Inflammation and its Role in Disease

Kaysen GA.Division of Nephrology, Department of Medicine, University of California, Davis, CA 95616, USA. gakaysen@ucdavis.edu Specific laboratory tests and physical findings are available to the practicing clinician that should raise the suspicion of inflammation. Inflammation is related to specific clinical outcomes. Once identified, changes in clinical practice may affect the level of inflammation in individual and or groups of dialysis patients with the hope that these changes may in turn affect outcome in a positive manner. Standard clinical tests and observations associated with inflammation are hypoalbuminemia, erythropoietin resistance, decreased iron saturation accompanied by high ferritin, frailty, low serum creatinine, reduced total and LDL-cholesterol, and increased C reactive protein (CRP). Inflammation is strongly associated with loss of physical function, dyslipidemia (low LDL- and HDL-cholesterol, increased triglycerides), and anemia that is unresponsive to erythropoietin. Inflammation is associated with cardiovascular events, increased hospitalization, and death. Correctible causes of inflammation are tunneled dialysis catheters, arteriovenous grafts, catheter infection, periodontal disease, poor water quality, and dialyzer incompatibility. Obesity also is a source of cytokines but may be less amenable to treatment. Inflammation is multifactorial in dialysis patients. Some sources are recognizable and correctable, such as vascular access type, clinical infection, and water quality, and some are not. Inflammation is strongly associated with outcome.

CHINESE MEDICAL VIEW OF INFLAMMATION
o Obviously the ancient Chinese did not have access to our modern scientific understanding of inflammation. They would differentiate diseases according to established principles of pattern discrimination. By applying these same principles to today’s disease patterns we can gain an understanding of how the ancient Chinese medical doctors would have viewed and treated inflammatory conditions.

o The flow of Qi and Blood plays a very big role in the understanding of health and disease in Chinese Medicine. So blockages in the flow of Qi and Blood are one of the first patterns to examine when trying to understand inflammatory conditions from a Traditional Chinese Medical perspective. Qi and Blood can become blocked in any part of the body — the organs, muscles, head, back, extremities or joints. If the blockage is due to what is known as Qi Stagnation it will cause a feeling of distention or soreness that fluctuates in intensity and location. If the blockage is due to Blood Stagnation it will be characterized by painful swelling or sharp, stabbing pain at a specific fixed location. Blood Stagnation can also be due to Deficiency of Qi, Heat in the Blood, Blood Deficiency and Interior Cold. The Liver is the organ most affected by stagnation of Qi. (See our article entitled Liver Qi Constraint for more on this subject.)

o Other Chinese Medical patterns to consider when looking at inflammatory conditions are: Damp Heat, Dampness and Wind-Damp among others. Wind-Damp consists in the invasion of Wind and Damp manifesting in itchy skin, skin rashes, fever, occipital stiffness, body aches, a feeling of heaviness and swollen joints.

RESEARCH ON THE BENEFITS OF ACUPUNCTURE FOR INFLAMMATION
o In a study published in Neurosci Lett. 2002 Feb 8;319(1):45-8 by Son YS et al entitled “Antipyretic effects of acupuncture on the lipopolysaccharide-induced fever and expression of interleukin-6 and interleukin-1 beta mRNAs in the hypothalamus of rats” they concluded that acupuncture stimulation may be effective for reducing elevated body temperature induced by bacteria inflammation, and part of its action may be mediated through the suppression of hypothalamic production of pro-inflammatory cytokines.

o In a study published in Am J Chin Med 2003;31(6):955-65 by Sekido R et al entitled “Differences of electroacupuncture-induced analgesic effect in normal and inflammatory conditions in rats.” they concluded that peripheral opioid receptors are involved in electroacupuncture during inflammatory conditions.

o In a study published in Acupunct Electrother Res. 2000;25(3-4):155-63 by Nepp J et al entitled “Tolosa Hunt Syndrome – intractable pain treatment with acupuncture?” they concluded that acupuncture seems to be a good additional method for reduction of intractable pain.

