Document 6430011

Therapeutic Nutrition
by Gina L. Nick, PhD, ND
Chief Scientific Officer at Longevity Through Prevention, Inc.
Phone: 866-587-4622 x702 • Fax: 866-587-4622 • E-mail: [email protected]
P.O. Box 6936 • Laguna Niguel, California 92677 USA
www.LTPonline.coni
Natural Therapies for the Prostate Gland
A Scientific Review of Nutrient and Herbai Combinations that Promote Prostate Health
The prostate is a walnut-sized gland that sits at the base of
the male bladder, surrounding the prostatlc urethra. As part of
the reproductive system, this gland secretes seminal fluid,
energizes sperm and provides for it a favorable alkaline medium.
The prostate is subject to several disease states including
infection, hypertrophy and cancer, causing pain, urinary
frequency and urgency, inability to urinate, painful urination and
sexual dystunction.
Benign prostatic hyperplasia (BPH). prostate cancer, and
prostatitis are its most common disorders. More than 50% of
men in their sixties and as many as 90% of men in their seventies
and eighties are diagnosed with BPH. resulting in 375,000
hospital slays each year in the United States alone. Prostate
cancer is second only to cancer of the lung as the leading cause
of cancer death among men. Each year, more than 100,000
new cases of prostate cancer occur in the US, and more than
30,000 deaths are caused annually by this disease.' The good
news is that over the past 20 years, the survival rate for prostate
cancer has increased from 67% to 97%.^
Unfortunately, benign prostatic hyperplasia (BPH) and
prostate cancer do not have a known etiology, making
prevention difficult and treatment less than ideal. Standard
lines of treatment for these conditions, including pharmacological
preparations, surgical and non-surgicai procedures, hoid
significant risks. Additionally, as new theories about the
functioning of the prostate gland develop, scientists are
questioning the effectiveness and the rationale behind the
continued use of these treatment modalities. A close review of
the medical literature verifies the safety and efficacy of nutritional
and botanical therapeutic agents such as Serenoa repens (saw
palmetto), Urtica dioica (stinging nettle root), Prunus
africanum (pygeum), essential fatty acids, selenium, green
tea extract, tomatoes and zinc to promote and maintain
prostate health and alleviate urologic symptoms. In addition,
select amino acids, in relatively physiologic doses, exhibit
promising clinical results for the prostate patient. These natural
ingredients effect a positive change in prostate health without
the associated risk of adverse reactions. Following is a review
of the most common prostate conditions and available treatment
options, including a compretiensive evaluation of herbal and
nutrient therapies for the prostate gland, scientific validity,
positive patient outcomes, and incidences of negative side
effects.
Benign Prostatic Hyperplasia
(BPH; Prostate Enlargement; Lower Urinary Tract
Symptoms (LUTS)
As a man ages, his prostate gland typicaliy begins to eniarge.
The medical community has no well-defined reason for this
phenomenon, which is identified as benign prostatic hyperplasia
(BPH). benign prostatic hypertrophy, or lower urinary tract
symptoms (LUTS). This condition does not generally cause
symptoms until a man reaches the age of 50. with the majority
of associated problems peaking by age 70. BPH causes the
prostate gland to constrict the urethra, making micturition
increasingly difficult. As the bladder is forced to contract against
increasing resistance, the bladder muscle (the detrusor)
becomes hypertrophied and irritable. As the condition
progresses, the bladder becomes unable to empty completely,
and finally to empty at all. Residual urine in the bladder sets the
stage for serious bladder infections and kidney malfunction.
Symptoms of BPH include:
Reduced caliber and force of urine stream
Frequent urination (particuiarly in the evening)
Urinary urgency
Leaking or dribbling
Urinary retention (inability to pass urine)
Occasionally, a man may not realize that he has a urinary
obstruction until he finds himself unable to urinate at all.
Physicians refer to this type of episode as acute urinary retention,
which can be triggered by a wide variety of drugs with
antioholinergic side effects, both prescription and over-thecounter, such as anti-depressants, cold and allergy medications.
These medications can tighten the bladder outlet, resulting in
urinary retention. Alcohol, cold temperatures or a long period of
immobility can also cause urinary retention when there is a partial
obstruction present. Severe BPH can have serious long-term
health effects such as urinary tract infections, bladder or kidney
damage, bladder stones, painful intercourse, and incontinence.
Conventional Therapies for BPH
Finasteride (Proscar®), terazosin (Hytrin®), doxazosin
(Cardura®). and tamsulosin (Flomac®) are medications
approved by the FDA for the treatment of BPH. These
Pharmaceuticals aim at blocking DHT production or relaxing the
prostatic urethra sphincter. Specifically, finasteride (Proscar®)
inhibits the production of dihydrotestosterone (DHT), while
terazosin (Hytrin®), doxazosin (Cardura®), and tamsulosin
(Flomac®) force smooth muscle relaxation of the prostate and
bladder neck. Nonsurgical treatments include transurethral
microwave procedures (TUMT) and transurethral needle ablation
(TUNA). Surgical treatments include open, laser and
TOWNSENO LETTER tor DOCTORS A PATIENTS - AUGUST/SEPTEMBER 2004
transurethral (TURP) surgery. These treatments remove or
destroy sections of the prostate gland. Botanical and nutritional
therapies for BPH focus on decreasing the size of the prostate
gland, preventing abnormal ceil growth, and supplying the gland
with nutrients to decrease the risk of infection, while maintaining
hormonal balance and preserving the complete gland.
A Closer Look at Finasteride (Proscar)
Finasteride (Proscar®), a popular prescription for BPH,
functions by interfering with the action of 5 alpha-reductase, the
enzyme that converts testosterone into DHT in the prostate
gland. DHT is an androgen that stimulates the synthesis of
specific proteins and causes prostate cells to proliferate. The
theory behind finasteride is that the body is producing too much
testosterone and ultimately DHT, which is causing abnormal cell
proliferation. By blocking the action of 5 alpha-reductase, the
prostate gland should shrink.
