normalized moderate hypertension.
Reports on the improvement of mental condition,
skin and hair quality correspond to results obtained with
climacteric women. Pycnogenol improved significantly
Table 2. Analgesics consumption in Pycnogenol/placebo group
during the time of the treatment
Pycnogenol group Placebo group
Same level 62% 82%
Increased dosage 0% 10%
Decreased dosage 38% 8%
Consumption of analgesics
Patients in the Pycnogenol group could reduce the
intake of analgesics or NSAIDs to ahigher percentage
than patients under placebo (Table 2). In contrast, 10%
of patients had to increase the dose of analgesics in the
placebo group but no higher dose was needed in the
Pycnogenol group.
Data of clinical chemistry
Basic biochemical parameters (glucose, uric acid,
parameters of lipid profile – total cholesterol, HDL-
cholesterol, LDL-cholesterol, TAG, hCRP, gamma-
glutamyl transferase, alkaline phosphatase, aspartate
aminotransferase, alanine aminotransferase) were inves-
tigated in serum obtained from fasting venous blood.
All average values of biochemical parameters were in
the physiological range before the trial in both groups.
None of the analysed biochemical parameters raised
or decreased beyond the range of physiological values
after 3 months of Pycnogenol or placebo administra-
tion. No statistically significant change of any biochemi-
cal parameter was observed.
Adverse effects
No serious adverse effects (SAEs) were reported. In the
Pycnogenol group, one patient with previous myocardial
infarction left the study because of chest pain, another
patient because of bad breath. In the placebo group,
three patients left the study because of worsening of
pain, one left because of gastric pain, one patient felt
ill. Four patients from the Pycnogenol group and eight
patients from placebo group were excluded because of
non-compliance.
Additional observations
Elevated blood pressure decreased in six patients
in the Pycnogenol group and in two patients in the
placebo group. Ten patients reported an improvement
of mental condition (be longer awake, better learning,
better memory) in the Pycnogenol group vs three in
the placebo group, four noted an improvement of skin
quality and three an improvement of hair quality (stronger
hair, less loosening of hair). In the placebo group, blood
pressure decreased in two patients and three patients
reported an improvement of mental condition. In the
Pycnogenol group, an ophthalmologist registered a
decrease of intraocular pressure in one patient.
Copyright © 2008 John Wiley & Sons, Ltd. Phytother. Res. 22, 1087–1092 (2008)
DOI: 10.1002/ptr
1092 P. CISAR ET AL.
Acknowledgements
This study was supported by Horphag Research Ltd, partly by VEGA
Grant No. 1/2294/05, 1/1157/04 and 1/3037/06 of Ministry of Education
of Slovakia and Mind and Health, civil association.
PC, RJ, PR and ZD planned the study and prepared the manuscript.
PC and RJ performed the clinical part of the study. IW performed
the statistical analysis. JV assisted with the manuscript and recruited
patients. ML assisted at the clinical part of the study. KS and JM
treated blood samples before analyses and organized blood procedure.
All authors read and approved the final manuscript.
The authors wish to thank to Assoc. Prof. P. Blazicek from
Bratislava for analyses of basic biochemical parameters on Hitachi
911 automatic analyser and Mrs L. Chandogová and L. Míková for
their technical assistance.
mental condition and appearance of skin in Taiwanese
women in adouble-blind, placebo-controlled study
(Liao et al., 2007).
CONCLUSION
Pycnogenol offers an interesting alternative to treatment
of early knee OA with NSAIDs or analgesics because
of its low rate of unwanted effects and its efficacy. As
a concomitant supplement, Pycnogenol may spare the
use of NSAIDs, thus reducing unwanted effects.
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