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Effect of Pycnogenol Supplementation on Blood Pressure: A Systematic Review and Meta-analysis

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Background Pycnogenol exhibits many biological activities, including control of blood pressure (BP). However, the reported results are inconsistent because of varied characteristics of participants and quality of studies. Thus, a meta-analysis was conducted to examine the effect of Pycnogenol supplementation on BP. Methods This literature search of PubMed, the Web of Science and the Cochrane library was performed in May 2016 to identify eligible studies. Reference lists of the retrieved articles were also reviewed. Either a fixed-effects or, in the presence of heterogeneity, a random-effects model was used to calculate the effect of combined treatment. Results We identified nine trials involving 549 participants who received Pycnogenol supplementation ranging from 150 mg/d to 200 mg/d. Compared with the control, the pooled estimate of change in systolic and diastolic BPs were −3.22 mmHg (95% CI: −6.20, −0.24) and −3.11 mmHg (95% CI: −4.60, −1.62), respectively. Subgroup analyses showed higher BP reduction among hypertensive participants or those who received intervention for more than 12 wk. However, this significant reduction was not observed in well-designed trials. Conclusion This meta-analysis with nine trials provides better evidence that Pycnogenol exerts beneficial effects on BP.
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Iran J Public Health, Vol. 47, No.6, Jun 2018, pp.779-787 Review Article
779 Available at: http://ijph.tums.ac.ir
Effect of Pycnogenol Supplementation on Blood Pressure:
A Systematic Review and Meta-analysis
Zheng ZHANG 1, Xing TONG 1, Yu-Lu WEI 1, Lin ZHAO 2, *Jia-Ying XU 2, *Li-Qiang
QIN 1
1. Dept. of Nutrition and Food Hygiene, School of Public Health, Soochow University, Suzhou, China
2. Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, School of Radiation Medicine
and Protection, Soochow University, Suzhou, China
*Corresponding Authors: Email: qinliqiang@suda.edu.cn
(Received 16 Mar 2017; accepted 09 Sep 2017)
Introduction
People have shown keen interest in herbal medi-
cine with the hope that they can improve their
health condition through diet or consumption of
natural compound. Pycnogenol is a nutritional
supplement used as a phytochemical remedy
worldwide (1). The term Pycnogenol was intend-
ed to serve as a scientific name for this class of
polyphenols (2); however, this term essentially
refers to a specific blend of procyanidins extract-
ed from a French maritime pine bark. Pycno-
genol is standardized to 70%±5% procyanidins;
the extract also contains catechin, taxifolin, and a
range of phenolic acids, represented by cinnamic
acid and benzoic acid derivatives (1).
Pycnogenol supplementation produces various
potentially protective effects against chronic dis-
eases, such as metabolic syndrome, obesity,
dyslipidemia, diabetes and hypertension (3). We
Abstract
Background: Pycnogenol exhibits many biological activities, including control of blood pressure (BP). Howev-
er, the reported results are inconsistent because of varied characteristics of participants and quality of studies.
Thus, a meta-analysis was conducted to examine the effect of Pycnogenol supplementation on BP.
Methods: This literature search of PubMed, the Web of Science and the Cochrane library was performed in
May 2016 to identify eligible studies. Reference lists of the retrieved articles were also reviewed. Either a f ixed-
effects or, in the presence of heterogeneity, a random-effects model was used to calculate the effect of com-
bined treatment.
Results: We identified nine trials involving 549 participants who received Pycnogenol supplementation ranging
from 150 mg/d to 200 mg/d. Compared with the control, the pooled estimate of change in systolic and diastolic
BPs were -3.22 mmHg (95% CI: -6.20, -0.24) and -3.11 mmHg (95% CI: -4.60, -1.62), respectively. Subgroup
analyses showed higher BP reduction among hypertensive participants or those who received intervention for
more than 12 wk. However, this significant reduction was not observed in well-designed trials.
Conclusion: This meta-analysis with nine trials provides better evidence that Pycnogenol exerts beneficial ef-
fects on BP.
Keywords: Pycnogenol, Blood pressure, Randomized controlled trial, Meta-analysis
Zhang et al.: Effect of Pycnogenol Supplementation on Blood Pressure
Available at: http://ijph.tums.ac.ir 780
particularly focus on its effect on blood pressure
(BP). An early animal study found that systolic
blood pressure (SBP) and diastolic blood pres-
sure (DBP) decreased in a dose-dependent man-
ner after intravenous administration of pine bark
extract to SD rats (4). A long-term animal study
reported a slight but significant SBP reduction in
spontaneously hypertensive rats treated with
Pycnogenol for 6 wk (5). In fact, the effect of
Pycnogenol on human BP has gained increased
research attention. A randomized controlled trial
(RCT) showed that oral administration of Pycno-
genol reduced SBP to the normal value in hyper-
tensive patients (6). A subsequent RCT indicated
that Pycnogenol supplementation in hypertensive
patients reduced the need for nifedipine, a calci-
um antagonist used as a coronary vasodilator (7).
However, the sum of BP deceased by 1.0 mmHg
in Pycnogenol-treated group and even by 1.9
mmHg in placebo group after a 12-wk interven-
tion (8). The discrepancies in BP-lowering effect
are mainly attributed to inter-study variations in
terms of inclusion criteria, trial design, supple-
mental dosage, and duration of intervention.
Therefore, we conducted a meta-analysis to ex-
amine whether or not Pycnogenol supplementa-
tion is beneficial in lowering BP and investigate
the potential sources of heterogeneity across
studies.
Methods
Search strategy and study selection
We follow the Preferred Reporting Items for Sys-
tematic Reviews and Meta-Analysis (PRISMA)
guidelines in the report of this meta-analysis (9).
We conducted a systematic literature search of
PubMed, the Web of Science and the Cochrane
library through May 2016, using the following
search terms: “pycnogenol OR maritime pine
bark OR proanthocyanidin” in combination with
“blood pressure OR hypertension OR endothelial
OR flow-mediated dilation OR vascular”. No
restrictions were imposed. Reference lists were
also reviewed. We did not contact the authors of
the primary studies for additional information.
We also did not try to consider the unpublished
studies. Trials were included in the analysis if they
were RCT and clearly reported the dosage of
Pycnogenol supplementation, intervention dura-
tion and BP levels before and after the trials.
Studies in Pycnogenol combined with drug
treatment included if the control group was also
treated. If more than one time point for the fol-
low up was reported, the data from the longest
period were used. Likewise, the data from the
highest dose were used when more than one dose
was administered for supplementation. In the
case of multiple publications with dupli-
cate/overlapped data for the same trial, the arti-
cle with more detailed information was selected.
Data extraction and quality assessment
We recorded the following characteristics of each
study: first author’s name, publication year, and
study design, sample size, study period, daily dose
of Pycnogenol, intervention period. We also ex-
tracted the following participant characteristics:
gender, mean age, health condition, baseline BP
and change in BP of each study. The Jadad score,
a scale that ranges from 0 to 5 according to the
descriptions of randomization, blinding and re-
porting of participant withdrawals, was used to
measure the quality of each study (10).
Data synthesis and analysis
For parallel trials, the net changes in each out-
come in the intervention and control groups were
reported as differences between mean values be-
fore and after treatments. For crossover trials, net
changes were calculated as differences in the post
treatment values of each group. Cohen method
was used to combine SD. Studies with no report-
ed SD values had their values imputed from
standard errors, the confidence interval (CI) or P-
values using a standard formula. If only SD for
the baseline and final values were provided, SD
for the net changes were imputed according to
the method of Follmann using a correlation coef-
ficient of 0.5 (11).