Merck sponsored a double-blind placebo controlled study
using finasteride (Proscar®) that demonstrated significant
reductions in DHT,^ improvements in urinary function," and
decreases in prostate volume^ in men with BPH. A bias may be
present considering the sponsor of this research although there
are more pressing issues regarding the use of finasteride. First,
finasteride (Proscar®) only decreases the size of the prostate
gland by 18% even though it reduces DHT levels by a surprising
80%. Further, only37%of men using the drug for an entire year
experience any symptom improvement. Sexual side effects of
finasteride include decreased libido, impotence, and
ejaculatory disorders.^ Finasteride (Proscar®) also
increases a man's risk of developing prostate cancer.^ While
this drug is in fact lowering DHT levels, it is clearly not promoting
the health of the prostate gland. Moreover, the theory that DHT
is the primary cause of abnormal cell growth is scientifically
invalid, since a dramatic decrease in DHT levels plays a minimal
role in preventing abnormal cell growth, and may even promote
it. This theory represents a narrow and disconnected view of
prostate function. A man's serum testosterone level falls as he
ages. If testosterone causes BPH, then why would a man's risk
of developing BPH increase as his levels of testosterone
decrease? There is clearly more to this picture than that which
medical scientists currently accept as fact.
The answer to this dilemma might be the growing imbalance
between estrogen and testosterone levels in aging men. While
estrogen levels remain relatively unchanged, testosterone or
androgen levels fall dramatically as a man ages. However, in
the stroma of the prostate (the area of tissue where BPH is
thought to develop), DHT levels remain constant, while estrogen
levels dramatically increase. The stroma produces additional
estrogen (specifically estradiol) from testosterone in a process
known as aromatization. Human sex hormone-binding globulin
(SHBG) also affects the estrogen/testosterone ratio, since levels
of SHBG increase with age. Normally, androgens like
testosterone have an affinity for SHBG and cause cell
proliferation. Medical researchers are discovering, however, that
estrogen binds to SHBG as well, causing abnormal cell
proliferation in the prostate. This information becomes
particularly pertinent when viewed in light of the mechanisms of
action of saw palmetto, nettle root and pygeum (discussed in
detail in subsequent sections of this paper), and their clinical
efficacy in the prevention and treatment of BPH and cancer.^
TOWNSEND LETTER tor DOCTORS & PATIENTS - AUGUST/SEPTEMBER 2004
Natural Therapies for Prostate
A Cioser Look at Prostate Surgery
Most physicians recommend removal of the enlarged part of
the prostate as the best long-term solution for patients with BPH.^
After any surgery for BPH, a Foley catheter is temporarily
inserted through the penis to drain urine from the bladder into a
collection bag while the surgical site is healing. This catheter
frequently causes infection and recurring painful bladder spasms.
Sexual function is affected in up to 30% of surgical cases,
including retrograde ejaculation (which causes sterility).
Furthermore, surgery for BPH does not prevent future prostate
problems since a portion of the gland remains. Finally, scar tissue
from the surgery typically forms in the urethra and causes
narrowing (which is what the surgery is supposed to relieve).
Patients with severe BPH who have already failed botanical and
nutrient combinations and drug therapies may require surgical
intervention to restore urinary flow. In order to prevent surgical
intervention, it is essential to utilize noninvasive therapies at
the onset of BPH symptoms or before. Medical professionals
use pharmaceutical agents and surgical treatments as a
standard approach to managing patients with moderate BPH.
The risks of such therapies can outweigh their benefits. However,
other scientifically valid therapies, including key nutrient and
herbal combinations, are at least as effective clinically, without
the associated risks.
Prostate Cancer
Cancer of the prostate gland is the most commonly diagnosed
non-dermatologicai cancer among men. It is a leading cause of
cancer death among American men, second only to lung cancer,
in the United States, more than 30,000 men die each year from
prostate cancer. One in five men will develop prostate cancer in
his lifetime, and three percent of those will die from it.
The condition occurs when normal prostate cells turn
cancerous (malignant) and divide at an unreasonable rate. It
most often develops in the region of the prostate closest to the
rectum. African-American men, men aged 65 and older, and
men who have a first-degree relative with prostate cancer are
at an increased risk. Black Americans have the highest incidence
in the world. Interestingly, there is a direct correlation between
intake of animal fat and the risk of getting prostate cancer. The
National Cancer Institute established that total consumption of
animal fat directly relates to the risk of advanced prostate cancer.
Red meat has the strongest positive association with advanced
prostate cancer.'° It is critical to note that the association is only
with saturated animal fat. In fact, essential fafty acids (EFAs),
given in the correct ratios, may prove to be a key in preventing
prostate cancer, and even promoting the health of the gland.
Symptoms
There are essentially no warning signs for early prostate
cancer. As the cancer advances, some men may experience
symptoms similar to those associated with BPH (urinary
frequency, urgency, pain with urination, etc.) or a urinary tract
infection.
Eariy Detection and Treatment
There is no scientific evidence that provides a definite link
between early detection and even treatment of prostate cancer
and the incidence of deaths caused by this disease." Further, if
67
Natural Therapies for Prostate
a health professional diagnoses a man with early stage prostate
cancer, it is highly likely that he will then be required to undergo
invasive evaluation. If this evaluation results in cancer detection,
then standard treatments are generally employed. Standard
treatments such as surgery, radiation therapy, hormonal
therapy and occasionally chemotherapy have serious side
effects including incontinence (lack of bladder control),
impotence (inability to have an erection), and even death.''
