Food and Nutrition for Disease Prevention

• discovery of increase prevalence of NCDs in men stemming from areas where childhood mortality was higher
• low birth weight = proxy for poor prenatal nutrition --> associated with T2D, CVD & high bp
• first 1000d as key timeperiod for health
  • high plasticity --> can backfire in case of maternal malnutrition due to (epigenetic) imprinting
  • evidence on humans almost impossible to obtain due to duration, but evidence from animals available

Direct medical costs

• monetary value
• ressources others have to invest in order to cure/take care of diseased person
  • can extend to family and non-professionals/non-medical persons
• in CH: healthcare
  • about 1/3 of of illness-related expenses amount to healtcare in CH
    • 9730.- Fr/y per capita
    • in CH costs are high but when adjusted for purchasing power, expenses become 20% higher (and more realistic) as opposed to 50% difference in absolute means

Production losses

• of the person affected
• also measured in monetary fashion --> usually based on salary of individual x time
• different types of production loss
  • partial loss: absenteeism (some weeks/months) or presneteeism (reduced workload/pensum)
  • total loss: permanent disability or death
  • potential loss: suboptimal development and cognitive weknesses, e.g. LMIC with stunting/nutrient deficiencies
• how to measure production losses
  • questionnaires to capture how often/long employers absent/reduced workload
  • administrative data to assess partial or total disability
  • epidemiological data for premature mortality
    • additionally impared physical and cognitive development in LMIC
• production losses in CH
  • mental and musculoskeletal disorders have greatest impact --> chronic and very low mortality cause long absence
    • more "deadly" NCDs have comparable low impact, but also because mortality higher

DALYs

• disability and loss in quality of life measured in DALYs, not monetary
• DALY two components: time and weight of disease
  • YLD: years lived with disability --> non lethal but disabling condition
  • YLL: years of life lost
• severity reflect by DALY weight and must be defined --> worldwide questionnaires
  • chornic diseases realtively low weight
  • mental diseases and pain high weight
  • good correlation between different cultures shows agreement on severity of different conditions
• In CH
  • neoplass responsible for large part of YLL
  • musculoskeletal diseases for YLD --> larger impact than YLL, typical for country with good healthcare system
  • DALY burden has  declined by about 30% in last 30 years --> big progress

Dimensions of healthcare costs in CH

• by service
• by type of service provider
• by type of financing instance
• by illness and disease
  • defined using the GBD study
    • costs for pregnancy, aesthetics and similar not included
    • co-morbidities separated

Malnutrition

• Importance of oral nutritional therapy
  • prevalence of malnutrition increases during hospital stay (vgl Bild: nutritiona lstatus deteriorates...)
    • 55% of served food returned --> flight attendant experiment
  • affects therapy outcome and mortality
    • improving nutrition during hospital stay is economic
    • daily requirements of many nutrients not met, depending on which requirements chosen, 53-70% --> nutrition in hospital setting is highly insufficient
• Reasons for malnutrition (kennste)
  • Clinical: Nausea, Cancer, infections, low BMI --> can affect hunger and appetite hormones
  • Non-clinical
    • mastication problems
    • monotonous food
    • food temperature & serving times
• Identification of patients at risk of malnutritoin or suffering from malnutrition
  • high risk patients: low BMI, disease-related weight loss
  • geriatric and oncology most commonly affected
• procedure of malnutritoin identification
  • Risk screening
    • using screening tools: NRS 2002
  • Diagnostic assessment
    • phenotypic: low FFM measured via DXA/BIA, unintentional weight-loss
    • etiologic: low food intake, disase-related difficulties eating
  • Diagnosis
    • at least one phenotypical and one etiological criterion
  • Severity Grading
    • moderate --> vgl Bild
    • severe --> BMI<18.5, NRS >= 3, >10% weight loss in past 6m, serum albumin < 30g/l
• prevalence
  • worldwide about 25%, same for CH

Parenteral Nutrition

• indications
  • access to stomach blocked
    • anatomical reasons: cancer
    • gut dysfunctional: perforation, obstruction...
  • tube feeding unsafe
    • excessive vomiting: pregnant women
  • patients who require bowel rest
    • acute gastroenteritis, radiation etheropathy, high output fistulas
  • major clinical indications
    • Acute and critically ill patients
    • Post acute patients (eg after surgery)
    • Pre operative malnutrition
    • Home parenteral nutrition (eg short bowel)
• contraindications
  • gastrointestinal tract fully operational
  • no access to veins (vena subclavia most common)
• Delivery systems
  • bags/containers with different nutrients that can easily be mixed
    • All in one options also available
  • Home parenteral nutrition
    • for chronic intestinal failure
    • short bowel syndrome or Crohn's
    • cancer patients with intestinal failure --> most common
• must take present and future into account: assure safety and nutritional balance for existing benign condition (ex short bowel) + prevent future complications related to nutrition
• will affect QoL and may become unsuited in an unpredictable time span due to laignant comorbidities
• complications often occur in PN and can be reduced via monitoring
  • metabolic
    • Refeeding syndrome
    • Hyperglycaemia and hypoglycaemia
    • Hypertriglyceridaemia
    • Hepato biliary complications (HPN)
    • PN induced bone disease (HPN)
  • technical
    • early: pneumothorax, bleeding
    • late: vein thrombosis
  • infections --> local can develop to systemic
  • monitoring
    • anthropos: monitor weight, arm cicrumferences, BIA --> indicator for muscle mass
    • funtion: check hand grip strength
      • lab results of bioechical, haematological, microbiological values