The heterogeneity between the studies was tested
using the Cochran’s Q test at the P<0.10 level of
significance and quantified by the I² statistic,
Iran J Public Health, Vol. 47, No.6, Jun 2018, pp. 779-787
781 Available at: http://ijph.tums.ac.ir
which describes the inconsistency across studies
(12). In the presence of significant heterogeneity,
the random-effects model was used to calculate
the pooled effect size, otherwise, the fixed-effects
model was applied (13). To explore the possible
influences of study design and participants char-
acteristics, we further conducted pre-specified
subgroup analysis stratified by study design (dou-
ble blind vs. non-double blind design; parallel vs.
cross-over design), hypertension status, Jadad
score, and duration of supplementation. We also
performed a sensitivity analysis, in which a single
trial was omitted each time and the effect size
was recalculated to investigate its influence on
the overall effect size. Potential publication bias
was assessed using Begg’s funnel plots and Eg-
ger’s regression test at the P<0.10 level of signifi-
cance (14).
All analyses were conducted by using STATA
version 14.0 (StataCorp, College Station, TX,
USA). P<0.05 was considered statistically signifi-
cant, except where otherwise specified.
Results
Search results
We initially found 148 articles, the majority of
excluded based on their title and abstract. After
reviewing the full text of the remaining 33 stud-
ies, 22 studies were excluded because they did
not record BP at the baseline or after interven-
tion. Among the remaining 11 potentially rele-
vant articles, two studies were excluded because
they measured an acute effect or they did not in-
clude a control group. Finally, Nine trials were
included in our meta-analysis (6, 8, 15-21) (Fig.
1).
Fig. 1: Flow chart of study selection
PRISMA 2009 Flow Diagram
Records identified through
database searching
(n =145)
Screening
Included
Eligibility
Identification
Additional records identified
through other sources
(n =12)
Records after duplicates removed
(n =148)
Records excluded
(n =116)
Full-text articles assessed
for eligibility
(n =33)
24 excluded
Did not report the BP data
(n=22)
Studies included in
qualitative synthesis
(n =11)
Studies included in
quantitative synthesis
(meta-analysis)
(n =9)
2 excluded
Measured acute effect (n =1)
Did not report the BP data (n =1)
Zhang et al.: Effect of Pycnogenol Supplementation on Blood Pressure
Available at: http://ijph.tums.ac.ir 782
Study characteristics
Table 1 shows the characteristics of the included
trials. These trials were published from 2001 to
2015; 5 were conducted in Italy, 2 in USA, and 1
each in Switzerland and Japan. A parallel design
was used in seven trials and a cross-over design
was used in the two other trials. Five trials em-
ployed double-blind method, one trial was an
open label-study, and three trials did not mention
anything about blinding. Sample sizes varied from
16 to 130 with 276 participants in the supple-
mental groups and 273 in the control groups. The
mean age varied from 22.4 yr old to 63.1 yr old.
Except in Nishioka’s trial, which involved health
young men, the other trials evaluated patients
with borderline hypertension, hypertension, met-
abolic syndrome, type 2 diabetes mellitus
(T2DM), or coronary artery disease. A drug
against hypertension was used in two trials (18,
19) and a drug against diabetes was used in one
trial (21). These drugs were used both in the in-
tervention and control groups. The amounts of
Pycnogenol were 150 (five trials), 180 (one trial)
and 200 (three trials) mg/d. No other nutritional
elements, vitamins, or drugs were used. However,
some trials required participants to receive a die-
tary education or to follow the guidelines of
healthy lifestyle during the observation period
(15, 16, 18). The Jadad score of these trials was
relatively low, and only four trials had a score of
not lower than 3.
Table 1: Characteristic of the trials and participants in this meta-analysis
Author
(yr)
Country
Design
Sample size
(interven-
tion
/control)
Health status
Sex
(M/F)
Age
(yr)
Baselin BP (mmHg)
Daily
Dose
(mg)
Dura-
tion
(week)
Jadad
score
Inter
vention
Control
Hu (2015)
Italy
P
16/16
Borderline
hypertension
18/4
44.5
132.2
/84.3
134.3/85
150
12
1
Belcaro
(2013)
Italy
P
64/66
Metabolic
syndrome
64/66
45.5
144
/87.6
143.2/87.2
150
25
2
Enseleit
(2012)
Switzer-
land
X, DB
23/23
Coronary artery
disease
19/4
63.1
125.8
/75.0
124.8/73.9
200
8
4
Cesarone
(2010)
Italy
P
29/26
Hypertension
34/21
53.7
188
/96.3
186/96
150
25
2
Drieling
(2010)
USA
P, DB
64/66
Metabolic
syndrome
82/48
55
132.6
/78.6
133.2/79.9
200
12
5
Stuard
(2010)
Italy
P, O
31/27
Metabolic
syndrome
31/27
58.7
189.3
/97.2
188.8/95.2
150
25
2
Nishioka
(2007)
Japan
P, DB
8/8
Health
16/0
22.4
114.2
/62.2
115.6/64.3
180
2
4
Cesarone
(2006)
Italy
P, DB
30/30
Diabetes
34/26
59
131(4)
/88(3)
133/85
150
4
2
Hosseini
(2001)
USA
X, DB
11/11
Hypertension
14/8
50.3
139.4
/93.4
139.9/93.8
200
8
3
P: parallel; X: cross-over; O: open; DB: double blind
Effect of Pycnogenol supplementation on BP
Compared with the control group, the interven-
tion group was associated with an average net
change in BP ranging from -6.70 to 1.50 mmHg
for SBP and -7.00 to 0.20 mmHg for DBP. A
trend toward intervention-related reduction in
SBP was observed in seven trials, with six trials
showing a significant reduction. In addition, a
trend toward intervention-related reduction in
DBP was observed in eight trials, with a signifi-
cant reduction in five trials. The tests for hetero-
geneity indicated that the supplemental effect
significantly varied across studies (P<0.001 for
SBP and DBP), and I2 values were 96.8% for SBP
and 93.2% for DBP. Thus, the random-effects
model was used. The overall pooled estimates of
Iran J Public Health, Vol. 47, No.6, Jun 2018, pp. 779-787
783 Available at: http://ijph.tums.ac.ir
the effect of Pycnogenol were -3.22 mmHg (95%
CI -6.20, -0.24; P=0.034) for SBP and -3.11
mmHg (95% CI -4.60, -1.62; P<0.01) for DBP
(Fig. 2).
Subgroup and sensitivity analyses
Table 2 shows the results of the subgroup anal-
yses. When trials were stratified according to
study design, the effect of supplementation on
BP was not observed in trials with a double-blind
design. Pycnogenol supplementation did not af-
fect SBP when trials were stratified by parallel
and crossover design. However, the effect of
supplementation on DBP was observed in trials
with a parallel design. No effect of Pycnogenol
supplementation on SBP was observed in trials
with Jadad scores ≥3.
