Homeopathy and the Microbiome a Key to Lyme and Other Chronic Diseases

Home , Heel (corporation), Homeopathic dilutions, Homeoprophylaxis

Homeopathy and the Microbiome A key to Lyme and other chronic diseases

Ronald D. Whitmont, MD, President, The American Institute of Homeopathy Clinical Assistant Professor, Family and Community Medicine New York Medical College

Discussion Goals

• The Human Microbiome • An Epidemic of Chronic Disease • Chronic Lyme Disease • Homeopathy

The Human Microbiome Microbiome

• An ecology of symbiosis • Synonymous with health • Damage leads to Dysbiosis • Dysbiosis triggers inflammation The Human Microbiome Project

• Launched in 2008 by the NIH • Multicenter Research Project • Genetic Sequencing Technology

http://www.hmpdacc.org/

The Human Microbiome Project

– Nasal passages – Oral cavity – Skin – Gastrointestinal tract – Urogenital tract

http://www.hmpdacc.org/

Ecological Complexity

Metagenomic studies reveal that the human microbiome is comprised of an exceedingly complex group of different ecological niches existing throughout the body

Nature. 2007 Oct 18; 449(7164): 804–810. The human microbiome project: exploring the microbial part of ourselves in a changing world. Turnbaugh PJ, Ley RE, Hamady M, et al. DOI: 10.1038/nature06244

The Supra-Organism

– A symbiotic group of human and microbial cells – Working collectively for the benefit of the whole

Medical Hypotheses. 74(2),2010:214215. The human superorganism – Of microbes and men. Sleator RD. (Ed) DOI: 10.1016/j.mehy.2009.08.047

The Supra-Organism

A collection of ecosystems dependent on: – Diversity – Balanced ecology – Symbiosis

Genome Biology 201314:R1. Biogeography of the ecosystems of the healthy human body. Zhou Y, Gao H, Mihindukulasuriya KA, et al. DOI: 10.1186/gb-2013-14-1-r1

The Human Microbiome

The microbial genome complements the human genome

Nature. 2007 Oct 18; 449(7164): 804–810. The human microbiome project: exploring the microbial part of ourselves in a changing world. Turnbaugh PJ, Ley RE, Hamady M, et al. DOI: 10.1038/nature06244

The Human Microbiome

Traits integral to: • Nutrition • Development • Immunity • Health

PLOS/One: June 13, 2012. Analyses of the Microbial Diversity across the Human Microbiome. Li K, Bihan M, Yooseph S, et al. DOI: 10.1371/journal.pone.0032118

The Human Microbiome

Regulates development and function of the immune system

Cell Host & Microbe. Control of Brain Development, Function, and Behavior by the Microbiome. Sampson TR, Mazmanian SK. DOI: 10.1016/j.chom.2015.04.011

Colonization

Begins in the placenta

Science Translational Med 21 May 2014;6(237): 237ra65 The Placenta Harbors a Unique Microbiome. Aagaard K, Ma J, Antony KM, et al. DOI: 10.1126/scitranslmed.3008599. Most Critical Period

Before birth until two years of life

Nutr.Reviews;65(6):259- 299. Perinatal and Neonatal Manipulation of the Intestinal Microbiome: a Note of Caution. Neu J. DOI: 10.1111/j.1753- 4887.2007.tb00305.x

Medications Damage the Microbiome

• Antibiotics, antifungals, antivirals • PPI’s • Glucocorticosteroids? Antihistamines? • SSRI’s? HRT? Chemotherapy? • Immunosuppressant's? Vaccines? Antibiotics

• Disrupt ecology of the microbiome • Alter microbiota via: – Overgrowth of resistant organisms – Inhibition and destruction of sensitive organisms

Science 2012; 336(6086):1255-1262. The Application of Ecological Theory Toward an Understanding of the Human Microbiome. Costello EK, Stagaman K, Dethlefsen L. DOI: 10.1126/science.1224203 Antibiotics

Promote fungal (viral?) overgrowth

Infect Immune 2004;72(9): 4996–5003. Role of Antibiotics and Fungal Microbiota in Driving Pulmonary Allergic Responses. Noverr MC, Noggle RM, Toews GB, et al. DOI: 10.1128/IAI.72.9.4996-5003.2004

Antibiotics and Asthma

Maternal antibiotic use in pregnancy associated with 89% increased risk of childhood asthma (p<0.0001)

Medscape Ob/Gyn Women’s Health November 27, 2016 Coverage from the American College of Allergy, Asthma & Immunology (ACAAI) 2016 Annual Scientific Meeting. http://www.medscape.com/viewarticle/872028?nlid=110951_25 81&src=WNL_mdplsnews_161202_mscpedit_obgy&uac=2427 86PX&spon=16&impID=1245995&faf=1

Asthma and Antibiotics in the First Year of Life

• 1-2 Courses  20% increased risk • 3-4 Courses  30% increased risk • > 4 Courses  50% increased risk

Chest 2007;131(6):1753-9. Increased risk of childhood asthma from antibiotic use in early life. Kozyrskyj AL, Ernst P, Becker AB. DOI: 10.1378/chest.06-3008

Asthma and Antibiotics in the First Year of Life

• Risk of asthma was highest in children receiving more than four courses of antibiotics • Broad-spectrum cephalosporin use was more common in these subpopulations of children

Chest. 2007;131(6):1753-9. Increased risk of childhood asthma from antibiotic use in early life. Kozyrskyj AL, Ernst P, Becker AB DOI: 10.1378/chest.06-3008