One treatment option for men with early-stage prostate cancer
is "watchful waiting." Since many prostate cancers are small
and grow slowly, physicians may opt to shun treatment altogether
(watchful waiting), which is an accepted approach to managing
the condition. A benefit of this method is that it avoids any
potential side effects that may occur with other forms of
treatment, fylen choosing this method of treatment (or lack
thereof) often turn to nutrient and botanical therapies as a means
of safety treating their cancer. Interestingly, a study completed
at the University of Pennsylvania Hospital'^ found that one third
of all prostate cancer patients supplement medical treatment
with complementary therapies.
Prostatitis
Acute bacterial prostatitis is an acute infection of the
prostate gland. Bacteria usually migrate to the prostate from
the urinary system. As the infection advances, the gland begins
to swell, causing sudden symptoms of painful, urgent and
frequent urination. Other symptoms include fever and chills, and
pain over the bladder, lower back and between the testicles and
rectum (the perinea! area). The standard medical treatment for
acute prostatitis is usually intravenous antibiotics until the fever
breaks, followed by 4-6 weeks (or longer) of oral antibiotic
therapy, It is critical that one seeks medical attention promptly if
he experiences fever-associated pain in the areas described
above.
Chronic bacterial prostatitis is usually symptomatic,
causing vague, persistent, low back and perineal pain, urinary
urgency and frequency, and painful urination. Standard medical
treatment is oral antibiotic therapy for 2 to 3 months. Patients
can also experience prostatitis that is not the result of a bacterial
invasion. This condition is referred to as chronic non-bacterial
or non-infectious prostatitis. Chronic non-bacterial prostatitis
is more common than bacterial prostatitis, and has the same
symptom picture. Having no known cause, healthcare
professionals find it difficult to treat. It does not respond to
antimicrobial agents. Serenoa repens {saw palmetto), Urtica
dioica (stinging nettle root), Prunus africanum (pygeum), zinc,
selenium, green tea extract, tomatoes, amino acid therapy, and
essential fatty acid therapy are effective and safe treatment
options for nonbacterial, non-infectious prostatitis.
Botanical and Nutritional Therapeutic Options for
Prostate Conditions
Serenoa repens (Saw Palmetto)
Description and Medical History: Saw palmetto is native
to North America. It is a member of the fan palm family and has
characteristic sharp edges that can literally "saw" through
clothing, hence its common name, saw- palm-etto. The plant
produces a one-seeded dark brown-to-black berry that is
harvested and used in the preparation of phytomedicines.
Researchers now focus on the lipophilic medicinal extracts of
these berries, although one should not ignore its historic use as
a whole berry preparation. Traditionally used for the treatment
of prostate conditions, saw palmetto was appropriately referred
to as the "old man's friend." Touted for its effectiveness in
reducing prostate inflammation, alleviating chronic urinary tract
infections, and increasing sperm count, this herb has
demonstrated the added benefit of increasing sex drive in
Known Medicinal Constituents
• Lipoid constituents: Phytosterois, particularly beta-sitosterol,
tri, di, and monoglycerides, and free fatty acids
• Flavonoids and polysaccharides
Indications for Use (specific to prostate health)
• Mild to moderate benign prostatic hyperplasia"*'^
• Non-infectious (non-bacterial) prostatitis"
• Prostate cancer'^ '^
Possible Mechanisms of Action
• Has alpha-adrenoreceptor and calcium blocking activities
(antagonists) that function to relieve urinary urgency by
reducing the smooth muscle contractions of the bladder
sphincter^"
• Inhibits the binding of
DHT to androgen
Table 1.1 Double Blind Placebo-Controlled Clinical Trials of Saw palmetto Extract in BPH Patients
receptor sites in the
* of Patients
% Reduction in
cytosolic component
Dally Dosage
% Increase in
Tolerabillty
Saw palmetto
Urinary
(mg/b.id.)
Peak Urinary
of
Reaearchers
of prostate cells^'"
group (SP) vs.
Frequency
Regime
Therapy
Fiow Rate
Placebo
(at night)
• Inhibits prolactininduced
prostate
160 X 1-3 mo
SP: 14
Excellent
Taaca et al. (1985)
SP: 74%
SP; 26%
growth"
Placebo: 5%
Placebo: 13
N;A
Placebo: 39%
• tnihibits the binding of
Reece Smith at al. (1986)
160 x 3 mo
SP:33
SP: 35%
Excellent
SP: 36%
Placebo; 37
Placebo: 35%
growth stimulating
N/A
Placebo: 36%
EmIII et al. (1983)
Unclear x 1 mo
SP:15
SP: 33%
estrogen to receptor
Excellent
SP: 50%
Placebo: 15
Placebo: 2%
N/A
Placebo: 13%
sites on the prostate
Descotes et al. (1995)
160 x 1 mo
SP:62
SP: 29%P-:0.05
Good
SP: 33%P<0.05
cells and reduces the
Placebo: 94
Placebo: 9%
N/A
Placebo: 18%
number of estrogen
N/A
Good
CuMer et al. (1985)
160 x 2-3 mo
SP & Placebo: 146
SP: 33%P<0,001
and
androgen
N/A
Placebo: 15%
N/A
receptors in the
SP:47
SP: 50%P<0 001
Excellent
Champault et at. (1984)
160 x 1 mo
SP: 46%P<0,001
nuclear fraction of the
Placebo: 41
Placebo: 5%
Placebo: 15%
N/A
prostate celP*
Boccafoachi i Annoscfa
160 x 2 mo
SP:11
SP: 43%P<0.05
SPi 5S%P<0.05
Excellent
(1983)
P <0.001 - < 0.05 VS. placebo
Placebo: n
Placebo: 32%
Placebo: 19%
N/A
TOWN5END LETTER tor DOCTORS & PATIENTS ~ AUOUST/SEPTEMBER 2004
•
•
Exhibits mild 5-alpha reductase inhibition activity in the
prostate gland^^^^
Inhibits tfie arachadonic acid cascade via the inhibition of
cyctooxygenase and 5-Npoxygenase in the prostate^'
Double-Blind Clinical Trials with Saw Palmetto in BPH
Wiit et al.'^^ conducted a systematic review and quantitative
meta-analysis of the existing evidence regarding the therapeutic
efficacy and safety of saw palmetto plant extracts in men with
mild to moderate benign prostatic fiyperplasia (BPH). The
researchers evaluated 18 randomized controlled trials that
included 2,939 men with a mean age of 65 years. Sixteen of
these studies (89%) were double-blinded and placebo controlled,
and the mean duration of fhe studies was 63 days. The
researchers measured the efficacy of saw palmetto extracts in
affecting urologic symptoms, urine flow, residual urine volume,
prostate size and nocturia. The study participants (that were
treated with saw palmetto) and their physicians reported
significant improvements in BPH symptoms compared to the
placebo group. The men had decreased urinary tract symptom
scores overall, fewer episodes of nocturia (-0.76 times per night),
and an increase of peak urine flow rates (1.93 mUs [95% Cl,
0.72-3.14]). All trials In this meta-analysis produced similar
improvement in urinary tract symptoms arid urinary flow
rates when measured against finasterlde, and were
associated with significantly fewer adverse side effects.
