Food and Nutrition for Disease Prevention

Non-communicable diseases

• global trend for NCDs is increasing while communicable, neonatal and maternal diseases decrease
  • injuries remain indifferent
• affect men and women to same degree
• costs: high because ncds are chronic diseases
  • usually remain for a lifetime or difficult to reverse (obesity, cancer)
  • expensive medication and treatment (antibiotics or other medication against communicable diseases less expensive)

Epidemiological shift

• improvement in hygene, reduction in childhood mortality and healthcare improve --> mosrtality decreases --> demographics: more aged individuals --> higher NCD risk
• shift from traditional foods to Westernized diet --> obesity and chronic diseases as well as chronic burden of malnutrition increase

• 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