o In a study published in Exp Neurol 2004 Sep;189(1):189-96 by Liu XY et al entitled “Electro-acupuncture stimulation protects dopaminergic neurons from inflammation-mediated damage in medial forebrain bundle-transected rats” they concluded that the neuroprotective effect of electroacupuncture on the dopaminergic neurons may stem from the collaboration of its anti-inflammatory and neurotrophic actions.

o In a study published in Am J Chin Med 2004;32(2):269-79 by Sekido R et al entitled “Corticotropin-releasing factor and interleukin-1 beta are involved in the electroacupuncture-induced analgesic effect on inflammatory pain elicited by carrageenan” they concluded that the release of corticotropin-releasing factor or IL-1 elicited by electroacupuncture may trigger the release of opioid peptides within inflamed tissue which may activate peripheral opioid receptors and inhibit the pain.

o In a study published in the Am J Chin Med 2003;31(2):315-20 by Wozniak PR et al entitled “Anti-phlogistic and immunocompetent effects of acupuncture treatment in women suffering from chronic pelvic inflammatory diseases” the authors concluded that acupuncture treatment of pelvic inflammatory disease exhibits a clear anti-inflammatory and immunocompetent effect.

ROLE OF INFLAMMATION IN DISEASE
o Alzheimer’s Disease
v Giri et al noted that in Alzheimer’s disease one finds increased deposition of amyloid peptide A beta and also an increased presence of monocytes and macrophages in the vessel wall and activated microglial cells in the brain. Alzheimer’s disease patients show increased levels of proinflammatory cytokines by activated microglia. (Giri et al 2003)

v According to an article in Alternative Medicine magazine by Guthrie although the mechanism causing Alzheimer’s disease is not fully understood, neurologists believe the brain’s immune cells rally to attack a form of plaque that signals Alzheimer’s disease. The ensuing skirmish creates inflammation that may spur progression of the disease.

o Asthma
v Inflammatory cells, such as activated eosinophils and neutrophils are associated with increased levels of IL-5, IL-8 and of proinflammatory mediators. Viruses, but also endotoxin or allergen exposure, are able to recruit neutrophils, via an IL-8 production by activated macrophages or epithelial cells. Together, these inflammatory mediators are responsible for the diffuse bronchial inflammation. Activated T cells may also be related to the pathogenesis of severe asthma. The persistence of inflammatory cells in bronchi, particularly neutrophils, which respond poorly to corticosteroids, could be in part responsible for the epithelial damage, the extensive mucus plugging, and the abnormalities of epithelial and endothelial permeability which are associated with severe acute asthma. (Tillie-Leblond et al 2005)

v Bronchial provocation with allergen induces a prompt early phase immunoglobulin E (IgE) – mediated decrease in bronchial airflow followed in many patients by a late-phase IgE mediated reaction with a decrease in bronchial airflow for 4-8 hours. Initially, there is recruitment of leukocytes from the bloodstream to the airway by activated DC4 T-lymphocytes. The activated T-lymphocytes also direct the release of inflammatory mediators from eosinophils, mast cells, and lymphocytes. In addition, the subclass 2 helper T-lymphocytes subset of activated T-lymphocytes produces interleukin (IL)-4, IL-5 and IL-13. IL-4 in conjunction with IL-13 signals the switch from IgM to IgE antibodies. The cross-linkage of two IgE molecules by allergen causes mast cells to degranulate, releasing histamine, leukotrienes, and other mediators that perpetuate the airway inflammation. IL-5 activates the recruitment and activation of eosinophils. The activated mast cells and eosinophils also generate their cytokines that help to perpetuate the inflammation. (Fireman 2003)

o Cancer
v During chronic inflammatory processes an excess of free radicals and DNA-reactive aldehydes from lipid peroxidation (LPO) are produced, which deregulate cellular homeostasis and can drive normal cells to malignancy. (Bartsch & Nair 2001)

v A study done by O’Byrne and Dalgleish in 2001 concluded that chronic inflammation may lead to the production of reactive oxygen species and metabolites such as malondialdehyde within affected cells that may in turn induce DNA damage and mutations and, as a result, be carcinogenic. They proposed that the conditions provided by a chronic inflammatory environment are so essential for the progression of the neoplastic process that therapeutic intervention aimed at inhibiting inflammation, reducing angiogenesis and stimulating cell mediated immune responses may have a major role in reducing the incidence of common cancer.

