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Twice a month you will receive an email with a discussion of several new studies on various supplements and natural medicine topics and their practical interpretation by Ray Sahelian, M.D. We will mention research updates on natural treatment options for autoimmune diseases as we come across them.

When our body encounters something foreign in its environment it needs to be able to mount an immune response against that substance to protect itself from potential harm. In order to do this effectively it must be able to recognize what is self in order to respond to non-self or foreign. In autoimmune diseases there is a failure to recognize some part of self, with potential serious consequences.
   Autoimmune disease disorders result in destruction of one or more types of body tissues, abnormal growth of an organ, or changes in organ function. The disorder may affect only one organ or tissue type or may affect multiple organs and tissues. Organs and tissues commonly affected by autoimmune disorders include blood components such as red blood cells, blood vessels, connective tissues, endocrine glands such as the thyroid or pancreas, muscles, joints, and skin. Frequently more than one autoimmune disease will be seen in the same person, as well as an increased susceptibility to bacterial infection.

Supplements that may be useful in autoimmune conditions
Research in this area has just started and my goal is to update you with information on potential supplements that could be helpful in reducing the severity of an autoimmune disease or perhaps helping to treat it. Please keep in mind that we know very little at this point and you should consult with your doctor before making any changes in your treatment plans.

Vitamin D - Most people think of Vitamin D in terms of bone strength. New research indicates that vitamin D inhibits proinflammatory processes by suppressing the enhanced activity of immune cells that take part in the autoimmune reaction. Supplementation of vitamin D may be therapeutically beneficial particularly for Th1 mediated autoimmune disorders. Some reports imply that vitamin D may even be helpful in multiple sclerosis and diabetes type 1.

What are some types of Autoimmune disease?
There are several recognized conditions that are considered autoimmune disease. Here they are in alphabetical order:

Alopecia Areata leads to hair loss

Autoimmune encephalomyelitis - alpha lipoic acid may be helpful, see study below.

Autoimmune hemolytic anemia (AIHA) and immune mediated hemolytic anemia (IMHA)

Autoimune myositis is usually divided between polymyositis and masticatory muscle myositis.

Autoimmune Disease Research Update
The flavones luteolin and apigenin inhibit in vitro antigen-specific proliferation and interferon-gamma production by murine and human autoimmune T cells.
Biochem Pharmacol. 2004 Aug 15;68(4):621-9.
Plant-derived flavonoids are inhibitors of various intracellular processes, notably phosphorylation pathways, and potential inhibitors of cellular autoimmunity. In this study, the inhibiting effects of various flavonoids on antigen-specific proliferation and interferon-gamma (IFN-gamma) production by human and murine autoreactive T cells were evaluated in vitro. T-cell responses were evaluated for the human autoantigen alpha B-crystallin, a candidate autoantigen in multiple sclerosis, and for the murine encephalitogen proteolipid protein peptide PLP (139-151). The flavones apigenin and luteolin were found to be strong inhibitors of both murine and human T-cell responses while fisitin, quercetin, morin and hesperitin, members of the subclasses of flavonoles and flavanones, were ineffective. Antigen-specific IFN-gamma production was reduced more effectively by flavones than T-cell proliferation, suggesting that the intracellular pathway for IFN-gamma production in T cells is particularly sensitive to flavone inhibition. These results indicate that flavones but not flavanoles or flavanones are effective inhibitors of the potentially pathogenic function of autoreactive T cells. The effects of flavones were the same for human and murine autoreactive T cells, stressing the usefulness of animal models of autoimmunity for further studies on the effects of flavonones on autoimmune diseases.

