THE
STANDARD
Volume 1, No. 1
BPH: The Natural Approach
Thomas G. Guilliams Ph.D.
There are many conditions for which natural ingredients are therapeutic
equivalents to the pharmaceutical alternative. Benign Prostatic
Hyperplasia (BPH), in particular, is a condition where natural medicine seems to be
far superior to the synthetic drugs, but the answer is more complete than
simply Saw Palmetto Extracts.
BPH is an age-related non-malignant enlargement of the prostate gland.
It is
a hyperplasia, in that it is due to increased numbers of cells, as
opposed
to a hypertrophy (an increase in cell size). BPH is very common,
effecting
almost 10% of the men in their 4th decade and increasing every decade
thereafter. According to the National Institute on Aging more than half
of
the men in their 60's have BPH and among men in their 70's and 80's the
figure may be as high as 90%.
As the prostate enlarges, it causes compression of the urethra
preventing
the bladder from adequately releasing urine. Decreased caliber and force
of
urination are classic signs. Residual urine, distention of the bladder
and
more frequent urination (especially at night) and urinary tract
infections
are common. Enlargement of the prostate is usually confirmed by digital
rectal examination.
There are two primary features involved with prostate enlargement. The
major
one being hyperplasia, the non-malignant increase in the number of
cells;
and the second being prostatitis, the inflammation of the prostate. We
shall
consider hyperplasia first and then discuss the implications of
inflammation.
Prostate cells, like most cells, are stimulated to grow by
various growth factors. Several studies have shown that epidermal growth
factor (EGF) and basic fibroblast growth factor (bFGF) are responsible
for
stimulating prostate cell growth (1,2).
Studies have also linked
increased
levels of bFGF in the prostate with the occurrence of BPH (3).
Basically,
growth factors are ultimately responsible for the increase in cell
proliferation; but they are not the root problem.
While these growth factors are common to many cell types, in the adult
prostate they are stimulated primarily through the androgen receptor.
The
two major androgen hormones involved are testosterone (T) and
dihydrotestosterone (DHT). When these hormones bind to the androgen
receptors on prostate cells, a complex set of secondary messages are
sent
that signal the cell to produce and secrete growth factors. These growth
factors then bind to growth factor receptors on the same or adjacent
prostatic cells, causing another complex set of secondary signals,
resulting
in mitosis and cell growth (division). Understanding BPH requires an
understanding of how all of these factors effect one another, and how
the
changing hormonal shifts in elderly men relate to BPH.
As men age, serum levels of testosterone drop while the levels of
estrogens
and prolactin increase. While these may have only subtle effects on
other
systems, the prostate gland is sensitive to these changes. Both
testosterone
and DHT bind to the androgen receptor, but DHT binds 5 times stronger
than
testosterone. Therefore, even though the levels of testosterone are
lower,
the conversion of testosterone to DHT via the enzyme
5-a-reductase, keeps the androgen receptors
activated to stimulate
growth
factor production. This androgen receptor stimulation is increased by
the
action of another hormone, sex hormone binding globulin (SHBG) and
estrogen.
When SHBG is bound to its receptor on the prostate cells and is also
attached to estrogen, it is able to sensitize (or amplify) the androgen
signal (4,5,6).
In fact, it may be the very minute increase in estrogen
levels that convert a normal androgen signal to one that causes
hyperplasia.
Estrogens also play a role in inhibiting the degradation of testosterone
and
DHT via hydroxylation. Another factor that may play a role is the
increased
activity of the
5-a-reductase enzyme, and androgen binding
when prolactin is bound to
prostatic cells.
Prostatitis describes any inflammation of the prostate,
whether it is caused by a bacterial infection or not. Inflammation of
the
prostate from bacterial infections is often related to BPH since the
frequencies of urinary tract infections (UTI) increase as retention of
urine
in the bladder increases. Both chronic and acute bacterial prostatitis
are
seen and should be treated much like chronic and acute UTIs. A chronic,
non-bacterial prostatitis has also been seen in a large group of men.
This
form of inflammation seems to be associated with an elevated white blood
cell count and abnormal inflammatory cells in the prostate secretion. It
is
thought that this could possibly be some form of autoimmune response.
