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What Does Digestion Have to do with Hormones Anyway? A presentation by Dr. Holly Lucille, ND, RN SPONSORED BY: A Gut Check for Many Ailments! “The gut is important in medical research, not just for the problems pertaining to the digestive system but also problems pertaining to the rest of the body” ~~ Pankaj J. Pasricha, chief of the division of gastroenterology and hepatology at Stanford University School of Medicine. 2 Outline Principle Anchors Digestive Review Causes of Impaired Digestion Consequences of Impaired Digestion – Adrenal Involvement & Allostatic Load – Thyroid Involvement – Impermeability & Inflammatory Response – Liver Involvement • Pathway to Healing • Decreasing Allostatic Load • Addressing Acute Concerns • • • • 3 54-year old female presents with several chronic complaints • Persistent fatigue • Stubborn weight gain • Trouble sleeping (both getting and staying to sleep) • Absolutely no sex drive “I am dead down there” • Vaginal dryness • Hair thinning • Hot flashes and night sweats • Feelings of despair • Chronic stress and anxiety • Memory loss 4 CC: “I have menopause” • LMP: 16 months ago • Seen several practitioners • RX’d with BHRT, SHRT variety of doses/routes • Watches “Dr. Oz” religiously, tried “detox patches” • No significant relief of symptoms 5 Laboratory Signs • • • • • • E2 = 1.0 pg/ml Pg = 20 pg/ml L Pg/E2 Ratio = 20 L Testosterone = 17 pg/ml L DHEA-s = 4.5 ng/ml AM Cortisol 10 ng/ml H (1.0-1.5) (25-100) (50-100) (20-50) (3-10) (3-8) • Chemistry: slightly elevated LDL’s, Vitamin D 27 • CBC: slightly low ferritin and RBC’s • Thyroid: slightly elevate TSH (4.2) 6 Anchor • • • • • • • • • • PMS Fatigue Weight Gain Night Sweats Thinning Hair Disruptive Circadian Rhythm Mood Fluctuations Depression Anxiety Etcetera 7 Anchor Point “Medicine is not only a science; it is also an art. It does not consist of compounding pills and plasters; it deals with the very processes of life, which must be understood before they may be guided.” ~Philipus A. Paracelsus 8 First Do No Harm • Listen • Least Invasive First • Many Modalities Before Drugs and Surgery • Hormone “Replacement” Therapy HARM 9 Identify and Treat the Cause • Health Detectives • Think Things Through • Not Simply Suppress Symptoms • Get to the Root • Heal From the Inside Out 10 Treat the W(hole) Person • “Heal the Hole” • Usually Clinical Presentation is Multifactorial in Cause • Self Knowledge, Beliefs and Attitude • Myriad of Relationships 11 Doctor as Teacher • Knowledge vs. Understanding • Understanding = Patient Empowerment • Solid Rationale Behind Recommendation • Normal Variants 12 Prevention is the Cure • Symptoms as Guidepost • Disconnect from the Deeper Issues • Real Disease Continues 13 Healing Power of Nature “IN ANY SITUATION..HEALTH WILL OCCUR WHEN THE CONDITONS FOR HEALTH EXIST AND DISEASE IS A PRODUCT OF CONDTIONS THAT ALLOW FOR IT” ~Dr. Jared Zeff 14 Women’s Health & Digestion • 42.2 million visits with diseases of the digestive system as the primary diagnosis • More than 1 in 4 have at least one variety of GI condition—that’s 60 – 70 million Americans • Gastrointestinal (GI) distress is more than twice as common in women as in men – Malabsorption – Dysbiosis (e.g., possibly pathogenic yeast or bacterial infection) – IBS – Leaky Gut Syndrome – Celiac Disease – Constipation Centers for Disease Control and Prevention. Available at: http://www.cdc.gov/nchs/fastats/digestiv.htm. Accessed March 10, 2011. National Digestive Diseases Information Clearinghouse (NDDIC) web site. Available at: http://digestive.niddk.nih.gov/statistics/statistics.htm#sources. Accessed March 10, 2011. 