Alpha-lipoic acid is effective in prevention and treatment of experimental autoimmune encephalomyelitis.
J Neuroimmunol. 2004 Mar;148(1-2):146-53.
Alpha-lipoic acid (alpha-LA) is a neuroprotective metabolic antioxidant that has been shown to cross the blood brain barrier. We tested whether alpha-LA is capable to prevent MOG35-55-induced experimental autoimmune encephalomyelitis (EAE), an established model of multiple sclerosis (MS). Daily oral administration of alpha-LA, starting at the time of immunization, significantly prevented EAE progression as compared to control mice. This was associated with a reduction of CNS infiltrating T cells and macrophages as well as decreased demyelination. We then tested alpha-LA in a therapeutic protocol aimed at suppressing EAE after its onset. Intraperitoneal (i.p.), but not oral, administration of alpha-LA significantly prevented disease progression when compared to vehicle-treated controls. Our data indicate that alpha-LA can effectively interfere with the autoimmune reaction associated with EAE through mechanisms other than its antioxidant activity and supports further studies on the use of alpha-LA as a potential therapy for MS.

Effects of dietary omega3 and omega6 lipids and vitamin E on proliferative response, lymphoid cell subsets, production of cytokines by spleen cells, and splenic protein levels for cytokines and oncogenes in MRL/MpJ-lpr/lpr mice.
J Nutr Biochem. 1999 Oct;10(10):582-97.
Omega3 Fatty acid rich fish oil (FO) and vitamin E may delay the progress of certain autoimmune diseases. The present study examined the mechanisms of action of omega3 lipids and vitamin E in autoimmune-prone MRL/lpr mice suffering from extensive lymphoproliferation, lupus-like symptoms, and accelerated aging. To determine whether the effects of omega3 lipids in autoimmune disease is linked to vitamin E levels, weanling female MRL/lpr and congenic control MRL/++ mice were fed diets containing 10% corn oil (CO) or 10% FO at two levels of vitamin E (75 IU or 500 IU/kg diet) for 4 months. The appearance of lymph nodes was delayed in the mice fed FO, and higher levels of FO offered further protection against the appearance of lymph nodes.  The observations from this study suggest that both FO and vitamin E modulate the levels of specific cytokines, decrease the levels of proinflammatory cytokines, inflammatory lipid mediators, and c-myc, and increase TGF-beta1 levels in spleens of MRL/lpr mice and thus may delay the progress of autoimmune diseases.

Does diet have a role in the aetiology of rheumatoid arthritis?
Proc Nutr Soc. 2004 Feb;63(1):137-43.
Although dietary factors have been extensively studied in many chronic diseases, the role of diet in the epidemiology of rheumatoid arthritis (RA) has received little attention. Fruit and vegetables and dietary antioxidants are thought to play a protective role in the pathogenesis of CVD and some cancers, but few studies have investigated these dietary components in the aetiology of RA. Fish oil supplementation has consistently been shown to have a beneficial effect on the symptoms of established RA, but it is not known whether the PUFA present in fish oils can reduce the risk of developing the disease. There is evidence that RA is less severe in the southern Mediterranean countries, such as Italy and Greece, where oil-rich fish, fruit, vegetables and olive oil are consumed in greater amounts than in many other countries. Overall, the evidence for a role of diet in the aetiology of RA is limited to a small number of observational studies of very different designs. Recently, it was demonstrated that lower intakes of fruit and vegetables and dietary vitamin C are associated with an increased risk of developing inflammatory polyarthritis in a free-living population in Norfolk, UK. These findings provide further evidence for a role of diet in the development of inflammatory arthritis, although the mechanisms involved are uncertain.

