contdiet

"Focused on the Prostate since 1996"

Is PCA a Nutritional Disease? (Fair, Urol 12/97)

Green Tea (Ahmad, JNCI 12./97)

Saw Palmetto Warning: Problems with Detecting Prostate Cancer? (Oncology Times, 1997)

Urology 50(6): 840-848, December 1997

Cancer of the Prostate: A Nutritional Disease ?
William R. Fair, Neil E. Fleshner, and Warren Heston

The title of this review, "Cancer of the Prostate:
A Nutritional Disease?," reflects the increasing
evidence that nutrition may play a significant role
in the prevention and/or progression of prostate
cancer. The question underscores the limited data
available and the need for more intensive study of
the role of diet and prostate cancer. We herein re-
view currently available clinical data and supple-
ment these data with experimental observations on
the effects of dietary manipulation. The available
data, although scanty, provide some fascinating
observations that with further study may dramati-
cally influence our approach to the issues of tumor
prevention, progression, and perhaps, therapeutic
interventions as they relate to prostate cancer.
Much publicity has been given to the relation of
diet to breast and colon cancer, but little attention
has been devoted to diet and prostate cancer. Yet,
there are data indicating that diet may be a more
significant factor in the behavior of prostate cancer
than in either breast or colon cancer, and these data are reviewed herein.

[The full-text article contains sections on the influence of dietary fat, Vitamins, and Selenium]

CONCLUSIONS
We have reviewed the evidence that nutri-
tional factors play a role in the progression rate
of prostate cancer and may help to explain the
geographic variation in the incidence observed.
However, without well-controlled prospective tri-
als, the attractive hypothesis that nutrition plays a
role in tumor progression remains simply an at-
tractive hypothesis. To date, no definite proof of a
preventive effect has been shown in a study that
will withstand rigid scientific scrutiny. The oppor-
tunity exists, however, for the urologic commu-
nity, working together with experts in the area of
nutrition, not only to advance our understanding
of prostate tumorigenesis, but to rebut those critics
of modern medical technology who claim that we
have ignored the total or holistic approach to heal-
ing. The combination of nutritional guidance and
dietary intervention strategies to augment, not re-
place, current therapy will enable urologists to ap-
proach the issues of prevention and treatment of
prostate cancer in the best traditions of both scien-
tific and holistic medicine, with our patients as the
ultimate beneficiaries.

© 1997, Elsevier Science Inc.

Persons interested in receiving a photocopy of the full-text article (9 pages including 61 references) may send $5 and a self-addressed envelope to:

OUR Lab, 5500 Western Ave, Oklahoma City, OK 73118; "Attn: Fair Nutrition Article"

Journal of the National Cancer Institute, Volume 89, Issue 24: December 17, 1997.

Report. Green tea constituent epigallocatechin-3-galate and induction of apoptosis and cell cycle arrest in human
carcinoma cells

N Ahmad, DK Feyes, A-L Nieminen1, R Agarwal and H Mukhtar*

Departments of Dermatology and 1Anatomy, School of Medicine, Case Western Reserve University, 11100 Euclid Avenue,
Cleveland, OH 44106, USA, *Corresponding author

Background and Purpose: The polyphenolic compounds present in green tea show cancer chemopreventive effects in many
animal tumor models. Epidemiologic studies hae also suggested that green tea consumption might be effective in the prevention
of certain human cancers. We investigated the effect of green tea polyphenols and the major constituent,
epigallocatechin-3-gallate, on the induction of apoptosis (programmed cell death) and regulation of cell cycle in human and
mouse carcinoma cells.

Methods: Human epidermoid carcinoma cells (cell line A431), human carcinoma keratinocyte (cell line HaCaT), human
prostate carcinoma cells (cell line DU145), mouse lymphoma cells (cell line L5178Y), and normal human epidermal
keratinocytes (NHEKs) were used. Apoptosis was assessed by 1) the formation of internucleosomal DNA fragments by
agarose gel electrophoresis, 2) confocal microscopy, and 3) flow cytometry after tagging the DNA fragments by fluorescence
label. The distribution of cells in different phases of the cell cycle was analyzed by flow cytometry.