v Betulinic acid, a pentacyclic lupane-type triterpene, from Chaga (Inonotus obliquus):
Chaga has been used in Eastern Europe, especially in Russia, as a folk medicine since the 16th century for treating cancer. Betulinic acid, a main compound found in Chaga powdered extract, is a selective inhibitor and inducer of apoptosis of many cancers (and HIV), including human melanoma. NF-κB inhibition has shown to be one of the many mechanisms through which betulinic acid suppresses melanoma and other cancers.

o Cardiovascular Disease
v The process of inflammation is now believed to be the etiological event that precedes the development and the continual process of atherosclerosis. This process, beginning with an injury or change in the endothelial wall of the artery, causes an alteration in the intimal layer that increase leukocyte, LDL, and platelet adhesion to the endothelium. Possible causes of “dysfunctional endothelium” include: free radical damage from environmental exposure; hypertension and its proinflammatory effects (smooth muscle lipoxygenase activity and oxide radical formation; direct toxic effects of homocysteine; infections with Chlamydia pneumonia and herpes viruses; and advanced glycosylated end-products (the result of an oxidation reaction with glucose that results in a type of oxidant commonly found in the blood of diabetics).

v Most risk markers for cardiovascular disease have a pro-inflammatory component, which stimulates the release of a number of active molecules such as inflammatory mediators, reactive oxygen species (ROS), nitric oxide and peroxynitrite from endothelial, vascular smooth muscle and immune cells in response to injury.

v Risk factors for cardiovascular disease that have a pro-inflammatory component include LDL cholesterol, smoking, infection, homocysteine, ischemia, oxidant damage, interleukin-6, lipoprotein (a), high sensitivity C-reactive protein (hs-CRP), serum intracellular adhesion molecule-1 and apolipoprotein-B. One common link among these risk factors is the activity and metabolism of nitric oxide (NO).

v Oxidized or modified LDL is a recognized source or damage to the endothelial wall. The presence of oxidized LDL promotes the expression of growth factors and chemotactic proteins, causing an expanding inflammatory response and up-regulating monocyte replication to increase macrophage populations. The mediators of the inflammatory response: IL-1, TNF-α, IL-6, macrophage colony stimulating factor, etc, all increase the binding of LDL to the endothelium and smooth muscle to further up-regulate the inflammatory response.

v During the development of atherosclerosis, macrophages interact with vascular endothelial cells, medial smooth muscle cells and infiltrated inflammatory cells, particularly T cells and dendritic cells. Unquenched intracellular reactive oxygen species (ROS) induce monocytes to differentiate into macrophages. These cells then accumulate cholesterol esters in the cytoplasm, which leads to foam cell formation in lesion development. (Foam cells are fatty cells that together form the fatty streak – the first identifiable characteristic lesion of advanced atherosclerosis).

v Further recruitment of monocytes and macrophages can occur by the release of cytokines from the endothelium and vascular smooth muscle as part of the inflammatory cycle. As a result, the atheromatous plaque core becomes rich in macrophages as the plaque ages. A vicious cycle ensues of endothelial cell activation that induces the expression of vascular cell adhesion molecule (VCAM-1) and monocyte chemo-attractant proteins (MCP-1), leading to increased monocyte/macrophage recruitment into the intima. This results in a soft plaque that increases the risk of unstable angina, thrombosis and acute myocardial infarction.

v Growing evidence indicates that chronic and acute overproduction of reactive oxygen species (ROS) under pathophysiologic conditions is integral in the development of cardiovascular diseases. ROS mediate various signaling pathways that underlie vascular inflammation in atherogenesis: from the initiation of fatty streak development through lesion progress to ultimate plague rupture. (Madamanchi 2004) When the plaque finally ruptures causing debris to barricade the artery it is disastrous.

