1、慢性病的環境因素分析第1頁，共55頁，2022年，5月20日，0點3分，星期四What We Will CoverEnvironmental factors are key drivers of many common chronic diseasesEnvironmental factors alter key biological pathways leading to chronic diseaseImportant environmental determinants of health include:Food system/nutrition and dietToxic chemi

2、calsBuilt environment / physical activityPsychological & socioeconomic stressExamples of cross cutting solutions for healthy people & a healthy environment第2頁，共55頁，2022年，5月20日，0點3分，星期四Scope & Context of the ProblemA century of change in natural, built and social environments has caused major changes

3、 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

4、 of people at risk of chronic diseases of aging like Alzheimers and Parkinsons diseases, among others. Environmental factors play a key role in health across the lifespan. Thus they offer a major prevention opportunity.第3頁，共55頁，2022年，5月20日，0點3分，星期四The Changing Environment and Disease PatternsDuring

5、the past century, human activity has altered virtually all aspects of the worlds 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 soci

6、alize 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.第4頁，共55頁，2022年，5月20日，0點3分，星期四Environment Drives

7、 Chronic DiseaseWestern Disease ClusterDiabetes ObesityAbnormal LipidsMetabolic SyndromeCardiovascular DiseaseFood system/DietFossil FuelsSocioeconomic StressChemicalsBuilt Environment/ TransportationInflammationDisrupted Insulin SignalingOxidative Stress Alzheimers ParkinsonsAltered PathwaysEnviron

8、mental FactorsChronic Disease第5頁，共55頁，2022年，5月20日，0點3分，星期四Profound Public Health Impact Of Environmentally-Driven Western Disease ClusterObesity/overweight 2/3 US adults, prevalence x2 in 25 yrs Pre/Diabetes 40% US adults, prevalence DM x2 over 20 yrs Cardiovascular disease still leading cause of de

9、ath. Hypertension increasing. /nchs/FASTATS/lcod.htm, Hajjar 03Metabolic syndrome = early signs of other cluster diseases; 35% adults, 55%60 yrs Ford ES 05Alzheimers disease 84 yrs old, 5.3M Alzheimers Assoc.第6頁，共55頁，2022年，5月20日，0點3分，星期四Alzheimers Disease/dementiaNot an inevitable feature of normal

10、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.第7頁，共

11、55頁，2022年，5月20日，0點3分，星期四Parkinsons DiseaseProgressive 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

12、double by 2030.* Due to the lack of registries and baseline data on Parkinsons Disease, the figures used here are estimates. 第8頁，共55頁，2022年，5月20日，0點3分，星期四Alzheimers and Parkinsons DiseasesCharacterized by: abnormal protein deposits chronic inflammationabnormal oxidative stressMany neuroscientists ar

13、e beginning to think of some neurodegenerative diseases along a continuum, without clearly distinct boundaries in clinical or pathological manifestations 第9頁，共55頁，2022年，5月20日，0點3分，星期四Continuum of Age-Associated Cognitive Impairment第10頁，共55頁，2022年，5月20日，0點3分，星期四Environment Drives Chronic Disease Earl

14、y 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, commu

15、nity, society and ecosystem. Basic Principles第11頁，共55頁，2022年，5月20日，0點3分，星期四Toxic exposuresoxidative stressObesity, hypertension,Cardiovascular disease, diabetesAlzheimers, dementia, ParkinsonsLow birth weightEarly life experiences can influence later-life health, diseaseAging begins at conception第12

16、頁，共55頁，2022年，5月20日，0點3分，星期四Multiple Factors Interact to Influence Health & Diseasebuiltenvironmentdiseasestressenergychemicalsnutrients第13頁，共55頁，2022年，5月20日，0點3分，星期四An ecological health framework considers the individual in the context of family, community, society, and ecosystem.第14頁，共55頁，2022年，5月2

