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Effects of Dietary Flaxseed Lignan Extract on Symptoms of Benign Prostatic Hyperplasia

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A flaxseed lignan extract containing 33% secoisolariciresinol diglucoside (SDG) was evaluated for its ability to alleviate lower urinary tract symptoms (LUTS) in 87 subjects with benign prostatic hyperplasia (BPH). A randomized, double-blind, placebo-controlled clinical trial with repeated measurements was conducted over a 4-month period using treatment dosages of 0 (placebo), 300, or 600 mg/day SDG. After 4 months of treatment, 78 of the 87 subjects completed the study. For the 0, 300, and 600 mg/day SDG groups, respectively, the International Prostate Symptom Score (IPSS) decreased -3.67 +/- 1.56, -7.33 +/- 1.18, and -6.88 +/- 1.43 (mean +/- SE, P = .100, < .001, and < .001 compared to baseline), the Quality of Life score (QOL score) improved by -0.71 +/- 0.23, -1.48 +/- 0.24, and -1.75 +/- 0.25 (mean +/- SE, P = .163 and .012 compared to placebo and P = .103, < .001, and < .001 compared to baseline), and the number of subjects whose LUTS grade changed from "moderate/severe" to "mild" increased by three, six, and 10 (P = .188, .032, and .012 compared to baseline). Maximum urinary flows insignificantly increased 0.43 +/- 1.57, 1.86 +/- 1.08, and 2.7 +/- 1.93 mL/second (mean +/- SE, no statistical significance reached), and postvoiding urine volume decreased insignificantly by -29.4 +/- 20.46, -19.2 +/- 16.91, and -55.62 +/- 36.45 mL (mean +/- SE, no statistical significance reached). Plasma concentrations of secoisolariciresinol (SECO), enterodiol (ED), and enterolactone (EL) were significantly raised after the supplementation. The observed decreases in IPSS and QOL score were correlated with the concentrations of plasma total lignans, SECO, ED, and EL. In conclusion, dietary flaxseed lignan extract appreciably improves LUTS in BPH subjects, and the therapeutic efficacy appeared comparable to that of commonly used intervention agents of alpha1A-adrenoceptor blockers and 5alpha-reductase inhibitors.
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JOURNAL OF MEDICINAL FOOD
J Med Food 11 (2) 2008, 000–000
© Mary Ann Liebert, Inc. and Korean Society of Food Science and Nutrition
DOI: 10.1089/jmf.2007.602
Effects of Dietary Flaxseed Lignan Extract on Symptoms of
Benign Prostatic Hyperplasia
Wei Zhang,
1
Xiaobing Wang,
1
Yi Liu,
1
Haimei Tian,
1
Brent Flickinger,
2
Mark W. Empie,
2
and Sam Z. Sun
2
ABSTRACT A flaxseed lignan extract containing 33% secoisolariciresinol diglucoside (SDG) was evaluated for its ability
to alleviate lower urinary tract symptoms (LUTS) in 87 subjects with benign prostatic hyperplasia (BPH). A randomized, dou-
ble-blind, placebo-controlled clinical trial with repeated measurements was conducted over a 4-month period using treatment
dosages of 0 (placebo), 300, or 600 mg/day SDG. After 4 months of treatment, 78 of the 87 subjects completed the study.
For the 0, 300, and 600 mg/day SDG groups, respectively, the International Prostate Symptom Score (IPSS) decreased 3.67
1.56, 7.33 1.18, and 6.88 1.43 (mean SE, P .100, .001, and .001 compared to baseline), the Quality of Life
score (QOL score) improved by 0.71 0.23, 1.48 0.24, and 1.75 0.25 (mean SE, P .163 and .012 compared
to placebo and P .103, .001, and .001 compared to baseline), and the number of subjects whose LUTS grade changed
from “moderate/severe” to “mild” increased by three, six, and 10 (P .188, .032, and .012 compared to baseline). Maximum
urinary flows insignificantly increased 0.43 1.57, 1.86 1.08, and 2.7 1.93 mL/second (mean SE, no statistical sig-
nificance reached), and postvoiding urine volume decreased insignificantly by 29.4 20.46, 19.2 16.91, and 55.62
36.45 mL (mean SE, no statistical significance reached). Plasma concentrations of secoisolariciresinol (SECO), enterodiol
(ED), and enterolactone (EL) were significantly raised after the supplementation. The observed decreases in IPSS and QOL
score were correlated with the concentrations of plasma total lignans, SECO, ED, and EL. In conclusion, dietary flaxseed lig-
nan extract appreciably improves LUTS in BPH subjects, and the therapeutic efficacy appeared comparable to that of com-
monly used intervention agents of 1A-adrenoceptor blockers and 5-reductase inhibitors.
KEY WORDS:
benign prostatic hyperplasia
enterodiol
enterolactone
flaxseed
lignan
lower urinary tract
symptoms
secoisolariciresinol diglucoside
1
INTRODUCTION
B
ENIGN PROSTATIC HYPERPLASIA
(BPH) is a physiological/
pathological phenomenon widely occurring in the older
male population. BPH is the most common cause of lower
urinary tract symptoms (LUTS) mainly clinically manifested
as urinary blockage and storage. BPH subjects are often
physically bothered by and psychologically burdened from
the symptoms. One commonly accepted mechanism caus-
ing BPH is an imbalance of testosterone and dihydrotestos-
terone in the circulation and/or prostate tissue. Usually, in
patients of pre-BPH or BHP, the enzyme 5-reductase (5R)
excessively catalyzes dihydrotestosterone production from
testosterone, and dihydrotestosterone stimulates prostate tis-
sue proliferation via binding with -adrenergic receptors.
This mechanism has been previously reviewed by Andriole
et al.,
1
Tahmatzopoulos et al.,
2
and Anglin et al.
3
Natural plant compounds containing estrogenic activity
have been investigated for their influence on various hor-
monally sensitive end points. The class of phytoestrogens,
consisting of hydroxylated bicyclobenzylbutane diol deriv-
atives, also known as lignans, has been observed epidemi-
ologically to be correlated with reductions in prostate can-
cer incidence.
4,5
Flaxseed and flaxseed derivatives are one
of the richest dietary sources of plant lignans, with the prin-
cipal one being secoisolariciresinol (SECO), found naturally
as the diglycoside (secoisolariciresinol diglucoside [SDG]).
Recently, flaxseed is increasingly used in the human diet be-
cause of its potential benefits, including cardiovascular pro-
tection
6–8
and prostate health enhancement.
9,10
The concen-
trations of SDG in flaxseed vary with its different cultivars.
Eliasson et al.
11
reported that SDG concentrations in 27
flaxseed species ranged from 1.19% to 2.59% for ()-SDG
and 0.22% to 0.5% (wt/wt) for its diastereoisomer, (-)-SDG.
Westcott et al.
