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Functional Medicine Protocol for Autoimmune Diseases: Balancing the Immune System

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Functional Medicine Protocol for Autoimmune Diseases: Balancing the Immune System

Over 80 autoimmune diseases have been identified, affecting an estimated 50 million people in the United States. 8 million more have autoantibodies, which indicates an increased risk of developing an autoimmune disease in the future. The prevalence of autoimmunity appears to be increasing in the United States in recent decades. The US National Institutes of Allergy and Infectious Disease estimates that autoimmune diseases incur a cost of $100 billion to the US healthcare system annually. With the increasing prevalence of autoimmune diseases and the high cost burden of treating them, interest in functional medicine as a treatment avenue for managing autoimmune diseases has increased.


What Are Autoimmune Diseases?

Our immune system is made up of organs, white blood cells, antibodies, and chemicals. When this system works properly, it is able to identify which cells are our own and which are foreign so it can protect us against invaders that can cause illness. In individuals with autoimmune diseases, the immune system loses self-tolerance. This means it is no longer able to differentiate between our own cells and foreign invaders, causing it to attack healthy cells, tissues, and organs.

Some of the most common autoimmune diseases include Systemic Lupus Erythematosus (SLE), Sjogren’s Syndrome, Rheumatoid Arthritis (RA), Type 1 Diabetes, Multiple Sclerosis (MS), Hashimoto’s Thyroiditis, and Crohn’s disease. Autoimmune diseases can be organ-specific, in which the immune response is directed against a single organ, like Hashimoto’s thyroiditis or Type 1 Diabetes. Alternatively, they can also be systemic, in which several organs can be affected, like SLE.

Most autoimmune diseases are chronic without definitive cures. The goal of treatment is to alleviate symptoms and try to control future tissue damage. (4)

Autoimmune Disease Signs and Symptoms

Signs and symptoms of autoimmune diseases can vary depending on which autoimmune disease the patient has and which tissues or organs are being affected. Areas that are often affected include blood vessels, connective tissue, endocrine glands (like the thyroid), joints, muscles, red blood cells, and skin. Some common symptoms include: 

  • Fatigue
  • Joint pain and swelling
  • Dizziness
  • Muscle Pain
  • Skin problems
  • Abdominal pain or digestive issues
  • Recurring fever
  • Swollen glands

What Are The Possible Causes of Autoimmune Diseases?

While the exact cause of autoimmune diseases is unknown, a variety of factors can play a role in their development.

Immune System Dysregulation

The development of an autoimmune disease occurs when there are autoreactive lymphocytes that cause tissue damage. Dysfunctional regulatory mechanisms and immune cells, along with inflammatory cytokines, play a role in this response. (31)


Evidence from familial clustering, genome studies, and twin studies have shown that individuals can inherit a genetic predisposition for developing an autoimmune disease. The genetic heritability of autoimmune diseases can vary, though. For example, Crohn’s disease has a very high genetic heritability, while others, like Systemic Sclerosis, have low genetic heritability. (39)

Environmental Exposures

Several environmental agents have been found to increase the risk of developing autoimmune diseases. Some of these possible environmental exposures include mercury, smoking, pesticides, air pollution, and tetrachloroethene (a chemical used in dry cleaning). Increasing oxidative stress has been suggested as a possible mechanism by which these exposures can play a role in the development of autoimmune diseases. (26)


Retrospective studies show that 80% of individuals report high levels of stress prior to the onset of an autoimmune disease.  The Hypothalamic-Pituitary-Adrenal (HPA) Axis releases glucocorticoids like cortisol that are known to affect the function of the immune system. (43, 44)


Exposure to infectious organisms may induce the development or exacerbation of autoimmune diseases. For example, associations between SLE and both EBV and CMV have been observed. One way in which bacteria and viruses are thought to influence autoimmunity is through a process called molecular mimicry, in which foreign substances have a very similar structure to substances in the body, which confuses the immune system.

Some infections might even provide protection against the development of autoimmunity. Inverse associations between parasitic infections and autoimmune disease have been observed. Furthermore, in areas with low prevalence of parasite infections, the prevalence of autoimmune diseases is rising. (1)

Gut Health

The different microorganisms that reside in the gastrointestinal tract, known as the microbiome, play an important role in influencing the immune system. Some commensal bacteria support the development of certain immune cells, called regulatory T cells, that help to control immune responses and can prevent autoimmunity. Other commensal bacteria can promote the activity of immune cells involved in inflammation. Alterations of the microbiome (dysbiosis) have been observed in autoimmune diseases. (1, 14)

The lining of the gastrointestinal tract should be a semi-permeable barrier. This means it allows for the transport of water and nutrients but prevents partially digested food particles, toxins, and microbes from leaving the intestines. In cases of intestinal permeability, or leaky gut, these substances can enter the body and promote inflammation. Some research has suggested that intestinal permeability can increase the risk of developing an autoimmune disease. 

