INTRODUCTION TO ENDOBIOGENY: AN INTEGRATIVE APPROACH TO MEDICINE

1. INTRODUCTION TO ENDOBIOGENY:AN INTEGRATIVE APPROACH TO MEDICINE By: Jean Claude Lapraz, MD Kamyar M. Hedayat, MD

2. OBJECTIVES • Introduce Endobiogeny and its component elements: • Detailed history • Detailed physical exam • Classical labs and imaging studies • Biology of Functions • Integrative assessment, then… • Therapeutic strategy • Example: application of the concepts of Endobiogeny to the clinical condition of Polycystic Ovarian Syndrome (PCOS) • Discuss opportunities to learn the Endobiogenic method

3. Vignette • 23 year old female presents with 4 year history of oligomenorrhea, hirsutism, acne, failure to conceive, 30 pounds weight gain. • Laboratory studies reveal low-normal TSH, normal T3, T4, estradiol, dihydro-testosterone, androstenedione, but elevated fasting blood glucose. • Ultrasound of uterus, ovaries unremarkable • History suggests Polycystic Ovarian Disease, but endocrine, radiological studies are normal. Does this woman have an endocrine disorder or not?

4. Introduction An introduction to the Endobiogenic concept A brief review of the history of medicine and its schools of thought

5. Endobiogeny • The integrative study of the functional mechanisms of regulation of the organism in its basic structure during homeostasis as well as its functional response to internal and external stressors: • As a whole system • In its individual units of function • core metabolism • cell, tissue and organ • in and of themselves and in relationship to each other • Endobiogeny evaluates the qualitative and quantitative state of the human organism and its internal milieu.

6. EXAMPLE: QUANTITATIVE ASSESSMENT • Consider a car factory to be like the ovaries. Does the number of cars (amount of estrogen) produced tell you how efficiently the factory (ovaries) is functioning or how well the cars produced drive? • A quantitative assessment of productivity tells you how many cars are being produced (serum estrogen levels), but not how well those cars drive (endocrine and metabolic activity of estrogen). • For example, if the output of cars meets demand, but the gear shifter is faulty (altered estrogen-receptor binding), each car carries fewer people than its normal capacity due to decreased torque. In this case, more cars will be needed to carry people. • “Normal” factory output for this company (body) is insufficient to meet demand

7. EXAMPLE: QUALITATIVE ASSESSMENT • But what about a qualitative assessment? There may be supply issues—not enough steel available. The factory cannot produce cars without steel (cholesterol as a precursor to estrogen production) • Perhaps there are not enough workers on the assembly line (Follicle stimulating hormone) and the workers present are over-worked and will soon decline in productivity (pituitary stress). • Perhaps there are ample supplies and workers, but the manager is inefficient (hypothalamus) in managing the factory, not regulating supply and demand issues.

8. Example: Qualitative assessment • Perhaps the manager is efficient, but the workers do not always follow his directives (altered thresholds of responsiveness). • Thus, it is clear that both a quantitative and qualitative assessment of physiological and endocrine activity is necessary to properly understand disease and health.

9. Endocrine management • Thus, Endobiogeny views the endocrine system as the manager of the body, the controller of anabolism and catabolism—which is what life itself is at every level from the cell to the structure of the universe: • destruction and reconstruction • expansion and contraction • growth and apoptosis • birth and death

10. LEVELS OF MANAGEMENT IN THE BODY Internal terrain Neuro-transmitters Mind-Body Mental-Emotional Neuro-Endocrine Endobiogeny Cell receptors Standard Medicine Enzymes, co-factors, vitamins Functional Medicine External Terrain Environmental Medicine Toxins, Microbes, Metals

11. Philosophy • Endobiogeny integrates the rational and empirical schools of medicine with philosophy to create a single coherent system of medicine: • PHILOSOPHY: TheEndobiogenic approach begins with the ontology (reason for existence) of structures and physiology • This leads to a logical approach to understanding structural weaknesses in the organism as well as determining the true cause of disease

12. Rationalism • The rational school of medicine has been the predominant Western school of medicine: • Relies on deductive reasoning, anatomy and physiology as the basis of its approach to illness. • Nosology: Patients are categorized by disease, and diseases are categorized by symptoms • Medications are chosen based on biochemical or empirical effects on symptoms or physiological signs such as blood pressure or laboratory measurements • Biomedicine (Allopathy) is the best-known form of rational medicine • Modern herbalism has rationalist tendencies