Results: Treatment of A431 cells with green tea polyphenols and its components, epigallocatechin-3-gallate, epigallocatechin,
and epicatechin-3-gallate, resulted in the formation of internucleosomal DNA fragments, characteristic of apoptosis. Treatment
with epigallocatechin-3-gallate also resulted in apoptosis in HaCaT, L5178Y, and DU145 cells, but not in NHEK. Confocal
microscopy and flow cytometry confirmed the findings. The DNA cell cycle analysis showed that in A431 cells,
epigallocatechin-3-gallate treatment resulted in arrest in the G0-G1 phase of the cell cycle and a dose-dependent apoptosis.

Conclusions: Green tea may protect against cancer by causing cell cycle arrest and inducing apoptosis. It needs to be
evaluated in human trials.

Saw Palmetto Warning: Problems with Detecting Prostate Cancer?

Arnaldo F.Trabucco, M.D., F.I.C.S. on Saw Palmetto
Department of Surgery, Division of Urology
Catholic Medical Center of Brooklyn & Queens, New York

Oncology Times (January 1997)

Address for correspondence:
Arnaldo F. Trabucco, M.D., F.I.C.S.
29-22 30th Avenue
Long Island City, New York 11102
Tel#: (718) 956-3115 or (718)672-3600
E-mail: ATRABUCCO@pol.net

The purpose of this letter is to alert physicians and the general public to the potential
implications regarding the detection and treatment of prostate cancer involved with the use
of an alternative supplement sold in health food stores called saw palmetto.

Prostate cancer is the most commonly diagnosed cancer in American men. In 1996, an
estimated 317,100 new cases of prostate cancer, and 41,400 deaths from prostate cancer
will be found, among men in the United States. It is the second most common cause of
death in men older than 55. Early detection is the most important factor for cure! We are
detecting prostate cancer within the past decade with increasing frequency, and many
patients with this condition are receiving such treatments as radical prostatectomy and
radiation therapy for cure. Although refinements in PSA-based testing have contributed
substantially to the increased detection rate of prostate cancer, the incidence of disease was
increasing dramatically even before the detection of PSA was possible.

Self medication for prostate disorders has increased throughout the U.S. and the rest of the
world. Saw palmetto in particular raises concerns for urologists regarding their ability to
diagnose and treat prostate cancer. I have seen many patients who have placed themselves
on this herb. Its use is advised in advertisements and other marketing for treatment and
prevention of benign prostatitic hyperplasia (BPH), prostatitis, and "urinary difficulty" in
men.

The extract comes from the berries of the palm tree saw palmetto (Serenoa Repens,
Serenoa Serrulata), which is indigenous in the Atlantic southeast coast of North America
from South Carolina to Florida and native to the West Indies.The plant grows six to 10 feet
tall, with a crown of large spiny-leaves that form a circular, fan-shaped outline. The berries
are deep red-brown or black and are oblong and about one inch long.

The extract from these berries is cheap and easy to purchase. Word has been spread via
direct marketing, as well as by advertisements in magazines and throughout the Internet.
Reports, mostly in the European literature, suggest that use of saw palmetto can decrease
the size of the prostate and improve urinary symptoms (dose dependent) after months of
use.[1] No "well done" long-term, double-blind, placebo-controlled studies of saw palmetto
have been done to date.[2]

Although saw palmetto does not affect certain hormonal levels, there is clinical evidence,
however, to suggest that its mechanism of action is similar to that of the commonly
prescribed prostate drug finasteride (Proscar).