Antibiotics and Asthma

• Adjusted odds ratio of 4.05 if ABX used in 1st year of life • Adjusted odds ratio of 1.64 if ABX used after 1st year of life

Clinical & Experimental Allergy;29,(6)1999:766–771. Antibiotic use in early childhood and the development of asthma. Wickens, Pearce, Crane, et al. DOI: 10.1046/j.1365-2222.1999.00536.x

Over the past four decades, there has been a significant increase in allergy and asthma in westernized countries, which correlates with alterations in fecal microbiota (microflora) and widespread use of antibiotics

Infect Immune 2004;72(9): 4996–5003. Role of Antibiotics and Fungal Microbiota in Driving Pulmonary Allergic Responses. Noverr MC, Noggle RM, Toews GB, et al. DOI: 10.1128/IAI.72.9.4996-5003.2004

Pediatrics

Since 1980, the prevalence of many chronic diseases, including Asthma has nearly tripled

MMWR Surveillance for Asthma -- United States, 1960-1995 Mannino DM, Homa DM, Pertowski CA. https://www.cdc.gov/mmwr/preview/mmwrhtml/00052262.htm

Asthma • The leading cause of chronic illness in U.S. children • One of the fastest growing chronic conditions in developed nations

Population Reference Bureau. Childhood Asthma: A Growing American Epidemic Carlson JE, Stroebel C. http://www.prb.org/Publications/Articles/2001/ChildhoodAsthm aAGrowingAmericanEpidemic.aspx Asthma

Between 1980-1994: • The total number of affected children increased by 75% • In children younger than 4 years, it increased by 160%

Population Reference Bureau. Childhood Asthma: A Growing American Epidemic Carlson JE, Stroebel C. http://www.prb.org/Publications/Articles/2001/ChildhoodAsthmaAGrowingAmerica nEpidemic.aspx Antibiotics

Use in the first year of life associated with increased risks of asthma, rhino-conjunctivitis and eczema

J Allerg Clin Immunol 2009;124(5):982–989. Antibiotic use in infancy and symptoms of asthma, rhinoconjunctivitis, and eczema in children 6 and 7 years old: International Study of Asthma and Allergies in Childhood Phase III. Foliiaki S, Pearce N, Bjorksten B. DOI: 10.1016/j.jaci.2009.08.017

Pediatrics

The Incidence of skin and food allergies nearly doubled between 1997 - 2011.

NCHS Data Brief. Trends in Allergic Conditions Among Children: United States, 1997–2011. Jackson KD, Howie LD, Akinbami LJ. http://www.cdc.gov/nchs/data/databriefs/db121.pdf Allergies and the Microbiome

Studies using animal models of allergy have provided direct evidence that a robust microbiome provides protection against allergic responses

Encyclopedia of Immunobiology Microbiome and Allergy;5:336–345. Oxford: Academic Press, 2016. Esser-von Bierren J, Harris, N. DOI: 10.1016/B978-0-12-374279-7.16005-9

Allergies and the Microbiome

A lifestyle characterized by high standards of hygiene, overuse of antibiotics, and the consumption of highly processed foods is associated with a high incidence of allergic diseases

Encyclopedia of Immunobiology Microbiome and Allergy;5:336–345. Oxford: Academic Press, 2016. Esser-von Bierren J, Harris, N. DOI: 10.1016/B978-0-12-374279-7.16005-9

Atopy in Anthroposophically

Raised Children Lower Prevalence of atopy than in children from conventional families – Fewer vaccinations – Fewer antibiotics – Higher levels of probiotics in diet – More use of homeopathy

Lancet. 1999;353:1485-88. Atopy in children of families with an anthroposophic lifestyle. Alm JS, Swartz J, Lilja G, et al.

Diversity of Microbiome

“Diversity dictates the stability of ecosystems.”

Science 06 July 2007. Stability and Diversity of Ecosystems. Ives AR, Carpenter SR. Diversity in the Gut

Rich, balanced and diverse bacterial communities seem to be perceived as “self” and induce a quick maturation of the immune system and gut responses

Immunity; 41(1) 2014:152–165. Foxp3+ T Cells Regulate Immunoglobulin A Selection and Facilitate Diversification of Bacterial Species Responsible for Immune Homeostasis Kawamoto S, Maruya M, Kato LM. DOI: 10.1016/j.immuni.2014.05.016 Diversity in the Gut

Poor and unbalanced bacterial communities are apparently perceived as “non-self” and induce inflammatory responses aimed at eliminating it

Immunity; 41(1), 2014:152–165. Foxp3+ T Cells Regulate Immunoglobulin A Selection and Facilitate Diversification of Bacterial Species Responsible for Immune Homeostasis Kawamoto S, Maruya M, Kato LM. DOI: 10.1016/j.immuni.2014.05.016 Diversity in the Gut

• Diversity reduces inflammation • Lack of diversity (dysbiosis) triggers inflammation

• The opposite of Symbiosis • An ecological imbalance between organisms within the ecology of the microbiome • Inversely proportional to diversity

Altern Med Rev 2004;9(2):180-197. The Causes of Intestinal Dysbiosis: A Review. Hawrelak JA, Myers SP.

Dysbiosis

• Can occur anywhere on body • Triggers inflammation

Therapeutic Advances in Gastroenterology May 2013; 6(3):215-229. Microbial dysbiosis and colon carcinogenesis: could colon cancer be considered a bacteria-related disease? Sobhani I, Amiot A, Le Baleur Y.

