Phytotherapy Reviews &
Commentary
by Donald
J. Brown, ND
Comparing Saw Palmetto Extract and Finasteride
for BPH
Carraro JC, Raynaud JP, Koch G, et al. Comparison
of phytotherapy (PermixonŽ) with finasteride in the treatment
of benign prostate hyperplasia: A randomized international
study of 1,098 patients. Prostate 1996; 29:231-40.
Summary: A six month, double-blind
randomized equivalence study compared the effects for the
saw palmetto extract PermixonŽ
to the 5a-reductase inhibitor, finasteride (ProscarŽ). The
study enrolled 1,098 men over the age of 50 years with moderate
benign prostatic hyperplasia (BPH) and used the International
Prostate Symptom Score (IPSS) as the primary end-point. Men
were randomized to receive either 160 mg of PermixonŽ twice
daily or finasteride at a single daily dose of 5 mg. Patients
who had received either a-adrenergic receptor antagonists
or other phytomedicines (e.g. Pygeum africanum or nettle
root) were required to undergo a 2 week washout period prior
to beginning treatment. Each patient was evaluated pre-study,
and at 6, 13, and 26 weeks. At each visit, peak and mean urinary
flow rates were measured, the IPSS was determined, and the
patient was asked to complete quality of life and sexual function
questionnaires. Additionally, at weeks 13 and 26, patients
underwent transrectal and abdominal ultrasound examinations
to assess prostatic volume and postvoid residual urine as
well as blood chemistries, CBC, and serum prostate-specific
antigen (PSA) assay (a baseline PSA was also performed). Of
the 1,098 patients randomized to treatment, 553 received PermixonŽ
and 545 received finasteride. Of these 951 completed the study
with a total dropout of 16% in the PermixonŽ group and 11%
in the finasteride group. Both treatments were determined
to decrease the symptoms of BPH equally. PermixonŽ decreased
the IPSS by 37% compared to 39% for finasteride. Quality of
life improved in both groups 38% for PermixonŽ and 41% for
finasteride. Peak urinary flow improved by 25% in the PermixonŽ
compared to 30% in the finasteride group. Finasteride markedly
decreased prostatic volume (18%) and PSA (41%) while PermixonŽ
had minimal effect on volume (6% decrease) and no effect on
PSA. Patients receiving PermixonŽ had minimal complaints of
decreased libido and impotence while this was more common
in the finasteride group. Dysuria was more frequent in the
finasteride group while urinary retention was higher for the
PermixonŽ group, but the differences did not exceed 1% for
these complications.
Commentary: In the Feb/Mar 1997
TLfDP, I reported on the 3 year, open-label study with
435 BPH patients showing the efficacy of the commercial saw
palmetto extract known in Europe as IDS 89.1
In the commentary, I made brief mention of this study which
was unpublished at the time. The study was initially presented
at the Third International Consultation on BPH in Monaco,
June 26-29, 1995. According to an editorial in the same issue
of Prostate, the presentation raised quite a stir at
the conference.2
The editorial is largely complimentary and brings out some
solid criticisms of the study including the lack of a placebo
arm and the absence of a placebo run-in period. It is important
to note that the study also indicates that finasteride did
seem to work more effectively in reducing prostate size in
men with larger prostates due to BPH while PermixonŽ was more
effective in reducing the lower urinary tract symptoms (LUTS)
of men with smaller prostate size. This is consistent with
other studies on finasteride and one of the reasons it has
recently come under fire.3 However,
it also demonstrates the difficulty in trying to present clear
parameters for demonstrating efficacy in the treatment of
mild to moderate BPH. The use of LUTS has been recommended
as a response to the lack of clarity in diagnosing BPH based
on prostate size, urine flow, and subjective symptoms.
PermixonŽ
is the original liposterolic extract of saw palmetto berries
(Serenoa repens) created by the pharmaceutical division
of Pierre Fabre in France. The hexane extract is comprised
of free (90%) and esterified (7%) fatty acids, sterols, polyprenic
compounds, and flavonoids. This particular extract was the
template for current liposterolic extracts manufactured using
either ethanol or CO2 extraction. As is the case with all
liposterolic extracts, the therapeutic dose is 320 mg daily.
Therapeutic results should be expected in six to eight weeks
but it is important to remember that the new rule of thumb
for determining clinical efficacy with BPH is six months or
longer. As has been reported in previous reviews on saw palmetto,
the liposterolic extract is largely devoid of the side effects
noted for prescription BPH drugs.