17、0日，0點3分，星期四Altered PathwaysEnvironment Drives Chronic DiseaseEnvironmental FactorsInflammationDisrupted Insulin SignalingOxidative StressChronic DiseaseMechanisms of Action第15頁，共55頁，2022年，5月20日，0點3分，星期四Defined by microscopiccharacteristics & laboratory test: inflammatory cells & mediatorsCLASSICAL C

18、ONCEPTOF INFLAMMATIONDefined by appearance. “Calor, dolor, rubor, tumor.” Heat, pain, redness, swelling.The New Concept of Inflammation“Atherosclerosis is an inflammatory disease.” (2) Ross, Russell. Atherosclerosis An Inflammatory Disease. NEJM 1999, 340(2); 115-126.第16頁，共55頁，2022年，5月20日，0點3分，星期四第1

19、7頁，共55頁，2022年，5月20日，0點3分，星期四Insulin Signaling = Normal MetabolismInsulin signaling blood sugar artery disease triglycerides第18頁，共55頁，2022年，5月20日，0點3分，星期四Insulin signaling blood sugar artery disease triglyceridesInflammationOxidative stressDisrupted Insulin Signaling = Inflammatory Metabolism第19頁，共55

20、頁，2022年，5月20日，0點3分，星期四Altered PathwaysEnvironment Drives Chronic DiseaseEnvironmental FactorsChronic DiseaseFood System/Diet第20頁，共55頁，2022年，5月20日，0點3分，星期四 Novel Nutrients Are Pervasive, Promote Inflammatory Metabolism第21頁，共55頁，2022年，5月20日，0點3分，星期四Whats “Novel” in the Western Diet?“Hypothetical schem

21、e of fat, fatty acid (6, 3, 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 pr

22、eceding 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.Years% of calories from fatmg/day第22頁，共55頁，2022年，5月20日，0點3分，星期四High Glycemic Carbohydrates Increase the Risk of Chronic DiseaseHigh glycemi

23、c carbohydrates break down quickly during digestion, rapidly releasing glucose (sugar) into the bloodstream. Plasma Insulin,mg/dlTime, minsINSULINEMIC RESPONSELow glycemic foodHigh glycemic food第23頁，共55頁，2022年，5月20日，0點3分，星期四第24頁，共55頁，2022年，5月20日，0點3分，星期四Properties of Fatty AcidsOmega-3 Omega-6 Satur

24、atedFood Perishable Durable Increased inSystemShort shelf life Processed foods factory farmed Increased in Long shelf life animals pasture- fed animalsImmuneAnti-inflammatory Inflammatory & InflammatoryProperties Anti-inflammatory Evolutionary Recent marked Recent marked Recent markedContextdecline

25、increase increase第25頁，共55頁，2022年，5月20日，0點3分，星期四Omega-3, (Omega-6) Insulin signaling blood sugar artery disease triglyceridesInflammationOxidative stressNovel Nutrients Disrupt Insulin Signaling, Drive Inflammatory MetabolismSaturated fatAntioxidants High Glycemic CarbohydratesFructose 第26頁，共55頁，2022

26、年，5月20日，0點3分，星期四Increase risks saturated and trans fatshigh glycemic carbohydrateslack of fruits/vegetables/omega 3sexcess omega 6s?Reduce risks fruits, vegetablesomega 3slow glycemic carbohydratesMediterranean dietInfluence of Nutritionon Chronic Disease 第27頁，共55頁，2022年，5月20日，0點3分，星期四Benefits of Me

27、diterranean-Type Diet on Chronic Disease RiskClinical intervention studies70% heart attacks, cardiac death & total mortality DeLogeril 9460% cardiac events in CVD patients* Ornish 9850% metabolic syndrome Esposito 0439% in CRP Esposito 04insulin resistance Esposito 04 weight Esposito 04Prospective o