v Data suggest that cytokine-induced endogenous iNOS (inducible nitric oxide synthase) expression and activity have key functions in increasing endothelial survival and maintaining function. Thus suppression of iNOS expression or limited substrate supply, as has been reported to occur in atherosclerosis patients, appears to significantly contribute to endothelial dysfunction and death during oxidative stress. (Hemmrich et al 2003)

v There is increasing evidence that systemic inflammation and insulin resistance constitute interrelated events that contribute to atherosclerosis. Circulating IL-6 levels, by inducing either hypertension in women or insulin resistance in men, constitutes a significant proatherogenic cytokine, as suggested by recent studies in which the serum IL-6 concentration was an independent predictor of cardiovascular mortality. (Fernandez-Real et al 2001)

v Inflammation (as quantified by CRP) appears to be associated with a significant prothrombotic status and endothelial dysfunction. (Apetrei 2004) CRP levels are markers of atheromatous plaque vulnerability and coronary artery disease activity. (Arroyo-Espliguero et al 2004)

v It can now be hypothesized that atherosclerosis may be an inflammatory disease that contributes to derangement of the vascular NO (nitric oxide) metabolic pathway and to increased oxidant stress. Recognizing that atherosclerosis is a multi-factorial inflammatory process lends to the assumption that anti-inflammatory nutrients might mitigate the disease.

o Inflammatory Bowel Disease
v Crohn’s disease and ulcerative colitis are chronic inflammatory bowel diseases of unknown origin. However the chronic immune stimulation of these conditions may be due to an imbalance of pro-inflammatory and inhibitory cytokines. (Lehmann 2003)

v It is well known that immune responses in the intestine remain in a state of controlled inflammation, suggesting that not only active suppression by regulatory T (TR) cells play an important role in the normal intestinal homeostasis, but also its dysregulation leads to the development of inflammatory bowel diseases. (Kanai & Watanabe 2004)

v The precise cause(s) of Crohn’s disease and ulcerative colitis are unknown. From animal models and human studies it is well established that gut bacteria flora are essential for inducing the bowel inflammation. (Chandran et al 2003)

v For more information on inflammatory bowel disease we invite you to read the section entitled “Inflammatory Bowel Disease, Crohn’s Disease and Ulcerative Colitis” in our article on Gastro-Intestinal Disorders on our website.

o Insulin Resistance & Obesity
v Inflammation is a hyper-resistinemic state in humans, and cytokine induction of resistin may contribute to insulin resistance in endotoxemia, obesity and other inflammatory states. Adipocyte-derived resistin is a circulating protein implicated in insulin resistance in rodents, but the role of human resistin is uncertain because it is produced largely be macrophages.(Lehrke et al 2004)

v In a study done by Chen et al in 2004 they concluded that elevated levels of inflammatory markers are positively and independently associated with insulin resistance.

v Obesity and type 2 diabetes are associated with a state of abnormal inflammatory response. The state of chronic inflammation typical of obesity and type 2 diabetes occurs at metabolically relevant sites, such as the liver, muscle and most interestingly, adipose tissues. When TNF-alpha activity is blocked in obesity, either biochemically or genetically, the result is improved insulin sensitivity. (Hotamisligil 2003)

v Several lines of evidence suggest that obesity per se constitutes a low-grade inflammatory state. Elevated CRP levels have consistently been demonstrated in overweight and obese adults, even among young adults aged 17-39 years. The relationship between CRP and insulin might be due to insulin resistance itself. Insulin attenuates IL-6 type cytokine stimulation of most acute phase protein genes in human hepatoma cells. Thus, the relative lack of insulin action, as found in insulin resistance, would not be able to block IL-6 actions, leading to a prolonged acute phase reaction.