12
presented a range of SDG concentrations
from 0.97% to 3.09% (wt/wt) in eight varieties of defatted
flaxseed meals. The SDG metabolites, enterodiol (ED) and
enterolactone (EL), can weakly bind to estrogen receptors,
1
Tumor Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union
Medical College, Beijing, People’s Republic of China; and
2
James R. Randall Research
Center of Archer Daniels Midland Company, Decatur, Illinois
Manuscript received 26 September 2007. Revision accepted 26 December 2007.
Address reprint requests to: Sam Z. Sun, Ph.D., James R. Randall Research Center, Archer
Daniels Midland Company, 1001 Brush College Road, Decatur, Illinois 62521,USA,
E-mail: sun@admworld.com
and isoflavones together with SDG represent commonly
consumed phytoestrogens in the human diet.
It has been documented that the SDG metabolites, ED
and EL, can inhibit 5R.
13
Thus, supplementation with a lig-
nan-rich flaxseed extract may help to relieve LUTS in BPH
subjects. Currently, there have been no peer-reviewed re-
ports describing the use of flaxseed lignan extract to treat
BPH subjects. We conducted this clinical trial using a lig-
nan-rich extract (consisting of one-third SDG) to investigate
its effects on the clinical symptoms in BPH subjects. Plasma
lignan concentrations of SECO, ED, and EL were measured
and correlated with the treatment effects on LUTS.
MATERIALS AND METHODS
Study design
Eighty-seven Chinese men diagnosed with BPH, 55–80
years old, were included in this randomized, placebo-con-
trolled, double-blind clinical study. Eligible subjects had
prostate volume of 30 cm
3
, an International Prostate
Symptom Score (IPSS) of 7 points, and a maximal uri-
nary flow rate (Q
max
) between 5 and 15 mL/second and were
not sensitive or allergic to flax. Subjects also had normal
serum -glutamyl transferase and alanine aminotransferase
values, serum creatinine 110 mol/L, and blood urea ni-
trogen 7.1 mg/dL. Subjects were not to have used any
drugs, herbs, flax-containing products, or other nonpre-
scription preparations for treating BPH-related symptoms
within 4 weeks of screening. Each subject, who met the cri-
teria and agreed to participate in the study, carefully read
and signed the consent form.
Eighty-seven subjects were randomly assigned into the 0
mg (placebo), 300 mg, or 600 mg/day SDG groups (n 29
in each). Daily dosage was delivered by administering two
tablets at breakfast and two at dinner (two tablets 2 times).
Subjects were counseled not to change their regular dietary
patterns and physical activities. All subjects were requested
to revisit the clinic monthly. At the time of each return, any
concerns and any adverse reactions were recorded, and treat-
ment tablets were refilled. At baseline and the end of months
2 and 4, a 20-mL blood sample was drawn following an
overnight fast. Compliance was evaluated by subject in-
quiry, tablet counts, and plasma lignan concentrations. The
study protocol was approved by the Clinical Trial Evalua-
tion Board of the Tumor Hospital and Institute in Beijing,
People’s Republic of China.
Study material
The flaxseed lignan extract, containing approximately
33.0% SDG, 15.1% coumaric acid glucoside, 8.1% ferulic
acid glucoside, 15.6% hydroxymethylglutaric acid, and the
rest water and other components (Beneflax™, Archer
Daniels Midland Co., Decatur, IL), was formulated to de-
liver the targeted daily SDG doses in four tablets (each tablet
contains 0, 75, or 150 mg of SDG). Placebo tablets con-
taining food-grade maltodextrin (combined with food grade
colors to approximate the color of the flaxseed extract) were
prepared to match the size, shape, and color of SDG-con-
taining tablets. In addition to flaxseed lignan extract or
placebo material, tablets were formulated with commonly
used excipient ingredients. Prepared tablets were analyzed
for SDG content and then released to the study upon con-
firmation of appropriate SDG levels.
Clinical examination and measurements
Demographic information of age, medical history, mar-
riage status, occupation, education level, and current med-
ications were noted. Biochemical measurements, including
plasma total cholesterol, triglyceride, glucose, blood urea ni-
trogen, creatinine, alanine aminotransferase, and -glutamyl
transferase, were determined using standard laboratory
methods and relevant experimental kits (Roche Diagnostics,
Indianapolis, IN). Clinical evaluations included genitouri-
nary tract physical examination, prostate digital rectal ex-
amination, urine bacterial count, urination data (such as
maximal and mean urinary flow rate using Dynamic
Uroflowometry [model ZNC-961A, Weixin Electronics,
Chengdo, People’s Republic of China]), and prostate and
bladder volume (using a Philips HDI 5000 Ultrasonic Di-
agnostic System, Bothell, WA). The residual volume of
urine was calculated by differences between initial bladder
urine volume and voided volume. Data on IPSS and Qual-
ity of Life score (QOL score) were collected using standard
questionnaire forms (2003 American Urology Association
Guideline on the Management of BPH: Diagnosis and Treat-
ment Recommendations). For the IPSS, seven questions re-
lated to urinary symptoms were asked, and scores from 0 to
5 were given for each question (the higher score, the worse
symptoms). For QOL scores, only one question was asked.
The question and its scoring are: If you were to spend the
rest of your life with your urinary condition just the way it
is now, how would you feel about that? Score 0 is for “De-
lighted,” 1 for “Pleased,” 2 for “Mostly satisfied,” 3 for
“Mixed,” 4 for “Mostly dissatisfied,” 5 for “Unhappy,” and
6 for “Terrible.” Like the IPSS, the higher the score for QOL,
the worse the quality of life, and vice versa. Based on the
grading criteria of the American Urological Association for
BPH symptom, subjects with IPSS of 7 were considered
as having a mild grade of LUTS, 8–19 were considered as
having moderate grade, and 20 as having a severe grade
of LUTS. Safety evaluation for the treatment was based on
a questionnaire aimed to monitor adverse events, including
vertigo, headache, fatigue, constipation, nausea, vomiting,
abdominal pain, rashes, digestive abnormality, and sexual
dysfunction. LUTS, blood biochemistry, SECO, ED, and EL
were determined at baseline and the end of months 2 and 4.
Plasma SECO, ED, and EL measurements were deter-
mined using a liquid chromatography/tandem mass spec-
trometry method (model 1100 liquid chromatograph [Agi-
lent, Palo Alto, CA] and model 14000 mass spectrometer
[Applied Biosystems, Foster City, CA]).
14
Briefly, a 100-
2 ZHANG ET AL.
L plasma sample was mixed with 100 L of
-glu-
curonidase (containing 1,200 units of the enzyme activity),
the sample was incubated for 24 hours at 37°C, and after
400 L of ethyl acetate was added, the test tube was vor-
tex-mixed for 3 minutes. The sample mixture was further
centrifuged for 2 minutes at 170 g, and the upper ethyl ac-
etate layer was collected and dried under N
2
. One hundred
microliters of high-performance liquid chromatography sol-
vent (methanol/ammonium acetate [5 mmol/L], 70:30) was
added to dissolve the dried material. A 5-L sample was in-
jected into the liquid chromatography/tandem mass spec-
trometry system. The recovery rates of the method ranged
from 79% to 105.6% with coefficients of variations
19.4%. The lower detection limits for plasma SECO, ED,
and EL were 5, 1, and 1 ng/mL, respectively.