Fig. 2: Pooled estimates of Pycnogenol supplementation on systolic blood pressure (SBP) and diastolic blood pres-
sure (DBP). WMD, weighted mean difference
With regard to baseline BP, BP was significantly
reduced in hypertensive participants displaying an
SBP of ≥140 or DBP of ≥90, but not in their
counterparts. SBP was also significantly reduced
only among trials wherein the intervention dura-
tion was >12 wk, and DBP reduction tended to
Zhang et al.: Effect of Pycnogenol Supplementation on Blood Pressure
Available at: http://ijph.tums.ac.ir 784
be greater in these trials. Subgroup analyses ac-
cording to mean age and daily dose were not per-
formed because of narrow ranges.
Analysis examining the influence of an individual
trial on the overall effect size by omitting one
trial at each turn yielded a range feom -2.78
mmHg (95% CI: -5.91, 0.35, P=0.08) to -3.98 mmHg
(95% CI: -5.65, -2.30, P<0.01) for SBP and from -
2.64 mmHg (95% CI: -4.09, -1.18, P<0.01) to -3.46
mmHg (95% CI: -5.15, -1.77, P<0.01) for DBP. The
pooled estimate of Pycnogenol on SBP became
insignificant after excluding the studies of Stuar
(P=0.08), Cesarone (P=0.06), or Hu (P=0.06).
Unfortunately, heterogeneity still existed when
any trial was omitted.
Publication bias
Visual inspection of the funnel plots showed
some asymmetry (Fig. 3). However, Results from
Begg’s and Egger’s tests also did not indicate the
evidence of publication bias (SBP: Begg P=0.60,
Egger P=0.12; DBP: Begg P=0.92, Egger
P=0.14).
Fig. 3: Funnel plot of Pycnogenol supplementation
on systolic blood pressure (SBP) and diastolic blood
pressure (DBP). WMD, weighted mean difference
Table 2: Subgroup analyses according to study design and participants’ characteristics
Groups
N
SBP
DBP
Net Change
(95% CI)
P
1
I
2 (%)
P
2
Net Change (95%
CI)
P
1
I
2 (%)
P
2
Total
9
-3.22 (-6.20, -0.24)
0.034
96.8
<0.001
-3.28 (-5.26, -1.30)
<0.001
95.7
<0.001
Study design
DB
5
-0.97 (-3.52, 1.58)
0.457
82.7
<0.001
-2.31 (-5.12, 0.51)
0.109
92.1
<0.001
Non-DB
4
-5.22 (-6.59, -3.85)
<0.001
46.3
50.133
-3.87 (-6.17, -1.57)
<0.001
90.5
<0.001
Parallel
7
-3.17 (-6.55, 0.22)
0.067
97.5
<0.001
-3.53 (-5.24, -1.82)
<0.001
94.9
<0.001
Cross-over
2
-3.14 (-8.29, 2.01)
0.232
52.6
0.146
-1.28 (-3.28, 0.72)
0.208
0
0.923
BaselineBP(mmHg)
SBP<140 or DBP<90
5
-1.07 (-3.73, 1.59)
0.430
91.0
<0.001
-2.14 (-4.39, 0.11)
0.062
92.3
<0.001
SBP≥140 or DBP≥90
4
-5.81 (-6.66, -4.95)
<0.001
0
0.943
-4.31 (-6.43, -2.20)
0.002
80.2
0.002
Jadad Score
≥3
4
-0.54 (-3.46, 2.38)
0.718
64.6
0.037
-1.25 (-1.48, -1.01)
<0.001
0
0.916
3
5
-4.52 (-6.33, -2.71)
<0.001
77.7
0.001
-4.53 (-6.78, -2.28)
<0.001
92.2
<0.001
Duration
12week
6
-1.58 (-4.20, 1.03)
0.234
89.9
<0.001
-2.04 (-4.04, -0.05)
0.044
90.4
<0.001
>12week
3
-5.79 (-6.66, -4.93)
<0.001
0
0.854
-4.91 (-6.63, -3.19)
<0.001
58.5
0.090
P1 value of subgroup analysis via Z-test, P2 value for heterogeneity
DB: double blind; SBP: systolic blood pressure; DBP: diastolic blood pressure
Discussion
This meta-analysis is the first to report that Pyc-
nogenol supplementation significantly reduced
SBP and DBP by approximately 3 mmHg. This
BP-lowering effect was also supported by two
observational studies, which provided the BP
control rate. In a trial, 100 mg of Pycnogenol was
Iran J Public Health, Vol. 47, No.6, Jun 2018, pp. 779-787
785 Available at: http://ijph.tums.ac.ir
administered in hypertensive patients for 12 wk.
As a result, 15 mg of nifedipine was sufficient to
lower the BP to normal value compared with use
of 21.5 mg in the control group (7). In another
study that includes T2DM patients receiving
pharmaceutical treatment showed that 58.3% of
the Pycnogenol-treated subjects achieved BP
control at the end of 12 wk. However, only
20.8% of the subjects maintained control in the
control group (22). A considerable normalization
of SBP and DBP was reported after 2 months of
supplementation of OPC-3 in subjects with met-
abolic syndrome, whereas minimal changes were
found in the control group (23).
Although the precise mechanisms were not fully
understood, the BP-lowering effect of Pycno-
genol involves angiotensin converting enzyme
(ACE) inhibition, nitric oxide (NO) production,
and antioxidation and anti-inflammatory activi-
ties. Pine bark extract exerted inhibitory effect on
ACE with concentration of 50% inhibition as
34.7μg/ml (4). Two trials included in this meta-
analysis evaluated the effects of Pycnogenol as an
adjunct to ACE-inhibitor ramipril for treatment
of hypertensive patients. Administration of rami-
pril plus Pycnogenol exerted a significantly great-
er effects on BP than that of ramipril alone
(18,19). ACE inhibitor should reduce serum an-
giotensin-II level and improve flow-mediated
vasodilation. However, plasma level of angioten-
sin II was not lowered to a considerable extent in
Pycnogenol group, compared with that in the
control group (7). Thus, further studies required
to investigate Pycnogenol as an ACE inhibitor in
the clinically relevant action.
On the other hand, Pycnogenol enhances the en-
dothelial production of NO through the enzyme
nitric oxide synthase (NOS). An in vitro study
showed that Pycnogenol relaxes the adrenaline-
induced contractions in the aortic blood vessels
of rat. This response was due to enhance NO
levels because the NOS inhibitor reverses the
relaxation, and this response in turn is reversed
by addition of L-arginine, the normal substrate
for NOS (24). In Nishioka’s trial, Pycnogenol
supplementation for 2 wk significantly augment-
ed the response of forearm blood flow to acetyl-
choline, an endothelium-dependent vasodilator
acetylcholine. Interestingly, administration of
NOS inhibitor completely abolished this re-
sponse, suggesting that Pycnogenol plays a role
by increasing NO production (20). Oxidative
stress is important in the development and
maintenance of hypertension. Belcaro directly
quantified reactive oxygen metabolites by using
the free radical analytical system in patients with
metabolic syndrome and found that reduction in
oxidative stress was significantly more pro-
nounced after 6 months in the Pycnogenol sup-
plementation group than that in the control
group (16). In another study, healthy subjects re-
ceived Pycnogenol for 6 wk and their plasma ox-
ygen radical absorbance capacity significantly in-
creased. Interestingly, this antioxidant activity
returned to the baseline value after a 4-wk wash-
out period (25). In addition to its antioxidant ac-
tivity, Pycnogenol demonstrated an anti-
inflammatory activity. C-reactive protein (CRP),
the most widely known inflammatory factor, is
associated with vascular stiffness, BP, and athero-
sclerosis (26). In an RCT involving patients with
osteoarthritis, Pycnogenol supplementation for 3
months significantly reduced plasma CRP com-
pared with that in the control group; in addition,
Pycnogenol reduced plasma free radicals (27).
