Restore and Maintain treatment protocol Combating inflammation through the modulation of eicosanoids Inflammation Inflammation is the normal response of a tissue to injury and can be triggered by a number of causes including infection, compromised blood flow, and invading pathogens (such as bacteria or viruses). If the immune system failed to respond, and no inflammation occurred, the damage caused by the resulting infection would fail to heal. In contrast, if the inflammatory response continues unnecessarily, this can lead to further damage. Therefore the inflammatory response must be a tightly regulated system. 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 specialised cells of the immune system from the blood into the injured tissues followed by a cascade of biochemical events that further matures the response. The inflammatory response is then followed by a series of downplaying signals to halt the inflammatory process once the immune crisis is over. It thus follows that poorly regulated, prolonged or inappropriate inflammation, also known as chronic or low-grade inflammation ( silent inflammation ) increases susceptibility to illness and disease. Eicosanoids and inflammation The key to regulating inflammation is through the modulation of a group of hormones called eicosanoids. The eicosanoid system consists of both pro-inflammatory products that drive the immune and inflammatory processes and anti-inflammatory products that act to reverse the process. Thus, with the correct signalling, the inflammatory response can be both switched on and switched off appropriately. Overproduction of pro-inflammatory products or reduced production of anti-inflammatory products can result in continued production of inflammatory products the hallmark of silent inflammation. Not surprisingly, the majority of anti-inflammatory drugs are targeted to reduce the production of pro-inflammatory eicosanoids. It is, however, possible to mediate the production of pro-inflammatory eicosanoids through natural dietary means.
Regulating eicosanoids through diet The group of polyunsaturated fats known as omega-3 and omega-6 are the precursors to all eicosanoids. The omega-3 fatty acid alpha-linolenic acid (ALA) and the omega-6 fatty acid linoleic acid (LA) are essential to the body and must be consumed in the diet. It is from these two shortchain fatty acids that the long-chain eicosanoid-producing fatty acids are produced. ALA converts to the anti-inflammatory eicosanoid-producing omega-3 eicosapentaenoic acid (EPA). LA converts to dihomo-gamma-linolenic acid (DGLA), which then converts to either a series of anti-inflammatory eicosanoids or to arachidonic acid (AA), the precursor to inflammatory eicosanoids. The route DGLA takes is dependent on levels of omega-3 and will favour the production of AA when omega-3 levels are low. The two omega families (6 and 3) share and compete for the enzyme known as delta-6 desaturase that is involved in the production of EPA, DGLA and AA and if one of the two families dominates within the diet, that family will hog the available supply of delta-6 desaturase, resulting in an unbalanced production of long-chain omega-3 and omega-6 and their derived eicosanoids. As Western diets are often much lower in omega-3 than omega-6, the conversion of ALA to EPA is consistently low in most people; excess LA is free to convert to inflammatory AA with potential health consequences, as observed in many Western associated diseases. Furthermore, AA is directly present in animal and dairy products and especially high in those animals that have been fed on grains rich in LA. Whilst EPA is present in fish and shellfish, our intake of marine sourced EPA is low in comparison to intake of omega-6-rich food. Given that many fish species present concerns over contamination with PCBs, dioxins and methylmercury, advised consumption levels fall short of the amount needed to offer therapeutic levels of EPA. Highly purified EPA supplements, in contrast, offer a safe and convenient method of achieving the high cellular levels required to reduce inflammation and restore immune balance.
The physiological actions of eicosanoids AA derived eicosanoids Condition EPA and/or DGLA derived eicosanoids increased risk sudden cardiac death decreased risk increased coronary heart disease decreased increased platelet aggregation decreased more vasoconstriction less reduced blood flow improved higher blood pressure lower higher triglycerides lower worse rheumatoid arthritis improved more pain less more inflammation less more major depression less less mood elevation more less mood stabilisation more The AA:EPA ratio The specific ratio of the principal omega-3 and omega-6 fatty acids AA and EPA provides valuable information on the measure of the body's eicosanoid balance. As a useful indicator of general health status, managing the AA:EPA ratio can offer significant long-term health benefits and reduce the risk of developing chronic low-grade inflammation. A low AA:EPA ratio of less than 3 but not less than 1.5 indicates a better balance of anti-inflammatory to inflammatory eicosanoids in the body. If the body reaches a ratio of 7 or over, this suggests that the body is in a state of silentinflammation and at a higher risk of developing inflammatory-based conditions. Anything exceeding a ratio of 15 means a high level of inflammation, common to many inflammatory conditions.