13. Rationalism (cont.) • Endobiogeny is based upon: • Modern physiology and contemporary understanding of neuro-endocrinology • Consideration of role of genetic polymorphisms, environmental toxins, stress, cytokines, cells, organs, and their products of metabolism in the origins of health and illness. • Consideration that the organism contains in itself a fundamental auto-pathogenicity (potential for a specific disorder) which implies a particular risk of disease. • Endobiogeny considers the mechanistic, reductionistic concepts of life insufficient to explain the complexity of the human organism • Endobiogeny treats the person, not the disease, thus rejecting standardized treatment protocols

14. Empiricism • Refers to a system of medicine where the practitioner’s impression of illness and assessment of the individual’s expression of dysfunction is the basis of treatment. • Empirical medicine considers the energetics of the individual as well as the energetics of the treatment • Chinese medicine and Homeopathy are forms of empirical medicine.

15. Empiricism (cont.) • Endobiogeny shares an emphasis on detailed history and careful physical exam to understand the unique physical and emotional antecedents of disease and its physiognomic expressions in the individual • However, Endobiogeny seeks to find coherence in this information through physiological explanations • In sum, Endobiogeny is an integration that takes into account various levels of the individual: physical, emotional and mental, in their relationship with the endocrine management of the body and everything under its control with its regulatory mechanisms

16. Integration of data • Endobiogeny integrates: • History • Physical Exam • Laboratory data and imaging • To reach a conclusion regarding the current, dynamic physiological state of the individual in order to formulate a treatment strategy which addresses: • the identified imbalances individually • as well as in their relationship to other imbalances

17. Treatment Options • Endobiogenic treatments consist of various therapeutic elements based on their safety and efficacy with no prejudice to the origin of the treatment: • Phytotherapeutic elements • Homeopathic elements • Pharmaceuticals elements: reasoned usage based on severity of symptoms, of degree or lack of compensatory physiology. • Physical manipulations: craniosacral, myofascial, etc. • Diet and Nutrition • Trace elements • Stress modification, hydrotherapy, acupuncture, etc.

18. Individualized medicine • Endobiogeny is individualized medicine based on: • The patient’s symptomization of illness within the context of the global functioning of the organism • The physician’s determination of the signs of physiological and endocrine dysfunction • The physician’s objective assessment of endocrine relationships • The particular physical, physiological, psychological and emotional realities of the individual.

19. Conclusion • Endobiogenic treatment is determined by the totality of the person: • Static and dynamic aspects of the patient’s constitution • Etiology, ontology, and integration of symptoms • Adaptive and maladaptive aspects of physiology

20. The Endobiogenic Method

21. Patient history • HISTORY: A detailed history of antecedent events, including perinatal history, childhood personality, illnesses, vaccinations and important emotional events is solicited to establish the constitutional and functional endocrine state of the patient. • Dietary preferences, sleep habits, dreams, menstrual history, various aspects of behavior and review of systems are explored to establish neuro-endocrine patterns • The trajectory of structural hormonal imbalances is followed throughout life, not just with respect to the outward manifestation of illness and dysfunction

22. Physical Exam • A detailed physical exam from head to toe evaluates the phenotypic expression of neuro-endocrine relationships • Because the endocrine system manages both the structural integrity of the body as well as its functional expression, one is able to look for the phenotypic expressions of endocrine activity and correlate it with the internal state of the patient • Many of these findings are easily explained by classical endocrinological assessment of hormonal activity

23. Laboratory studies • Classical lab data is based on binary considerations: • disease vs. no disease • normal vs. abnormal value • The patient in our vignette presented with normal levels of all the relevant hormones. Can we conclude that these hormones are functioning normally, or even that their relative levels are appropriate? • Of course not. The history, symptoms and physical exam suggest otherwise. • Thus, it is self-evident that binary considerations cannot be applied with any real assurance of its functional relevance to a system as complex as the human body.