15 National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, November 1996 Journal of Women's Health 2010;6 ;1-14. Digestion Review: Heal the Whole Mouth • Saliva (amylase) Stomach • HCl, pepsin, chyme Duodenum • Bile, pancreatic enzymes Pancreas: Neutralize Enzymes Liver: Bile & cholesterol Gallbladder: Bile Storage Small Intestine • Absorption of 90% of nutrients Large Intestine • Waste products, bacteria, toxins Rectum • Fecal matter 16 Causes of Impaired Digestion • Lifestyle (e.g., not chewing, overeating, food choices, cooking) • Enzyme deficiencies • pH imbalances (e.g., hypochlorhydria, pancreatic bicarbonate deficiency) • Endocrine imbalances (e.g., gastrin, cholecytokinin, secretin secretion imbalance) • Aging • Stress • Certain disease states • Surgery, radiation, chemotherapy • Prescription medications (e.g., PPIs,H2 agonists, antibiotics) 17 Pathway of GI Dysfunction Impaired Digestion Dysbiosis Intestinal Toxemia Oxidative Stress Intestinal Inflammation Intestinal Permeability Defects Lack of digestive enzymes, poor diet, cooked foods, stress, etc. Bacteria acting on undigested food (endotoxins: skatoles, phenols, formaldehyde etc.) Toxemia and altered terrain (e.g. pH) lead to gut flora imbalance Gut lining compromised by continual attack of endotoxins, oxidation and, inflammation 18 Causes of Dysbiosis • • • • • • • • • Impaired digestion Hypochlorhydria Antibiotics Ethanol NSAIDS Stress Slow transmit time, decreased peristalsis Impaired immune status Dietary factors (e.g. low fiber, excess meat) Altern Med Rev. 2004 Jun;9(2):180‐97. Gut. 2004 Jan;53(1):1‐4 19 Consequences of Intestinal Dysbiosis • GI symptoms (gas, bloating, constipation, diarrhea) • Chronic intestinal inflammation, IBD • Intestinal permeability defects • Increased endotoxemia • Increased risk of cancer • Hormonal imbalances & subsequent SYMPTOMS • Systemic reactions to bacterial endotoxins & antigens Altern Med Rev. 2004 Jun;9(2):180‐97. Gut. 2004 Jan;53(1):1‐4 20 Dysbiosis and Hormonal Symptoms • Effects of Candida – Hypoadrenia – Hypothyroidism – Liver dysfunction tock S. Conquering Candida International Journal of Alternative & Complementary Medicine 1993;:24. Trowbridge JP, Walker M. The Yeast Syndrome. Bantam Books London 1986. Trowbridge JP. An Update on the Yeast Syndrome. Health News & Review 1992;2:10. Smith LH Trouble in the thyroid: keeping out fires lit Health News & Review 1992;2:6. Passwater RA, Cranton EM. Trace Elements, Hair Analysis and Nutrition Keats Publishing Inc Connecticut 1983. 21 Candida and Hypoadrenia • Possesses E and P receptors and those binding adrenal steroids • Exogenous sex hormones (HRT, OC) feed • Toxins have direct cytotoxic effect on adrenals via increasing free radical activity and decreasing Tcell activity • Interfere with Acetyl CoE A which decreases synthesis of adrenal steroids 22 Adrenal Anchor Points • Built in Back Up • “Stress Glands” • Produce Cortisol and Other Hormones • Controls the Immune Response in the GI Tract • Can be a Spectrum of Dysregulation • Compensative Mechanisms 23 Allostasis: The Problem • Modern day stress response and reaction occurs an estimated 60 times per day – stress is persistent! • No fight, no flight, no turn off • NO RECOVERY PERIOD! No Recovery Stress Event Nutrients used Hormones Released Body Responds 24 Hormone Synthesis Pathway 25 Candida and Thyroid Dysregulation • Candida receptor sites can bind thyroxine and render it physiologically unavailable • Candida is associated with zinc deficiency • Damage to the thyroid gland form candidainduced free radical activity and auto-immunity is possible 26 Thyroid Anchor Points • Thyroid function is a relay race • Regulates aerobic and anaerobic metabolism of every cell in the body • Proper gut flora required for peripheral conversion • Nutrient dependent 27 Intestinal Permeability Issues • Catastrophic permeability defects are usually only triggered by serious insults (i.e., trauma, burns, and