Table 1.1 highlights seven key placebo-controlled clinical
trials with a liposferolic extract of saw palmetto, all of which were
a part of the recent systematic review by Wiit et al.^^ In six out of
seven of the studies, urinary frequency was dramatically
decreased in the saw palmetto treatment group as compared to
the placebo group. The saw palmetto group experienced a
significant improvement in peak flow rates (26-50%) compared
to the placebo group (2-35%). While symptom soore evaluations
are a valuable means of analyzing outcomes, the researchers
did not routinely complete these evaluations since many of the
studies were done before this methodology was widely
accepted. ^^
Finasteride vs. Saw Palmetto Extract
Carraro et al,^° completed the largest international
comparative trial for the treatment of BPH. This double-blind
study compared the therapeutic effects of finasteride versus saw
palmetto extract in 1,098 patients with moderate BPH.The most
critical observation of this comparative trial was that saw
palmetto extract does not have a significant effect on serum
PSA levels or prostate volume. With this knowledge,
physicians do not need to be concerned that saw palmetto will
affect PSA levels and mask prostate cancer. This ciinicai
evidence aiso makes it clear that the primary action of saw
Table 1.2 Double-Blind Trial Comparing the Therapeutic Effects
of Saw Palmetto Extract with Finasteride in Patients with
Moderate
Treatment
Saw Palmetto Extract
Fmasteride
Dally Dosage
5 mg
320 mg
Quality of Life
38% improvement
4 1 % improvement
Peak Flow Rate
25%
30% p<0.05
-18%p<0/001
Prostate Volume
-6%
No Changs
-41%p<0/001
PSA
IPSS
-37%
-39%
'Patients reported more sexual dysfunction with finasteride and reported a
significantly higher number of incidences of impotence and decreased iibido
p<0.001 on sexual function score
IPSS= Iniemationai Prostate Symptom Score
PSA= prostate-specific antigen
TOWNSEND LETTER lor DOCTORS & PATIENTS - AUGUST/SEPTEMBER 2004
Natural Therapies for Prostate
palmetto is not its abliity to inhibit 5-aipha reductase, since
PSA levels remained relatively constant. Table 1.2 further
highlights the results of this study.
Overview: Ciinicai Effects of Saw Palmetto (Serenoa repens)
• Decreases urinary urgency
• Decreases perineal pain
• Decreases nocturnal (nighttime) frequency
• Increases urinary flow rate
• Prevents infections due to residual urine
• Reduces residuai urine
• improves quality of iife for BPH patients
Contraindications
Pregnancy and lactation: it is possible that Saw palmetto
may be unsafe for pregnant and lactating women due to its
antiandrogen and estrogenic activity.^'
Side Effects
Tolerability is generally excellent for Saw palmetto although
it can in rare instances cause headache or mild gastrointestinal
disturbances.^°
Possible Interactions with Drugs
May interfere with oral contraceptives and hormone therapy
due to it antiestrogen effect.^''
Possible Interactions with Herbs and other Dietary
Supplements - None known
Possible interactions with Lab Tests
None: Saw palmetto does not have a significant effect on
serum PSA
Recommended Dosage
Lipophilic Extract: 160 mg b.i.d., according to research
studies referenced in this review (may be reduced if combining
with dried berries)
Dried berry: .5-1 gram t.i.d.
Urtica dioica (Stinging Nettie Root)
Description and Medical History: Nettle is a weed that has
a particular affinity for nitrate-rich soil, found in most temperate
regions of the world. Its root and rhizome (the parts used today
for the treatment of prostate conditions) are long and yellowbrown in color According to the Eclectics, nettle root (including
the rhizome) relieved bronchial and asthmatic trouble. Healers
also used nettle as a diuretic and astringent, and as a treatment
for joint aliments.^^ Its high lignan content made it an attractive
fiber source before the introduction of flax seeds.
As mentioned earlier in this review, estrogen and androgens
such as testosterone bind to SHBG and cause cell proliferation.
As a man ages, his SHBG levels increase, making him more
susceptible to abnormal cell proliferation. Today, researchers
are finding the high lignan content of nettle to be
responsible for the root's ability to bind to SHBG (sex
hormone binding giobuiin), a key to its potential use as a
prostate cancer remedy.^^^'' This strong affinity for SHBG
limits the amount of testosterone and estrogen that can bind
to it and influence cell proliferation.
Natural Therapies for Prostate
Known Medicinal Constituents
• Scopoletin (a coumarin)
• Lignans (Urtica dioica agglutinin [UDA],
(-)-secoisolaricirestnol)
• Sterols and steryl glycosides (including sitosterols)
Indications for Use (specific to prostate heaith)
• Mild to moderate benign prostatic hyperplasia'*-'*
• Non-infectious (non-bacterial) prostatitis"-^*^
• Prostate cancer"
demonstrated a marked improvement in urinary flow rates from
15.50 to 17.5 ml/sec. However, the group receiving the saw
palmetto/ nettle extract demonstrated a further statistically
significant increase in urinary flow rate with continued therapy
for one year.
