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Do the Benefits of Botanical and Physiotherapeutic Hepatobiliary Stimulation Result From Enhanced Excretion of IgA Immune Complexes?

By Alex Vasquez, DC, ND

A cornerstone of science-based holistic health care, foremost among which is naturopathic medicine, is a profound and inviolable appreciation of the interconnected nature of various organs and body systems.

By comparison, simplistic conceptualizations founded on the erroneous presumption that body systems function separately have become scientifically untenable and intellectually unsatisfying as biomedical research has continued to affirm holism and refute the isolationistic reductionism upon which the allopathic-pharmaceutical paradigm is founded. For example, these days, to think that the immune system functions separately from the body's ability to "detoxify" is clear indication of an incomplete education.

The naturopathic profession is unique in its affirmation of holism in general and the importance of nutrition, gastrointestinal function and "detoxification" in particular. Within the profession, the importance of these tenets is accepted beyond the need for explication; however, a periodic review of these concepts and the ongoing molecular elucidation of the mechanisms involved is worthwhile, both for students and experienced clinicians.

Detoxification involves numerous mechanisms and organ systems, and the hepatic contribution of xenobiotic oxidation and conjugation1 is only one part of this multifaceted phenomenon that serves to remove harmful substances from the body. In addition to xenobiotic detoxification, proper hepatobiliary function appears necessary for the clearance of toxins, including toxic metals, as demonstrated by a recent study showing that the fatigue associated with chronic cholestasis appears to be due, in part, to the accumulation of manganese in the blood and brain.2 In addition to its role in the clearance of heavy metals, proper hepatobiliary function also is necessary for the removal of immune complexes. In this article, I will focus on the "detoxification" of immune complexes and review the potential relevance of hepatobiliary stimulation in the treatment of rheumatic diseases. This article derives from and extends several of my recent publications on the topic of integrative musculoskeletal medicine.3

Clinical Significance of Immune Complexes in Rheumatic Diseases and Autoimmunity

Immune complexes are polymeric combinations of antigens and antibodies that are the natural resultant of the humoral immune response toward a vast array of antigens, whether environmental allergens, microbial antigens or endogenous autoantigens. Since the inherent structure of each immunoglobulin allows it to bind to two antigens simultaneously, immunoglobulins can "cross-link" several antigens, leading to the formation of multiple antigen-antibody chains, which form immune complexes. Immune complexes contribute to the pathophysiology and clinical manifestations of many so-called "allergic" and "autoimmune diseases" when deposited in skin, vascular walls, synovium, and renal glomeruli for the production of a localized inflammatory reaction that results in the clinical manifestations of dermal erythema (e.g., the facial rash of lupus), vasculitis, arthritis, and glomerulonephritis, respectively.4 IgG and IgM immune complexes localize an inflammatory response wherever they are deposited, via the activation of inflammation in general and the complement cascade (classical pathway) in particular, whereas IgA immune complexes also stimulate a local inflammatory response, but activate the alternate pathway of the complement cascade. IgG and IgM immune complexes are preferentially removed from the circulation by the spleen and hepatic reticuloendothelial cells, whereas IgA immune complexes are preferentially consumed by hepatocytes and then excreted in the bile. IgG, IgM, and IgA immune complexes are pathogenic in nearly all autoimmune musculoskeletal diseases. Proof that tissue damage and clinical manifestations seen in rheumatic diseases are caused directly by immune complexes is evidenced by high efficacy of immunoadsorption5 and plasmapheresis6,7 (techniques for removing immune complexes) in patients with lupus. Evidence strongly suggests that IgA immune complexes directly contribute to tissue damage in IgA nephropathy,8 Henoch-Schonlein purpura,9 rheumatoid vasculitis,10 rheumatoid arthritis,11 lupus, and Sjogren's syndrome.12 The fact that IgA immune complexes mediate tissue damage and that these same immune complexes are eliminated via the liver and biliary system13,14 provides the rationale for the use of botanicals and physiotherapeutics that promote liver function and bile flow. Numerous experimental studies in animals have shown that circulating IgA immune complexes are taken up by hepatocytes and then secreted into the bile for elimination15,16 and bile duct obstruction retards systemic clearance of IgA immune complexes.17

Hepatobiliary Excretion of IgA Immune Complexes

Antigen-IgA complexes are phagocytized by hepatocytes and delivered largely intact directly into the bile. This is the most efficient means of disposing of antigens resistant to hydrolytic degradation due either to their size or physiochemical configuration. IgA immune complexes are taken up by hepatocytes and then secreted into the bile for elimination. The fact that bile duct obstruction retards systemic clearance of IgA immune complexes and that restoration of bile flow reduces serum IgA levels by enhancing biliary IgA excretion in animals18 and humans19 proves the importance of ensuring optimal hepatobiliary function and supports the use of botanical and physiological therapeutics that facilitate bile flow.

Stimulation of Bile Flow: Physiotherapeutics and Phytotherapeutics

Naturopathic physicians have used botanical medicines and physiotherapeutics since the (re)birth of the profession in North America more than 100 years ago,20 and the safety and effectiveness of many naturopathic interventions have been documented in numerous allopathic journals.

