The interaction of inflammation and pain has long been a complex scientific puzzle. Inflammation helps the body to heal wounds and repel toxic attacks. When health is restored, the enzymes that caused the inflammation are turned off. As scientists have explored inflammation over many decades, they have learned that many of the same enzymes and mechanisms are involved in turning inflammation both on and off. Recently discovered metabolites called resolvins play a critical role in this process, and understanding of their role has shed surprising new light on how one of the oldest pain-killers, aspirin, works. For details, click here. "Controlling inflammation: a fat chance?" J. Exp. Med., Vol 201, No 5, March 7, 2005 671-674 This Research Update column highlights articles related to recent scientific inquiry into the process of human aging. It is not intended to promote any specific ingredient, regimen, or use and should not be construed as evidence of the safety, effectiveness, or intended uses of the Juvenon product. The Juvenon label should be consulted for intended uses and appropriate directions for use of the product.

By Benjamin V. Treadwell, Ph.D.

Certain fats, known as essential fats because our cells cannot synthesize them, are required to remain healthy. Two major categories of essential fats are the omega 6 and omega 3 fats. They are so labeled to designate the carbon atom where the most distal double bond is located (either the 6th or 3rd carbon in from the terminal carbon atom of the respective fatty acid). The omega 6 fatty acids are generally associated with promoting inflammation and pain, whereas the omega 3 fatty acids seem to be the nice guys who douse the fire and soothe the pain.

For maximum health we need both types, but as recent research is demonstrating, biological systems and pathways virtually always involve self-regulating events to maintain a delicate and healthy balance. Today's article is about how we can help promote a healthy, pain-free balance through diet, and by taking a reasonably safe dietary supplement along with a modest amount of an old plant-derived analgesic.

How can diet promote a healthy omega 6 / omega 3 balance?

Our human ancestors evolved in coastal areas and consumed large quantities of marine animals, as well as plants containing high levels of the omega 3 fatty acids. The estimated early human intake ratio of the omega 6 fatty acids to the omega 3 was approximately 1:1. In the modern western diet this ratio has deviated significantly, and is currently estimated to be as high as 20:1, skewed towards the inflammatory omega 6 fatty acids. Why? First, we eat a significant amount of meat from grain-fed animals, and due to putative advances in agriculture, the grain is low in the omega 3 and high in the omega 6 fats. Furthermore, the omega 3 fats are more susceptible to destruction by techniques used in processing various plants to make oils, such as vegetable oils. The consequence is a preponderance of the omega 6 fats in these oils. So, in effect we are consuming a pro-inflammatory diet. "We are what we eat" is painfully true with respect to the fats in our diet.

If the omega 6 fats are pro-inflammatory, why do we need them?

The omega 6 fats are converted into numerous important metabolic products, some of which function as signaling molecules to inform the cell of invasion by a toxic agent, such as a bacteria or virus. These molecules activate cells and mediators of the immune system, and cause subsequent inflammation (leaky blood vessels which promote redness and swelling), all for the purpose of eliminating the pathogen.

What stops this inflammatory process?

How does the tissue shut off the immune system once the pathogen is eliminated? The omega 3 fats activate the pathway leading to the resolution of the inflamed condition.

It is truly amazing that we survive as long as we do with so many complex mechanisms involved in maintaining our health. Research data, generated from a number of laboratories working together, reveal how one switch can activate two opposing pathways. It turns out that the same enzyme (COX-2), acting on an omega 6 fatty acid to produce inflammatory signaling molecules, can also act on omega 3 fatty acids to produce anti-inflammatory molecules. How is this possible? It appears that when these functionally very different molecules interact with certain enzymes and chemical receptors, they can twist them into either pro-inflammatory or anti-inflammatory units. Once the inflammation has reached some critical point, the omega 3 fatty acids become prominent and interact with the enzyme, COX-2, which converts the omega 3 fat to a metabolite that induces production of a newly discovered class of anti-inflammatory metabolites, the resolvins (for resolution of inflammation). The resolvin binds to a receptor, which in turn activates anti-inflammatory pathways. If all is in balance, the net result is the elimination of the pathogen and the return of the tissue from an inflamed war-zone condition to normal pain-free tissue.

Where does aspirin come into the story?

Unfortunately, as we all know, aches and pains don't always disappear quickly after an infection or inflammation-producing trauma. This delay in resolution of inflammation is more common with age, and is exacerbated by an imbalance in the ratio of the omega 6 – omega 3 fats. It has been discovered that aspirin, a partial inhibitor of the COX-2 enzyme, can largely convert this enzyme to a machine that prefers acting on the omega 3 fats. Therefore, the anti-inflammatory resolvins are produced in significantly greater amounts. Consequently the tissue is more likely to return to a normal pain-free state.

It is now believed that at least part of the positive effect of aspirin on cardiovascular health is due to the production of the anti-inflammatory resolvins. Cardiovascular disease, inflammatory bowel disease, and others involve an inflammatory component, and there is now evidence that certain neurological degenerative disorders such as Alzheimer's disease are associated with excess inflammation. The symptoms of these diseases may be attenuated by aspirin and a healthy ratio of omega 6 to omega 3.