OPC-3 supplementation for 2 months also dra-
matically lowered plasma CRP, but exerted minor
effects in the control group (23).
The results of subgroup analysis indicated that
BP-lowering effect was observed among hyper-
tensive patients in the trials. Thus, participants
with higher baseline BP, who mostly needed
treatment, were more likely to benefit from Pyc-
nogenol supplementation. On the other hand, BP
reduction was more pronounced in trials with
intervention duration of more than 12 wk. There-
fore, a longer period is required to improve BP
condition. However, subgroup analysis did not
reveal BP-lowering effect among trials with dou-
ble-blind design and cross-over design, and SBP-
lowering effect among trials with Jadad scores
≥3. Open label and the lack of clear data collec-
tion techniques resulted in the low Jadad scores
in these trials. The lack of rigorous RCT design
Zhang et al.: Effect of Pycnogenol Supplementation on Blood Pressure
Available at: http://ijph.tums.ac.ir 786
was the main limitation of this meta-analysis.
In addition to individual design, this meta-
analysis was limited by a considerable heteroge-
neity across studies. In term of characteristics of
participants, the trials involved patients with hy-
pertension, metabolic syndrome, diabetes, and
healthy subjects. Healthy status may differently
influence the effect of Pycnogenol on BP re-
sponse. In addition, genetic background or a
gene-diet interaction could be the sources of het-
erogeneity across studies. BP decrease diversely
responses to ACE inhibitor between Whites and
Blacks (28). Inclusion of various races in Driel-
ing’s trial was possibly resulted in failure to ob-
serve the effect of the supplementation (8). In
term of intervention, we did not perform sub-
group analysis according to supplemental dosage
because of the narrow range between 150 and
200 mg per day. Moreover, Pycnogenol is not
easily standardized and mixed with monomer,
dimer, and trimer chemical components obtained
from pine bark extracts (29). This phenomenon
may account for variations in physiologic effects
among different trials. Furthermore, some trials
tested Pycnogenol as an adjunct to conventional
pharmacologic treatment and some trials required
the participants to receive a healthy lifestyle edu-
cation; both have probably masked the effects of
Pycnogenol on BP. In term of outcome, not all
trials were originally designed to investigate the
BP-modulating properties of Pycnogenol.
Conclusion
The findings demonstrated the favorable effects of
Pycnogenol supplementation on BP reductions
especially among hypertensive participants. How-
ever, the biological significance of findings should
be interpreted with caution because of the hetero-
geneity and low-quality design of individual trials.
Ethical considerations
Ethical issues (Including plagiarism, informed
consent, misconduct, data fabrication and/or fal-
sification, double publication and/or submission,
redundancy, etc.) have been completely observed
by the authors.
Acknowledgements
This work was supported by grants from the Na-
tional Natural Science Foundation of China
(Nos. 81273067, 81472974 and 81673101), and
the "Blue Project" of Jiangsu Province to Li-
Qiang Qin.
Conflict of interest
The authors declare that there is no conflict of
interest.
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... People have a hope that they can improve their health through diet or consumption of natural compounds. Accordingly, they have shown interest in herbal medicine (Zhang et al., 2018). Many people believe that natural remedies are harmless. ...
... Pycnogenol is a dietary supplement used as a phytochemical remedy worldwide. It is in polyphenols class (Zhang et al., 2018). It is a flavonoid plant extract obtained from the grown Pinus pinaster (Pinus maritima) on the southwest coast of France (Becit et al., 2017). ...
... It is a flavonoid plant extract obtained from the grown Pinus pinaster (Pinus maritima) on the southwest coast of France (Becit et al., 2017). Standardized to 70±5% procyanidins; the other parts taxifolin, catechin and a range of phenolic acids, represented by benzoin acid and cinnamic acid derivatives (Zhang et al., 2018). Pine tree bark in ancient times as a cough syrup, treats inflammatory diseases, wound healing, prevent bleeding, and dental pain (Becit et al., 2017). ...
... While the results have not been consistent, pycnogenol supplementation has been shown to reduce the systolic and diastolic blood pressure (32). The effect is mediated via nitric oxide (NO) production (32) or angiotensin converting enzyme (ACE) inhibition (33) and /or reduction of endothelin -1 (17). In our study, blood pressure was reduced after oligopin treatment for 3 months, although the difference was not significant. ...
... In our study, blood pressure was reduced after oligopin treatment for 3 months, although the difference was not significant. As most of our study participants displayed wellcontrolled blood pressure levels (97.5% SBP<140 mmHg, 85% DBS <90 mmHg) at the baseline, we postulate that oligopin supplementation could exert favorable effects on blood pressure only among hypertensive patients (16,33,34). On the other hand, the subgroup analysis in the recent meta-analysis indicated that the effect of this extract on blood pressure was more prominent in the trails with a longer intervention duration (>12 weeks) (32). ...
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Background A double blind clinical trial was performed to evaluate whether the polycystic ovary syndrome (PCOS)-specific serum markers and metabolic parameters would change in the women with PCOS during the three-month administration of oligopin. Methods In this double-blind multicenter trial, we randomly assigned 80 PCOS women, based on a 1:1 ratio, to receive oligopin (n= 40) or maltodextrin as placebo (n = 40) for up to 3 months. As PCOS-specific outcomes, we investigated the changes in testosterone, sex hormone binding globulin (SHBG), free androgen index (FAI), dehydroepiandrosterone (DHEA), follicle-stimulating hormone ( FSH ) and luteinizing hormone ( LH ). Secondary end points were metabolic (fasting glycaemia, hemoglobin A1c (HbA1c), lipids, insulin resistance (HOMA-IR)), anthropometrics parameters and blood pressure from the baseline to the end of treatment. We investigated serum transaminase, alkaline phosphatase (ALP), creatinine (Cr) and blood urea nitrogen (BUN) levels as hepatic and kidney outcomes, respectively. Results The first participant was enrolled on April 18, 2018, and the last study visit took place on May 14, 2019. PCOS-specific serum parameters did not change during the three-month administration of oligopin (p > 0.05), except for a small increase in the FSH levels (p=0.03). Oligopin neither changed the metabolic profile nor the anthropometric parameters or blood pressure. ALP levels was significantly increased in placebo group, as compared with oligopin (p=0.01). Conclusion Oligopin supplementation does not seem to be exerting a beneficial effect on both hormonal and metabolic parameters in the women with PCOS. Clinical Trial Registration www.irct.ir , identifier IRCT20140406017139N3.
... Although not consistent, pycnogenol supplementation has been shown to reduce systolic and diastolic blood pressure (23). The effect is mediated via nitric oxide (NO) production (23) or angiotensin converting enzyme (ACE) inhibition (24) and /or reduction of endothelin -1 (25). In our study, blood pressure was reduced after oligopin treatment for 3 months, although the difference was not signi cant. ...
... In our study, blood pressure was reduced after oligopin treatment for 3 months, although the difference was not signi cant. As most of our study participants displayed well controlled blood pressure levels (97.5% SBP<140 mmHg, 85% DBS <90 mmHg) at the baseline, we postulated that oligopin supplementation could exert favorable effects on blood pressure only among hypertensive patients (20,24,26). On the other hand, the subgroup analysis in recent meta-analysis indicated that the effect of this extract on blood pressure is more prominent in trails with longer intervention duration (>12 weeks) (23). ...
