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Ama and Leaky GutMerging the Science of Western Medicine

with the Ancient Wisdom of Ayurveda

2020 NAMA Annual ConferenceClayton Bell, M.D.

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• Ayurveda: Chronic disturbed agni occurs from gunaaccumulation due to multiple hetus. This produces a chronic ama condition which affects the tight junctions of the gut allowing prasara stage from abhyantara to bahyamargh producing systemic symptoms of ama

• Functional Integrative Medicine: Chronic gastrointestinal system dysfunction occurs via cumulative effects from multiple etiologies. This combination of factors can lead to transintestinal permeability by loosening of intestinal tight junctions. Partially digested food antigens, bacteria, etc. may leave the intestinal lumen and elicit systemic immune reactions and/or inflammation.

Ama and Leaky Gut

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Leaky Gut Flow Chart

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Abnormal presentation of luminal constituents to the mucosal immune system, caused by dysfunction of the intestinal epithelial barrier.

Transintestinal Permeability

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Leaky Gut Triggers

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Stress: COVID-19

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• Increased epithelial permeability is found in subgroups of patients at high risk for the development of autoimmune diseases such as Crohn's disease and have been found to precede disease recurrence.

• Disease recurrence can follow times of increased psychological stress. environmental stress increases gastrointestinal permeability.

• Increased epithelial permeability after stress was shown in all regions of the gastrointestinal tract and seemed to be mediated by adrenal corticosteroids. Stress-induced increases in epithelial permeability disappeared after adrenalectomy or pharmacologic blockade of glucocorticoid receptors.

• Dexamethasone treatment of control animals increased gastrointestinal permeability and mimicked the effects of stress.

• Conclusions: Psychological stress may increase gastrointestinal permeability, allowing luminal constituents access to the mucosal immune system.

Stress -> Leaky Gut -> Crohn’s

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Celiac Disease

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Healthy Intestinal Villi

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Damaged Intestinal Villi

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Microbiome Effects

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• Mrs. Shay Morgan is an extremely pleasant 31-year-old female who works in university medical clinic.

• Recently diagnosed with severe Rheumatoid Arthritis. • Started on prednisone, methotrexate and Enbrel

(etanercept)– Etanercept is a recombinant DNA-derived protein composed of tumor necrosis factor

receptor (TNFR) linked to the Fc portion of human IgG1. Etanercept binds tumor necrosis factor (TNF) and blocks its interaction with cell surface receptors. TNF plays an important role in the inflammatory processes and the resulting joint pathology of rheumatoid arthritis (RA), polyarticular-course juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), and plaque psoriasis.

• History of anxiety which is severely exacerbated by acute onset of RA pain and cost of medications (Enbrel $5,900 per month).

• Referred to Integrative Health by her colleagues for nutritional interventions and natural healing modalities.

Case Report: Shay Morgan

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Food Sensitivity IgG Testing

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• Began with IFM 30-day Elimination Diet (dairy, gluten, eggs, soy, peanuts, corn, beef and pork).

• Food Sens IgG Panel:– Avoid: dairy, egg, asparagus, green bean, pineapple,

brewer’s yeast (beer), xantham gum.– Many moderate IgG reactions– High candida screen

• Discovered she was sensitive to nightshades.• Implemented stress resiliency practices including

psychotherapy and TRE (Tension and Trauma Releasing Exercises).

• Started on Turmeric 1,000 mg twice daily, Fish Oil (4 grams EPA + DHA), and Saccharomyces boulardii.

Case Report: Shay Morgan

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• Rheumatoid Arthritis pain significantly improved.• Was able to return to work, begin holding her child,

and even start riding horses again.• Tapered off prednisone, recently stopped MTX on 3/9/20.• Medical Symptoms Questionnaire Score dropped from

63 to 18 to 5 over past 9 months.• MSQ Musculoskeletal subscale dropped from 20

(maximum score) to merely 3.• Extremely happy to have her life back and eager to

share nutritional improvements with colleagues, family, and friends.

• Her physician coworkers now inquire about dietary changes during our lunches together.

Case Report: Shay Morgan

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• TNFs are major mediators of inflammation and inflammation-related diseases.

• FDA approved treatment for osteoarthritis, inflammatory bowel disease, psoriasis and ankylosis.

• Drugs include the chimeric TNF antibody (infliximab), humanized TNF-α antibody (Humira) and soluble TNF receptor-II (Enbrel) and are associated with a total cumulative market value of more than $20 billion a year. ($15,000 – 20,000 per person per year).

• These drugs must be injected and have enough adverse effects to be given a black label warning by the FDA.

TNF-a Blockers

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• Curcumin (diferuloylmethane), a component of turmeric (Curcuma longa) that is very inexpensive, orally bioavailable and highly safe in humans.

