Men: How to Reduce Prostate Cancer Risk (science article)

note; this is long, but state of the art summary from Life Extension Foundation, lef.org. They are obviously plugging some of their products, 5-Loxin, but overall I find their integrity and research to be near the top of their field. Article covers why Omega-3 oils (fish) and aspirin or certain foods prevent or heal acids that cause cell mutation. In Taoist view, you can manage the jing level (cellular division, ancestral patterns) to control the process rather than supplements or chemicals. Or use both, we have wide choices as humans. – Michael

Some Common Sense Approaches
For Reducing Prostate Cancer Risk

We know that free radical-induced damage to DNA genes can cause cancer, but oxidative
stress may only partly to blame for most prostate cancers.

While prostate cancer is not usually diagnosed until men reach older ages, it can be
initiated 15-25 years prior to clinical manifestation. In fact, there is convincing evidence
that the initiating DNA damage inflicted by estrogen to prostate cells can occur before a
man is even born!

Studies show that as early as the second and third trimester of life, exposure to elevated
estrogens in the womb can initiate prostate cancer that may not manifest for 80 years.
Lifetime exposure to higher than normal estrogen may be a contributing factor to the
development of prostate cancer. There is no evidence that antioxidants like vitamin E and
selenium would protect against this kind of prostate cancer induced by prolonged excess
estrogen exposure.

Please don’t feel helpless about this, as it requires more than mere initiation for cancer to
fully develop. What one eats and other lifestyle factors have an enormous impact on
whether they develop prostate cancer, even if they are genetically predisposed.

The cause of all cancers

Cancer can be defined in one sentence as follows:

“Cancer is the accumulation of mutations in genes that regulate cellular proliferation.”

All cancers are caused by gene mutations. Every time a cell divides, there are slight
mutations to one’s genes. Oxidative stress accelerates gene mutation, but is by no means
the primary factor. While selenium and vitamin E reduce some types of oxidative stress,
the aged men in the study published by the American Medical Association had already
sustained considerable genetic mutations that are not reversible by taking antioxidants.

Fortunately, there are nutrients that have been shown to favorably reverse the gene
alterations involved in cancer initiation and progression. The most promising is vitamin
D, which has been shown to cut prostate cancer risks in half. Serum levels of vitamin D
were not assessed in the study used to bash vitamin E-selenium, so it was not possible to
know which men had protective levels of vitamin D and which had insufficient or even
deficient levels. If men in the placebo group had even slightly higher vitamin D status,
they would have been less likely to contract prostate cancer.

Failure to test for vitamin D status is not the fault of the researchers conducting this
study. It was not known when the study was designed that vitamin D conferred such as
strong protective effect against prostate and other cancers.

The fundamental issue here is that we cannot expect to suppress the fires of oxidative
stress (with nutrients like alpha tocopherol-selenium) and then see seven decades of
genetic damage magically reverse itself.

Eating your way to prostate cancer

Cancer cells lurk in the prostate glands of most aging men, yet only one in six men is
ever diagnosed with prostate cancer. If one looks at what is required for a single cancer
cell to develop into a detectable tumor, it becomes obvious that natural barriers exist to
protect people against full-blown cancer.

Unfortunately, the dietary choices of most men living in the modern Western world
circumvent the body’s natural protective barriers. The end result is that most men
unwittingly provide biological fuel for existing prostate cancer cells to propagate and
metastasize.

Fortunately, an understanding of the biological roles of diet and specific nutrients can
enable aging men to achieve a considerable amount of control over whether isolated
cancer cells in their prostate gland will ever show up as a clinically diagnosed disease.

The impact of the food we ingest on cell growth and death is so pronounced that it can be
identical to the effects displayed by anti-cancer drugs. As it relates to the study showing
that alpha tocopherol-selenium did not prevent prostate cancer, if the study participant’s
diet was not taken into consideration, then the findings would be so severely skewed as
to have no meaning. Read on to see what we mean.

