Food and Nutrition for Disease Prevention
752-6102-00L
752-6102-00L
Kartei Details
Karten | 68 |
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Sprache | English |
Kategorie | Biologie |
Stufe | Universität |
Erstellt / Aktualisiert | 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)
- cancer patterns--> cancer type and total prevalences differ between countries
- 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
- insulin resistance as key driver of cancer
- 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
- Red and processed meats: 1.2% increase
- 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
- Overall chance of contact between carcinogens & enterocytes is reduced
- 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
- CVD: increasing rates ever since population infectious diseases could be prevented/reduced --> opulations ages and becomes prone to CVD
- 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
- most nutritional sciences studies do not fulfil criteria sufficiently, so causality remains weak
- 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
- do not necessarily correlate with actual CVD mortality, although increase risk factors --> use of hard facts as more reliable information
- 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
- intermediate risk factors & soft vs hard outcomes
- 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
- negative impact on risk factors but associations show decrease in mortality
- 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
- high agreement:
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
- many studies suggesting beneficial effects of moderate alcohol consumption may be biased due to overestimation + residual confounding of moderate drinkers vs abstainers
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
- fat and muscle mass not distinguished
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!
- leptin (&insulin) activates catabolic pathway --> stops eating, be active!
- 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
- dopaminergic system rewards for eating
- 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
- reduce blood pressure
- reduce burden of co-morbidities
- reduce sedentariness
- limit sugar intake & improve nutrition in the entire family
- choice of foods
- preparation
- portions
- rythm
- company
- increase self-esteem and conflict-management
- 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
- nutritional pyramid
- 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
- E exp:
- 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
- lipogenesis for fat storage
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
- 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
- transport & storage
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
- problems
- medication for weight loss: 5-15% weight reduction
- GLP-1 analogs (liraglutide)
- also effective at reducing co-mordbidities, such as dyslipidemia
- Leptin replacement
- GLP-1 analogs (liraglutide)
- 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?)
- 8 weeks of very low calorie intake --> responders and non-responders defined as weight loss > 5% BW
- 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
- 2nd bile acids (TCA GCA TCDCA), involved in gut microbiome
- 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
- De novo lipogenesis
- 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
- inadequate maternal nutrition
- 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
- growth & development
- 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
- first half pregnancy: increased obesity, because hypothalamic centers affected
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
- mother
- 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)
- neural connectivity: functional complexity also increases --> synaptogenesis
- 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