Environmental Drivers of Chronic Disease Based on the report Environmental Threats to

1. Environmental Drivers of Chronic Disease Based on the report Environmental Threats to Healthy Aging by Jill Stein MD, Ted Schettler MD, MPH, Maria Valenti and Ben Rohrer 2010 Greater Boston Physicians for Social Responsibility (www.psr.org/Boston) and The Science and Environmental Health Network (www.sehn.org)

2. What We Will Cover Environmental factors are key drivers of many common chronic diseases Environmental factors alter key biological pathways leading to chronic disease Important environmental determinants of health include: Food system/nutrition and diet Toxic chemicals Built environment / physical activity Psychological & socioeconomic stress Examples of cross cutting solutions for healthy people & a healthy environment

3. Scope & Context of the Problem • A century of change in natural, built and social environments has causedmajor changes in the patterns and distribution of diseases. • We are seeing dramatic increases in chronic diseases, and at younger ages, many of which, such as diabetes, are themselves risk factors for dementia. • The over- 65 population will nearly double by 2030 to more than 71 million, sharply increasing the number of people at risk of chronic diseases of aging like Alzheimer’s and Parkinson’s diseases, among others. • Environmental factors play a key role in health across the lifespan. Thus they offer a major prevention opportunity.

4. The Changing Environment and Disease Patterns During the past century, human activity has altered virtually all aspects of the world’s ecosystems: Pervasive spread of synthetic chemicals; air and water pollution. Industrialized food supply. Destruction of critical natural habitats, stressing ecosystems. Climate change. How we live, eat, work, play and socialize have substantially changed: Built environments have increased social isolation for many people; reduced physical activity. Growing income gap increases disease risk. Diseases of civilization - obesity, diabetes, cardiovascular disease, hypertension.

5. Environment Drives Chronic Disease Chronic Disease Environmental Factors Altered Pathways • Western Disease Cluster • Diabetes • Obesity • Abnormal Lipids • Metabolic Syndrome • Cardiovascular Disease • Inflammation • Disrupted Insulin • Signaling • Oxidative Stress • Food system/Diet • Fossil Fuels • Socioeconomic Stress • Chemicals • Built Environment/ • Transportation Parkinson’s Alzheimer’s

6. Profound Public Health Impact Of Environmentally-Driven Western Disease Cluster • Obesity/overweight – 2/3 US adults, prevalence x2 in ~25 yrs http://www.cdc.gov/chronicdisease/resources/publications/AAG/obesity.htm • Pre/Diabetes – 40% US adults, prevalence DM ~x2 over 20 yrsCowie 09, http://apps.nccd.cdc.gov/DDTSTRS/default.aspx • Cardiovascular disease – still leading cause of death. Hypertension increasing. http://www.cdc.gov/nchs/FASTATS/lcod.htm, Hajjar 03 • Metabolic syndrome = early signs of other cluster diseases; 35% adults, ~55%>60 yrs Ford ES 05 • Alzheimer’s disease – ½ >84 yrs old, 5.3M Alzheimer’s Assoc.

7. Alzheimer’s Disease/dementia Not an inevitable feature of normal aging. Progressive impairment of memory and multiple other cognitive functions, severe enough to interfere with daily functioning. Expected to triple by mid-century to over 13 million. Likely caused by varying combinations of genetic and environmental factors. Annual costs in US over $150 billion.

8. Parkinson’s Disease Progressive movement disorder that includes tremors, stiffness, and slow movement. May lead to severe disability. Likely caused by variable combinations of genetic and environmental factors. About 50,000 new cases annually in US.* Prevalence in US expected to double by 2030.* *Due to the lack of registries and baseline data on Parkinson’s Disease, the figures used here are estimates.