Omega 3 Fatty Acids: The First Line of Defense

Diets high in omega-6 fats and saturated fats are associated with greater prostate cancer
risk, whereas increased intake of omega-3 fats from fish has been shown to reduce risk.
Based on consistent epidemiological findings across a wide range of human populations,
scientists have sought to understand why eating the wrong kinds of fat (saturated and
omega-6 fats) provoke a stimulatory effect on prostate cancer.
To ascertain what happens after we eat bad fats, all one has to do is look at the metabolic
breakdown pathways that these fats follow in the body, as shown in the chart in this
document (Figure 1). For example, let us assume that for dinner, you eat a steak (a source
of saturated fat) and a salad, along with a typical salad dressing of soybean and/or
safflower oils (sources of omega-6 fats).
As can be seen in the Figure 1 flow chart, saturated and omega-6 fats convert to
arachidonic acid in the body. The meat itself contains arachidonic acid. One way that the
body rids itself of excess arachidonic acid is by producing a dangerous enzyme called 5-
lipoxygenase (5-LOX). New studies show conclusively that 5-LOX directly stimulates
prostate cancer cell proliferation via several well-defined mechanisms. In addition,
arachidonic acid is metabolized by 5-LOX to 5-HETE, a potent survival factor that
prostate cancer cells utilize to escape destruction.
Figure 1 clearly demonstrates how consuming a diet of foods rich in arachidonic acid
directly provokes the production of the dangerous 5-LOX enzyme, which can promote
the progression of prostate cancer. In addition to 5-HETE, 5-LOX also metabolizes
arachidonic acid to leukotriene B4, a potent pro-inflammatory agent that causes
destructive reactions throughout the body and inflicts severe damage to the arterial wall.
One reason that fish oil supplements have become so popular is that their beneficial
EPA/DHA fatty acids can help reduce production of arachidonic acid in the body. As
shown in Figure 1, if arachidonic acid levels are reduced, there would be a corresponding
suppression of 5-LOX, 5-HETE, and leukotriene B4.
Once one understands the lethal 5-lipoxygenase (5-LOX) cascades, it is easy to see why
people who excessively consume foods rich in arachidonic acid, and those who do not
reduce the production of excessive arachidonic acid metabolites, are setting themselves
up for prostate cancer and a host of inflammatory diseases (including atherosclerosis).
Men in the AMA-published study who took alpha tocopherol-selenium supplements, but
consumed foods high in arachidonic acid and not enough omega-3s were more likely to
develop prostate cancer. The researchers who designed this study might not have known
to correct for this confounding factor when the study was designed.

5-LOX Is Over-expressed in Prostate Cancer
Based on studies showing that consumption of foods rich in
arachidonic acid is greatest in regions with high incidences of
prostate cancer scientists sought to determine how much of the
5-LOX enzyme is present in malignant versus benign prostate
tissues.
Using biopsy samples taken from living human patients, the
researchers found that 5-LOX levels were an astounding six-

Figure 1. Flow chart showing
how the body metabolizes
common foods via the 5-
lipoxygenase (5-LOX)
pathway.

fold greater in malignant prostate tissues compared to benign tissues. This study also
found that levels of 5-HETE (a 5-LOX metabolite that prevents prostate cancer
destruction) were 2.2-fold greater in malignant versus benign prostate tissues.
The scientists concluded this study by stating that selective inhibitors of 5-LOX may be
useful in the prevention or treatment of patients with prostate cancer.

5-LOX Promotes Tumor Growth Factors
As the evidence mounts that ingesting “bad fats” increases prostate cancer risk, scientists
are evaluating the effects of 5-LOX on various growth factors involved in the
progression, angiogenesis, and metastasis of cancer cells.
One study found that 5-LOX activity is required to stimulate prostate cancer cell growth
by epidermal growth factor (EGF) and other cancer cell proliferating factors produced in
the body. When 5-LOX levels were reduced, the cancer cell stimulatory effect of EGF
and other growth factors was diminished.
In a mouse study, an increase in 5-LOX resulted in a corresponding increase in vascular
endothelial growth factor (VEGF), a key growth factor that tumor cells use to stimulate
new blood vessel formation (angiogenesis) into the tumor. 5-LOX inhibitors were shown
to reduce tumor angiogenesis along with a host of other growth factors. In both androgen-
dependent and androgen-independent human prostate cancer cell lines, the inhibition of
5-lipoxygenase (5-LOX) has consistently been shown to induce rapid and massive
apoptosis (cancer cell destruction).

Nutrients That Suppress 5-LOX
Health-conscious people already take nutrients like fish oil that help to lower 5-LOX
activity in the body. Studies show that lycopene and saw palmetto extract also help to
suppress 5-LOX. The suppression of 5-LOX by these nutrients may partially account for
their favorable effects on the prostate gland.

As humans age, however, chronic inflammatory processes can cause the over-expression
of 5-LOX in the body. For maturing males, the result of excess 5-LOX may be the
epidemic of prostate cancer observed after the age of 60.

