January 2005

Arthritis and COX‑2

by Dr. Howard Loomis

For some years now, scientists have known that the pain of arthritis is associated with inflammation and high levels of the naturally occurring enzyme cycloxygenase‑2 (COX‑2). They also know that when COX‑2 is inhibited, inflammation and pain are reduced.

Drugs such as rofecoxib and celecoxib effectively block COX‑2 and bring relief to arthritis patients, but as we've seen recently in the case of VIOXX, the side effects can have dire ‑‑ even fatal ‑‑ consequences.

Is there a way to inhibit COX‑2 enzymes without increasing the risk of heart attack, without damaging the liver or kidneys, and without upsetting the digestive tract? Prescription drugs haven't solved this problem and perhaps never will. But maybe you can provide relief for your arthritic patients. To do so, you'll need to know how COX‑2 enzymes fit into the clinical picture of arthritis.

Background

COX‑2 enzymes and their cousins, LOX‑2 enzymes, are found within every cell. They are essential in the final metabolic pathway in the body's utilization of fatty acids. In other words, COX‑2 enzymes respond to the type and amount of fatty acids in the diet, so their action can be good or bad depending the individual's diet.

Essential fatty acids

The need to inhibit COX‑2 enzyme activity is caused by a disturbance or imbalance of linoleic acid, linolenic and arachidonic acids in the body. It is a deficiency of linoleic and linolenic acid and an excess of arachidonic acid that creates detrimental COX‑2 activity.

There are four primary fatty acids in our diet: linoleic, linolenic, arachidonic, and eicosapentanoic.

***  Linoleic acid is unsaturated and cannot be produced by the body and therefore must be included in the diet. It's found in plants and seeds and clearly promotes growth and prevents dermatitis.

***  Linolenic acid (Omega‑6) is unsaturated and cannot be synthesized by humans. It, too, is found in plants and seeds and does not prevent dermatitis, but does promote growth.

***  Arachidonic acid (Omega‑6) is polyunsaturated and can be converted from linoleic acid and therefore is not absolutely essential. It's found in animal fat. It prevents dermatitis but does not promote growth.

***  Eicosapentanoic acid (Omega‑3) is found in fish oils and is a polyunsaturated fatty acid. EPA is not considered to be an essential fatty acid since fish oils are low in linoleic acid. This makes it less saturated than fats from animal sources but not as unsaturated as oils from plant sources.

Linoleic acid conversion to GLA

All four of these fatty acids provoke COX‑2 activity, but each fatty acid will produce a different result.

First, let's look at linoleic acid. It is acted upon by the Delta‑6 desaturase enzyme that converts linoleic acid into gamma‑linoleic acid (GLA). This is an essential step in fatty acid metabolism and activity of this enzyme is found to be deficient in all chronic viral infections, during menopause, and in the aging process.

Any prolonged stress will interfere with its production since adequate nutrients (protein, vitamins and minerals) are not being delivered to the cells for its formation. Specifically, caffeine, colas, chocolate, and hydrogenated oils reduce its effectiveness. Small amounts of alcohol stimulate its production, but excessive alcoholic intake reduces its formation.

Once GLA is formed, it's quickly and easily converted to dihomogamma‑linolenic acid (DGLA).

Next, all the fatty acids ‑‑ DGLA, linolenic, arachidonic, and EPA ‑‑ are acted upon within cell membranes by enzymes specifically designed to convert them into eicosanoids. This occurs in almost all cells, except red blood cells.

Eicosanoid formation

The two final enzyme pathways that convert all fatty acids to eicosanoids are: a) Cyclo‑oxygen‑ase (COX‑2) enzymes, which convert fatty acids to prostaglandins and thromboxanes; and b) Lipo‑oxygen‑ase (LOX) enzymes, which convert any fatty acid to leukotrienes.

Eicosanoids are a group of compounds including prostaglandins, leukotrienes, and thromboxanes. Eicosanoids have short‑lived hormone‑like effects at low concentrations. For example, they indirectly cause or mediate:

1. The inflammatory response, especially those associated with rheumatoid arthritis and psoriasis

2. The production of pain and fever

3. The regulation of blood pressure

4. The induction of blood clotting

5. Several reproductive functions, such as the induction of labor 6.

Regulating the sleep/wake cycle

What I've described so far is quite normal and necessary to maintain health. But dietary indiscretions can cause big problems. It's important to remember that each of these enzymes will act on any fatty acid. The critical point is that the resulting eicosanoid will differ based on the fatty acid acted upon and the amount formed.

Excessive eicosanoid formation from arachidonic acid (Omega‑6) from animal fats can be connected directly to most degenerative processes in the body from asthma and arthritis to heart disease and cancer.

Eicosanoids from EPA (fish oils) produce eicosanoids of moderately quality.

Linoleic acid and linolenic acid from plant sources produce eicosanoids of very high quality. But, in the presence of high insulin levels and low glucose‑tolerance factor, the Delta‑5 desaturase enzyme converts DGLA (from plants) into arachidonic acid (from animals) with undesirable results. This is associated with an excessively high simple carbohydrate dietary intake.

(Dr. Loomis welcomes input on the subjects covered in this column. To make a comment or ask a question, write to him at 6421 Enterprise Lane, Madison, WI 53719. Visit www.loomisenzymes.com online or call 800‑662‑2630 for information on upcoming Loomis Institute seminars.)