Statistical analysis
Some variables measured in this study were scored, or-
dinal, or non-normally distributed. Consequently, where ap-
propriate, changes from baseline values were used in statis-
tical analysis. After descriptive statistics, Mixed Model pro-
cedures were used to test the proposed treatment effects on
changes of LUTS-related measurements (including IPSS,
QOL, Q
max
, residual volume of urine, and prostate volumes)
using the data of the placebo group as reference (Dunnett
adjustment). The response variation of individual subjects
to the treatment was considered as a random factor, and the
time point by month of the measurements was regarded as
a repeated factor. General Linear Model procedures were
used to test the treatment effects within subjects, and base-
line data were used as a comparative reference. The changes
in number of subjects having mild symptom between and
within groups after treatment were compared using
2
or
Fisher’s exact statistics. Concentration changes of plasma
SECO, ED, EL, and total lignans were also compared be-
tween and within subjects. The data of plasma lignan con-
centrations were non-normally distributed (right-skewed).
The data were therefore logarithm-transformed into ap-
proximately normal distribution before analysis. Moreover,
DIETARY FLAXSEED LIGNAN EXTRACT AND BPH 3
T
ABLE
1. B
ASELINE
C
HARACTERISTICS OF
S
UBJECTS
Treatment
SDG 0 mg (n 24) SDG 300 mg (n 29) SDG 600 mg (n 25)
Age (years) 69.67 0.94 70.73 1.08 67.52 1.01
BMI (kg/m
2
) 24.05 0.43 24.12 0.44 25.37 0.63
TC (mmol/L) 4.70 0.17 4.66 0.12 4.61 0.17
TG (mmol/L) 1.65 0.18 1.54 0.12 1.64 0.26
Glucose (mmol/L) 5.11 0.23 5.13 0.25 5.86 0.63
IPSS 18.25 1.28 19.24 1.14 19.21 1.16
QOL score 3.79 0.12 4.07 0.13 4.00 0.14
Q
max
(mL/second) 11.26 1.47 11.54 1.14 10.82 1.10
Residual volume of urine (mL) 153.71 22.65 140.79 23.16 203.30 40.19
Prostate volume (mL) 41.01 2.35 42.67 2.32 46.66 3.73
ALT (U/L) 20.04 1.91 24.13 3.31 23.60 2.26
GGT (U/L) 29.83 1.82 28.30 4.71 26.60 2.31
BUN (mmol/L) 6.14 0.37 5.90 0.23 5.93 0.29
Creatinine (mol/L) 77.29 3.07 82.70 2.66 79.72 3.59
Data are mean SE values. No statistical differences were observed between groups for the parameters measured. ALT, ala-
nine aminotransferase; BMI, body mass index; BUN, blood urea nitrogen; GGT, -glutamyl transferase; TC, total cholesterol; TG,
triacylglycerol.
T
ABLE
2. S
UMMARY OF
T
REATMENT
E
FFECTS OF
F
LAXSEED
L
IGNAN ON
LUTS
IN
BPH S
UBJECTS
0 mg SDG (n 24) 300 mg SDG (n 29) 600 mg SDG (n 25)
Variable 2 months 4 months 2 months 4 months 2 months 4 months
IPSS 6.0 1.55* 3.67 1.56 4.97 1.32** 7.33 1.18** 7.0 1.41** 6.88 1.43**
QOL score 0.91 0.23* 0.71 0.23 1.34 0.18** 1.48 0.24*** 1.79 0.23
a,
*** 1.75 0.25
b,
***
Q
max
(mL/second) 1.0 1.53 0.43 1.57 0.29 1.13 1.86 1.08** 2.0 1.17 2.7 1.93
Residual volume (mL) 48 31.39 29.4 20.46 7.1 21.07 19.2 16.91 76.1 23.68* 55.62 36.45
Prostate volume (mL) 5.65 1.05** 5.39 0.92** 3.59 1.25* 6.46 1.2** 6.26 1.54** 6.6 1.22**
Subjects with IPSS 7 4 4 4 7* 7* 10**
Data are mean SE values for the differences of data at month 2 or 4 minus baseline data. A patient with IPSS 7 is considered to have mild LUTS.
At baseline, the numbers of subjects with mild symptoms in each group were 1.
Compared to placebo,
a
P .05,
b
P .01; compared to baseline, *P .05, **P .01, ***P .001.
correlations between the changes of IPSS, QOL, and Q
max
and plasma lignan concentrations were determined. A sta-
tistical value of P .05 was considered as a statistical
threshold of significant difference. SAS software version 9.1
(SAS Institute, Cary, NC) was employed for data process
and analysis.
RESULTS
Seventy-eight of 87 subjects completed the study. Nine
subjects dropped out (four needed other treatment, two had
a heavy travel schedule, one relocated, and two did not give
a reason). The baseline demographic and clinical character-
istics of subjects are shown in Table 1. No statistical dif-
ference was noted between groups for the baseline data.
Table 2 shows the changes in IPSS, QOL, Q
max
, residual
volume, prostate volume, and the number of subjects hav-
ing mild LUTS. Plasma lignan concentrations and correla-
tions between the changes of LUTS and lignan concentra-
tions are reported in Tables 3 and 4.
As specified in Table 2, all three treatment groups had
significant IPSS decreases compared to baseline after 2
months (all P .001). However, after 4 months, only the
SDG treatment groups remained significantly different from
baseline. No statistically significant difference between
groups was obtained for IPSS decrease. For QOL score, an
overall significant treatment effect of SDG was observed
(P .007 for the model) between groups (Table 2). The ob-
served significance on QOL score mprovement was obtained
from the 600 mg SDG group (P .035 at month 2 and P
.012 at month 4 compared to the placebo, respectively). No
significant treatment effect was reached in the 300 mg SDG
group (P .175 compared to the placebo). Within both
SDG treatment groups, significant QOL score improvement
was observed at month 2 and 4 (compared to baseline, P
.01 or 0.001 either at month 2 or 4). Within the placebo
group, although QOL scores were also improved, the im-
proved values were smaller, and the statistical significance
only appeared at month 2 (P .05).