Based on the cumulative knowledge that 5-LOX can promote the invasion and metastasis
of prostate cancer cells, it would appear advantageous to take aggressive steps to suppress
this lethal enzyme. The good news is that a natural 5-lipoxygenase (5-LOX) inhibitor is
now available and has been added to a popular formula used to maintain healthy prostate
function.

In addition to potentially suppressing prostate cancer, the successful inhibition of 5-LOX
should also slow the progression of atherosclerosis.
5-LOXIN®: Nature’s 5-LOX Inhibitor
Specific extracts from the Boswellia plant selectively inhibit 5-lipoxygenase (5-LOX).
This is not surprising when one considers that various boswellia extracts have been used
for centuries in India as anti-inflammatory agents.
In several well-controlled human studies, boswellia has been shown to be effective in
alleviating various chronic inflammatory disorders. Scientists have discovered that the
specific constituent in boswellia responsible for suppressing 5-LOX is AKBA (3-O-
acetyl-11-keto-B-boswellic acid). Boswellia-derived AKBA binds directly to 5-LOX and
inhibits its activity. Other boswellic acids only partially and incompletely inhibit 5-LOX.
Methods to extract high concentrations of AKBA from boswellia have been intensively
investigated due to AKBA’s potential in treating chronic inflammatory disorders. Even in
standardized boswellia extracts, however, biologically active AKBA makes up only 2-5%
of the final product.

Several years ago, researchers discovered how to obtain an economically viable boswellia
extract standardized to contain a greater than 30% concentration of AKBA. This 30%
AKBA extraction discovery was patented and given the trademark name “5-LOXIN®.
When tested against the best commercial boswellia compounds, 5-LOXIN® exhibited
better inhibitory action against 5-LOX.

MULTIPLE DANGERS OF EXCESS ARACHIDONIC ACID
In response to arachidonic acid overload, the body increases its production of enzymes
like 5-lipooxygenase (5-LOX) to degrade arachidonic acid. Not only does 5-LOX directly
stimulate cancer cell propagation,49,89-98 but the breakdown products that 5-LOX produces
from arachidonic acid (such as leukotriene B4, 5-HETE, and hydroxylated fatty acids)
cause tissue destruction, chronic inflammation, and increased resistance of tumor cells to
apoptosis (programmed cell destruction).30,37,99-103

It is important to understand that 5-LOX is not the only dangerous enzyme the body
produces to break down arachidonic acid. As can be seen in Figure 3, both
cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2)
also participate in the
degradation of arachidonic acid.

COX-1 causes the production of thromboxane A2, which can promote abnormal arterial
blood clotting (thrombosis), resulting in heart attack and stroke.104-109 COX-2 is directly
involved in cancer cell propagation,110-113 while its breakdown product (prostaglandin E2
) promotes chronic inflammation.103,114,115 Most health-conscious people already inhibit
the COX-1 and COX-2 enzymes by taking low-dose aspirin,106,115-119 curcumin,120-132
green tea,133-135 and various flavonoids such as resveratrol.136-138
A more integrative approach to this problem, however, would be to also reduce levels of
arachidonic acid, which is the precursor of 5-HETE and leukotriene B4.
5-LOXIN® Decreases Inflammation, Invasive Potential, Tumor Cell Adhesiveness,
and Angiogenesis

A rat study was conducted to evaluate the efficacy of 5-LOXIN® compared to the
popular anti-inflammatory drug ibuprofen. 5-LOXIN® reduced inflammation by 27%,
compared to 35% for ibuprofen.84 Another rat study compared 5-LOXIN® to the anti-
inflammatory steroid drug prednisone. 5-LOXIN® reduced inflammation by 55%, which
was similar to the prednisone used in the study.79,85 The significance of these findings is
that prednisone and ibuprofen can be toxic when used chronically, whereas natural 5-
LOXIN® is free of side effects.

Ibuprofen has demonstrated anti-cancer effects, most probably due to its inhibition of
cyclooxygenase-2 (COX-2), another enzyme that cancer cells use to facilitate their
growth and survival. As you have just learned, 5-LOXIN® functions to block the 5-LOX
enzyme. Since the effects of 5-LOXIN® and ibuprofen may be either additive or
synergistic, a clinical trial of a
combination of these agents is
warranted.

