Summary Diet and Health Lecture 1-14
Summary Diet and Health Lecture 1-14
Summary Diet and Health Lecture 1-14
Lecture 1 Epidemology
Epidemiology: distribution, aetiology (cause), how disease is controlled
Yes / no question
o Population (region, age, gender) representative target pop?
o Exposure (effect of x on ↓) Binary/continuous (smoking y/n or 1,2,3)
o Outcome Binary (disease y/n) or Continuous (stages)
Binary outcome:
- Incidence # new cases per 1000 person years
Study of 10 yrs with 10000p, 56 dies. 56 per 10x10000 = 0,56 per 1000
- Prevalence total cases x in target population now
- Mortality rate ≈ incidence
Crude mortality rate (all deaths)
Adjusted for age/gender/cause
o Age adjusted = # deaths in age group x 1000 x proportion
people in specific age group / population age group
Observational studies
- Ecological compare countries/large pop. Hypotheses generating (not for testing).
Causal relationship, because groups ipv individuals.
- Cross sectional retrospective to give prevalence in large pop. Hypothesis generating. Can
assess many outcomes and exposures. Not for rare diseases.
- Case control Odds ratio: Cases population compared to control. Rare conditions and
many risk factors. Recall bias: hard to remember exposure.
- Cohort Relative risk. Prospective: follows population over time. Many exposures
and outcomes. Time consuming. Recall bias. Need large population.
Experimental studies
- Randomized controlled trials (RCT): prospective. Real evidence cause and effect. Random
assignment to treatment or control group. Reduced selection bias and confounding.
Difficult to assess specific dietary regime
Meta-analysis
Statistics
Confidence interval: the degree of certainty in a sampling method.
Interpretation or results:
- Bias (Measurement errors or misclassifications leading to results that consistently deviate
from truth): Can be everywhere in study
1. Selection bias: Volunteers often deviate from
general population- healthier and educated?
2. Information bias: Under- or overreporting on
own health or nutrient intake
• Recall (memory) bias (circumstance may lead
to different «memory» of exposure)
- Confounding
• Any factor that influences outcome and associated with exposure
• Smoking and coffee drinking very often associated
• Particularly challenging when assessing intake of complete diet
• Adjustments; confounder measured and subgroups are excluded
Confounder associated with both exposure and outcome.
Can falsely claim that coffee increases risk of getting lung cancer if you
don’t correct for smoking: exclude smokers.
Cohort: high serum levels B-carotene decreased CVD risk (actually from F&V) but in Trails it seemed
to increase risk. Because high level B-carotene is associated with fruit & veggie intake (confounder).
- Causality: need:
• Sufficient cause: a factor triggers
disease every time (genetic)
• Necessary cause: outcome is
dependent on specific exposure (virus
influenza) Risk factors only give
probability, not sufficient or necessary
(smoking – lung cancer)
So causality can’t be proven, but concl OK if
• bias, confounding and chance have been
considered
• Bradford Hill’s criteria have been met
Lecture 2 Assessment Methods
Assessment methods depend on 4Ws: Why/what/who/when?
Nutrient assessment of individuals:
FFQs: Food frequency questionnaire (Retrospective)
Simple for association dietary habits and disease.
Limitations: low accuracy, recall bias, under and over reporting and only for groups.
(under and over-reporting can be adjusted for.)
Biomarkers see appendix ppL1+2 (vitamins and FA, water soluble vitamins, minerals)
Challenges:
- Ethnic pop: different traditions - Elderly: problems with recall and
- Children: problems with recall physical limitations for recording
diet
- Low income
- Pregnant women: changes in energy unhealthy (smoking)
& nutrient needs. Underreporting of
Anthropometric assessment:
Height, weight and circumferences. Primary method WHO: easy. Reference measurements
necessary. Measurements compared to international standard population (should be homogenous,
well-nourished and cross-sectional).
Use Z scores weight-for-height, weight-for-age, height-for-age, BMI-for-age.