Dysbiosis

• Acute: Triggers an adaptive immune inflammatory response

• Chronic: Drives chronic inflammatory disease

Gastroenterol Int. 1998;11:29-30. Antibiotic impact on intestinal microflora. Gismondo MR.

PPI’s and Microbiome

• Raise gastric pH • Alters GI microenvironment • Alters growth of organisms, including C. difficile

J Hosp Infect 2003;54(3):243–245. Proton pump inhibitors as a risk factor for Clostridium difficile diarrhoea. Cunningham R, Dale B, Undy B, et al. DOI: 10.1016/S0195-6701(03)00088-4

Maternal Exposure to PPI’s in Pregnancy and Asthma

• Danish Population Based Cohort • N= 197,060 • Adjusted odds ratio 1.41, (95% CI: 1.27–1.56)

Aliment Pharm Therapeut 2012;35(10):1190-1198. Prenatal exposure to acid- suppressive drugs and the risk of childhood asthma: a population-based Danish cohort study. Andersen ABT, Erichsen R, Farkas DK, et al. DOI: 10.1111/j.1365-2036.2012.05073.x

Diversity in the Gut

• Hookworm colonization reduces risk of asthma • 9 Studies • OR 0.50; 95% CI: 0.28–0.90

Am J Resp Crit Care Med. Vol. 174, No. 5 | Sep 01, 2006. Asthma and Current Intestinal Parasite Infection, Systematic Review and Meta-Analysis. Leonardi-Bee J, Pritchard D, Britton J, et al. DOI:10.1164/rccm.200603-331OC

Diversity in the Gut

Whipworm ova therapy induces remissions of active ulcerative colitis (UC)

Gastroenterology 2005; 128(4),:825–832. Trichuris suis therapy for active ulcerative colitis: A randomized controlled trial. Summers RW, Elliot DE, Urban JF. DOI: 10.1053/j.gastro.2005.01.005

Whipworm Therapy in UC

• Double Blinded Study • N=54 • 45% vs 17% Improvement

Gastroenterology 2005; 128(4),:825–832. Trichuris suis therapy for active ulcerative colitis: A randomized controlled trial. Summers RW, Elliot DE, Urban JF. DOI: 10.1053/j.gastro.2005.01.005

Malaria and Multiple Sclerosis

Eradication of malaria in an otherwise stable population induces the emergence of Multiple Sclerosis

Emerg Infect Dis. Program to eradicate malaria in Sardinia, 1946–1950. Tognotti E. 2009 Sep. http://wwwnc.cdc.gov/eid/article/15/9/08-1317 DOI: 10.3201/eid1509.081317.

Sardinia, Italy

Between 1946–1950, the Rockefeller Foundation conducted a large-scale Malaria eradication Project

Emerg Infect Dis. Program to eradicate malaria in Sardinia, 1946–1950. Tognotti E. 2009 Sep. http://wwwnc.cdc.gov/eid/article/15/9/08-1317 DOI: 10.3201/eid1509.081317.

Sardinia, Italy

267 metric tons of DDT were spread over the island which entirely eliminated Malaria

Emerg Infect Dis. Program to eradicate malaria in Sardinia, 1946–1950. Tognotti E. 2009 Sep. http://wwwnc.cdc.gov/eid/article/15/9/08-1317 DOI: 10.3201/eid1509.081317.

Incidence of Multiple Sclerosis, Sardinia, Italy

• Near zero prior to 1960 • 1.1/100,000 in 1965-69 • 5.8/100,000 in 1995-99

Neuroepidemiology. 2005;25(3):129-34. Increasing incidence of multiple sclerosis in the province of Sassari, northern Sardinia. Pugliatti M, Riise T, Sotgiu MA, et al. DOI: 10.1159/000086677

Incidence of Multiple Sclerosis, Sardinia, Italy

• 9.7/100,000 in 2003-07

Mult Scler 2011;17(11):1282-9. Epidemiology of multiple sclerosis in south-western Sardinia. Cocco E, Sardu C, Massa R, et al. DOI: 10.1177/1352458511408754

Current Prevalence of Multiple Sclerosis

• 224/100,000 in Sardinia • 90/100,000 in U.S.

PLOS One 2012; Population Based Study of 12 Autoimmune Diseases in Sardinia, Italy: Prevalence and Comorbidity. Sardu C, Cocco E, Mereu A. DOI: 10.1371/journal.pone.0032487

Sardinia, Italy

“A dramatically rapid change of the environment after the eradication of malaria has led the Sardinian immune system to abnormal responses… favoring increased MS incidence over the last four decades in Sardinia because of the eradication of malaria, 50 years ago.”

Medical Hypotheses 2008; 70(4):819-25. Hygiene hypothesis: Innate immunity, malaria and multiple sclerosis. Sotgiu S, Angius A, Embry A, et al. DOI: 10.1016/j.mehy.2006.10.069 Sardinia, Italy

Eliminating a stable/commensal parasite in the environment alters the microbiome and allows the phenotypic penetration of a disease of immune dysfunction

Medical Hypotheses 2008; 70(4):819-25. Hygiene hypothesis: Innate immunity, malaria and multiple sclerosis. Sotgiu S, Angius A, Embry A, et al. DOI: 10.1016/j.mehy.2006.10.069 Microbiome and Environment

Rapid environmental changes destabilize the microbiome, triggering dysbiosis and inflammation

EMBO Rep. 2012 Nov; 13(11): 968–970. The inflammation theory of Immunity; 41(1) 2014:152–165. Foxp3+ T Cells Regulate Immunoglobulin A Selection and Facilitate Diversification of Bacterial Species Responsible for Immune Homeostasis Kawamoto S, Maruya M, Kato LM. DOI: 10.1016/j.immuni.2014.05.016 Implications

The programming (and health) of both the innate and adaptive immune systems rely heavily on the diversity the microbiome and the environment

Cell 2005;122(1):107-18. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Mazmanian SK, Liu CH, Tzianabos AO. DOI: 10.1016/j.cell.2005.05.007.

