SAW PALMETTO

Evaluaciones de AltMedDex

DOSING INFORMATION
DOSAGE FORMS
A) MEDICINAL COMPONENTS:
1) BERRIES
a) The dried berries contain about 1.5% of a fruity-smelling oil containing saturated and
unsaturated fatty acids and sterols. About 63% of this oil is composed of free fatty acids
including capric, caprylic, caproic, lauric, palmitic, and oleic acids. The remaining portion is
composed of ethyl esters of these fatty acids and sterols, including beta-sitosterol and its
glucoside. Other components of the dried berries include carotenes, lipase, tannins, and
sugars (Bombardelli & Morrazzoni, 1997).
b) The lipid-soluble compounds may be the major pharmacological components. The
liposterolic extract used medicinally contains between 85% and 95% fatty acids and sterols.
It consists of a complex mixture of saturated and unsaturated free fatty acids, their methyland ethyl-esters (approximately 7%), long chain alcohols in free and esterified form, and
various free and esterified sterol derivatives. The free fatty acids in this extract are identified
by gas chromatography and mass spectrometry as: caproic acid (C6), capric acid (C8),
caprylic acid (C10), lauric acid (C12), myristic acid (C14), isomyristic acid (C14), palmitic acid
(C16), oleic acid (C18:1), and stearic acid (C18). Lauric and myristic acid are the major fatty
acids, accounting for approximately 30% of the fatty acid content. The identified alcohols
include those with n-C22, n-C23, n-C24, n-C26, n-C28, and n-C30 chains, phytol, farnesol,
and geranylgeraniol, in addition to high molecular weight unsaturated polyphenols. The
sterolic fraction is composed of beta-sitosterol, stigmasterol, cycloartenol, lupeol, lupenone,
and 24-methylcycloartenol. Many of these sterols are esterified with the fatty acids of the
extract (Bombardelli & Morrazzoni, 1997).
B) SYNONYMS
1) SERENOA REPENS

American dwarf palm tree

Cabbage palm
Dwarf palm tree
Dwarf palmetto
Fan palm
Fructus serenoae
Palma enana americana
Palmetto
Sabal
Sabal fructus
Sabal serrulatum
Saegepalmen
Saegepalmenfruechte
Sal palmetto berries
Saw palmetto
Scrub palm
Serenoa
Serenoa serrulata
Serenoapalmu

STORAGE AND STABILITY

A) CAPSULES, TABLETS, FRUITS
1) Store at room temperature, away from heat, moisture, and direct light.

ADULT DOSAGE
NORMAL DOSE
IMPORTANT NOTE
1) Dosing of herbal preparations is highly dependent on a variety of factors, such
as growing and harvesting conditions, plant parts and extraction methods used,
and the dosage form chosen by the manufacturer. Standardization to single
constituent markers has proven unreliable. Since no official standards have been
established to date to regulate the production of herbal medicines in the United
States, dosage ranges must be employed as guidelines.
See Drug Consult reference:" HERBAL SUPPLEMENTS - DOSING"
See Drug Consult reference:" HERBAL SUPPLEMENTS - SAFETY"

ORAL
1) BENIGN PROSTATIC HYPERTROPHY, tablet/capsule: 1 to 2 g/day saw palmetto
berry or 320 mg/day of the lipophilic extract either extracted with lipophilic solvents
(90% v/v) or super-critical fluid extraction with carbon dioxide (Blumenthal et al,
1998; Bach & Ebeling, 1996).

PEDIATRIC DOSAGE
A) Pediatric dosing not available.

PHARMACOKINETICS
ADME
DISTRIBUTION
DISTRIBUTION SITES
A) PROSTATE
1) Prostatic tissue uptake was greater than any other tissue, such as liver, seminal
vesicles, and genital organs in a study done with rats given the n-hexane lipidsterolic extract orally, supplemented with radiolabeled oleic, lauric, or betasitosterol. The most effective lipid agent in promoting absorption was oleic acid
(Chevalier et al, 1997).
EXCRETION
BREAST MILK
A) BREASTFEEDING: Unknown
1) Scientific evidence for the safe use of saw palmetto during lactation is not
available.
HALF LIFE
PARENT COMPOUND

A) ELIMINATION HALF-LIFE: 1.9 hours (De Bernardi et al, 1994).

1) Elimination half-life following a single 320 milligram dose in volunteers was 1.9
hours (De Bernardi et al, 1994).

CAUTIONS
CONTRAINDICATIONS
A) Hypersensitivity to saw palmetto or any of its components

PRECAUTIONS
A) Hormone-dependent cancer: No information is available about the action of this herb in
patients with hormonal diseases, such as breast cancer or prostate cancer. The herb has
demonstrated antiandrogenic (Dreikorn & Schonhofer, 1995), antiestrogenic (DiSilverio et al,
1992), and estrogenic actions in animals (Elghamry & Haensel, 1969).

ADVERSE REACTIONS
BLOOD
HEMORRHAGE
1) Intraoperative hemorrhage, including a blood loss of about 2000 cm(3), was
reported in a 53-year-old male who was taking saw palmetto. The prolonged
bleeding time normalized over 5 days after discontinuing saw palmetto.
Preoperative and postoperative prothrombin time and partial thromboplastin time
were normal. No other predisposing factors for hemorrhage were reported. The
prolonged bleeding time was most likely due to platelet dysfunction resulting from
inhibition of cyclooxygenase by saw palmetto (Cheema et al, 2001).

CARDIOVASCULAR
CARDIOVASCULAR EFFECTS
1) In a saw palmetto clinical trial for the treatment of benign prostatic hypertrophy,
305 patients completed the trial. Adverse effects were reported in 5% of patients
and included TACHYCARDIA, ANGINA PECTORIS, EXTRASYSTOLES, and
ANGIOPATHY (Braeckman, 1994). Mild HYPERTENSION was also reported as an
adverse effect (Plosker & Brogden, 1996). None of these reactions were serious.
2) POSTURAL HYPOTENSION (1.1%) was observed in subjects treated with oral
Serenoa repens 320 mg daily in a 12-month, randomized, double-blind,
comparative trial of a lipido-sterolic extract (Permixon(R)) and tamsulosin in the
treatment of benign prostatic hypertrophy (Debruyne et al, 2002).
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM EFFECTS
1) HEADACHE (8%), DIZZINESS (2.9%), FATIGUE (1.7%), and ASTHENIA (1.1%)
were observed in subjects treated orally with 320 milligrams Serenoa repens daily
in a 12-month randomized, double-blind, comparative trial of a lipido-sterolic
extract of Serenoa repens (Permixon(R)) and tamsulosin in the treatment of benign
prostatic hypertrophy (BPH) (Debruyne et al, 2002).
ENDOCRINE/METABOLIC
ENDOCRINE EFFECTS

1) Saw palmetto berries contain 18.9 milligrams/100 milliliters (mg/mL) betasitosterol and 0.022 mg/mL beta-sitosterol-D-glucoside (Schoepflin et al, 1966;
Haensel et al, 1964). Subcutaneously injected into immature female mice, betasitosterol is estrogenic. Pure beta-sitosterol is less than 1/10th as potent as
estradiol and the saw palmetto extract is about 1/10,000th as potent (Duke, 1985;
Elghamry & Haensel, 1969).
2) Permixon(R), a commercial product from France, was without estrogenic or
antiestrogenic effects in clinical trials (Stenger et al, 1982).
3) A combination product that contains saw palmetto (PC-SPES) is reported to
have estrogenic effects.
See Drug Consult reference:" PC-SPES: TREATMENT FOR PROSTATE CANCER"

