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Autoimmune Diseases
Updated: 05/18/2003

• Aging
• Autoimmune Dysfunction
• Supplements
• Summary
• Appendix A

Autoimmune diseases are characterized by the body's immune responses being directed against its own tissues, causing prolonged inflammation and subsequent tissue destruction. Autoimmune disorders can cause immune-responsive cells to attack the linings of the joints--resulting in rheumatoid arthritis--or trigger immune cells to attack the insulin-producing islet cells of the pancreas leading to insulin-dependent diabetes.

A healthy immune system recognizes, identifies, remembers, attacks, and destroys bacteria, viruses, fungi, parasites, and cancer cells or any health-damaging agents not normally present in the body. A defective immune system, on the other hand, wreaks havoc throughout the host by directing antibodies against its own tissues.

Any disease in which cytotoxic cells are directed against self-antigens in the body's tissues is considered autoimmune in nature. Such diseases include, but are not limited to, celiac disease, Crohn's disease, pancreatitis, systemic lupus erythematosus, Sjogren's syndrome, Hashimoto's thyroiditis, and other endocrinopathies. Allergies and multiple sclerosis are also the result of disordered immune functioning.

AgiNG

Age is recognized as an important factor in the appearance of autoimmune disease. In a paper that appeared in The Lancet in 1992, investigators measured healthy centenarians and unhealthy 60- and 70-year-olds and assessed the difference in physiological chemistry between the two groups. The most striking difference was that the healthy centenarians had very low levels of autoantibodies to their thyroid, adrenal, pituitary, hypothalamus (Mariotti et al. 1992). This has led some people to speculate that autoimmunity is the result of environmental exposure to foreign substances. Thus, the immune system may also be suppressed or weakened as a result of factors not associated with a degenerative disease, but due to the intake of alcohol, caffeine, tobacco, drugs, sugar, and of course poor diet and lack of sleep. These lifestyle factors can have a substantial effect on the trends of autoimmune diseases.

As we age, our autoimmune system declines in its effectiveness due in large part to oxidative damage caused by the recurrent presence of significant amounts of free radicals. In addition, proteins can become glycated, that is, a sugar molecule is attached to the protein. The accumulation of these glycated proteins in the body affects the immune system because the immune system sees them as altered proteins that have different structure and function (Monboisse et al. 2000; Sasaki et al. 2001; Collison et al. 2002). Regarding these substances as foreign, the immune system develops antibodies against them. The possibility of becoming allergic to oneself, with the associated autoimmunity and inflammation, increases as one accumulates these damaged glycated proteins.

The body is made up largely of proteins, so its health depends upon its freedom from damage (as through oxidation or glycation) and upon its timely removal as part of normal protein turnover. The body's antioxidant system and other lines of defense cannot completely protect proteins. Nature's second line of defense is the body's system for repairing or removing damaged proteins. While some protein repair mechanisms exist, it is difficult for the body to repair most protein damage. Yet, it is essential to efficiently remove aberrant and unneeded proteins to fully protect against autoimmune diseases.

Methods to protect against excessive protein glycation will be discussed later in this protocol.

Basic Pathways of Autoimmune DysfunctiON

Autoimmune diseases tend to be viewed as separate entities. A broader perspective, however, may reveal that shared mechanisms are the cause of disease, rather than just its byproduct. If this perspective were applied, patients would benefit from improved therapies and early intervention, before the development of irreversible tissue damage. As reported in the journal Hospital Practice, Dr. Majid Ali has long considered that there must be a single initial common pathway to all disease, including immune dysfunction.

One consideration is the continued exposure to heavy metals and environmental pollution that overload the immune system. On a daily basis, we battle with pesticides, herbicides, chemical fertilizers, industrial wastes, cigarette smoke, and automobile exhaust. Our air, water, and food in particular are full of toxic substances. There is no doubt that these toxins play a role in immune dysfunction. Even substances considered by most people as safe actually impair immune function. Sugar consumption in all forms (glucose, fructose, and sucrose) will impair the ability of white cells to destroy biological agents. This effect begins within a half hour and lasts for 5 hours. After 2 hours, immune function is reduced by 50% (Sanchez et al. 1973; Bernstein et al. 1977).