Activation of autoimmunity following use of immunostimulatory herbal supplements.
Lee AN, Werth VP.
Section of Dermatology, University of Chicago, IL, USA.
Arch Dermatol. 2004 Jun;140(6):723-7.
Evidence for the scientific basis of purported therapeutic effects and adverse effects of herbal supplements continues to grow. Many herbal supplements are touted for their immunostimulatory properties, and both in vitro and in vivo experiments have supported this claim. Although this explains their beneficial effects in preventing or curtailing disease, to our knowledge, no immunostimulatory herbal supplements have been reported to exacerbate disorders of immune system overactivity. We describe 3 patients whose autoimmune disease onset and/or flares correlated with ingestion of herbal supplements with proven immunostimulatory effects. Echinacea and the alga Spirulina platensis are implicated in 2 patients' flares of pemphigus vulgaris, and a supplement containing the algae Spirulina platensis and Aphanizomenon flos-aquae was ingested by a third patient days before both onset and a severe flare of dermatomyositis. The third patient showed heterozygosity for a tumor necrosis factor alpha (TNF-alpha) promoter polymorphism, leading to increased production of TNF-alpha, which may have predisposed her to developing dermatomyositis. Immunostimulatory herbal supplements may exacerbate preexisting autoimmune disease or precipitate autoimmune disease in persons genetically predisposed to such disorders. Increased production of TNF-alpha may play a role, although more research is needed to clarify the mechanisms of such phenomena.

Autoimmune questions
Q. I am also a physician in practice residing in Connecticut who is grateful to you for all your insight and contribution to the field of Complementary / Alternative Medicine. I have read some of your writings on hormonal therapy and autoimmmune disease and i find them very informative and interesting. I also routinely use supplements in my practice and take pride in practicing Integrative medicine which i hope one day will be ubiquitous. My question to you relates to what you consider are adequate hormone holidays for patients with autoimmune disease who are placed initially on Pregnenolone 25mg and DHEA 25mg or higher. In practice I may start with higher doses initially and then taper down to maintenance dosing of about 5 mg depending on response for the long term. Also on a more personal note i have family members who would like to see a physician experienced in the these areas of hormonal therapy ( As family members i would rather they see someone other than myself) within the greater New York area is there someone here you recommend. I don't have to tell you that it is hard to find physicians knowledgeable in this area. Dr. Sahelian once again thank you. I respect you as a mentor and look forward to your thoughts on these questions.
   A. I truly appreciate the positive feedback and hope you continue helping your patients heal. It is very difficult to know which patients will respond to hormonal therapy. I personally prefer the cautious approach and would not use a dosage greater than 10 mg. I have seen too many people with serious side effects on high doses, including cardiac rhythm disturbances. You may be fine treating quite a large number of people with higher dosages with no apparent side effects, but eventually you will come across a patient who will have a serious untoward response. I prefer trying less risky options first, such as diet with high amount of fish and lower amounts of omega 6 oils, fish oil supplements, flavonoids, and perhaps certain herbs. Hormones are a last resort. And even if DHEA and pregnenolone work initially, continuing their use is not practical due to eventual side effects. There's still much we need to learn about the use of nutrients and herbs for autoimmune conditions and hopefully more info will be published in the future regarding the natural approach to these conditions.

Q. Is it okay to take saw palmetto or lipoic acid for someone with an autoimmune condition?
   A. It's really difficult to predict how herbs and supplements interact with an autoimmune conditon or the medicines a person is taking to treat the autoimmune condition. I would suspect small amounts would be fine, but I can't be sure.

Q. I have found your site through researching my illness. I have autoimmune urticaria and rheumatoid arthritis. After struggling for 8 years with harsh steroids and immune suppressants i think i finally found a decent treatment. I have begun taking superoxide dismutase and cordyceps. I have followed the bottles directions for dosage. I have seen a dramatic improvement with both of my conditions. However I still am getting symptoms. I would like to increase the dosage of both the cordyceps and superoxide dismutase to see if i can completely control my illness. I am totally amazed at how well these supplements work for my autoimmune disease. I would recomend them for anyone looking to go the natural route for autoimmune disorders.
   A. Please keep us updated.

Q. Are EGCG, the green tea extract, and resveratrol helpful in autoimmune disease?
   A. I have not seen such research yet.

Q. Is polymyalgia rheumatica an autoimmune disease?
   A. It is not classified as an autoimmune disease.