“We’ve just spent the better part of a century doing our unwitting best to wreck the human- associated microbiota with a multifronted war on bacteria and a diet notably detrimental to its well-being.”

NYTimes Magazine. May 19, 2013:36-43,50,58-59. Some of My Best Friends are Bacteria. Pollan M.

“We have to stop looking at medicine as a war between invading pathogens and our bodies.”

New Yorker Magazine. Oct 22, 2012:39-39. Germs are Us. Interview with David A. Relman, Chief of Infectious Diseases VA Hospital Palo Alto, CA. Specter M. The germ theory of disease… is a gross “oversimplification”

The Lancet; 291(7551):1077-1081. Limitations of the Germ Theory. Stewart T, Path FC. DOI: 10.1016/S0140-6736(68)91425-6

Germ Theory

• Formulated before any knowledge of the microbiome • All about the eradication of micro-organisms; which is precisely what generates inflammation

The Lancet; 291(7551):1077-1081. Limitations of the Germ Theory. Stewart T, Path FC. DOI: 10.1016/S0140-6736(68)91425-6

Germ Theory

Ignores the role of ecological diversity in the microbiome as a foundation of health

Trends Ecol Evol 2011;26(4):202-9. New paradigms for the evolution of beneficial infections. Sachs JL, Essenberg CJ, Turcotte MM. DOI: 10.1016/j.tree.2011.01.010

Germ Theory

Neglects the benefits of infection: – Immune system maturation – Diversification of the microbiome – Appropriate inflammation – (Evolution of intracellular organelles)

Trends Ecol Evol 2011;26(4):202-9. New paradigms for the evolution of beneficial infections. Sachs JL, Essenberg CJ, Turcotte MM. DOI: 10.1016/j.tree.2011.01.010 “It goes against [Germ Theory] dogma to think that bacteria would make our immune systems function better... But the picture is getting very clear: the driving force behind the immune system are commensals.”

Scientific American. June 2012:37-43. The Ultimate Social Network. Ackerman J.

Infections

(bacterial, viral, fungal)

Challenge immune system and microbiome to develop: • Tolerance • Increase Diversity

Annu Rev Immunol. 2012; 30: 759–795. The Microbiome in Infectious Disease and Inflammation. Honda K, Littman DR DOI: 10.1146/annurev-immunol-020711-074937. Infections

Challenge immune system and microbiome to develop: • Immunity • Appropriate levels of inflammation

Annu Rev Immunol. 2012; 30: 759–795. The Microbiome in Infectious Disease and Inflammation. Honda K, Littman DR DOI: 10.1146/annurev-immunol-020711-074937. Implications

Without an ecologically diverse microbiome (impossible without an ecologically diverse environment), dysbiosis develops, and triggers inflammation

Cell 2005;122(1):107-18. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Mazmanian SK, Liu CH, Tzianabos AO. DOI: 10.1016/j.cell.2005.05.007.

Implications

Human health is directly linked to the diversity and stability of the microbiome, and by extension, to the environment

Cell 2005;122(1):107-18. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Mazmanian SK, Liu CH, Tzianabos AO. DOI: 10.1016/j.cell.2005.05.007.

-Review-

The Human Microbiome

• The Supra-Organism is part of a complex ecology between human, microbiome and environment

• Health is simply impossible when microbiome and environment are damaged

Chronic Disease

The Leading Cause of Death and Disability in the US

http://www.cdc.gov/chronicdisease/overview/

Chronic Disease “The great epidemic of our times, responsible for 75% of total health care costs and the majority of deaths in the US.”

Am J Med, 2015; 128(4):337–343 Health Care 2020: Reengineering Health Care Delivery to Combat Chronic Disease. Milani, RV, Lavie CJ. DOI: http://dx.doi.org/10.1016/j.amjmed.2014.10.047

Chronic Disease

• About half of all adults—117 million people—had one or more chronic health conditions in 2012 • 25% had two or more chronic health conditions

Prev Chronic Dis 2014;11:130389. Multiple chronic conditions among US adults: a 2012 update. Ward BW, Schiller JS, Goodman RA. DOI: 10.5888/pcd11.130389

Chronic Diseases

• Hypertension • coronary heart disease • Stroke • Diabetes • Cancer • Arthritis • Hepatitis • Kidneys disease • Asthma • COPD

Causes of Chronic Disease

-Lack of Physical Exercise -Hypertension -Hyperlipidemia -Poor Nutrition -Tobacco Use -Excessive Alcohol Use

www.cdc.gov/chronicdisease/overview/

Chronic Disease

Common denominator: inflammation

EMBO Rep. 2012 Nov; 13(11): 968–970. The inflammation theory of disease. The growing realization that chronic inflammation is crucial in many diseases opens new avenues for treatment. Hunter P. DOI: 10.1038/embor.2012.142 Chronic Disease

“Inflammation has long been a well-known symptom of many infectious diseases, but molecular and epidemiological research increasingly suggests that it is also intimately linked with a broad range of non- infectious diseases, perhaps even all of them.”