Regardless of the type of inflammation, metabolites such as
leukotrienes,
thromboxanes and prostaglandins; which are derived from arachidonic acid
via
the lipoxygenase or cyclooxygenase enzymes are involved.
Anti-inflammatory
agents that specifically block one or more of these pathways would be
helpful in reducing the inflammatory symptoms associated with
prostatitis.
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Several reviews exist on the current treatment approaches to BPH
(7,8).
What follows is a general overview and not a comprehensive review.
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Surgery
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Various forms of surgery are available to remove portions of
the
prostate. These tend to treat the enlargement with good success but have
unpleasant side effects such as decreased sexual function (impotence,
pain,
ejaculatory dysfunction) and bladder incontinence. Newer procedures such
as
trans-urethral resections or incisions can be done to remove portions of
the
prostate. These procedures work well for removing portions of the
prostate,
but do little to address the process that caused the enlargement to
begin
with. Complications of scar tissue and infections are not uncommon in
these
procedures.
Two types of drugs are primarily used, 5-a
reductase inhibitors
and
alpha andrenoceptor blockers (alpha-blockers). Finasteride (Proscar) is
the
most used 5-a reductase inhibitor. It blocks
the conversion of
testosterone
to DHT. Finasteride often requires 6 months to a full year before
significant results are evident. Alpha-blockers such as terazosin,
prazosin
and others act by relaxing the muscles around the prostate, relieving
many
of the symptoms of BPH. While having a more immediate effect on
symptoms, it
does not change the underlying problems associated with the enlarged
prostate (7,8,9)
It has been reported that a high protein diet inhibits
5-a-reductase activity, while a low protein diet
stimulates the enzyme. No large clinical studies have confirmed these results,
and other health
conditions may play a greater role in dictating the type of diet for the
individual with BPH. It has been shown that the combination of the amino
acids glycine, alanine, and glutamic acid relieves many of the symptoms
of
BPH in several studies. These studies are quite old
(10,11),
and further
research may be warranted as additional support during BPH.
The use of Essential Fatty Acids (EFAs) is important at all times, but
BPH
sufferers often are deficient in EFAs.The use of EFAs in the form of
Flaxseed Oil will provide both omega-3 (linolenic) and omega-6
(linoleic),
but much more linolenic. Linolenic acid is a precursor to many of the
"good"
prostaglandins, which will help suppress much of the
prostaglandin-induced
inflammation.
Zinc intake and absorption is critical for the prostate,
especially
during BPH. Zinc has been shown to reduce the size of the prostate and
the
symptoms in many of the patients with BPH (12,13).
Zinc is involved in
various aspects of androgen metabolism. As has been discussed earlier,
estrogen levels are increased in elderly men. Estrogen not only inhibits
the
hydroxylation of Testosterone and DHT; it also prevents the absorption
of
zinc. Zinc has been shown to inhibit the activity of 5
a-reductase (14).
Zinc also reduces prolactin binding to prostate receptors (15). While
the
exact levels of supplemental zinc have not been determined
experimentally, a
dose of approximately 50 mg (325% USRDA) should be both adequate and
safe.
Since zinc is known to reduce the absorption of copper, it is wise to
include copper (1 or 2 mg) with a daily zinc supplementation regimen.
The Liposterolic extract of
Saw Palmetto fruits (Serenoa repens, or Sabal serulata) has been used
extensively and for many years as the drug of choice for BPH in Europe
and
has been getting more and more attention here in the United States. The
fatty acids include capric, caprylic, caproic, lauric, palmytic, and
oleic.
The phytosterols include b-sitosterol, stigmasterol and others. The
liposterolic extract of Saw Palmetto has three major activities that
improve
BPH symptomology, they include: Inhibition of 5-
a-reductase (16,17,18,
19); Inhibiting the binding of DHT to prostatic cells
(20); and
Inhibiting
both Lipoxygenase and Cyclooxygenase (arachidonic acid cascades) (21).
Saw
Palmetto, by competing with both the enzyme and receptor that stimulates
growth factor secretion, inhibits hyperplasia.
A three-year trial of 309 men, comparing Saw Palmetto Extract to
Finasteride
(Proscar) showed a significant increase in urinary flow rate and a 50%
decrease in residual urine volume associated with the Saw Palmetto
group.