Nasogastric/enteral tube (enteral nutrition, EN)

• main goal: treat malnutrition and improve outcome
• performed if foods intake in coming 7 days anticipated to be insufficient or if malnutrition diagnosed
  • ethical consideration: EN must improve QoL --> if it prolongs suffering of a dying patient, it is unethical
  • prior to insertion of tube, expected benefit must be considered
• contraindications
  • gastrointestinal issues: obstruction of intestines + others (vgl Bild)
  • circulatory: schock, cardiac insufficiency
  • metabolic: coma, ketoacidosis (diabetes)
• Different accesses types for different durations
  • nasogastric & nasojejunal
    • short term less than 30d --> longer periods via parenteral or special types of enteral
  •  percutaneous endoscopic gastrostomy: PEG, PEG-J, D-PEG
    • access to stomach via inserted tube --> food injected into stomach with seringe (Dave having lunch)
• Complications
  • reflux
  • infections
  • malpositioning of tube in brain or lung
  • refeeding syndrome: reintroduction of food results in ATP generation, yet micronutrient deficiencies limit many biochemical processed so that organism is overtaxed putting the individual in a life threatening situation

Oral Nutritional Supplements

• first line adjuvant nutritional therapy
• different types
  • polymeric: entire foods, commercially available --> usually better tolerated and used most often
  • oligomeric: broken down macros --> peptides & micro's
  • disease specific: diabetes, CKD...
  • isolated macros
• Forticifaction of foods first step of malnutrition treatment, further step taken with sip feeds if fotification insufficient
• concinving evidence for the effectiveness of ONS in the clinical setting (multiple meta-analyses)

Oral Nutrition Hospital

• special types of criteria to adapt nutrition to patient
  • protein requirements can differ between patient groups
    • restricted: e.g. renal insufficiency
    • elevated: e.g. dialysis patients
  • Energy
    • elevated: malnutrition
    • restricted: obesity
  • medical indications
    • gastroenterogical: gluten free, lactose free...
    • speicial conditions: frc free, germ reduced, phenyl-alanine free
• Protected Mealtime Policy
  • assistance for people who need help (paralysis, e.g.)
  • give patients enough time to consume meal -->no doctors or nurses present
  • in between snacks to increase kcal intake
• Monitoring of food intake via supervisisoin of tray collection

Breastfeeding practices

• Timing
  • within one hour of birth
  • until up to age 2 or even beyond, on-demand
• exclusive breastfeeding for first 6 months
  • HIC: introduction of complemetary foods as of fifth month recommended
• rationale
  • no adverse outcomes on growth & natural (mother’s milk much more complex and rich in diverse nutrients/bioactives than formulas)
  • short-term (infancy)
    • decreased newborn mortality --> protects against diarrheal and pneumonic infections
      • sudden-infant-death syndrome (SIDS)--> two months reduce risk by 50%, longer breastfeeding further reduces risk of SIDS
      • compared to non/partially breastfed children: not breastfeeding increases infection-realted mortality 2x
    • beneficial effect on gut health --> necrotisation of enterocolitis prevented in pre-term infants
  • long-term (later life)
    • protective against neurodevelopmental delays
      • potential enhancement of motor development
    • protective against metabolic diseases (hypertension, diabetes, obesity)
    • protective against immune-related diseases (allergies, coeliac, IBS)
      • WHO meta-analysis: non or sporadically breastfed children prone to develop obesity whereas breastfeeding for at least 6 months protects children
    • Protective effect possibly mediated but gut microbiome modulation during first 1000d
      • Microbiota of breastfed infants differs from formula fed à more commensal, less pathogenic strains
    • Protective effects also for mother à diabetes, obesity, breast/ovarian cancer

Complementary feeding practices

• necessary to cover increased needs as of 6 motnhs that cannot be covered by mother's milk anymore
  • sub-oprtimal complementary feeding à stunting
• complementary foods (= first foods)
  • semi-solid and soft
  • complement mother's milk --> closes the gap between requirements covered by milk and requirements milk cannot cover but that the growing infant has
  • from month 6 to 23 --> some children ready earlier, around 4 months
  • 70% children WW are introduced to first foods, but only 20% with minimum diversity and frequency à breastfeeding from 12-23 months persists in 65% of cases WW
• weaning: stopping breastfeeding and switching over to semi-solid foods
• complemenary feeding practices & recommendations
  • quality of foods important:
    • ensure food variety by feeding at least 5/8 food groups
      • animal foods incl. mother’s milk
      • fruits & veggies
    • avoid empty calories --> high nutrient density foods important
    • Portion sizes: start with small portions, soft and little variety and 2-3 meals per day
    • Variety increase variety, volume and frequency of feeding
  • other important aspects & special situations
    • hygiene & proper food handling
    • use fortified foods if necessary
    • in case of illness --> increase drinking volume and offer favorite foods to ensure proper food intake
  • responsive feeding: watch out for and respect child’s reaction to feeding à foundation of (good) eating habits
  • early protein hypothesis: protein intake > protein requirements primes metabolism to become obese