This
study establishes another milestone for saw palmetto extract
as a viable option in the management of mild to moderate BPH.
More long-term trials are still needed as well as the logical
comparison of saw palmetto extract with a-adrenergic receptor
antagonists. It may be that the diverse mechanisms of action
found for saw palmetto and other phytomedicines are the best
approach to a condition for which we continue to have poor
clinical understanding.
References
1. Bach
D, Ebeling L. Long-term drug treatment of benign prostatic
hyperplasia results of a prospective 3-year multicenter
study using Sabal extract IDS 89. Phytomed 1996;
3:105-11.
2. Denis LJ.
Editorial review of Comparison of phytotherapy (PermixonŽ)
with finasteride in the treatment of benign prostate hyperplasia:
A randomized international study of 1,098 patients. Prostate
1996: 29:241-2.
3. Boyle
P, Gould AL. Prostate volume predicts outcome of treatment
of BPH with finasteride: Meta-analysis of randomized clinical
trials. J Urol 1996; 155:572A.
Treatment of Hyperkeratotic Plantar Lesions
with
Tagetes erecta
Khan MT, Potter M, Birch I. Podiatric treatment
of hyperkeratotic plantar lesions with marigold Tagetes
erecta. Phyother Res 1996; 10:211-4.
Summary:
Thirty adult patients with hyperkeratotic lesions (corn and
callus) and scheduled for surgery were entered in a double-blind,
placebo-controlled trial to determine the efficacy of topical
Tagetes erecta (African or Aztec marigold). The lesions were
of long-standing duration (greater than 2 years) and there
was no concomitant topical treatment. The study lasted eight
weeks with actual treatment lasting for the first four weeks
followed by observation at the end of weeks six and eight.
A pain diary was completed by patients throughout the trial
period and brought to the clinic on each visit. The size of
the lesion was measured by an independent assessor pretreatment
and on each visit. Patients were allocated to three different
groups: ten received topical marigold therapy with a protective
pad (Group A); ten received treatment with a topical placebo
and protective pad (Group B); and ten received topical marigold
treatment with no protective pad (Group C). Marigold preparations
used in the study included a paste, tincture and oil prepared
according to the British Patent Specification (1984), the
Homeopathic Pharmacopoeia of the US (1979), and the Homeopathic
Pharmacopoeia for Podologists (1986). Pre-operatively (week
one), all patients were instructed to apply either the active
or placebo tincture over the lesion. The overlying callus
was then removed and tincture re-applied. For Groups A and
B a 5 mm semi-compressed felt cavity pad was placed over the
lesion and either marigold or placebo paste placed in the
cavity. The cavity was covered with surgical tape. Group C
applied only the marigold paste covered with gauze and used
no cavity pad. These treatments were repeated weekly at weeks
2, 3 and 4. At the end of four clinic treatments, patients
self-treated at home with either marigold or placebo tincture.
The home regimen consisted of topical application of a few
drops of the tincture followed by oil and massaged into the
lesion. This was repeated twice a day for week 5, once daily
during week 6, three times weekly during week 7, and no treatment
during week 8. Tubiform foam was used over the lesion every
day for week 5 and three times during week 6. In comparison
to Group B, there was a significant reduction in callus width
(p<0.001), callus length (p<0.001),
and pain (p<0.001). Group A also fared better than Group
C pointing to the value of the protective pad in combination
with the marigold treatment.
Commentary: Hyperkeratotic lesions,
a.k.a. the ol corn and callus, are the most common dermatological
condition treated in podiatry practice. Treatment usually
consists of a combination of chemical, biomechanical, and
surgical interventions. The aim of treatment is to restore
the skin and subcutaneous tissue to normal and eliminate the
stresses responsible for the formation of corn and callus.
Most patients will require ongoing treatment.
Tagetes
erecta is also known by the common names African marigold,
Aztec marigold, and big marigold.1 This
species of marigold is not related to the common marigold
known as Calendula officinalis. However, it is interesting
that the topical application of the flowers of calendula is
used in conditions that are also indicated for Tagetes
erecta leaf and flower preparations. These include skin
ulceration and inflammatory skin conditions like atopic dermatitis.