“It is becoming increasingly evident that the lack of exposure to a variety of microorganisms, especially during early life, may result in the development of diseases such as type 1 diabetes, asthma, allergies, celiac disease, inflammatory bowel disease and obesity.”

J Perinatology (2011) 31, S29–S34; The developing intestinal microbiome and its relationship to health and disease in the neonate. Torrazza RM, Neu J. DOI:10.1038/jp.2010.172.

Chronic Disease

“According to the ‘hygiene hypothesis’, the decreasing incidence of infections in western countries and more recently in developing countries is at the origin of the increasing incidence of both autoimmune and allergic diseases.”

Clin Exp Immunol. 2010 Apr; 160(1): 1–9. The ‘hygiene hypothesis’ for autoimmune and allergic diseases: an update. Okada H, Kuhn C, Feillet H, et al. DOI: 10.1111/j.1365-2249.2010.04139.x

There is growing evidence that dysbiosis of the gut microbiota is associated with the pathogenesis of both intestinal and extra- intestinal disorders.

Microbial Ecology in Health & Disease 2015, 26:26191 Dysbiosis of the gut microbiota in disease. Carding S, Verbeke K, Vipond DT, et al. DOI: 10.3402/mehd.v26.26191

• Intestinal disorders include inflammatory bowel disease, irritable bowel syndrome (IBS), and coeliac disease • Extra-intestinal disorders include allergy, asthma, metabolic syndrome, chronic fatigue, cardiovascular disease, autoimmune disorders, and obesity

Microbial Ecology in Health & Disease 2015, 26:26191 Dysbiosis of the gut microbiota in disease. Carding S, Verbeke K, Vipond DT, et al. DOI: 10.3402/mehd.v26.26191

Dysbiosis

Antibiotic use is the single most common and significant cause

Gastroenterol Int. 1998;11:29-30. Antibiotic impact on intestinal microflora. Gismondo MR.

-Review- Chronic Disease

• The leading cause of morbidity and mortality in the U.S. today • A state of chronic inflammation

-Review- Chronic Disease

• A result of damage to microbiome leading to dysbiosis and inflammation • An iatrogenically driven epidemic

Chronic Lyme Disease Chronic Lyme Disease

A chronic inflammatory condition, a form of chronic dysbiosis Chronic Lyme Disease

• A diagnosis often based solely on clinical judgment rather than on well-defined clinical criteria and validated laboratory studies • AKA: Post Lyme Disease Syndrome

N Engl J Med 2007;357:1422-1430. A Critical Appraisal of “Chronic Lyme Disease”. Feder HM, Johnson BJB, O'Connell S. DOI: 10.1056/NEJMra072023 Chronic Lyme Disease

A diagnostic term used in North America and Europe for patients with persistent pain, neurocognitive symptoms, fatigue, or all of these symptoms, with or without clinical or serologic evidence of previous early or late Lyme disease

N Engl J Med 2007;357:1422-1430. A Critical Appraisal of “Chronic Lyme Disease”. Feder HM, Johnson BJB, O'Connell S. DOI: 10.1056/NEJMra072023 Chronic Lyme Disease

Despite resolution of the objective manifestations of infection after antibiotic treatment of Lyme, a minority of patients develop fatigue, musculoskeletal pain, difficulties with concentration or short-term memory, or all of these symptoms.

N Engl J Med 2007;357:1422-1430. A Critical Appraisal of “Chronic Lyme Disease”. Feder HM, Johnson BJB, O'Connell S. DOI: 10.1056/NEJMra072023 Chronic Lyme Disease

Once the diagnosis is made, patients are commonly treated for months to years with multiple antimicrobial agents

N Engl J Med 2007;357:1422-1430. A Critical Appraisal of “Chronic Lyme Disease”. Feder HM, Johnson BJB, O'Connell S. DOI: 10.1056/NEJMra072023 Chronic Lyme Disease No significant difference found between clinical responses of patients who received intravenous and oral antibiotics for 90 days and those who received placebo

N Engl J Med 2001; 345:85-92. Two Controlled Trials of Antibiotic Treatment in Patients with Persistent Symptoms and a History of Lyme Disease. Klempner MS, Hu LT, Evans J, et al. DOI: 10.1056/NEJM200107123450202 Chronic Lyme Disease "IV ceftriaxone therapy results in short-term cognitive improvement for patients with post- treatment Lyme encephalopathy, but relapse in cognition occurs after the antibiotic is discontinued”

Neurology 2008; 70(13): 992-1003. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Fallon BA, Keilp JG, Corbera KM,et al. DOI: 10.1212/01.WNL.0000284604.61160.2d Chronic Lyme Disease "There is substantial risk, with little or no benefit, associated with additional antibiotic treatment for patients who have long-standing subjective symptoms after appropriate initial treatment for an episode of Lyme disease.”

N Engl J Med 2007;357:1422-1430. A Critical Appraisal of “Chronic Lyme Disease”. Feder HM, Johnson BJB, O'Connell S. DOI: 10.1056/NEJMra072023 Chronic Lyme Disease

Antibiotic therapy causes considerable harm to patients treated for chronic Lyme disease or post–Lyme disease symptoms

Clin Infect Dis 2006;43:1089-1134. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Wormser GP, Dattwyler RJ, Shapiro ED, et al. Antibiotics “Affect various host immune responses adversely… including leukocyte chemotaxis, lymphocyte and monocyte transformation, antibody production, phagocytosis, and the microbicidal action of polymorphonuclear leukocytes.”