9. Alzheimer’s and Parkinson’s Diseases Characterized by: abnormal protein deposits chronic inflammation abnormal oxidative stress Many neuroscientists are beginning to think of some neurodegenerative diseases along a continuum, without clearly distinct boundaries in clinical or pathological manifestations

10. Continuum of Age-Associated Cognitive Impairment

11. Environment Drives Chronic Disease Basic Principles • Early life experiences can influence later-life health and disease. • Multiple factors interact to influence health & disease. • Environmental factors can alter natural pathways which in turn can lead to chronic disease. • An ecological health framework considers the individual in the context of family, community, society and ecosystem.

12. Early life experiences can influence later-life health, disease Obesity, hypertension, Cardiovascular disease, diabetes Toxic exposures oxidative stress Alzheimer’s, dementia, Parkinson’s Low birth weight Aging begins at conception

13. Multiple Factors Interact to Influence Health & Disease nutrients builtenvironment disease stress chemicals energy

14. An ecological health framework considers the individual in the context of family, community, society, and ecosystem.

15. Environment Drives Chronic Disease Chronic Disease Environmental Factors Altered Pathways Mechanisms of Action • Inflammation • Disrupted Insulin Signaling • Oxidative Stress

16. CLASSICAL CONCEPTOF INFLAMMATION Defined by appearance. “Calor, dolor, rubor, tumor.” Heat, pain, redness, swelling. The New Concept of Inflammation Defined by microscopiccharacteristics & laboratory test: inflammatory cells & mediators “Atherosclerosis is an inflammatory disease.” (2) Ross, Russell. Atherosclerosis – An Inflammatory Disease. NEJM 1999, 340(2); 115-126.

18. Insulin Signaling = Normal Metabolism Insulin signaling • ↓blood sugar • ↓artery disease • ↓triglycerides

19. Disrupted Insulin Signaling = Inflammatory Metabolism Insulin signaling Inflammation Oxidative stress • ↑ blood sugar • ↑artery disease • ↑triglycerides

20. Environment Drives Chronic Disease Chronic Disease Environmental Factors Altered Pathways Food System/Diet

21. Novel Nutrients Are Pervasive, Promote Inflammatory Metabolism

22. What’s “Novel” in the Western Diet? mg/day % of calories from fat Years “Hypothetical scheme of fat, fatty acid (ω6, ω3, trans and total) intake (as percentage of calories from fat) and intake of vitamins E and C (mg/d). Data were extrapolated from cross-sectional analyses of contemporary hunter-gatherer populations and from longitudinal observations and their putative changes during the preceding 100 years [75].” From AP Simopoulos, The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomedicine & Pharmacotherapy 56 (2002) 365-379.

23. High Glycemic Carbohydrates Increase the Risk of Chronic Disease High glycemic carbohydrates break down quickly during digestion, rapidly releasing glucose (sugar) into the bloodstream. INSULINEMIC RESPONSE Δ Plasma Insulin,mg/dl Low glycemic food High glycemic food Time, mins

25. Properties of Fatty Acids Omega-3Omega-6Saturated FoodPerishable Durable Increased in SystemShort shelf life Processed foods factory farmedIncreased in Long shelf life animals pasture- fed animals ImmuneAnti-inflammatoryInflammatory & Inflammatory Properties Anti-inflammatory EvolutionaryRecent markedRecent markedRecent marked Contextdecline increaseincrease

26. Novel Nutrients Disrupt Insulin Signaling, Drive Inflammatory Metabolism ↓Omega-3, (↑Omega-6) Fructose Insulin signaling Inflammation Oxidative stress • ↑ blood sugar • ↑artery disease • ↑triglycerides Saturated fat ↓Antioxidants High Glycemic Carbohydrates

27. Increase risks saturated and trans fats high glycemic carbohydrates lack of fruits/vegetables/omega 3s excess omega 6s? Reduce risks fruits, vegetables omega 3s low glycemic carbohydrates Mediterranean diet Influence of Nutritionon Chronic Disease