After 4 months, increases in Q
max
from baseline were
0.43 1.57, 1.86 1.08, and 2.7 1.93 mL/second
(mean SE, Table 2) in the placebo and 300 and 600 mg
SDG treatment groups, respectively. Although the Q
max
in-
creases (of 1.86 or 2.7 mL/second) would be clinically
meaningful, the large response variance and relatively small
sample size may have caused a lack of statistical signifi-
cance either between or within groups. Changes of residual
urine volume in bladder also showed no significant differ-
ence between or within groups. The variations of the data
are also large. Unexpectedly, prostate volumes were signif-
icantly reduced from baseline after 2 months of treatment
in all groups, and no statistical difference was observed be-
4 ZHANG ET AL.
T
ABLE
3. P
LASMA
L
IGNAN
C
ONCENTRATIONS
Concentration (ng/mL)
SDG Month Total lignan SECO ED EL
0 mg (n 24) 0 55.05 9.92 25.10 7.91 1.37 0.39 28.58 5.95
2 42.65 8.54 25.90 7.95 0.56 0.06 16.18 3.35
4 46.55 10.50 27.74 9.44 0.65 0.09 18.17 5.78
300 mg (n 29) 0 42.75 9.13 21.69 8.78 0.52 0.02 20.54 4.69
2 251.89 51.43 62.22 16.39 98.38 21.74 91.29 20.41
4 272.88 45.61 58.41 13.41 88.08 18.17 126.39 29.74
600 mg (n 25) 0 24.50 4.93 8.58 1.92 0.75 0.10 15.17 4.60
2 526.88 80.67 150.24 29.40 246.44 42.23 130.19 29.10
4 560.57 72.72 162.19 37.77 266.94 31.84 131.43 19.99
Data are mean SE values. Total lignan SECO ED EL. In the SDG treatment groups, all lignan concentrations significantly increased
either compared to placebo or baseline.
T
ABLE
4. S
PEARMAN
C
ORRELATIONS
B
ETWEEN
L
IGNAN
C
ONCENTRATIONS AND
LUTS R
ELIEF
Lignans SECO ED EL
IPSS
Correlation r 0.2878 0.2825 0.3266 0.1395
P value .0001 .0001 .0001 .0366
QOL score
Correlation r 0.4876 0.4187 0.5287 0.373
P value .0001 .0001 .0001 .0001
Q
max
Correlation r 0.1408 0.0639 0.1196 0.1653
P value .0424 .3592 .0854 .0171
changes from baseline values.
tween the treatment groups. And, it was noted that the SDG
treatment groups had more subjects whose LUTS grades
were reduced from moderate or severe to mild compared to
placebo at the end of 4 months (four in the placebo group,
seven in the 300 mg group, and 10 in the 600 mg group),
and only within-group statistical significances were reached
(P .05 and .01 compared to baseline, respectively) in
the SDG treatment groups (Table 2).
Table 3 gives the concentrations of plasma SECO, ED,
EL, and total lignan ( SECO ED EL) at baseline and
after 2 and 4 months of treatment. At baseline, the means
of total lignan concentrations among the three treatment
groups were relatively similar, from 24.5 to 55.05 ng/mL.
With flaxseed extract supplementation, concentrations of
SECO, ED, and EL all substantially increased compared to
placebo and baseline, and the profile of lignan distribution
changed from baseline. Among them, the increase of ED
concentration was proportionally greater than the others,
particularly with the higher dosing. The data indicate that
all three lignans can be absorbed into the circulation, and
lignan intake dose could influence the proportions of each
compound in plasma. Table 4 shows the correlations be-
DIETARY FLAXSEED LIGNAN EXTRACT AND BPH 5
FIG. 2. Comparison of treatment effect of drugs
and botanicals on maximum flow (Q
max
). Data are
from 1977 to 2007. Three classes of treatment agents
(AR blockers, 5R inhibitors, and botanicals) and two
kinds of clinical trials (placebo-controlled or non-
placebo) are included here. The Q
max
data are in-
creases from baseline. The green dots represent
non–placebo-controlled trials,
15,17–25,28–38
and the
red dots and circles represent placebo-controlled tri-
als.
42–49,51–60
The lines linking the red dots and cir-
cles indicate the treatment effects and correspond-
ing placebo effects. The data in blue are from the
current trial.
FIG. 1. Comparison of treatment effect of drugs and
botanicals on IPSS decrease. Data are from 1997 to
2007. Three classes of treatment agents (AR block-
ers, 5R inhibitors, and botanicals) and two kinds of
clinical trials (placebo-controlled or non-placebo) are
included here. The IPSS data are decreases from base-
line. The green dots represent non–placebo-controlled
trials,
15–41
and the red dots and circles represent
placebo-controlled trials.
42–60
The lines linking the
red dots and circles indicate the treatment effects and
corresponding placebo effects. The data in blue are
from the current trial.
tween plasma lignan concentrations and changes in IPSS,
QOL, and Q
max
expressed by Spearman correlation coeffi-
cients with corresponding P values. Total lignan, SECO, ED,
and EL were all significantly correlated with decreases of
IPSS and QOL score. And, only total lignan and EL were
significantly correlated with the increase of Q
max
.
No adverse effects were reported and no abnormal val-
ues of blood urea nitrogen, creatinine, alanine aminotrans-
ferase, and -glutamyl transferase were observed during the
entire study period.
DISCUSSION
LUTS is a common health problem resulting from BPH,
manifesting with daily physical and psychological burdens,
and yielding a lower QOL score. To date, considerable ef-
fort has been made on the development of effective inter-
vention agents for BPH using pharmaceutical approaches.
Currently, most commonly used noninvasive treatment
agents for BPH include 1A-adrenoceptor (AR) blockers,
5R inhibitors, and botanicals (such as saw palmetto extract).
Many clinical studies have investigated treatment effects of
these agents on BPH-linked LUTS; however, observed ef-
ficacies vary considerably. We surveyed treatment effects
on IPSS and Q
max
reported during the last 10 years and com-
pared them with the treatment result observed in this study
(Figs. 1 and 2). In general, the majority of trials were not
placebo-controlled. For those trials with placebo control, ob-
vious placebo effects exist, and in some trials, the effects of
active agent were similar to that of placebo.
Figure 1 shows the treatment effects of AR blockers, 5R
inhibitors, and botanicals on IPSS. Treatment efficacies are
expressed as IPSS decreases from baseline. For each treat-
ment agent, the IPSS decreases between placebo-controlled
and non-placebo trials are comparable. It seems that the
treatment of AR blockers could lower IPSS more efficiently
than did the other two types of agents, but it may not be true
because greater placebo effects also appeared in those AR-
blocker trials. The observed effect of the flaxseed lignan ex-
tract on improving IPSS in this study is similar to that of
AR blockers and other botanicals and appears to be more
effective than 5R inhibitors (Fig. 1). Treatment effects on
Q
max
from the surveyed clinical trials conducted during the
last 10 years are summarized in Figure 2 (also expressed as
changes from baseline). The treatment efficacies among the
three classes of agents are also comparable, although the
data from botanical trials have a much larger range. The
mean Q
max
increase from flaxseed lignan treatment in our
study is located around the median of Q
max
increases ob-
served in the surveyed drug trials (Fig. 2).
Ordinary dietary intake of SDG lignan is typically low.
Ingested SDG is broken down into SECO and ED and fur-
ther to EL in the intestine and colon. Although some publi-
cations provide EL or ED concentrations in human plasma,
few studies have reported plasma SECO concentrations and
how these three compounds are distributed in the circula-
tion. It is not clear whether the distribution of plasma lig-
nans solely depends upon absorption, further metabolism,
or a combination of both. The large SEs of mean plasma
lignan concentrations in this study may indicate that gut con-
version of dietary lignan can be considerably dissimilar be-
tween individuals. Several other studies by Nesbitt et al.,
61
Morton et al.,
62
and Kuijsten et al.
