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Flashcards 68
Language English
Category Biology
Level University
Created / Updated 07.03.2021 / 11.06.2021
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Cancer and Nutrition, Andersson

Cancer development

  • how does cancer develop?
    • phases
    • reasons/mechanisms
    • relation to age
    • what types of cancer are there?

Cancer development

  • can be somatic or inherited --> 90% somatic
    • functional gene on one of both chromosome pairs can compensate for mutation on other, e.g.: inherited mutation from mother can be compensated via euivalent gene inherited from father --> loss of function of both genes that will result in cancer
  • 3 phases: initiation, promotion and progression
  • cancer risk accumulates over time and is therefore higher in aged individuals
    • may affect all ages though
  • Cancer types
    • benign: slow cell multiplication
    • maligng: invades and destroys surrounding tissues, rapid cell growth
    • metastasis: affects multiple organs as cancerigenous cells spread throughout body
  • process requiring lots of time: cell's repair mechanisms (p53) are defect --> mutation is not corrected and persists in daughter-cells  --> becomes cancer / malignant as soon as cells multiply and invade other tissues
    • bad-luck-theroy: cells with high turnover are more susceptible to DNA errors
    • p53: guardian of the genome
      • mutated in >50% of cancers --> precancerous cells esacape apoptosis pathways (=quality control)
      • induces apoptosis if DNA errorr is detected

Cancer and Nutrition, Andersson

Cancer epidemiology

  • what are the most frquenent types of cancer?
    • How do demographics and socioeconomics affect this?
  • how do mortality and incidence behave now and in the future?

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

Cancer and Nutrition, Andersson

Cancer assessment tools

  • what kind of studies to assess cancer risk factors?

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

Cancer and Nutrition, Andersson

  • Nutrition and Cancer: how are both linked to one another?
  • What other modifiable risk factors exist and how to they affect cancer risk?

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

Cancer and Nutrition, Andersson

Give an overview of which factors increase or decrease cancer risk

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 and Nutrition, Andersson

 

  • What strategies exist to prevent cancer?
    • How do they work?
    • On what levels?

 

 

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

Cancer and Nutrition, Andersson

  • Which micronutrients affect cancer risk, and how?

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

Nutrition & CVD, Faeh

CVD epidemiology

  • how situation in CH
  • how do Swiss CVD trends compare to international CVD trends?
    • what are strengths and weaknesses of CH treatment and screening strategies?

 

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

Nutrition & CVD, Faeh

  • Diet and CVD evidence
    • What problems do nutritional sciences have ingeneral?
    • what problems are specific to RCTs?

 

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

Nutrition & CVD, Faeh

  • Illustrate how dietary risk and protective factors may impact on CVD risk
    • give example of specific/controverse foods

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

Nutrition and CVD, Faeh

  • How do these nutrients relate to CVD risk?
    • Trans-fats
    • SFA
    • CHO
    • Supplements 

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

Nutrition & CVD, Faeh

Ethanol

  • what does new evidence suggest?
    • give two reasons for flawed studies
  • changes in protective and risk factors: which ones ocurr and what dominaztes in the end?

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

Nutrition & CVD, Faeh

Nutrients and CVD: Salt

  • What is evidence for CVD and dietary salt ?
    • type of studies
    • type of CVD
  • Na intake in a broader spectrum
    • nutrition
    • hormones
  • Who might benefit from reduced salt intake?

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

Nutrition & CVD, Faeh

Dietary patterns to reduce CVD risk

  • What nutritional strategies exist to reduce CVD risk?
    • describe one strategy in detail
    • what is the evidence?
    • what have in common?

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,

Childhood Obesity, Lallemand

  • Factors influencing normal growth
  • growth phases
    • relate to nutrition
    • which factors other than nutrition affect growth?

 

  • 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

Childhood Obesity, Lallemand

Hormones

  • what are the hormones associated with
    • satiety
    • obesity
  • how does obesity affect these hormones?

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

Childhood Obesity, Lallemand

BMI

  • How is obesity defined using BMI?
    • what are common problems to BMI and how can they be adressed?
  • What methods other than BMI are used to define obesity?