GASTROINTESTINAL
GASTROINTESTINAL EFFECTS
1) DRY MOUTH (0.9%) was observed in subjects treated orally with 320 milligrams
(mg) Serenoa repens daily in a 12-month randomized, double-blind, comparative
trial of a lipido-sterolic extract of Serenoa repens (Permixon(R)) and tamsulosin in
the treatment of benign prostatic hypertrophy (Debruyne et al, 2002).
2) Mild gastrointestinal discomfort was reported in 2% of the subjects treated with
320 milligrams (mg) Serenoa repens daily compared to 6% in subjects treated with
480 mg Serenoa repens daily for 6 months in an open-label study of subjects with
marked prostatic obstruction and lower urinary tract symptoms (n=100). None of
the subjects withdrew from the study due to adverse events (Giannakopoulos et al,
2002).
3) DIARRHEA and MILD GASTRIC DISTRESS were reported by 2 of 41 patients
taking saw palmetto in a double-blind, randomized, placebo-controlled study. The
diarrhea caused the patients to withdraw from the study (Gerber et al, 2001).
4) Minor NAUSEA was reported in some large studies (Plosker & Brogden, 1996).
In one study, 3 of 72 patients reported nausea and VOMITING serious enough to
discontinue taking the drug (Reece-Smith et al, 1986).
5) Minor ABDOMINAL PAIN was occasionally reported in some large studies
(Plosker & Brogden, 1996). Abdominal distress was the cause for leaving one study
(Tasca, 1985).

KIDNEY/GENITOURINARY
GENITOURINARY EFFECTS
1) Ejaculation disorders (0.6%) and reduced libido (0.3%) were observed in
subjects treated orally with 320 milligrams (mg) Serenoa repens (Permixon(R))
compared with 4.2% and 1.1%, respectively, for tamsulosin for the treatment of
benign prostatic hypertrophy in a 12-month randomized, double-blind, comparative
trial. Six subjects in each treatment group developed acute URINARY RETENTION
with 7 subjects requiring hospitalization (Debruyne et al, 2002).
2) Reduced libido was reported in two of 100 subjects treated with Serenoa repens
(320 mg and 480 mg daily) in a 6-month open-label study of subjects with marked
prostatic obstruction and lower urinary tract symptoms. None of the subjects
withdrew from the study due to adverse events (Giannakopoulos et al, 2002).
3) Erectile dysfunction was reported in 1.1% of subjects treated with saw palmetto
daily compared with 4.9% (p less than 0.001) of subjects treated with finasteride in
a systematic review of randomized trials (Wilt et al, 2000).
4) Saw palmetto extract has not been associated with erectile dysfunction,
ejaculatory disturbance, or altered libido (Marks & Tyler, 1999).
5) Incubation of hamster oocytes in saw palmetto for one hour did not affect
sperm penetration or sperm motility (Ondrizek et al, 1999).
LIVER
HEPATIC EFFECTS

1) After using saw palmetto for 2 weeks for nocturia and urinary hesitancy, a 65year-old male developed CHOLESTATIC HEPATITIS. He discontinued the herbal
medication after the onset of JAUNDICE and severe pruritus. Serum laboratory
values on admission were: bilirubin 8.2 mg/dL, AST 1238 international units/L, ALT
1364 international units/L, and alkaline phosphatase 179 international units/L. A
liver biopsy performed 2 months later showed a parenchymal infiltrate of
neutrophils and lymphocytes involving the portal tracts, early bridging, and mild
periportal fibrosis. Liver function returned to normal 3 months after discontinuing
saw palmetto. Cholestasis may be hormonally-related due to the mechanism of
action of saw palmetto (Hamid et al, 1997).
2) Severe CHOLECYSTITIS was reported in a patient receiving saw palmetto.
However, a relationship between the herbal medication and cholecystitis could not
be causally established (Plosker & Brogden, 1996).

RESPIRATORY
RHINITIS
1) Rhinitis was observed in 8.6% of patients who received oral Serenoa repens 320
mg daily compared with 12% of patients who received tamsulosin in a 12-month,
randomized, double-blind trial (p=0.14) (Debruyne et al, 2002).
SKIN

PRURITUS
1) Pruritus, which resolved spontaneously, was cited in a case report of a patient
using saw palmetto for benign prostatic hyperplasia (Grasso et al, 1995).

MUSCULOSKELETAL
MUSCLE PAIN
1) Muscle pain has been reported as a minor adverse effect in a small percentage
of patients in clinical trials (Plosker & Brogden, 1996; Braeckman, 1994).

TERATOGENICITY/EFFECTS IN PREGNANCY
TERATOGENICITY
1) Studies have demonstrated that liposterolic extract had no teratogenic effects when
given at dosages up to 600 milligrams/kilogram in rats and rabbits (Bombardelli &
Morrazzoni, 1997).
EFFECTS IN PREGNANCY
1) Scientific evidence for the safe use of saw palmetto during pregnancy is not available.
2) Pregnant rats given saw palmetto fruits as 50% of their diets had suckling rats with
depressed growth, but the dams did not seem to be affected (Feurt & Fox, 1954).

DRUG INTERACTIONS
DRUG-DRUG COMBINATIONS
WARFARIN
1) Summary: Intraoperative bleeding was reported in a patient taking saw
palmetto (Cheema et al, 2001). Two cases of increased international normalized
ratio (INR) have been reported in patients taking a combination of saw palmetto,
pumpkin seed, and vitamin E (Curbicin(R)). One of the patients had been stable
using warfarin prior to starting Curbicin(R). The other patient was not taking any
concomitant anticoagulant therapy (Yue & Jansson, 2001). Caution is advised.
2) Adverse Effect: increased risk of bleeding
3) Clinical Management: Caution is advised if saw palmetto is taken with warfarin.

Monitor the INR and signs and symptoms of excessive bleeding.

4) Severity: moderate
5) Onset: delayed
6) Documentation: fair
7) Probable Mechanism: cyclooxygenase inhibition by saw palmetto
8) Literature Report:
a) Two cases of elevated international normalized ratio (INR) have been reported
associated with taking pumpkin seed (cucurbita), saw palmetto, and vitamin E. A
61-year-old male taking warfarin with stable INR (about 2.4) experienced an
increased INR of 3.4 after six days of taking five tablets of Curbicin(R) daily, an
herbal combination with pumpkin seed, saw palmetto, and vitamin E (10
milligrams/tablet). His INR returned to the therapeutic range within one week of
stopping Curbicin(R). A 73-year-old male not on anticoagulant therapy experienced
an INR of 2.1 during hospitalization for deterioration secondary to a common cold.
He had been taking Curbicin(R) three tablets daily for over one year. His INR
improved (1.3 to 1.4) with vitamin K treatment, then normalized to 1 after
stopping Curbicin(R) for one week (Yue & Jannson, 2001).
b) A 53-year-old male taking saw palmetto developed brisk bleeding during a
surgical procedure for resection of a brain tumor. In an attempt to control the
bleeding, the patient received four liters of crystalloid fluids, four units of packed
red blood cells, three units of pooled platelets, and three units of fresh frozen
plasma. The procedure was prematurely terminated and estimated blood loss was
two liters. Preoperative measures of prothrombin time (PT), activated partial
thromboplastin time (aPTT), complete blood count, and blood chemistry were
normal. No thromboprophylaxis was used prior to surgery. Postoperative PT and
aPTT were normal; however, bleeding time was prolonged to 21 minutes (normal
2 to 10 minutes). Two days after surgery, bleeding time remained prolonged at 14
minutes, which normalized over five days. Workup for bleeding disorders was
negative. The patient then disclosed his use of saw palmetto (Cheema et al,
2001).