Goodman and Gilman's The Pharmacological Basis of Therapeutics, 7th Edition. Gilman AG, Goodman LS, Rall TW, et al. MacMillan Publishing Co, N.Y.1985:1084. Antibiotics

Temporarily suppress acute inflammation via nonantimicrobial effects

Europ J Pharmacol.. Anti-inflammatory effects of macrolide antibiotics. Čulić O, Eraković V, Parnham MJ DOI: 10.1016/S0014-2999(01)01321-8

Antibiotics

Associated with increased risk of chronic inflammation, recurrent infections, and cancer

JAMA. 2004;291(7):827-835. Antibiotic Use in Relation to the Risk of Breast Cancer. Velicer CM, Heckbert SR, Lampe JW, et al. DOI:10.1001/jama.291.7.827

Antibiotics • Impair immune system • Alter the microbiome • Contribute to the development of dysbiosis • Promote chronic inflammation

Trends in Immunology;33(9), September 2012:459–466. Antibiotics, microbiota, and immune defense. Ubeda C, Pamer EG.

Chronic Lyme

Most cases of are remarkable for histories of repeated and prolonged overuse of antibiotics anteceding the acquisition of Lyme by many years, often beginning in early childhood

Clinical Observation: Whitmont, RD Chronic Lyme

Most cases demonstrate a downward spiral of worsening clinical impairment, directly proportional to the length (and spectrum) of antibiotic therapy

Clinical Observation: Whitmont, RD Chronic Lyme Disease Etiology?

– Chronic dysbiosis

-Review- Chronic Lyme Disease

• A diverse collection of symptoms • A chronic dysbiosis • Antibiotic administration worsens condition Dysbiosis “Solutions”

• Use more antibiotics? • Use probiotics, fecal transplants, etc.? • Suppress it with anti-inflammatory and disease modifying agents? • Shift paradigms…? Homeopathy Homeopathy • A 200 year old form of alternative Medicine • Currently used by more than 500 million worldwide • A form of Nanomedicine

Frontiers in Bioscience 2013;5(2):685-708. Adaptive network nanomedicine: an integrated model for homeopathic medicine. Bell I.

“Ironically, one of the most controversial systems of alternative medicine, homeopathy, could turn out to be one of the oldest and demonstrably safest forms of nanoparticle based treatment already used worldwide for infectious diseases.”

Eur J Integr Med 2013;5(2):126-40. Advances in Integrative Nanomedicine for Improving Infectious Disease Treatment in Public Health. Bell IR, Schwartz GE, Boyer NN, et al. DOI: 10.1016/j.eujim.2012.11.002

Homeopathy

Historically interpreted within a vitalistic and spiritual conceptual framework common in the 18th Century

The Organon of Medicine, 6th Ed. 1842. Hahnemann SC,

Homeopathy

A form of:

Adaptive Network Nanomedicine

Frontiers in Bioscience. Adaptive network nanomedicine: an integrated model for homeopathic medicine. 2013;5(2):685- 708. Bell I, Schwartz GE. Homeopathy Using Transmission Electron Microscopy (TEM), electron diffraction and chemical analysis by Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES), the presence of physical entities in extreme homeopathic dilutions, in the form of nanoparticles of the starting metals and their aggregates, has been confirmed

Homeopathy 2010;99(4):231-242. Extreme homeopathic dilutions retain starting materials: A nanoparticulate perspective. Chikramane PS, Suresh AK, Bellare JR, et al. DOI: 10.1016/j.homp.2010.05.006

Homeopathy Medicines in high potencies (30c and 200c) involving huge dilution factors (1060 and 10400 respectively) are many orders of magnitude greater than Avogadro’s number, and theoretically should not contain measurable remnants of the starting materials

Homeopathy 2010;99(4):231-242. Extreme homeopathic dilutions retain starting materials: A nanoparticulate perspective. Chikramane PS, Suresh AK, Bellare JR, et al. DOI: 10.1016/j.homp.2010.05.006

Homeopathy

Observable nanoparticle forms of source material (and silica) exist in all homeopathic potencies

Int J High Dilution Res. 2011;10:299-310. Homeopathy emerging as nanomedicine. Upadhyay RP, Nayak C. Nanoparticles

• Measure from 1-100 nm in diameter • Formed by: – Top-down milling from source material – Bottom-up self-assembly

Advanced Drug Delivery Rev 2011;63:427-40. Nanosizing for oral and parenteral drug delivery: a perspective on formulating poorly-water soluble compounds using wet media milling technology. Merisko-Liversidge E, Liversidge GG. Nanoparticles

Exhibit superior antioxidant properties than their respective bulk forms

J Agricult Food Chem 2012;60(21):5388-99. Antioxidant activities of curcumin and ascorbyl dipalmitate nanoparticles and their activities after incorporation into cellulose-based packaging films. Sonkaew P, Sane A, Suppakul P.

Nanoparticles

More effective drug delivery vehicles than conventional bulk form drugs • Reach selective targets more efficiently • Reduce total dosage needed • Cross Blood-Brain Barrier

Current Drug Deliv 2010;7:303-11. Nanoparticles: a promising therapeutic approach in atherosclerosis. Antoniades C, Psarros C, Tousoulis D, et al.

