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Life Extension Magazine

LE Magazine January 2001

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ARTHRITIS UPDATE
Drugs That Inhibit COX-2 May Cause Tissue Damage

by: William Faloon

Page 1 of 3

imageThe Scales Tilt on the Side of Nature

Drugs that inhibit the cyclooxyenase-2 (COX-2) enzyme have shown efficacy in alleviating inflammation and pain caused by arthritis. Celebrex and Vioxx are two popular COX-2 inhibitors that are being aggressively marketed to arthritis patients by drug companies.

A new study published in the Journal of Immunology(1) acknowledges the temporary benefits of COX-2 inhibitors, but identifies a potential long-term problem that could lead to cartilage and other tissue degeneration if these drugs are taken over an extended time period.

The authors of this study found that COX-2 inhibitors cause metabolic imbalances that can result in the over production of two toxic cytokines, tumor necrosis factor alpha (TNF-a) and interleukin one beta (IL1B). Both TNF-a and IL-1B have been shown to play a role in the cartilage destruction and the inflammation process.(2-4) TNF-a and IL-1B have been found to be elevated in the synovial fluid and the cartilage of osteoarthritis patients.(2,5) Thus, the short term beneficial effects of these agents on arthritic pain and inflammation may be achieved at the cost of an increased propensity to long term tissue damage caused by TNF-a and IL1B.

Too much TNF-a results in a host of aging-related disorders including autoimmune disease, congestive heart failure, insulin resistance and catabolic wasting.(6-10) When TNF-a attacks the linings of the joints, the result is inflammation, pain and eventual immobility.(11-13)

Over expression of the destructive cytokines TNF-a and IL-1B are not the only problem that COX-2 inhibitors may induce. While COX-2 inhibitors suppress an inflammatory fatty-acid called prostaglandin E2, they fail to block the formation of a joint-destroying cytokine called leukotriene B4.(14) This all helps explain why COX-2 inhibitors do not always provide complete relief from arthritis symptoms.

Natural solutions

The problem with most drugs is that they function via only one specific mechanism. By affecting just one metabolic pathway, biochemical imbalances can develop in the body that often result in the dangerous side effects characteristic of prescription drugs.

One approach to lowering both prostaglandin E2 (PGE2) and leukotriene B(4) is to eat cold-water fish and/or take fish oil supplements. The oil found in cold-water fish interferes with the production of leukotriene B(4) and PGE2 by suppressing their common precursor, arachidonic acid.(15-21) In one study, fish oil supplements given to rheumatoid arthritis patients reduced arachidonic acid levels by 33% compared to presupplement values.(22) Another human study showed fish oil lowering arachidonic acid levels by 26%.(23)

Fish oil also suppresses the joint-tissue destructive TNF-a and IL-1B cytokines, which helps explain why so many published studies demonstrate that fish oil is an effective arthritis therapy.(24-29) Studies on healthy volunteers and rheumatoid arthritis patients show that fish oil supplementation significantly inhibited production of proinflammatory cytokines!(30) On the other hand, the most recent study shows that COX-2 inhibiting drugs may boost destructive TNF-a and IL1B levels.(1)

How COX-2 inhibiting drugs work

Prostaglandins are hormone-like fatty acids that participate in many life functions. Not all prostaglandins are beneficial. Excess levels of prostaglandin E2 (PGE2) can cause inflammation. COX-2 inhibiting drugs (such as Celebrex and Vioxx) suppress production of PGE2 and are approved by the FDA as effective arthritis therapies.

Celebrex and Vioxx function specifically by inhibiting the enzyme cyclooxygenase-2 (COX-2). COX-2 is required to convert arachidonic acid into a destructive fatty-acid called prostaglandin E2 (PGE2).

The drugs Celebrex and Vioxx function as COX-2 inhibitors, but as you can see from the chart below, that still leaves the lipooxygenase pathway open to produce joint-destroying leukotriene B(4).

In experimental studies, the pharmacologically active components of the ginger root (gingerols) have been shown to inhibit both the cyclooxygenase and lipooxygenase pathways and the production of prostaglandin E2 and leukotrienes. No significant side effects have been reported using gingerols.(35-37)

Ginger oil is obtained by steam distillation of dried ginger root. In a study on rats,(38) arthritis was induced in the knee and paw by injection of bacilli, leading to inflammation. One group of rats was also given ginger oil by mouth for 28 days starting the day before the injection. The rats given ginger oil had less than half the knee and paw inflammation compared to the controls.

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Continued on Page 2
References on Page 3

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