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Health Protocols

Cancer Treatment: The Critical Factors

Step Nine: Inhibiting the 5-Lipoxygenase (5-LOX) Enzyme

As discussed in step 4 of this protocol: Inhibiting the Cyclooxygenase-2 (COX-2) Enzyme, the scientific literature has demonstrated that inflammation plays a pivotal role in the formation and progression of cancer.

The 5-lipoxygenase (5-LOX) enzyme is another inflammatory enzyme that can contribute to the formation and progression of cancer. Arachidonic acid—a saturated fat found in high concentrations in meat and dairy products—promotes elevation of the 5-LOX enzyme. A growing number of studies have documented that 5-LOX directly stimulates prostate cancer cell proliferation via several well-defined mechanisms.118-126 In addition, arachidonic acid is metabolized by 5-LOX to 5-HETE, a potent survival factor that prostate cancer cells utilize to escape destruction.121,127-130

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,121,131-140 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).120,127,141-145

Based on studies showing that consumption of foods rich in arachidonic acid is greatest in regions with high incidences of prostate cancer,119,120,125,131 scientists sought to determine how much of the 5-LOX enzyme is present in malignant versus benign prostate tissues. Using prostate biopsy samples, 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 were 2.2-fold greater in malignant versus benign prostate tissues.123 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.

As the evidence mounts that consuming saturated fats increase 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.120

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.146 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.147

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).119,131,148-151

As humans age, chronic inflammatory processes can cause the over-expression of 5-LOX in the body. Excess 5-LOX may contribute to the development and progression of prostate cancer in aging males.152

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. A critical approach to decreasing 5-LOX activity in the body is to decrease the consumption of saturated and omega-6 fats that contain high concentrations of arachidonic acid and high glycemic carbohydrates that contribute to arachidonic acid formation. Another worthwhile approach is to supplement with fish oil, which reduces 5-LOX activity in the body.153,154 Studies show that lycopene and saw palmetto extract also help to suppress 5-LOX.148,155-168 The suppression of 5-LOX by these nutrients may partially account for their favorable effects on the prostate gland.

Specific extracts from the boswellia plant selectively inhibit 5-lipoxygenase (5-LOX).169,170 In several well-controlled human studies, boswellia has been shown to be effective in alleviating various chronic inflammatory disorders.123,171-179 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.170,180

Researchers have discovered how to obtain an economically viable boswellia extract standardized to contain a greater than 20% concentration of AKBA. A novel boswellia extract has been developed that is 52% more bioavailable compared to standard boswellia extracts,181,182 thus providing a greater opportunity to suppress deadly 5-LOX and other cancer-promoting byproducts of arachidonic acid. This more bioavailable AKBA extraction discovery was patented and given the trademark name AprèsFlex.

How to Implement Step Nine

Decrease the consumption of saturated and omega-6 fats that contain high concentrations of arachidonic acid, such as meats, dairy products, and egg yolks, along with high-glycemic carbohydrates.

Consider supplementing with the following nutrients to suppress 5-LOX enzyme activity:

  • AprèsFlex: 100 to 400 mg daily
  • Fish oil: 2,100 mg of EPA and 1,500 mg of DHA daily with meals
  • Lycopene: 30 mg daily with meals
  • Curcumin (as highly absorbed BCM-95): 400 – 800 mg daily
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