Deconstructing Modern Illness: Idiopathic or Iatrogenic?

Are we causing more illness than we are solving?

1. Deconstructing Modern Illness Idiopathic or Iatrogenic?

2. You did then what you knew how to do, And when you knew better, You did better. Maya Angelou

3. Core Principles Pregnancy is an opportunity to break cycles of bad health Reproduction should be viewed from a much broader and longer perspective. Dad’s health matters At least one year pre-conception – postpartum year Transgenerational – can’t undue sins of our parents and grandparents, but we can protect our children and grandchildren Everything is connected – a more holistic and systems approach to health Health is complicated , disease is individual, we have a lot to learn If the symptoms don’t fit Dx categories, trust your gut and figure out what is wrong

4. Introduction Who, what and why?

5. Who am I? Mom, wife, jock, researcher, writer, women’s health advocate Background in maternal health and hormones More recently, medication adverse reactions, nutrition and mitochondrial damage

6. What I Do Officially

7. What I Really Do 150,000+ monthly views 1200+ articles and growing 150 guest contributors/writers 18 PhDs, 5 MDs, 2 DPTs Thousands of comments Cause trouble.

8. Listen and Learn

9. And Try to Untangle The untanglible .

10. What I Have Learned Environment matters More than genetics Health and disease are both sudden and slow Thresholds and tipping points All about the mitochondria Mitochondria determine everything Everything we think we know is wrong.

11. Let the Deconstruction Begin. Do we know what we think we know?

12. “There is often something sinister about familiar concepts. The more familiar or ‘natural’ they appear, the less we wonder what they mean; but because they are widespread and well-known, we tend to act as if we know what we mean when we use them.” Devisch , I. & Murray , S., 2009. doi:10.1111/j.1365-2753.2009.01232.x Just because it i s f amiliar Doesn’t make it right or true.

13. Framing the conversation

14. Implications of idiopathy Everything we don’t understand is idiopathic Illness of unknown origin is random – we cannot know the causes We have no responsibility for randomness Choices/behaviors don’t matter No need to study Can only treat but never cure or prevent

15. Cancer is random? “ These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to ‘bad luck ,’ that is, random mutations arising during DNA replication in normal, noncancerous stem cells .” Tomasetti & Vogelstein 2015. Science, Vol . 347, Issue 6217, pp. 78-81 DOI: 10.1126/science.1260825

16. Randomness absolves us of responsibility

17. Randomness means we can ignore things like this

18. And this… Pharmaceutical and environmental chemicals rearrange MLL Gene via topoisomerase inhibition Glyphosate (and other herbicides/pesticides), fluoroquinolone antibiotics, hormonal contraceptives, HRT and other drugs Topoisomerases manage nDNA , mtDNA replication and repair. MLL- related leukemias are not heritable, not found in germlines, but a result of exposure in utero (infant leukemia)  or during later child development (pediatric leukemia ).

19. 25-75 % of the symptoms reported in outpatient settings are considered medically unexplained. How much of medicine is idiopathic? Source: Smith , R.C. and Dwamena , F.C., 2007. Classification and diagnosis of patients with medically unexplained symptoms. Journal of general internal medicine, 22(5), pp.685-691.

20. Idiopathy exists, not because this stuff is unknowable, but rather, because we choose not to look. Source: Smith , R.C. and Dwamena , F.C., 2007. Classification and diagnosis of patients with medically unexplained symptoms. Journal of general internal medicine, 22(5), pp.685-691.

21. 70% OF OB/GYN CLINCAL PRACTICE GUIDELINES NOT BASED ON EVIDENCE For women… Idiopathy runs rampant.

22. 50% OF MEDICAL INTERVENTIONS UNPROVEN ONLY 35% KNOWN TO BE BENEFICIAL Source: BMJ Clinical Evidence, http:// clinicalevidence.bmj.com/x/set/static/cms/efficacy-categorisations.html For medicine in general We really don’t know what we think we know.