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Background: A double blind clinical trial was performed to evaluate whether polycystic ovary syndrome (PCOS)-specific serum markers and metabolic parameters would change in women with PCOS during three months administration of oligopin. Methods: In this double-blind multicenter trial, we randomly assigned 80 PCOS women, in a 1:1 ratio, to receive oligopin (n= 40) or placebo (n = 40) for up to 3 months. As PCOS- specific outcomes, we investigated changes in testosterone, sex hormone binding globulin (SHBG), free androgen index (FAI), dehydroepiandrosterone (DHEA), follicle-stimulating hormone (FSH) and increase luteinizing hormone (LH). Secondary end points were metabolic (fasting glycaemia, hemoglobin A1c (HbA1c), lipids, insulin resistance (HOMA-IR)), anthropometrics parameters and blood pressure from baseline to end of treatment. We investigate serum transaminase, alkaline phosphatase (ALP), creatinine (Cr) and blood urea nitrogen (BUN) levels as hepatic and kidney outcomes, respectively. Results: PCOS-specific serum parameters did not change during three months administration of oligpin (p > 0.05) except for small increase in FSH levels (p=0.03). Oligopin neither changed the metabolic profile nor the anthropometric parameters or blood pressure. ALP levels significantly increased in placebo group compared with oligopin (p=0.01). Conclusion: Oligopin supplementation does not seem to be exerting a beneficial effect on both hormonal and metabolic parameters in women with PCOS. The study was registered at www.irct.ir with the identifier number of IRCT20140406017139N3. Registered 22 December 2018 - Retrospectively registered.
... It has a protective effect against inflammatory diseases, hypertension, diabetes, and obesity, among others [32]. Furthermore, it has a beneficial effect on lung fibrosis and improves cognitive ability and cardiovascular health [33][34][35]. Pycnogenol has been recognized as a safe extracted bioactive compound according to scientific safety and preclinical toxicology records [36]. After ingestion of pycnogenol, the phenolic constituents are metabolized by the action of microbial enzymes to afford small bioactive byproducts that can be absorbed into the blood and transferred to tissues and organs [34]. ...
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Methotrexate (MTX) is one of the most commonly used chemotherapies for various types of cancer, including leukemia, breast cancer, hepatocarcinoma, and gastric cancers. However, the efficacy of MTX is frequently limited by serious side effects. Several studies have reported that the cytotoxic effect of MTX is not limited to cancer cells but can also affect normal tissues, leading to prospective damage to many organs. In the present study, we extensively investigated the molecular and microscopic basis of MTX-induced toxicity in different organs (liver, kidney, and heart) and explored the possible protective effect of pycnogenol, a polyphenolic component extracted from the bark of P. pinaster, to attenuate these effects. Biochemical analysis revealed that administration of MTX significantly reduced the function of the liver, kidney, and heart. Histological and immunohistochemical analysis indicated that MTX treatment caused damage to tissues of different organs. Interestingly, administration of pycnogenol (10, 20, and 30 mg/kg) significantly attenuated the deterioration effects of MTX on different organs in a dose-dependent manner, as demonstrated by biochemical and histological analysis. Our results reveal that pycnogenol successfully ameliorated oxidative damage and reduced toxicity, inflammatory response, and histological markers induced by methotrexate treatment. Taken together, this study provides solid evidence for the pharmacological application of pycnogenol to attenuate damage to different organs induced by MTX treatment.
... It has a protective effect against inflammatory diseases, hypertension, diabetes, and obesity, among others [32]. Furthermore, it has a beneficial effect on lung fibrosis and improves cognitive ability and cardiovascular health [33][34][35]. Pycnogenol has been recognized as a safe extracted bioactive compound according to scientific safety and preclinical toxicology records [36]. After ingestion of pycnogenol, the phenolic constituents are metabolized by the action of microbial enzymes to afford small bioactive byproducts that can be absorbed into the blood and transferred to tissues and organs [34]. ...
Article
Full-text available
Methotrexate (MTX) is one of the most commonly used chemotherapies for various types of cancer, including leukemia, breast cancer, hepatocarcinoma, and gastric cancers. However, the efficacy of MTX is frequently limited by serious side effects. Several studies have reported that the cytotoxic effect of MTX is not limited to cancer cells but can also affect normal tissues, leading to prospective damage to many organs. In the present study, we extensively investigated the molecular and microscopic basis of MTX-induced toxicity in different organs (liver, kidney, and heart) and explored the possible protective effect of pycnogenol, a polyphenolic component extracted from the bark of P. pinaster, to attenuate these effects. Biochemical analysis revealed that administration of MTX significantly reduced the function of the liver, kidney, and heart. Histological and immunohistochemical analysis indicated that MTX treatment caused damage to tissues of different organs. Interestingly, administration of pycnogenol (10, 20, and 30 mg/kg) significantly attenuated the deterioration effects of MTX on different organs in a dose-dependent manner, as demonstrated by biochemical and histological analysis. Our results reveal that pycnogenol successfully ameliorated oxidative damage and reduced toxicity, inflammatory response, and histological markers induced by methotrexate treatment. Taken together, this study provides solid evidence for the pharmacological application of pycnogenol to attenuate damage to different organs induced by MTX treatment. Keywords: cancer; methotrexate; toxicity; natural herbs; polyphenol; pycnogenol; MAPK; JNK; apoptosis; inflammation; molecular docking
... Clinical effects of PYC include: endothelium-dependent vasodilator activity (23), and anti-thrombotic effect as shown by numerous in vitro and in vivo investigations in animals and human clinical research studies (24,25). PYC prevents neurotoxicity and apoptotic cell death in oxidative stress status (26,27). ...
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Background: Traumatic brain injury (TBI) is one of the major health and socioeconomic problems in the world. Immune-enhancing enteral formula has been proven to significantly reduce infection rate in TBI patient. One of the ingredients that can be used in immunonutrition formulas to reduce inflammation and oxidative stress is pycnogenol. Objective: surveying the effect of pycnogenol on the clinical, nutritional and inflammatory status of TBI patients. Methods: This is double-blind, randomized controlled trial . Block randomization will be used. Intervention group will receive pycnogenol supplementation of 150 mg for 10 days. Control group will receive placebo for the same duration. Inflammatory status (IL-6, IL- 1β, C-reactive protein) and oxidative stress status (Malondialdehyde, total antioxidant capacity), at the base line, at the 5 th day and at the end of the study (10 th day) will be measured. Clinical and nutritional status will be assessed three times during the intervention. SOFA (sequential organ failure assessment) questionnaire for assessment of organ failure will be filled out every other day. The mortality rate will be calculated within 28 days of the start of the intervention. Weight, body mass index and body composition will be measured. All analyses will be conducted by initially assigned study arm in an intention-to-treat analysis. Discussion: We expect that supplementation of 150 mg pycnogenol for 10 days will improve clinical and nutritional status and reduce the inflammation and oxidative stress of the TBI patients.
... Some of these components have received considerable attention because of their anti-inflammatory, antimutagenic, antimetastatic, and anticarcinogenic activities. 9 Several studies have demonstrated the antimicrobial and antiviral activities of PBE. 12 Furthermore, PBE may protect against sarcopenia 13 and may help improve conditions relating to poor circulation, high blood pressure, 14 osteoarthritis, 15 and diabetes. 16 PBE has been reported to have cardiovascular benefits and aid in problems with circulation. ...