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
    •  

Childhood Obesity, Lallemand

Pathophysiology

  • How are hormones and hunger related?
    • why can hunger persist, how is this caused?
    • relate to neuronal aspects

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

Childhood Obesity, Lallemand

Pathophysiology

  • Microbiome: how affected by diet?
  • associations between obesity and antibiotics?

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

Childhood Obesity, Lallemand

Risk factors

  • what risk factors exist?
    • internal and external ones
    • other than physical
  • how can taste-perception affect 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

Childhood Obesity, Lallemand

  • Co-morbidities: 5 most common ones
    • what markers are commonly dyregulated in these comorbidities --> correlation with BMI
    • measuring techniques / assessment
    • reference / cut-off values
  • What nutrients have strong impacts on development of these co-morb or how are they related to them?

Arthrosis

  • orthopedic issues most common in obese children
  • ataxia / lack of motor control and malatriculation

Atherosclerosis & CVD

  • dyslipidemia
    • TG & HDL correlate with obesity in children
    • fructose intake, especially in processed form
  • high blood pressure
  • Impaired glucose tolerance / Diabetes / imapred fasting glucose
  • metabolic syndrome
    • present if 2 artherosclerotic-related risk factors + abdominal obesity diagnosed
  • Subclinical inflammation
    • correlates with total dietary fat and % En from fat
    • meat intake correlates with IL-6 and leptin

Liver cirrhosis

  • generally defined as NAFLD
    • liver enzymes elevated > 1.5 normal
    • ultra-sound of steatosis hepatitis
  • non-alsoholic steatohepatitis (NASH): histologic signs of fat infiltration >5%, fibrosis and inflammation
  • boys more susceptible to NAFLD due to testosterone --> fat deposition in abdominal area

Sleep apnea

  • neurocognitive deficit

Diabetes & insulin resistance

  • total E, fat SFA, and protein intake correlate with IR
  • insulin resistance diagnosis
    • fasting glucose, HOMA or QUICKI-sensitivity
    • acanthosis nigricans around neck as visual indicator of IR
    • cut-off values same as for adults
  • insulin resistance blocks glc import into cells, but not parallell effect of insulin on mitogenesis --> hyperactivated gene expression might cause cancer

Childhood Obesity, Lallemand

Therapy

  • What are the 6 goals
  • what approaches can be used, how are they characterized
    • what prerequisite important or what factor is important for effective treatment
    • how's education used to help children
  • timing: duration & follow-up
  • effectiveness: how many children participate and how effective treatment (in CH vs US)?
  • pharmacologic strategies: top or flop?

Strategies to adress childhood obesity

  • targets
    1. reduce blood pressure
    2. reduce burden of co-morbidities
    3. reduce sedentariness
    4. limit sugar intake & improve nutrition in the entire family
      • choice of foods
      • preparation
      • portions
      • rythm
      • company
    5. increase self-esteem and conflict-management
    6. improve parenting skills
  • timing & duration
    • prenatal: avoid antibiotics and ideally mother should not be obese at pregnancy
    • at age 7-10: increases in BMI best predictor of adulthood obesity
    • usually 1y therapy with 5y follow-up
    • long studies, expensive, but effective
  • Approach
    • group setting: & individual setting possible
    • multidisciplinary: sports, nutrition, psyche, behavior...
      • all participants loose weight regardless of starting condition
  • Education/simplification of information
    • nutritional pyramid
      • only water, not juices/soft drink
      • fruits and vegetables, daily
      • small portion of fish/meat
      • 3 dairy products/day
    • hand-size model used to easily explain portion size
    • 3-5 meals per day
    • ideally 10h fasting/d
    • PA pyramid
      • max 1h screen time
      • muscle mass and coordination improved through PA
      • depression reduced
  • Age of patients defines if her/his family is included in therapy or not (vgl Bild)
  • contraindications: lack of motivatino or effective treatment
    • motivation difficult to obtain --> only ~1% of Swiss children undergo therapy
  • pharmacologic interventions do not really represent a solution
    • usual medicine not allowed for children
    • leptin injections do not work --> antibody development
    • cannabinoids lead to depression
  • QoL and mental disease: absence of mental issues important for weight reduction
    • improved QoL correlates with lowered BMI

The role of metabolism and nutrition in metabolic disorders, Masoodi

Obesity

  • framework used to assess obesity-related complications
  • correlation between obesity and
    • co-morbidities
    • relative risk of mortality
  • #1 treatment strategy?