Z-value = standard deviation score (Observed – mean value / standard deviation of pop)
Biochemical assessment:
Objective, specific, shows intake over longer period of time, shows nature of diet (lots of veggies).
Some markers are misinterpreted. Measured in blood ipv organs where markers work…
Combination methods best (energy intake against PAL, intake fruit against biomarkers)
Delivery 40 weak after LMP = last menstruation period. Conception after 2 weeks.
3 equal trimesters. 1st (w0-8) embryonic, then fetal development
Birth weight depends on gestational age (av duration pregnancy = 266d). Low <2.5, Very low <1.5kg.
Low birthweight associated with risk of impaired neurodevelopment and CVD & diabetes later in life.
Obesity is a problem:
Mother: risk of gestational diabetes, pre-eclampsia, depression. Fetus: premature, death, large.
Pre-eclampsia: hypertension and protein in urine late in pregnancy (due to abnormal placenta?)
death mother and/or fetus. Diet interventions didn’t work (only Ca 2+ supplements)
Transition from breastmilk to complementary food between month 4-6. Gluten introduction reduces
wheat allergy. Not eat vegan. No cow’s milk <1yr. Commercial: proper intake essential nutrients.
Children: smaller and more frequent meals. Higher fat. Less fiber: satiety will reduce food intake.
Challenges: 1) obesity, 2) iron deficiency in puberty girls, 3) anorexia, 4) VitD and Ca 2 for bone
Different requirements:
Children: ca2+ for bones. Menstruation: iron. Elderly: vitamins and minerals due to lower food intake.
Lecture 4 Aging
20% Elderly >65: ↑lifespan increasing in world. Can nutrition improve healthy aging or slow it down?
Health challenges: largest risk factor disease. Cognitive (Alzheimer), disabilities, cancer / CVD /stroke
Changes:
- Total burned energies (energy expenditure) decreases
- Food intake reduced (undernutrition)
Elderly die of 1) heart disease, 2) cancer, 3) stroke, 4) diabetes, 5)
pneu/influenza, 6) COPD, 7) falling 1-3 is cause 60% of all deaths
Risk undernutrition
1) Degenerative loss muscle and bone mass
2) Reduced appetite due to
- Cholecystokinin (CCK) released after meal to suppress
hunger is elevated in elderly and sensitivity increased.
- Longer emptying time of stomach (increased satiety)
- Reduction of taste and smell in 50% elderly
Caloric restricted diet increases lifespan = 30% of normal (with all essential nutrients)
Cornaro 1500 restricted his diet to 350g of food daily and became 100yrs.
Through: - upregulating antioxidants
- nutrient sensing pathways
- suppressing insulin growth factor
o Infants and children in growth are vulnerable and should avoid veganism (and
vegetarianism): VitD and ω-3
o BMI falls abruptly after 60yrs, due to muscle loss. Too low in proteins?
Undernutrition Risk for developing world • Poor infrastructure and distribution of food
• People with tropical infections (Malaria) • Famine, war, migration
Undernutrition Risk for developed world • Overeating energy rich diet -> Obesity and
• Elderly micronutrient deficiency
• Drug addicts/alcoholism • Vegetarians (vegans)
• Refugees / homeless • Infections
• Eating disorders (Anorexia/Bullimi) • Menstruating women
Fibre: carbohydrate polymers >10 C monomers that are not hydrolysed by animal enzymes.
Lignin, carbohydrate (some starch) or synthetic. Fermentable by bacteria = prebiotics (soluble fibers)
Recommended intake 25-35g/day. Less diabetes and colorectal cancer.
Major disorders:
- Coeliac disease
- Inflammatory bowel disease (IBD)
Chron’s disease
Ulcerative colitis
- Irritable bowel syndrome (IBS)
Food hypersensitivity:
1) Food intolerance: non-immunologic adverse reaction to food (metabolic, pharma/toxic). Less
severe and slower onset.
2) Food allergy: immune response from exposure to certain food, proteins recognized by allergen-
specific immune cells. Most IgE-mediated foods (no coeliac). Fast cutaneous (skin) manifestation.