Oxidative stress plays a role in autoimmune diseases. It can be compared to a piece of metal rusting and results from the action of damaging molecules known as free radicals that are a natural byproduct of the body's metabolism. The electrically charged free radicals attack healthy cells, causing them to lose their structure and function and eventually destroying them. Free radicals are not only produced by our bodies, but they are also ingested from toxins and pollution in the air we breathe.

Chronic systemic inflammation is related to several autoimmune disorders, such as lupus, rheumatoid arthritis, Sjogren's syndrome, and fibromyalgia (see separate protocols on these topics). Inflammation can be traced to destructive cell-signaling chemicals known as cytokines that contribute to many degenerative diseases (Brod 2000). In rheumatoid arthritis, excess levels of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin 1(b) (IL-1b), and/or leukotriene B4 (LTB4), are known to cause or contribute to the inflammatory syndrome that ultimately destroys joint cartilage and synovial fluid. Certain nutritional supplements and low-cost prescription medications will often lower cytokine levels and control the inflammatory state.

Nutritional Supplements to Improve Autoimmune HealTH

• Protein
• Inflammation
• Free-Radical Damage
• Immune System
• GI Tract
• Stress
• Liver Health

The autoimmune system needs a good nutritional foundation over a long period of time to alleviate or reverse lifestyle autoimmune dysfunction and to assist with combating fully developed autoimmune diseases. The fundamental causal basis for autoimmune system boosting was shown in an early study that was designed to measure the serum concentrations of vitamin E, beta-carotene, and vitamin A in patients prior to developing rheumatoid arthritis or systemic lupus erythematosus. Two to 15 years after the volunteer patients had originally donated their blood to the serum bank (1974), the serum samples were assayed for vitamin E, beta-carotene, and vitamin A. Those patients who developed rheumatoid arthritis or lupus showed lower serum concentrations of vitamin E, beta-carotene, and vitamin A from 1974. Those who had the lowest serum level of beta-carotene in 1974 were the most likely to develop rheumatoid arthritis later in life (Comstock et al. 1997). This indicates the long-term importance of maintaining adequate vitamin status for the prevention of autoimmune diseases.

Slowing the Damage to Healthy Protein
Carnosine is a dipeptide amino acid found naturally in the body that helps to slow the formation of glycated protein end products. Recall that glycated protein may be unrecognizable to the immune system, thereby triggering an autoimmune attack. Since the normal removal of damaged protein declines with aging, slowing the development of protein crosslinking (glycation) may help to reduce an autoimmune reaction. In addition to its antiglycation effects, carnosine has been found to modulate immune system neutrophils, thus suppressing a response (Tan et al. 1998).

Reducing Inflammation
In a study conducted at the University of Texas Health Sciences Center, it was found that fish oil containing vitamin E delayed the onset of autoimmune diseases in autoimmune-prone mice (Venkatraman et al. 1994). Another study on the effects of vitamin E deficiency was conducted in the United Kingdom and reported in Inflammation Research (1995). It was found that dietary components that provide antioxidant effects may contribute to the treatment of inflammatory/autoimmune diseases (Amarakoon et al. 1995).

Supplementation with omega-3 essential fatty acids (EFAs) from fish, flax, or perilla oils--along with borage oil, evening primrose oil, or black currant seed oil, which contain the essential omega-6 fatty acid gamma-linolenic acid (GLA)--can alleviate many symptoms of autoimmune disease through their anti-inflammatory activity. Docosahexaenoic acid (DHA) extracted from fish oil may be as effective as some prescription medications in reducing inflammation.

Dehydroepiandrosterone (DHEA) is a prosteroidal hormone that decreases with aging. Decreases in DHEA levels have been linked to a number of chronic and degenerative diseases including cancer, coronary artery disease, depression, stress disorders, and neurological functioning (Straub et al. 1998). As a result of aging, immunity may become compromised due to dysregulation of cellular hormones (cytokines and growth factors) that govern the immune response. Too much or too little of various cytokines produces disease states or compromised responses to various challenges.