sepsis) • However, a low-level, chronic version of this gut permeability problem may also occur = "leaky gut syndrome“ • LGS is increasingly suspected as an underlying contributor to chronic autoimmune and other diseases – IBS – Allergy – Asthma 28 Constituents of the Intestine 29 Diabetes 2008 ;57:2555–62. Gut Permeability and Inflammation A Vicious Cycle • Diet • Lifestyle • Disease • Dysbiosis • Diet • Environment • Dysbiosis Release of cytokines Local and systemic inflamma0on An0gens and endotoxins exposure • Chronic disease • Injury • Allergy • Environment Increased gut permeability Increased intes0nal absorp0on of an0gens and endotoxins • Injury (e.g., burns) • Endotoxin • Environment 30 GI Permeability A Potential Cause of Autoimmune Disease Immune reaction forms against antigen T Cell B Cell Enzymes An0gen Enzy m es Enzy An0gen Enzy mes mes An0gen Leaky gut Enzymes GI mucosa inflammation leads to “leaky gut,” which allows transmigration of antigen 31 Abnormal Bowel Permeability and Inflammation • Stimulates classic hypersensitivity response • Causes “non-specific” activation of inflammatory pathways – IL6 – IL1 – TNF alpha 32 GI Permeability A Potential Cause of Vasomotor Symptoms • TNF Alpha produced mainly by macrophages, principle cytokine that mediates acute inflammation • Stimulates inflammation in the endothelial tissue cells, helps WBC migrate into the tissue space, helps macrophages secrete IL1 and PGE2, • Creates diapedesis ‘’’HOT FLASH’’’ 33 GI Dysfunction The Overburdened Liver • Over ½ gallon of blood/min • Performs over 500 functions – Master organ of metabolism (blood sugar, fats, vitamins, steroid hormones) – Metabolizes alcohol; breaks down medications – Maintains thousands of internal enzyme systems • Produces 500-1000 ml (≤1 quart) of bile per day • Increases Beta Glucuronidase, decrease in estrogen metabolism • Causes – Toxic exposure – Poor digestion compromising liver • Bacterial overgrowth impact on liver – Diet 34 Pathway to Healing Restore Healthy Digestion – Lifestyle • Food choices – Quality – Quantity • Dietary practices – Relax/focus • Blood flow to GI tract • Cephalic stage of digestion – Chewing • Mechanical breakdown • Chemical breakdown (saliva) • Relaxes lower stomach 35 Pathway to Healing Restore Healthy Digestion – Enzymes • Digestive enzymes break food down into smaller, absorbable components • Enzymes are produced by the body and present in food: – Metabolic – Pancreatic – Plant/fungal based • However… – Production declines with age • e.g., amylase – Decline in food quality/enzyme intake from food – Culinary habits (enzymes destroyed through cooking) 36 Acid-Stable Enzymes • Pure Plant Enzymes – also called fungal or microbial enzymes • Acid-Stable – Not inactivated in gastric environment – Offer digestive support in both acid and alkaline conditions • Unlike pancreatic enzymes, effective in patients with pH imbalances Human DigesXon and AbsorpXon. In: Wardlaw GM, Hampl JS. Perspec.ves In Nutri.on. New York, NY: McGraw‐Hill; 2007:79‐109. 37 DigesXon and AbsorpXon. In: Grodner M, Anderson SL, DeYoung S, ed. Founda.ons and Clinical Applica.ons of Nutri.on: A Nursing Approach. 2nd ed. St. Louis, MO: Mosby; 2000:149. Pathway to Healing Evidenced based Botanical Intestinal Support CLINICALLY STUDIED FOR EFFICACY IN YEAST BALANCE • Pau D’Arco (Tabebuia impetiginosa) Bark 300 mg/d • Undecylenic Acid (as calcium undecylenate) 300 mg/d • Caprylic Acid (as calcium, magnesium, and zinc caprylate complex) 225 mg/d ADDITIONAL SUPPORTIVE INGREDIENTS INCLUDE: • Vitamin A (as natural beta-carotene and mixed carotenoids) 1,500 IU/d • Zinc (as zinc caprylate complex) 1 mg/d • Grapefruit Fruit (Citrus paradisi) Extract 40:1 75 mg/d • L-Glutamic Acid HCI 150 mg/d • Calcium (as calcium carbonate, undecylanate, and caprylate complex)300 mg/d • Rosemary (Rosmarinus officinalis) 4:1 4.5 mg/d • Thyme (Thymus vulgaris) Aerial Parts Oil Extract 4:1 4.5 mg/d 38 Pathway to Healing Re-Establishing Normal Flora • Lactobacilli, Bifidobacteria and other bacteria are integral to healthy GI function and balance – Produce important enzymes, nutrients, antimicrobial substances, help to maintain immune function, luminal pH and resistance to pathogens (e.g., Candida) – Support of body’s natural detoxification processes – Improved digestion and nutrient absorption by improving gut barrier health – Regulation of peristalsis; improved bowel function – Improved cardiovascular health (cholesterollowering effects) 39 Pathway to Healing Resolving Dysbiosis • Probiotics are antagonistic to Candida albicans and other yeast organisms – Development of yeast infections associated with low lactobacilli population in vagina and intestines • Probiotics decrease intestinal inflammation and enhance mucosal integrity – Normalizes gut permeability • Probiotics modulate systemic immune activity 40 Viability of Commercial Preparations • Studies have shown low viability of Lactobacilli and Bifidobacteria in unprotected commercial preparations • Inspect the label – CFU = colony forming units – High number of CFU does not necessarily indicate a better or more effective product – Evaluate genus and species for appropriate applications – Number of CFUs should be based on expiration date, not on ‘date of manufacture’ Immunol Cell Biol. 2000 Feb;78(1):80‐8. J Dairy Sci. 2000 Apr;83(4):894‐907. Curr Issues Intest Microbiol. 2004 Mar;5(1):1‐8. 41 Pathway to Healing Rebuilding Intestinal Mucosa TARGETED INTESTINAL MUCOSAL SUPPORT: • L-glutamine 750–1,500 mg/d • N-acetyl-D-glucosamine (NAG) 375–750 mg/d • Phosphatidylcholine 75–150 mg/d • Gamma-linolenic acid (GLA) 200–400 mg/d TARGETED GASTRIC MUCOSAL SUPPORT: • Deglycyrrhizinated licorice (DGL) 400 mg QD to TID – Chewable form preferred – Take before meals 42 Nat Med J 2010 March;2(3):14–23. Pathway to Healing Protecting Intestinal Mucosa ANTIOXIDANT SUPPORT • Quercetin 400-800 mg/d • Ginkgo biloba (24% ginkgo flavone glycosides) 40–80 mg/d • Vitamin C 1,000–2,000 mg/d • Vitamin E 200–400 mg/d • N-acetyl-L-cysteine (NAC) 150–300 mg/d • Zinc 45–90 mg/d – Consider copper supplementation at 0.75–1.5 mg to accompany zinc intake 43 Nat Med J 2010;2:14–23. Pathway to Healing Removing Intestinal Toxins/Supporting the Liver • Xenobiotic burden is now unprecedented in human history • Endocrine disruptors linked to hormone-related conditions, autoimmune disease, cancer, etc. Common Hormone Disrupters Dioxins Solvents PesXcides Phthalates Polychlorinated biphenyl’s (PCB’s) Parabens Heavy metals Bisphenol‐A • Healthy diet is no longer adequate protection • Detoxification regimens can be simple or complex 44 Detoxication Factors Glutathione, NAC, CoQ10, Vitamins C and E, Selenium, QuerceXn, Milk Thistle Glutathione, NAC, Vitamin B12 and Folic Acid, Glycine, Glutamine, Taurine, Calcium D‐Glucarate 45 Pathway to Healing Assisting Estrogen Metabolism: Calcium D-Glucarate (CDG) • Calcium salt of D-glucaric acid naturally found in fruits and vegetables • Works in intestinal tract • Involved in estrogen removal • Inhibits beta-glucoronidase enzyme • Reduces the number of estrogen receptor sites • Toxins and estrogens bound for excretion stay bound 46 CDG Mechanism of Action Glucuronic Acid ExcreXon + TOXIN Congugates (or binds) toxins and estrogens for eliminaXon CDG Beta Glucuronidase Inhibits β‐ Glucuronidase acXvity Reverses congugaXon (releases toxins) 47 Decreasing Allostatic Load Controlling Cortisol • Effective Cortisol lowering – within 24 hours – Ashwagandha – stress resistance – L-Theanine – relaxation – Magnolia – anti-anxiety – Epimedium – neuroprotection – Phosphatidylserine – cortisol management • Maintaining healthy cortisol levels • Stress reduction and sleep improvement 48 An open label pilot study of the safety and effecXveness of a corXsol‐reducing combinaXon in healthy adults. 