Anaphylaxis: severe life threatening allergic reaction within minutes (to food).
Coeliac disease:
Inflammatory food allergy ipv food intolerance (is immune-mediated, not by IgE)
Intolerance to gluten proteins: prolamin (wheat=gliadin, barley = hordein, rye = secalin) and glutelin (wheat).
Gluten damages small intestine malabsorption nutrients.
Diagnosed: antibodies against transglutaminase (tTG) and flattening villi small intestine (athropy and
elongated crypts!).
Most common genetic disease worldy (1 /150). 20% of all Caucasians are affected. 2 mln don’t know.
Symptoms vary, asymptomatic exists. Deficiency in nutrients cause symptoms.
Children Adults
• Delayed weight gain and growth • Diarrhea / constipation and bloating
• Abdominal bloating and pain • Fatigue / Iron-deficiency anemia
• Chronic diarrhea or constipation • Depression
• Vomiting • Weight loss and bone loss
• Pale, smelling, fatty stool • Skin rash
• Lack of energy, fatigue, anemia • Arthritis
• Infertility
Process
:
1) Gluten (glutamin or prolamin) is degraded in gut lumen resistant fragment (a-gliadin)
2) Gluten fragment enters intestinal tissue.
Endogenous enzyme: tissue transglutaminase (tTG) in mucosa.
Deaminates (a-gliadins): glutamin glutamate = glutamic acid (negative charge)
3) Can be taken up by dendritic cells in vesicles so they can present glutamic acid.
4) Negative charge allows for binding to MHC locus HLA-DQ: fits better into pocket HLA-DQ2
Normally should not be presented: DQ2/8 is wrong kind that efficiently presents it.
Even in wrong constellation HLA: normally not recognized. Need other conditions as well.
5) Naïve CD4 T-cell responds to deaminated fragment presented by MHC locus on HLA-DQ
6) Active Th1-cells attack enterocytes with inflammatory cytokines.
7) Recruit immune cells inflammation
Treatment:
Reversible by exclusion of gluten. <20ppm gluten is gluten free. Oats OK (avenin less immunogenic).
Need to label food (gluten free I more expensive). And eat 1-1.2g Ca/day.
Chron’s disease:
Prevalence: 0.3% in cities.
Symptoms: Affects only intestine and/or patchy in colon: whole GI.
Abdominal pain, diarrhoea, rectal bleeding, weight loss, fever, malabsorption.
Treatment: Immunosuppressants, antibodies, pain relief, surgery.
Risk factor: Smoking.
Genetic predisposal: NOD2 gene (problems epithelial barrier function).
Ulcerative colitis:
Prevalence: 0.25-0.5 in Western cities. (Not genetically predisposed)
Symptoms: Affects only colon (distal to proximal): takes away certain parts.
Abdominal pain, diarrhoea, rectal bleeding, weight loss, fever
Treatment: Immunosuppressant, antibodies, pain relief or surgery.
Smoking relieves symptoms: anti-inflammatory.
Risk factors:
Microbiota dysbiosis: due to genetics, antibodies, diet (low fibre, high fat), pathogenic.
Microbiome: consensus inflammation is due to that bacteria get through epithelial barrier and
overwhelm system massive inflammation.
Hygiene hypothesis: urban societies too clean: reduced training immune system so reduced
tolerance to commensal bacteria.
Diet IBD:
Diet antigen/toxin cannot yet explain IBD.
But women with high fibre (from fruit/veg, not whole grains) have 40% reduction of Chron’s disease.
High intake of sugar increases symtoms and risk, but causation unclear.
High ratio between omeg-6 (inflammatory, plant oils) and omega-3 (anti, fish) increase risk
Complex picture: Smoking, VitD, hygiene, diet
Malnutrition from IBD: painful to eat + malabsorption + more energy expenditure: inflammation.
Chron’s disease has more problems: also affects colon and not only small intestine.
Specific deficiencies Chron’s: Folic acid and VitB12 (water soluble).
and VitD ( osteoporosis, fat soluble). Iron (anemia)
Macronutrient deficiency
gives increased risk infection
and bad growth in children.