 

 

Obesity & related complications

  • 4Ms: used to assess obesity complications
    • mental: form addition to psychosis and depression
    • mechanical: ostheoarthritis, chronic pain, sleep apnea
    • metabolic: T2D, CVD, dyslipidemia
      • obesity major risk factor for NAFLD, cancer, T2D, CVD
    • monetary: loss of job and lowered employability, disability, low income
  • Obesity can be present in absence of 4Ms, which are the dangerous co-morbidities of obesity
  • weight-loss as first and most important strategy to adress obesity and co-morbidities
  • BMI & mortality: x3 increase of mortality as of BMI >40
    • x 1.5 as of BMI 30
  • controllable vs non-controllable risk factors
    • genetics
    • lifestely, microbiome, diet

The role of metabolism and nutrition in metabolic disorders, Masoodi

Energy balance

  • how is E balance defined?
  • what (nutritional) factors influence E balance?

Fatty acids

  • structure: how are structure and quality related?
  • functions: what are the major classes/functions FA can take on

E balance

  • stored energy = E intake - E expenditure
    • E exp:
      • 70% BMR
      • 20% PA
      • 10% thermogenesis
    • E intake
      • 20-35 %En fat intake
      • type of ingested fats (SFA;MUFA;PUFA) defines diet's quality
  • Hormonal regulation
    • increase hunger: ghrelin
    • decrease hunger: leptin, CCK/GIP, GLP-1, PYY, insulin
      • leptin replacement therapy in children capable of reversing obesity
      • liraglutide: glp-1 receptor agonist --> stimulates insulin secretion/decreases excessive glucagon release
      • adipose tissue (leptin) hormonally active as well as stomach/gut (glp-1)
    • hormonal regulation > power of will --> addiction and uncontrollable fod intake in case of dysregulation
  • lipogenesis and lipolysis
    • lipogenesis for fat storage
      • fat stored in subcutaneous depots, can also accumulate in visceral fat --> spill over to ectopic in extreme case
    • lipolysis to release energy in case of fasting/starvation/food deprivation

Fatty acids

  • Structure
    • hydrocarbon chain
      • most FA have hydrocarbon chain attached to different backbones (e.g. glycerol)
    • carboxyl group
      • carbon chains sterified to head groups
      • head groups can also consist of protein or sugars
    • steroids & cholesterol: have no hydrocarbon chain
  • EFA
    • DHA and EPA technically not essential, but conversion rates too low and deficiency if not adequately consumed
    • ALA and LA essential according to terminology
  • Lipid diversity and different functions, 3 main categories
    • transport & storage
      • TAG, DAG, cholesterol
    • cell signalling
      • FA removed from membrane and converted by PLA2
      • PIP2/PIP3 and others (vgl Bild)
    • cell memrane
      • phsophatidil-cholin/serine
      • sphinglipids
      • can be cleaved from membrane and metabolized via PLA2 (phospholpase A2) --> become cell signaling FA

The role of metabolism and nutrition in metabolic disorders, Masoodi

Treatment strategies

  • common treatment strategies: explain shortly
    • how effective are they?
  • what are common problems to treatment?
  • How do different diets compare in their efficacy of reversing obesity?