v Endoplasmic reticulum stress is a central feature of peripheral insulin resistance and type 2 diabetes at the molecular, cellular and organismal levels. (Ozcan et al 2004)

o Rheumatoid Arthritis
v Monocytes and macrophages are indicated to have an important and versatile role in joint inflammation and destruction in rheumatoid arthritis. (van Roon et al 2004)

v The proinflammatory cytokines IL-1 and TNF-α are reported to play important roles in cartilage and bone degradation, with TNF- α occupying a primary position in the cytokine cascade through its ability to upregulate production of other cytokines, including IL-1, granulocyte-macrophage colony-stimulating factor, IL-6, IL-8 and IL-10. (Woolley & Tetlow 2000)

v Increased numbers of mast cells are found in the synovial tissues and fluids of patients with rheumatoid arthritis and at sites of cartilage erosion. Because the mast cell contains potent mediators, including histamine, heparin, proteinases, leukotrienes and multifunctional cytokines, its potential contributions to the processes of inflammation and matrix degradation have recently become evident.

v For more information on rheumatoid arthritis we invite you to read our article entitled Rheumatic & Arthritic Conditions on our website.

ANTI-INFLAMMATORY HERBS, FOODS AND SUPPLEMENTS
Although it is not possible to successfully treat all forms of inflammation with herbs, diet and supplements, progress is being made and there are several important strategies which are being developed which offer promising alternatives to NSAIDs, corticosteroids and COX-2 inhibitors. We summarize some of these strategies below:

o Omega 3 Fatty Acids
v Animal experiments and clinical intervention studies indicate that omega-3 fatty acids have anti-inflammatory properties and, therefore, might be useful in the management of inflammatory conditions. Many of the placebo-controlled trials of fish oil in chronic inflammatory disease reveal significant benefit, including decreased disease activity and a lowered use of anti-inflammatory drugs. (Simopoulus 2002)

v Subhuti Dharmananda, in an excellent article on the role of diet in inflammation, quotes from data provided by the NIH showing the omega 6 and omega 3 contents of herbal oils, fish oils and miscellaneous oils. At the top of the list are perilla seed oil with an omega-6 to omega-3 ratio of 1 to 5.33 and flaxseed oil with a 1 to 3.56 ratio. These are followed by fish oils;which are almost the only foods which contain long chain fatty acids (EPA and DHA), with ratios of 1 to 2.5 in the case of salmon. Of the miscellaneous oils ghee (clarified butter) has an omega 6 to omega 3 ratio of 1 to .64 and canola oil has a 1 to .46 ratio. Peanut oil, coconut oil and sunflower oil are at the bottom of the list and have no detectable omega-3 fatty acids.

v Fish oil provides an additional benefit, in that it reduces T-cell stimulation in the intestinal tract that may be involved in triggering inflammation and auto-immune responses. Over a period of years eating a diet high in omega-3 rich oils and low in omega-6 oils may reduce the vasoconstriction, platelet aggregation, and chronic arterial inflammation that lead to heart attacks and stroke. Similarly, it is believed that such a diet can reduce the incidence of certain cancers, such as prostate cancer and colon cancer, by a similar mechanism of reducing adverse eicosanoid effects.

v One should be aware that attempting to strongly control inflammation in acute manifestations such as asthma and arthritis by diet alone is much more difficult. Excessive use of omega-3 fatty acids, via supplementation, may actually have undesirable effects such as undesired level of immune suppression and serve as pro-oxidants (which can be partly countered by consuming antioxidants in the diet such as those found in tea, fruits and vegetables or taking additional supplements such as vitamins C and E).

v Lipid-lowering treatments such as tocotrienols and supplemental DHA/EPA and omega-3 rich diets can decrease the risk of atherosclerotic plaque rupture and subsequent thrombogenicity, as well as normalize the impaired endothelial function in hypercholesterolemic patients.

v A study done in 2002 by Maillard et al found a protective effect of n-3 fatty acids on breast cancer risk and their data supports the hypothesis that the balance between n-3 and n-6 fatty acids plays a role in breast cancer.

