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Life Extension Magazine March 2012
As We See It

Synthetic Alpha Tocopherol Shown to Increase Prostate Cancer Risk

We Predicted This Outcome!

By William Faloon

The First Line of Defense: Omega-3 Fatty Acids

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) provokes a stimulatory effect on prostate cancer.56-58

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 previous page (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 flow chart (Figure 1), 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 provoking a dangerous metabolizing pathway through 5-lipoxygenase (5-LOX). Studies show that 5-LOX products directly stimulate prostate cancer cell proliferation via several well-defined mechanisms.59-64 Arachidonic acid is metabolized by 5-LOX to 5-hydroxyeicosatetraenoic acid (5-HETE), a potent survival factor that prostate cancer cells use to escape destruction.65,66 Figure 1 clearly demonstrates how consuming a diet of foods rich in arachidonic acid directly provokes the production of dangerous 5-LOX products, which can promote the progression of prostate cancer. In addition to 5-HETE, 5-LOX also metabolizes arachidonic acid into leukotriene B4, a potent pro-inflammatory agent that causes destructive reactions throughout the body and inflicts severe damage to the arterial wall.67-73

Daily Use of Aspirin May Decrease Prostate Risks
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 non-steroidal anti-inflammatory (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.80

Aspirin inhibits the cyclooxygenase (COX-1 and COX-2) enzymes, which are also involved in the arachidonic acid inflammatory pathway.81,82 Like 5-lipoxygenase, COX-2 is known to promote the proliferation of prostate cancer cells.83

In the SELECT study used to discredit alpha tocopherol-selenium, the use of aspirin or ibuprofen by the placebo group may have reduced the prostate cancer risk more than what could be expected in those receiving alpha tocopherol and selenium who may not have been taking as much aspirin or other NSAIDs.

One reason that fish oil supplements have become so popular is that their beneficial EPA/DHA fatty acids can help reduce the production of arachidonic acid-derived eicosanoids in the body.74-79 As shown in Figure 1, if arachidonic acid levels are reduced, there would be a corresponding suppression of the 5-LOX products 5-HETE and leukotriene B4.

Once one understands the lethal metabolic cascades that occur in response to poor dietary choices, it is easy to see why people who excessively consume foods rich in arachidonic acid, and/or 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). A chart appearing later in this article clearly shows the destructive cascade initiated by excess arachidonic acid.

Men in the SELECT study who took alpha tocopherol-selenium supplements, but consumed foods high in arachidonic acid and not enough omega-3s, would be more likely to develop prostate cancer. The researchers who designed this study should have known to correct for this critical confounding factor, i.e. dietary patterns.

Multiple Dangers of Excess Arachidonic Acid
Multiple Dangers of Excess Arachidonic Acid

In response to arachidonic acid overload, the body increases its production of enzymes like 5-lipoxygenase (5-LOX) to degrade arachidonic acid. Not only do 5-LOX products directly stimulate cancer cell propagation,68,104,105 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).106-111

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 2, 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.112-116 COX-2 is directly involved in cancer cell propagation,103,117,118 while its breakdown product (prostaglandin E2) promotes chronic inflammation.111,119,120 Most health-conscious people already inhibit the COX-1 and COX-2 enzymes by taking low-dose aspirin,114,121-124 curcumin,92,125-136 green tea,137,138 and various flavonoids such as resveratrol.139,140

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.

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,59,60,64,84 scientists sought to determine how much of the 5-LOX enzyme is present in malignant versus benign prostate tissues.85

Using biopsy samples taken from living human patients, the researchers found that 5-LOX mRNA levels were an astounding sixfold greater in malignant prostate tissues compared with benign tissues. This study also found that levels of 5-HETE were 2.2-fold greater in malignant versus benign prostate tissues.85 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.59

In a mouse study, an increase in 5-LOX resulted in a corresponding increase in vascular endothelial growth factor, a key growth factor that tumor cells use to stimulate new blood vessel formation (angiogenesis) into the tumor. 5-lipoxygenase inhibitors were shown to reduce tumor angiogenesis along with a host of other growth factors.86 In both androgen-dependent and androgen-independent human prostate cancer cell lines, the inhibition of 5-LOX has consistently been shown to induce rapid and massive apoptosis (cancer cell destruction).60,84,87,88