23. Source: BMJ Clinical Evidence, http:// clinicalevidence.bmj.com/x/set/static/cms/efficacy-categorisations.html

24. Medication nation Mayo Clinic Reports 70% adults take prescription medications chronically 50% take 2 or more meds 20% take 5 or more meds “ Before the SSRIs, drugs were poisons that came with risks. Now they are fertilizers to be used as widely as possible, being given in ever larger amounts to children and the elderly - the only risks the authorities can see it would seem stem from not using enough of them .” David Healy

25. If only 50% of medications have sufficient evidence of efficacy, what happens when we combine multiple medications? Efficacy? Safety?

26. Can we really know what illnesses chronic polypharmacy use might spur if we’ve never bothered to ask the question?

27. If 25-75% of symptoms can be considered medically unexplained, how certain are we of our current diagnostics?

28. Maybe idiopathic is really iatrogenic?

29. The problem of iatrogenesis 3rd leading cause of death in hospitalized patients Estimated at 200,000-400,000 patients annually 6.8 % of cases were attributable to an adverse drug reaction 1964-1995 FDA/ADR data (2011) 2.1 to 2.7 million Americans suffer from an serious adverse drug reaction annually 128,000 result in death James, J.T., 2013. A new, evidence-based estimate of patient harms associated with hospital care. Journal of patient safety, 9(3), pp.122-128; Null , G., Dean, C., Feldman, M. and Rasio , D., 2005. Death by medicine. Journal of Orthomolecular Medicine, 20(1), pp.21-34; Makary , M.A. and Daniel, M., 2016. Medical error—the third leading cause of death in the US. Bmj , 353, p.i2139; Stokowski , L.A., 2016. Who believes that medical error is the third leading cause of hospital deaths. Medscape, May, 26Light, D.W., Lexchin , J. and Darrow, J.J., 2013. Institutional corruption of pharmaceuticals and the myth of safe and effective drugs; Light , D.W., Lexchin , J. and Darrow, J.J., 2013. Institutional corruption of pharmaceuticals and the myth of safe and effective drugs .. Even as currently defined.

30. Implications of iatrogenesis Presumes we know the scope of effects for a given treatment If 50% of treatments unproven, do we really know the scope of effects? Even when tested, often only tested in isolation, in men, with little application to real world uses Anything we don’t know is random or idiopathic We have no responsibility for randomness No need to study

31. Deconstructing Women’s Health Where idiopathy, iatrogenesis and willful ignorance intersect.

32. Women use more medications than men A review of insurance records for a 1 year period in 2010 showed: Women = 5 prescriptions Men = 3.7 prescriptions 68% of women versus 59% of men had one prescription for at least one medication for a chronic or acute condition during the study period.  Women’s Health 2012: The 20th Annual Congress ; https://www.washingtonpost.com/blogs/the-checkup/post/women-prescribed-more-drugs-than-men-but-dont-always-take-them-research-shows/2010/12/20/gIQAJm5hNS_blog.html?utm_term=.f913aa9f54a6

33. During Pregnancy 80% of women take at least one medication during pregnancy ~ 30% take 4 or more medications during pregnancy 60 % increase in medication use during pregnancy in 30 years

34. Most of these drugs were never safety tested with women No testing on drugs approved before 1993 Guidelines not enacted until 1998

35. Even after the regulations Per the GAO (2000) 52% of clinical trial participants women, mostly later phases Only 22% of early phase trials, where safety and dosing determined Per the IOM OWH (2010) Much the same

36. Here’s the thing Even though women are now allowed in clinical trials, there is no requirement for researchers/drug companies to determine whether women react differently than men to a medication before it is approved. So they don’t.

37. As a result Women suffer significantly more frequent and more severe adverse drug events Few notice because none of these reactions were documented in the first place Cardiovascular disease is the most common cause of death in American women and in recently recalled medications for heart disease there were disproportionately higher fatalities and serious adverse events in women than in men . – Cochrane Reports Idiopathic or iatrogenic?

38. Ethical conundrum Testing on women might impair reproductive capacity Medication use during pregnancy might harm the fetus BUT women use medications across the lifespan and during pregnancy If we’re not going to test, should we really be recommending these medications to women?

