Inflammatory Cascades ad NSAID’s

When tissues are injured a specific reaction to the injury takes place. A collection of irritants and other chemical mediators are released into the injured area to aid in stabilization of the injured tissue, protection against further injury, and stimulation of healing at the injury site. These factors are referred to as the inflammatory cascade. And it includes substances such as histamine, bradykinin and prostaglandins, which aid in vasodilation to the injured area; serotonin, which acts as a vasoconstrictor, and growth factors and cytokines which act to increase fibroblast and macrophage migration to the injury site. 1) This is the acute inflammatory response and it is essential to the healing process. It should be noted that this acute reaction is healthy and we do not want to impede this process. We do, however, wish t aid the healing process in order to resolve the acute inflammatory response before it passes into a chronic state of inflammation. It is th chronic state of inflammation that is always destructive to tissues and is equated to disease. (2) When repair is successful, inflammation becomes a limited phenomena. Some conditions such as asthma, allergies, autoimmune diseases, fibromyalgia, migraine headaches, osteoarthritis, peptic ulcers, and psoriasis comprise examples of perpetual or chronic inflammation. (3) It is these chronic conditions, hallmarked by pain and fatigue, that eventually lead to loss of function. The treatment that millions of people turn to each year is Non-Steroidal Anti-Inflammatory Drugs (NSAID's). However, long-term therapy has revealed an alarming list of adverse side effects associated with these drugs such as gastrointestinal bleeding, and suppression of inherent anti-inflammatory pathways and tissue repair. In addition, NSAID's have been linked to â€Å"leaky gut syndrome†, in which gut permeability is increased, allowing antigenic toxins to flood the systemic circulation via paracellular and transcellular absorption. (5) Thus, nutritional modification is the best way to guard against adverse reactions or side effects. More importantly, nutritional status is the foundation in which inflammation becomes modifiable. (3) The natural pH of the human body lies in a range between 6. 0 and 7. 4. 7) However, after an injury the pH of some tissues may fall well-below pH 6. 0, thus owing to a very acidic environment. This type of condition favors the inflammatory cascade. An acid environment is promoted by metabolism of glucose and triglycerides, and gastrointestinal bacterial metabolism of unabsorbed carbohydrates, fats, and proteins. (9) Thus, acid production depends on the diet. Also, meats and grains are a source of potential acids, whereas fruits and vegetables are a potential source of bases. 9) Therefore, a reduction in the amount of meats and grains along with a concomitant increase in the amount of fruits and vegetables would bring about a more balanced tissue pH, which in turn would favor an anti-inflammatory condition throughout the body. The production of pro-inflammatory cytokines is essential to the inflammatory response. However, overproduction of these chemicals may be detrimental. The omega-3 (n-3) polyunsaturated fatty acids suppress inflammation by decreasing the production of pro-inflammatory cytokines. 6) Some sources of n-3 fatty acids are flaxseed oil, green, leafy vegetables, and cold water fish such as salmon, sardines, and mackerel. (7) Omega-3 fatty acid works by decreasing the release of arachidonic acid, a pro-inflammatory substance, from cell membranes, and by competing for the same enzymes that generate highly reactive inflammatory chemicals. (3) In addition, supplementation of the diet with n-6 oils was found to be effective in reducing pain and sweeling in patients with rheumatoid arthritis and has been shown to be effective in the management of eczema, pms, mastalgia, and multiple sclerosis. 8) Some good sources for n-6 oils are evening primrose and black currant seed oil. Free-radicals (oxidants) are very reactive and unstable molecules that can cause damage to proteins, fats, cell membranes, and DNA. (10) When free-radicals attack, for example cell membranes, the remnants of the cell then become â€Å"information† for neighboring cells to begin the inflammatory process. (3) Thus, oxidation by free-radicals can pose a serious problem to tissues. Antioxidants, therefore, are needed to protect tissues from being destroyed by free-radicals. Essentially, polyunsaturated fatty acids in cell membranes are attacked by oxidants, thereby producing even more potent free-radicals. But, in the presence of antioxidants, these free-radicals can be reduced to a more stable and unreactive form, thus sparing other cells from damage. (7) Some important antioxidants are: Vitamins C and E, and the minerals zinc and selenium. Since many antioxidants work at different biochemical junctures, a broad spectrum approach to antioxidant therapy or supplementation should be followed. In addition, concentrated food extracts such as ginger, curcumin from tumeric root, and bromelain from pineapple can help attenuate skeletal muscle injury by modulating the inflammatory event. (11) Foods which contain copious amounts of antioxidants are: garlic, onions, carrots, green vegetables, broccoli, Brussels sprouts, cabbage, cauliflower, tomatoes, and citrus fruits. In addition, red wine and grape juice contain phenolic compounds that provide protection against heart disease, cancer, diabetes, and hypertension. (12)