v Supplementing the diet of tumor-bearing mice or rats with oils containing (n-3) (omega-3) or with purified (n-3) fatty acids has slowed the growth of various types of cancers, including lung, colon, mammary and prostate. Used alone, an (n-3) supplement may be a useful alternative therapy for patients who are not candidates for standard toxic cancer therapies. (Hardman 2004)

o Olive oil
v Olive oil, considered amongst the most healthful oil, contains a relatively large amount of oleanolic acid, which may help block eicosanoid production; olive oil can have a favorable effect, but not by providing large amounts of omega-3 fatty acids, of which it contains less than 10%.

v Research on the monounsaturated fatty acid olive oil and its components suggest it plays an important role in the prevention of heart disease. There are multiple mechanisms by which olive oil might impact the development of atherosclerosis: reduction of hypertension and LDL oxidation, beneficial changes in lipid ratios and reduction of macrophage uptake of LDL cholesterol. Several studies have shown phenolic compounds extracted from extra-virgin olive oil significantly inhibited the oxidation of LDL cholesterol. Other polyphenolic compounds from green tea, red wine Glycyrrhiza glabra and Zingiber have also been found to inhibit the oxidation of LDL cholesterol.

o Curcumin
v Curcumin has been used for the treatment of inflammatory diseases and exhibits a variety of pharmacological effects such as anti-inflammatory activity. Results of a study by Abe et al show that curcumin exhibits an inhibitory effect on the production of IL-8, monocyte inflammatory proetin-1alpha, monocyte chemotactic protein-1, and TNF-alpha by PMA- or LPS-stimulated monocytes and alveolar macrophages. (Abe et al 1999) (Curcumin is an extract of the spice known as turmeric (Curcuma longa).

v Curcumin, boswellic acid, oleanolic acid, allicin, berberine, quercetin and the tea catechins inhibit COX and/or LOX enzymes. Boswellic acid, asiatic acid and betulinic acid are all being investigated for anti-inflammatory and potential anticancer effects. Medicinal herbs that contain oleanolic acid are ligustrum, forsythia and swertia.

o Ursolic acid
v Ursolic acid, a component of several herbs used in Chinese medicine, is a moderately strong inhibitor of both COX-2 and 5-LOX. Ursolic acid is known for its ability to inhibit skin inflammation. In general plants that contain ursolic acid also contain oleanolic acid and vice versa. Ursolic acid is one of the main waxy components on apples that contributes to the smooth shiny appearance. Plants rich in ursolic acid include Greek sage (Salvia triloba), oleander, rosemary, lavender and thyme. In vitro studies have shown ursolic acid to be about twice as effect as an anti-inflammatory compared to indomethacin – a potent NSAID.

v Ursolic acid and oleanolic acid (pentacyclic triterpenoids) possibly exert an anti-inflammatory action in the prostate by inhibiting glucosyl transferase, which is involved in proteoglycan metabolism in connective tissue. (Kozai 1987)

o Alpha-linolenic acid
v Alpha-linolenic acid appears to decrease cardiovascular disease risk by inhibiting
vascular inflammation and endothelial activation beyond its lipid-lowering effects. (Zhao et al 2004)

v In a study by Rallidis et al in 2003 it was concluded that dietary supplementation with alpha-linolenic acid for 3 months decreases significantly C-reactive protein, serum amyloid A and IL-6 levels in dyslipidaemic patients.

v A study by Bemelmans et al in 2004 found that a six-fold increased alpha-linolenic acid intake lowers C-reactive protein, when compared to a control diet high in linoleic acid.

o Arginine
v Many studies suggest nitric oxide (NO) is a potent endogenous anti-atherogenic molecule that suppresses key processes in atherosclerosis. Nitric oxide is produced through the action of the enzyme nitric oxide synthase on the amino acid arginine to produce nitric oxide and citrulline. A study done by Tong and Barbul in 2004 concludes that arginine modulates the development of atherosclerotic cardiovascular disease, improves immune function in healthy and ill patients, stimulates wound healing in healthy and ill patients and modulates carcinogenesis and tumor growth.

v Arginine is an amino acid found in most protein foods and which is converted by the enzyme endothelial nitric oxide synthase into nitric oxide. Foods high in arginine include carob, chocolate, coconut, dairy products, gelatin, meat, oats, peanuts, soybeans, walnuts, white flour, wheat and wheat germ.

v The administration of L-arginine and vitamin E has been shown to improve endothelium-dependent vascular function in subjects with high asymmetric dimethylarginine (ADMA) levels. (ADMA is a potent inhibitor of nitric oxide synthase (NOS)).

v Supplementing with arginine (as it has been shown to compete with ADMA) prevents the inhibition of eNOS by this endogenous inhibitor. Arginine normalizes endothelial vasodilation in hypercholesterolemic/hypertensive and hyperhomocysteinemic patients.

o Corydalis
v An extract from corydalis has shown strong anti-inflammatory activity. (Lin et al 2002)

v The results of a controlled clinical trial suggest that Corydalis yanhusuo and Angelica dahuricae have potential clinical value for treating mild to moderate pain. (Yuan et al 2004)

o Other Useful Herbs, Foods and Supplements
v Supplementing with antioxidants can reduce the oxidative stress strongly implicated in endothelial dysfunction. Vitamins C and E, lipoic acid, glutathione, and superoxide dismutasecan increase the bioavailability of NO, reduce oxidative stress and increase DDAH activity.

v Lipoic acid plays a crucial role in preventing atherosclerosis. It induces the production of NO and inhibits the activation of monocyte chemo-attractant protein-1. It also improves NO-mediated vasodilation in diabetic patients.

v Reduction of homocysteine by vitamins B6, B12 and folate is crucial in reducing cardiovascular risk and oxidant stress associated with elevated plasma levels.

v Vitamin E resides in the lipid domain of biological membranes and plasma lipoprotein, where it prevents lipid peroxidation of polyunsaturated fatty acids. Because vitamin E is the most important antioxidant for preventing lipid peroxidation, vitamin E adequacy may significantly impact the rate of cancer cell proliferation and the response to cancer chemotherapy. Vitamin E has been shown to effectively reverse the inhibitory effect of lipid peroxidation on cell proliferation.

v Vitamin C is a versatile water-soluble antioxidant. It protects against lipid peroxidation by scavenging reactive oxygen species in the aqueous phase before they can initiate lipid peroxidation.

v Boswellia decreases leukotriene synthesis that is responsible for maintaining inflammation and edema. (Bruneton, 1995; Gupta et al, 1997) Boswellic acid inhibits 5-LOX and is used as an anti-inflammatory for arthritis, Crohn’s disease and asthma.

v Two studies have shown that doses of 1.1 to 1.4 g GLA in borage seed oil reduces joint inflammation significantly. (Pullman-Mooar, 1990; Leventhal, 1993)

v Dandelion root may have potential use as an anti-inflammatory agent in inflammatory conditions. (Tito et al, 1993 & Mascolo et al, 1987)

v Substituting walnuts for monosaturated fat in a Mediterranean diet improves endothelium-dependent vasodilation in hypercholesterolemic subjects. This finding might explain the cardioprotective effect of nut intake beyond cholesterol lowering.

v Eat a diet rich in fruits and vegetables with lots of berries, cherries and dark leafy greens as sources of antioxidants, which neutralize the free radicals that may cause inflammation. High fruit and vegetable consumption has been associated with decreased plasma CRP and homocysteine levels suggesting they may play a role in the reduction of heart disease. (Nick 2004)

v When consuming meats, preference should be given to those from grass-fed animals rather than corn-fed animals, as the meat of the former will have some omega-3 fatty acids, while the latter will not (corn provides almost no omega-3 fatty acids.).

v Research has shown that the following herbs and nutrients also exhibit anti-inflammatory properties: juniper, feverfew, garlic, ginkgo, nettle, probiotics, proteolytic enzymes, scutellaria and tylophora.