39. Possible solutions Animal testing Use meds only sparingly in pregnant women Intense post market surveillance Might temper some of the risks

40. What do human females and male rodents have in common? Apparently, they are equivalent.

41. Source: Beery , A., & Zucker , I. (2011). Sex Bias in Neuroscience and Biomedical Research.  Neuroscience and Biobehavioral Reviews, 35 (3) , 565-572 .; https://genderedinnovations.stanford.edu/case-studies/animals.html

42. No one considered Until 2014! that males and females might be different

43. Perhaps it’s not about ethics at all, but rather, expediency.

44. Long, inglorious history Used from 1957-1961 as anti-emetic, hyperemesis mostly in Europe 2000-100,000 children born with severely malformed limbs FDA denied approval Thalidomide - prescribed for morning sickness Of medicating women.

45. Diethylstilbestrol (DES) – to prevent miscarriage At least 3 generations affected: sons, daughters and grandchildren Without research 5-10 million women from 1940-1970s FDA approved, no research Late 50s-60s first research: increased risk of miscarriage Multi-generational damage (cancer, organ malformation, more) Used in farm animals Caused cancer in farm hands, miscarriage and illness in animals Banned in 1958 in animals Still used in women for another 20+ years

46. Or dubious research

47. For male satisfaction

48. And for social reasons 1959-1970s physicians and researchers from the Royal Children’s Hospital and the University of Melbourne gave adolescent girls of tall stature DES to stunt growth. The rationale behind treating tall girls was so they could do ballet, buy clothes more easily, and find boyfriends and husbands . Source : Lee & Howell , Tall girls: the social shaping of a medical therapy. Arch Pediatr Adolesc Med.  2006 Oct;160(10):1035-9 . When Being a Tall Girl was a Medical Condition: DES and the Tall Girls

49. And then covering it up Used as a pregnancy test 1960s-70s Equivalent to 13 morning after pills or 157 oral contraceptive pills January 1975, Dr William Inman, principal medical officer for the British Government, had found that women who took a hormone pregnancy test “had a five-to-one risk of giving birth to a child with malformations”. Dr Inman wrote to Primodos’s German manufacturer, Schering, so the firm could “take measures to avoid medico-legal problems”, rather than recall the drug. A later document explains that Dr Inman destroyed the materials on which his findings were based, “to prevent individual claims being based on his material” . Source : http ://www.telegraph.co.uk/news/2017/03/18/new-evidence-claims-against-pregnancy-test-drugs-linked-birth/

50. It’s worse for pregnant women There are no data for [insert vaccine] administered to pregnant women to inform vaccine-associated Package insert Available data on [insert vaccine] administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy. There were no developmental toxicity studies of [insert vaccine] performed in animals. It is not known whether [insert vaccine] is excreted in human milk. Data are not available to assess the effects of on the breastfed infant or on milk production/excretion . Despite all marketing to the contrary, most medications and vaccines were never tested for use during pregnancy. Source: Package inserts

51. We never learned With little evidence of safety and efficacy We continue to drug women

52. And for children Only 10-20% of medications for pediatric use have been tested in children Pharmacokinetic and pharmacodynamic research developed in adult males Rampant off-label for kids, particularly kids in foster care Sources: Conroy , S., McIntyre, J., Choonara , I., & Stephenson, T. (2000). Drug trials in children: problems and the way forward.  British Journal of Clinical Pharmacology ,  49 (2), 93–97. http://doi.org/10.1046/j.1365-2125.2000.00125.x ; FDA, https :// www.fda.gov/Drugs/ResourcesForYou/Consumers/ucm143565.htm ; http://pharmaceuticalcommerce.com/brand-marketing-communications/pediatric-drug-market-finds-its-own-pathway / “In the absence of rigorous pediatric clinical trial data, physicians are forced to act as if children are just ‘small adults’ with a smaller weight, and then interpret the adult data to adjust the dose. But statistically, we know that approach only works in 6% of the cases .”

