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. Studies show, however, that specific dietary and supplementation measures can play a significant role in long-term management of these conditions, with respect to preserving joint integrity, reducing pain and inflammation, improving quality of life and extending years of functional living.
Clinical and preclinical studies have identified three main biological targets that can be favorably influenced in these patients using nutrition and supplementation-based interventions. These include:
- Suppressing Inflammatory Eicosanoids
- Inhibiting Inflammatory and Hyperproliferative Cytokines and Transcription Factors
- 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, as an 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%) 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 dihommo 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 cofactors and coenzymes 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 non-steroidal 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 over secretion of TNF-alpha (primarily for activated macrophages) activates the down-stream 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.
The exciting news for complementary practitioners is the revelation that certain natural agents act as natural bioregulators of TNF-alpha and Nuclear Factor kappa beta. Natural agents such as curcumin, quercetin, Vitamin B6, and catechins have shown an ability to down-regulate the effects of TNF-alpha and Nuclear Factor kappa beta in cases where macrophages are over zealous. At the same time these agents do not inhibit the release of these cytokines and transcription factors when they are required to help fight infection or induce apoptosis of emerging cancer cells. These bioregulatory effects are indeed unique and noteworthy, as no drugs created to date can provide such bioregulatory influences on these important pathways. Curcumin is derived from the spice turmeric, quercetin is the most abundant flavonoid in nature, and catechins are found in green tea to an appreciable degree.
Thus in addition to the natural anti-inflammatory supplement I recommend containing curcumin, white willow extract, ginger and boswellia (as described previously), I also recommend additional supplementation with quercetin (usually 1000 – 2000 mg per day), and suggest that the patient replace coffee with 3-5 cups of green tea (preferably decaffeinated green tea) daily.
A final consideration is that vitamin D supplementation has been shown to up-regulate the synthesis and release of interleukin-4 from various immune cells. Interleukin-4 has established anti-inflammatory effects. (37-49). As such, I recommend that autoimmune patients consider taking 5,000 – 10,000 IU of Vitamin D daily, unless they suffer from sarcoidosis or hyperparathyroidism. Vitamin D also has other important bioregulation effects on the immune system, which may be helpful to patients with autoimmune disease. When taking supplements in this range it is important to monitor blood vitamin D levels to ensure it does not exceed 250nmol/L.
Bioregulation of the immune system has also been shown to be valuable in the management of autoimmune disease. Certain agents (e.g. thymus hormones), including various supplements, have been shown to down-regulate the secretion of TNF-alpha by activated macrophages, and provide other immune-modulating effects on immune cells, which have produced favorable outcomes in patients with various autoimmune conditions. Bioregulation implies that these nutrients can boost immune activity when immune function is weak or compromised, and suppress over-zealous behavior of immune function in patients with autoimmune conditions, reducing symptoms and episodes of exacerbation.
In some cases doctors inject patients with thymus peptide hormones (e.g. Zadaxin). However, certain natural supplements also provide significant immune modulation. My favorites include reishi mushroom extract and astragalus. Reishi mushroom extract has also been shown to inhibit the effects of Nuclear Factor kappa beta, as outlined above, making it a multi-modal agent in the complementary management of autoimmune conditions. (50-61). In addition, probiotic and prebiotic supplementation (FOS and Inulin) have also show important immune bioregulator effects in patients with various autoimmune diseases, as well as in cases of eczema (62,63).
Autoimmune disease presents a daunting clinical challenge for medical and complementary health practitioners alike. As such, an aggressive proactive program is required, which must address the main molecular features and biological targets of these diseases to help tame them and provide patients with improved symptom control, quality of life and an ability to slow down or halt the progression of the disease. The main biological and molecular targets of importance to complementary health practitioners include specific eicosanoids, cytokines, transcription factors as well as immune modulation. In regard to diet and supplementation there is sound scientific support for practitioners to provide patients with following recommendations in the complementary management of autoimmune conditions, especially when joint involvement is a key feature of the disease:
- Decrease intake of high fat animal products (exception is fish), as well as trans-fats, deep fried and pan-fried foods. Using olive oil and other monounsaturated fat-rich oils, in place of oils rich in linoleic acid is also beneficial to decrease synthesis of PG-2 eicosanoids.
- Essential Fatty Acid Supplementation: 3-6 capsules per day of a supplement containing 400 mg each of fish, flaxseed and borage seed oil.
- High Potency Multiple Vitamin and Mineral: providing 1000 mg vitamin C, 400 IU vitamin E, 100-200 mcg selenium, B-50 complex, 200-300 mg magnesium, and all vitamins and minerals from A-zinc
- Natural Anti-Inflammatory Supplement: providing a combination of curcumin, white willow extract, ginger and boswellia, at meaningful dosages and proven standardized grades.
- Immune and Detoxification Supplement: providing meaningful dosages of reishi mushroom extract, astragalus, indole-3 carbinol and milk thistle.
- Glutathione Support Supplement: the body cannot absorb glutathione from the intestinal tract to an appreciable degree. Supplements containing N-acetyl cysteine, alpha lipoic acid, L-glutamine and silymarin (from milk thistle) have been shown to increase cellular levels of glutathione, an important immune modulating, antioxidant and detoxification tripeptide.
- Quercetin: 1000 – 2000 mg
- Vitamin D: 5000 – 10,000 IU – requires blood monitoring of vitamin D levels
- Additional Antioxidants if necessary (e.g., Vitamin C: 2000 -5000 mg, Vitamin E: 1000-1600 IU, Selenium: 200-500 mcg, Beta-carotene: 25,000 -50,000 IU)
- Probiotic and/or Prebiotic Supplementation: 2x daily.
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