Treatment strategies

  • bariatric surgery
    • problems
      • rebound: tendency for weight regain after many years, still not back to baseline weight
      • some patients develop NAFLD
      • cost --> restricted to severly obese subjects
    • most effective treatment
    • severe impact on patient physiology
  • medication for weight loss: 5-15% weight reduction
    • GLP-1 analogs (liraglutide)
      • also effective at reducing co-mordbidities, such as dyslipidemia
    • Leptin replacement
  • lifestyle intervention
    • modest interventions based on simple recomendations ("eat less, move more") are capable of reducing body weight by <5% --> not enough to reduce risk of co-morbidities
    • intensive interventions: require adherence, program to follow, can reduce weight by up to 10%
      • IF, low calorie intake
      • prone to yoyo effect
  • overall problem: effectiveness depends on patient's individual characteristics + no clear and effective treatment for obesity available
    • metabolic challenge (fasting) to assess metabolic state of patient
    • hormonal state of patient aslo assessed
    • solution: stratify patients into groups that are most responsive to certain treatment

Dieting

  • Atkins, Zone Diet, Weight Watchers, and Ornish Diet tested against each other: all reduce weight by max 5%, co-morbidities are reduced but reappear after certain time
    • either reduce portion size, increase protein intake, limit calories --> different strategies
  • ketogenic diet
    • not yet proven to work in obesity, perhaps in combination with surgery
    • effective in epileptic patients

 

The role of metabolism and nutrition in metabolic disorders, Masoodi

Personalized medicine

  • based on an exmaple seen in classe, explain:
    • study design, goal & outcomes
    • participants
      ...to find ways to personlize medicine in the context of obesity

Personalized medicine; example of DIOGENES Study

  • Study presenten (DIOGENES) with three parts
    • 8 weeks of very low calorie intake --> responders and non-responders defined as weight loss > 5% BW
      • very well controlled: food replacement (how check for adherence and avoidance of other foods?)
  • responders undergo second part of study: 26 weeks on different kinds of diet (high/low GI and high/low protein)

DIOGENES Study

  • non-responders are studied to identiffy how hormones (glp-1 and insulin), glycemia, lipidemia and nutrient interact
  • phenotyping: used to stratify non-responders into sub-groups who may have a chance of betterment with tailored treatment
    • hypothesis: non-responders have other lipid signature and therefore do not respond to specific nutrient
  • lipidomics: specific lipids as markers for responsiveness to alternative treatments
    • uses pre-clinical data (cell and animal model) to establish relationships between lipid & glucose metabolism --> non-responders screened for these
    • non-responders' lipid, glucose and hormone moetabolism (glp1) is assessed to study relationship between nutrient & metablolic markers
  • functional foods: to positively influence metabolism
  • goal: design treatment for non-responders

The role of metabolism and nutrition in metabolic disorders, Masoodi

DIOGENES Study

  • what outcomes did study observe: explain
  • what differences were observed between responders and non-responders?
    • metabolic
    • phenotype
  • what paragidgms were challenged?
  • How did preclinical studies confirm findings of study?

DIOGENES Study

  • genotyping: identification of reponder and non-responder group
  • Matsuda index: glycemic outcome is improved in responders
    • improvement of this more important than sheer weight loss because it reflects a positive change in metabolism --> persists to follow-up
  • BMI
    • responders lose more weight than non-responders
    • challenge of paradigm: does weight loss necessarily reflect improvement in metabolism?
      • weight loss independent of imprvoement in matsuda index possible
      • non-responder: no association between weight loss and glycemic outcome
  • Identified pathways differing between responders and non responders --> can be used to deisgn treatment for non-responders
    • De novo lipogenesis
      • upregulated in non-responders
    • bile acid metabolism
      • 2nd bile acids (TCA GCA TCDCA), involved in gut microbiome
        • baseline values can be used as predictive markers because already differ before intervention
    • ARA metabolism
      • involved in inflammation --> low grade inflammation --> diseases + IR
    • fatty acid oxidation
      • responders: better than non-resp in b-ox as well as ketone body synthesis
      • stimulation of this pathway may be helpful in treatment of non-responders
  • genes: key genes regulating lipogenesis in adipocytes sign. different between resp./nonresp.
    • SCD; FASN, FASN1; FASN2
  • microbiome
    • fecal transplant from obese to germ free mouse
    • hypothesis: transplant must provoke change in metabolism --> can be used to study
    • outcomes: previously observed pathays change --> confirmation that microbiome contributes to different reponses between resp/nonresp.
      • ARA pathways
      • 2ndary bile acid

unfertig: Bilder

Nutrition in obstetrics, Quack

  • Why balanced nutrition important during pregnancy?
  • what are the factors influencing pregnancy outcomes
  • what relations exist between birth weight and onset of adult NCDs

