Eating your way to prostate cancer.
Unfortunately, the dietary choices of most men living in the modern Western world circumvent the body's natural protective barriers. Th e end result is that we unwittingly provide biological fuel for existing prostate cancer cells to propagate and metastasize.
Good news: If you understand the biological roles of diet and specific nutrients, you'll be able to achieve a considerable amount of control over whether isolated cancer cells in your prostate gland will ever show up as a clinically diagnosed disease.
So keep reading, because what you learn here can make a difference between bad news and good news in your future.
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. Unlike synthetic drugs, however, the proper dietary constituents produce no side effects and confer additional health benefits.
All cancers begin when genes that regulate cellular proliferation become so damaged that they can no longer control normal cell division. For example, scientists are actively engaged in clinical research using selenium because it helps protect specific genes that enable cells to divide normally. (2-5) The limitation of a nutrient like selenium, however, is that it may not be able to reverse accumulated damage (mutations) to such cell-regulating genes.
Prostate cell genes are especially prone to mutations early in the course of human life. This has been demonstrated by autopsy findings of prostate cancer cells in younger men who never knew they had the disease. (6)
Doctors continue to wonder why so many men with active cancer cells in their prostate glands do not progress to overt disease. One answer may relate to the discovery of a particular enzyme that prostate cancer cells use to propagate, infiltrate, and metastasize. A large volume of published research indicates that this enzyme functions via multiple pathological pathways to facilitate prostate cancer at various stages. (7-21) The encouraging news is that this enzyme can be suppressed via dietary modification and the use of dietary supplements, many of which are already being utilized by health-conscious men today.
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. (22-29) 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) provokes 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 on the right (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).
[FIGURE 1 OMITTED]
As can be seen in Figure 1, both saturated and omega-6 fats convert to arachidonic acid in the body, whereas 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. (2,26,30-36) In addition, arachidonic acid is metabolized by 5-LOX to 5-HETE, a potent survival factor that prostate cancer cells utilize to escape destruction. (31,37-40)
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. (41-47)
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). (2,30,35,48,49)
5-LOX IS OVEREXPRESSED 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, (26,30,35,49) 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-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. (33)
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. (30)
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. (50) 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). (26,49,51-54)
NUTRIENTS THAT SUPPRESS 5-LOX
Health-conscious people already take nutrients like fish oil that help to lower 5-LOX activity in the body. (20,21) Studies show that lycopene and saw palmetto extract also help to suppress 5-LOX. (51,55-68) 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[R]: NATURE'S 5-LOX INHIBITOR
Specific extracts from the Boswellia plant selectively inhibit 5-lipoxygenase (5-LOX). (69,70) This is not surprising when one considers that various boswellia extracts have been used for centuries in India as anti-inflammatory agents. (71)
In several well-controlled human studies, boswellia has been shown to be effective in alleviating various chronic inflammatory disorders. (72-82) Scientists have discovered that the specific constituent in boswellia responsible for suppressing 5-LOX is AKBA (3-O-acetyl-11-keto-Bboswellic acid). Boswellia-derived AKBA binds directly to 5-LOX and inhibits its activity. (70) Other boswellic acids only partially and incompletely inhibit 5-LOX. (70,83)
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[R]. When tested against the best commercial boswellia compounds, 5-LOXIN[R] exhibited better inhibitory action against 5-LOX.
5-LOXIN[R] DECREASES INFLAMMATION, INVASIVE POTENTIAL, TUMOR CELL ADHESIVENESS, AND ANGIOGENESIS
A rat study was conducted to evaluate the efficacy of 5-LOXIN[R] compared to the popular anti-inflammatory drug ibuprofen. 5-LOXIN[R] reduced inflammation by 27%, compared to 35% for ibuprofen. (84) Another rat study compared 5-LOXIN[R] to the anti-inflammatory steroid drug prednisone. 5-LOXIN[R] 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[R] is free of side effects.
Ibuprofen has demonstrated anticancer 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[R] functions to block the 5-LOX enzyme. Since the effects of 5-LOXIN[R] and ibuprofen may be either additive or synergistic, a clinical trial of a combination of these agents is warranted.
Tumor necrosis factor-alpha (TNF-[alpha]) is a dangerous pro-inflammatory cytokine that often increases in aging people. In a gene-chip study, 5-LOXIN[R] blocked the expression of many genes that are sensitive to the pathological effects of TNF-[alpha]. (84)
From the standpoint of keeping prostate cancer cells in check, 5-LOXIN[R] was shown to prevent the TNF-[alpha]-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. (86)
Prostate cancer cells use adhesion molecules (known as VCAM-1 and ICAM-1) to facilitate their spread throughout the body. 5-LOXIN[R] was shown to prevent the up-regulation of these adhesion molecules, which are directly involved in inflammatory 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. (87)
A plethora of research documents the role of chronic inflammatory mediators such as 5-lipooxygenase (5-LOX) and tumor necrosis factor-alpha (TNF-[alpha]) in the manifestation and progression of prostate and other cancers. (7-19,30,31,33,49,52-54,87,88)
The typical American diet is high in omega-6 fatty acids, saturated fats, and arachidonic acid. Over-consumption of these foods, and under-consumption of omega-3 fatty acids, contribute significantly to systemic chronic inflammatory states.
Boswellia extracts have been thoroughly studied as natural remedies for inflammatory disorders. A patented extract from boswellia called 5-LOXIN[R] has potent ability to inhibit the enzyme 5-LOX, preventing the formation of protein-degrading enzymes, and protecting against inflammation-induced events that can promote tumor angiogenesis.