Suppressing Arachidonic Acid Byproducts

Suppressing Arachidonic Acid Byproducts

Health-conscious people take nutrients like fish oil, curcumin, and lycopene that help to lower 5-LOX activity in the body.84,89-96

A rat study showed that gamma tocopherol, but not alpha tocopherol, exhibited potent reduction of PGE2 and leukotriene B4, powerful pro-inflammatory end products of the COX-2 and 5-LOX pathways, respectively.97 A review of several studies indicates that combinations of alpha and gamma tocopherol optimally reduce end products (such as PGE2 and leukotriene B4) of arachidonic acid breakdown in the body.18,98,99

Extracts from the boswellia plant selectively inhibit 5-lipoxygenase (5-LOX).100,101 A novel boswellia extract has been developed that is 52% more bioavailable compared to standard boswellia extracts102 thus providing a greater opportunity to suppress deadly 5-LOX and other cancer-promoting byproducts of arachidonic acid.

As humans age, overexpression of the enzymes 5-LOX and COX-2 typically occurs. For maturing males, excess levels of these pro-inflammatory enzymes may contribute to the epidemic of prostate cancer observed after the age of 60.103

Based on the cumulative knowledge that 5-LOX, COX-2, and their breakdown products can promote the invasion and metastasis of prostate cancer cells, it would appear advantageous to take aggressive steps to suppress these lethal enzymes.

For the unfortunate men who received only alpha tocopherol in the SELECT study, the suppression of gamma tocopherol that occurred in their bodies presumably exposed them to higher levels of cancer-promoting byproducts of arachidonic acid. Interestingly, selenium has shown 5-LOX-inhibiting effects, which may partially explain why men receiving selenium and alpha tocopherol-alone did not show a statistically significant increase in prostate cancer.

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 isoflavones141-150 protect against a host of diseases, including prostate cancer. If the men in the SELECT placebo group ate an even slightly healthier diet, then they would be expected to enjoy a lower rate of prostate cancer compared with men who took the alpha tocopherol-selenium supplements but ate fewer 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 dispel a misleading notion about testosterone causing prostate cancer.151 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 SELECT trial that only used alpha tocopherol and/or selenium. If men receiving the supplements had lower testosterone levels, they would conceivably have a higher rate of prostate cancer.

Too Many Factors Involved in Prostate Cancer Causation

The SELECT study was designed based on prior studies showing sharply lower risks of prostate cancer in men who consumed vitamin E and selenium.152-158 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 one or two nutrients would result in less prostate cancer developing in these older study subjects. There are too many other causes that should have been factored in when the SELECT study was originally designed.

It is encouraging that a plethora of new research findings have identified definitive ways for aging men to drastically slash their risk of developing prostate and other cancers.

Arachidonic Acid's Destructive Cascade

Conclusion

Life Extension long ago warned of increased disease risk in those who only took alpha tocopherol supplements without also taking gamma tocopherol.

Leaving out gamma tocopherol is not the only flaw in the SELECT study. It is rather conspicuous, however, since men supplemented with alpha tocopherol experienced a 45-48% depletion in gamma tocopherol levels by six months that was sustained during the course of the initial 5.5-year median trial period.11

The facts revealed in this rebuttal to the SELECT study identify a fundamental problem confronting researchers who seek to “prove” whether a certain supplement prevents a disease. There are too many “other” factors involved in the development and progression of prostate cancer, including low levels of testosterone, increased levels of estrogen, coexisting diabetes or metabolic syndrome, low vitamin D intake, and increased dietary saturated fats.159 These confounding factors therefore make it difficult to study just one or two compounds and expect to come up with a valid finding.

To emphasize today’s sense of urgency, the aging population will contract prostate cancer at epidemic levels unless aggressive changes are implemented immediately. That’s because mutated cells in the prostate glands of aging males are already on the verge of maturing into full-blown cancer.

This is why we encourage Life Extension members to consume healthy diets and supplements that have been shown to sharply reduce prostate cancer incidence. There is not enough time left in our generation’s projected life spans to withstand the kind of scientific design flaws seen in the SELECT study, the medical establishment’s bias against supplements, and arbitrary standards set by the pharmaceutical monopoly.

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.

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