24. Laboratory studies • Biological systems are complex, multi-tiered, dynamic interrelated and integrated systems Yeast Protein Interaction Network Integrated, inter-related system Bader and Hogue (2002) Nature

25. Integrated systems • Objective quantitative data (laboratory values) are required to assess the organism • However, one must be able to provide functional descriptions of quantitative and qualitative activity both within a particular unit of activity, from one unit to another, as well as within the system as a whole • Only then can a truly dynamic and individualized assessment of the patient occur

26. Laboratory studies • The endocrine system, as the manager of the metabolic activity of the body, is the ideal object of evaluation. • Serum levels of hormones reflect neither the degree of stimulation needed nor the metabolic costs incurred in producing a particular hormone. • Raison CL, Miller AH. When not enough is too much: the role of insufficient glucocorticoid signaling in the pathophysiology of stress-related disorders. Am J Psychiatry. Sep 2003;160(9):1554-1565 • Chiam K, Tilley WD, Butler LM, Bianco-Miotto T. The dynamic and static modification of the epigenome by hormones: A role in the developmental origin of hormone related cancers. Biochem Biophys Acta. Apr 2009;1795(2):104-109. • Gerhard I, Waibel S, Daniel V, Runnebaum B. Impact of heavy metals on hormonal and immunological factors in women with repeated miscarriages. Hum Reprod Update. May-Jun 1998;4(3):301-309.

27. Laboratory studies • Serum levels of hormones only reflect quantitative organ output, not functional activity, which can be affected by: • Hormone receptor binding (affected by over- or under-expression of other hormones)1 • Intracellular messenger activity1 • Epigenetic changes2 • Heavy metal toxicity3, etc. • Raison CL, Miller AH. When not enough is too much: the role of insufficient glucocorticoid signaling in the pathophysiology of stress-related disorders. Am J Psychiatry. Sep 2003;160(9):1554-1565 • Chiam K, Tilley WD, Butler LM, Bianco-Miotto T. The dynamic and static modification of the epigenome by hormones: A role in the developmental origin of hormone related cancers. Biochem Biophys Acta. Apr 2009;1795(2):104-109. • Gerhard I, Waibel S, Daniel V, Runnebaum B. Impact of heavy metals on hormonal and immunological factors in women with repeated miscarriages. Hum Reprod Update. May-Jun 1998;4(3):301-309

28. Laboratory studies • The ideal system of measurement of biological processes thus should examine the metabolic products of hormonal management of cellular activity • Thus, the ideal laboratory system must • Reflect the complex, integrated and dynamic nature of biological systems • Describe the functionality of the system in its • Qualitative function • Quantitative function • Individual unit, relative to other units and as a whole • Assess the organism at the metabolic and interstitial level

29. Biology of functions • The Biology of Functions (BoF) quantifies functional abilities of the organism, before and after theeffects of adaptation to stressors. Because functionality is dynamic, a dynamic, integrated and evolutionary methodology must be used instead of static lab values • BoF is based on a number of specific indices defined by mathematical relations between commonly used blood analysis data • The algorithms that permit the calculation of these indices are based on the physiological relations that exist between the direct or indirect products of hormonal activity: cells, hormones or enzymes (eosinophils, TSH and LDH, for example).

30. Biology of Functions • These relations allow one to visualize the functioning of the organism at every level: maintenance of homeostasis, adaptation, recovery after aggression, immunity, etc. • Each function is quantified by an index, specified by a level of activity. The index expresses the actual activity of that function, both in and of itself and in relation to the metabolic and tissue needs of the organism. • The whole set of indices gives an evolutionary assessment of an individual body’s functionality, system by system, organ by organ.

31. Biology of functions • SUMMARY: Biology of Functions: • Allows one to determine: • Pathogenic tendencies of the organism • The stage of development and the degree of severity of a potential pathology (i.e. cancer, cardiac disease, degenerative neurological disease) • Can be used as a tool to track • the natural development of pathology • To derive a rational therapeutic treatment • To evaluate the efficacy of the treatment over time

32. Polycystic ovarian syndrome (PCOS) An Endobiogenic Approach

33. Beyond binary relationships • PCOS is a good example of how allopathic medicine is beginning to realize the importance of the qualitative relationship of hormones rather than quantitative ones in and of themselves. The following ratios have been found to be helpful in diagnosing PCOS: • Estradiol to Dihydro-testosterone ratio (Endocr Regul. 2008 Mar;42(1):13-6) • Glucose to Insulin ratio <4.5 (Endocrinol Metab Clin North Am. 1999 Jun; 28(2):397-408, vii.) • LH to FSH ratio >3 (Endocrinol Metab Clin North Am. 1997 Dec; 26(4):893-912.)