DOHaD Framework

• environmental stressors prime organism à organism becomes prone to diseases if environment changes / is not-well prepared to environment
  • genetic
  • epigenetics
    • DNA
    • Histone
    • Chromatin structure
    • miRNA
• trajectories in early life more modulable/plastic, relatively low effort and pronounced impact on later life
  • little known on how breastfeeding and complementary feeding affect epigenetics and microbiota
    • obesity incidence more strongly correlated with microbiome at 3 months than at 12 months
  • partial breastfeeding with additional formula à microbiota more similar to formula-fed infants
  • breastfeeding/mother’s milk has epigenetic effects
• epigenome and microbiome interact with phenotype and early nutrition à 1000d for microbiota modulation

Risks and complications of eating disorders

• Types
  • Anorexia nervosa (AN)
    • typical symptoms: worry about body shape, self-esteem linked to weight/appearance, fear of gaining weight
    • 1.2% women
    • weight 15% below expectation
    • BMI < 17.5 kg/m2
    • weight loss caused by active or non-active measures
      • active: vomiting, laxatives
      • non-active. eating-restriction
    • always a behavioral and psychologic features
  • Bulimia nervosa (BN)
    • typical symptoms (same as AN): worry about body shape, self-esteem linked to weight/appearance, fear of gaining weight
    • normal weight, but preoccupation with weight --> self-esteem related to weight
    • high food intake due to food attacks --> 1/week
    • vomiting to compensate for food attacks
  • Binge eating
    • food intake >>> during at least 3 months
    • characteristic behavior: fast and abnormally bulky food intake despite absence of hunger followed by disgust and guilt
• Characteristics
  • often slowly and gradually developing bnormal eating behavior with tendency of becoming chronic
  • eating disorder is hidden from family/friends and third parties
  • profound impact on life: physical, psychological, professional, and social
• Co-morbidities
  • mostly psychatric nature
    • high rates of suicidal tendencies amongst eating disorders
    • difficulties to assess own and other's emotions
    • difficulties to see big picture, obsessive with details
  • mortality in anorexic people ~6%
  • hormonal foundation: leptin-like effect observed in AN
    • increased activation of HPA and HPG (gonads) axes --> reduced BMD, increased physical activity but also reduced reproductive activity
  • organ specific --> vgl Bild
    • gastric emptying
    • osteoporosis --> 40% of patients have low BMD
    • amenorrhea --> fertility affected
    • cortical brain atrophy

Multifactorial etiology

• Biological and genetic factors
  • genome-wide association found 8 loci involved in AN
  • pre- and perinatal factors:
    • infections during pregnancy
    • SGA
    • birth complications
    • feeding disorders in infant
    • childhood: obsessive, perfectionistic behavior
  • Neuro
    • alteratino in the dopaminergic system leads to self-starvation becoming a trigger of motivation --> viscous cicle
• Personality and individual experiences
  • Character traits
    • low self-esteem
    • obsessiveness
    • anxiety
    • emotional inhibition
  • trauma
    • sexual abuse or other trauma
    • strict diets in family
    • critical experiences towards appearance/weight/eating
• Socio-cultural factors
  • beauty standards
    • fashion standard
  • overabundance of food
  • unhealthy role models

Therapy

• interdisciplinary --> communication is key!
  • medical entities (family physician, specialists, gynecologists, dentists, internal medicine)
  • employer
  • social services
  • psychiatry
• target patients as well as patient's surrounding
  • get insight and enhance trust, and motivate change
  • family, relationship
  • work
• major goals
  • reach at least BMI = 18.5 or stabilize weight if normal BMI
  • normalize eating habits --> 3 meals/d with 2-3 snacks
  • treat comorbidities (somatic/psychiatric)

Bone homeostasis

• Bone basics
  • trabecular: 15.25% calcified
  • cortical bone: 80-90% calcified,
  • cells
    • osteoblasts & osteoclasts: build/resorb bone
    • osteocytes: derive form osteoblasts and represent mature cell, 80-90% of bone
• renewal every 10 years
• peak bone mass between age 30 and 40
  • gender differences:
    • women have lower BMD to begin with --> 60-80% genetically inherited, rest modulated by environment
    • menopause-caused fall in estrogen results in greater bone resorbtion and therefore lower BMD in females