Functional Medicine Labs to Test for Root Cause of Autoimmune Diseases

Diagnosing an autoimmune disease can often take longer than diagnosing other health conditions because the symptoms overlap with many other diseases (3). Certain blood tests can be helpful in diagnosing autoimmune conditions. Functional medicine tests can provide additional information about underlying causes contributing to immune system dysregulation.

Screening Tests

There are initial blood tests that can be ordered that can indicate the possibility of an autoimmune disease being present. The complete blood count (CBC) test might show signs of anemia. A complete metabolic panel (CMP) could show increased creatinine (a marker of kidney function), increased liver enzymes, or increased muscle enzymes. Sedimentation rate (ESR) and C-reactive protein (CRP) are often elevated in the presence of inflammation. Anti-nuclear antibodies (ANA) are a type of autoantibody commonly seen in autoimmune diseases. If ANA is positive, an extractable nuclear antigen (ENA) test can be ordered to help identify more specifically which autoimmune disease is present. Other, more specific markers can be ordered if other autoimmune conditions are being considered. Rheumatoid Factor (RF) and anti-cyclic citrullinated peptide (CCP) screen for Rheumatoid Arthritis. Anti-nuclear cytoplasmic antibodies (ANCA) screen for vasculitides. Thyroid stimulating hormone (TSH), thyroid-stimulating hormone receptor antibodies (TRAb), thyroid-peroxidase (TPO) antibodies, and thyroglobulin (Tg) antibodies screen for autoimmune thyroid conditions. (33)  

Comprehensive Stool Test

The Gut Zoomer measures over 300 microorganisms, markers of intestinal inflammation, and markers of digestion and absorption. This test is useful in identifying any dysbiosis or infections that can contribute to immune dysfunction and inflammation. Zonulin, a potential marker of intestinal permeability, is also measured.

Environmental Exposures 

The Urine Toxic Metals test can identify exposures to metals, like mercury, that can increase the risk of autoimmune diseases The Environmental Toxins profile measures 39 different toxicants, including markers of pesticide exposure and inhaled exposures like gasoline and cigarette smoke. 


As discussed earlier, certain viral infections have been associated with an increased risk of developing an autoimmune disease. The Viral Screen detects chronic infection with four major viruses, including EBV, CMV, HSV-1, and HSV-2. 

Adrenal Testing

The Adrenocortex Stress Profile measures cortisol and DHEA through multiple saliva samples throughout the day to demonstrate the diurnal rhythm of cortisol and diagnose any HPA axis dysfunction due to chronic high stress.

Autoantibody Testing

Autoantibodies may be present for years before the development of autoimmune diseases and can predict future risks. The Array 5 - Multiple Autoimmune Reactivity Screen measures predictive antibodies for certain diseases and identifies potential tissue damage in various body organs. This is a good test for patients concerned about their future risk of developing autoimmune diseases and who want to be proactive.

Additional Lab Tests 

The following tests might also be helpful:

Sleep Study

Disordered sleep, with or without apnea, may contribute to the development of autoimmune diseases. Sleep apnea, for example, increases the levels of inflammatory chemicals that are associated with autoimmune disease. Sleep studies can be ordered to see if any therapies are warranted. (22, 38)

Cardiometabolic Panel

People diagnosed with autoimmune disease have an increased risk of cardiovascular disease. A systemic inflammatory disorder may increase the risk of and accelerate endothelial injury, leading to atherosclerosis. The Cardiac Health panel measures lipids, lipoproteins, essential fatty acids, and markers of vascular inflammation and cardiac stress to help monitor cardiovascular disease risk.