Table 2.1.
Saw Palmstto/Nattle
Bool Trial"
IPSS
Urinary Flow Rates
320mg Saw Palmetto
Extract + 240 mg Nettle
Root Extract tor 6 months
18.3-11.1
(40% decreasa
In aymptoma) p<0.05
Improved from
14.65- 17.95 ml/sec
(23% Improvement)
Placebo
for
6 months
19.0-1706
(7% decrease In
symptoms) p<0.05
Improved from
15.05- 15.50 ml/3oc
(4% Improvement)
IPSS = Intemstlonal Prostate Symptom Score
Possible Mechanisms of Action
• Inhibition of sodium-potassium ATPase from BPH tissue,
thereby decreasing androgen response^
• Reduction of human sex hormone-binding globulin (SHBG)
activity due to lignans found in nettle root ^ ^
• Antagonism of the pathway by which SHBG leads to the
induction of androgen-responsive genes"
• Inhibition of human leukocyte elastase (HLE), a marker In
prostatitis and associated lower urinary tract infections
•
•
Weak inhibition of DHT binding to cytosolic androgen
receptors in the prostate^^
Inhibition of aromatase, thereby inhibiting the conversion of
androgens to estrogens"
Placebo Controlled Clinical Trials Involving Stinging
Nettle Root in BPH patients
The popular use of stinging nettle root extract in Germany
encouraged the onset of numerous clinical trials. Collectively,
these trials demonstrated the benefits of using nettle root tor
the treatment of BPH. In a 1996 placebo controlled trial,
Engeimann et a l / " successfully demonstrated that nettle root
extract was superior fo placebo in terms of the International
Prostate Symptom Score (IPSS).The study included 41 subjects
with mild BPH, observed for a period of 3 months. In an older
placebo controlled trial (1987)," 79 patients with BPH were given
either nettle root extract or placebo for as long as two months.
The dosage was 600 mg per day for the duration of the study.
Nettle root proved to be better than the placebo in all parameters
that were measured including urinary flow, residual urine and
urinary volume. In 1985, Vontobel et a l . " conducted a placebo
controlled clinical trial that demonstrated a significant
improvement in urinary flow and micturition volume, and an
impressive decrease in SHBG (p<0.0005). The study included
50 patients that were prescribed 600 mg of nettle root extract
daily for approximately two months.
Placebo Controlled Clinical Trials of Stinging Nettle Root/
Saw Palmetto Combination Therapies
Metzker et a l . " completed a double blind placebo controlled
clinical trial involving 40 BPH patients that took either a placebo
treatment or a mixture of nettle root and Saw palmetto extracts
for 6 months. The experimental group showed a dramatic
improvement in IPSS (International Prostate Symptom Score)
as compared to the placebo group. Additionally, urinary flow rates
improved significantly in the experimental group compared to
the placebo group. Details of this study are highlighted in Table
2.1. The 6-monfh double blind treatment was followed by an
open-label extension. Interestingly, the placebo group
70
Sokeland et al.''' completed another comparison trial with
finasteride and a saw palmetto/nettle root extract.
Table 2.2
Saw Palmeno/Nettle
Root vs. Finastetide
Rnasieiide Group
Saw Palmetto/
Nettle Root Group
Daily
Dosage
5mg
160 mg
saw palmetto
llposterolic extract/
120 mg nettle
root extract b.i.d
Duration
12 months
12 months
IPSS (International
Prostate Symptom
Score) % Change
47% Improvement
-S.6 point change
42% (mprovemant
•4.8 point change
This randomized, double-blind, muiticenter clinical trial
involved 543 patients suffering from BPH stages I and II. Both
therapies proved to be similar in effectiveness in all areas
including: IPSS scores, urination times, and urinary flow rate.
The major difference was in tolerability. Patients tolerated herbal
therapy better than finasteride. The finasteride group reported
more adverse events including diminished ejaculation
volume, erectile dysfunction and headaches. Table 2.2
highlights dosages, duration and IPSS scores for this study.
Overview: Clinical Effects of Stinging Nettle Root
(Urtica dioica)
• Decreases urinary urgency
• Decreases nocturnal (nighttime) frequency
• Encourages hormonai balance
• Increases urinary flow rate
• Prevents infections due to residual urine
• Reduces residual urine
• Reduces risk of abnormal prostate cell proliferation
• Improves quality of life for BPH patients
Contraindications and Warnings
Pregnancy and lactation: insufficient reliable information.
Avoid using unless under the strict supervision of a qualified
healthcare practitioner. Benign prostatic hyperpiasia (BPH)
therapies and prostate cancer therapies should be monitored
by a qualified healthcare practitioner.
Side Effects
Tolerability is generally excellent for netlle root.**
Possible Interactions with Drugs: None known
Possible Interactions with Herbs and other Dietary
Supplements: None known
Possible Interactions with Lab Tests: None known
TOWNSEND LETTER tor DOCTORS ft PATIENTS - AUOUST/8EPTEMBER 2004
Recommended Dosage
Dried extract (5:1) 600-1200 mg/day, according to research
studies referenced in this review
'Use stinging nettle root for prostate symptoms, not to be
confused with white dead nettle, which is primarily used for
inflammation of the mucous membranes.