It is also interesting to note the common use of Tagetes
erecta preparations in podiatry practices in Great Britain
for the treatment of skin and nail conditions. The chemical
action of the flower and leaf preparation includes pain relief
and tissue softening in cases of hyperkeratotic lesions.2
It should also be noted that preparations labeled marigold
oil are usually derived from Tagetes erecta, Tagetes minuta,
or Tagetes patula.3
This
study points to the need to expand our marigold awareness
and consider wider use of Tagetes species for many
of the topical applications typically reserved for Calendula
officinalis. Other applications for Tagetes species
include verrucae, onychomycosis, and decubitus ulcers.4,5
References
1. Leung
AY, Foster S. Encyclopedia of Common Natural Ingredients
Used in Foods, Drugs, and Cosmetics. New York: John
Wiley & Sons, 1996, 482-3.
2. Saify
ZS. Tagetes, the herb that cures corns and callosities.
J Br Assoc Hom Chiropodists 1988; 2:24-5.
3. Tisserand
R, Balacs T. Essential Oil Safety: A Guide for Health
Care Professionals. London: Churchill Livingstone, 1995,
7-8.
4. Khan MT. Treatment
of onychomycosis with marigold therapy. J Br Assoc Hom
Chiropodists 1992; 8:12-16.
5.
Rawal RS, Devitt R, Kahn MT: Treatment of verrucae pedis
using marigold therapy. J Br Assoc Hom Chiropodists 1988;
4:9-12.
Selected Herbal Summaries/Updates
Note: Id like to thank Dr. Eric
Yarnell for the preparation of these summaries and the permission
to print them in this column.
Buckwheat Tea, Rutin and Venous Insufficiency
Ihme N, Kiesewetter H, Jung F, et al. Leg
edema protection from a buckwheat herb tea in patients with
chronic venous insufficiency: A single-center, randomized,
double-blind, placebo-controlled clinical trial. Eur J
Clin Pharmacol 1995; 50:443-7.
Summary: For two weeks, the 77 male
and female volunteers in this study drank a placebo tea consisting
of Malva sylvestris or M. neglecta (mallow)
leaves. The mallow tea contained only minute amounts of flavonoids.
For the next 12 weeks they were randomly assigned to drink
three cups daily of either the placebo tea or Fagopyrum
esculentum (buckwheat) tea standardized to contain 5%
total flavonoids. Rutin was considered the primary active
constituent of the buckwheat tea, and study participants drinking
the study tea received 270 mg of rutin daily. Ten patients
dropped out of the study for reasons unrelated to the treatment.
Change in total leg volume was reduced significantly in patients
drinking buckwheat tea compared to those drinking the mallow
tea. This was largely due to prevention of accumulation of
extra fluid in the legs of participants drinking buckwheat
tea. Venous diameter assessed sonographically showed no difference
between the groups. Capillary permeability, assessed using
fluorescence angiography, was improved in both groups but
the difference in favor of the buckwheat tea fell short of
significance. Symptoms were improved in both groups though
not significantly more in the treatment group compared to
the placebo group. There were no reported adverse events from
drinking buckwheat tea.
Safety of Echinacea
Parnham MJ. Benefit-risk assessment of the
squeezed sap of the purple coneflower (Echinacea purpurea)
for long-term oral immunostimulation. Phytomed 1996;
3:95-102.
Summary: A review of the safety of
echinacea (Echinacea purpurea) is presented in this
paper. The mechanism of action of echinacea is first considered,
particularly the action of the polysaccharide, arabinogalactan.
The author specifically mentions echinaceas ability to stimulate
neutrophil phagocytosis and cytokine secretion by macrophages.
Transient lymphopenia and changes in the CD4/CD8 ratio are
considered the result of redistribution of lymphocytes to
areas of infection in response to echinacea. Very high doses
(1,000 times greater than typically used) are immunosuppressive.
The author cites data showing a lack of mutagenicity and a
very low acute toxicity for echinacea.
Various
studies in humans using intramuscular, intravenous and oral
echinacea for the treatment of infections of the respiratory
tract, urinary tract, uterus, vagina and breast are considered.
Use of intramuscular echinacea preparations for short periods
in children has been shown to be completely safe, as has longer
term (up to 12 weeks) use of oral echinacea in adults and
children. Intravenous echinacea preparations cause a predictable
response attributed to cytokine production: fever, shivering,
nausea and transient lymphopenia. These effects are considered
part of the beneficial action of echinacea and not side effects.
Additionally, one study showing therapeutic benefit and lack
of toxicity in patients with rheumatoid arthritis is mentioned.
Benefits in many of these studies are seen only in persons
with mild to moderate immune compromise.