CLINICAL APPLICATIONS
PLACE IN THERAPY
A) SUMMARY OF SCIENTIFIC EVIDENCE: Numerous controlled clinical trials have documented
the effectiveness of saw palmetto in the treatment of benign prostatic hypertrophy (BPH)
symptoms such as urine flow, dysuria, nocturia, residual urine, urgency, prostate volume, and
subjective complaints. However, conflicting data indicate saw palmetto fruit extract was no
more effective than placebo in reducing lower urinary tract symptoms in BPH in a double-blind,
multicenter, randomized trial. In comparison studies, saw palmetto and alfuzosin were equally
efficacious and a combination of saw palmetto and cyproterone produced a significant
decrease in prostate volume. Results were inconclusive when comparing finasteride and saw
palmetto, whereas prazosin was slightly more efficacious than saw palmetto.
B) COMMON USES IN COMPLEMENTARY AND ALTERNATIVE MEDICINE: The main clinical use
of saw palmetto is for a variety of urinary tract conditions in men including benign prostatic
hyperplasia and urinary tract infection. Topical saw palmetto ointment has been used for
androgen-induced acne.
C) HISTORICAL USES: Saw palmetto has been historically used as a treatment for prostate
enlargement and chronic cystitis as well as a mild diuretic.
D) TOUTED USES: Saw palmetto has been touted as an aphrodisiac, to increase sperm
production, and to produce breast enlargement; however, no clinical evidence has been

presented.
E) REGULATORY/SAFETY INFORMATION: Saw palmetto is approved by the German
Commission E for the treatment of urinary problems of benign prostatic hyperplasia stage I
(abnormal frequent urination, nocturia, delayed onset of urination, and weak urinary stream
and stage II (urge to urinate and residual urine) (Blumenthal et al, 1998). The American Herbal
Products Association rated saw palmetto as class I (can be safely consumed if used
appropriately) (McGuffin et al, 1997). Saw palmetto is available as a dietary supplement in the
United States under the Dietary Supplement Health and Education Act of 1994 (DSHEA).
See Drug Consult reference:" HERBAL SUPPLEMENTS - SAFETY"
See Drug Consult reference:" GERMAN COMMISSION E - APPROVED HERBS"
See Drug Consult reference:" BOTANICAL SAFETY HANDBOOK TERMS - DEFINITIONS"
See Drug Consult reference:" THE DIETARY SUPPLEMENT HEALTH AND EDUCATION ACT OF
1994"

MECHANISM OF ACTION/PHARMACOLOGY
A) MECHANISM OF ACTION
1) SUMMARY: In human studies, saw palmetto's mechanism of action in the treatment of
benign prostatic hyperplasia (BPH) may have multiple sites of action and involves
antiandrogenic, antiestrogenic, and estrogenic properties (Stenger et al, 1982; Elghamry &
Haensel, 1969).
a) Although the primary action of saw palmetto for treatment of BPH is related to its
testosterone-altering effects, in animal and tissue studies anti-inflammatory, antineoplastic,
cholesterol-blocking, enzyme inhibition, platelet inhibition, and protein synthesis inhibition
properties have been observed (Stenger et al, 1982; Elghamry & Haensel, 1969).
2) ANTIANDROGENIC EFFECTS:
a) The effect of the liposterolic extract of serenoa on experimental prostate enlargement was
investigated in three groups of rats: shams treated with serenoa extract (sham rats),
castrated animals treated with estradiol and testosterone (castrated rats), and castrated
animals treated with estradiol/testosterone and treated with serenoa extract (castrated and
treated rats). Following three months of continuous hormonal treatment, the weight of
prostates in estradiol/testosterone-treated castrated rats was significantly increased in
comparison with sham-operated rats. Such an increase started rapidly, reached a maximum
by 30 days and remained at a plateau or slightly declined thereafter. The increase of prostate
total weight induced by the hormone treatment was inhibited by administration of serenoa
extract. The weight was significantly lower at day 60 and day 90 for the dorsal and lateral
regions of the prostate. The weight of the ventral region of the prostate was significantly
lower after 30 and 60 days treatment with LSESR. These results demonstrated that
administering serenoa extract to hormone-treated castrated rats inhibited the increase in
prostate wet weight (Paubert-Braquet et al, 1996).
b) The lipophilic-sterol extract inhibited the formation of testosterone metabolites in a study
done on cultures of epithelial cells and fibroblasts from benign prostatic hyperplasia and
prostatic cancer tissues (Newall et al, 1996).
c) Saw palmetto lipophilic extract significantly reduced the amount of radioactive
dihydrotestosterone and radioactive testosterone uptake by cytol receptors of 11 human
tissues (el-Sheikh et al, 1988).
d) In animal and tissue studies, a hexane extract of the berries appeared to have
antiandrogenic properties by inhibiting the enzyme testosterone-5-alpha-reductase which
converted testosterone to dihydrotestosterone. It also inhibited 3-ketosteroid reductase from
converting dihydrotestosterone to an androgen compound and has a direct action on the
estrogen receptors (Champault et al, 1984; Sultan et al, 1984).
1) In a double-blind study of 35 men with benign prostatic hyperplasia, 18 were given saw
palmetto extract 160 milligrams twice daily and 17 were given placebo. At the end of the 90
day study, both androgen, estrogen, and progesterone receptors from prostate tissue

samples were evaluated by two different techniques. The results from the androgen receptor
analysis demonstrated there was no change in the number of cytosol androgen receptors,
but the number of nuclear androgen receptors was significantly lower in the saw palmetto
group (60% of the placebo group were positive for the nuclear receptor compared to 10% in
the saw palmetto group). These results indicated that the saw palmetto extract probably
competitively blocks the translocation of the cytosol androgen receptor to the nucleus
(DiSilverio et al, 1992). Saw palmetto acts directly at the level of the androgen receptor
(Carilla et al, 1984).
e) In vitro studies demonstrated that lipophilic extract competitively inhibited
dihydrotestosterone from binding to cellular sites and nuclear androgen receptor sites,
causing increased metabolism and excretion of dihydrotestosterone (Sultan et al, 1984).
3) ANTIESTROGENIC EFFECTS:
a) In a double-blind study of 35 men with benign prostatic hyperplasia (BPH), 18 received
saw palmetto extract 160 milligrams twice daily and 17 received placebo. At the end of the 90
day study, both androgen, estrogen, and progesterone receptors from prostate tissue
samples were evaluated by two different techniques. Men receiving the saw palmetto extract
had significantly lower cytosol and nuclear receptor values for estrogen and progesterone
compared to the placebo group. Since the progesterone receptor content is linked to
estrogenic activity, the results of the evaluation implied that the saw palmetto extract exerted
significant antiestrogenic effect. Antiestrogenic agents inhibited stromal prostatic mass growth
in BPH patients (DiSilverio et al, 1992).
4) ANTI-INFLAMMATORY EFFECTS:
a) Antiedemic effects have been noted in rat, mice, and guinea pigs. Hexane extracts have
demonstrated anti-inflammatory activity (Breu et al, 1992; Champault et al, 1984; Tarayre et
al, 1983; Wagner et al, 1981). A possible mechanism is inhibition of histamine-induced
pathways, increasing the capillary permeability (Stenger et al, 1982).
1) An in vitro study using human polymorphonuclear neutrophils (PMN) demonstrated that
the anti-inflammatory effects may be due to inhibition of 5-lipoxygenase metabolites and the
production of PMN cells (Paubert-Braquet et al, 1997).
2) There is an inhibitory influence on the biosynthesis of the inflammatory arachidonic acid
metabolites. In vitro tests done with fruit extracts demonstrated inhibition of cyclooxygenase
and 5-lipoxygenase pathways (Breu et al, 1992).
3) The anti-inflammatory effect may be due to a polysaccharide with a molecular weight
over 100,000 (Wagner & Flachsbarth, 1981; Wagner et al, 1981).
5) ANTINEOPLASTIC EFFECTS:
a) Two acylglycerides (l-monolaurin and l-monomyristen) were isolated from a 95% ethanol
extract of the powdered fruits. These two substances demonstrated some activity in a brine
shrimp lethality test against renal (A-498 cells) and pancreatic (PACA-2) human tumor cells. A
borderline cytotoxicity was demonstrated against human prostatic (PC-3) cells (Shimada et al,
1997).
1) There was weak cytotoxic activity and some cell proliferation inhibition in CA-PC3 cell
cultures using 50 micrograms/milliliter (mcg/mL) of a sterol extract. When 10 mcg/mL was
used, there was some cell proliferation stimulation. At a concentration of 400 mcg/mL, a
weak cytotoxic activity was reported. Levels were measured using tritium-labeled thymidine
uptake (Ravenna et al, 1996).