Pygeum africanum (Pygeum)
Description and Medical History: Pygeum, sometimes
referred to as African Plum Tree, is a large evergreen tree that
grows in the higher plateaus of southern Africa. The Eclectics
and otfier healers traditionally collected the bark of the tree,
ground it into a powder, and prescribed it as a tea for genitourinary conditions. It was also used as an aphrodisiac, and as a
remedy for "madness.""'^ Medical researchers now consider
pygeum bark to be a scientifically vaiid and clinically
effective remedy for functional symptoms of benign
prostatic hyperplasia (BPH) that include nocturia, dysuria,
mictritional disorders, and bladder fullness." ' '•
Known Medicinal Constituents
• Phytosterols (including beta-sitosterol, beta-sitosterone and
campesterol)
• Ferulic esters of long chain fatty acids
• Pentacyclic triterpenes (including oleanolic, crataegolic and
ursolic acid)
Indications for Use (specific to prostate health)
• Mild to moderate benign prostalic hyperplasia."*^"
• Non-infectious (non-bacterial) prostatitis^^'
• Prostate cancer^
Possible Mechanisms of Action
• Beta-sitosterols found in Pygeum inhibit prostaglandin
synthesis, thereby reducing the abnormally high levels of
prostaglandins normally found in BPH patients.^
• Pygeum prevents bladder contractile dysfunction, thereby
reducing risk of prostalifis and/or BPH complications."^
• Pygeum is a potent inhibitor of prostatic fibroblast proliferation
via its ability to inhibit protein kinase C activation. Rapidly
growing benign and malignant cells require protein kinase C
•
•
•
•
Pygeum antagonizes 5-lipoxygenase metabolite production,
thereby decreasing bladder hyperreactivity and prostate
inflammation.^^
Ferulic acid esters reduce prostatic cholesterol levels, thereby
limiting synthesis of testosterone.^
Triterpens, including oleanolic, crataegolic and ursolic acid
decrease inflammation in prostate tissue.
Pygeum competes with androgen precursors.^
Placebo-Controlled Clinical Trials Involving Pygeum
Bark and BPH patients
Pygeum bark extract is a popular treatment in Europe,
particularly in central and Eastern Europe. Breza et al.*"
conducted a multicenter trial in central Europe in 1998 to
determine the efficacy and safety of using Pygeum africanum
extract in the treatment of BPH. The researchers evenly
distributed 85 patients with mild to moderate BPH among three
centers. IPSS scores decreased by 40% and quality of life scores
by 32%. There was also a statistically significant reduction in
nocturnal frequency (32%) although urinary flow parameters
remained unchanged. The researchers reported a particularly
TOWNSEND LETTER lor DOCTORS & PATIErfTS - AUGUST/SEPTEMBER 2004
Natural Therapies for Prostate
satisfactory safety profile. An interesting aspecf of this study
was the researchers' decision to follow the patients after the
initial treatment for an additional month with no treatment. The
results of the treatment remained positive even after it was
stopped, indicating a persistent therapeutic activity. Table 3.1
highlights the results of this study.
Table 3.1
Pygeum aMcanum
extract in the
treatment of BPH"
IPSS
Two month period
or treatment with
50 mg, b.i.d.
One month tollow-up
with no treatment
40% mean
Improvement
Maintained ciinicai
improvement
QOL (Quality of Life)
3 1 % mean
improvemanl
32% mean reduction
Maintained ciinical
improvement
Nocturnal Frequency
Toierabiiity of Treatment
Maintained clinical
improvement
Excellent
N/A
Subjects: 85 men aged 50-75 with mild to moderate BPH
IPSS=lntemational Prostate Symptom Score
Chatelain et al.*^ completed a more recent study that
compared the efficacy and safety of Pygeum africanum extract
at different dosages. Tfiis randomized, double blind study
included 209 patients in its first phase (2 months long using
either 50 mg twice daily or 100 mg once daily) and 174 patients
in its second phase (10-month, open phase using 100 mg once
daily). IPSS, quality of life (QOL) and maximum flow rate (Q,^,.)
improved significantly in all patients, and both treatments had
similar efficacy. The researchers reported a satisfactory safety
profile after using 100 mg per day for a period of 12 months.
Table 3.2 summarizes the significant results of this study.
Table 3.2 Comparison
of Efficacy and Safety
ot Pygeum atricanum
Extract Administered
as 50 mg bid and
100 mg q d ' '
Group A:
50 mg Twice Dally
Group B:
100 mg Once Daily
IPSS (2 month
comparative phase)
38% mean
improvement
35% mean
improvement
QOL (2 month
comparative phase)
Oman [2 month
comparative phase)
Toierabiiity (2 month
comparative phase)
10 Month Open Phasa
28% mean
improvement
16% increase
28% mean
improvement
19% increase
Exceilent
Excellent
100 mg Onc« Dally
IPSS
Qmax
46% Improvement
15% increase
Toierabiiity
Excellent
Overview: These clinical trials coupled with the results of
earlier in vitro trials clearly show that Pygeum africanum
bark extract:
• Decreases nocturnal frequency
• Decreases urinary urgency
• Improves quality of life for BPH patients
• Inhibits prostate cell proliferation
• Reduces prostate size
• Reduces residual urine
• Does not affect serum hormone levels
• Is very well tolerated
71
Natural Therapies for Prostate
DHT. which is causing abnormal cell proliferation. By blocking
the action of 5 alpha-reductase. the prostate gland should
shrink."
Contraindications
Pregnancy and lactation: insufficient reliable information.
Avoid using unless under the strict supervision of a qualified
healthcare practitioner.
Alanine. Glutamine, and Glycine
In 1958, Feinblatt and Gant*^' completed a controlled crossover study using a combination of alanine, glutamine and glycine
to treat BPH symptoms. The study included 40 men with
confirmed BPH, After 3 months on the amino acid combination,
the authors reported that delayed micturition was either relieved
or reduced by 70%. nighttime urinary frequency was reduced
by 95%. urinary urgency decreased by 8 1 % and urinary
frequency decreased by 73%.These preliminary results inspired
the work of Damrau in 1962. He conducted a controlled study
that included 45 cases of uncomplicated BPH in an experimental
group and 40 cases of uncomplicated BPH in a control group.