Osteoporosis

• loss of bone mass (quantity) and deterioration of bone archtecture (quality)
• consequences
  • greater fracture risk
    • most commonly spine, hip or wrist fractured
    • 5-6% of falls actually result in fracture
  • collapsed vertebra --> tooped posture
• prevalence
  • gender differences --> 20% females, but also 5% males affected
  • worldwide variance in prevalence assumed to have genetic reason, not nutritional
  • 75% of osteoporotic fractures in >70 year-olds
  • risk for first fracture differs between gender (50% or more for females vs 20% males), but not for second fracture: 20% both gender
    • risk for second fracture highest in the year following the first fracture
• cost & disease burden
  • 13'000€/hospitalization --> greater than cancer, heart, and stroke combined due to greater prevalence of osteoporosis fractures than other
• link to sarkopenia
  • fear of falling reduces mobility and thereby muscle mass --> ultimately increases fall risks
  • muscle strength correlates with BMD

Sarcopenia

• prevalence: 20-75%, depending on population and source of information
• consequences
  • poor hospital outcomes, risk of falls, loss of independence
• definition and diagnosis not always clear --> muscle mass measurements, handgrip strength
• muscle strength via handgrip
  • peak in early adulthood
  • bi-phasic decline --> gradual as of age 40, substantial as of age 50
• etiology
  • systemic inflammation
  • ageing-associated processes
    • reduced autophagy
    • loss of mitochondria with additional decline in mitochondrial function
    • impared stem cell regeneration
  • los protein intake and negative protein turnover --> decrease in MyoPS and MitoPS
• Risk factors
  • sarcopenic obesity
  • extreme weight loss
  • drugs & pharmacological therapy --> ACE inhibitors
  • smoking & alcohol
  • sedentariness
  • genetic/intrsinsic factors: gender, sex hormone deficiency, comorbidities
• Prevention
  • sarcopenia considered to be a nutritional disorder
  • lifestyle interventions effective
    • exercise: less conclusive evidence
    • nutrition: evidence more equivocal and in favor of greater protein intakes
  • pharmacological treatments use hormone replacement --> testo / SARMs

Risk assessment

• Risk factors
  • clinical --> vgl Bild
  • BMT-D score --> assessed using DXA
    • < -1 SD: osteopenia
    • <= -2.5 SD: osteoporosis
    • <= -3 SD: severe osteoporosis
  • BMD is integrated into the FRAX algorithm  (fracture risk assessment tool) with clinical risk factors to predict 10-y risk for certain fractures
  • sometimes no BMD assessemtn available (e.g. men or subsequent to typical fracture) --> recommended treatment if:
    • FRAX risk > treshold (country specific)
    • fracture of hip, vertebrae, proximal humerus, pelvis, distal arm
• who to screen
  • essentially, screening is recommended to postmenopausal women, especially >65y 
  • men >70 recommended to screen depending on Consensus/Foundation

Calcium

• requirements increase slightly after 50y from 800 to 1000 mg/d
• recommendations
  • 800-1200 mg/d
  • foods preferred source
  • addition of vitamin D in institutionalized individuals
• calcium rich foods: mostly dairy and animal-based, although present in many fruits and vegetables too
  • average intake in Western 700-900 mg/d
  • dairy product effective in preventing the decline of BMD, but not in its restauration
    • under debate: evidence for persisting bone loss in postmenopausal women despite intakes of Ca of 300 - 2000 mg/d
• supplements
  • supplements sometimes necessary to meet recommendations --> 30-50% of older women in western countries prescribed supplements
  • uptake kinetics between dairy and supplemental Ca differs
    • supplements peak vs dairy plateaus --> potential mechanism for vascular complications, but not yet clearly identified
• Evidence
  • may increase risk of vascular diseases
  • inconsistent results on fracture reduction (meta-analysis)
    • reduction total fractures and vertebral fractures but not forearm or hip
    • often supplementes combined with vitamin D --> no additional effect
    • overall: no convincing evidence and, if any beneficial effects of Ca on BMD, then only minor
  • increased BMD by 1% after 1y --> not cost-effective

Vitamin D

• deficiency
  • serum 25(OH)-D best marker for Vit D status
  • disagreement regarding cut-off values but unanimity that <25 nmol/l severe deficiency
  • values <50 nmol/l increase from Northern Europe to Western/Southern/Eastern Eruope and up to 80% of individuals deficient in Middle East --> more sun not necessarily more Vit D
• Evidence
  • link to muscle function
    • mechanistic
      • muscle has vit-D-receptor (VDR) and converts it to 25OH-D --> supplementation increases VDR expression
      • deficiency affects mostly type 2 fibers
    • lower strength & functional decline in vit D deficient individuals observed in observational studies
    • supplementation shows reduced fall incidence
  • Lancet meta-analysis suggests no benefit of vit D supplementation to decrease fall incidence
    • negligable effect on vit D vs control as well as high vs low dose
    • small effect on selected populations (es = 0.83)
    • critiqued by mani experts in the field
      • biased study selection: no studies of vit D an calcium --> 40% of high quality data not included in meta-analysis
      • deffectiveness of daily dose of 800-1000 IU well established
  • Dosing
    • 2000 IU no effect on fall and fracture incidence
      • DO-HEALTH
      • doses of 20'000 IU/d for prolonged period may increase risk of falls
    • 800 IU usual recommendation to at-risk population (elderly and little exposure to sunlight)
    • >4000 IU not recommended, unless malabsorbtion
• Supplementation & approach
  • in case of deficiency, supplementation is required and likely to reduce risk of falls
  • replete individuals are unlikely to benefit from supplementation