Factors influencing pregnancy outcomes

  • genetic: maternal birth weight correlates with ponderal index of offspring
    • no correlation for paternal birth weight and PI
    • ponderal index: comparable to BMI, reflects body weight/volume ratio, m^3
  • nutritional
    • intrauterine environment pre-programmes fetus to later life --> under/overnutrition negative impact
    •  
  • environmental
    • epigenetics: will interfere between environment/nutrition and genotype and can lead to mismatch between phenotype and its environment (postnatal hyperinsuliemic response to food after in utero starvation)

Birth weight & adult-onset NCDs

  • Barker: SGA newborns become adults and undergo developmental programming. Due to mismatches, these individuals develop a "thrifty" phenotype, i.e. that is likel to conserve as much E as possible. Consequently, they gain weight and become prone to NCDs: obesity, hypertension, diabetes, and cardiovascular disease
    • low BW correlates with greater mortality (vgl Bild)
  • animal model: SGA births can catch up normo-weight births in postnatal period of adequate nutrition is provided, however, eventually resulting in obesity --> plausible that orexigenic mechanisms involved
  • high birthweigt (>4000-4500g):
    • linear increase in risk for overweight as of 2300g

Quack

IUGR

  • causes: name multiple factors causing IUGR
  • consequences: for child, beyond growth
  • give an example
    • how does timing of an insult affect IUGR regarding the three trimesters?

Intrauterine growth retardation (IUGR)

  • causes
    • inadequate maternal nutrition
      • see Dutch famine
    • chronic diseases: congenital heart diseases, CKD, hyperthyroidism
    • lifestyle factors: smoking, alcohol, drugs
    • chormosomal abdonmalities --> trisomie 21
    • placental issues affecting maternal-fetal circulation
  • consequences
    • growth & development
      • restricted growth and development of muscle and other organs
      • vascular development affected
    • hormonal
      • Insulin: IR as well as lowered insulin secretion in offspring possible
      • HPPA: overactivation
    • metabolic
      • glc uptake in liver reduced
  • example: Dutch Famine --> time of exposure dictates how undernutrition will affect offspring
    • first half pregnancy: increased obesity, because hypothalamic centers affected
      • first trimester most vulnerable compared to other 2
    • last trimester and first motnhs of life: reduced obesity rates, because adipose tissue development affected negatively

Quack

Macronutrients

  • what recommendations during pregnancy (1/2/3rd trimester)?
  • what recommendations specifically to CHO/PRO/FAT
    • what consequences possible if CHO metabolism derailed
    • how fats related to birth complications?
      • what nutrient can reduce risk of these complications?

CHO

  • physiological IR to increase glc delivery to fetus
  • gestational diabetes
    • definitions vgl Bild
    • consequences: likelihood of insulin-related complications/diseases increases for mother and child postpartum

PRO

  • daily protein intake recommendations vg Bild
  • cohort study in CH
    • 1/3 CH women, classified into socioeconomic classes --> protein intake assessed
    • average protein intake 69g/d --> deliver babies with normal weight

FAT

  • PUFAs important --> 200mg DHA/d
  • Fish consumption encouraged to pregnant women, alternatively supplementation
    • supplementatino only effective in case of deficiency, overdosing increases risk of preterm delivery
    • ideal range of omega-3 between 4.1 and 4.9% (of erythrocyte DHA?)
    • 11% risk reduction for preterm delivery with Omega-3 supplementation
  • increased fat intake increases likelihood of vaginal infection (Gardnerella)

Quack

Micronutrients 1

  • two most common deficient micronutrients: WHO recommendations
    • consequences of deficiency on birth outcomes
  • Folic acid: particularities, effective?
  • Ca: effective? What good for?