2006. Unpublished. Decreasing Allostatic Load Lavender Oil • Clinically studied • Effective anxiety relief without common side effects from alternatives • Non-habit forming • Convenient, once daily dosing 49 Lavender Oil HAMA = Hamilton Anxiety Scale 50 Safe, Natural Symptom Relief • Isopropanolic Black Cohosh extract – Over 90 published scientific papers and presentations on efficacy and safety – Clinical research findings: • Up to 70% reduction in menopause symptoms after 12 weeks of use – Hot flashes, night sweats, sleep disturbances, mood swings • In one study, women experienced a 50% or more reduction in daily hot flashes after four weeks of use • Particularly effective for women in early stages of menopause Liske. J Women Health Gend Based Med 2002 Mar;11(2):163‐74. Pockaj BA et al. Cancer Invest. 2004;22:515–21. 51 Black Cohosh – Proven Safety • Initially considered a phytoestrogen – Proven Untrue • Now thought to act as selective estrogen receptor modifier – Acts like estrogen in brain, bone and vaginal tissue – Does NOT act like estrogen in breast or uterine tissue • In cell studies, did not promote growth of breast cancer cells • Used safely in short-term studies by women with a history breast cancer and women using tamoxifen or raloxifene • Does not increase breast density or risk of breast cancer reoccurrence1,2 • Does not impact liver function (no liver toxicity)3 • No significant adverse effects Zepelin HH, et al. Int J Clin Pharmacol Ther. 2007;45(3):143‐54. Hirschberg AL, et al. Menopause. 2006;14(1):1‐8. Naser B, et al. Menopause. 2011;18(4): 1‐10. 52 Additional Information • 11 lb weight gain in last 2 years • Chronic post nasal drip • Alternating constipation/diarrhea, gas/boating • Occasional gastroesphageal reflux • Unexplained/undiagnosed occasional skin rash ___Past Medical History__ • Chronic sinus infections with antibiotic use • MVA in 1987 with whiplash tx with PT __ Family History__ • Negative 53 Additional Information • G3 P3 • Medication: occasional OTC sleep aid • Supplements: occasional “one-a-day” • Exercise: “used to” but currently none • Diet: SAD with heavy dairy “I love cheese” • Alcohol: 2-4 times per week, every weekend • Caffeine: two cups in the morning “to get going” • Stress: Increased with “full time mom” vocation __Physical Exam__ • Iris contraction test --- + • BP: 100/62 • Slight ankle swelling 54 Assessment 1. Suspected HPA axis dysregulation 2. Suspected dysbiosis and subsequent permeability issues -CDSA: revealed dysbiosis, positive growth of Citrobacter diversus, Candida albicans, non-Candida strains (dubliniensis) No growth of Lactobacilli, low growth Bifidobacteria , elevated Beta-Glucaronidase and putrefactive SCFA -Intestinal Permeability Assessment: elevated lactulose/ mannitol ratio -Vitamin D: 24 55 Management • Diet and Lifestyle – BTD & Intentional Movement, dcr etoh & caff. • Safe, Natural Symptom Relief & Sleep Restoration – Black Cohosh – Lavendar Oil – Cortisol Managing Formula • 5 R’s! – Remove irritants – Reinoculate with proper flora – Replenish nutrients & antioxidant support/enzyme – Repair the gut lining – Restore normal function the liver 56 Outcome • 6 Week follow up: – Increase ability to fall asleep at night with less stress during the day “fuse is longer” – Decrease in the incidence of hot flashes and digestive disturbance, continued diarrhea – Lost 6 lbs, feeling more energetic • 3 Month follow up: – Felt “remarkably better” – Absence of vasomotor symptoms – At an ideal weight – Healthy bowel movements – Hair filling in – “Happy again” 57 Conclusion ~~ Digestion has EVERYTHING to do with “hormones”…..and then some~~! Thank You! 58