Need diet high in calories
and protein.
35-40kcal and 1-1.5g protein
per kg ideal body
weight/day. Liquid
supplements.
Irritable bowel Syndrome (IBS)
Syndrome of separate conditions. Not structural, but functional. Abdominal pain, affect work & life.
Most frequent GI disorder: 50% of Rome’s disorders = GI. Affects 10-30% western pop. More women.
4 types:
1) IBS-D (Diarrhea common, most)
2) IBS-C (Constipation common)
3) IBS-M (D and C)
4) IBS-U (Neither)
Treatment: no cure.
- 65% symptoms related to specific food: exclusion diets.
- Exercise
- Probiotics and fecal transplantation (more Lactobacillus and bifidobacter).
- Antidepressive medicine
- IBS-D: antidiarrhea medicine and serotonin antagonists to reduce motility gut.
- IBS-C: fibre (faster transit), laxatives (osmosis), pro-secretory = open Cl - channels.
Exclusion diets:
- Palaeolithic diet
- No carbohydrates diet
- Dairy free
- Low fibre gluten free
- Yeast and sugar free
- Low FODMAP (70% feel better)
PODMAP = Fermentable, Oligosaccharides, disaccharides, monosaccharides and Polyols.
Monomers that can easily reach colon and be fermented by bacteria: don’t make certain metabolites
that make IBS overreact.
New: fructan, rather than gluten increases symptoms in patients with self reported gluten sensitivity:
may have IBS and are sensitive to FODMAPs (Fructan in bread).
FODMAPs lead to high osmotic load (more water in) and readily fermentable substrate (more gas
production) luminal dissension symptoms.
Lecture 8 Metabolic Syndrome
MetS: disorder of E balance in body: collection of symptoms that occur together.
Symptoms: (need IR and 2 of 4)
Insulin resistance (top 25% FI values world) High fasting plasma glucose (>6.1 mmol/L)
Abdominal obesity BMI>30 Dyslepidemia: Low serum HDL (<1mmol/L)
Hypertension: high blood pressure >140/90 and high serum triglycerides (TG >2mmol/L)
120 blood pressure at age 20. Increases 1 mm per year because arteries stiffen over time.
Most studied: Mediterranean, unhealthy western (meat, sugar), healthy western (recomm), vegetarian.
Nutrients:
Simple carbohydrates: Monosaccharides: glucose, galactose, fructose. Gl+Ga = milk. Sucrose: Gl+Fr
Fatty acids: - Saturated
- Mono-unsaturated fatty acids (olive oil)
- Poly-unsaturated (w6=plant oils, w3=fish.
ω6 = linoleic acid, converted to AA: important inflammation signaller (ibuprofen blocks
AA and pain stimulating metabolites). ω3 = a-linolenic acid in rapseedoil, but need to
supplement it with fishoil, because it is inefficiently converted to DHA). Need to take no
more than 6x more ω6 than ω3. Western diet has lot of ω6. Both essential FA.
- Trans fatty acid (processed vegetable oils: butter. Major villain CVD)
Lecture 9 Cardio Vascular Disease
CVD = Diseases that involve heart and blood vessels. Heart and brain severely affected
Atherosclerosis is starting point CVDs (arterial wall thickens as build up lipids and cells)
Heart infarction when blood supply is totally blocked (into bloodstream).
Coronary heart disease = completely blocked coronary artery by blood clots and plaque builup.
Ischemic heart disease = partially blocked “
Cerebrovascular disease= blockage blood vessels supplying the brain.
LDL: delivers cholesterol to tissue (plasma cholesterol is LDL-bound). Gets into cell wall CVD.
HDL: removes excess cholesterol from tissues and brings it back to liver directly or via CM/VLDL.
So: ratio HDL:LDL decides CVD.
So: liver produces VLDL and Cholesterol (most cholesterol not from diet)
Atherosclerosis
Lipid cleaved into monoglycerides and fatty acid taken up in intestine enterocytes.