• Can block TNF-α action and production in in vitro models, in animal models and in humans.

• Evidence for curcumin's activities against all diseases for which TNF blockers are currently being used.

• “This golden spice may help provide the solution”.

Curcuma longa (Turmeric)

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Golden Oats with Ghee

• Ghee contains high levels of butyric acid which acts as primary fuel source for enterocytes (intestinal absorptive cells).

• Medicinal Ayurvedic breakfast to potentially help heal leaky gut.

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Oats prevent Leaky Gut

• Oats supplementation prevents gut leakiness. • Rats were gavaged for 12 weeks with alcohol (starting

dose of 1 g/kg increasing to 6 g/kg/day over the first 2 weeks) or dextrose, with or without oats supplementation (10 g/kg/day).

• Oxidative stress and injury were assessed by measuring colonic mucosal inducible nitric-oxide synthase (iNOS) (by immunohistochemistry), nitric oxide (colorimetric assay), and protein carbonylation and nitrotyrosination(immunoblotting).

• Colonic barrier integrity was determined by assessing the integrity of the actin cytoskeleton (immunohistochemistry) and the integrity of tight junctions (electron microscopy).

21• 154 lb person = 70 kg. 70 grams EtOH = 5 standard drinks (14 g EtOH per drink)• Study went as high as 30 alcoholic mouse drinks per day

Standard Drinks

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Alcohol & Leaky Gut

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Oats prevent Leaky Gut

• Oats supplementation prevented alcohol-induced oxidative stress to colonic epithelium.

• Protection from ethanol induced disorganization of the actin cytoskeleton and disruption of tight junctions.

• We conclude that oats supplementation attenuates EtOH-induced disruption of intestinal barrier integrity, at least in part, by inhibiting EtOH-induced increases in oxidative stress and oxidative tissue damage.

• Oats may be a useful therapeutic agent—a nutraceutical—for the prevention of alcohol-induced oxidative stress and organ dysfunction.

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“All disease begins in the gut”.- Hippocrates

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• Leaky gut leads to chronic inflammation and systemic reactions throughout the body.

• Our microbiome is vital for strong agni and preventing leaky gut.

• Food as Medicine forLeaky Gut: turmeric,ghee, oatmeal. Avoidexcess alcohol.

Clinical Pearls

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Clayton Bell, MDUniversity of Tennessee Medical Center

Cwbell@utmck.edu501-626-2448

Namaste

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• Aggarwal, B., et al. Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers. Br J Pharmacol. 2013 Aug;169(8):1672-92. doi: 10.1111/bph.12131.https://www.ncbi.nlm.nih.gov/pubmed/23425071

• Ballantyne, Sarah. The Paleo Approach: Reverse Autoimmune Disease and Heal Your Body. January 28, 2014. https://www.thepaleomom.com/comes-first-leaky-gut-dysfunctional-immune-system/

• Drugs.com Price Guide: Enbrel. March 2, 2020. https://www.drugs.com/price-guide/enbrel

• Forsberg, G., et al. Presence of bacteria and innate immunity of intestinal epithelium in childhood celiac disease. Am J Gastroenterol. 2004 May;99(5):894-904. https://www.ncbi.nlm.nih.gov/pubmed/15128357

• Harvard Health Letter. Getting out the gluten. Published: June, 2009 https://www.health.harvard.edu/staying-healthy/getting-out-the-gluten

• Institute of Functional Medicine. Applying Functional Medicine in Clinical Practice: Gut Dysfunction. 2019.

Citations

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• Meddings, J., Swain, M. Environmental stress–induced gastrointestinal permeability is mediated by endogenous glucocorticoids in the rat. Gastroenterology. Volume 119, Issue 4, October 2000, Pages 1019-1028. https://doi.org/10.1053/gast.2000.18152

• NIH National Institute on Alcohol Abuse and Alcoholism: What Is A Standard Drink? https://www.niaaa.nih.gov/what-standard-drink

• Psychopharmacology. Oxford University, UCLA Division of Digestive Services. Brain Mapping Center at UCLA.

• Samuelson, D. et al. Regulation of Lung Immunity and Host Defense by the Intestinal Microbiota. Frontiers in Microbiology 6 (1085). October 2015. DOI: 10.3389/fmicb.2015.01085

• Tang, Y., et. al. Oats Supplementation Prevents Alcohol-Induced Gut Leakiness in Rats by Preventing Alcohol-Induced Oxidative Tissue Damage. Journal of Pharmacology and Experimental Therapeutics June 1, 2009, 329 (3) 952-958; DOI: https://doi.org/10.1124/jpet.108.148643 http://jpet.aspetjournals.org/content/329/3/952

Citations