53. We’re addicted Psychotropics prescribed in the US 274,000 infants (0-1 year olds) 370,000 toddlers (1-3 year olds) “Prescriptions of powerful antipsychotics such as Risperdal for infants and very young children have also sharply risen. Office visits for childhood bipolar disorder have risen 40-fold over the past decade in the U.S .” To solving problems with pills and looking away when problems arise.

54. If drugs are not tested in women or children and thus, their effects in women are unknown, they can easily be disregarded and labeled as idiopathic. If they are idiopathic, rather than iatrogenic, there is no need to investigate or even acknowledge side effects as real. For all intents and purposes, they simply do not exist.

55. For example Lupron – GnRHa Chemically castrates Developed for male prostate cancer Tested on 6 healthy men One low dose for a drug to be used repeatedly and chronically at higher doses Approved for Women with endometriosis, fibroids, heavy bleeding IVF Children with precocious puberty, gender dysphoria

56. Considered perfectly safe by many practitioners No recognition chemical castration might cause problems Depletes gonadal hormones Hormones have receptors everywhere and are involved with a myriad of functions beyond reproduction With very little research pre – or post-market, symptoms are considered idiopathic or hysteric.

57. It’s not safe Lupron damages the mitochondria, perhaps irrevocably.

58. How bad is it? Really bad.

59. Because we don’t recognize the possibility of ill-effects They effectively do not exist.

60. We are drowning in a sea of toxins

61. Environmental toxic soup “Unlike the current system in Europe, the 60,000-plus chemicals in production when the US’s TSCA took effect 39 years ago continued to be used without any safety reviews. Most are still in use today, although some have since filed toxicity data. The US allows the use of  many chemicals that are banned elsewhere , and its primary chemicals law has failed to keep up with thousands of chemicals currently in use, including the approximately 2,000  new chemicals introduced each year .” Source: https ://www.theguardian.com/lifeandstyle/2015/feb/13/us-senate-toxic-chemicals-law-health-safety Friday 13 February 2015 13.41 EST

62. That remain in our bodies Certain polychlorinated biphenyls, organochlorine pesticides, PFCs, phenols, PBDEs, phthalates, polycyclic aromatic hydrocarbons, and perchlorate were detected in 99–100% of pregnant women . The median number of detected chemicals by chemical class ranged from 4 of 12 PFCs to 9 of 13 phthalates. Across chemical classes, median number ranged from 8 of 17 chemical analytes to 50 of 71 chemical analytes . BPA and tOP were detected in 92.6% and 57.4% of the persons, respectively...Females had statistically higher BPA LSGM concentrations than males ( p = 0.043). Children had higher concentrations than adolescents ( p < 0.001), who in turn had higher concentrations than adults ( p = 0.003).

63. Affecting generations to come

64. What would normally filter the damage Has been compromised.

65. Maternal nutrient deficiency is rampant Oxidative stress caused by free radicals has been implicated in many studies of the etiology of preeclampsia ( 38 ). Because ascorbic acid and vitamin E inhibit free radical formation, a double-blind randomized trial was conducted in 283 women who had either a previous history of pregnancy complications or an abnormal ultrasound ( 39 ). The supplement provided 1000 mg ascorbic acid and 400 IU vitamin E daily from week 16–22 of pregnancy, and resulted in a 76% reduction in preeclampsia, and a 21% reduction in indicators of endothelial activation and placental dysfunction . Evidence from experimental animals supports the concept that in addition to primary deficiencies, secondary embryonic and fetal nutritional deficiencies can be caused by diverse factors including genetics, maternal disease, toxicant insults and physiological stressors that can trigger a maternal acute phase response. These secondary responses may be significant contributors to the occurrence of birth defects. An implication of the above is that the frequency and severity of pregnancy complications may be reduced through an improvement in the micronutrient status of the mother . Micronutrient status in fetal and early life may alter metabolism, vasculature, and organ growth and function, leading to increased risk of cardiometabolic disorders, adiposity, altered kidney function, and, ultimately, to type 2 diabetes and cardiovascular diseases.

