In many cases of autoimmune disease, especially those affecting the joints (e.g., rheumatoid arthritis), the patient is seldom provided with evidence-based nutrition and supplementation practices from their medical practitioner.
Clinical and preclinical studies have identified three main biological targets that can be favorably influenced using nutrition and supplementation-based interventions: 1) suppressing inflammatory eicosanoids; 2) inhibiting inflammatory and hyperproliferative cytokines and transcription factors; and 3) immune modulation (bioregulation of immune system).
Eicosanoid Synthesis and Inflammation
The inflammatory process involves the synthesis of prostaglandin series-2 (PG-2) eicosanoids. PG-2 eicosanoids are derived exclusively from the polyunsaturated fat known as arachidonic acid, which is found at appreciable levels in many domestic meat products. The over-ingestion of linoleic acid (from corn, sunflower, safflower and mixed vegetable oils, for example) also encourages the conversion of linoleic acid to arachidonic acid via desaturation and elongation biochemical pathways. Thus, reducing intake of high-animal-fat products and using oils that are higher in monounsaturated fats (e.g., olive oil) in place of linoleic acid-rich vegetable oils help to reduce the synthesis of PG-2 eicosanoids.
It is also well-documented that omega-3 fats and supplementation with gamma-linolenic acid (GLA) produces anti-inflammatory effects via their conversion to prostaglandin series-3 (PG-3) and prostaglandin series-1 (PG-1) hormones, respectively. PG-3 and PG-1 are known to have anti-inflammatory effects. The precursor to prostaglandin series-3 eicosanoids is eicosapentaenoic acid (EPA), an omega-3 fat found in cold-water fish and fish oil. However, docosahexaenoic acid (DHA) can be converted to EPA within the body. DHA is also found in fish and fish oil. Alpha-linolenic acid can also be converted to EPA via desaturation and elongation enzymes. Alpha-linolenic acid is an omega-3 fat found at high levels (58 percent) in flaxseed oil.
To increase synthesis of PG-1, many patients supplement with borage seed oil, black currant oil and/or evening primrose oil. The GLA in these oils can be converted into dihomo gamma linolenic acid, which can then be converted into anti-inflammatory PG-1 eicosanoids.
As such, studies support a second step in controlling the production of inflammatory eicosanoids, which involves daily supplementation with essential fatty acids (EFA's), as explained above.1-6 Based on the available data, I personally feel that a supplement combining 400 mg each of fish oil, flaxseed oil and borage oil is the ultimate EFA supplement for autoimmune patients and those with other inflammatory conditions. This combination is also a very cost-effective formula and makes EFA supplementation practical for long-term patient compliance. I recommend 3-6 capsules per day, depending on the severity of inflammation. (I also recommend 2-3 capsules per day for general prevention of cancer, heart disease, Alzheimer's disease, general well-being, and to promote healthy skin texture.)
Studies also suggest that certain antioxidants (vitamin C, vitamin E, selenium, beta-carotene etc), as well as certain B vitamins (e.g., vitamin B6) and magnesium, act as co-factors and co-enzymes to hasten the synthesis of anti-inflammatory PG-1 and PG-3 eicosanoids from their precursor polyunsaturated fatty acids. Various clinical studies have shown important anti-inflammatory outcomes and improved patient management of various autoimmune and other inflammatory conditions, using supplementation with meaningful dosages of antioxidants, B vitamins and/or magnesium.
Vitamin B6 and antioxidants may also inhibit the inflammatory effects of tumor necrosis factor alpha, a cytokine that is known to perpetuate the inflammatory and hyperproliferative processes in many autoimmune diseases.7-17 (We will examine these cytokines, as well as nuclear transcription factors, in the next section.)
A third way in which patients can suppress the synthesis of inflammation-promoting PG-2 is via supplementation with herbs that directly inhibit cyclo-oxygenase and lipoxygenase enzymes. These enzymes are responsible for the conversion of arachidonic acid into PG-2. Certain herbal agents including curcumin, white willow extract, ginger, boswellia and others have shown significant effects on reducing various inflammatory conditions, including autoimmune diseases, in clinical trials. Thus, I also recommend a supplement containing curcumin, white willow extract, ginger and boswellia, which delivers therapeutic dosages of their active constituents. Patients usually require 1-3 capsules, three times per day, to achieve control of their inflammatory condition. These natural agents work in a similar way as aspirin, ibuprofen, COX-2 inhibitors and some other nonsteroidal anti-inflammatory drugs, but without the risk of gastrointestinal bleeding or liver and kidney toxicity.18-36
Inflammatory Cytokines and Nuclear Transcription Factors: Hallmark Features of Autoimmune Disease
In recent years it has been identified that in many autoimmune diseases, macrophages (and some other immune cells, to a lesser degree) secrete disproportionately high levels of a cytokine known as tumor necrosis factor alpha (TNF-alpha). In turn, TNF-alpha encourages other immune cells (and some non-immune cells, such as endothelial cells) to increase the translocation of nuclear factor kappa beta (a cytoplasm-based protein) to the nuclear DNA of the cell.
Acting as a transcription factor, nuclear factor kappa beta up-regulates genes that code for the synthesis of inflammatory and hyperproliferative cytokines, such as interleukin 1,6,8. Thus, in autoimmune diseases, the oversecretion of TNF-alpha (primarily for activated macrophages) activates the downstream effects of nuclear factor kappa beta on specific genes that promote the release of inflammatory and hyperproliferative cytokines. These events are a hallmark feature of many autoimmune diseases.
Pharmaceutical companies have introduced drugs that inhibit the action of TNF-alpha. These drugs demonstrate anti-inflammatory effects, but are associated with a myriad of untoward and undesirable side effects, including lymphoma, infections, congestive heart failure, demyelinating disease, a lupus-like syndrome, induction of auto-antibodies, injection site reactions, systemic side effects and opportunistic infections.
The reason for this is that under certain situations, the release of TNF-alpha is desirable to help fight infections and encourage programmed cell death (apoptosis) of emerging cancer cells. Thus, drugs that impose a complete blockade to the effects of TNF-alpha are associated with many adverse side effects, as described previously.
Editor's note: Part 2 of this article appears in the July 29 issue and explores other nutritional considerations in managing autoimmune diseases.
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