In aging animals, the addition of DHEA has normalized deranged cytokine levels, including a primary inflammatory factor called interleukin-6 (IL-6) (Araghi-Niknam et al. 1998). In the aged test animals, serum IL-6 was elevated ninefold from normal. After administration of DHEA or dehydroepiandro-sterone-sulfate (DHEA-S), IL-6 dropped to within 15% of youthful levels. In the same studies, it was shown that antibodies directed toward self rose fivefold with aging, but after 2 weeks on DHEA-S fell by over 50% (Spencer et al. 1996).

In a study of ten women with the autoimmune disease Sjogren's syndrome, all were shown to have decreased serum concentrations of DHEA-S and an increased cortisol/DHEA-S ratio compared with healthy controls (Valtysdottir et al. 2001).

Lessening Free-Radical Damage
Antioxidants are a broad group of compounds that destroy or neutralize free radicals in the body, thereby protecting against oxidative damage to cells caused by the normal aging process or daily exposure to pollutants and toxic substances. Antioxidants are found naturally in healthy food, especially fruits and vegetables. The most effective of the antioxidants include vitamin C, vitamin E, green tea extract, beta-carotene, grape seed-skin extract, coenzyme Q10 (CoQ10), and selenium.

• Vitamin C may be the most important water-soluble antioxidant, having an ability to scavenge both reactive oxygen and nitrogen radicals. In controlled studies, vitamin C has demonstrated antiatherogenic, anticarcinogenic, antihistaminic, and immunomodulatory benefits.
• Vitamin E is a fat-soluble, essential nutrient for humans. Increased risk for coronary artery disease, Alzheimer's disease, and cancer has been reported in regard to vitamin E deficiency.
• Green tea belongs to the flavonoid family. Green tea catechins are potent free radical scavengers and have also demonstrated anticarcinogenic, anti-inflammatory, antiatherogenic, and antimicrobial activity.
• Beta-carotene is a dietary precursor to vitamin A. Beta-carotene has demonstrated immunomodulatory effects in male nonsmokers and has demonstrated increased lymphocyte counts in healthy male smokers. Beta-carotene's antioxidant activity may prevent oxidative damage to DNA and inhibit lipid peroxidation.
• Grapeseed-skin proanthocyanadins have demonstrated several antioxidant activities, including inhibiting the oxidation of damaging LDL cholesterol. Other research has shown tumor-protective, cardio-protective, and liver-protective benefits.
• CoQ10 has shown antioxidant activity within the mitochondria and cellular membrane. CoQ10 levels decline with aging and are strongly related to increased cardiovascular disease, especially congestive heart failure. Supplemental CoQ10 has shown usefulness in treating periodontal disease and boosting energy levels.
• Selenium is a trace mineral that is essential for healthy immune function, providing protection to immune cells from stress-induced oxidative damage and neutralizing the effects of some toxic metals. Low dietary intake of selenium is associated with cardiovascular disease and certain cancers.

Modulating the Immune System
The immune system functions because of adequate amounts of circulating antibodies. Antibodies are proteins with a unique concave region (combining site) in which they can combine with foreign proteins (antigens). Antigens are most often surface molecules found on the membrane of invading or diseased cells. After the antigen and antibody combine, the new complex produces a number of changes that inactivate or kill the invading cell. This function is known as humoral or antibody-mediated immunity. Lymphocytes are the most numerous cells of the immune system and are responsible for antibody production. B-cells are lymphocytes that produce humoral immunity.

T-cells are lymphocytes formed in the thymus shortly before and after birth. When T-cells come into contact with foreign antigens, the antigen binds to protein on the surface of the T-cell, making it sensitized. Sensitized T-cells destroy invading pathogens by releasing a specific and toxic poison to the cells of bound antigens. T-cells can also indirectly destroy toxic invaders by releasing a substance that attracts macrophages to the area that will ingest and destroy (phagocytose) the pathogen. This function is known as cell-mediated immunity. T-cells regulate natural killer cell activity and the body's inflammatory response to disease.

In a healthy body, circulating antibodies attack and destroy pathogenic invaders by means of humoral or cell-mediated immunity. In autoimmune disease, circulating antibodies seek, attack, and destroy self-antigens found in healthy tissue (see the following table for examples).