6) ANTIHYPERLIPIDEMIC EFFECTS:
a) Phytosterols have improved benign prostatic hyperplasia (BPH). A double-blind study
consisted of 200 men receiving beta-sitosterol (20 milligrams) or placebo three times daily.
The beta-sitosterol produced an increase in maximum urine flow rate from a baseline of 9.9
milliliters/second (mL/s) to 15.2 mL/s and a decrease in mean residual urinary volume of 30.4
mL from 65.8 mL (Berges, 1995).
b) Sitosterols have been given orally as a treatment for atherosclerosis. There are sitosterols
in saw palmetto which compete with cholesterol for absorption sites in the gastrointestinal
tract (Tyler et al, 1981).
7) ENZYME INHIBITION EFFECTS:

a) Acetylcholine
1) Lipidic (0.3 to 1 milligram/milliliter) and saponifiable extracts of saw palmetto antagonized
the contracting effect of acetylcholine (0.1 to 100 micromoles) on rat urinary bladders. The
results were concentration dependent (Gutierrez et al, 1996).
b) Lipoxygenase
1) A study done in cell cultures at a concentration of 18 micrograms/milliliter inhibited
lipoxygenase (Breu et al, 1992).
c) Hydroxysteroid (3-alpha) dehydrogenase
1) The sterol extract, in doses of 5.7 units/milliliter of saw palmetto, demonstrated inhibitory
effects on hydroxysteroid (3-alpha) dehydrogenase (androgen metabolism) in humans
(Sultan et al, 1984).
d) 5-alpha-reductase (5aR)
1) There are two isoforms of 5-alpha-reductase (5a-R). The lipido-sterol extract of saw
palmetto (LSESr) inhibited both in insect cell cultures. LSESr illustrated non-competitive
isozyme type 1 and uncompetitive inhibition for isozyme 2. The inhibition may be due to
modulating the membrane environment of 5-alpha-reductase (Iehle et al, 1995).
2) An in vitro examination of the structural necessities of free fatty acids in saw palmetto
which caused 5-alpha-reductase (5a-R) inhibition demonstrated a strongly polar end-group
and a molecular skeleton allowing non-polar interactions with 5a-R were necessary
(Niederprum et al, 1994).
3) 5a-R was inhibited by saw palmetto lipid extract at a concentration (IC50) of 0.025
milligram/milliliter. The test was done in vitro on human foreskin fibroblast (Hagenlocker et
al, 1993).
4) In a study of 20 men with benign prostatic hyperplasia who had testosterone, follicle
stimulating hormone, and luteinizing hormone measured before and after 30 days of
treatment, no differences in hormone levels were demonstrated. The 20 men were given 160
milligrams of a lipophilic extract of Serenoa repens twice daily. The mechanism of action
does not involve serum hormone level reductions (Casarosa et al, 1988).

8) ESTROGENIC EFFECTS:
a) In a 3-month, double-blind, controlled study of men with benign prostatic hyperplasia
(BPH), saw palmetto demonstrated estrogenic and antiprogesterone activity demonstrated by
estrogen and progesterone receptor action (DiSilverio et al, 1992).
b) Saw palmetto berries contain 18.9 milligrams/100 milliliters (mg/mL) beta-sitosterol and
0.022 mg/mL beta-sitosterol-D-glucoside (Schoepflin et al, 1966; Haensel et al, 1964).
Subcutaneously injected into immature female mice, beta-sitosterol is estrogenic. Pure betasitosterol is less than 1/10th as potent as estradiol and the saw palmetto extract is about
1/10,000th as potent (Duke, 1985; Elghamry & Haensel, 1969).
c) Permixon(R), a commercial product from France, was without estrogenic or antiestrogenic
effects in clinical trials (Stenger et al, 1982).
9) PLATELET INHIBITION EFFECTS:
a) Saw palmetto is not used to inhibit platelet function. Rat studies using a concentration of
700 micrograms/milliliter did not have an effect on arachidonic acid transformations (Tarayre
et al, 1983).
10) PROLACTIN INHIBITION EFFECTS:
a) A study done on Chinese hamster ovary cells determined that saw palmetto extract may
inhibit prolactin-induced prostate growth by inhibiting several steps of prolactin receptor
signal transduction (Vacher et al, 1995).
11) PROTEIN SYNTHESIS STIMULATION EFFECTS:
a) One study demonstrated a weak ability to stimulate protein synthesis when using 25 to 50
micrograms/milliliter of the sterol extract in cell cultures (Sultan et al, 1984).
12) SPASMOLYTIC EFFECTS:
a) The spasmolytic effect of the lipidic fraction of saw palmetto is at least partially due to
sodium/calcium exchanger activation and interference with intracellular calcium mobilization.
Protein synthesis is also involved (Gutierrez et al, 1996a).

1) Total lipidic and saponifiable extracts of saw palmetto produced a dose dependent
relaxation on rat aorta tonic contractions produced by noradrenaline and on tonic
contractions of rat uterus induced by potassium chloride. The effect is related to the
inhibition of calcium ions inward flow, acting at the plasma membrane level (Gutierrez et al,
1996).
2) Calcium is not required to obtain the relaxation. Calcium ion flux inhibition is not the main
mechanism of action. Maximal relaxation was greater than 90% in both cases. The effective
concentration where there was 50% relaxation (EC50) was significantly lower with the lipidic
fraction in the uterine study, but there was no difference in the aorta study (Gutierrez et al,
1996).
3) dL propranolol (1 micromole) potentiated the effects of the extracts; cycloheximide (10
micrograms/milliliter) antagonized the effect of the lipidic but not the saponifiable extract.
Haloperidol (1 micromole) did not inhibit the spasmolytic effect. Neither genistein (a tyrosine
kinase inhibitor) (10 micromoles) nor alpha difluoromethyl-ornithine (an ornithine
decarboxylase inhibitor) (10 millimoles) had any effect on the relaxation response. These
effects are not produced by receptor activation because the beta-blocker propranolol and the
dopamine receptor antagonist haloperidol did not inhibit the effect (Gutierrez et al, 1996).
b) Spasmolytic activity was tested in guinea pigs using an extract produced by a 95%
ethanolic extract in a concentration of 0.15 milligram/milliliter. The dose had some
spasmolytic activity in the bladder, ileum, and vas deferens against potassium chloride or
norepinephrine-induced contractions (Odenthal, 1996).