RELATED ARTICLE: 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.
[FIGURE 3 OMITTED]
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. In fact, if we focus on the metabolic pathways involved in arachidonic acid production and metabolism, we can understand why selective inhibitors of only the COX-2 enzyme, such as Vioxx[R] and Celebrex[R], may be associated with an increased risk of heart attack and stroke. (139,140) The fault lies not within the specific drug (Vioxx[R], for example), but rather in a misguided approach that involves blocking only one of the pathways leading from arachidonic acid metabolism (the COX-2 pathway), while ignoring the three other enzymatic pathways (COX-1, 5-LOX, 12-15 LOX) through which arachidonic acid can be metabolized.
Vioxx[R] primarily blocks the COX-2 metabolic pathway of arachidonic acid, yet Americans taking this class of drug continued to overindulge in foods rich in arachidonic acid, which resulted in excess production of toxic 5-HETE, 12-15-HETE, and hydroxylated fatty acids. A focus on decreasing consumption of arachidonic acid--as well as inhibiting arachidonic acid production by means of fish oil and reducing consumption of insulin-stimulating carbohydrates--was completely ignored by the physicians who prescribed these drugs.
While Merck, the manufacturer of Vioxx[R], is now being sued, Vioxx[R] was not the sole cause of the side effects seen in patients taking this drug. The primary culprit was the failure of scientists and physicians to take into account the basic biochemistry of omega-6 fatty acid and arachidonic acid metabolism. If patients prescribed COX-2 inhibitors were (1) advised to decrease their intake of omega-6 fats and arachidonic acid, (2) shown how to block arachidonic production by increasing their fish oil consumption and decreasing their carbohydrate intake, and (3) advised to take steps to inhibit the COX-1 and 5-LOX pathways, the side effects attributed to Vioxx[R] may never have occurred.
RELATED ARTICLE: Daily use of aspirin may decrease prostate risks.
Most Life Extension members take aspirin to reduce their risk of heart attack and stroke. A new study shows that taking one aspirin tablet (325 mg) every day may lower the risk of prostate enlargement.
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)
RELATED ARTICLE: Eating your way to prostate cancer: what you need to know.
* Prostate cancer cells are present in most men, yet only one in six men is ever diagnosed with the disease. Natural barriers help to protect some men from developing clinically diagnosable prostate cancer.
* Poor dietary choices can break down the body's innate defenses against the development of prostate cancer, while fueling its proliferation and spread. Consuming a healthy diet and specific protective nutrients can provide significant support against prostate cancer.
* A comprehensive strategy to fight prostate cancer should focus on inhibiting the 5-lipoxygenase (5-LOX) enzyme, which is central to the cancer's propagation, infiltration, and spread. This can be done by limiting intake of foods that contain or stimulate arachidonic acid and thus increase 5-LOX production, such as red meat, egg yolks, dairy products, saturated and omega-6 fats, and high-glycemic carbohydrates. Healthier dietary choices are cold-water fish, fish oil, and sesame lignans.
* Certain nutrients protect the prostate by suppressing 5-LOX activity and production of metabolites. These include fish oil, (20,21) lycopene, (51) and saw palmetto. (68) A novel extract of the boswellia plant called 5-LOXIN[R] strongly inhibits 5-LOX.
* 5-LOXIN[R] exerts powerful anti-inflammatory effects and blocks the expression of enzymes and cytokines that can lead to the proliferation and spread of cancer.
* Excess arachidonic acid in the body stimulates not only prostate cancer, but also processes that lead to heart attack, stroke, and chronic inflammation. Health-conscious people can reduce arachidonic acid's toxic effects by eating a healthy diet and utilizing cyclooxygenase (COX) inhibitors, which inhibit the toxic byproducts of arachidonic acid metabolism. COX inhibitors include aspirin, curcumin, green tea, and resveratrol.
* Blocking both the LOX and COX pathways, in addition to making wise dietary choices, is essential to limiting the dangerous effects of arachidonic acid, including cancer and heart disease.
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By William Faloon Reviewed and critiqued by Stephen B. Strum, MD, FACP (Life Extension Scientific Advisory Board Member)
CANCER-PROMOTING EFFECTS OF 5-LOX Tumor Growth Factor Cellular Effects Epidermal Growth Stimulates tumor cell Factor (EGF) proliferation Vascular Endothelial Stimulates angiogenesis, Growth Factor (VEGF) tumor growth, and metastasis Tumor Necrosis Induces matrix Factor-Alpha (TNF-[alpha]) metalloproteinases, increases invasiveness and metastasis; Induces NF-kappaB, increases cell adhesion molecules (I-CAM, V-CAM) Cellular Effects Inhibited by Stimulates tumor cell 5-LOXIN [R] proliferation Stimulates angiogenesis, 5-LOXIN [R] tumor growth, and metastasis Induces matrix 5-LOXIN [R] metalloproteinases, increases invasiveness and metastasis; Induces NF-kappaB, 5-LOXIN [R] increases cell adhesion molecules (I-CAM, V-CAM) Figure 2. 5-lipoxygenase (5-LOX) acts as biological fuel for cancers by stimulating EGF (epidermal growth factor), VEGF (vascular endothelial growth factor), and other growth factors. Tumor growth factors that enhance cancer cell proliferation, invasiness, and metastasis can be inhibited by a natural product called 5-LOXIN [R]
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