Conventional Treatment for Autoimmune Diseases

Treatments can vary depending on which autoimmune diseases are present. The main goal in the management of autoimmune disease is to control symptoms, limit inflammatory damage, and try to extend the periods of remission. Immunosuppressants like steroids, hydroxychloroquine, and methotrexate can be prescribed. Biologics and Jak-2 inhibitors are also utilized. These medications target specific parts of the immune system instead of being broadly immunosuppressive. (23)

Integrative Medicine Protocol for Autoimmune Diseases

The conventional treatments for autoimmune diseases incur high financial costs, are often not entirely effective, and can have potentially serious side effects, like diabetes, high blood pressure, osteoporosis, and infections. Since autoimmune diseases can be challenging to manage with medications alone, functional medicine practitioners can create personalized treatment protocols to address the underlying factors that might be driving immune system dysregulation in autoimmunity.

Therapeutic Diet For Autoimmune Diseases

Although no definitive association between diet and autoimmune disease has been established, some scientists believe that a Western-style diet might be a contributing factor. A Western diet is characterized by high fat and cholesterol intake, excess sugar and salt intake, and frequent consumption of processed foods. These dietary habits have been linked to many chronic inflammatory health conditions.  

The Mediterranean Diet is an eating pattern that emphasizes the intake of vegetables, fruit, beans, lentils, nuts, and healthy fats from olive oil and fish. This style of eating can help to reduce inflammation. Studies have shown its benefit in some autoimmune diseases like SLE, psoriasis, and RA. (37, 48)  

An Autoimmune Paleo (AIP) Diet is a type of elimination diet that removes foods that have the potential to stimulate inflammation. Grains, legumes, nightshades, dairy, eggs, nuts and seeds, coffee, alcohol, processed foods, and refined sugar are all removed. (27, 32)

Best Supplements For Managing Autoimmune Diseases

The following supplements have evidence for supporting autoimmune diseases:

Vitamin D

Vitamin D can modulate the immune system, and low levels have been seen in autoimmune diseases. Research has indicated that supplementing with Vitamin D can reduce the risk of developing an autoimmune disease by 22%.

Fish Oil

Omega-3 polyunsaturated fatty acids also have immunomodulatory effects. The omega-3 polyunsaturated fatty acids found in fish oil, EPA and DHA, are particularly effective. Supplementing with fish oil was found to decrease the risk of developing an autoimmune disease by 15%.


Probiotic supplementation is used to repopulate the gastrointestinal tract with important commensal bacteria. These bacteria exercise immunomodulatory effects and help to maintain a healthy intestinal barrier. Research has shown promise for probiotic supplementation in multiple autoimmune diseases, including RA, SLE, and MS.


Curcumin is an extract from the curcuma longa plant. It has anti-inflammatory and antioxidant capabilities. It can also help in treating intestinal permeability. Curcumin supplementation has shown benefit in multiple autoimmune diseases. Piperine, from black pepper, can be added to curcumin supplements to increase bioavailability. (7, 20, 41)


Glutathione is an antioxidant that helps to optimize lymphocyte functioning. Oxidative stress and depletion of glutathione are commonly seen in autoimmune diseases. Restoring glutathione levels can help to improve immune system function. (36, 47)

When To Retest Labs

How often labs should be performed for monitoring will depend on the autoimmune disease, the disease severity, and the history and severity of flares.



The prevalence of autoimmune diseases is increasing. These diseases are usually chronic in nature, and there are significant costs and potential pitfalls associated with conventional treatments. Functional medicine testing and treatment protocols provide additional therapeutic avenues for a more holistic approach to care to improve the quality of life in patients diagnosed with autoimmune diseases.

The information provided is not intended to be a substitute for professional medical advice. Always consult with your doctor or other qualified healthcare provider before taking any dietary supplement or making any changes to your diet or exercise routine.
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Lab Tests in This Article