Nanomedicine

Distinct advantages: • Targets specific cells • Doses last longer • Therapeutic effects are magnified (up to 1000 times)

Autoimmunity 2009;42:368-72. Imaging inflammation in real time- future of nanoparticles. Hueber AJ, Stevenson R, Stokes RJ, et al. Nanoparticles

Multiple selective effects: • Apoptosis • Anti-inflammatory • Antioxidant • Immunomodulatory

PLoS ONE 2011 ;6e26684. PLGA, PLGA-TMC and TMC-TPP nanoparticles differentially modulate the outcome of nasal vaccination by inducing tolerance or enhancing humor immunity. Keijzer C, Slutter B, van der Zee R, et al. Nanoparticles

• Reduced side effects • Greater efficacy • Lower costs

Methods in Enzymology 2012;508:271-94. Nanotechnology as a promising strategy for alternative routes of insulin delivery. Reis CP, Damge C.

Nanoparticles • At high doses: – Trigger stronger pharmacological effects • At low doses: – Mobilize non-pharmacological, biological adaptation, hormesis and endogenous amplification mechanisms

Homeopathy, 99 (2010), pp. 231–242. Extreme homeopathic dilutions retain starting materials: a nanoparticulate perspective. Chikramane PS, Suresh AK, Bellare JR, et al. Nanomedicine • Supports the patient's adaptive networks leading to functional self reorganization as a biological network • Host expression of a more robust cellular defense system against infections and other stressors

European Journal of Integrative Medicine; 5(2):126–140. Advances in integrative nanomedicine for improving infectious disease treatment in public health. Bell IR, Schwartz GE, Boyer NN. DOI: 10.1016/j.eujim.2012.11.002.

Homeopathy • The world’s oldest form of clinical nanomedicine • Thousands of published case studies in worldwide database • Demonstrated effectiveness in a wide range of acute and chronic conditions Plasmodium infected Mice

Significant inhibitory effects on parasite multiplication in vivo

Homeopathy 2006;95:223-228. Effects of homeopathic medications Eupatorium perfoliatum and Arsenicum alabum on parasitemia of Plasmodium berghei-infected mice. Lira-Salazar G, Marines-Montiel E, Torres-Monzon J, et al. DOI: 10.1016/j.homp.2006.06.003

Antiviral Effects

• In vitro • Human pathogenic enveloped and non-enveloped RNA and DNA viruses

Can J Physiol Pharmacol 2007;85:1084-90. In vitro evaluation of the antiviral effects of the homeopathic preparation Gripp-Heel on selected respiratory viruses. Glatthaar-Saalmuller B. DOI: 10.1139/Y07-100

Antiviral Effects Significant reductions of infectivity in: – Human herpesvirus 1, Human adenovirus C serotype 5, Influenza A virus, Human respiratory syncytial virus, Human parainfluenza virus 3, Human rhinovirus B serotype 14, and Human coxsackievirus serotype A9

HIV/AIDS • A group of studies found specific physical, immunologic, neurologic, metabolic, and quality-of-life benefits, including improvements in lymphocyte counts and functions and reductions in HIV viral loads in HIV/AIDS.

J Alternat Complement Med 2003;9:133-41. Controlled clinical trials evaluating the homeopathic treatment of people with human immunodeficiency virus or acquired immune deficiency syndrome. Ullman D. DOI: 10.1089/107555303321223008

Leptospirosis

• Homeoprophylaxis prepared from dilutions of four circulating strains of Leptospirosis • N=2.3 million in high risk epidemic region

Homeopathy 2010;99:156-66. Large-scale application of highly-diluted bacteria for Leptospirosis epidemic control. Bracho G, Varela E, Fernandez R, et al. DOI: 10.1016/j.homp.2010.05.009

Leptospirosis • Significant decrease of disease incidence found in intervention regions • Increased incidence observed in non-intervention regions • Intervention region incidence fell below historic median

Homeopathy 2010;99:156-66. Large-scale application of highly- diluted bacteria for Leptospirosis epidemic control. Bracho G, Varela E, Fernandez R, et al. DOI: 10.1016/j.homp.2010.05.009

Chronic Disease

• 24 month follow-up • N=3981 • 97% Chronic Disease

BMC Public Health 2005;5:115-122. Homeopathic medical practice: Long-term results of a cohort study with 3. Witt CM, Lüdtke R, Baur R, et al. DOI:10.1186/1471-2458-5-115 981 patients. Chronic Disease • Disease severity decreased significantly (p < 0.001) • For adults and young children, major improvements were observed for quality of life • Younger age and more severe disease at baseline were factors predictive of better therapeutic success

BMC Public Health 2008;8:413-421. How healthy are chronically ill patients after eight years of homeopathic treatment? – Results from a long term observational study. Witt CM, Lüdtke R, Mengler N, et al. DOI:10.1186/1471-2458-8-413

Chronic Disease Most frequent diagnoses: – migraine, tension type headache, sleep disorders, depression, anxiety disorders, multiple eczemas, psoriasis, allergic dermatitis, allergic rhinitis, allergies, dysmenorrhea, multiple infections, hypertension, low back pain, asthma

Chronic Disease • Disease severity decreased significantly (p < 0.001) • Physical and mental quality of life sores increased considerably • Younger age, female gender and more severe disease at baseline were factors predictive of better therapeutic success

Homeopathy and the

Microbiome

“Homeopathic potencies are capable of completely altering the bacterial flora of the bowel, and this fact has been demonstrated in many hundreds of cases”

Br Hom J 1936;26:163-188. The Potentised Drug and its Action on the Bowel Flora. Paterson J.

