Now that we're through all the weird stuff, let's get to THE CURE! First though, it's important that you know a bit about inflammation and what exactly it is we're treating. Inflammation (Latin: inflamatio, to set on fire) is the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells or irritants. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. In the absence of inflammation, wounds and infections would never heal and progressive destruction of the tissue would compromise the survival of the organism. However, an inflammation that runs unchecked can also lead to a host of diseases including atherosclerosis and rheumatoid arthritis. Inflammation can be classified as either acute or chronic. Acute inflammation is the initial response of the body to harmful stimuli and is achieved by the increased movement of plasma and leukocytes from the blood into the injured tissues. Prolonged inflammation, known as chronic inflammation, leads to a progressive shift in the type of cells which are present at the site of inflammation and is characterized by simultaneous destruction and healing of the tissue from the inflammatory process. Inflammation Wikipedia http://en.wikipedia.org/wiki/Inflammation 1. Acute - Swelling Stage 2. Subacute - Regenerative Stage 3. Chronic - Scar Tissue Maturation and Remodeling Stage Swelling Stage: During this stage there is inflammation, redness and swelling due to the vascular changes. There is exudation of cells and chemicals that cause the swelling and the pain. Secondarily, the chemical irritants are neutralized, the area is sealed off from surrounding tissue and circulation is impaired. Symptoms are pain at rest and aggravated by activity. Subacute Stage: The time of healing and repair. Noxious chemicals are further neutralized. New capillary beds growing into the damaged areas are supported by connective tissue growth (collagen fibers) and together form granulation buds. This new tissue is fragile and must be handled gently as it is easily injured. Visible signs of inflammation subside. Remodeling Stage: Signs of inflammation are absent and scar tissue is maturing. Maturation refers to the growth of the fibroblasts to fibrocytes and remodeling refers to the organization of and shrinking of collagen fibers along lines of stress. "Stages of Inflammation." Julie Onofrio, LMP, www.thebodyworker.com/physio_inflammation_overview.htm Although reduction of inflammation has been the key focus of medicine, there are surprisingly few clinical markers to quantify its intensity. The most obvious non-invasive marker is pain. As with pain, the other observations of classical inflammation (fever, redness, and swelling) are all mediated by pro-inflammatory eicosanoids. Blood markers of classical inflammation are also relatively crude. These include increased white cell counts, exceptionally high levels of C-reactive protein (CRP), and increased red cell sedimentation rates. Recently very low levels of CRP have been advanced as a marker of inflammation (5-8), but because of its rapid increase with acute infection, the use of this marker as an indicator of chronic low-level inflammation remains controversial. There are two types of inflammation. The first is classical inflammation that hurts because of organ damage. This is what forces you go to a doctor. The second type is far more insidious and far more dangerous. I call this silent inflammation. This type of inflammation causes no pain therefore you do nothing to stop it. But after years, if not decades of constant inflammatory attack, there is enough organ damage that you call it chronic disease. Silent inflammation, on the other hand, can be considered the precursor to classical inflammation and is best measured by the ratio of two essential fatty acids in the blood. One is arachidonic acid (AA). the omega-6 essential fatty acid building block of pro-inflammatory eicosanoids, and the other is eicosapentaenoic acid (EPA), the omega-3 essential fatty acid building block of several important anti-inflammatory eicosanoids. Silent inflammation is an indicator of the inflammatory potential at the cellular level. It is not a disease, but high levels of silent inflammation are the first indication that you are no longer well. There is no drug that can reverse silent inflammation, but the anti-inflammatories can. Silent Inflammation, Dr. Barry Sears, Official Science Site of the Zone Diet, Sep 2009 