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Life Extension Magazine

LE Magazine February 2007
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Eating Your Way to Prostate Cancer


By William Faloon
Reviewed and critiqued by Stephen B. Strum, MD, FACP (Life Extension Scientific Advisory Board Member)

5-LOXIN®: 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-B-boswellic 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®. 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. 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® and Celebrex®, may be associated with an increased risk of heart attack and stroke.139,140 The fault lies not within the specific drug (Vioxx®, 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® 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®, is now being sued, Vioxx® 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® may never have occurred.

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.

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.

Tumor necrosis factor-alpha (TNF-α) 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-α.84

From the standpoint of keeping prostate cancer cells in check, 5-LOXIN® was shown to prevent the TNF-α-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® 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

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

Conclusion

A plethora of research documents the role of chronic inflammatory mediators such as 5-lipooxygenase (5-LOX) and tumor necrosis factor-alpha (TNF-α) 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® 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.

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® strongly inhibits 5-LOX.
  • 5-LOXIN® 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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