28、bservation studies80% diabetes Martinez-Gonzalez 0831% all-cause & cardiovascular mortality, 22% cancer mortality*calculated from Sofi 08 73% Alzheimers mortality Scarmeas 0725-30% Parkinsons disease Gao 0778% childhood asthma maternal diet Chatzi 08*10% low fat, vegetarian diet + exercise, stress r

29、eduction*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 p

30、oint adherence scale to yield a calculated 31% all-cause & CV mortality and a 22% in cancer mortality.第28頁，共55頁，2022年，5月20日，0點3分，星期四Benefits of Sustainably-Produced FoodNutritional benefits:Generally higher levels of vitamins, minerals and phytochemicals (often dependent on soil quality) Higher Omeg

31、a-3 contentOrganic 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 第29頁，共55頁，2022年，5月20日，0點3分，星期四Altered PathwaysEnvironment Drives Chronic Disea

32、seEnvironmental FactorsChronic DiseaseToxic ChemicalsAir pollution, Lead and other heavy metals, some Pesticides,Bisphenol A and other Endocrine Disruptors第30頁，共55頁，2022年，5月20日，0點3分，星期四第31頁，共55頁，2022年，5月20日，0點3分，星期四LeadCumulative occupational exposure cognitive impairment Shih 20072x risk Parkinsons

33、 Coon 2006Cumulative community exposure cognitive impairment Shih 2006Up to 15 years cognitive aging Weisskopf 2004Animal studies of early life exposureLate-life Alzheimers markers Basha 2005, Lahiri 2007 第32頁，共55頁，2022年，5月20日，0點3分，星期四PesticidesParkinsons DiseaseHuman studies - 24/31 studies show ri

34、sks for PD. (OR 1.6-7) Brown 2006Animals - Rotenone & paraquatdamage 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 2005Cognitive decline/dementiaLow level fungi

35、cides in vineyards 3.5x poor attention, memory Baldi 2001 Occupational exposure in men associated with 2x risk of developing AD Baldi 2003Insulin Resistance, metabolic syndrome Lee 2006, 2007, 2007Some persistent pesticides show strong dose-response relation to insulin resistance and metabolic syndr

36、ome. 第33頁，共55頁，2022年，5月20日，0點3分，星期四 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 200

37、8 2-fold Insulin Resistance. Lang 2008 Bisphenol A polycarbonate第34頁，共55頁，2022年，5月20日，0點3分，星期四Insulin signaling blood sugar artery disease triglyceridesInflammationOxidative stressEnvironmental Factors Disrupt Insulin Signaling, Drive Inflammatory MetabolismEndocrine Disruptors -BPA, dioxins, PCBs,

38、some pesticides Saturated fatHigh Glycemic CarbohydratesAir PollutionAntioxidants Omega-3 Fructose SomePesticidesLead, other heavy metals第35頁，共55頁，2022年，5月20日，0點3分，星期四Altered PathwaysEnvironment Drives Chronic DiseaseEnvironmental FactorsChronic DiseaseBuilt EnvironmentPhysical Activity第36頁，共55頁，202

39、2年，5月20日，0點3分，星期四Health Benefits of Physical ActivityReduced ongoing levels of oxidative stress and inflammatory burden. Brooks 2008, Attipoe 2008Inversely associated with the risks of Alzheimers/dementia and cognitive decline. Rovio 2005Subjects at risk for AD who walked 150 min. per week showed im

40、provements in cognition while the control group showed no net change from baseline at 1.5 yrs. Lautenschlager 2008Increasing physical activity at any age improves physical and emotional wellbeing.第37頁，共55頁，2022年，5月20日，0點3分，星期四Walkable Cities Projects Community GardensFarmers MarketsRails to TrailsLi

41、vable Communities Enhance Healthy Aging第38頁，共55頁，2022年，5月20日，0點3分，星期四Cuba- lost fossil fuelsbiking, walking, local plant-based food physical activity 50%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 W