For example, several animal studies[3, 4] suggest that saw palmetto has a similar effect on
competitively inhibiting the binding of dihydrotestosterone (DHT) and blocking the
conversion of testosterone to DHT, via its inhibition of 5-alpha reductase. Saw palmetto's
primary therapeutic action is to inhibit 5-alpha reductase in forming DHT and to a lesser
extent, 3-alpha reductase, and to block the action of DHT to receptors on prostate cells via
3-ketosteroid reductase. Research has also shown an anti-inflammatory[5] and
antiestrogenic[3, 6,7] effect of Serenoa Repens. Use of saw palmetto in patients with BPH
results in reduction in the size of the prostate.[5 ]

With finasteride, however, studies have shown that 6 to 12 months of treatment with 5 mg
of finasteride daily can reduce prostate volume, DHT, and prostate-specific antigen (PSA)
levels by 50 percent.[8] Therefore, any patient placed on finasteride must have a baseline
PSA and digital rectal examination.The mechanism of action mimics the pharmacologic
action of finasteride, which has recently been documented to be of little physiologic value
compared with a placebo or alpha blockers.[9]

The purified extract of saw palmetto contains 85% to 95% fatty acids and sterols.
Unfortunately, there are many forms of this extract on the market, containing additives and
many combinations of other herbs, vitamins, and minerals. Consequently the consumer does
not know exactly what he is purchasing.

Saw palmetto has been used in Europe for more than 20 years. Research there, however,
has included clinical studies showing its clinical urologic effects versus a placebo. [10] Only
one study measured the PSA levels prematurely after 3 months "the treatment did not
significantly alter PSA concentrations in these patients."[13] However 5-alpha reductase
inhibitors will reduce the PSA levels by average of 50% after 6-12 months of use,
invalidating this study on PSA. Consequently of most significance is the lack of well planned
"long term clinical studies" concerning the effects of saw palmetto on "lowering the PSA"
levels after 6-12 months!

Any interference with PSA makes this test useless as a diagnostic tool for prostate cancer.
The use of saw palmetto is not regulated by the FDA (its use falls under the guidelines for
food supplements). In my own clinical practice, I have seen many patients on saw palmetto
who were embarrassed to bring this to my attention. I have also noticed a dramatic drop in
PSA levels when patients have been on this herb for many months, making my clinical
diagnostic determination of prostate cancer more complex. Any 5-alpha reductase
inhibitor--whether saw palmetto or finasteride--will reduce PSA significantly.

I quote Dr. Julian Whitaker in his book, Prostate Report-Prevention and Healing[11]:
"When one of my patients has an elevated PSA, I don't rush him off for a biopsy. Instead, I
encourage him to go on a low-fat diet, and I prescribe a daily course of serenoa repens
extract, 360 mg a day, along with zinc and a regimen of antioxidant vitamins and minerals.
We then recheck his PSA level periodically, and it has been my clinical experience that, in
many cases, the PSA gradually falls."

This is an example of how an underlying condition, possibly prostate cancer, can potentially
be concealed by losing the sensitivity of the PSA diagnostic test.

Although refinements in PSA-based testing have contributed substantially to the increased
detection of early prostate cancer, the incidence of the disease is increasing dramatically
although the detection by PSA-incidence is falling since 1992. [12] Possibly the confusion in
the literature about when to and who to treat prostate cancer has contributed to this decline.
So has the introduction of medical therapy with 5-alpha reductase inhibitors and herbs
introduced during the same time period. The most disturbing aspects of self-treatment with
such herbal remedies are their potential effects in masking PSA, which has revolutionized
our ability to pick up prostate cancer. If one curtails the ability to detect prostate cancer by
PSA, many cancers will progress undetected until it is too late, resulting in Stage D Disease.

As a clinical urologist, I feel that the public deserves and has the right to know these
possible consequences--further research is needed. I am not saying that saw palmetto or
finasteride should never be used, but only that they should be used with careful medical
supervision and after obtaining a baseline PSA and digital rectal exam. Although saw
palmetto is an herb, we must treat it as a medicine. Since saw Palmetto can act as a 5-alpha
reductase inhibitor, thereby potentially interfering with PSA levels in men and decrease
prostate cancer detection, it is imperative that men get a baseline PSA level (as is
recommended by the FDA for Finasteride, but not for the unregulated use of Saw
Palmetto). Men self -medicating themselves with this herb are not aware of this detrimental
effect.