Micronutrients

  • recommended intake of different micros changes with course of pregnancy

Folic acid

  • important before conception --> spina bifida roots in first 4 weeks after conception in case of deficiency
  • supplementation may reduce risk of complications by 75! --> very strong impact on birth outcomes and therefore worthwhile
  • reduces risk of
    • spina bifida
    • cleft lip
    • inherited heart defects
    • possibly autism & preterm delivery

Iron

  • most common deficiency worldwide, 32% in Swiss women --> more of a third-world problem
  • increases risk of
    • IUGR
    • Anemia and iron deficiency in child
    • SGA birth

Iodine

  • Iodine supplementation (200mcg(d) does not seem to affect IQ in children at age 5-6
    • WHO rec: 250 mcg/d
    • supplementation unlikely to harm but potentially without benefit
  • severe iodine deficiency rather uncommon, but mild one common!
  • Evidence
    • neurodevelopment improved in cases of severe iodine deficiency --> controversy from observational studies regarding IQ of children born to iodine sufficient/insufficient mothers
    • mother may adapt to low iodine availability and maintain euthyroidism in child

Calcium

  • correlation with preeclampsia (<140/90 mmHg) --> higher Ca intake, lower hypertension
    • observational data: indigenous people consuming greater amounts of Ca have lower preeclamsia prevalence (Ethiopians, Maya)
  • pathophysiology
    • hypertension leads to preterm delivery and neonatal death
    • preeclampsia not treatable during pregnancy! prevention as only strategy
  • in CH: recommendation of 1g/d for pregnant women as well as general population
    • most women (non-pregnant) do not reach these recommendations
    • can be covered via ~2L of mineral water (vgl Bild)
  • WHO rec: 1.5-2g/d for women with low Ca intake
  • evidence: cochrane reviews
    • 2014: reduced risk or preeclampsia
    • 2018: high Ca supplementation >1g/d may reduce risk in case of low-Ca diets
      • supplementation not feasibl in third world due to expensiveness and bulkyness (1kg for 20 weeks supply)

Quack

Micronutrients 2

  • Fat-soluble vitamins
  • animal-sourced vitamins
  • recommendations
    • to vegans & vegetarians
    • generall foods to avoid

Vitamin A

  • only vitamin with risk of overdosing during pregnancy. hypervitaminosis A leads to:
    • malformation of lungs, skull, eyes and heart
  • liver not recommended to pregnant women

Vitamin D

  • deficiencies associated with
    • mother
      • gestational diabetes & hypertension
      • preterm delivery & cesarean
    • child
      • cardiac issues: cardiomyopathy, hypocalcemic tetany --> wekaness/tetany, dysphagia
      • respiratory tract: asthma, obstructive lung diseases
  • screening: in CH first pregnancy visit checks for 25OH-D levels via questionnaire and serum levels
    • 55% of white and 83% of black Swiss women have D deficiency

B12

  • supplementation and monitoring necessar for vegans
  • B12 deficiency has (severe) consequences --> vgl Bild

Recommendations

  • Foods to avoid:
    • raw eggs, meat, and milk
    • certain cheeses
    • liver
  • Vegans & veggies
    • supplement iron, B12
    • possibly supplement Ca, n-3
    • monitor closely

Quack

  • Explain:
    • FOAD
    • DOHaD
  • What health impact does pregnancy have on mothers? (short)

Life course model & fetal origins of adults disease

  • risk for NCDs accumulates throughout life, inluding fetal life
  • periconceptional and intrauterine period most susceptible to genetic changes due to environment --> prevention must start here and girls and women health improved
    • more cost-effective to intervene in fetal than later life
    • intrauterine environment prepares child to food scarcity --> clashes with urban overnutrition
  • common associations
    • meternal micronutrient deficiences and/or undernutrition and/or overweight/diabetes --> IGUR --> thrifty phenotype
    • low brth weight --> IR
  • offspring (when girls become adult, pregnant women) becomes macrosomic: exaggerated adiposity, pancreatic islet dysfunction with tendancy to develop diabetes and similar NCDs at young age --> population's nutritional past has lare impact on population's health

Pregnancy on maternal health

  • weight retention
  • gestational diabetes persiting after birth --> T2D
  • Osteoporosis

Nutrition, Aging & Alzheimer; Troesch

EPA, DHA

  • what functions do the LCPUFA take on that are related to AH?
  • what does traditional and newer evidence suggest?
  • what is low DHA/EPA intake associated with (and what not)?
  • how do EPA and DHA interact with other important nutrients?
  • what have internvetion studies shown?