B) REVIEW ARTICLES
1) ENGLISH
a) A review on the mechanism of action and clinical studies pertaining to saw palmetto
concluded that saw palmetto may have a significant effect on urinary flow rates and symptom
scores (Gerber, 2000).
b) Controlled trials involving phytotherapeutic agents for the treatment of benign prostatic
hypertrophy are critiqued (Lowe et al, 1998) and a meta-analysis of 18 recent trials involving
saw palmetto is available (Wilt et al, 1998).
c) The causes and methods of treatment of benign prostatic hypertrophy are discussed and
comparisons made between synthetic agents and phytopharmaceuticals used in treatment
(Bach et al, 1997).
d) The pharmacology and therapeutic effects of saw palmetto in the treatment of benign
prostatic hyperplasia are reviewed (Plosker & Brogden, 1996).

THERAPEUTIC USES
BENIGN PROSTATIC HYPERTROPHY
1) OVERVIEW:

EFFICACY: Adult, possibly effective

DOCUMENTATION: Adult, excellent
2) SUMMARY:

- Increasing doses of saw palmetto fruit extract

were no more effective than placebo in reducing
lower urinary tract symptoms in benign prostatic
hyperplasia (BPH) in a double-blind,
multicenter, placebo-controlled, randomized
trial (n=369) (Barry et al, 2011); however, a
systematic review of 18 randomized clinical
trials (n=3000) conducted between 1983 and 1997
concluded that saw palmetto or saw palmetto

herbal combination products provided some

benefit in controlling lower urinary tract
symptoms and flow measures (Wilt et al, 2000).

- A lipido-sterolic extract of Serenoa repens

exhibited similar efficacy to tamsulosin in
the treatment of benign prostatic hypertrophy
in a 12-month, randomized, double-blind,
multicenter, international trial (n=704)
(Debruyne et al, 2002).

- Saw palmetto extract had no effect on levels

of testosterone, dihydrotestosterone, folliclestimulating hormone, luteinizing hormone
(Strauch et al, 1994; Casarosa et al, 1988;
Reece-Smith et al, 1986), or PSA (Braeckman,
1994).
3) ADULT:
a) In a double-blind, multicenter, placebo-controlled, randomized trial (n=369),
increasing doses of saw palmetto fruit extract were no more effective than placebo in
reducing lower urinary tract symptoms (LUTS) in male patients with benign prostatic
hyperplasia (BPH). Patients were randomized to receive saw palmetto extract 320
mg/day, with dose escalations to 640 mg/day at week 24 and 960 mg/day at week 48,
or placebo. The patients had a mean age of 61 years, were 80% white, and had a mean
American Urological Association Symptom Index (AUASI) score of 14.6 (SD, 4.5). For the
primary outcome of a change in AUASI score from baseline to 72 weeks, there was no
difference in the saw palmetto group at any dose level (mean score decrease, -2.2
points) and the placebo group (mean score decrease, -2.99 points) (1-sided p=0.91).
There was also no difference between the groups in the secondary outcomes of quality
of life (International Prostate Symptom Score), nocturia (AUASI), peak flow rate, postvoid residual volume, and PSA level, or in the scores for several indices (BPH Impact
Index, International Index of Erectile Function scale, Male Sexual Health QuestionnaireEjaculatory Dysfunction scale, International Continence Society male incontinence scale,
Jenkins Sleep Dysfunction scale, and the National Institutes of Health Chronic Prostatitis
Symptom Index) (Barry et al, 2011).
b) A systematic review of 18 randomized clinical trials comprising approximately 3000
subjects conducted between 1983 and 1997 concluded that saw palmetto or saw
palmetto herbal combination products provided some benefit in controlling lower urinary
tract symptoms and flow measures in men with benign prostatic hypertrophy (BPH). The
majority of trials evaluated the effectiveness of oral doses of 320 mg saw palmetto daily
for a mean duration of 9 weeks, although doses tested ranged from 100 mg to 640 mg
daily and trial duration ranged from 4 to 48 weeks. Saw palmetto improved urinary
symptoms (measured using a variety of scales), nocturia, peak urine flow, mean urine
flow, and residual urine volume by 28%, 25%, 24%, 28%, and 43%, respectively,
compared with placebo. Similar adverse events were reported in treatment and placebo
subjects; all were considered mild. Efficacy of saw palmetto was comparable to
finasteride in control of urinary symptoms, nocturia, and flow measures in subjects with
BPH in the one comparative study included in this analysis. Significantly more subjects
treated with finasteride exhibited erectile dysfunction (4.9%) compared with subjects
treated with saw palmetto (1.1%) (p less than 0.001). Trials were included in this
analysis only if the following criteria were met: subject inclusion criteria was
symptomatic BPH, the therapy evaluated was saw palmetto or saw palmetto herbal
combination products, placebo-control or other active-control, and treatment duration
was at least 4 weeks. Of the trials included in this analysis, 16 used double-blind
methodology, 14 included placebo controls, and 4 evaluated herbal combination

products containing saw palmetto. Interpretation of the results of this analysis should be
viewed with caution due to inherent flaws related to the data available for analysis.
Problems identified included use of variable doses and preparations of saw palmetto,
lack of consistency in outcome measures between studies, use of non-validated urologic
symptom scales in the majority of trials evaluated, and short duration of the study (Wilt
et al, 2000; Wilt et al, 1998).
c) A lipido-sterolic extract of Serenoa repens (Permixon(R)) exhibited similar efficacy to
the alpha-blocker tamsulosin in the treatment of benign prostatic hypertrophy (BPH) in a
12-month randomized, double-blind, multicenter international trial (n=704; mean age
65.5 years). Following a 4-week placebo lead-in period, subjects were randomly
assigned to oral therapy with 320 mg Serenoa repens daily or 0.4 mg tamsulosin daily
for 12 months. Reductions of 4.4 in the International Prostate Symptom Score (IPSS)
compared to baseline (mean IPSS=15.3 at baseline) were observed after treatment for
one year in both groups (differences between groups were not significant). Significant
differences between groups were not observed in IPSS score for irritative or obstructive
symptoms. Peak urinary flow was increased by 1.79 mL/sec in subjects treated with
Serenoa repens compared with 1.89 mL/sec in subjects treated with tamsulosin
(difference was not significant). Prostate volume was reduced slightly (0.99 cubic mL) in
subjects treated with Serenoa repens compared to a slight increase (0.22 cubic mL) in
subjects treated with tamsulosin although this difference was not significant. No
significant changes were observed in serum prostate specific antigen (PSA) in either
group. Significant differences between groups were not observed in sexual function as
evaluated using the male sexual function questionnaire (MSF-4). Six subjects in each
group developed acute urinary retention that resulted in hospitalization in 4 tamsulosin
subjects and 3 Serenoa repens subjects. Ejaculation disorders were present in 4.2% of
subjects treated with tamsulosin compared to 0.6% of subjects treated with Serenoa
repens (p=0.001). Other adverse events were similar between groups and included
rhinitis, headache, dizziness, fatigue, asthenia, postural hypotension, dry mouth, and
reduced libido. Withdrawals were similar between groups, with 542 subjects completing
the study. Important inclusion criteria for this study included IPSS greater than or equal
to 10, maximum urinary flow rate between 5 to 15 mL/sec, voided volume of at least
150 mL, residual urine volume less than 150 mL, prostate volume of at least 25 mL, and
PSA levels less than 4 nanograms/mL (Debruyne et al, 2002).
d) In a 2-year open-label study, a lipido-sterolic extract of Serenoa repens (Permixon
(R)) was a safe and efficacious treatment for benign prostatic hypertrophy (BPH)
(n=155; mean age 65.3 years). Subjects with symptomatic BPH for greater than 6
months and an International Prostate Symptom Score (IPSS) of 6 or higher (mean 12.8)
entered a one-month single-blind, placebo lead-in period followed by oral treatment with
160 milligrams (mg) Serenoa repens twice daily for 2 years. Progressive improvement
over the 2-year period was observed for the main efficacy outcome, IPSS. Reductions in
IPSS total score compared to baseline of 31%, 38.6%, 40.6%, and 41.4%, respectively,
were observed at 6, 12, 18, and 24 months (p=0.001). Quality of life measures were
also significantly improved compared to baseline beginning at 6 months and continuing
throughout the study (p less than 0.001). Significant increases in maximum urinary flow
rate compared to baseline of 34.7%, 27.2%, 7.9%, and 9.5%, respectively, were
observed at 6, 12, 18, and 24 months (p value not provided). Although maximum
urinary flow rate was observed to gradually decrease at all time points after the 6
months treatment measurement, maximum urinary flow rate remained significantly
higher than that observed at baseline at all measurement points. Significant
improvements in sex life as evaluated using the male sexual function questionnaire
(MSF-4 score) compared to baseline were observed at 18 and 24 months (p less than
0.001). At 6 months, a 14.6% reduction in prostate volume was noted. No further
changes in prostate volume were noted for the duration of the trial. No changes were
observed in prostate specific antigen (PSA) levels, plasma hormone levels, hematologic
and biochemical measurements, or vital signs. Three subjects withdrew from the study
due to lack of efficacy. Adverse events occurred in 5.8% of subjects but none were
attributed to Serenoa repens. Other inclusion criteria included maximum urinary flow
rate between 5 to 15 milliliters/second (mL/s), voided volume between 150 to 400 mL,