Tumor necrosis factor-alpha
(TNF-?) is a dangerous pro-
inflammatory cytokine that
often increases in aging people.
In a gene-chip study, 5-
LOXIN® blocked the
expression of many genes that
are sensitive to the pathological
effects of TNF-?.

From the standpoint of keeping
prostate cancer cells in check,
5-LOXIN® was shown to
prevent the TNF-?-induced
expression of a protein-
degrading enzyme called
matrix metalloproteinase
(MMP). Cancer cells use the
MMP enzyme to tear apart
natural barriers in the body that
would normally encase them.

Prostate cancer cells are
notorious for inducing the production of this enzyme that causes containment structures
within the prostate gland to vanish, thus enabling the mutated (cancerous) prostate cells
to break through healthy prostate tissue and eventually metastasize.

Prostate cancer cells use adhesion molecules (known as VCAM-1 and ICAM-1) to
facilitate their spread throughout the body. 5-LOXIN® was shown to prevent the up-
regulation of these adhesion molecules, which are directly involved in inflammatory

FIGURE 3. ARACHIDONIC ACID’S DESTRUCTIVE
CASCADE
To better understand the pathways by which
arachidonic acid can cause arthritic, carcinogenic, and
cardiovascular conditions, the flow chart below shows
how arachidonic acid cascades down into damaging
compounds in the body.

processes.85 Chronic inflammation is tightly linked to the induction of aberrant
angiogenesis used by cancer cells to facilitate the growth of new blood vessels
(angiogenesis) into tumors.

DAILY USE OF ASPIRIN MAY DECREASE PROSTATE RISKS
Researchers studied 2,447 men over 12 years, examining them every other year. After
adjusting for age, diabetes, hypertension, and other factors, they found that men who took
a daily aspirin or another NSAID (like ibuprofen) reduced their risk of moderate or
severe urinary symptoms by 27% and lowered their risk of an enlarged prostate by 49%.
Even more intriguing was the finding that men who consumed aspirin or another NSAID
were 48% less likely to have an elevated level of prostate-specific antigen (PSA), the
protein measured in the blood that helps detect prostate cancer.141

Aspirin inhibits the cyclooxygenase (COX-1 and COX-2) enzymes, which are also
involved in the arachidonic acid inflammatory pathway. Like 5-lipoxygenase, COX-2 is
known to promote the proliferation of prostate cancer cells.114

The use of aspirin or ibuprofen by the group receiving the placebo may have reduced the
prostate cancer risk more than what could be expect in those receiving alpha tocopherol
and selenium.

Soy, lignans, and cruciferous vegetables

Men who regularly consume certain plant foods have sharply lower rates of prostate
cancer. Studies show that cauliflower, broccoli, flax lignans and soy isoflavones protect
against a host of diseases, including prostate cancer. If the men in the placebo group ate
an even slightly healthier diet, then they would be expected to enjoy a lower rate of
prostate cancer compared to men who took the alpha tocopherol-selenium supplements
but ate less cancer-preventing plant foods.

Low testosterone increases prostate cancer risk

In a book authored by Harvard University experts titled Testosterone for Life, detailed
findings are presented that dispels a misleading notion about testosterone causing prostate
cancer. These researchers meticulously document their observations that men with low
levels of testosterone have higher prostate cancer risks.

This finding provides another confounding factor that skews the results of the alpha
tocopherol-selenium study. If men receiving the supplements had lower testosterone
levels, they would conceivably have a higher rate of prostate cancer.

Risk of supplementing with only alpha tocopherol

We now know that when alpha tocopherol is taken by itself, it displaces critically
important gamma tocopherol in our cells. An abundance of evidence points to the gamma
tocopherol form of vitamin E as the most protective against prostate cancer. By
supplementing aging men with only alpha tocopherol, scientists may have unwittingly
increased prostate cancer risk in the men participating in the recent JAMA study by
depriving prostate cells of critical gamma tocopherol.

Too many factors involved in prostate cancer causation

The alpha tocopherol-selenium study was designed based on prior studies showing
sharply lower risks of prostate cancer in men who consumed these nutrients. It was also
based on the premise that protecting genes against oxidative stress would reduce prostate
cancer incidence in aged men.

We now know of dozens of factors involved in the development of full-blown prostate
cancer. One could not expect that taking just two nutrients would result in less prostate
cancer developing in these study subjects. There are too many other causes that have to
be factored in and were not known when the study was designed long ago.

It is encouraging that over the past twelve years, a plethora of new research findings have
identified definitive ways for aging men to drastically slash their risk of developing
prostate cancer.