  1. Anaya, J.-M., Shoenfeld, Y., Cervera, R., & Arango, M.-T. (2013). Infection and autoimmune diseases. In Autoimmunity: From bench to bedside (pp. 303–320). essay, Universidad del Rosario.
  2. Anderson, S. (2022, June 6). How to talk to your patients about leaky gut: An overview. Rupa Health.
  3. Autoimmune diseases: Causes, symptoms, what is it & treatment. Cleveland Clinic. (2021).
  4. Autoimmune disorders. Mount Sinai Health System. (n.d.).
  5. Bigleyj. (2023, June 28). A little of this and that: Your guide to the AIP diet. Cleveland Clinic.
  6. Blumberg, R. S., Dittel, B., Hafler, D., von Herrath, M., & Nestle, F. O. (2012). Unraveling the autoimmune translational research process layer by layer. Nature Medicine, 18(1), 35–41.
  7. Bright, J. J. (2007). Curcumin and autoimmune disease. Advances in Experimental Medicine and Biology, 425–451.
  8. Christ, A., Lauterbach, M., & Latz, E. (2019). Western diet and the immune system: An inflammatory connection. Immunity, 51(5), 794–811.
  9. Cloyd, J. (2023a, March 17). A functional medicine protocol for crohn’s disease. Rupa Health.
  10. Cloyd, J. (2023b, May 12). Revolutionizing Integrative Medicine Multiple Sclerosis Treatment Options: Evidence based nutrition approaches plus essential specialty labs for Optimal Patient Care. Rupa Health.
  11. Cloyd, J. (2023c, August 25). A root cause medicine protocol for patients with rheumatoid arthritis: Testing, therapeutic diet, and supportive supplements. Rupa Health.
  12. Conner, V. (2022, July 13). This virus has infected over 90% of the adult population. yet many never experience any symptoms. Rupa Health.
  13. Cox, A. D. (2022, September 8). 4 herbs and supplements that may help control type 1 diabetes. Rupa Health.
  14. De Luca, F., & Shoenfeld, Y. (2018). The microbiome in autoimmune diseases. Clinical and Experimental Immunology, 195(1), 74–85.
  15. DePorto, T. (2023, June 6). Omega 3’s: The Superfood nutrient you need to know about. Rupa Health.
  16. Dinse, G. E., Parks, C. G., Weinberg, C. R., Co, C. A., Wilkerson, J., Zeldin, D. C., Chan, E. K., & Miller, F. W. (2020). Increasing prevalence of antinuclear antibodies in the United States. Arthritis & Rheumatology, 72(6), 1026–1035.
  17. Diorio, B. (2023, March 17). How to test for hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Rupa Health.
  18. Durante, A., & Bronzato, S. (2015). The increased cardiovascular risk in patients affected by autoimmune diseases: Review of the various manifestations. Journal of Clinical Medicine Research, 7(6), 379–384.
  19. Fasano, A. (2020). All disease begins in the (leaky) gut: Role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases. F1000Research, 9, 69.
  20. Ghosh, S. S., He, H., Wang, J., Gehr, T. W., & Ghosh, S. (2018). Curcumin-mediated regulation of intestinal barrier function: The mechanism underlying its beneficial effects. Tissue Barriers, 6(1).
  21. Hahn, J., Cook, N. R., Alexander, E. K., Friedman, S., Walter, J., Bubes, V., Kotler, G., Lee, I.-M., Manson, J. E., & Costenbader, K. H. (2022). Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: Vital randomized controlled trial. BMJ.
  22. Hsiao, Y.-H., Chen, Y.-T., Tseng, C.-M., Wu, L.-A., Lin, W.-C., Su, V. Y.-F., Perng, D.-W., Chang, S.-C., Chen, Y.-M., Chen, T.-J., Lee, Y.-C., & Chou, K.-T. (2015). Sleep disorders and increased risk of autoimmune diseases in individuals without sleep apnea. Sleep, 38(4), 581–586.
  23. Immunosuppressants. Cleveland Clinic. (n.d.). 
  24. Immunosuppressive medication for the treatment of autoimmune disease. American Academy of Allergy Asthma & Immunology. (n.d.).
  25. Khakham, C. (2023, March 7). Top medical evidence supporting curcumin’s health benefits. Rupa Health.
  26. Khan, M. F., & Wang, H. (2020). Environmental exposures and autoimmune diseases: Contribution of gut microbiome. Frontiers in Immunology, 10.
  27. Konijeti, G. G., Kim, N., Lewis, J. D., Groven, S., Chandrasekaran, A., Grandhe, S., Diamant, C., Singh, E., Oliveira, G., Wang, X., Molparia, B., & Torkamani, A. (2017). Efficacy of the autoimmune protocol diet for inflammatory bowel disease. Inflammatory Bowel Diseases, 23(11), 2054–2060.