residual urine volume less than 150 mL, prostate volume of at least 25 cubic
centimeters, and PSA levels of less than 4 nanograms/mL (Pytel et al, 2002). The validity
of efficacy results of this study should be interpreted with caution due to methodological
flaws, including open-label study design and lack of a placebo control group.
e) A lipido-sterolic extract of Serenoa repens (Permixon(R)) was effective in improving
subjective and objective parameters of benign prostatic hypertrophy (BPH) in subjects
with mild to moderate disease in an open-label study (n=75; 52 to 78 years). Subjects
with an International Prostate Symptom Score (IPSS) of less than 19 (mean 8.2)
received oral treatment with 160 milligrams (mg) Serenoa repens twice daily for 9 weeks
(n=57) or no treatment (n=18; controls). IPSS total score and quality of life index point
reductions of 26.8% and 18.2%, respectively, were reported compared to baseline (p
less than 0.001) in subjects treated with Serenoa repens while no changes were
observed in the control group. Maximum urinary flow rate increased by 6% while
opening detrusor pressure and detrusor pressure at maximum flow decreased by 12.6%
and 12.8%, respectively, compared to baseline in subjects treated with Serenoa repens
(p less than 0.001). Subjects treated with Serenoa repens also exhibited a 12.6%
reduction in residual urine volume compared to their baseline levels (p less than 0.05).
Similar improvements were not observed for any of these measurements in control
subjects. Mean prostate volume was reduced in subjects treated with Serenoa repens
while it was increased in the control group (differences were not significant compared to
baseline in either group) (Al-Shukri et al, 2000). A similar open-label study reported
similar efficacy in improving subjective and objective parameters of benign prostatic
hypertrophy (BPH) for two dose levels of a lipido- sterolic extract of Serenoa repens
(Libeprosta(R)) in subjects with marked obstruction and lower urinary tract symptoms
(n=100; average age 63.67 years) (Giannakopoulos et al, 2002). The validity of the
results of these studies should be interpreted with caution due to methodological flaws,
including open-label study design, non-randomization, and lack of a placebo control
group.
f) A combination product containing saw palmetto, cernitin, B-sitosterol, and vitamin E
improved subjective but not objective symptoms of benign prostatic hyperplasia (BPH)
compared to placebo in a randomized clinical trial (n=144). Subjects were randomly
assigned to receive two tablets of a combination product containing 286 milligrams (mg)
of saw palmetto/phytosterol (saw palmetto standardized to 40% to 50% free fatty acids/
B-sitosterol standardized to 43%), 378 mg cernitin, and 100 international units of
vitamin E daily or placebo for three months. After treatment for three months, mean
total American Urological Association Symptom Index (AUA) score was reduced by 33%
in subjects treated with the combination herbal product compared to a 18% reduction in
subjects treated with placebo (p=0.014). Subjects treated with the herbal combination
product exhibited a 90% improvement in the total AUA score over three months
treatment compared to placebo (p=0.009). Improvement of 242% in daytime urinary
frequency and 258% in nocturia were also observed compared to placebo over the
three-month treatment period (p=0.031 and p less than 0.001, respectively). No
significant differences were observed between groups on measures of maximum and
average urinary flow rates, residual urine volumes, or prostatic specific antigen (PSA)
levels. Adverse events in the treatment group included flatulence (n=3), headache
(n=1), urinary tract infection (n=1), herpes zoster (n=1), and right arm laceration
(n=1). Important inclusion criteria included no evidence of cancer, maximum urinary
flow rate between 5 to 15 milliliters/second (mL/s), and voided volume greater than 100
mL (Preuss et al, 2001). It is not known if this study incorporated any type of blinding.
g) A saw palmetto herbal blend caused involution of the prostatic epithelium in men
with symptomatic and uncomplicated BPH. The study included ambulatory men (n=44),
45 to 80 years, who participated in a six-month randomized, double-blind, placebocontrolled trial. Men were randomized to receive 106 milligrams (mg) saw palmetto
herbal blend or placebo three times daily with meals. The herbal blend consisted of saw
palmetto (106 mg), nettle root extract (80 mg), pumpkin seed oil extract (160 mg),
lemon bioflavonoid (33 mg), beta-carotene (190 international units), and other minor
ingredients. Prostate epithelial contraction was significant, especially in the transition
zone, and histological studies revealed an increase in the atrophy rate from 17.8% at