The age, weight and height of all subjects were closely matched.
The experimental group received the combination amino acid
therapy daily for three months. Table 4.1 reveals the results of
this study.
Side Effects
Tolerability is generally excellent for Pygeum africanum
bark*'**although some researchers speculate that it may. in rare
instances, cause nausea and mild abdominal pain.^
Possible Interactions with Drugs: None known
Possible Interactions with Herbs and other Dietary
Supplements: None known
Recommended Dosage: 100-200 mg lipophitic extract (1214%) per day in 6-8 week cycles, according to research studies
referenced in this review
'It is advisable to be mindful o( the source for pygeum used
since over harvesting may be threatening the species}.^
Green Tea
The Prostate Cancer Research Institute reports on its web
page^" that green tea and a lipid-extract from it contain several
pharmacologically active chemicals in the flavonol group of
polyphenois known as catechins. In addition to being antioxidants and free-radical scavengers, these compounds inhibit
the expression of oncogene and the action of three enzymes
believed to play a role In oncogenesis. They have demonstrated
anti-cancer activity In laboratory mice carrying human prostate
and breast cancers and mouse lung and skin cancers.
Two catechins found In green tea, epicatechin gallate (ECG),
and epigallocatechln-3 gallate (EGCG) are inhibitors of 5-alpha
reductase which may be effective in the treatment of 5 alpha
dihydrotestosterone-dependent abnormalities, such as benign
prostate hyperpiasia and prostate cancer. It may be possible
that these catechins are regulating androgen action in the
prostate gland. As described earlier in this article, 5 alphareductase is the enzyme that converts testosterone into DHT in
the prostate gland, DHT is an androgen that stimulates the
synthesis of specific proteins and causes prostate cells to
proliferate. The theory behind 5-alpha reductase blocking agents
is that the body is producing too much testosterone and ultimately
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72
Tabta 4.1 Amino Actd Therapy for 8PH (Modified from Damrsu f*')
Symptoms
Amino Acid
Group
1% showing
comolete
or partial
relief of
Bymptom)
Placetx}
Group
(% showing
complete
or oariial
reUBfol
syn^itom)
Amino Acid
Oroup
(% showing
eomotf
relief of
symptom)
Placebo
Group
(% showing
comoltta
relief of
symptom)
IS
5
42
11
5
33
IB
0
9
0
23
0
Nocturia
50
Urgency
Frequency
Ddlay In starting
86
43
SO
15
Difficulty malntaimng
urination
46
15
11
Damrau*'^confirmed the results of the original study conducted
by Feinblatt and Gant^' on the safety and efficacy of using a
combination of alanine, glutamine. and glycine in the treatment
of BPH. Damrau reported that he observed no side effects in
the experimental group.
In 1978 Cuervo et a l . " studied the effects of the amino acid
combination (aianine. glutamine. gtycine) together with the herb.
Prunus artjorea. They determined that the inclusion of the amino
acids with the herb led to a considerable reduction in the duration
of treatment for BPH patients resulting in significant financial
savings. This study included 100 patients with prostatic
adenoma, prostatitis. and BPH.
In Japan, this amino acid combination Is available as
Paraprost for the treatment of BPH. Maekawa** compared the
effects of Paraprost with another drug. Cernilton, on BPH. This
mutticenter double blind study included 192 patients with BPH.
The researchers determined that Paraprost (the amino acid
combination) was more than moderately effective In 46.3% of
the patients studied. Yamaguchi et al. (1990) also compared
the effects of Paraprost with another drug (a selective alpha 1adrenoreceptor blocker) in a double-blind multi-institutional
study They observed 77 patients with BPH and determined that
Paraprost significantly improved obstructive and irritative
symptoms, and reduced the incidence of residual urine.
The combination of these three amino acids - alanine,
glutamine and glycine - offers favorable clinical results for the
patient with BPH. The therapy appears to enhance the positive
effects of herbal prostate medicines.
TOWNSEND LETTER for DOCTORS A PATIENTS - AUGUST/SEPTEMBER 20M
Zinc
The prostate gland has a unique characteristic of storing
remarkably high levels of zinc. In fact, healthy prostate tissue
contains a higher concentration ot zinc than any other tissue in
the human body. It is no coincidence that the level of zinc in
the prostate gland declines dramatically in patients with
BPH, and even more so In patients with prostate cancer.
Zaicheick et al.'^^ studied 109 patients with BPH (50 cases) and
prostate cancer (109 cases). The researchers used transrectai
punch biopsy of prostate and radionuclide-induced energy
dispersive X-ray fluorescent analysis to determine zinc
concentrations in prostate tissue. They showed that the zinc
content in cancerous prostate tissue was dramatically less than
the concentration found in healthy prostate tissue. Specifically,
zinc content of the normal prostate was 1018 micrograms/g dry
tissue (M+/-124) compared to 146 M+/-10 in the cancerous
prostate tissue. Costello et at.^ound an interesting correlation
between citrate metabolism in the prostate, zinc accumulation,
and prostate cancer. They determined that, in addition to zinc,
the prostate accumulates and secretes exceptional levels of
citrate from prostate epithelial cells. These cells will not secrete
normal amounts of citrate if the zinc level in prostatic
mitochondria drops. Specifically, the accumulation of zinc inhibits
an enzyme that causes citrate oxidation. Thus, in patients with
prostate cancer, as the level of zinc in the prostate drops, the
threat of citrate oxidation increases. Perhaps the most
Interesting finding was that prolactin and testosterone
regulate the concentration of zinc in the epithelial cells that
produce citrate. Numerous medical researchers have made
the correlation between zinc levels and BPH and
Despite this correlation, there has been
little support for further investigation of the
nutritional etiology of BPH and prostate
cancer. It is also important to note that
preliminary research suggests that over
supplementation with zinc (over 100 mg
per day) for prolonged periods may
increase risk of prostate carcinogenesis.