28. Benefits of Mediterranean-Type Diet on Chronic Disease Risk Clinical intervention studies 70% ↓ heart attacks, cardiac death & total mortality DeLogeril 94 60%↓ cardiac events in CVD patients* Ornish 98 ~50% ↓ metabolic syndrome Esposito 04 39% ↓ in CRP Esposito 04 ↓insulin resistance Esposito 04 ↓ weight Esposito 04 Prospective observation studies 80% ↓ diabetes Martinez-Gonzalez 08 ~31% ↓ all-cause & cardiovascular mortality, 22% ↓ cancer mortality**calculated from Sofi 0873% Alzheimer’s mortalityScarmeas 07 25-30% ↓ Parkinson’s disease Gao 07 78% ↓ childhood asthma maternal diet Chatzi 08 *10% low fat, vegetarian diet + exercise, stress reduction **For every 2 point increase in adherence (on a 9 point scale), risk reductions were observed of 0.91 for all cause mortality, 0.91 for CV mortality, 0.94 for occurrence and mortality from neoplasm. To convey the implications of these findings, we have applied the risk reductions across a 9 point adherence scale to yield a calculated ~31% ↓ all-cause & CV mortality and a 22% ↓ in cancer mortality.

29. Benefits of Sustainably-Produced Food • Nutritional benefits: • Generally higher levels of vitamins, minerals and phytochemicals (often dependent on soil quality) • Higher Omega-3 content • Organic samples contained higher concentrations of polyphenols and antioxidants in 75% of the matched pairs representing those nutrients • Benefits for farm workers and communities: • Reduced exposure to pesticides

30. Environment Drives Chronic Disease Chronic Disease Environmental Factors Altered Pathways Toxic Chemicals Air pollution, Lead and other heavy metals, some Pesticides, Bisphenol A and other Endocrine Disruptors

32. Cumulative occupational exposure ↑ cognitive impairment Shih 2007 2x risk Parkinson’s Coon 2006 Cumulative community exposure ↑cognitive impairment Shih 2006 Up to 15 years cognitive aging Weisskopf 2004 Animal studies of early life exposure Late-life Alzheimer’s markers Basha 2005, Lahiri 2007 Lead

33. Parkinson’s Disease Human studies - 24/31 studies show ↑ risks for PD. (OR 1.6-7) Brown 2006 Animals - Rotenone & paraquatdamage dopaminergic neurons in striatal region of brain Uversky VN 2004 - Combinations of maneb and paraquat; prenatal exposure “primes” the brain, increasing adult susceptibility Cory-Slechta 2005 Cognitive decline/dementia Low level fungicides in vineyards 3.5x poor attention, memory Baldi 2001 Occupational exposure in men associated with 2x risk of developing AD Baldi 2003 Insulin Resistance, metabolic syndromeLee 2006, 2007, 2007 Some persistent pesticides show strong dose-response relation to insulin resistance and metabolic syndrome. Pesticides

34. Bisphenol A • Found in polycarbonate plastic, resins, sealants. • Exposures are nearly ubiquitous. • Endocrine disruptor, oxidative stress. • Causes fat accumulation & insulin resistance at low levels (animals). Alanso-Magdelena 2006, Wada 2007 • 3-fold ↑ Cardiovascular disease. Lang 2008 • 2-fold ↑ Insulin Resistance. Lang 2008 polycarbonate

35. Environmental Factors Disrupt Insulin Signaling, Drive Inflammatory Metabolism ↓Omega-3 Fructose Insulin signaling Inflammation ↓Antioxidants Oxidative stress • ↑ blood sugar • ↑artery disease • ↑triglycerides Saturated fat Lead, other heavy metals Some Pesticides Air Pollution Endocrine Disruptors - BPA, dioxins, PCBs, some pesticides High Glycemic Carbohydrates

36. Environment Drives Chronic Disease Chronic Disease Environmental Factors Altered Pathways Built Environment Physical Activity

37. Health Benefits of Physical Activity Reduced ongoing levels of oxidative stress and inflammatory burden. Brooks 2008, Attipoe 2008 Inversely associated with the risks of Alzheimer’s/dementia and cognitive decline. Rovio 2005 Subjects at risk for AD who walked 150 min. per week showed improvements in cognition while the control group showed no net change from baseline at 1.5 yrs. Lautenschlager 2008 Increasing physical activity at any age improves physical and emotional wellbeing.