baseline to 10.7% after six months of saw palmetto herbal blend (p less than 0.01). The
clinical effects, such as the International Prostate Symptom Score (IPSS), uroflowmetry,
and post void residual urine volume had a slight advantage in the saw palmetto group
versus the placebo group. No significant change was noticed in prostate specific antigen
or prostate volume. No serious adverse effects were demonstrated in the treatment
group. Results cannot be attributed to saw palmetto alone because a combination herbal
blend was used (Marks et al, 2000).
h) A fixed combination of extracts of saw palmetto fruit (Serenoa repens) and nettle
root (Urtica dioica) (PRO 160/120) produced the same effect as the 5-alpha-reductase
inhibitor finasteride in men with benign prostatic hyperplasia (BPH), regardless of the
baseline prostate volume. The study assessed a subgroup of men (n=431), 50 to 88
years, who participated in a 48-week randomized, multicentre, double-blind clinical trial.
The patients were randomized to receive either two capsules of PRO 160/120 and one
placebo capsule or 5 milligrams (mg) finasteride capsule and two placebo capsules
(double-dummy method). Prostate volumes at baseline were similar in the two groups
and the clinical exam was done at six-week intervals during the double-blind period and
at the end of the 48-week treatment period. The maximum urinary flow increased from
baseline values after 24 weeks by 1.9 (5.6) milliliter(mL)/second with PRO 160/120 and
by 2.4 (6.3) mL/second with finasteride. There was not a statistically significant
difference between the two groups (p=0.52). Patients with small prostates (less than or
equal to 40 mL) had similar improvements, with mean values of 1.8 (5.2) mL/second
with PRO 160/120 and 2.7 (7.4) mL/second with finasteride. The outcome for men with
prostates of greater than 40 mL was similar, at 2.3 (6.1) and 2.2(5.3) mL/second,
respectively. The improvement in the International Prostate Symptom Score (IPSS) was
similar in both groups, but the PRO 160/120 had better tolerability and less adverse
effects than finasteride. Results of this study suggest that the efficacy of treatment with
finasteride or PRO 160/120 cannot be predicted by the patients' baseline prostate
volumes (Sokeland, 2000).
i) A 50% reduction in residual urine volume, a 6.1 mL/sec increase in peak urine flow,
and a lower rate of deterioration in the treated patients was reported in a prospective,
multicenter study completed over 3 years. A hexane extract (320 mg/day) was
evaluated in 435 patients with benign prostatic hyperplasia (Bach & Ebeling, 1996).
j) Saw palmetto significantly reduced the International Prostate Symptom Score (IPSS)
in 46 evaluable patients with lower urinary tract symptoms (LUTS) resulting from benign
prostatic hypertrophy. Patients received saw palmetto 160 milligrams twice daily for six
months in this non-randomized, open-label trial. A significant improvement in mean IPSS
was evident at two, four, and six-month evaluations (p less than 0.001) and 85% of
patients showed improvement. A greater than 50% improvement in IPSS was observed
in 21% at two months, 30% at four months, and 46% of patients at six months. No
significant change in peak urinary flow rate, post void residual urine volume, bladder
pressure, or serum prostate specific antigen (PSA) was observed. The investigators
noted that changes in IPSS may be due to a placebo effect, considering the study design
and that urodynamic changes may not have been detected due to patient selection
(58% without bladder obstruction) and/or sample size (Gerber et al, 1998).
k) Almost 75% of 38 benign prostatic hyperplasia (BPH) patients who were treated with
saw palmetto extract for a year reported improved subjective complaints, an increase in
flow rates from 10.36 milliliters/second (mL/s) to 14.44 mL/s, a 10.6% reduction in the
size of the prostate, and a reduction of 47 milliliters of residual urine. Ninety percent of
the patients reported that urinary retention decreased or disappeared. The study was
open and uncontrolled and results were confirmed by Student t test. The dose was 320
milligrams of the extract IDS89/day (Kondas et al, 1996).
l) Saw palmetto extract was significantly more effective than placebo in a double-blind,
randomized, placebo-controlled, multicenter study of 176 benign prostatic hyperplasia
(BHP) patients who were non-placebo responders in other studies. The patients were
given either 160 milligrams of the extract twice a day or placebo. Results of the study
are listed below: Symptom/saw palmetto group/placebo group. Decreased dysuria
severity/31.3%/16.1% decrease; daytime urinary frequency/31% decrease/unchanged;
decreased nocturnal urinary frequency/32.5%/ 17.7; and increased mean peak urinary

flow/28.9%/8.5% (Descotes et al, 1995).

m) Some improvement was observed in benign prostatic hyperplasia (BPH) symptoms
after 45 days and 90 days in another study. About 88% of the patients and 88% of the
physicians considered the treatment to be beneficial. Five hundred and five patients with
mild to moderate symptoms of BPH were treated with oral Prostaserene(R) (saw
palmetto extract) 160 mg twice daily. The final number of patients evaluated after 90
days of treatment was 305. Patients were evaluated for urinary flow rates, residual
volume, prostate size, and subjective improvement (patients and physicians). Subjective
evaluations of treatment made by patients after 45 and 90 days of treatment were quite
favorable. After 45 days, 83% of patients estimated the drug was effective. After 90
days, the percentage increased to 88%. Similarly, global evaluations made by physicians
after 45 and 90 days demonstrated 81% and 88% effectiveness, respectively. The
objective evaluations demonstrated remarkable improvements in all measurements.
Maximum urinary flow increased from 9.8 to 12.2 mL/sec, mean urinary flow increased
from 5.8 to 7.4 mL/sec, prostatic volume decreased from 40,348 to 36,246 mm(3), and
the international prostate symptom score decreased from 19 to 12.4. Serum PSA
concentrations were not altered during treatment. Only 5% of patients experienced side
effects (Braeckman, 1994).
n) Reduction in edema and congestion of the prostate was reported in a prospective,
randomized, double-blind study of eight benign prostatic hyperplasia (BPH) patients who
were evaluated by open prostatectomy. Prostate morphological changes occurred in
patients on Sabal extract IDS89. All types of prostate hypertrophy were found, including
predominately stromal, predominately glandular, and mixed type. The placebo group (10
patients) had marked edema and mucoid degeneration of the periglandular stroma or
stromal nodules and intraglandular congestion. The study group (eight patients)
demonstrated significant improvement in mucoid degeneration, intraglandular
congestion, congestive prostatitis, and glandular stromal edema. The study lasted 12
weeks and the dose was 320 milligrams of Sabal extract (IDS89) three times a day
(Helpap et al, 1995).
o) Obstructive symptoms, residual volume, and mean and maximum urine flow rates
were significantly improved in a study of 42 patients with stage two or three benign
prostatic hyperplasia who were treated for 12 months with a daily dose of 320
milligrams. Routine laboratory examinations, rectal digital examination, duration of
urination, duration of urination until maximum flow, maximum flow rate, urine volume,
suprapubic ultrasound examination, nocturia, feeling of urine residual, dribbling, and
hesitancy were measured at three, six, and twelve months. Improvement was observed
in all areas (Romics et al, 1993).
p) In a drug monitoring study, 1334 outpatients with benign prostatic hyperplasia (BPH)
were treated for 12 weeks with an extract from the fruits of Sabal serrulata. Under this
treatment, the volume of residual urine decreased on average by 37% and nocturia
decreased by 54%. The percentage of patients with dysuric pain decreased from 75% to
37%. The efficacy of the drug was rated good to excellent in more than 80% of the
cases. Good to excellent tolerability was reported by more than 95% of the patients. The
improvement in the irritative symptoms may be considered relevant in terms of
improvement in the quality of the life of the patients and justifies this form of treatment
(Vahlensieck et al, 1993).

COMPARATIVE EFFICACY
ALFUZOSIN
1) SUMMARY:
a) Comparable treatment results of maximum and mean urine flow, residual urine
volume, and bladder irritability were obtained in a double-blind study of Serenoa repens
and alfuzosin (Grasso et al, 1995).
2) BENIGN PROSTATIC HYPERTROPHY (BPH):

a) Alfuzosin was statistically better in producing a rapid onset of action concerning

obstructive symptoms, but in other measures, such as irritative score, maximum and
mean urine flow, and residual urine volume, the two methods of treatment were
comparable. This was a study of 63 BPH patients who participated in a 3-week, doubleblind, comparative parallel-group study. One group took alfuzosin 2.5 mg 3 times a day
while another group took Serenoa repens 160 mg twice a day. Efficacy was determined
by clinical symptoms, urinary flow rates, and residual urinary volume (Grasso et al,
1995).