Evidence from journals such as the Archives of Internal Medicine suggests the primary physiotherapeutic intervention for the stimulation of bile flow is the enema. Enemas are differentiated from colonics in that enemas generally are delivered as a single insertion of water with a modest volume (generally 1-2 quarts [1-2 liters]), whereas colonics generally employ numerous insertions and removals of water, the total volume of which might exceed several gallons (>4-8 liters). Relatedly, the purpose of an enema is to stimulate normal function, while colonics are used to mechanically cleanse the bowel of debris in a manner analogous to the removal of dirt by hand washing under running water. Colon irrigations were endorsed by the American Medical Association for the adjunctive treatment of numerous health problems as late as 1932, when Bastedo21 published a review in The Journal of the American Medical Association endorsing and encouraging their use. In that same year, the New England Journal of Medicine documented the value of colon irrigation in the treatment of mental disease.22 In 1939, Snyder23 wrote a review article published in the prestigious Medical Clinics of North America in which he extolled the clinical benefits of colonics and enemas and lamented the decline in their use, which he attributed to doctors and nurses not having the time or inclination to administer the procedure.

While these articles were important for documenting the safety and clinical benefits of colonics and enemas, the 1929 work of Garbat and Jacobi24 published in Archives of Internal Medicine is of particular interest because of their skill in radiographically documenting the stimulation of bile flow directly from the liver in response to low-volume (e.g., 150 cc) enemas. The flow of bile begins within 10-30 minutes following the enema, and continues for the next 30-60 minutes. The bile flows directly from the liver without contraction of the gallbladder. Given that IgA immune complexes are removed from the circulation by the liver into the bile, we are justified in speculating that the hepatobiliary stimulation induced by enemas might facilitate amelioration of disease manifestations mediated by IgA immune complexes.

Phytomedicinal stimulation of bile flow can be accomplished by any number of botanical medicines, which generally are used in combination in clinical practice. Whether in experimental models or in clinical practice, botanicals that stimulate bile secretion from the liver and/or expulsion from the gallbladder include beets, ginger,25 curcumin/turmeric,26 Picrorhiza,27 milk thistle,28 Andrographis paniculata29 and Boerhaavia diffusa.30 Greater celandine (Chelidonium majus) has been shown in animal studies to stimulate bile flow;31 however, the herb has been shown to cause hepatitis and cholestatsis in several case reports in humans.32,33

Clinical Implications

The majority of rheumatic diseases are caused, at least in part, by the formation and deposition of immune complexes in skin, arteries, joints, kidneys and other body tissues. IgA immune complexes contribute to the pathogenesis of many autoimmune conditions. IgA immune complexes are preferentially removed from the systemic circulation by the hepatobiliary route. Animal models and human studies have shown that biliary obstruction retards the expulsion of IgA immune complexes and results in higher serum levels of these immune complexes. Conversely, interventions that stimulate bile flow likely are to help the liver cleanse the serum of immune complexes and lead to clinical improvement in rheumatic diseases mediated by immune complexes. The simple, safe and minimally invasive, low-volume enema has been shown to stimulate bile flow that lasts for 30-60 minutes. Numerous botanical medicines have been shown to safely and effectively stimulate bile flow. Thus, enemas and cholagogic botanical medicines might mediate their clinical benefits, at least in part, by promoting clearance of IgA immune complexes from the blood into the bile for expulsion. Thus, when administered correctly under professional supervision in appropriate patients, phytophysiologic hepatobiliary stimulation might prove a useful adjunct in the treatment of immune complex disease. Clinical studies with pre- and post-treatment measurements of serum immune complexes are warranted to determine if daily treatment with enemas/colonics and the specific botanicals listed above results in a reduction in serum immune complexes and if this reduction results in clinical improvement in patients with rheumatic IgA-immune complex diseases.

References

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  3. Vasquez A. "Integrative Orthopedics" and "Integrative Rheumatology." See www.OptimalHealthResearch.com for additional details. Also see: Nutritional and botanical treatments against silent infections and gastrointestinal dysbiosis, Commonly overlooked causes of neuromusculoskeletal inflammation and chronic health problems. Nutritional Perspectives, January 2006: www.OptimalHealthResearch.com/part6.
  4. Jancar S, Sanchez Crespo M. Immune complex-mediated tissue injury: a multistep paradigm. Trends Immunol, January 2005;26(1):48-55.
  5. Braun N, Erley C, Klein R, et al. Immunoadsorption onto protein A induces remission in severe systemic lupus erythematosus. Nephrol Dial Transplant, September 2000;15(9):1367-72.
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  19. Sung JJ, Leung JC, Tsui CP, et al. Biliary IgA secretion in obstructive jaundice: the effects of endoscopic drainage. Gastrointest Endosc, November 1995;42(5):439-44.
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About the Author: Dr. Alex Vasquez graduated from Western States Chiropractic College in Portland, Ore., in 1996, and then enrolled in the naturopathic medicine program at Bastyr University. By the time he graduated from Bastyr in 1999, Dr. Vasquez had published 13 articles in magazines and peer-reviewed medical journals and was a recognized authority on disorders of iron metabolism. Dr. Vasquez was later appointed to teach rheumatology, orthopedics, and radiographic interpretation at Bastyr. For family reasons, Dr. Vasquez returned to his hometown of Houston in 2002 and started a new private practice of natural medicine.

 



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