Protein

• 1.2-1.5 g/kg/d to overcome anabolic resistance --> often unfeasible due to lack of appetite, too much food, mastication problems...
  • 25-30g protein per meal required
• Evidence for protein & bone health
  • moderate evidence: protein with Ca and vit D might improve BMD and
  • amount: higher protein intakes are generally better than low in terms of bone health --> no effects on bone biomarkers
    • meta-analysis across life-course shows different result depending on data used
      • non-adjusted: greater protein intake associated with better bone health
      • covariate adjusted: no association between amount or type of protein and fractures
  • higher protein intakes have at least no deleterious effects
  • type: soy and animal-based protein seem indifferent in terms of how they affect bone health

Cancer prevalence

• most frequent cancers vgl Bild
  • cancer patterns--> cancer type and total prevalences differ between countries
    • suboptimal food storage (curing --> high salt ; no fridge --> mold (aflatoxin)
    • LMIC affected by cancers related to poverty and infections --> digestive tract affected
    • high income countries: lung (smoking?), breast prostate (hormonal imbalances)
    • lifestyle factors: much higher cancer prevalences overall --> many-fold or less many-fold increase depending on cancer type (vgl. slide 36)
• mortality lower in high income countries because of treatment options
• Trend predicts stabilization of prevalence but increase in total numbers because of increase of world population
• comparison between countries only possible with proper age-standarization --> higher aged associated with greater risk, so age needs to be accounted for

Lifestyle factors

• migrants studies: people with same genetic background living in different environment, on population level
• twin studies: as migrant studies but on an individual or lower scale level
• correlational studies: e.g. meat intake vs cancer prevalence or cancer deaths
  • will inly show trends, not highest quality data
  • national and international levels possible --> std for age imporant for comparison
• Time-trend studies: ??
• case-control: ??
• intervention studies: ??
• Cohort studies
  • current state of the art in cancer research
  • FFQ + biomarkers used
  • long-term, prospective studies

Tools

• questionnaires: food, lifestyle and risk factors such as e.g. smoking
  • carcinogens usually found in toxicology and mechanistic studies --> informs questionnaires (and vice versa)
• biomarkers: b-carotene

Nutrition

• body / cell require nutrients for cell cycle and proper functioning
• Hormonal imbalances drive cancer development
  • overfeeding, diabetes --> fats and sugars
  • obesity second largest known risk factor for cancer
    • waist circumference correlates with breast cancer
    • weight loss reduces risk of cancer
    • often accompanied by other cancer promoting states --> inflammation, lack of fibre ==> obese cancer patients are more likely to die of cancer due to obesity (or other way around?)
  • menopause: increase in risk due to changes in hormones --> lower pre-menopausal risk for same cancer type (breast)
  • pregnancy: hormonal changes during/after pregnancy protect women
• hallmarks activated via obesity
  • insulin resistance as key driver of cancer
    • increase in estrogen due to reduced SHBG --> estrogen-dependent tumors
    • higher IGF1 levels
    • hyperglycemia --> anaerobic oxidation = cancerigenous
    • inflammation
• importance of exercise
  • reduces inflammation, improves insulin sensitivity, stabilizes weight
  • convincing evidence for reduces colon cancer

Multiple nutritional factors influence cancer risk

• Increase risk
  • Red and processed meats: 1.2% increase
    • Red and processed meats increase risk for colorectal cancer, white meat and fish decrease it marginally
    • Nitrosamines, saturated fats and ROS stress due to heme as potential drivers
  • Alcohol
    • Genotoxicity of acetaldehyde + other à vgl Bild
    • Increases risk for many cancers
    • Decreases risk for kindey cancer
• Decrease risk
  • Dairy and fish decrease certain cancer risks à vgl Bild
  • Fibre
    • Overall chance of contact between carcinogens & enterocytes is reduced
      • Faster transit times
      • Binding of carcinogens
      • Greater bulk à lower likelihood of contact
    • Reduce insulin resistance
    • Bioactive compounds of wholegrains
  • Fruit
    • Decrease in cancer risk limited

Cancer prevention

• Individual level
  • Healthy weight and physically active
  • Diet rich in fruits, vegetabes and beans
  • Limit intake of SSB, red meat, fast food, alcohol
  • Do not use supplements for cancer prevention
  • Breast feed
• Government
  • Incentives to fruit and vegetable consumption
  • Clear nutritional labels
  • Nutritional education and personalized advice
  • Healthy meals for the masses à schools, workplaces, institutions

Micronutrients

• B-carotene
  • Plasma levels have sotrnger correlation with cancer prevention than dietary intake à shows that plasma markers are more reliable
  • Supplementation increased cancer incidence in asbestos workers and smokers
    • B-carotene not recommended for cancer prevention, backed up by meta-analysis
    • Doses of 20-30mg/d
    • study had to be stopped
    • no deleterious effects observed with vit A and E
• Folate
  • Double edged sword: due to methylation, folate can promote cancer growth once tumorous cells have developed
  • Higher intake not found to increase cancer risk in 5.5y RCTs yet
  • Epidemiological studies show inverse relation between intake and development of colorectal cancer