63
examined plasma ED
and EL concentrations using flaxseed or SDG supplemen-
tation. In these studies, wide ranges and large SDs for mean
ED and EL concentrations were also reported. The large
variance for plasma lignan concentrations appears to be a
common attribute in all these studies, including ours, and
likely depends on the profiles of particular gut microflora.
The mechanism by which flaxseed lignan extract could
relieve IPSS and improve QOL score remains unclear, ex-
cept for a possibility that EL and ED inhibit the activity of
5R as previously reported.
13
To our knowledge, the current
study is the first clinical trial using flaxseed lignan extract
to address LUTS in BPH subjects. Considering that SDG is
a phytoestrogen,
64
the observed treatment effects may be
linked to its potential antagonistic action on male hormone
conversion or receptor binding, such as testosterone or di-
hydrotestosterone. The significant correlation between IPSS
or QOL score improvement and plasma lignan concentra-
tions suggests that lignans may be the functional agents in
the preparation tested. However, we cannot rule out that
some other compounds in the flaxseed lignan extract may
also play a role, such as coumaric acid glucoside or ferulic
acid glucoside. The latter compounds provided approxi-
mately 15% and 8% of the composition of the extract, re-
spectively. These compounds have some antioxidant fea-
tures due to their phenolic chemical structures. Also, it
remains unclear if synergistic effects exist among the lig-
nans, coumaric acid, and ferulic acid.
There are limitations in the current study. First, the sam-
ple size is relatively small, which could create larger data
variances and weaken statistical power. This may account
for certain variables not reaching statistical significance,
even if there were substantial changes between or within
groups. Second, the study period was short, and this aspect
may impede finding the maximum treatment efficacy and
diminish time needed for placebo effect to normalize. Third,
similar to other BPH studies, an obvious placebo effect oc-
curred in our study.
In conclusion, this study indicates that dietary lignan-rich
flaxseed extract can appreciably relieve LUTS and improve
quality of life in BPH subjects. The observed plasma lignan
concentrations provide a primary determination of absorp-
tion and plasma distribution of dietary flaxseed lignans. The
correlations between the plasma lignan concentrations and
the improvements in IPSS and QOL score suggest they may
be the key functional components. The efficacy of flaxseed
lignan appeared to be comparable to that of commonly used
drugs (AR blockers or 5R inhibitors) and botanicals. Con-
sidered together with safety data and nonadverse effects, the
flaxseed lignan extract should be further evaluated as a nat-
ural alternative for LUTS management or intervention in
BPH populations.
6 ZHANG ET AL.
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8 ZHANG ET AL.
... In the 2 articles (7%) investigating L.usitatissmum as registered products (i.e. LinumLife EXTRA and Beneflax), significant improvements of IPSS (n = 2; P<0.001, P<0.01, respectively) and PV (n = 2; P<0.05, P<0.01, respectively) were reported in both articles (Simons et al., 2015;Zhang et al., 2008). Additional outcomes that improved were Qmax; P<0.01 (n = 1), QoL; P<0.001 (n = 1), and PRV; P<0.001 (n = 1); NS (n = 1). ...
... Ligans provide a source of phytoestrogens, where secoisolariciresinol diglycoside (SDG) is the most prominent along with matairesinol, pinoresinol, lariciresinol and isolariciresinol (Kajla et al., 2015;Parikh et al., 2019;Singh et al., 2011). In this systematic review, L. usitatissmum extract, specifically SDG, was used in the treatment of BPH as either LinumLi-feEXTRA or Beneflax (Simons et al., 2015;Zhang et al., 2008). A significant improvement of IPSS and PV was reported in both articles. ...
... A significant improvement of IPSS and PV was reported in both articles. Zhang et al. reported a significant improvement of Qmax and QoL (Zhang et al., 2008). PRV was reported to have significantly improved in one article, while insignificantly improving in the other article using L. usitatissmum as the intervention (Simons et al., 2015;Zhang et al., 2008). ...
Article
Full-text available
Background : The use of herbal medicine and alternative medicine is reported to be in up to 50% of prescriptions for benign prostate hyperplasia (BPH) in Europe, along with an increased global interest for holistic medicinal approaches. This study aimed to systematically review the published evidence investigating the use of herbal medicines as a treatment for BPH in clinical trials based on PRISMA guidelines. Methods : A literature search was conducted using PubMed, Cochrane, Medline, and Scopus databases, including English language clinical trials (Jadad score of ≥ 4) that investigated herbal medicine as a sole intervention, reporting at least one of the following outcomes: International Prostate Symptom Score (IPSS); American Urological Association Symptom Index (AUASI); Maximum Urinary Flow Rate (Qmax); Post-void residual volume (PRV); Prostate volume (PV); Serum Prostatic Specific Antigen (PSA); Quality of Life (QoL) Scores. Results : Following article screening, 28 articles were included. The most frequently studied herbs in isolation or in combination were Serenoa repens (54%), Urtica dioica (14%), Cucurbita pepo (14%), lycopene (14%), Pygeum africanum (14%) and Linum usitatissimum (7%). These herbal-based formulations mostly improved the symptoms associated with BPH (IPSS/AUASI, Qmax, PSA, QoL scores, PRV and PV). This review further discusses these herbs and the outcomes, with a focus on the potential mechanisms of action. Conclusions : There are limited high quality clinical trials investigating herbal medicine on BPH, where S. repens is significantly more represented than other popular herbs for BPH, such as C. pepo, U. dioica, P. africanum, and lycopene. Although the included studies broadly found positive positive results for standardised outcomes for LUTS and urinary flow, there was great variability in the study designs requires caution in interpretation. As these herbs are supported by in vivo and in vitro studies on potential mechanisms of actions, comparison of efficacy of mono-herbal and poly-herbal approaches, standardized extract based on identification of active constituents, as well as dosage and long-term safety.
... terrestris), Maghz tukhm-i-kaddu shireen (Cucurbita pepo), Babuna (Matricaria recutita), Alsi (Linum usitatissimum), Anisoon (Pimpinella anisum), and Khayareen (Cucumis sativus) have been found to reduce symptoms and improve QoL in BPH patients [64]. Flaxseed and pumpkin seed have also been observed to be effective when used individually [65,66]. Acupuncture is also contributing for better prostate health, improving BPH symptoms and QoL [67]. ...
... Medicines such as C. pepo (Maghz tukhm-i-kaddu shireen) [66], Linum usitatissimum (Alsi) [65], T. terrestris (Kharkhask), P. anisum (Anisoon), C. sativus (Maghz tukhm-ikhyarein), and M. recutita (Babuna) are considered to be effective in alleviating these symptoms [64]. Most of these medicines were also found to have anti-inflammatory, 5alpha-reductase inhibitor, and anti-tumor properties [64]. ...