66. The food we eat Isn’t really food High calorie malnutrition

67. It’s food like

68. We’re told it’s real food “ Everything nature can do, man can do so much better and more profitably .” ‘ Natural’ cheese that matures in 72 hours. Preservatives prevent produce browning And if we can’t, then re-define ‘Clean labeling’ removes the most glaring industrial ingredients and replaces them with substitutes that sound natural and benign . “For the salesman, this preparation was a technical triumph, a boon to caterers who would otherwise waste unsold food. There was a further benefit: NatureSeal is classed as a processing aid, not an ingredient, so there’s no need to declare it on the label, no obligation to tell consumers that their “fresh” fruit salad is weeks old . ” But it isn’t.

69. Industrial food production Highly processed food-like products Sugar, carbs, fats and chemicals Genetically culled produce 70% reduced nutrient content With no genetic variation ( 96%) Glyphosate, toxic adjuvants and more Chemically laden meats Heavy antibiotics, antibiotic resistant bacteria, growth and other hormones Has stripped our food of critical nutrients

70. It’s an industrial descaling agent Used to remove minerals from pipes Does the same in our bodies Blocks critical enzymes and amino acids Disrupts vitamin A metabolism Weakens the blood brain barrier Carcinogenic, mutagenic, teratogenic and an endocrine disruptor Topoisomerase inhibitor Glycine analog Mineral chelator Would kill all the plants if not genetically altered to withstand the toxin And a powerful antibiotic.

71. A perfect storm Of pharmaceutical and environmental toxicants.

72. But, cancer is random? And most women’s symptoms are psychosomatic – until they aren’t’.

73. Consequences The rise of random ill-health.

74. Suffering from a multitude of chronic illnesses

75. With generational effects

76. Increase in childhood illness 1-68 children develop autism Neurodevelopmental and behavioral problems on the rise 1 in 13 children food allergies 1 in 1000 – 10,000 children with autoimmune disorder (celiac, JA, TD1) JAMA Pediatr . 2013;167(2): 141-148; Psychiatry (Edgmont). Aug 2005; 2(8): 14–19 ; Arch Gen Psychiatry. 2012;69(12): 1247-1256 ; BMC Pediatrics 2013, 13:40  3 ; JAMA. 2014;311(17):1778-1786 . Idiopathic or random?

77. Something is not working Spend more healthcare Highly vaccinated Taking lots of meds That were never tested on over half the population Of those, only 50% considered effective Embrace environmental/industrial chemistry Living sicker With increasingly complicated but ‘random’ diseases Dying younger

78. How can we reasonably assert Which health issues are idiopathic and which are caused by us?

79. Except in rare cases Most modern illness is iatrogenic – caused by us Our choices individually and collectively Diet, lifestyle, pharmaceutical and environmental decisions “I believe the collective denial of lifestyle disease is the reason cardiology is in an innovation rut. This denial is not active or overt. It is indolent and apathetic… This is how I see modern cardiology. Our tricks can no longer overcome eating too much and moving too little. We approach health but never get there. If you waddle, snore at night, and cannot see your toes while standing, how much will a statin or ACE inhibitor or even LCZ696 help?” Mandrola , J., 2015. Heart Disease and Lifestyle: Why Are Doctors in Denial? Medscape. http://www.medscape.com/viewarticle/837975 A hard truth that none of us wants to admit

80. Now what? Who cares whether we call it idiopathic or iatrogenic, how do we fix this mess?

81. Easy answer Stop eating food-like products looking for medical solutions to what are lifestyle issues Go back to basics What does your body need and is it getting it?

82. More complicated answer Find the root causes of illness and fix them Stop treating symptoms Learn the chemistry Become an expert in your/your family’s health Own your health Share what you learn with others Build the knowledge base Publish/post online if you can Entire model has to change.

83. What I have learned It’s all about the mitochondria. Feed them well and life will be good.

84. Mitochondria 1000-2000 per cell Fuel source for cells Convert food to ATP Sit at center of cell survival Sense and respond to all threats Masters at adapting to toxic environments – until they aren’t Seemingly endless repertoire of survival cascades Threshold and tipping points

85. But that’s not all they do Mitochondria control just about everything Energy Steroidogenesis Inflammatory and immune activation/deactivation Ca2+ homeostasis (cell excitotoxicity) Apoptosis/necrosis Damage at your own risk.