42、eight Loss on Cardiovascular Disease and Diabetes Mortality in Cuba, 1980-2005. AJE 166, 12; Sept. 19, 2007Sustainable Food & Transportation Solutions:The Cuba Example第39頁，共55頁，2022年，5月20日，0點3分，星期四Green Space Reduces Stress, Mortality, Improves Cognitive FunctionShortens post surgical recovery time,

43、 reduces need for pain medications. Ulrich 84Attention deficits improve after a walk in the park. Effect = methylphenidate. Taylor 08Access to green space reduces the effect of poverty on mortality by 50%. Mitchell 08第40頁，共55頁，2022年，5月20日，0點3分，星期四Insulin signaling blood sugar artery disease triglyce

44、ridesInflammationOxidative stressEnvironmental Factors Disrupt Insulin Signaling, Drive Inflammatory MetabolismObesityEndocrine Disruptors -BPA, dioxins, PCBs, some pesticides InactivitySaturated fatHigh Glycemic CarbohydratesAir PollutionAntioxidants Omega-3 Fructose Lead, other heavy metalsSomePes

45、ticides第41頁，共55頁，2022年，5月20日，0點3分，星期四Altered PathwaysEnvironment Drives Chronic DiseaseEnvironmental FactorsChronic DiseaseSocio-Economic StressDepression, poverty, violence, inadequate health care第42頁，共55頁，2022年，5月20日，0點3分，星期四Socioeconomic, Psychosocial StressorsStress, depression risk for CVD, AD

46、Sesso, Kario, OwnbyPeople with lower SE status are at risk for exposure to multiple environmental hazards damage.Lead + stress cognitive impairment Glass 2009Lead + air pollution CV autonomic dysfunction Park 2008第43頁，共55頁，2022年，5月20日，0點3分，星期四People who live in neighborhoods that lack social cohesio

47、n, sidewalks, or safety limit their exercise and have an increased risk of depression and possibly obesity. Berke EM 07, Molnar BE 04Effects of the Built Environment on Health第44頁，共55頁，2022年，5月20日，0點3分，星期四Insulin signaling blood sugar artery disease triglyceridesInflammationOxidative stressEnvironme

48、ntal Factors Disrupt Insulin Signaling, Drive Inflammatory MetabolismObesityEndocrine Disruptors -BPA, dioxins, PCBs, some pesticides InactivitySaturated fatHigh Glycemic CarbohydratesAir PollutionAntioxidants Omega-3 Fructose Lead, other heavy metalsSomePesticidesStress第45頁，共55頁，2022年，5月20日，0點3分，星期

49、四Multiple Factors Interact to Influence Health & Disease第46頁，共55頁，2022年，5月20日，0點3分，星期四Environmental FactorsChronic Disease Altered Biological Pathways Greenhouse GasesClimate Crisis Heat, drought, storms, fires, ice sheet instability, sea level rise, loss of glacial irrigation, refugees, food insecu

50、rity/starvation,tropical diseases Environmental Factors Drive Chronic Disease and the Climate Crisis 第47頁，共55頁，2022年，5月20日，0點3分，星期四Solutions forHealthy People & A Healthy Planet第48頁，共55頁，2022年，5月20日，0點3分，星期四Major Illnesses Are PreventablePersonal Actions to Profoundly Reduce Risks Personal Level “Ap

51、proaches to Healthy Living” Eat healthy whole, fresh, unprocessed, plant based foods Avoid toxicants whenever possible Exercise Be socially engaged 第49頁，共55頁，2022年，5月20日，0點3分，星期四Localized, diversified and sustainable food production Clean, renewable energy air pollution, chemical exposuresMass trans

52、it that connects with bike paths and sidewalks can reduce air pollution & obesityChemical regulatory reform“Safer substitute” programs and green product design toxic exposures, ecosystem, wildlife contamination; job creationUniversal health care disease prevention & equitable health care.Major Illnesses Are PreventablePolicy Initiatives to Profou