... U Trial 2dLinum usitatissimum extract vs. placebo [65]: It is also a double-blind placebo-controlled study where safety and efficacy of flaxseed extract, 300 mg and 600 mg per day for 4 months duration, was investigated against the placebo. To make the relation more comprehensible, here we have shown only the comparison between flaxseed extract (600 mg) and placebo. ...
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Objective: Conventional treatments for benign prostatic hyperplasia (BPH) like 5alpha-reductase inhibitors and invasive surgery are associated with some obvious side effects. Conversely, evidence, though limited, has shown that alternative medicines are safer and have potential to improve the lower urinary tract symptoms (LUTS) and quality of life in addition to improving sexual dysfunction in patients with BPH. The current article aimed to include an overview of BPH, different ways of its management, and particularly its appreciation in Greco-Arab (Unani) system of medicine, one of the alternative medicinal systems. Methods: PubMed, Scopus, ScienceDirect, Web of Sciences, Google Scholar databases and classical texts of Greco-Arab medicine were searched for data collection. Results: In Unani system of medicine, BPH, traced under the headings of Waram unuq al-mathana (bladder neck swelling) and Insidad majra-i-mathana (bladder outlet obstruction), has been managed for centuries with herbal medicines yet demanding a comprehensive scientific validation. Among the herbs, Cucurbita pepo, Tribulus terrestris, Urtica dioica, and Linum usitatissimum are worth mentioning. Conclusion: For achieving the goal of LUTS-free ageing men, and safer and cost-effective future management of BPH, Unani herbal medicine could hopefully prove beneficial.
... Similar to what has been reported on animal models [52,53], a strong utility of dietary flaxseed lignan extract in improving BPH-related LUTSs, compared to that of alpha1Aadrenoceptor blockers and 5alpha-reductase inhibitors, has been reported by Zhang et al. [69]. These authors conducted a randomized clinical trial in which a placebo, 300, or 600 mg/day of secoisolariciresinol diglucoside, a flaxseed extract, were administered to 87 patients affected by BPH and found a decrease in IPSS and improvement of quality of life score and LUTSs, respectively [69]. ...
... Similar to what has been reported on animal models [52,53], a strong utility of dietary flaxseed lignan extract in improving BPH-related LUTSs, compared to that of alpha1Aadrenoceptor blockers and 5alpha-reductase inhibitors, has been reported by Zhang et al. [69]. These authors conducted a randomized clinical trial in which a placebo, 300, or 600 mg/day of secoisolariciresinol diglucoside, a flaxseed extract, were administered to 87 patients affected by BPH and found a decrease in IPSS and improvement of quality of life score and LUTSs, respectively [69]. Conversely, it has been shown that pumpkin seed extract did not have any benefits on BPH compared to the placebo over a 1-year period [70]. ...
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Interest in the role of dietary patterns has been consistently emerging in recent years due to much research that has documented the impact of metabolism on erectile dysfunction (ED) and/or benign prostatic hyperplasia (BPH). We conducted a non-systematic review of English articles published from 1964 to September 2021. The search terms were: (“dietary patterns” OR “diet”) AND/OR (“erectile dysfunction”) AND/OR (“benign prostatic hyperplasia”). In the present review, we have highlighted how the association between dietary patterns and two of the most frequent pathologies in urology, namely erectile dysfunction and benign prostatic hyperplasia, is present in the literature. The data suggested that a diet that is more adherent to the Mediterranean diet or that emphasizes the presence of vegetables, fruits, nuts, legumes, and fish or other sources of long-chain (n-3) fats, in addition to reduced content of red meat, may have a beneficial role on erectile function. At the same time, the same beneficial effects can be transferred to BPH as a result of the indirect regulatory effects on prostatic growth and smooth muscle tone, thus determining an improvement in symptoms. Certainly, in-depth studies and translational medicine are needed to confirm these encouraging data.
... In phytotherapy trials, the changes in TPV were from -5.1% to +2.91% and in PSA from -4.2% to -1.0% [63][64][65][66][67][68][69][70]. A trial with 12-month follow-up reported +14.7% increase in TPV and +8.8% increase in PSA [66]. ...
... [63][64][65][66][67][68][69][70]. Four Sr trials reported non-significant changes in TPV as compared to placebo [SMD:0.12(95%CI:-0. ...
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Introduction: The clinical effect of pharmacotherapy on prostate morphometric parameters is largely unknown. The sole exception is 5α-reductase inhibitors (5-ARI) that reduce prostate volume and prostate-specific antigen (PSA). This review assesses the effect of pharmacotherapy on prostate parameters effect on prostate parameters, namely total prostate volume (TPV), transitional zone volume (TZV), PSA and prostate perfusion. Material and methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) reporting on morphometric parameters' changes after pharmacotherapy, as primary or secondary outcomes. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RCTs' quality was assessed by the Cochrane tool and the criteria of the Agency for Healthcare Research and Quality. The effect magnitude was expressed as standard mean difference (SMD). The study protocol was published on PROSPERO (CRD42020170172). Results: Sixty-seven RCTs were included in the review and 18 in the meta-analysis. The changes after alpha-blockers are comparable to placebo. Long-term studies reporting significant changes from baseline, result from physiologic growth. Finasteride and dutasteride demonstrated large effect sizes in TPV reduction ([SMD]: -1.15 (95% CI: -1.26 to -1.04, p <0.001, and [SMD]:-0.66 (95% CI: -0.83 to -0.49, p <0.001, respectively), and similar PSA reductions. Dutasteride's effect appears earlier (1st vs 3rd month), the changes reach a maximum at month 12 and are sustained thereafter. Phosphodiesterase-5 (PDE-5) inhibitors have no effect on morphometric parameters. Phytotherapy's effect on TPV is non-significant [SMD]: 0.12 (95% CI: -0.03 to 0.27, p = 0.13). Atorvastatin reduces TPV as compared to placebo (-11.7% vs +2.5%, p <0.01). Co-administration of testosterone with dutasteride spares the prostate from the androgenic stimulation as both TPV and PSA are reduced significantly. Conclusions: The 5-ARIs show large effect size in reducing TPV and PSA. Tamsulosin improves perfusion but no other effect is evident. PDE-5 inhibitors and phytotherapy do not affect morphometric parameters. Atorvastatin reduces TPV and PSA as opposed to testosterone supplementation.
... According to the evidence from an RCT carried out in 87 patients with BPH, the flaxseed extract secoisolariciresinol diglucoside (SDG) at the dose of 300 or 600 mg/day reduced the international prostate symptom score (IPSS), increased the QoL score, and improved the grade of lower urinary tract symptoms (LUTS) (from moderate/severe to mild). The efficacy of flaxseeds was also compared to that of α1Ablockers and 5α-reductase inhibitors [23]. ...