CYPROTERONE
1) SUMMARY:
a) In a double-blind investigative study of Serenoa repens and cyproterone, a reduction
in prostate volume was noted (DiSilverio et al, 1993).
2) BENIGN PROSTATIC HYPERTROPHY (BPH):
a) A statistically significant difference in prostate volume reduction was noted between a
combination therapy group and two other groups who used monotherapy with Serenoa
repens extract or cyproterone. The study was a multicenter, double-blind investigation of
BPH patients who were using Serenoa repens plus cyproterone acetate (DiSilverio et al,
1993).
FINASTERIDE
1) SUMMARY:
a) Finasteride demonstrated a significant reduction in prostate size and lowered serum
dihydrotestosterone more effectively in several comparison studies with Permixon(R)
(extract of Serenoa repens) (Carraro et al, 1996; Strauch et al, 1994; Rhodes et al,
1993).
b) A combination of saw palmetto and stinging nettle extract was better-tolerated and
equivalent in efficacy for BPH symptoms to finasteride in a double-blind, randomized,
multicenter trial (Sokeland, 2000).
2) BENIGN PROSTATIC HYPERTROPHY (BPH):
a) A combination of saw palmetto and stinging nettle extracts was equivalent in efficacy
to finasteride but was better-tolerated. In a multi-center, double-blind, randomized
study, after a two-week placebo run-in period, men 50 to 88 years received either PRO
(Prostagutt forte(R), a combination of saw palmetto 160 milligrams (mg) and stinging
nettle 120 mg) two capsules and one placebo daily or finasteride 5 mg with two placebo
capsules daily for 48 weeks. Subjects were examined at baseline, 48 weeks, and at sixweek intervals during the study. Maximal urine flow, mean urine flow rate, voided
volume and duration, time to flow rate increase, prostate volume via ultrasonography,
quality of life, and International Prostate Symptom Scores (IPSS) were measured at each
examination. At the end of the study, prostate volume in the PRO group had decreased
from 42.7 to 42.4 milliliters (mL) and in the finasteride group it decreased from 44 to
37.2 mL (p=0.52). In subgroup analysis by prostate size, mean scores decreased with
no significant differences between the treatment groups or for differing prostate size.
The maximal urine flow rate increased in both treatment groups, without a significant
difference between groups. IPSS scores also decreased in both groups during the study,
with no significant difference between groups. In the PRO group, 52 patients
experienced a total of 74 adverse events and in the finasteride group, 54 patients
experienced 96 adverse events (Sokeland, 2000).
b) Finasteride may produce a reduction of prostate volume of up to 30% with a slight
improvement in uroflow and no significant change in urine residual volume. One study of
1098 patients demonstrated a 37% reduction in the Prostate Symptom Score (IPPS) for
finasteride and a 39% reduction of IPPS for saw palmetto (Permixon(R)). Finasteride
reduced prostate size by 18% while Permixon(R) only reduced prostate size by about
6%. In other variables, they were about equal (Carraro et al, 1996).
c) About 10.7% of patients discontinued treatment due to finasteride adverse effects. In
one 3-year, prospective, multicenter study, the adverse effects with saw palmetto were
only 1.8%, while the residual urine volume was decreased by 50% and the peak urinary

flow increased by 6.1 milliliters/minute (Bach et al, 1997).

d) Thirty-two healthy males were randomized and given either finasteride (Proscar(R)) 5
milligrams daily (n=10), saw palmetto (Permixon(R)) 80 milligrams twice daily (n=11),
or placebo (n=11) for one week. The inhibition of 5-alpha-reductase was measured. At
twelve hours into the experiment and with only one dose being given, finasteride
lowered the serum dihydrotestosterone level by 65%. After multiple doses, the range
was minus 52% to minus 60%. No significant difference was observed between
finasteride and saw palmetto. No statistically significant difference was demonstrated
between finasteride and placebo except on day three and six (Strauch et al, 1994).
e) In a seven-day clinical trial of 32 males, patients were divided randomly into groups
receiving finasteride 5 milligrams/day, Permixon(R) (extract of Serenoa repens) 320
milligrams/day, or placebo. Serum levels of testosterone and dihydrotestosterone were
compared. Finasteride exerted more potent inhibition of 5-alpha-reductase compared to
saw palmetto extract (Rhodes et al, 1993).

PRAZOSIN
1) SUMMARY:
a) Prazosin was slightly more effective in controlling symptoms of bladder irritation than
Serenoa repens (Semino et al, 1992).
2) BENIGN PROSTATIC HYPERTROPHY (BPH):
a) Forty-five patients with BPH were entered into a comparative study of prazosin versus
Serenoa repens extract. After 12 weeks, flow rates and various subjective measures
were evaluated. Prazosin was only slightly more advantageous in controlling the irritative
symptoms (Semino et al, 1992).
PYGEUM AFRICANUM EXTRACT
1) SUMMARY:
a) In patients with prostatic adenomas, a comparison of Serenoa repens and pygeum
africanum found the extract of Serenoa repens significantly more effective in improving
urologic parameters (Duvia et al, 1983).
2) BENIGN PROSTATIC HYPERTROPHY (BPH):
a) The effectiveness and tolerability of Serenoa repens extract and pygeum africanum
extract (EPA) were compared in 30 patients with prostate adenomas. Serenoa repens
therapy was superior in the clinical parameters measured, reducing dysuria, nocturnal
frequency, and prostate size, and increasing voiding rate. Those parameters were
measured at the beginning of the study and at the end of the 30-day trial. Serenoa
repens extract did not induce side effects while EPA created gastric disturbances in two
(13%) patients (Duvia et al, 1983).

TAMSULOSIN
1) SUMMARY:
a) Permixon(R) and tamsulosin were equally effective in men with urinary tract
symptoms secondary to benign prostate hypertrophy (BPH) (Debruyne et al, 2002).
2) BENIGN PROSTATIC HYPERTROPHY (BPH):
a) Permixon(R) and tamsulosin are well-tolerated and equally effective in men with
lower urinary tract symptoms secondary to benign prostatic hypertrophy (BPH).
Permixon(R) is a lipido-sterolic extract of Serenoa repens (LSESr; saw palmetto). It has
antiproliferative activity and is a non-competitive inhibitor of 5-alpha-reductase type one
and two. In this double-blind study, men (n=704; mean age 65.5 years) with
symptomatic BPH were randomized to receive either oral tamsulosin (0.4 milligram
(mg)/day or oral Permixon(R) (320 mg/day). After 12 months, both treatments produced
a similar decrease in total International Prostate Symptom Score (I-PSS). Patients with
severe symptoms experienced the greatest reduction in I-PSS total score. Tamsulosin
achieved full activity at three months and this was maintained until study completion
while continuous improvements were observed throughout the study for Permixon(R).
No differences were observed between treatment groups in irritative and obstructive
symptom improvements. Peak urinary flow rate (Qmax) increased similarly in both

treatment groups (50% of patients experienced a 20% increase). Prostate volume

decreased in the Permixon(R) group and increased in the tamsulosin group. Neither
treatment significantly affected total prostate-specific antigen (PSA) levels. Both
treatments were well-tolerated with a similar overall incidence of adverse effects;
however, ejaculation disorders occurred more frequently with tamsulosin than with
Permixon(R) (4.2% versus 0.6%, respectively; p=0.001) (Debruyne et al, 2002).
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