AA:EPA ratio - A measure of silent inflammation Range Inflammation Long-term health 1.5 to 3.0 low excellent 3.1 to 6.9 moderate good 7.0 to 14.9 elevated moderate > than 15 high poor Treating chronic low-grade inflammation Developing an anti-inflammatory treatment regime is one that prevents or reduces the accumulation of AA from the diet. By reducing AA we reduce the substrate for the formation of inflammatory eicosanoids. The introduction of a two-step programme of supplementation works in a two-pronged approach. Pre-loading the body with pure ethyl-epa acts favourably to restore a healthy omega-6:omega-3 ratio. Once this is achieved and the optimal balance of AA:EPA eicosanoids is restored, we introduce the substrate for the formation of DGLA eicosanoids by the inclusion of gamma-linolenic acid (GLA), the direct precursor to DGLA. In addition to yielding antiinflammatory eicosanoids, DGLA competes with AA for enzymes needed for eicosanoid production, inhibiting the production of inflammatory products from AA. Therefore EPA works with GLA to soften the inflammatory effects of AA and its products.
Step 1 - Restore Marine EPA 90% ultra-pure & vitamin E E-EPA 90 is the purest ethyl-epa concentrate available without prescription, suitable for counteracting omega-3 deficiencies and restoring a healthy omega-6 to omega-3 ratio that reflects favourably on the production of AA:EPA eicosanoids. Step 2 - Maintain Marine EPA 70% & plant GLA Vegepa E-EPA 70 combines the benefits of 70% ethyl-epa concentrate extracted from marine anchovy oil with GLA and triterpene antioxidants from organic evening primrose oil. This unique formulation is designed to balance and maintain a healthy balance of omega-3 and omega-6 derived actions of E-EPA-90. eicosanoids. Vegepa E-EPA 70 is the ideal follow-on treatment once a healthy omega-6 to omega-3 ratio has been restored by the therapeutic Which conditions would benefit from the restore and maintain regime? It is suggested that inflammation plays a role in the initiation and progress of all diseases. Given that deficiencies in omega-3 are related to inflammatory conditions, it is not surprising that EPA and EPA/GLA supplementation is beneficial to the majority.
Examples of inflammatory-based conditions Depression Bipolar disorder Schizophrenia Irritable bowel syndrome Fibromyalgia Neuropathy Myalgic encephalomyelitis (chronic fatigue syndrome) Inflammatory bowel disease: (Crohn s disease, ulcerative colitis) Cancer Metabolic syndrome Diabetes Huntington s chorea Alzheimer s disease Chronic pain syndromes Fatty liver disease Rheumatoid arthritis Skin conditions (eczema, psoriasis, dermatitis) Cachexia High blood pressure Arrhythmia High cholesterol High triglycerides Heart failure Thyroid disorders Neurodevelopmental disorders (autism, dyslexia, dyspraxia, ADHD) Dosing guide The following table offers a general guide to dosing which is based on the severity of symptoms described. Capsules should ideally be split into a minimum of two doses daily and should always be taken with food, preferably a meal containing some fat to aid absorption. Symptom severity Step 1 Restore E-EPA 90 capsules/day Step 2 Maintain Vegepa E-EPA 70 capsules/day Severe 5-6 6-8 Moderate 3-4 4-5 Mild 1-2 2-3 For more information on the Restore and Maintain treatment protocol, or for detailed information on specific conditions, please contact our in-house nutrition scientist Dr Nina Bailey on 0845 1300424 or email ninab@igennus.com.