We are in a new world where patients are more inclined to self-treat their medical
conditions with alternative means. I believe that there is some merit to this, with proper
guidance by qualified individuals. The escalating cost of medicines in the US has provoked
Americans to seek more cost-effective approaches, which is one of the many dilemmas that
our present health care system has to address promptly.

Doctors need to be better educated about nutrition and alternative medicine. Physicians in
the U.S. are not informed about alternative botanical medicine; we are far behind the
European community in this regard. I believe that there are many benefits to botanical
treatments for many ailments when combined with nutritional approaches. We must
discover the alternative approaches that are accessible to us, while simultaneously using
these remedies when appropriate and combining them with conventional medical treatment.
We must start to incorporate this into our medical schools and residency programs so that
we maintain the doctor-patient relationship.

To render a proper diagnostic evaluation, doctors and patients must communicate with each
other, which means that patients should inform their doctors about their use of any
over-the-counter vitamins, minerals, or herbs. A man who treats himself may have a fool for
a patient!

Arnaldo F. Trabucco, M.D.
Department of Surgery, Division of Urology
Catholic Medical Center of Brooklyn & Queens
St. Johns Hospital
Elmhurst, NY

References:

1. Weisser H., Tunn S., Behnke B., Krieg M.: Effects of the sabal serulata extract IDS 89
and its subfractions on 5 alpha-reductase activity in human benign prostatic hyperplasia.
Prostate 1996; 28:300-306.

2. Lowe F., Ku J.: Phytotherapy in treatment of benign prostatic hyperplasia: A critical
review. Urology 1996; 48:12-20.

3. Carilla E., et al: Binding of Permixon, a new treatment for prostatic benign hyperplasia, to
the cytosolic androgen receptor in the rat prostate. J. Steroid Biochem 1984; 20:521-523.

4. Sultan C., et al: inhibition of androgen metabolism and binding by a liposterolic extract of
serenoa repens B in human foreskin fibroblasts. J. Steroid Biochem 1984; 20:515-519.

5. Di Silverio F., et al: Plant extracts in BPH. Minerva Urol Nefrol 1993; 45:143-149.

6. Di Silverio F., et a.: Evidence that Serenoa Repens extract displays antiestrogenic activity
in prostatic tissue of benign prostatic hypertrophy. Eur. Urol 1992; 21:309-314.

7. Briley M., et al: Permixon, a new treatment for benign prostatic hyperplasia, acts directly
at the cytosolic androgen receptor in rat prostate. Br. J. Pharmacol 1983; 79:327.

8. Stoner E.: 5 Alpha-reductase inhibitors/finasteride. Prostate suppl. 1996; (6): 82-87.

9. Lepor H., Willford W.D., et al: The efficacy of terazosin, finasteride, or both in benign
prostatic hyperplasia. Veterans Administration Cooperative Studies Benign Prostatic
Hyperplasia Study Group. N. Engl. J. Med. 1996; 335:533-539.

10. Dreikorn K., Schonhofer PS: Status of phytotherapeutic drugs in treatment of benign
prostatic hyperplasia. Urologe A 1995 Mar; 34(2): 119-129.

11. Whitaker J.: The Prostate Report--Prevention and Healing, chapter 7, p 44. 1994,
Phillips Publishing, Inc.

12. Stephenson R., et a.: "The fall in incidence of prostate carcinoma: On the down side of
a prostate specific antigen induced peak in incidence"--Data from the Utah Cancer
Registry. Cancer 1996; 77: 1342-1348.

13.Braeckman J.: The extract of sereona repens in the treatment of benign prostatic
hyperplasia: a multicenter open study.Current Therapeutic Research (Vol. 55, No. 7,
July, pp 776-785) 1994.

Dr. Trabucco advises that this article was published in the January 1997 issue of "Oncology Times".