Article
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Melanoma is the most aggressive type of skin cancer due to its rapid metastasis with a high recurrence rate following conventional therapy. Pine bark extract (PBE) from Pinus maritima contains numerous phenolic compounds and functions as a potent antioxidant. The present study aimed to analyze the potential anticancer properties of PBE on human malignant melanoma A375 cells. The chemical composition of PBE was determined by high-performance liquid chromatography/photodiode array detector. The effects of PBE on cell death, migration, and invasion were determined using xCELLigence Technology real-time cell analysis. Annexin/propidium iodide flow cytometry and Hoechst 33342 staining were conducted to detect cell apoptosis. PBE induced apoptosis and inhibited cell migration and invasion. Cleaved caspase-3 expression and activity were significantly increased ( P < 0.01) in cells treated with PBE compared with control cells. PBE ameliorated hydrogen peroxide (H 2 O 2 )-induced reactive oxygen species (ROS) formation. Treatment of the cells with PBE in the presence of H 2 O 2 led to significant ( P < 0.001) reduction of matrix metallopeptidase-9, which is a mediator responsible for advanced melanoma. PBE induces A375 programmed cell death and suppresses cellular invasion by attenuating the ROS-dependent pathway associated with MMP-9 reduction.
... It is classified as GRAS (generally recognized as safe) in the USA [22]. Clinical effects of PYC include endothelium-dependent vasodilator activity [23] and anti-thrombotic effect as shown by numerous in vitro and in vivo investigations in animals and human clinical research studies [21,24]. PYC prevents neurotoxicity and apoptotic cell death in oxidative stress status [25,26]. ...
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Full-text available
Background Traumatic brain injury (TBI) is one of the major health and socioeconomic problems in the world. Immune-enhancing enteral formula has been proven to significantly reduce infection rate in TBI patient. One of the ingredients that can be used in immunonutrition formulas to reduce inflammation and oxidative stress is pycnogenol. Objective surveying the effect of pycnogenol on the clinical, nutritional and inflammatory status of TBI patients. Methods This is double-blind, randomized controlled trial. Block randomization are used. Intervention group will receive pycnogenol supplement 150 mg for 10 days. Control group will receive placebo for the same duration. Inflammatory status (IL-6, IL- 1β, C-reactive protein, IL-10) and oxidative stress status (Malondialdehyde, total antioxidant capacity), at the base line, at the 5th day and at the end of the study (10th day) are measured. Clinical and nutritional status will be assessed three times during the intervention. SOFA (sequential organ failure assessment) questionnaire for assessment of organ failure filled out every other day. The mortality rate will be asked within 28 days of the start of the intervention. Weight, body mass index and body composition are measured. All analyses will be conducted by initially assigned study arm in an intention-to-treat analysis. Discussion we will expect supplementation of 150 mg pycnogenol improves clinical and nutritional status of the TBI patients and reduces inflammation and oxidative stress in the 10 days of intervention.
Article
Objective This study aimed to evaluate the efficacy of Pycnogenol (PYC) and its antioxidant and antiapoptotic effect in an experimental hypoxic-ischemic (HI) rat model. Study Design A total of 24 Wistar albino rats who were on the seventh postnatal day were divided into three groups with developed HI brain injury model under the sevoflurane anesthesia: 40 mg/kg PYC was given to Group A, saline was given to Group B, and the sham group was Group C. Neuronal apoptosis was investigated by terminal deoxynucleotidyl transferase dUTP nick end labeling and immunohistochemically stained manually with primer antibodies of tumor necrosis factor-α and interleukin-1β. Results The neuronal cell injury was statistically lower in the PYC treatment group. Conclusion This is the first study that investigates the role of PYC in the HI brain injury model. PYC reduces apoptosis and neuronal injury in the cerebral tissue of the rats. PYC may be a protective agent against hypoxic-ischemic encephalopathy. Key Points
Article
Background: Pine bark (Pinus spp.) extract is rich in bioflavonoids, predominantly proanthocyanidins, which are antioxidants. Commercially-available extract supplements are marketed for preventing or treating various chronic conditions associated with oxidative stress. This is an update of a previously published review. Objectives: To assess the efficacy and safety of pine bark extract supplements for treating chronic disorders. Search methods: We searched three databases and three trial registries; latest search: 30 September 2019. We contacted the manufacturers of pine bark extracts to identify additional studies and hand-searched bibliographies of included studies. Selection criteria: Randomised controlled trials (RCTs) evaluating pine bark extract supplements in adults or children with any chronic disorder. Data collection and analysis: Two authors independently assessed trial eligibility, extracted data and assessed risk of bias. Where possible, we pooled data in meta-analyses. We used GRADE to evaluate the certainty of evidence. Primary outcomes were participant- and investigator-reported clinical outcomes directly related to each disorder and all-cause mortality. We also assessed adverse events and biomarkers of oxidative stress. Main results: This review included 27 RCTs (22 parallel and five cross-over designs; 1641 participants) evaluating pine bark extract supplements across 10 chronic disorders: asthma (two studies; 86 participants); attention deficit hyperactivity disorder (ADHD) (one study; 61 participants), cardiovascular disease (CVD) and risk factors (seven studies; 338 participants), chronic venous insufficiency (CVI) (two studies; 60 participants), diabetes mellitus (DM) (six studies; 339 participants), erectile dysfunction (three studies; 277 participants), female sexual dysfunction (one study; 83 participants), osteoarthritis (three studies; 293 participants), osteopenia (one study; 44 participants) and traumatic brain injury (one study; 60 participants). Two studies exclusively recruited children; the remainder recruited adults. Trials lasted between four weeks and six months. Placebo was the control in 24 studies. Overall risk of bias was low for four, high for one and unclear for 22 studies. In adults with asthma, we do not know whether pine bark extract increases change in forced expiratory volume in one second (FEV1) % predicted/forced vital capacity (FVC) (mean difference (MD) 7.70, 95% confidence interval (CI) 3.19 to 12.21; one study; 44 participants; very low-certainty evidence), increases change in FEV1 % predicted (MD 7.00, 95% CI 0.10 to 13.90; one study; 44 participants; very low-certainty evidence), improves asthma symptoms (risk ratio (RR) 1.85, 95% CI 1.32 to 2.58; one study; 60 participants; very low-certainty evidence) or increases the number of people able to stop using albuterol inhalers (RR 6.00, 95% CI 1.97 to 18.25; one study; 60 participants; very low-certainty evidence). In children with ADHD, we do not know whether pine bark extract decreases inattention and hyperactivity assessed by parent- and teacher-rating scales (narrative synthesis; one study; 57 participants; very low-certainty evidence) or increases the change in visual-motoric coordination and concentration (MD 3.37, 95% CI 2.41 to 4.33; one study; 57 participants; very low-certainty evidence). In participants with CVD, we do