www.drsears.com/AntiInflammatoryNutrition/tabid/380/Default.aspx "Anti-Inflammatory Medicine: Dietary Modulation of Eicosanoids" Inflammation Research Foundation, Marblehead, MA www.inflammationresearchfoundation.org C-reactive protein A protein found in the blood, the levels of which rise in response to inflammation (i.e. C-reactive protein is an acute-phase protein). Its physiological role is to bind to phosphocholine expressed on the surface of dead or dying cells (and some types of bacteria) in order to activate the complement system via the C1Q complex. CRP is synthesized by the liver in response to factors released by fat cells (adipocytes). It is a member of the pentraxin family of proteins. It is not related to C-peptide or protein C. CRP is a member of the class of acute-phase reactants, as its levels rise dramatically during inflammatory processes occurring in the body. CRP is used mainly as a marker of inflammation. Apart from liver failure, there are few known factors that interfere with CRP production. Measuring and charting CRP values can prove useful in determining disease progress or the effectiveness of treatments. Blood, usually collected in a serum-separating tube, is analysed in a medical laboratory or at the point of care. Various analytical methods are available for CRP determination, such as ELISA, immunoturbidimetry, rapid immunodiffusion, and visual agglutination. "The physiological structure of human C-reactive protein and its complex with phosphocholine." Thompson, D; Pepys, MB; Wood, SP (February 1999). Structure 7 (2): 169–77. doi:10.1016/S0969-2126(99)80023-9. PMID 10368284. "C-reactive protein: a critical update." Pepys, MB; Hirschfield, GM (June 2003). J Clin Invest 111 (12): 1805–12. doi:10.1172/JCI18921. PMC 161431. PMID 12813013. "Adipokines: molecular links between obesity and atheroslcerosis." Lau, DC; Dhillon, B; Yan, H; Szmitko, PE; Verma, S (May 2005). Am J Physiol Heart Circ Physiol 288 (5): H2031–41. doi:10.1152/ajpheart.01058.2004. PMID 15653761. "C reactive protein." Wikipedia en.wikipedia.org/wiki/C-reactive_protein Silent Inflammation Silent inflammation is the first sign that your body is out of balance and you are no longer well. You can't feel it, but it is affecting your heart, your brain, and your immune system. There are three underlying hormonal changes that are linked to silent inflammation. They involve the overproduction of three distinct types of hormones: o Eicosanoids o Insulin o Cortisol "A Silent Killer in Our Midst" Dr. Barry Sears, Zone Health.com www.zoneliving.com (2005) Eicosanoid A lipid mediator of inflammation derived from the 20-carbon atom arachidonic acid (20 in Greek is "eicosa") or a similar fatty acid. The eicosanoids include the prostaglandins, prostacyclin, thromboxane, and leukotrienes. eicosanoids can be considered "super-hormones" capable of modulating the immune system either by turning on the inflammatory response ("bad" eicosanoids) or turning off the inflammatory response ("good" eicosanoids) depending on which type of an eicosanoid a cell produces. Unlike typical hormones that are produced by a particular gland, every cell in your body is capable of producing eicosanoids. In essence, you have about 100 trillion eicosanoid glands, and the goal of anti-inflammatory medicine is to maintain an appropriate balance of the "good" and "bad" eicosanoids by controlling the levels of their molecular building blocks in the membranes of each cell in the body. Here are some examples of chronic diseases that result from an excess production of "bad" eicosanoids. o Heart disease o Stroke o Hypertension o Arthritis o Cancer o Asthma o Depression o Alzheimer's Eicosanoids form the command center of your immune system. Knock them out completely, and the immune system gets knocked out as well. This occurs in those who have immune-deficiency diseases, such as AIDS. Long-chain omega-3 fatty acids reduce pro-inflammatory eicosanoids, whereas omega-6 fatty acids increase the production of pro-inflammatory eicosanoids. Dr. Barry Sears, Official Science Site of the Zone Diet, www.drsears.com MedicineNet www.medterms.com/script/main/art.asp?articlekey=25922 "Anti-Inflammatory Medicine: Dietary Modulation of Eicosanoids" Inflammation Research Foundation, Marblehead, MA www.inflammationresearchfoundation.org "A Silent Killer in Our Midst" Dr. Barry Sears, Zone Health.com www.zoneliving.com (2005) Insulin Insulin is the storage