This is based on an epidemiological
study'^ where confounding variables
exist, including concurrent high dose
supplement intake of other ingredients
such as calcium. Nevertheless, it does
elucidate the point that more is not
necessarily better with dietary
supplement intake.
Tablets
Tomatoes
Compared
to other
known
carotenoids, lycopene is considered by
experts to be one of the most potent
antioxidants. with its unsurpassed singletoxygen quenching capacity. An
impressive number of clinical trials and
epidemioiogical studies demonstrate the
statistically significant association
between consumption of lycopene in
foods, such as tomatoes and prostate
health. However, most of the
investigations are plagued by the
uncertainties common to dietary
therapeutics - the variability in food
content of the agent under investigation.
Chewable Wafers
Subllngual
Tablets
Enteric-Coated
Tablets
Controlled
Release
Tablets
Gelatin Capsules
Vegetarian
Capsules
Powdered
Formulas
TOWNSEND LETTER for DOCTORS & PATIENTS - AUGUST/SEPTEMBER 2004
Natural Therapies for Prostate
its isoforms, the multiple unknown interactions between the
suspect chemical and the many other ingredients in the host
food, influences of other dietary variables, and even the
pharmacokinetics of the agent in the human body. Nevertheless,
accumulated evidence to date supports a benefit from lycopene
in one form or another, and more so when obtained from whole
foods, in reducing the risk of prostate cancer."
Selenium
Selenium may have potent anti-cancer properties. Results
from laboratory experiments suggest that selenium-enriched
broccoli activates certain anti-cancer transcription pathways in
mouse livers.'" Dog data suggest that dietary selenium
supplementation decreases DNA damage and increases
epithelial cell apoptosis within the aging canine prostate.''^
One of several prospective human selenium studies to show
a positive effect on cancer was published in 1996 in JAMAJ^
The researchers had originally chosen only skin cancer but
included prostate, lung and coiorectal seven years into the 13year study because of positive results.The study included almost
1000 men from regions of the US with mean plasma selenium
concentrations in the lower range of US levels. The doubleblinded, randomized study gave 200 micrograms of selenium
as brewer's yeast, or placebo, daily for 4.5 years and followed
the subjects for an additional 6.4 years. Total cancer incidence
(77 cases versus 119), prostate cancers (13 versus 35),
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73
Natural Therapies for Prostate
colorectal cancers (8 versus 19), and lung cancers (17 versus
31) were all significantly iower in the selenium group than in the
placebo group. There was no detectable increase in adverse
effects from the supplementation. Because the study was small
and not originally planned for the significant endpoints and the
population was in the lowest range of selenium levels, it is
considered preliminary and in need of verification. Nevertheless,
it strongly suggests a beneficial and safe role for this supplement.
A population study carried out on 212 cases and 233 controls
found a modest negative correlation between serum selenium
levels and the incidence of prostate cancer." The inverse
association with selenium was strongest among men with low
serum concentrations of u-tocopherol, another antioxidant.
of pain and suffering for the male patient. After reviewing
the various conditions associated with prostate disease,
including benign prostatic hyperplasia (BPH), prostatitis,
and even cancer, and examining the standard iines of
treatment for these conditions, herbal and nutrient
medicines appear to be an important primary or
compiementary therapy for the male patient experiencing
sub-optimal prostate health.
References
1.
2.
3.
4.
5.
6.
7.
Essential Fatty Acids
The body synthesizes some fat on its own, but there are
also fats that the body is incapable of manufacturing known as
"essential fatty acids" or EFAs. They are the omega 3 (alphalinolenic) and omega 6 (linoleic) fatty acids. Essential fatty acids
are required constituents of every membrane in the body. Classic
signs of deficiency include depression, mood disorders, memory
loss, hyperactivity. anxiety, dry flaking skin, inflammation, arthritic
pain, bursitis, decreased bone density, easy bruising, muscle
spasms, food allergies, fatigue, increased body fat, sub-clinical
and clinical hypoglycemia, hormonal imbalance and dry hair.
EFAs are required to maintain the health of every living cell in
the body. They maintain the fluidity of cellular membranes, aid
in producing and balancing hormones, and play an essential
role in managing inflammation. From essential fatty acids the
body produces many compounds including a group of
components known as prostaglandins. Interestingly, the word
prostaglandin comes from the fact that these products of
fatty acid metabolism were originally found In the prostate
gland (prosta - gland - in). Prostaglandins regulate every organ
system in the body. One essential rate-limiting enzyme in the
transformation of EFAs into the important prostaglandins is 5-6desaturase. Interestingly, zinc deficiency blocks this enzyme.
Other factors that block this enzyme include trans fatty acids.
vitamin B3 and B6 deficiencies, toxic chemicals, alcohol, and
some viruses.
A study conducted by medical researchers in Korea
established a connection between BPH, prostate cancer, and
essential fatty acids. Yang et al.'" examined the role of dietary
fatty acids in benign and malignant prostate disease by
comparing serum fatty acid levels in normal controls, patients
with prostate cancer, and patients with BPH.They also looked
at the relative difference in omega 3/omega 6 fatty acid ratios
between the three groups. The omega 3/omega 6 fatty acid ratios
decreased progressively from control (largest fraction) to BPH
to prostate cancer (lowest fraction) indicating that BPH patients
have less omega 3 fatty acids in their serum, and prostate cancer
patients have significantly less omega 3 fatty acids in their serum.
This is a landmark study, as it makes a direct correlation between
omega 3 fatty acid deficiencies and prostate disease (BPH and
cancer).
Researchers are still not clear on wtiat the entire purpose
of the prostate gland is and the extent of its functions. What
the medical community does know is that it is a critical gland
of the male reproductive system and that when this gland
is diseased in any way, it can cause a tremendous amount
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TOWNSEND LETTER f o r DOCTOHS & PATIENTS - AUGUST/SEPTEMBER 2004
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