38. Walkable Cities Projects Community Gardens Farmer’s Markets Rails to Trails Livable Communities Enhance Healthy Aging

39. Sustainable Food & Transportation Solutions:The Cuba Example Cuba- lost fossil fuels ↑biking, walking, local plant-based food ↑physical activity50% ↓obesity 50% ↓mortality: DM 51%, CVD 35%, stroke 20%, all cause 18% Franco M et al. Impact of Energy Intake, Physical Activity, and Population-wide Weight Loss on Cardiovascular Disease and Diabetes Mortality in Cuba, 1980-2005. AJE 166, 12; Sept. 19, 2007

40. Shortens post surgical recovery time, reduces need for pain medications. Ulrich ‘84 Attention deficits improve after a walk in the park. Effect = methylphenidate. Taylor ’08 Access to green space reduces the effect of poverty on mortality by ~50%. Mitchell ‘08 Green Space Reduces Stress, Mortality, Improves Cognitive Function

41. Environmental Factors Disrupt Insulin Signaling, Drive Inflammatory Metabolism ↓Omega-3 Fructose Insulin signaling Inflammation Oxidative stress • ↑ blood sugar • ↑artery disease • ↑triglycerides Saturated fat Obesity ↓Antioxidants Inactivity Lead, other heavy metals Air Pollution Some Pesticides Endocrine Disruptors - BPA, dioxins, PCBs, some pesticides High Glycemic Carbohydrates

42. Environment Drives Chronic Disease Chronic Disease Environmental Factors Altered Pathways Socio-Economic Stress Depression, poverty, violence, inadequate health care

43. Socioeconomic, Psychosocial Stressors • Stress, depression risk for CVD, ADSesso, Kario, Ownby • People with lower SE status are at risk for exposure to multiple environmental hazards ↑damage. • Lead + stress ↑cognitive impairment Glass 2009 • Lead + air pollution ↑CV autonomic dysfunction Park 2008

44. People who live in neighborhoods that lack social cohesion, sidewalks, or safety limit their exercise and have an increased risk of depression and possibly obesity. Berke EM 07, Molnar BE 04 Effects of the Built Environment on Health

45. Environmental Factors Disrupt Insulin Signaling, Drive Inflammatory Metabolism Fructose ↓Omega-3 Insulin signaling Inflammation Oxidative stress • ↑ blood sugar • ↑artery disease • ↑triglycerides Stress Saturated fat Obesity ↓Antioxidants Inactivity Lead, other heavy metals Air Pollution Some Pesticides Endocrine Disruptors - BPA, dioxins, PCBs, some pesticides High Glycemic Carbohydrates

46. Multiple Factors Interact to Influence Health & Disease

47. Environmental Factors Environmental Factors Drive Chronic Disease and the Climate Crisis Climate Crisis Heat, drought, storms, fires, ice sheet instability, sea level rise, loss of glacial irrigation, refugees, food insecurity/starvation, tropical diseases ↑ Greenhouse Gases Altered Biological Pathways Chronic Disease

48. SolutionsforHealthy People & A Healthy Planet

49. Major Illnesses Are PreventablePersonal Actions to Profoundly Reduce Risks Personal Level – “Approaches to Healthy Living” • Eat healthy – whole, fresh, unprocessed, plant based foods • Avoid toxicants whenever possible • Exercise • Be socially engaged

50. Localized, diversified and sustainable food production Clean, renewable energy↓air pollution, chemical exposures Mass transit that connects with bike paths and sidewalkscan reduceair pollution & obesity Chemical regulatory reform “Safer substitute” programs and green product design  ↓ toxic exposures, ecosystem, wildlife contamination; job creation Universal health care disease prevention & equitable health care. Major Illnesses Are Preventable Policy Initiatives to Profoundly Reduce Risks