 

DHA & EPA

  • important for resolution of inflammation, counteract chronic inflammation
    • traditional understanding: EPA counterbalances ARA by production os less inflammatory eicosanoids
    • newer evidence: EPA-derived resolvins avoid overshoot of inflammation, DHA responsible for resolution of inflammation à both important to balance inflammatory reactions
    • n-3 FA also involved in methylation
  • DHA in neurons, EPA blood vessels
  • Intake of EPA and DHA associated with
    • vascular and neuronal markers of Alzheimer’s
    • not associated with cognitive impairment
    • trend for microbleeds
  • Supplementation studies
    • Beneficial effect on DNA methylation à may counteract inflammation
    • 2.2 g/d:
      • increase in cortical integrity and grey matter volume in certain parts of the brain
      • no improvement in cognitive function but executive function and verbal fluency
  • Interaction with B-vitamins (Oulhaj, 2016)
    • Higher intake of DHA improves effect of B-vitamin son cognitive function, EPA much less effective
    • B vitamins have no effect of n-3 are low, only in upper normal range

Nutrition, Aging & Alzheimer; Troesch

B-Vitamins

  • What pathway are b-vitamins involved in?
    • to what degree can pathway be affected and what are the consequences?
  • What is B deficiency associated with?
  • What effects observed with supplementation?

B-Vitamins

  • involved in DNA methylation, Phospholipid & myelin synthesis, and NT synthesis
    • depending on B vitamin, parts or all pathways are blocked (transsulfuration, remethylation via SAM, etc)
  • impaired one-carbon metabolism affects cognitive function in different ways
    • high homocysteine associated with vascular complications
    • low SAM levels associated with neurodegeneration
    • important to assess entire one-carbon metabloism --> screening only for homocysteine may overlook other parts of the pathway running too high/low
  • Supplementation with B12, Folate, B6slightly above RDA slows brain atrophy by 53% in elderly with mild cognitive imparment and baseline high homocysteine values
    • attenuation of atrophy = attenuation of further decline in cognitive function

Nutrition, Aging & Alzheimer; Troesch

Vitamin D

  • What role in neuronal tissue?
  • deficiencies
    • how common?
    • association with AH: explain different data/study types
  • supplementation studies: what was observed?

Vitamin D

  • deficiency and inadequacy defined differently --> vgl Bild
  • deficiency even in sunny countries (burka)
    • observational data: low levels associated with Alzeiherms (ES = 1.32)
    • cochrane-review: no effect of Vit D on Alzheimers
  • pleiotropic effects, inclusing in neurons
    • reulation of many neuronal processes (cell differentiation, cognition, ox damage prevention, etc)
    • reduce inflammation
    • clear amyloid plaque
  • Supplementation
    • 800 IU/d, 1 year: serum 25OH-D increases, markers for amyloid-b plaques reduced, cogintive function improved in intervention group --> requires confirmation in larger trials, but promising

Nutrition, Aging & Alzheimer; Troesch

Vitamin E

  • supplementation or food?
  • relation to genetics
  • supplementation studies: what outcomes and why important ?
    • how do supplementation studies relate to ESPEN?

Vitamin E

  • particularly beneficial effects as antioxidant, however
    • must come from foods
    • genetic non-responders: carriers of APOEɛ4 --> non-deterministic (can cause Alzheimer but will not necessarily)
  • high dose: 2000 IU (RDA x10) for 2 years delays progression of Alzheimers by ~19%
    • caregiver time reduced --> important factor because decreases burden to relatives as well as costs for institutionalized patients
    • no safety issues
    • clashes with ESPEN guidelines --> very conservative (similar to cochrane reviews), builds on amount of studies, so innovative aproaches gain less attention

Nutrition, Aging & Alzheimer; Troesch

  • Alzeheimer: pathophysiology, definition
    • how does disease modulate treatment?
  • What approaches currently most effective?

