LE: Life Extension Update 2001.03.16

From: Technotranscendence (neptune@mars.superlink.net)
Date: Fri Mar 16 2001 - 20:49:15 MST



Researchers discover a mechanism of cancer chemoprevention; WHAT'S HOT:
Reconsideration suggested for heparin as antimetastatic agent; PROTOCOL:
Thrombosis Prevention; FEATURED PRODUCTS OF THE WEEK: Phytofood; Grape
Seed-Skin Extract; LIFE EXTENSION MAGAZINE: Very berry - and grape too!

Researchers discover a mechanism of cancer chemoprevention

Despite a few recent seemingly contradictory studies featured in the
media, it is generally accepted that vegetables and fruits confer a
preventive benefit against the development of cancer. Their mechanism of
action was once believed to be that of the antioxidants such as
beta-carotene and vitamin C which many of them contain, however the past
few decades have witnessed the identification of specific phytochemicals
within many plants that appear to have an anticancer effect. How they
exert this effect was the subject of two studies that appeared in the
March 13 2001 issue of the journal, Proceedings of the National Academy of
Sciences (PNAS) and an accompanying commentary. In one study, conducted at
Johns Hopkins University, researchers defined the role of the gene nrf2,
believed to be involved in the induction of phase 2 enzymes such as
glutathione S-transferases and NAD(P)H:quinone oxidoreductase which exert
a protective effect against carcinogens. Mice lacking the nrf2 gene showed
increased sensitivity to the carcinogen benzopyrene and an inability of
oltipraz, an anticancer substance found in cabbage, to protect them. In
control mice, oltipraz reduced the number of gastric tumors by 55%
compared to mice lacking the gene. It was found that the control mice
experienced a significant induction of phase 2 enzymes, whereas mice
lacking nrf2 had almost none. This demonstrates the role of nrf2 in the
induction of these protective enzymes as well as reconfirms the role of
oltipraz in cancer prevention. It was noted that because of their
mechanism of action, the effects of the chemopreventive agents are likely
to be longer lasting, necessitating less frequent dosing to derive their

In the PNAS commentary, the author explores the understanding of plants'
chemopreventive ability. Phase 1 cytochrome p450 enzymes detoxify in a
manner which eliminates the majority of toxins, but the reaction can in
some cases activate the chemical into a toxin or cancer-causing mutagen.
Phase 2 enzymes then detoxify these resultant chemicals. Research has
indicated that the mechanism of action of the cancer preventive chemicals
in plants is itself that of a toxin or an imitation of one. The toxic
molecules in plants evolved as their defense against predators and our
adaptive response evolved because we ate these plants. These molecules
activate our detoxification enzymes and can affect our response to other
toxins and carcinogens.

One might speculate that since phytochemicals such as oltipraz could
potentially be toxins, there might be a dose at which their benefit in
protecting against cancer is exceeded by their own toxicity.

Research team member Paul Talalay, MD summarized, "The new work is a
result of 20 years' research and confirms that raising the levels of phase
2 enzymes can offer a highly effective way to achieve protection against

Reconsideration suggested for heparin as antimetastatic agent

Heparin is a well known anticoagulant drug used in the treatment of blood
clots and heart attack, as well as prophylactically in some cases to
prevent clotting during and after surgery. Studies in mice with cancer
have shown that heparin administration leads to decreased metastasis and
prolonged survival, but heparin's antimetastatic mechanism remained
unelucidated. Tumor spread in mice occurs through the formation of
complexes of tumor cells with white blood cells and platelets, which are
blood cells necessary for clotting, but heparin's effects in preventing
metastasis are not primarily due to its anticlotting ability. It was found
that heparin inhibits P-selectin-mediated interactions of platelets with a
substance called mucin on the cancer cell surface. The study's researchers
noted that while a single dose of heparin only prevented this interaction
for a few hours, it was found to prevent longterm metastasis when the mice
were examined six weeks later. Similar results were seen in another
experiment in which heparinized mice examined twelve weeks following tumor
injection, demonstrating that metastasis was prevented, not just delayed.

Thrombosis prevention by Calin V Pop, MD

In patients affected with different tumors, disorders concerning blood
clotting are frequently observed. The biological processes leading to
coagulation are probably involved in the mechanisms of metastasis. About
50% of all cancer patients, and up to 95% of those with metastatic
disease, show some abnormalities--a prethrombotic state--in the
coagulation-fibrinolytic system. Thromboembolic complications are seen in
up to 11% of cancer patients, and hemorrhage occurs in about 10%.
Thromboembolism and hemorrhage, as a whole, are the second most common
cause of death after infection.

In one study, subclinical changes in the coagulation-fibrinolytic system
were frequently detected in lung cancer patients. Five conventional tests
and one new test of blood coagulation--that is, platelet count (P),
prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen (F),
and D-dimer of fibrin (DD)--were prospectively recorded in a series of 286
patients with new primary lung cancer. A prethrombotic state (depicted by
a prolongation of PT, PTT, and increase of D-dimer of fibrin) was
significantly associated with an adverse outcome.

