With the fanfare of a holiday parade, drug companies last year unveiled two new Cox-2 inhibitor drugs-Celebrex and Vioxx-to treat arthritis, inflammation, premenstrual syndrome, and potentially even cancer. All the hoopla paid off. Since then, doctors have written more than seven million prescriptions for these "super aspirin" drugs, earning hundreds of million dollars for their makers.
Cox-2 is short for cyclooxygenase-2, one of the key enzymes that helps the body produce inflammatory hormone-like compounds called prostaglandins and cytokines. Cox-2 is essential-without it, we wouldn't be able to fight infections or heal injuries. But when the body overproduces Cox-2, the result is chronic inflammation and pain.
The intensive marketing and advertising of Cox-2 inhibitors obscured why many people overproduce the enzyme. Too much Cox-2 appears to result from imbalances and deficiencies of certain nutrients. Rather than correct these underlying dietary problems, pharmaceutical Cox-2 inhibitors only mask the most visible symptoms. Relatively minor dietary changes, plus some vitamin and herbal supplements, correct the underlying problems.
Problems with Cox-2 Inhibitor Drugs
For years, people have used nonsteroidal antiinflammatory drugs (NSAIDS), such as ibuprofen, to treat the inflammation and pain associated with rheumatoid arthritis and osteoarthritis. NSAIDS ease inflammation by inhibiting the activity of both Cox-2 and Cox-1, the latter an enzyme that helps maintain homeostasis (biological equilibrium) protect the stomach lining. Because stomach ulcers occur in about 25 percent of NSAID users, pharmaceutical companies worked to develop NSAIDS that blocked only the activity of Cox-2. The idea was that a selective Cox-2 inhibitor would reduce inflammation but not irritate the stomach.
The motivation was profiting from a potentially huge market. An estimated 40 million Americans suffer from some form of arthritis. In a typical year, physicians write about 60 million prescriptions for NSAIDS-to say nothing of their over-the-counter sales. However, each year some half-million people develop complications from NSAIDS, with an estimated 80,000 people requiring hospitalization and 8,000 dying.
Though touted for their relative safety, Cox-2 inhibitors may be far more hazardous than originally believed. While gastrointestinal problems with Cox-2 inhibitors occur less frequently, they can be severe. Just four months after the FDA approved Celebrex, 10 deaths from the drug were reported. One study has even suggested that Cox-2 is important to the gut and healing ulcers, suggesting that pharmaceutical tampering with the enzyme may not be wise.
The Double-Edged Sword of Inflammation
Nutrients supply the most basic building blocks of the body's powerful inflammatory compounds. The "parent" nutrient is linoleic acid, found in many foods but especially concentrated in vegetable oils (e.g., corn, soy, and safflower oils). The body converts linoleic acid to the omega-6 family of fatty acids, including arachidonic acid. Cox-2 plays a critical role in converting arachidonic acid to the hormone-like prostaglandin E2 (PGE2) and to the cytokines interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFa), all of which promote inflammation.
According to Robert F. Grimble, Ph.D., of the University of Southampton, England, once an infection or injury stimulates production of IL-1 and TNFa, these two proinflammatory compounds can further stimulate each other, as well as IL-6. In addition, IL-1 and TNFa trigger the production of free radicals, which encourage the production of more proinflammatory cytokines. The proinflammatory reaction essentially feeds on itself, setting the stage for chronic inflammation. ,
Ideally, the body balances these compounds with a group of antiinflammatory compounds that originate with alpha-linolenic acid, found in cold-water fish, leafy green vegetables, and flaxseed. The body converts alpha-linolenic acid to the omega-3 family of fatty acids, which include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Preformed EPA and DHA are also found in cold-water fish.
Much of the problem with inflammatory disorders actually stems from a lopsided imbalance in dietary intake of the omega-6 and omega-3 fatty acids-and the consequential cascade in proinflammatory activity. Artemis Simopolous, M.D., director of the Center for Genetics, Nutrition and Health in Washington, D.C., has shown that people historically consumed roughly equal amounts of the proinflammatory omega-6 fatty acids and the antiinflammatory omega-3 fatty acids.
However, over the past 30 years or so, Americans have replaced much of their dietary saturated fat (a bystander, so far as inflammation is concerned) with omega-6 fatty acids. Simopoulos estimates that people are now eating 20 times more omega-6s than omega-3s. From a biochemical standpoint, this sets the stage for powerful and chronic proinflammatory reactions.
Indeed, inflammation plays a role in many diseases, including arthritis, gingivitis and most of "-itis" diseases. Recent research has pointed to the role of inflammation in heart disease, stroke, and even Alzheimer's disease. In addition, Bruce N. Ames, Ph.D., of the University of California, Berkeley, has estimated that chronic inflammation and infection cause about one-third of all cancers.