  28. Liu, Q., Yu, Z., Tian, F., Zhao, J., Zhang, H., Zhai, Q., & Chen, W. (2020). Surface components and metabolites of probiotics for regulation of intestinal epithelial barrier. Microbial Cell Factories, 19(1).
  29. Liu, Y., Alookaran, J., & Rhoads, J. (2018). Probiotics in autoimmune and inflammatory disorders. Nutrients, 10(10), 1537.
  30. Mackay, I. R. (2000). Tolerance and autoimmunity. BMJ, 321(7253), 93–96.
  31. Maholy, N. (2023, June 8). The impact of stress on autoimmune diseases: Exploring the potential of stress-reduction techniques. Rupa Health.
  32. McNeill, J., Zinn, C., Mearns, G., & Grainger, R. (2023). What is the efficacy of the Autoimmune Protocol (AIP) diet in people with rheumatoid arthritis? A mixed-methods pilot intervention study. NSNZ 2022.
  33. Moore, T. L., & Dalrymple, A. M. (2016). Laboratory studies in autoimmune diseases. Missouri Medicine, 113(2), 118–122.
  34. Neibling, K. (2023, March 22). Molecular mimicry as a mechanism of autoimmune disease. Rupa Health.
  35. Orbeta, R. (2022, April 1). 8 signs and symptoms of an autoimmune disease. Rupa Health.
  36. Perricone, C., De Carolis, C., & Perricone, R. (2009). Glutathione: A key player in autoimmunity. Autoimmunity Reviews, 8(8), 697–701.
  37. Phan, C., Touvier, M., Kesse-Guyot, E., Adjibade, M., Hercberg, S., Wolkenstein, P., Chosidow, O., Ezzedine, K., & Sbidian, E. (2018). Association between Mediterranean anti-inflammatory dietary profile and severity of psoriasis. JAMA Dermatology, 154(9), 1017.
  38. Phillips, B. G., Wang, Y., Ambati, S., Ma, P., & Meagher, R. B. (2020). Airways therapy of obstructive sleep apnea dramatically improves aberrant levels of soluble cytokines involved in autoimmune disease. Clinical Immunology, 221, 108601.
  39. Putting a stop to Leaky Gut. Harvard Health. (2018, December 1).
  40. Ramos, P. S., Shedlock, A. M., & Langefeld, C. D. (2015). Genetics of autoimmune diseases: Insights from population genetics. Journal of Human Genetics, 60(11), 657–664.
  41. Ravi, N., Choday, S., Shantha Kumar, V., KC, A., Parisapogu, A., Ojinna, B., Tran, H. H.-V., Sherpa, M. L., Shrestha, N., & Mohammed, L. (2022). The key role of glutathione compared to curcumin in the management of systemic lupus erythematosus: A systematic review. Cureus.
  42. Smyth, M. C. (2017). Intestinal permeability and autoimmune diseases. Bioscience Horizons: The International Journal of Student Research, 10. 
  43. Song, H., Fang, F., Tomasson, G., Arnberg, F. K., Mataix-Cols, D., Fernández de la Cruz, L., Almqvist, C., Fall, K., & Valdimarsdóttir, U. A. (2018). Association of stress-related disorders with subsequent autoimmune disease. JAMA, 319(23), 2388. 
  44. Stojanovich, L., & Marisavljevich, D. (2008). Stress as a trigger of autoimmune disease. Autoimmunity Reviews, 7(3), 209–213. 
  45. Suurmond, J., & Diamond, B. (2015). Autoantibodies in systemic autoimmune diseases: Specificity and pathogenicity. Journal of Clinical Investigation, 125(6), 2194–2202.
  46. Sweetnich, J. (2023, June 28). Top functional medicine lab tests that can help individualize treatment for patients with Hashimoto’s thyroiditis. Rupa Health.
  47. Tewthanom, K. (2008). Correlation of lipid peroxidation and glutathione levels  with  severity of systemic lupus erythematosus: A pilot study from Single Center. Journal of Pharmacy & Pharmaceutical Sciences, 11(3), 30.
  48. Tsigalou, C., Konstantinidis, T., Paraschaki, A., Stavropoulou, E., Voidarou, C., & Bezirtzoglou, E. (2020). Mediterranean diet as a tool to combat inflammation and chronic diseases. an overview. Biomedicines, 8(7), 201.
  49. U.S. Department of Health and Human Services. (2022). Autoimmune diseases. National Institute of Environmental Health Sciences.
  50. Weinburg, J. L. (2022, November 16). 4 science backed health benefits of the Mediterranean diet. Rupa Health.,fatty%20liver%20disease%20(NAFLD).
  51. Yang, C.-Y., Leung, P. S., Adamopoulos, I. E., & Gershwin, M. E. (2013). The implication of Vitamin D and autoimmunity: A comprehensive review. Clinical Reviews in Allergy & Immunology, 45(2), 217–226.
  52. Yoshimura, H. (2023, May 8). A functional medicine systemic lupus erythematosus (SLE) protocol: Testing, diagnosing, and treatment. Rupa Health. 
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