34. Where to proceed? • Despite a growing recognition that the binary nature of laboratory evaluations in not sufficient to understand the spectrum of disease expression, Allopathic medicine lacks an integrated assessment of ontology, etiology and treatment of physiological derangements • Case in point: Standard of care for PCOS is to treat each endocrino-metabolic derangement separately from each other without considering their inter-relationship • There is no explanation for why only 50% of PCOS patients are obese or why serum hormone levels may be normal despite physical exam findings suggesting otherwise, or why polycystic ovaries are not a sine qua non of PCOS

35. Reductionistic treatment plan • The allopathic treatment of PCOS consists of a piecemeal approach to inhibiting individual hormones with no concern for how it may affect the global functioning of the organism in its anabolic and catabolic activity • Hirsutism: spironolactone , oral contraceptives 1 • Menstrual irregularities: Oral contraceptives , metformin,pioglitazone, spironolactone • Hyperglycemia, Hyperinsulinemia: Metformin; pioglitazone • Infertility: clomiphene, letrozol, metformin, pioglitazone 1. Drug treatments for polycystic ovary syndrome. Radosh L . American Family Physician, April 15, 2009

36. Endobiogenic approach • The Endobiogenic approach considers the ontological role of all these endocrino-metabolic and tissular derangements as being linked to the body’s management of a fundamental structural or functional problem • Prolactin can be elevated during chronic stress • Hyperestrogenism is often an attempt to overcome Prolactin’s suppression of LH secretion of progesterone for ovulation

37. Endobiogenic approach • Hyperandrogenism: caused by DHEA from the adrenal gland, which is over-stimulated due to the stress state, and by testosterone from the ovaries due to LH excess, insulin excess, and/or increased theca cell enzyme activity.1 • Hypercholesterolemia with low HDL cholesterol: Cholesterol is the source of all sex hormones and corticosteroids, which are needed to make more and more testosterone, estrogen and progesterone. HDL removes cholesterol from tissues which would be counterproductive to the demand of the tissues for more cholesterol. • Hyperglycemia and hyperinsulinism reflect an attempt to meet the huge anabolic demands of the body with an appropriate amount of short term energy substrate • The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome • Nelson VL, Qin KN, Rosenfield RL, Wood JR, Penning TM, Legro RS, Strauss JF 3rd, McAllister JM. J Clin Endocrinol Metab. 2001 Dec;86(12):5925-33.

38. Biology of functions (BoF) • Endobiogenic approach to PCOS involves understanding the totality of endocrinologic, neurologic and metabolic disturbances in relationship to each other. • A few examples of the 157 indices of the biology of functions are discussed as relevant to PCOS • When interpreting the BoF, the endocrine system is understood in its • classical vertical activity (i.e. CRHACTH Cortisol), • horizontal activity (i.e. Dopamine CRH TRH Prolactin), and • radial activity (i.e. TRH Prolactin Insulin; Estrogen + Cortisol Luteinizing Hormone)

39. Categories of BoF • Hypothalamic and pituitary level assessment of responsiveness to stimulation and feedback: • -MSH/α-MSH • FSH #1 index • LH #1 index • Index of Estrogen-Somatotropic axis:

40. Biology of functions • Role of Adrenals vs. Gonads in producing androgens (Androgenic index) • Efficiency of FSH and LH in producing estrogens and androgens, respectively (Gonadotropic index) • Anabolic activity of estrogen (Quantative organo-tissular estrogen yield index) • Progesterone activity (Progesterone index)

41. Biology of Functions • The role of the Hypothalamic-Pituitary-Adrenal axis can be examined in various ways to understand the role of each endocrine gland in adaptive and maladaptive responses to stress • Circulating Cortisol Index • Aromatization of Estrogen Index • Adrenal cortex index

42. Biology of Functions • Role of the Somatotropic axis in general adaptation, maladaptation, and metabolic derangements can also be examined: • Prolactin index • Insulin index • Insulin resistance index • Growth Hormone (GH) growth score • Somatostatin index