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Introduction. Obesity exposes individuals to the risk of chronic inflammation of the prostate gland. Aim and design of the study. A longitudinal clinical study was conducted on selected overweight/obese patients with male accessory gland inflammation (MAGI) to evaluate the effects of body weight loss on their urogenital symptoms. Materials and methods. One hundred patients were selected and assigned to two groups undergoing two different nutritional programs. The first group (n = 50) started a Mediterranean diet (MedDiet) and the second (n = 50) a very-low-calorie ketogenic diet (VLCKD). Before and after three months on the diet, each patient was evaluated for body weight, waist circumference, and MAGI symptoms. The MAGI was assessed using the Structured Interview about MAGI (SI-MAGI), a questionnaire previously designed to assess the symptoms of MAGI. The questionnaire explores four domains, including urinary symptoms, ejaculatory pain or discomfort, sexual dysfunction, and impaired quality of life. Finally, in the two groups, the frequency of an α-blocker used to treat urinary tract symptoms was also evaluated. Results. Patients on MedDiet experienced significant amelioration in urinary symptoms and quality of life. Patients under VLCKD reported not only significant improvement of the same parameters, but also in ejaculatory pain/discomfort and sexual dysfunction. Finally, the percentage of patients on VLCKD taking the α-blocker decreased significantly. Moreover, patients under VLCKD showed a greater loss of body weight than those following the MedDiet. Discussion. The results of this study support the effectiveness of VLCKD in improving the symptoms of patients with MAGI. This improvement involved all of the domains of the SI-MAGI questionnaire and became manifest in a relatively short time. We suggest that a ketogenic nutritional approach can be used in overweight/obese patients with MAGI.
... year versus only about $10, -a year for daily flax. This study found they both work just as well as each other but in case of the flax seed without all the negative side effects except possibly a bit more flatulent when the body is not yet acclimated to a higher level of dietary fibrous food [37,38]. ...
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I also very much like to share the following about flax seeds because it is next to for example turmeric and salicylic acid for me amongst the most interesting plant compounds I am enthusiastic about and discovered about through learning and in accordance with this course part of playing a role in treatment of cardiovascular diseases. Furthermore, I would very much like everyone to know more about flax seeds including you. >the relatively in proportion high phytoestrogen lignan precursors containing which are metabolized in the lignans in the human body by gut bacteria which we can then absorb [39] and relatively high alpha-linolenic acid ALA containing dietary brown-golden hard hulled (that keeps them fresh) raw ground/grinded/milled/crushed (to make sure our body can use it an such that they do not pass right through us) flax seeds (also called linseeds, vlaszaad, vlas, FX, FS and lijnzaad) and not just the flax seed oil from the flax seed plant linum usitatissimum in the family linaceae (also called vlasfamilie and flax family) are usable as >Antihypertensive for people with relatively hypertensive elevated blood pressure because it is one of the most potent antihypertensive effects ever achieved by a dietary intervention [1, 6]. The action mechanism is that dietary flaxseed reduces central aortic blood pressure without cardiac involvement but through changes in a group of fatty acid metabolites involved in inflammation in the bloodplasma as pro-inflammatoire called the long chain omega-6 fatty acid arachidonic acid (which is relatively highly prevalent in body damaging foods such as a relative high amount of animal food products and culinary oils) derived pro-inflammatoire oxylipins leukotoxin diols which may be by inhibiting the enzyme and thus the lowering the activity of the enzyme that makes these pro-inflammatory oxylipins which in turn may lower blood pressure [2, 3, 4, 5]. This is possibly by molecular compounds including the precursor of the cardioprotective long-chain n-3 fatty acids alpha-linolenic acid (ALA) present in flax seed which effect was independelty shown in a 12-week long dietary intervention placebo-controlled trial study of people with dyslipidaemic significantly lowering systolic and diastolic blood pressure as compared to safflower oil, in which systolic blood pressure rose and diastolic blood pressure stayed about the same [19]. A 6 (six) month prospective double-blinded placebo-controlled randomized trial for potential hypertension alleviation showed that eating ground flax seeds every day dropped their systolic blood pressure number about 10 (ten) points and their diastolic blood pressure number by about 7 (seven) points dropping cutting brain stroke risk almost in half by 46 [%], lowering risk of coronary heart disease with 29 [%], and for those persons who started out with a systolic blood pressure number far over 140 got a 15-point drop [6]. This is more than 2 (two) times better than and thus more than comparable to powerful angiotensin converting enzyme (ACE) inhibiting drugs like enalapril (also called kadril, vasotec, renitec, and enacard), which may drop pressures as follows: systolic blood pressure number only by 5 (five) and diastolic blood pressure number only by 2 (two) points; and amlodipine (also called norvasc and amlor) which may drop pressures as follows: systolic blood pressure number by 8 (eight) and diastolic blood pressure number only by 3 (three) points; and cardizem (also called diltiazem, diltiazem
... Flaxseed has approximately 57% ALA in 100g of oil (Barceló-Coblijn & Murphy, 2009) and is one of the richest sources of ALA. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are converted from ALA in the body, have anti-inflammatory factor and have effect on reducing the risk of many chronic diseases like atherosclerosis, cardiovascular disease (CVD), cancer and hyperlipidemia (Zhang, et al. 2008;Simopoulos, 2002). Although in literature the con-version efficacy of ALA to EPA and DHA is mentioned to be below 0.6% in animal models (Su, et al. 2001), many literatures have related the hypocholesterolemic effect of flaxseed to high ALA content of flaxseed oil (Vijaimohan, et al. 2006;Riediger et al. 2008). ...
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The current review aimed to provide a comprehensive overview of Bioactive compounds and pharmacological uses, of Linum usitatissimum, and to list its significant therapeutic benefits. From various studies, researchers specified the pharmacological properties of flaxseed. The phytoconstituents like lignan and ? linolenic acid are the richest of flaxseeds. It is also a chief source for soluble fiber, high-quality protein, and antioxidants. Its long trip from old era to the 21st century from being a medication in old age opened the way for a broad populace. Linolenic acid, linoleic acid, lignans, polysaccharides cyclic peptides, alkaloids, cadmium and cyanogenic glycosides were some of the biologically active chemicals and elements. Flaxseed extracts containing lignan or ? linolenic acid were often the focus of biological and clinical research. Some beneficial outcomes for health include decreasing cardiovascular illnesses, atherosclerosis, diabetes, cancer and arthritis, osteoporosis, and autoimmune illnesses, as well as neuroscience. Some Proteins present in flaxseed helps in prevention and cure for cardiovascular disease and reinforce the immune system. This present review focuses briefly on a pharmacological properties and laboratory outcomes of flaxseed diet.
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This chapter introduces the epidemiology, risk factors, and pathophysiology of benign prostatic hyperplasia (BPH) in adult men. It starts by introducing the magnitude of BPH in the American population and presenting an overview of how BPH leads to bothersome lower urinary tract symptoms (LUTS) in many affected men. It then discusses the epidemiology of the condition and literature-supported risk factors. Next, our current understanding of the pathophysiological mechanisms that contribute to BPH is explored. The workup involved in making a diagnosis of BPH is briefly explained, followed by a broad discussion of treatment options, including medical and surgical options. Finally, an introduction to the relationship between BPH and diet is presented. By the end of the chapter, several key topics critical to understanding the scope of BPH are explained.