hormone that drives nutrients into cells. It is vital for your survival since it allows cells to either store nutrients or immediately use them for energy. Without adequate levels of insulin, your cells would literally starve to death. And this is exactly what happens in type 1 (childhood-onset) diabetes, in which the patient is producing no insulin. (In fact, only a small percentage of diabetics have this type of diabetes.) Without injections of insulin, death is the inevitable outcome. But most of us are much more likely to have the opposite problem: we make way too much insulin. This is bad news, since it is excess insulin that makes you fat and keeps you fat. Excess insulin's link to silent inflammation stems from the fact that it increases the production of arachidonic acid (AA), the building block for all pro-inflammatory eicosanoids. And if that isn't bad enough, recent research shows that insulin induces inflammation by increasing the production of interleukin-6 (IL-6), a pro-inflammatory cytokine that causes the formation of C-reactive protein, another marker for silent inflammation. The bottom line: controlling insulin is essential if you want to reverse silent inflammation and move toward a state of wellness. "A Silent Killer in Our Midst" Dr. Barry Sears, Zone Health.com www.zoneliving.com (2005) Cortisol (hydrocortisone) A steroid hormone, or glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat, protein and carbohydrate metabolism. When your body is in a constant state of silent inflammation, it reacts to it by having your adrenal glands pump out high amounts of cortisol, the primary anti-inflammatory hormone used to decrease excess inflammation. We tend to think of cortisol as a stress hormone, but in reality it is an anti-stress hormone. At the cellular levels all stress creates an inflammatory state caused by an over-production of pro-inflammatory eicosanoids. Cortisol is sent out to lower the levels of these eicosanoids, which is fine over the short run when stress is temporary. But having a high level of constant silent inflammation means you are going to have high levels of cortisol on a permanent basis, causing a number of nasty consequences such as increasing insulin resistance (which makes you fatter), killing nerve cells (which makes you dumber), and depressing your entire immune system (which makes you sicker). This is the collateral damage that comes from increased silent inflammation. "Cortisol" Wikipedia, en.wikipedia.org/wiki/Cortisol "First Aid USMLE Step 1" Tao Le et al. (2009) "A Silent Killer in Our Midst" Dr. Barry Sears, Zone Health.com www.zoneliving.com (2005) Arachidonic Acid (AA) This is the 20-carbon length long-chain omega-6 fatty acid that is the immediate precursor of many eicosanoids that increase inflammation. Egg yolks, fatty red meat, and organ meats are rich sources of arachidonic acid. "Anti-Inflammatory Medicine: Dietary Modulation of Eicosanoids" Inflammation Research Foundation, Marblehead, MA www.inflammationresearchfoundation.org Eicosapentaenoic Acid (EPA) This is the 20-carbon length long-chain omega-3 fatty acid that that inhibits the formation of arachidonic acid (AA). Fish oils are the richest source of EPA. "Anti-Inflammatory Medicine: Dietary Modulation of Eicosanoids" Inflammation Research Foundation, Marblehead, MA www.inflammationresearchfoundation.org AA/EPA ratio (A Measure of "Silent" Inflammation) This unique test measures the ratio of arachidonic acid (AA) to eicosapentaenoic acid (EPA) in plasma. This ratio of the principle omega-3 and omega-6 fatty acids is a measure of the body's eicosanoid balance. Balancing the eicosanoids in the body is an excellent way for managing heart disease and other chronic and inflammatory processes. When Good Fat Turns Bad, a lower AA/EPA ratio indicates a better balance of "good" and "bad" eicosanoids in your body. An AA/EPA ratio of less than 3 but not less than 1.5 is considered to be ideal. It is no longer considered "well" to have a ratio greater than 10. Anything exceeding 15 means a high level of inflammation in the blood (Toxic Fat Syndrome) and requires immediate dietary attention. Dr. Barry Sears, Official Science Site of the Zone Diet, www.drsears.com "Anti-Inflammatory Medicine: Dietary Modulation of Eicosanoids" Inflammation Research Foundation, Marblehead, MA www.inflammationresearchfoundation.org

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