While the finasteride group also showed improvements, they were not as
significant as the Saw Palmetto group, and there were almost 6 times
more
dropouts in the finasteride group due to unpleasant side effects (22).
There
have been many clinical trials done with Saw Palmetto extracts showing
effective treatment of BPH.
Standard dosages of Saw Palmetto Extracts are those which yield from 270
to
305 mg of fatty acids per day (often 320 mg of an 85-95% fatty acid
extract). Fatty acid extracts of 85-95% are oil extracts and are in soft
gel
capsules. Powdered extracts are also available and are usually
standardized
anywhere from 20% to 55% fatty acids.
Extracts of Stinging Nettle root (Urtica dioica
L.)
have been used, singly or in combination with other botanicals for the
condition of BPH (22,24,25).
Nettles root extract, as well as Saw
Palmetto
extract, are both approved by the German government as treatments for
BPH.
While the mechanism has not been fully elucidated, two activities have
been
identified in nettle root extracts that may be responsible for the
activity.
The first is the inhibition of prostate Na+/K+ ATPase enzyme
(26). By
inhibiting this crucial enzyme, prostate cells are prevented from
proliferating and therefore, this inhibits hyperplasia. The second
activity
is an interference of the human sex-hormone binding globulin (SHBG). By
interfering with SHBG and its receptor, nettles root extracts prevent
the
estrogen-induced amplification of the androgen signal, which is thought
to
be one of the major players in BPH (27,28).
A common mixture of 120 mg
of
nettles root extract with 160 mg of saw palmetto is used for many
clinical
trials.
The Extract of Pygeum africanum bark has been used for
more
than 20 years in France in patients suffering from BPH. The mechanism
has
not been fully worked out, but a few of the activities are known. Pygeum
extracts are known to inhibit the proliferative effects of growth
factors
such as EGF, bFGF, and IGF-I. This activity was able to inhibit the
prostatic growth in an animal model, even when the cells were stimulated
to
grow (29). This activity makes pygeum extract an excellent synergist
with
saw palmetto because routes other than the androgen receptor may
stimulate
growth signals. Additionally, Pygeum extracts antagonize the production
of
metabolites in the 5-Lipoxygenase pathway (30).
This activity will
further
reduce the inflammatory process in the prostate. Pygeum extracts have
been
dosed anywhere from 50-200 mg per day with excellent results.
The natural treatment approach to BPH is one of the triumphs of natural
medicine. It is quite unfortunate that more health care professionals
have
not taken advantage of these approaches with the millions of patients
with
this condition. The mechanisms are clear, the results even more clear,
and
physicians should feel more than confident using any number of products
with
these ingredients.
- Marengo SR, and Chung LW. An orthotopic model for the study of growth
factors in the ventral prostate of the rat: effects of epidermal growth
factor and basic fibroblast growth factor. J Androl. 1994; 15(4): 277-286
[PubMed]
- Levine AC, M. Ren, GK Huber, and A Kirschenbaum. The effects of
androgen,
estrogen, and growth factors on the proliferation of cultured fibroblast
derived from human fetal and adult prostates. Endocrinology 1992,
130(4): 2413-2419
[PubMed]
- Story, MT; KA Hopp, DA Meier, FP Begun, and RK Lawson. Influence of
transforming growth factor beta 1 and other growth factors on basic
fibroblast growth factor level and proliferation of cultured human
prostate-derived fibroblasts. Prostate 1993; 22(3): 183-197.
[PubMed]
- Rosner W, DJ Hryb, MS Khan, AM Nakhla, and NA Romas. Sex
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- Feinblatt HM and JC Gant.
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[PubMed]
- Bush IM, et al; Zinc and the Prostate.
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- Fahim M, et al; Zinc treatment for the
reduction of hyperplasia of the prostate. Fed Proc 35: 361, 1976.
- Leake A, GD Chisholm, and FK Habib.
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[PubMed]
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[PubMed]
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[PubMed]
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with its receptor on human prostatic membranes. Planta Med 1995; 61(1): 31-32.
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BPH: A General Review
Hyperplasia
Treatment: