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Autoimmune Disease
Susan Colebank
04/26/2004 Autoimmune Disease by Susan Colebank The principal role of the immune system is to defend the body against infection. The body, in turn, has safeguards in place to prevent the immune system from attacking its own tissues. However, these safeguards can become breached, resulting in the body warring with itselfand resulting in an autoimmune disease. The body can turn against anything, including its own blood, digestive tract, eyes, glands, heart, joints and lungs. Everyone has autoimmunity to some degree. This concept of autoimmunity as the cause of human illness is relatively new, and it was not accepted in the mainstream of medical thinking until the 1950s and 1960s, reported the Autoimmune Disease Research Center at Baltimore-based Johns Hopkins. Autoimmune diseases are defined as diseases in which the progression from benign autoimmunity to pathogenic autoimmunity occurs. A heterogeneous family consisting of chronic and disabling illnesses, autoimmune diseases encompass more than 80 conditions, including psoriasis, rheumatoid arthritis, Type I diabetes and inflammatory bowel diseases (IBDs) such as Crohns disease and ulcerative colitis. Those suffering with autoimmune diseases often endure disability, hospitalizations, outpatient visits and decreased productivity. Most of all, autoimmune sufferers experience an impaired quality of life because of losses in function, such as loss of joint mobility from rheumatoid arthritis. Autoimmune diseases are not contagious. Most research points to genetics, environment and lifestyle factors as the reasons behind the development of this family of diseases. Particular autoimmune disorders are frequently classified into organ-specific (e.g., Type I diabetes) and non-organ-specific (e.g., rheumatoid arthritis) disorders. They are chronic conditions, and the majority of those afflicted are under the age of 35 when first diagnosed. Collectively, autoimmune diseases affect approximately 5 percent to 8 percent of the U.S. populationaround 14 million to 22 million people; to put this in perspective, 8.9 million Americans are currently living with cancer. And while cancer has been seen to affect more men than women (half of men versus a third of women), autoimmune diseases are one of the top 10 leading causes of death in women. In fact, approximately 75 percent of these diseases occur in womenmost frequently during their childbearing years, since estrogen is believed to increase susceptibility to autoimmune diseases. Hormones are thought to play a role, because some autoimmune illnesses occur more frequently after menopause, others suddenly improve during pregnancy, with flare-ups occurring after delivery, while still others will get worse during pregnancy, reported the Office of Womens Health in Washington. The cause behind the onset of autoimmune diseases is far from clear cut. Recently, though, scientists have discovered that the presence of undigested DNA left over from dead cells can elicit an immune response in the fruit fly, prompting researchers to question whether an analogous autoimmune response could be triggered in humans.1 According to the National Institutes of Health (NIH), the current belief behind autoimmune disease is that regulatory cells become defective. Regulatory immune cells, when working properly, keep autoimmune disease in check by preventing the migration of pathogenic T cells into target organs and releasing cytokines that counteract tissue-destructive inflammation. Suppressing the immune system is one way to treat autoimmune diseases, but Johns Hopkins researchers report such blanket defenses are probably not ideal. For instance, one of the immune systems constituents, interferon-gamma, helps prevent tissue damage in mice given a condition similar to a heart-damaging autoimmune disease in humans.2 In treating autoimmune disease, its possible that treatments that alter the immune systems overall function could make one autoimmune disease better but make a second one worse, said Noel Rose, M.D., Ph.D., a professor of pathology at Johns Hopkins. Outside factors influencing autoimmune disease include infections, UV irradiation, cold temperatures and emotional stress. For example, sunlight not only acts as a trigger for the autoimmune disease lupus, but it can actually worsen the disease. These environmental factors are also closely related to oxidative stress. Excessive oxidative stress is thought to have an important role in the pathogenesis of autoimmune diseases by enhancing the inflammation, inducing apoptotic cell death, and breaking down the immunological tolerance. Looking at patients with rheumatoid arthritis, oxidative stress was found to induce cellular responses, including apoptosis and gene activation.3 Antioxidants may play a role in immune function, particularly with respect to autoimmunity, NIHs Autoimmune Diseases Coordinating Committee reported. The committee added supplementation with antioxidants and manipulation of fatty acid intake (namely, increasing omega-3 fats) may ultimately play a significant role in preventing and treating these diseases. And the market for autoimmune ingredients is thriving. Psoriasis More than 4.5 million Americans have psoriasisor about 1 in 50. The condition often appears between the ages of 15 and 35, but can develop at any age and is slightly more prevalent in women than men. Skin is a major target of oxidative stress due to reactive oxygen species (ROS) that originate in the environment and in the skin itself, according to the National Institute of Environmental Health Sciences. ROS are generated during normal metabolism, are an integral part of normal cellular function and are usually of little harm because of intracellular mechanisms that reduce their damaging effects. However, increased or prolonged free radical action can overwhelm ROS defense mechanisms, contributing to the development of cutaneous diseases and disorders. Recently, it has been suggested that increased ROS production and deficient function of antioxidant systems activities may be involved in the pathogenesis of psoriasis.4 For example, one study of 22 psoriatic patients (12 women and 10 men) and matched controls showed there was an imbalance in the oxidant-antioxidant system in psoriasis.5 One antioxidant, selenium, appears to be a factor in the disease. Selenium serum levels have been found to be depressed and related to the severity of the disease in psoriasis patients who have had the disease for three years or more.6 On the botanical antioxidant front, French maritime pine bark extract may have therapeutic potential in patients with inflammatory skin disorders such as psoriasis.7 In particular, the extract (as Pycnogenol, a registered trademark of Horphag Research Ltd.) down-regulates factors responsible for psoriasis development.8 Another botanically derived antioxidant is aloe vera. In a study to evaluate the clinical efficacy and tolerability of topical aloe vera extract, 60 patients with slight to moderate chronic psoriasis were given either a 100 g tube of aloe (at a concentration of .5 percent) or placebo to be applied three times daily for five consecutive days per week for four weeks. The treatment was well tolerated by all the patients; 25 out of 30 patients (83.3 percent) saw improvements in their condition compared to the placebo cure rate of two out of 30 (6.6 percent).9 Skin possesses the capacity to biosynthesize, metabolize and interconvert a variety of lipids. Polyunsaturated fatty acids have a central role in the induction of some skin diseases, such as psoriasis, possibly due to the skins antioxidant imbalance.10 In fact, the low incidence of psoriasis, as well as rheumatoid arthritis, in Eskimos has been attributed to their high dietary intake of eicosapentaenoic acid (EPA) from fish and marine mammals and their inherently low levels of arachidonic acid (AA).11 And in a study using EFA-deficient hairless mice, linoleic acid (LA) reduced DNA synthesis and returned epidermal histology to that of normal skin. Rheumatoid Arthritis Rheumatoid arthritis (RA), the most crippling form of arthritis, affects approximately 2.1 million Americans and attacks two to three times more women than men, according to the Centers for Disease Control and Prevention (CDC). The average onset for RA is between the ages of 20 and 45. Oxidative stress and low antioxidant status have been found in patients with RA. In particular, researchers have found RA patients have lower serum levels of vitamins A, C and E compared to healthy controls.12 Chronic inflammation affects antioxidant levels in RA, particularly vitamin A, which may in turn lead to a predisposition for higher LDL cholesterol levels, possibly explaining the high risk of cardiovascular disease in patients with RA.13 In addition, plasma levels of retinol have been seen to be inversely related to factors related to RA,14 and RA sufferers also have significantly lower levels of beta-carotene.15 Vitamin E has been shown to reduce pain in RA patients, possibly by decreasing proinflammatory cytokines and lipid mediators.16 And, in a cohort study of approximately 30,000 women aged 55 to 69 years at baseline, the 152 cases of identified RA indicated levels of vitamins E and C were inversely associated with RA.17 And in a cross-sectional study of 37 RA patients, researchers from the Jean Mayer USDA (U.S. Department of Agriculture) Human Nutrition Research Center on Aging at Tufts University, Boston, found markers of vitamin B6 status were inversely associated with disease activity and severity, synovial burden and pain in patients with RA.18 According to the researchers, these findings also raised the possibility that impaired vitamin B6 status is a result of inflammation. Vitamin D may also lower the risk of developing RA, particularly in older women.19 In approximately 30,000 women 55 to 69 years old who were free of RA at the beginning of the study, 152 subjects developed RA over 11 years. Inverse associations were found for both dietary and supplemental vitamin D and RA risk; subjects in the highest tertile of vitamin D intake had a 33-percent lower risk of developing RA compared to those in the lowest tertile. Intake of certain antioxidant micronutrients, particularly supplemental zinc, may be protective against the development of rheumatoid arthritis.20 And copper-zinc superoxide dismutase (provided by Albion Advanced Nutrition in Clearfield, Utah) supplementation improved RA parameters.21 RA patients may also experience a significant reduction in disease activity by adopting a Mediterranean-type diet. In a study at Ume University, Sweden, where RA sufferers were randomized to a Mediterranean-type diet or a control diet for three months, those on the Mediterranean diet experienced raised plasma levels of vitamin C and retinol, which were seen to positively affect RA disease activity.22 In a study of RA sufferers, a dose-response relationship was established up to a dose of 2.6 g/d fish oil, equivalent to about 1.6 g/d EPA. In these experiments, EPA was the omega-3 fatty acid responsible for improvement, although it was seen that dietary AA had to be reduced first for EPA to have a clinical benefit. 23 In particular, omega-3 fatty acids contained in ingredients such as flaxseed may aid RA by suppressing the production of inflammatory mediators.24 In addition, findings from a research review have also indicated that gamma linoleic acid (GLA), an omega-6, may have potential benefits in improving pain associated with RA.25 It may work by suppressing the release of interleukin-1beta, which may protect against the chronic inflammation of RA.26 Poor nutrient status in RA patients has been reported and some drug therapies, such as nonsteroidal anti-inflammatory drugs (NSAIDs) prescribed to alleviate RA symptoms that increase the requirement for some nutrients since the drugs reduce their absorption. Supplementation with long-chain omega-3 polyunsaturated fatty acids (PUFAs) consistently demonstrates an improvement in symptoms and a reduction in NSAID usage, said researchers out of Cambridge, England.27 The present evidence suggests that RA patients should consume a balanced diet rich in long-chain omega-3 PUFAs and antioxidants. Fatty acids may also make good partners with other ingredients that benefit RA patients. According to researchers from Purdue University in West Lafayette, Ind., the beneficial effects of conjugated linoleic acid (CLA) on bone biology in rats appear to be dependent on the level of omega-3 and -6 fatty acids in the diet.28 Velvet antler, found to contain the wellknown bone-builder chondroitin sulfate, is another product to turn to when trying to ease arthritic symptoms. When 40 RA patients took placebo or two, four or six capsules of velvet antler while continuing to take their regular arthritis medicines, those in the highest dose group (215 mg/d) had more improved symptoms than the placebo group.29 Human studies have shown undenatured Type II collagen may also alleviate symptoms associated with RA. Several studies have shown significant improvement in symptoms when patients were supplemented with undenatured Type II collagen (as Benicia, Calif.- based InterHealths UC-II), including improved joint mobility and flexibility, reduced joint pain and, in some patients, complete remission of symptoms.30 Hyaluronic acid (HA), found in both velvet antler and chicken collagen, is responsible for the viscous and elastic properties of synovial fluid, which is critical for healthy joint function. HA appears to have the same ability as chondroitin sulfate to reduce free radical production in collagen-induced arthritis, which is promising news in the lives of RA sufferers.31 Type I Diabetes Type I diabetes, previously called insulindependent diabetes mellitus or juvenile-onset diabetes, develops when the bodys immune system destroys pancreatic beta cells, which are the only cells that make the hormone insulin. This form of diabetes usually strikes children and young adults, although disease onset can occur at any age. Data out of the University of Pittsburgh suggests offspring of Type I diabetic parents may be at high risk of developing other autoimmune disorders during childhood, since pediatric diabetes is considered the tip of an autoimmune iceberg.32 Type I diabetes is marked by free radicals very early in the disease processlevels that worsen over the course of the diseasewith oxidative stress having an impact on both metabolic and vascular functions.33 Researchers out of Jeonju, Korea, reported on the protective effects of green teas epigallocatechin gallate (EGCG) on betacell destruction in insulin-dependent diabetes. They concluded EGCG may be a possible therapeutic agent for the prevention of diabetes mellitus progression.34 In addition, an aqueous solution of green tea polyphenols was found to inhibit lipid peroxidation in a diabetic rat model, scavenging hydroxyl and superoxide radicals in vitro.35 One study investigating other flavonoids (as Daflon 500, which is made up of the flavonoids 90-percent diosmin and 10-percent hesperidin) in a group of 28 Type I diabetic patients found they had no side effects and experienced decreased diabetic parameters, possibly due to protecting vitamins C and E from oxidative damage.36 And in a rat model, 50 mg/kg/d of the flavonoid quercetin was found to be more effective than 80 mg/kg/d at ameliorating diabetes-induced changes in oxidative stress.37 In an oxidative condition such as Type I diabetes, Gymnema montanum leaf extract may eliminate reactive free radicals that may otherwise affect normal cell functioning; it was seen to do this in a rat model in which Gymnema montanum was administered orally at a doses of 50 mg/kg, 100 mg/kg and 200 mg/kg of body weight for 30 days.38 And in another model of Type I diabetes and rats, an alcohol extract of Gymnema montanum was seen to increase levels of the antioxidants vitamins C and E. In particular, administration of 200 mg/kg for three weeks resulted in a significant reduction in blood glucose and an increase in plasma insulin, although 50 mg and 100 mg produced no significant benefits.39 Other antioxidants aiding in Type I diabetes include vitamin D and vanadium. The active form of vitamin D, 1,25-dihydroxyvitamin D3, has been seen to prevent Type I diabetes in non-obese diabetic mice and may be a safe way to reduce the incidence of Type I diabetes in subjects who are genetically at risk.40 And, researchers in Kyoto, Japan, noted many trials show vanadiums potential for treating diabetes, and a particular ionvanadyl sulfateand its complexes not only treated or relieved Type I diabetes, but may prevent its onset. A rat study further demonstrated these preventive effects; rats given vanadyl sulfate supplementation for 60 days did not show the increase in blood glucose levels that was apparent in the control group.41 As with most of the autoimmune diseases, fatty acids also play a part in Type I diabetes development and treatment. It is suggested that the negative correlation surrounding breast-feeding, insulin resistance and diabetes mellitus can be related to the presence of significant amounts of long-chain polyunsaturated fatty acids in human breast milk.42 Later in life, supplementation with omega-3 and -6 long-chain fatty acids may prevent diabetes mellitus by enhancing antioxidant status and suppressing the production of cytokines.43 Chromium supplementation may also improve insulin sensitivity and has been used as adjunct treatment of diabetes mellitus in humans. In one study using dogs with insulintreated diabetes, dogs were given 200 mcg/d of chromium picolinate and then bumped up to 200 mcg/d of chromium picolinate twice daily. Results of this study suggest that, at a dosage range of 20 mcg/kg/d to 60 mcg/kg/d, chromium picolinate caused no beneficial or harmful effects in insulin-treated diabetic dogs.44 However, in research out of the Beltsville, Md.-based USDA Human Nutrition Research, chromium was seen to increase insulin binding to cells, raise insulin receptor numbers and activate insulin receptor kinase, leading to increased insulin sensitivity. Additional studies are urgently needed to elucidate the mechanism of action of chromium and its role in the prevention and control of diabetes, the researchers concluded.45 Inflammatory Bowel Diseases Inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohns diseaseare chronic gastrointestinal conditions of unknown etiology. It is estimated that as many as 1 million Americans have IBDwith that number evenly split between UC and Crohns.
UC is characterized by inflammation and ulcers found in the lining of the large intestine. The inflammation usually occurs in the rectum and lower part of the colon, but it may affect the entire colon. UC occurs in people of any age, but most often it starts between ages 15 and 30 or, less frequently, between ages 50 and 70. Crohns disease causes inflammation in the small intestine, but it can affect any part of the digestive tract. Like ulcerative colitis, Crohns can lead to ulcers in the lining of the large intestine. In Crohns, the increased production of reactive oxygen species from activated neutrophils may reduce plasma concentrations of antioxidant vitamins and result in increased oxidative stress.46 Vitamin E and C supplementation has been seen to result in a significant reduction in oxidative stress in patients with inactive or mildly active Crohns.47 The balance between oxidant and antioxidant systems may be important in the pathogenesis and maintenance of tissue injury in UC, too. For instance, investigators out of Istanbul reported administration of vitamin E and selenium significantly reduced the severity of colonic lesions in ulcerative colitis.48 Selenium deficiency has been seen in Crohns disease,49 especially after long-term parenteral nutrition, since the mineral is not usually a part of this therapy.50 Interestingly, mineral status is not the same between the two diseases. In a study involving 74 children with IBD (38 with UC and 36 with Crohns), serum mineral levels were analyzed. Selenium was lower in cases of both diseases compared to controls; zinc levels were lower in those with Crohns disease, while those with UC had levels that were the same as the controls; and copper levels were higher in those with Crohns than in either the controls or UC patients.51 Patients with Crohns disease often experience iron deficiency, especially since this population limits its diet to control the disease.52 Irondeficiency anemia, then, is a frequent complication of Crohns. However, treatment with iron salts (i.e., ferrous sulfate) is often unsatisfactory and is associated with gastrointestinal side effects. Use of a ferrous iron bisglycine amino acid chelate (as Ferrochel from St. Clair Shores, Mich.- based Albion Advanced Nutrition) has been shown to treat iron deficiency anemia more efficiently and without GI side effects associated with iron salts. A trial from the Universidad de San Carlos, Guatemala, found adolescents with iron-deficient anemia who were given 30 mg of iron as Ferrochel reported no gastric side effects even as the dosage increased hemoglobin values as effectively as 120 mg/d of iron as ferrous sulfate.53 Other types of antioxidants have shown potential in preventing the full onslaught of UC. In a rat model of ulcerative colitis, aloe vera and coenzyme Q10 (CoQ10) given as a mixture of 25 mg/kg was seen to reduce oxidative stress parameters substantially via pre-treatment.54 And, in research out of the University of Texas, San Antonio, long-term use of aloe vera (from Broomfield, Colo.-based Aloecorp) did not cause any obvious harmful and deleterious side effects, which could make it beneficial for the prevention of age-related pathology.55 Another ingredient exerting anti-inflammatory and antioxidant benefits is melatonin, which researchers report should be considered for prevention or treatment of ulcerative colitis. Melatonin may have a direct effect on many gastrointestinal tissues but may also influence the digestive tract indirectly via the central nervous system and the sympathetic and parasympathetic nerves. Melatonin prevents ulcerations of gastrointestinal mucosa by an antioxidant action, reducing secretion of hydrochloric acid, stimulating the immune system, fostering epithelial regeneration and increasing microcirculation.56 And with melatonin given at doses of 5 mg/kg and 10 mg/kg, colon mucosal damage in models of rat colitis was significantly decreased.57 Although some reports have indicated that antioxidants as well as fatty acids are important therapeutic alternatives in the management of IBD, the beneficial effects have yet to be translated into clinical practice.58 However, according to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), omega-3 fatty acids may benefit people with UC by interfering with the inflammatory process. And, omega-3 fatty acids may have a role to play in the treatment of Crohns, especially since Crohns patients often suffer from malnutrition.59 Crohns disease and UC are both mainly developed in areas with high bacterial concentrations, such as the terminal ileum and cecum in Crohns disease and the rectum in ulcerative colitis. In recent years, overwhelming evidence has shown IBD to be the result of an overly aggressive immune response toward ubiquitous luminal antigens, especially commensal bacteria and their byproducts.60 Probiotics are thought to modify disease by favorably altering bacterial composition, immune status and inflammation. In a review out of Yale on IBD treatments, success was seen with Escherichia coli Nissle strain in UC and with a multiple-organism product (VSL#3 from VSL Pharmaceuticals in Fort Lauderdale, Fla.) on Crohns disease.61 In addition, Saccharomyces boulardii has been seen to benefit Crohns disease, and one particular study also found UC patients benefited when given the yeast in doses of 250 mg three times a day for four weeks.62 Autoimmune diseases include a large range of inexplicable conditions where an individual has little to no control over the development of the disease. As researchers investigate the root of these diseases, there are options in the natural products industry that may be able to alleviate some of the pain and discomfort that characterize these conditions.
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