CVD epidemiology

• CH
  • CVD: increasing rates ever since population infectious diseases could be prevented/reduced --> opulations ages and becomes prone to CVD
    • Since 1980 and current trend: declining CVD mortality --> CH one of the highest ranking countries in terms of ortality because time to reach hospital after event is short and treatment excellent
    • cancer: trend remains stable
  • mortality vs.  incidence values available for CVD
    • changes in mortality are due to treatment or screening --> decrease in mortality due to improvements in treatment
    • changes in incidence reflect efficacy of preventive measures
    • CH: decreasing mortality but increase in incidence, especially for males --> treatment has improved, preventive measures seem ineffective
  • Age as an important factor for CVD: mortality increases as of 65, at 85+ becomes most common cause of death
    • individuals <65 can still suffer from CVD
  • death remain stable while hospitalization is increasing --> screening improved? (slide 8)
    • healthcare and socioeconomic burden big, despite decreasing mortality
  • Regional and societal differences
    • higher class less prone to CVD --> also less smokers
    • Romandie less affected than Deutschschweiz
• International
  • trends also declining
  • similar trends in US, DE, FR, and CH
  • Switzerland ranks amongst lowest CVD mortality countries --> treatment and screening efficacous

Diet and CVD evidence

• Bradford-Hill Criteria --> vgl Bild
  • most nutritional sciences studies do not fulfil criteria sufficiently, so causality remains weak
    • Coffeexception: fulfils many criteria, incl linearity
• Problems of evidence in nutritional sciences
  • intermediate risk factors & soft vs hard outcomes
    • do not necessarily correlate with actual CVD mortality, although increase risk factors --> use of hard facts as more reliable information
      • coffe affects risk factors negatively but has positive outcome on CVD risk
      • n-3 improves blood TAG but not CVD mortality
    • CVD deaths more convincing than increased TAGs or intermediate risk factors
  • residual confounding: confounding factors that cannot be adjusted for / controlled
    • age/smoking/gender can be adjusted for, but impossible to adjust for behavior/mindset --> fish consumers likely to behave differently than non fish consumers
  • sponsoring
    • margarine industry sponsored some studies on saturated fats to increase fear of butter
  • causality difficult/impossible to find/relate to certain food
    • relating one nutrient to certain outcome never possible because diet comprises many foods
    • diet affects hormones --> E storage and metabolism modulated
    • meal will affect thermogenic effect
    • microbiota as intermediate player
• Problems specific to RCTs --> vlg Bild
  • control of exposures difficult in long run --> yet CVD needs time to develop
  • behaviour adapted when aware of control --> not realistic behaviour
  • forcing people to artificially follow a protocol that would never been adhered to in real life
    • low salt intake --> hard to adhere to and unrealistic, additionally only marginal benefits
  • time-dependent results --> diseases only show up late, difficult to maintain RCT for so long
  • vulnerable populations (with hypertension or with case of CVD) usually used --> not translatable to general population

Foods and CVD

• food groups: all-cause mortality rarely linear --> U-shaped relations
• many prospective cohort studies with very limited causality
• Some RCTS available but still with limitations
• examples
  • meat: inconsistency and low point estimates (Waht does that mean?), but more consitent when looked at meat preservatives, many animal studies
  • dairy: weak scientific evidence with conflicting results, some beneficial except for prostate cancer
    • strong evidence for preventive effects on diabetes → impact on gut microbiome/fermetation (less sugar)
  • fish: effect overstimated and dependent on region (preparation, freshness), maybe real advantage is replacement of red meat with fish
    • protein swap (slide 33): fish, milk and poultry protein comparable impact on CVD risk, plant protein might lower while eggs and processed meats might increase CVD risk
  • SSB
    • moderate increase for CVD --> meta-analysis found no effect on stroke, but CHD and hypertension
    • effect mediated via IR, obesity, hypertension ? --> unknown
    • substantial residual confounding: food choices of aware/unaware person not adjustable
    • swaping sugar for artificial sweeteners --> may decrease weight but might increase risk of CVD
  • Coffee (& tea)
    • negative impact on risk factors but associations show decrease in mortality
      • acrylamide, increase in LDL cholesterol and blood pressure
      • maximal benefit @ 4 cups/d
• expert consens as most reliable source of information --> vgl table
  • high agreement:
    • beneficial: DASH, high potassium intake, fibre, fruits and vegetables, seeds, yoghurt
    • harmful: artificial fats (partilly hdrogenated vegetable oils), high sodium, SSB, refined sugar
  • medium agreement
    • beneficial: seafood, n-3, olive oil, phenolic compounds
    • harmful: moderate Na, high GI foods
  • low agreement
    • beneficial: cheese, low fat-milk
    • harmful: dietary cholesterol, eggs, butter, unprocessed red meats