Homeopathy and Lyme

Disease

The judicious use of the classical homeopathic method has proven itself clinically effective in preventing and treating illnesses like Lyme disease in all its clinical stages.

J Am Inst Homeopathy 1997;90(4) :186-198 Homeopathy and Lyme Disease. Whitmont RD.

Homeopathy and Lyme

Disease

Clinical experience demonstrates that the judicious use of homeopathic medicines applied through the Classical homeopathic approach is an excellent method of treating and curing Lyme disease.

J Am Inst Homeopathy 1997;90(4) :186-198 Homeopathy and Lyme Disease. Whitmont RD.

-Review- Homeopathy

• The oldest continuously utilized form of nanomedicine worldwide • Effective in a wide range of conditions including – Acute infections – Chronic inflammatory illness – Chronic Lyme Disease -Review- Homeopathy

Advantages: – Ecologically sustainable – Selective targeting – Compatible with microbiome – Ready to go! A Case Report of Chronic Lyme Disease Treated Homeopathically

Initial Consultation:

A 92-year-old Caucasian male retired physician presented with complaints of “Chronic Lyme Disease”

Main Symptoms

• Multiple tick bites over previous year • Living in Lyme endemic region

Main Symptoms

• Initial Rx: Doxycycline 100mg POBID for 28 days, followed by Cefdinir 600mg POQD for an additional 26 days

• Initial improvement in symptoms while being treated, followed by relapse and worsening symptoms shortly after discontinuing antibiotics

Main Symptoms

• Brain fog • Depression • Vertigo: Worse after rising in the morning • Nausea with intolerance of spices and fatty foods • Prefers warm environments, fresh air • “Clicking” in neck • Night sweats • Fatigue: “great effort” to do deskwork. Has not gone outdoors in previous 2 months • Generalized Weakness with lack of energy

Medical History

• Multiple urinary complaints including chronic urinary retention, hesitancy, incontinence, nocturia • Recent UTI treated with Ciprofloxacin • Life-long history of frequent recurrent antibiotic use (at “any sign” of cold or infection) • IBS • Gastroparesis

Medical History

• Chronic recurrent sinusitis treated repeatedly with antibiotics • Hiatal hernia • Osteopenia

Medical History

• Degenerative Disc Disease (DDD) of Spine • Prostate cancer s/p radiation and chemotherapy • Abdominal Aortic Aneurism (AAA)

Physical Examination

• Tall, thin, frail Caucasian male • Appeared older than stated age • Pectus excavatum • Pale skin • No apparent distress • Vital signs and physical examination otherwise unremarkable and noncontributory

Diagnostic Assessment

Antibiotic overuse and abuse with evidence of chronic dysbiosis manifesting as: • IBS • Chronic sinusitis • Chronic Lyme/Post Lyme Syndrome

Dysbiosis leading to chronic malabsorbtion and malnutrition contributing to: • Osteopenia • Fatigue

Therapeutic Intervention

• Classically Prescribed Homeopathic Medicine, 200c • One Single Dry Dose By Mouth

Classical Homeopathic

Prescribing • Depends on the total clinical pattern of biopsychosocial symptoms • Relies on: – Individual salience – State dependency in the host to elicit beneficial rather than adverse effects

Global Advan Health Med 2014;3(1):36-53. Integrative Nanomedicine: Treating Cancer with nanoscale natural products. Bell I, Sarter B, Koithan M, et al. 1 Month Follow-up

• “Doing much better” • Nausea is “mild”, worse in morning after rising, better by noon • Vertigo only “once in a while”, usually with nausea. • Still Feels head isn’t “level”, not “even-keeled” • Nocturia “improved”

Therapeutic Intervention

• Classically Prescribed Homeopathic Medicine, 200c • One Single Dry Dose By Mouth

3 Month Follow-up

• “Very pleased over last 6 weeks” • Gradual improvement in energy • No nausea • No GI distension • No recurrent sinusitis or UTI

3 Month Follow-up

• No vertigo • No Brain fog • No more urinary incontinence • Asks: “How do you discourage old friends from staying too long?”

1 Year Follow-up

• No recurrence of symptoms • No repetition of medicine • Feels strong and fit

• “I’m doing very well for 94. I have no complaints. If I continue how I am I will be very satisfied.”

-Conclusion- The Microbiome

• An ecology • Directly related to Health

-Conclusion- The Microbiome

Damaged by conventional medications, poor diet, and overuse of hygiene

-Conclusion- The Microbiome

• Damage results in dysbiosis • Dysbiosis triggers chronic inflammation

-Conclusion- Chronic Inflammatory Disease

An iatrogenic epidemic A direct consequence of the “Germ Theory” in practice

-Conclusion- Chronic Lyme Disease

A form of chronic dysbiosis

-Conclusion- Homeopathy

• A form of adaptive network nanomedicine • A 200 year+ track record • Demonstrated superior efficacy in treating and preventing chronic inflammatory disease

-Conclusion- Homeopathy

• Already in use worldwide • A time honored methodology of evaluation and prescription • Safe, effective and inexpensive when used according to established guidelines

-Conclusion- Homeopathy

In light of data from the microbiome, further investigation and use of homeopathy is definitely warranted

-Conclusion- Homeopathy

Demonstrates clinical effectiveness in chronic Lyme disease “Rather than rejecting the entire filed of homeopathy for its originally vitalistic interpretations, it is time for modern scientists to examine seriously the nanomedicine implications of Hahnemann’s empirical findings for integrative health care.”