43. Biology of Functions • Psychological factors contributing to stress can also be quantified • Global mental activity: Ketonic index • Internal dialogue: Adaptogenic index • Emotional etiology of stress response: Thyroid relaunching index adjusted

44. Clinical phytotherapy • Endobiogeny has developed a rational system of clinical phytotherapy based on clinical studies, empirical observations and traditional herbalism • Elevated Prolactin: Strawberry leaf (Fragaria vesca) mother tincture reduces pituitary and adrenal stress response through reduction of ACTH, TSH and Prolactin and aromatization of Adrenal androgens to estrogen • Elevated Androgens-Estrogen ratio: hops (Humulus lupulus) has estrogenic activity and inhibits LH, reducing total gonadal androgens1 1) Milligan SR, Kalita JC, Pocock V, et al. The endocrine activities of 8-prenylnaringenin and related hop (Humulus lupulus L.) flavonoids. J Clin Endocrinol Metab. Dec 2000;85(12):4912-4915.

45. Clinical phytotherapy • Clinical phytotherapy (cont.) • Estrogen activity: Chaste tree (Vitex agnus castus) is highly efficacious in its ability to alter receptor sensitivity to estrogen and modulate prolactin activity allowing for increased progesterone activity, restoring prospects for fertility1,2 • Insulin Resistance: Wolfberry (Lycium barbarum) as a fluid extract or bulk herb reduces insulin resistance3 • Liu J, Burdette JE, Sun Y, et al. Isolation of linoleic acid as an estrogenic compound from the fruits of Vitex agnus-castus L. (chaste-berry). Phytomedicine. Jan 2004;11(1):18-23.; • Loch EG, Selle H, Boblitz N. Treatment of premenstrual syndrome with a phytopharmaceutical formulation containing Vitex agnus castus. J Womens Health Gend Based Med. Apr 2000;9(3):315-320. • Zhao R, Li Q, Xiao B. Effect of Lycium barbarum polysaccharide on the improvement of insulin resistance in NIDDM rats. Yakugaku Zasshi. Dec 2005;125(12):981-988.

46. Other treatments • Nutritional support • Omegas 3 and 6 (cell wall stability, decreased inflammation, improved gonadotropic activity1) • Magnesium and Calcium (noradrenaline, acetylcholine production, activity and recycling) • B complex (management of stress) • Diet: low in inflammatory foods such as refined flours and sugar to reduce insulin secretion and insulin resistance, androgen activity2 • Stress relief: cognitive behavioral therapy, meditation, yoga, massage therapy, acupuncture • 1) Sidani M, Campbell J. Gynecology: select topics. Prim Care. Jun 2002;29(2):297-321, vi; 2) Smith R, Mann N, Makelainen H, Roper J, Braue A, Varigos G. A pilot study to determine the short-term effects of a low glycemic load diet on hormonal markers of acne: a nonrandomized, parallel, controlled feeding trial. Mol Nutr Food Res. Jun 2008;52(6):718-726.

47. Conclusions

48. Conclusions • Endobiogeny is the study of the internal milieu of the organism within itself and in its relationship with its environment, stressors, etc. from the standpoint of the endocrine system as the manager of human life • It combines in an integrative understanding: • a philosophical consideration of the ontology of structures and functions of the body, • a rational approach to understanding physiology • an empirical assessment of history and symptoms • utilization of a dynamic, integrative and integrated metabolic assessment of endocrine management of the organism called the “Biology of Functions” • an integrated assessment of all clinical data to obtain a precise understanding of maladaptive physiology • In order to create a rational, individualized treatment plan

49. Conclusions • The Biology of Functions is an algorithmic assessment of the qualitative and quantitative relationships of hormones in terms of metabolic activity from nuclear, cellular, tissue, organ and system-wide perspectives • The Biology of Functions allows for an objective, longitudinal assessment of the effects of therapy over time • Endobiogeny relies on phytotherapy, oligotherapy, and diet as well as lifestyle modification as its preferred methods of ameliorating physiological imbalances • It reserves the use of synthetic drugs for urgent cases, or when the body is not able to establish an equilibrium by the effects of functional regulation

50. Resources • To learn more about Endobiogeny: • Web: • Genearal information: • www.endobiogeny.com • Biology of Functions demonstration: • http://extranet.endobiogenics.com/en/