Fats

• trans-fats
  • most problematic of fats in regards to CVD mortality and total
  • industrial trans fats consistently show to increase CHD risk & mortality
  • ruminant trans-fats less conclusive data --> some even beneficial on T2DM (perhaps reason for protective effects of dairy on T2DM)
• saturated fats
  • saturated fats less conclusive data than trans-fats
  • some studies sponsored by margarine industry
  • replacement of kcal from SFA by other E sources affects CVD risk --> vlg Bild
    • AHA concludes that MUFA and especially PUFA should replace SFA for CVD risk reduction

Carbohydrate

• low-carb diets: not protective in the long run --> U-shaped relation with CVD risk
  • CHO source not taken into account
• all cause mortality U-shaped with optimal intake at 50-60 %En
• Whole grain: curve flattens out --> benefit up to ~60g/d

Supplements

• High dose of D3, A, b-carotene all shown to increase mortality (in specific populations)
• primary or secondary prevention with supplements is not evidence-based
• Ca supplements can even increase risk of CVD at higher doses
• main message: not suitable for primary prevention because of lack of evidence
  • drugs may not be adequate either in primary prevention, e.g. statins

Ethanol

• improves intermediate risk factors
  • fibrinogen: prevent clotting
  • increases HDL levels
  • adiponectin: promotes b-ox & increases insulin sensitivity --> lowered in metabolic syndrome
• worsen other intermediate risk factors
  • combined with beneficial influences, Lausanne study showed that despite increase in HDL, the increase in syst BP outweighs the benefit and leads to increased CAD risk
  • study in heavy drinkers
  • wine increases HDL, beer increase TAG
• Protective effect of alcohol likely to be biased finding
  • many studies suggesting beneficial effects of moderate alcohol consumption may be biased due to overestimation + residual confounding of moderate drinkers vs abstainers
    • moderate drinkers vs abstainers have different behaviors and the beneficial effect of mderate drinking might be overestimated
  • Selection biases in observational studies:
    • moderate drinkers not only adopt drinking but also particular lifestyle and have survived until study recruitment + are congintively fit enough to be enrolled --> selection bias
  • Risk thresholds for alcohol consumption:
    • Shows dose-dependent risk for different CVD-related disease depending on alcohol intake. Recent data, suggests no benefit of moderate alcohol intake on overall CVD mortality

Sodium an CVD risk

• fact: higher Na intake increases blood pressure in hyper- and normotensive individuals --> intermediary risk factor, so not necessarily increased CVD risk
  • question to ask: does reduction in salt intake result in lowered disease risk? (it does undeniably lower BP)
  • BP can be reduced without lowering Na intake --> normal salt DASH diet ==> further improvement with low Na DASH diet
  • target population who may benefit from salt reduction
    • very high salt intake population: >12g/d
    • hypertensive population
    • elderly
• Normotensive and hypertensive individual's risk for CVD depending on salt intake is different
  • U-shaped for hypertensive
  • flattened out for high intake
• TOHP (trials of hypertension prevention): Na reduction with mortality assessed --> minimal risk but big effort --> not worth it
  • Evidence on Na intake mostly from obeservations studies --> questionable
• Sodium intake vs potassium intake on different CVD-related risks
  • stroke: <5g safe zone --> increased risk with higher intake
  • myocardial infarction: not associated with Na intake
  • potassium intake:
    • linear, negative association with all CVD related risks
• K/Na excretion
  • greater K excretion generally associated with lower CVD risk
  • risk will depend on ratio, not absolute Na intake --> low Na intake with low K intake worse than higher Na intake with higher K intake --> high fruit and vegetable intake
• RAAS system
  • could explain small reduction (if any) in CVD risk of Ny intake --> hormonal counter regulation of Bp increasing hormones
  • lowered Na intake result in increase of, amongst other, stress hormones --> damages other tissues

Mediterranean Diet

• characteristics
  • no salt limits
  • low red (processed) meat
  • high unprocessed fruits and vegetable intake
  • protein mostly from plants or fish/poultry
  • High-quality olive oil as main source of fat
• much greater effect than low-fat diets (WHI study vs PREDIMED)
• overall, moderate risk reduction observed in prospective and RCT studies

DASH

• very similar to MedDiet
• version with salt reduction (50mmol/d) --> even more effective at reducing BP (does not mean CVD risk is reduced)

Other diets

• Nordic diet, Japanese diet, Harvard Diet...
• rely on similar features: high in fruits and vegetables, unprocessed,

• growth charts: increase in height and weight for boys and girls
  • different charts (WHO)
  • target height: mean between father and mother
• growth phases
  • infancy: first year of life mostly dependent on nutrition, less genetics / hormones
  • puberty: nutrition required to meet E demands of growing individual
    • Thyroid hormones involved as of 2 years of life
• Factors influencing growth
  • emotional stability --> especially eraly childhood
  • favorable socioeconomic conditions
  • absence of significant morbidity --> celiac disease
  • genetics: will define height but growth less dependent on it than nutrition

hormones

• satiety signals:
  • PYY, GLP-1 --> catabolic pathways (decrease food intake and increase E expenditure) --> dysfunctional in case of obesity
  • Ghrelin --> anabolic effect --> increases food intake and decreases energy expenditure (motivation to exercise)
• obesity signals: leptin & insulin