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Objective: While the lipido-sterolic extract of Serenoarepens (LSESr)—Permixon®—has been shown to have an equivalent efficacy to finasteride in patients with benign prostatic hyperplasia (BPH), to date, there has been no valid comparison of phytotherapy with α-blockers. The aim of this study was to assess the equivalent efficacy of Permixon and tamsulosin.Methods: Eight hundred and eleven men with symptomatic BPH (I-PSS≥10) were recruited in 11 European countries for a 12-month, double-blind randomized trial. After a 4-week run-in period, 704 patients were randomly assigned to either tamsulosin 0.4mg/day (N=354) or Permixon 320mg/day (N=350). I-PSS, QoL and Qmax were evaluated at baseline and periodically for 1 year. Prostate volume and serum prostate-specific antigen (PSA) were measured at selection and at endpoint. The endpoint analysis was performed on the per-protocol population of 542 patients (tamsulosin: N=273; Permixon: N=269).Results: At 12 months, I-PSS decreased by 4.4in each group and no differences were observed in either irritative or obstructive symptom improvements. The increase in Qmax was similar in both treatment groups (1.8ml/s Permixon, 1.9ml/s tamsulosin). PSA remained stable while prostate volume decreased slightly in the Permixon-treated patients. The two compounds were well tolerated, however, ejaculation disorders occurred more frequently in the tamsulosin group.Conclusion: This study demonstrates that Permixon and tamsulosin are equivalent in the medical treatment of lower urinary tract symptoms in men with BPH, during and up to 12 months of therapy.
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Objectives. The purpose of this open-label study extension was to assess the long-term safety and efficacy of finasteride in the treatment of men with benign prostatic hyperplasia (BPH).Methods. A Phase III North American BPH trial originally enrolled 895 men, 297 of whom were randomized to receive finasteride 5 mg. An enlarged prostate gland by digital rectal examination, symptoms of urinary obstruction, and a maximal urinary flow rate of less than 15 mL/s were required for entry. Patients who completed the initial 12-month, double-blind, placebo-controlled study were invited to participate in an open-label extension for 4 additional years.Results. Of the 297 patients initially randomized to receive finasteride 5 mg, 259 completed 12 months in the double-blind period and 186 completed 48 months of open-label therapy. Prostate volume reached a nadir of −24.6% at month 24, and the effect was maintained through month 60. Compared with baseline values, month 60 prostate volume was decreased by 22.7% (P
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Objectives. To compare the long-term effects of finasteride (5 mg/day) and placebo in patients with moderate symptoms of benign prostatic hyperplasia (BPH).Methods. Patients aged 50 to 75 years, with at least two urinary symptoms indicating moderate BPH, and an enlarged prostate, were followed in a 2-year double-blind, randomized, placebo-controlled multicenter study. The effects of finasteride versus placebo were assessed by total symptom score (modified Boyarsky), obstructive symptom score, maximal urinary flow rate, prostate volume, and urologic end points (acute urinary retention, BPH-related surgical intervention).Results. Of the 3270 men enrolled, 3168 contributed data to the safety analysis, and 2902 to the efficacy evaluation. Significantly greater improvement with finasteride compared to placebo was observed at 12 and 24 months for total symptom score (mean −2.9 versus −1.9 at 12 months, P ≤0.001; −3.2 versus −1.5 at 24 months, P ≤0.001), obstructive symptom score (mean −1.9 versus −1.3 at 12 months, P ≤0.001; −2.1 versus −1.1 at 24 months, P ≤0.001), maximal urinary flow rate (mean +1.2 versus +0.6 mL/s at 12 months, P = 0.010; +1.5 versus +0.7 mL/s at 24 months, P = 0.002), and prostate volume (mean −14.2 versus +5.4% at 12 months, P ≤0.01; −15.3 versus +8.9% at 24 months, P ≤0.001). Greater improvements in placebo-adjusted total symptom score occurred in men with large prostates than in men with small prostates (mean −2.4 versus −1.1 at 12 months; −3.2 versus −1.3 at 24 months, placebo-adjusted data, P = 0.053). Fifteen of 1450 men (1.0%) in the finasteride group experienced an acute urinary retention event, compared with 37 of 1452 (2.5%) in the placebo group, and the corresponding figures for surgery were 51 of 1450 (3.5%) and 86 of 1452 (5.9%), respectively. The hazard rate for occurrence, computed using the log-rank statistic, decreased by 57% for acute urinary retention and by 40% for surgery accompanied by finasteride therapy compared to placebo.Conclusions. Finasteride causes long-term symptomatic improvement and reduces the risk of acute urinary retention or surgery. Men with enlarged prostates benefit most from finasteride treatment.
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Objectives. To evaluate the long-term efficacy and safety of once-daily tamsulosin (0.4 and 0.8 mg), a unique selective alpha1A-adrenoceptor antagonist in patients with benign prostatic hyperplasia (BPH).Methods. This trial extended a 13-week, Phase III multicenter placebo-controlled, double-blind outpatient trial for an additional 40 weeks. Of 618 patients, 418 (68%) continued into the extension phase on the same double-blind medication and dose. The primary efficacy parameters were total American Urological Association (AUA) symptom score and maximum urinary flow (Qmax).Results. The mean changes in AUA symptom score from baseline to end point were statistically significant in all groups (P
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The activities of lignans and neolignans which directly or indirectly affect the cardiovascular system are reviewed. The results from molecular screening methods and animal models are included and an attempt to identify the molecular features which might influence some of the activities is made. The question of the benefit of low levels of circulating lignans in an organism is considered.
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Background: The objective of this open randomized clinical study was to compare the short-term efficacy and safety of three alpha-1 blockers, prazosin, terazosin and tamsulosin, in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Methods: The study comprised 121 patients with symptomatic BPH who were randomized to receive 0.5 mg of prazosin twice daily, 0.5 mg of terazosin twice daily or 0.1 mg of tamsulosin once daily for the initial 2 weeks. The doses were doubled for the next 2 weeks. The primary variables assessed were a symptom score, changes in maximum and average urinary flow rate (Qmax and Qave), postvoid resisual urine volume and blood pressure. Results: The percentage changes in the total symptom score from baseline were 38, 39 and 26% at 4 weeks by prazosin, terazosin and tamsulosin, respectively. Terazosin produced significantly higher improvement in four out of nine individual symptoms than tamsulosin (P < 0.05). A significant increase in Qmax or Qave in uroflowmetry was obtained in the prazosin and tamsulosin groups. Blood pressure remained unchanged in normotensive patients, but significantly decreased in hypertensive patients except for the tamsulosin group. Adverse events were minimal in all treatment groups. Conclusions: The efficacy and safety profiles were different among the alpha-1 blockers at standard doses. Tamsulosin appears to be safer than the others for aged patients or patients with hypertension who have impaired blood pressure regulation, while terazosin is significantly effective in improving symptomatic score when compared with the others examined. It is recommended that the alpha-1 blocking agent and its optimal dose are selected on the basis of the baseline characteristics of the patients with symptomatic BPH.