86. All they ask of us is to feed them well To get from food to ATP O2 (mitochondria need to breathe) Lots of nutrients >24 vitamins and minerals And not hurl too many poisons at them. Source: https ://www.invitehealth.com/ARTICLE-nutrition-and-fibromyalgia.html

87. Western diet = high calorie malnutrition. We don’t. Nutrient deficiency alone will damage mitochondria, evoke chronic and complicated illness and can lead to death.

88. All pharmaceutical, environmental, and industrial chemicals damage the mitochondria and deplete nutrients. But wait, there’s more…

89. Mitochondria are targets Sensors of cell danger

90. Poor nutrition, high toxic load Foundation from which most parents-to-be approach reproduction With the cascade of ill-health already in progress.

91. Net result “These are partial defects. Mitochondrial dysfunction doesn’t really cause anything, what it does is predisposes towards seemingly everything. It’s one of many risk factors in multifactorial disease. It can predispose towards epilepsy, chronic fatigue, and even autism, but it doesn’t do it alone. It does it in combination with other factors, which is why in a family with a single mutation going through the family, everyone in the family is affected in a different way. Because it predisposes for disease throughout the entire system .” Dr. Richard Boles, Geneticist Complicated disease processes that affect everything and don’t fit our neat little diagnostic categories.

92. How prevalent is mitochondrial disease or dysfunction? “Disorders of the mitochondrial respiratory chain affect at least 1 in 8000 of the population , making them among the most common genetically determined diseases.” Patrick Chinnery , Medical School, Newcastle upon Tyne. Prevalence is likely underestimated because functional mitochondrial damage is often overlooked and most mitochondrial deficits, especially those emerging later in life, remain undiagnosed. Not widely recognized 1 in 500

93. Energy is key Insufficient mitochondrial ATP Cells adapt alternative, less efficient energy pathways Cancer pathways or they die Mitochondria activate danger protocols and deactivate extraneous tasks Cells die, tissues die, organs die , and we die (sometimes slowly and painfully, sometimes quickly)

94. How important are nutrients Cells cannot ‘breathe’ without certain vitamins and minerals Thiamine and magnesium Nutrient deficiency causes cellular hypoxia No obstruction necessary Brain and heart most adversely effected

95. During pregnancy

96. Direct Mitochondrial membrane permeability changes Alter channel open times Activate death pathways Indirect Block critical nutrient co-factors for ATP Alters hormone activity (endocrine disruptors) Activate/deactivate critical transcription and repair proteins (epigenetics) Cycle of damage Toxic Exposures Medications, Vaccines, Environmental Cell death & disease

97. Cascade of ill health

98. Not just about mom mDNA passed from mom-child, But mitochondria rely on nuclear DNA to function (~90%) If Dad is unhealthy and nutrient deficient, dysfunctional mitochondria are possible in the offspring, even if mom is healthy Dad’s health matters too!

99. Long before conception The lifetime of unhealthy habits affect your mitochondria Mitochondria have memories Cleaning up a few months before conception is good but not good enough Should consider health of both parents at least a year before conception Health has to be considered

100. Nutrients minimize damage Nutrient deficiency maximizes damage.

101. All comes back to nutrients

102. Avoid the toxins Clean up the diet Feed the deficiencies

103. Idiopathy versus iatrogenesis When presented with complicated case, a disease process that doesn’t seem to fit into any one category Remove the notion of randomness/idiopathy Return the notion of responsibility Figure it out (together) Think mitochondria Ask What the patient needs to be healthy Are they getting it Fix it

104. Websites LucineHealthSciences.com I Business HormonesMatter.com I online journal, medication adverse events surveys Social Media Facebook pages: Hormones Matter, Lucine Women Community Twitter: @ chanatlucine , @ hormonesmatter Email : [email protected] or [email protected] How to find me