Obesity is defined using either BMI, BIA/DXA/Skinforld, or waist/hight ratio

• defined as BMI > 97th percentile (overweight >90)
  • WHO classification used for adults and IOTF for children: correlation between fat mass and obesity never been assessed for children, but likely to correlate, similarly to adults
  • healthy control children selected based on maother's health status: all continents, non-smoking, godd socioeconomic status
  • New Swiss BMI Reference also uses 97th percentile, but perhaps more
• definition using waist/hight ratio
  • waist circumference > 2 SD
  • waist/hight ratio > 0.5
• definition using BIA
  • >25% (20-25%) fat mass in boys
  • >30% fat mass in girls

BMI

• problems
  • fat and muscle mass not distinguished
    • !! prevalence can decrease but actually decrease in muscle mass and not fat mass, due to low PA
  • height strong impact on BMI value --> short statured children will have lower BMI despite being overweight/obese --> respect weight-for-height charts
  • weight-for-height charts
    • valid until age of about 5 years
    • preferred over BMI in short or high statured children

BIA to assess fat mass and not muscle mass

• skin folds difficult in children beacause fat very compact
• obesity >25% fat mass in boys and 30% in girls
• DXA also used

Waist circumference

• obesity defined as
  • waist/height < 0.5 --> individual is used as own reference, therefore useful
  • waist CF > 2 SD; based on reference charts that takes age into account, as well as waist/hight ratio
• measures abdominal fat which is associated with comorbidities: hypertension, IR in children, CVD
  • reflects abdominal fat, around the liver, dangerous!
  • <88cm for females; <105cm for males
• either waist or hip circumference used, reference table available for both
  •  

Pathophysiology

• Satiety
  • set-point of satiety upregulated if E intake and E expenditure are out of balance for prolonged period --> remains elevated despite fat/weight loss --> yoyo-effect
• Energy intake should be adapted to PA of child

Hormones

• CNS receives signals via blood and nerves
• obesity signals --> dysregulation of set-point between accelerating (anabolic) and decelerating (catabolic) pathways
  • leptin (&insulin) activates catabolic pathway --> stops eating, be active!
    • leptin and insulin resistance result in loss of breaking/decelerating signals --> hyperactivation of anabolic pathway
  • NPY anabolic pathway --> eat, stop moving!
• Reward system & neurological aspects of obesity
  • dopaminergic system rewards for eating
    • very active in child's brain
  • Ghrelin release from stomach also rewarding
  • addictive power of food
    • addiction: amount of food needs to increase to trigger satisfaction (example with mouse)
    • advertisement of fatty/sweet foods to children should be limited
• Adipose tissue is homronally highly active
  • cytokines --> inflammation and macrophage activation
  • induce insulin resistance
  • activates thrombogenic messengers
  • activation of sympathetic activates adipocyte proliferation (?)
  • vagus increases insulin's anabolic effect on adipocytes

Microbiome

• many effects (vgl Bild)
  • suppress b-ox in muscle tissue
  • increase in fermenting enzymes
  • monosacch absorbtion
  • increase in SCFA, which interact with recpetors --> increase in PYY --> satiety
  • inhibit lipolysis
• microbiome changes in response to Western diet --> mice become fat
  • artificial sweeteners negatively affect microbiome --> tendency to obesity
• use of antibiotics in first year of life associated with obesity

pre-natal: U-shaped risk of under/overnutrition

• maternal undernutrition prepares fetus to food scarcity --> hyperinsulinism after birth if food plentiful
• maternal, prenatal overweight also increases risk of hyperinsulinusm and obesity as adult (x2.2)
• genetics: 25-50% --> environment and lifestyle play greater role
  • environment: many factors leading to a toxic surrounding, resulting in increased food intake, lower food density as well as lower PA (vgl Bild)

parental overweight

• overall most impactful risk factor (44% compared to ~10% for other common risk factors)
• regardless of parental status, overweight is carried over into adulthood more often if obesity develops in adolescence
• children of obese parents are more likely to become and remain obese thourghout life

physical activity & screen time

• 60min/d of PA only met by children up to 12y
• associations between number of cars and television viewing in a family more impactful on obesity than fat intake
• decrease in performance of recruits reflecting decreased PA and fitness
• differences amongst Swiss regions, genders and cultural background --> female expats the least physically active, Swiss Germans the most

nutrition

• taste-development in tuero --> sweet foods consumed during pregancy modulate taste preferences of child
• breast feeding
• nighttime feeding problematic --> important to respect "fasting period" in infants of about 10h

smoking during pregnancy

• increases likelihood of obesity by about 14%

socioeconomic factors

• education as remedy against toxic environment is difficult to obtain in low socioeconomic classes
• chlidren with migrational background more susceptible to obesity --> being fat culturally appraised

sleep duration

• less than 10.5h/night
• hypothesis: lack of a fasting period or lack of GH and its lipolytic effects, also stress reduction with sleep and relation between stress and IR

psychiatric risk factors

• ADHD and increasde impuslivity associated with overweight
• depression --> obese children suffer from emotional eating
• stress, including pre-school children
• strongly reduce QoL and self confidence --> QoL as low as cancer patients