not know whether pine bark extract decreases diastolic blood pressure (MD -3.00 mm Hg, 95% CI -4.51 to -1.49; one study; 61 participants; very low-certainty evidence); increases HDL cholesterol (MD 0.05 mmol/L, 95% CI -0.01 to 0.11; one study; 61 participants; very low-certainty evidence) or decreases LDL cholesterol (MD -0.03 mmol/L, 95% CI -0.05 to 0.00; one study; 61 participants; very low-certainty evidence). In participants with CVI, we do not know whether pine bark extract decreases pain scores (MD -0.59, 95% CI -1.02 to -0.16; one study; 40 participants; very low-certainty evidence), increases the disappearance of pain (RR 25.0, 95% CI 1.58 to 395.48; one study; 40 participants; very low-certainty evidence) or increases physician-judged treatment efficacy (RR 4.75, 95% CI 1.97 to 11.48; 1 study; 40 participants; very low-certainty evidence). In type 2 DM, we do not know whether pine bark extract leads to a greater reduction in fasting blood glucose (MD 1.0 mmol/L, 95% CI 0.91 to 1.09; one study; 48 participants;very low-certainty evidence) or decreases HbA1c (MD -0.90 %, 95% CI -1.78 to -0.02; 1 study; 48 participants; very low-certainty evidence). In a mixed group of participants with type 1 and type 2 DM we do not know whether pine bark extract decreases HbA1c (MD -0.20 %, 95% CI -1.83 to 1.43; one study; 67 participants; very low-certainty evidence). In men with erectile dysfunction, we do not know whether pine bark extract supplements increase International Index of Erectile Function-5 scores (not pooled; two studies; 147 participants; very low-certainty evidence). In women with sexual dysfunction, we do not know whether pine bark extract increases satisfaction as measured by the Female Sexual Function Index (MD 5.10, 95% CI 3.49 to 6.71; one study; 75 participants; very low-certainty evidence) or leads to a greater reduction of pain scores (MD 4.30, 95% CI 2.69 to 5.91; one study; 75 participants; very low-certainty evidence). In adults with osteoarthritis of the knee, we do not know whether pine bark extract decreases composite Western Ontario and McMaster Universities Osteoarthritis Index scores (MD -730.00, 95% CI -1011.95 to -448.05; one study; 37 participants; very low-certainty evidence) or the use of non-steroidal anti-inflammatory medication (MD -18.30, 95% CI -25.14 to -11.46; one study; 35 participants; very low-certainty evidence). We do not know whether pine bark extract increases bone alkaline phosphatase in post-menopausal women with osteopenia (MD 1.16 ug/L, 95% CI -2.37 to 4.69; one study; 40 participants; very low-certainty evidence). In individuals with traumatic brain injury, we do not know whether pine bark extract decreases cognitive failure scores (MD -2.24, 95% CI -11.17 to 6.69; one study; 56 participants; very low-certainty evidence) or post-concussion symptoms (MD -0.76, 95% CI -5.39 to 3.87; one study; 56 participants; very low-certainty evidence). For most comparisons, studies did not report outcomes of hospital admissions or serious adverse events. Authors' conclusions: Small sample sizes, limited numbers of RCTs per condition, variation in outcome measures, and poor reporting of the included RCTs mean no definitive conclusions regarding the efficacy or safety of pine bark extract supplements are possible.
Article
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Extracts from pine tree bark containing a variety of flavonoids have been used in traditional medicine. Pycnogenol is a proprietary bark extract of the French maritime pine tree (Pinus pinaster ssp. atlantica) that exerts antioxidative, anti-inflammatory, and anti-platelet effects. However, the effects of Pycnogenol on endothelial dysfunction, a precursor of atherosclerosis and cardiovascular events, remain still elusive. Twenty-three patients with coronary artery disease (CAD) completed this randomized, double-blind, placebo-controlled cross-over study. Patients received Pycnogenol (200 mg/day) for 8 weeks followed by placebo or vice versa on top of standard cardiovascular therapy. Between the two treatment periods, a 2-week washout period was scheduled. At baseline and after each treatment period, endothelial function, non-invasively assessed by flow-mediated dilatation (FMD) of the brachial artery using high-resolution ultrasound, biomarkers of oxidative stress and inflammation, platelet adhesion, and 24 h blood pressure monitoring were evaluated. In CAD patients, Pycnogenol treatment was associated with an improvement of FMD from 5.3 ± 2.6 to 7.0 ± 3.1 (P < 0.0001), while no change was observed with placebo (5.4 ± 2.4 to 4.7 ± 2.0; P = 0.051). This difference between study groups was significant [estimated treatment effect 2.75; 95% confidence interval (CI): 1.75, 3.75, P < 0.0001]. 15-F(2t)-Isoprostane, an index of oxidative stress, significantly decreased from 0.71 ± 0.09 to 0.66 ± 0.13 after Pycnogenol treatment, while no change was observed in the placebo group (mean difference 0.06 pg/mL with an associated 95% CI (0.01, 0.11), P = 0.012]. Inflammation markers, platelet adhesion, and blood pressure did not change after treatment with Pycnogenol or placebo. This study provides the first evidence that the antioxidant Pycnogenol improves endothelial function in patients with CAD by reducing oxidative stress.
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Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30
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We investigated benefits of Pycnogenol(R) as an adjunct to hypotensive medication in metabolic syndrome patients with micro-albuminurea. Fifty eight patients were treated with Ramipril and a subgroup received Pycnogenol in addition for six months. Colour Doppler duplex ultrasound was employed for cortical flow measurements. Blood pressure decreased with Ramipril from 188.8/95.2 to 128.2/90.2, with additional Pycnogenol from 189.3/97.2 to 122.2/85.3 (P<0.05). Kidney function improved in both groups, with 24 hour urinary albumin decreasing from 88.8 to 68.9 mg with Ramipril and from 89.3 to 42.2 mg with additional Pycnogenol (P<0.05). In both groups treatment lowered serum creatinine, with combination treatment being significantly more effective. Cortical flow velocities significantly increased with Ramipril from systolic 17.2 +/- 3.1 to 23.8 +/- 2.0 cms-1 and diastolic 4.2+/-2.8 to 2.0+/-3.1 cms-1. The addition of Pycnogenol was more effective, improving cortical flow from systolic 18.2+/-2.2 to 27.2+/-2.9 cms-1 and diastolic 4.1+/-2.2 to 9.8+/-2.1 cms-1 (P>0.05). C-reactive protein (CRP) levels decreased marginally with Ramipril, but significantly with Pycnogenol from 2.17 to 1.62 mg/dL. Pycnogenol significantly lowered fasting blood glucose to 102.3 +/- 11.2 mg/mL and HbA1c to 6.9 +/- 0.3 %. The Pycnogenol group showed a significantly lowered BMI, from baseline 26.5+/-0.9 to 25.0+/-1.2 kgm-2, without reaching statistical significance versus control. Only a limited improvement of blood lipid profile was found in both groups. Pycnogenol should be further investigated for kidney function.
Article
The inhibitory effects of a procyanidin containing extract from the bark of Pinus pinaster Sol. and its fractions on the angiotensin converting enzyme (ACE) in vitro were studied. The extract and all three fractions showed a significant inhibitory action on this enzyme in a dose-dependent manner. The IC50 value of the extract was 34,7 μg/ml and of the most active fraction containing oligomeric procyanidins 2,7 μg/ml. Investigations in vivo showed a significant decrease of blood pressure after intravenous administration to Sprague-Dawley rats also in a dose-dependent manner. It is assumed that this hypotensive action is due to a strong inhibitory effect of procyanidins on the angiotensin converting enzyme in a non-competitive manner.