Anticoagulant treatment of cancer patients, particularly those with lung
cancer, has been reported to improve survival. These interesting, although
preliminary, results of controlled trials lent some support to the
argument that activation of blood coagulation plays a role in the natural
history of tumor growth. Recently, two studies compared the effectiveness
of standard heparin with low molecular weight heparin (LMWH) in the
treatment of deep vein thrombosis (DVT). In both studies, mortality rates
were lower in the patients randomized to LMWH. The analysis of these
deaths reveals a striking difference in cancer-related mortality.

Cancer-related mortality with standard heparin was 31%, versus 11% with
low molecular weight heparin. This difference cannot solely be attributed
to thrombotic or bleeding events. Since large numbers of cancer patients
were included in the studies, it seems unlikely that ones with more
advanced tumors were present in the standard heparin group. While it also
is possible that standard heparin increases cancer mortality, such an
adverse effect has not been previously reported. These considerations
suggest that low molecular weight heparin might exert an inhibitory effect
on tumor growth. If your oncologist will not test for thrombotic risk
factors, contact the Life Extension Foundation at (800) 544-4440.


The discovery of cancer preventing phytochemicals has prompted The Life
Extension Foundation to create a new multi-vegetable powder to provide
concentrated doses of plant extracts that are well documented to reduce
the risk of many forms of cancer.

Broccoli contains some of the most effective cancer preventing compounds
including sulphoraphane, phenethylisothiocyanate, indole-3-carbinol and
chlorophyll. Tomatoes contain p-coumaric acid, chlorogenic acid and
lycopene. Cabbage contains 3-indole-carbinol, oltipraz, brassinin and
phenethyl isothiocyanate. Parsley has been shown to boost liver production
of glutathione-S-transferase, which detoxifies synthetic chemical
carcinogens. Carrots contain beta- carotene and xanthophyll. A Candadian
study has shown that eating carrots reduced the incidence of breast cancer
in post-menopausal women. Another study published in Japan has shown that
eating carrots reduced the risk of breast and cervical cancer in younger

Grape seed-skin extract

One of nature's most potent antioxidants are the proanthocyanidins.
Highlights of the product are as follows:

1. Proanthocyanidins contain 95% oligomeric proanthocyanidins of free
grape seed extract (11% higher content than pycnogenol and free from
solvent residues).
2. They are powerful, natural and hypoallergenic free radical scavengers
and antioxidants.
3. They are a highly bioavailable bioflavonoid complex which is rapidly
absorbed and distributed throughout the body within minutes.
4. They have fifty times greater antioxidant capability than vitamin E and
twenty times greater activity than vitamin C in vitro.
5. Proanthocyanidins inhibit the enzymes which lead to histamine
6. They help increase the effectiveness of Vitamin C by acting as a
carrier and as a restorer of oxidized Vitamin C by working with

Very berry - and grape too!

Plants usually contain complex mixtures of phenolic compounds, including
simple phenolic acids, quercetin, catechins, epicatechins,
proanthocyanidins and anthocyanins. Wine is estimated to contain over two
hundred phenolic compounds, though it is known that proanthocyanidins are
the major bioactive polyphenols. The range of health benefits of
polyphenols is extremely wide. Known primarily as potent antioxidants,
they have also been reported to show antibacterial and antiviral action,
to be anticarcinogenic, antiangiogenic, anti-inflammatory and
anti-allergic. Various polyphenols have been shown to inhibit platelet
aggregation and lipid peroxidation, as well as promote vasodilation and
improve microcirculation. They can also chelate metals. Other benefits of
high intake of polyphenols may include fewer cavities (an anti-caries
action), improved kidney function, younger- looking skin and even the
promotion of hair growth.

Besides the need to minimize the oxidation of LDL cholesterol, one needs
to consider the role of platelet aggregation in arterial disease. Platelet
aggregation is the first step in the formation of clots, which may lead to
heart attack or stroke. Part of the effectiveness of aspirin in preventing
heart attacks lies in its ability to inhibit platelet aggregation and thus
the formation of clots. Dr. Lester Packer demonstrated that Pycnogenol, an
extract from pine bark that is similar in composition to grape seed
extract, "works better than aspirin in terms of controlling platelet
aggregation, but without the unwanted side effects associated with
aspirin. Pycnogenol reduced human smoking-induced platelet aggregation to
the same extent as a five-time-higher dose of aspirin" (p. 127). This is a
very dramatic finding, suggesting that cardiac patients especially should
consider taking Pycnogenol or grape seed extract for preventive purposes.

Epidemiological studies confirm that those who consume plenty of
polyphenol-rich foods and beverages have a lower risk of cancer. We are
always being urged to eat more fruits and vegetables. There has been
little guidance, however, as to which fruits and vegetables should be
particularly emphasized. There is reason to think that berries should be
very high on the list.

Visit our website at www.lef.org

If you have any questions, comments or suggestions concerning this issue
or past issues of Life Extension Update, or on any other life extension
topic, send them to ddye@lifeextension.com

For longer life,

Dayna Dye
Editor, Life Extension Update
Life Extension Foundation

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