Dementia

  • Alzheimer (AH) most common form of dementia
  • age most important risk factor for developing dementia
  • pathophysiology laregly related to chronic/systemic inflammation
    • progressive diseases (NCD)
    • BBB permeability decreases --> cytokines enter neural tissue --> hyperactivaiton of microglial cells and astrocytes --> neuroinflammation --> irreversible neuronal damage
    • lifestyle modulates inflammatory state (vgl Bild)

Preventive approach

  • most promising because
    • no actual treatment available
    • dementia develops over time and manifests at irreversible stage
  • role of nutritional intervention
    • treats body as a whole --> can tackle oxidative stress, inflammation, and micronutrient deficiences
  • involves nutrition & lifestyle factors
    • due to progressiveness of disease, intervention requires flexible nutritional management

Nutrition, Aging & Alzheimer; Troesch

  • Nutritional approaches to prevent Alzheimer's
  • what are the risk factors?
  • what are protective factors?
    • lifestyle --> most promising
    • nutrition
    • associated diseases --> most preventable

Nutrition

  • Mediterranean Diet
    • antioxidants: brain areas affected by AH usually antioxidant depleted --> attenuate neuro-oxidative stress
    • fibre: supports healthy microbiome à often dysfunctional in AH patients due to polymedication
  • supplementation of antioxidants (A, E, C, Se and/or Zn at no defined level --> people either choose supplement freely or tka eno supplements, prospective) --> ~30% reduction in cognitive impairment & decline
  • healthy diet in general protective (RR ca 0.5)

Lifestyle

  • exercise allows to maintain muscle mass
    • myokines beneficial effect on metabolism + anti-inflammatory
    • protein pool
  • small weight loss beneficial at age 50-75
  • cognitive activity most protective stategy: at older age as well as schooling as teenager

Risk factors (vgl Bild)

  • cerebral microbleeds
  • sleep disturbances
  • depression
  • diabetes
  • hypertension: most preventable risk factor
  • obesity
  • stress

Nutrition and Brain, Baumgartner

Brain and cognitive development

  • what processes are ongoing: use specific terms
  • what makes first 1000d to the most important phase of brain development?
  • how does brain grow and maturate?
    • in terms of size
    • in terms of neurons and their connection and functionality
  • what affects brain development beyond nutrition?

Direct impact on brain and neural development

  • time-frame: 1000 days from concenption onwards are most important period of brain development
    • neural plasticity: brain's capacity to adapt to stimulus (good/bad) --> also capability to overcome insults and its longterm consequences
    • neural plasticity related to vulnerability: allows to overcome insults but can also take irreversible damage --> vulnerability usually outweighs plasticity
    • aged brain is less plastic and therefore more robust towards insults, but also less able to recover
  • Brain development
    • neural tube = kick-off of brain development --> 4 weeks postconception
    • brain size 25% at birth and 75% at age 2 (1000d mark; 100% = adult brain)
    • Growth curve with two phases: steepest from conception to ~1.5y, then less steep up to age 4 and after 6 least steep
      • neural connectivity: functional complexity also increases --> synaptogenesis
        • redundand connections: synaptogenesis runs off backwards after age of 8 --> important & existing connections strengthened, unnecessary ones removed
      • different brains functions develop at different time points: basic survival functions have priority, executive functions (PFC) last --> development depends on area and processes (maybe ones that depend on environment come after ones independent thereof)
    • lifetime supply of neurons available at birth --> need to be connected via synaptogenesis
      • neurogenesis still possible throughout life
    • Myelination: crucial for brain maturation because allows rapid signal transmission through complex circuitry
      • oligodendrocytes myelinate axons, process only starts postnatal
    • 3 TM
      • corticl areas
      • myelination --> iron deficiency common and dangerous (vgl Kärtchen iron
      • hippocampus

Indirect effect

  • physical activity and possibility to explore the surroundings --> input to the brain
  • relationship to parents and caregivers
    • caregiver's status also affected by nutrition and if bad, liekly to affect child's brain development