Article
The present review provides an update of the biological actions of Pycnogenol® in the treatment of metabolic syndrome and related disorders such as obesity, dyslipidaemia, diabetes and hypertension. Pycnogenol® is a French maritime pine bark extract produced from the outer bark of Pinus pinaster Ait. Subsp. atlantica. Its strong antioxidant, antiinflammatory, endothelium-dependent vasodilator activity, and also its anti-thrombotic effects make it appropriate for targeting the multifaceted pathophysiology of metabolic syndrome. Clinical studies have shown that it can reduce blood glucose levels in people with diabetes, blood pressure in mild to moderate hypertensive patients, and waist circumference, and improve lipid profile, renal and endothelial functions in metabolic syndrome. This review highlights the pathophysiology of metabolic syndrome and related clinical research findings on the safety and efficacy of Pycnogenol®. The results of clinical research studies performed with Pycnogenol® are discussed using an evidence-based, target-oriented approach following the pathophysiology of individual components as well as in metabolic syndrome overall. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
Article
Aim: This registry study aimed to evaluate the effects of supplementation with pycnogenol on altered endothelial function (EF) in borderline hypertensive, hyperlipidemic and hyperglycemic subjects without atherosclerotic changes in their main arteries and no coronary artery disease. Methods: Flow mediated dilatation (FMD) and endothelium-independent (EID) dilatation were measured with brachial ultrasound after occlusion. Also, after occlusion, laser Doppler (LDF) flux and distal straingauge flow were measured. Oxidative stress (oxstress) was evaluated at 8 and 12 weeks. 93 subjects with borderline symptoms were enrolled into the study: 32 hypertensives, 31 hyperlipidemics, 30 hyperglycemics. All participants were instructed to follow the best available management to control their symptoms. In addition to best management, half of the subjects in each group used 150 mg/day Pycnogenol(®). 31 normal subjects were included as control. Results: After 12 weeks metabolic values and blood pressure were back to normal in all subjects. Values were slightly better under Pycnogenol(®). FMD increased after 8 weeks from an average 5.3;3.4% to 8.2;2.2% with a further increase to 8.8;3.1% (P<0.05) at 12 weeks. No effects were found in controls and normal subjects. EID of normal subjects was consistently higher with 26%. LDF skin flux increased with Pycnogenol(®) at 8 weeks and 12 weeks. The final flux increase was not different from normal values. In controls flux after occlusion was not improved at 8 weeks; there was a significant but minor increase at 12 weeks. Flux increases were superior in all Pycnogenol(®) subjects. In Pycnogenol(®) subjects, limb flow after occlusion increased at 8 weeks with a further increase at 12 weeks. In controls inclusion flow after occlusion was comparable at 8 and 12 weeks. Oxidative stress was significantly decreased in Pycnogenol(®) subjects at 8 and 12 weeks. Minor differences were observed in controls. Conclusion: This open registry study indicates that Pycnogenol(®) improves EF in preclinical, borderline subjects in a macro-microcirculatory model. This observation may suggest an important preventive possibility for borderline hypertensive, hyperglycemic and hyperlipidemic subjects.
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C-reactive protein (CRP), the prototypical acute-phase reactant, is one of the most widely known biomarkers of cardiovascular disease. Circulating levels of CRP are clinically used to predict the occurrence of cardiovascular events and to aide in the selection of therapies based on more accurate risk assessment in individuals who are at intermediate risk. This paper reviews the role of CRP in hypertension. In hypertensive individuals, CRP levels associate with vascular stiffness, atherosclerosis and the development of end-organ damage and cardiovascular events. Data suggest that some anti-hypertensive medications may lower CRP levels in a manner independent of their effect on blood pressure. In individuals who are normotensive at baseline, CRP levels have been shown in multiple cohorts to foretell the development of hypertension on follow-up. Whether genetic variability that influences circulating levels of CRP independent of environmental and behavioral factors can also be used in a similar manner to predict the change in blood pressure and development of hypertension is controversial. In addition to its role as a biomarker, experimental studies have unraveled an active direct participation of CRP in the development of endothelial dysfunction, vascular stiffness and elevated blood pressure. CRP has also been implicated as a mediator of vascular remodeling in response to injury and cardiac remodeling in response to pressure overload. Emerging data may reveal novel vascular inflammatory pathways and identify new targets for treatment of vascular pathology.Journal of Human Hypertension advance online publication, 14 November 2013; doi:10.1038/jhh.2013.111.
Article
Background: Pycnogenol is a bark extract from the French maritime pine (Pinus pinaster) consisting of a mixture of bioflavonoids. Bioflavonoids are also components of a wide variety of edible plants, fruits, and vegetables and act as antioxidants and iron chelators. Pycnogenol is a mixture of water-soluble procyanidins, catechin, taxifolin, and phenolcarbonic acids. It has been used as a dietary supplement for years. Hypertension, or a blood pressure higher than 140/90 mm Hg, is the most common risk factor for cardiovascular and cerebrovascular morbidity and mortality.Purpose: The aim of the study was to test a possible protective effect of oral Pycnogenol, administrated for eight weeks to non-smoking, mildly hypertensive patients.Methods: Pycnogenol, 200 mg/day, or placebo was provided to eleven subjects (seven men and four women) with systolic blood pressure of 140–159 mm Hg in a double blind, randomized, cross-over study and/or diastolic blood pressure of 90–99 mm Hg for eight weeks. The subject’s blood pressure was taken during supplementation, and the serum level of thromboxane was measured.Results: A significant decrease in the systolic blood pressure was observed during Pycnogenol supplementation. However, Pycnogenol’s lowering of diastolic blood pressure did not reach statistical significance when compared to placebo. Serum thromboxane concentration was significantly (p < 0.05) decreased during Pycnogenol supplementation.Conclusion: Supplementation of Pycnogenol is effective in decreasing systolic blood pressure in mildly hypertensive patients.
Article
This open, controlled study evaluated the effects of 6 month supplementation with Pycnogenol® maritime pine bark extract on health risk factors in subjects with metabolic syndrome. Pycnogenol® was used with the aim of improving risk factors associated with metabolic syndrome, central obesity, elevated triglycerides (TG), low HDL cholesterol, high blood pressure and fasting blood glucose. Sixty-four subjects (range 45-55 years) presenting with all five risk factors of metabolic syndrome were included, and Pycnogenol® was administered for 6 months. A group of 66 equivalent subjects were followed up as controls. In the 6-month study Pycnogenol® supplementation 150 mg/day decreased waist circumference, TG levels, blood pressure and increased the HDL cholesterol levels in subjects. Pycnogenol lowered fasting glucose from baseline 123 ± 8.6 mg/dl to 106.4 ± 5.3 after 3 months and to 105.3 ± 2.5 at the end of the study (p < 0.05 vs controls). Men's waist circumference decreased with Pycnogenol from 106.2 ± 2.2 cm to 98.8 ± 2.3 cm and to 98.3 ± 2.1 after 3 and 6 months. Women's waist decreased from 90.9 ± 1.6 cm to 84.6 ± 2.1 cm and to 83.6 ± 2.2 cm after 3 and 6 months. Both genders waist circumference reduction was significant as compared to controls at both time points. In addition, plasma free radicals decrease in the Pycnogenol group was more effective than in the control group (-34.6%; p < 0.05). In conclusion, this study indicates a role for Pycnogenol® for improving health risk factors in subjects with metabolic syndrome. Copyright © 2013 John Wiley & Sons, Ltd.