Repackaged with proteins to form chylomicrons (CM) goes to lymph to blood and delivers FA to
tissues (eventually liver)
Event 1: Accidental flux of LDL into intima blood vessel (because of epithelial damage) oxidized.
Event 2: Monocyte come into intima from blood and mature into macrophages.
Event 3: Macrophages take up oxidized LDL foam cells
Event 4: Apoptosis burst: release lot of fats = fibrous cap due to smooth muscle activation
plaque in vessel: recruit immune system.
Event 5: Plaque gets so big it ruptures
Many cells have receptor LDL and can reduce level LDL by degrading it to bile acid.
Patients that lack LDL receptors LDL accumulation in blood: hypercholesterolemia CVD.
Reduce cholesterol (Statins = cholesterol lowering medicine: inhibits liver synthesis) less LDL
Epidemiology
Ischaemic heart disease and stroke are top global causes of deaths.
CVD 30% all global deaths (double all cancers). More in low/middle income countries
Western part EU, USA and Australia has low prevalence CVD to Eastern EU (Russia, Mongolia).
(while big meat consumption Australia and USA)…
France lowest age adjusted death rates caused by CVD in EU (paradox! Cuz red wine/fruit?).
Bulgaria 66% of it’s deaths by CVD.
CVD is declining after 1975 in the world.
What does the global differences and change with time of CVD tell us?Global differences
Japanese men get CVD later in life.
Margarine: trans FA: molecule less bend than cis fatty acid. Lead to high levels LDL and upregulate
levels HDL!
Industrial transfats shows increased risk mortality, not from normal diet.
Mortality increased by replacing saturated fat with plant based oils: ω6 (linoleic acid) increased
cholesterol. More easily oxidized LDL-ω6
Hypertension
Condition that counts to MetS. Increases with age and family history.
High systolic blood pressure 140/90mmHg.
Sodium correlates with hypertension. Average sodium intake 4g/d, recommended 1.5g.
Create more osmotic pressure more water more blood pressure.
Blood pressure reduced by K+ (banana) and fruit and vegetables. Increased by Na+ from NaCl.
LDL lowered by fibre, statins, fruit and veggies and omega-6 (vegetable oil) (good, but ratio ω 3/6)
Increased by saturated FA, trans FA and unfiltered coffee.
Thrombogenicity (inflammation)
decreased by omega-3 (Fish)
Lecture 10
Diabetes
Diabetes mellitus = to pass through (drink a lot) – sweet/honey (lots of sugary urine).
Metabolic disorder with chronic hyperglycaemia (high levels of blood glucose) due to defect of
insulin production/action. With disturbances of carbohydrate, fat and protein metabolism .
Chemical inside Langerhans inlet cells = insulin. Synthetic insulin 1975.
Untreated death. Cause of blindness, kidney failure, hearth attacks, stroke and lower limb
amputation. Now: increased risk of CVD.
Type1: yough people
Type2: later age, obesity.
Prevalence.
>400 million diabetics worldwide. Global prevalence rises in low and middle income countries. 7 th
cause death in 2030.
Diabetes Type 1
Autoimmune disorder (antibodies against β-cell antigens). Pancreas damaged. Stops producing
insulin and glucagon.
In young age.
Causes: - genetic risk (HLA class II)
- environmental risk (toxins/infection/gut microbiota?) Different in monozygotic twins.
Treatment: insulin injection. Blood glucose monitoring (fingerprick). Autopumps give precise amount.
Future: immunotherapy to inhibit immune attack pancreatic cells. Regeneration of
pancreatic stem cells. Articficial pancreas. Glucagon treatment?
No insulin, so no uptake of glucose. Blood sugar keeps increasing, so body tries to get rid of it by
secreting it through urine, but water will follow.
Symptoms: itching, urinating, tired, drink much water and always hungry (insulin signals satiety).
Cells need to use energy, so will use fat: weight loss.
Due to lack glycagon: patients can develop fatty liver.
Hypoglycaemia: diabetics can suddenly need sugary food/drinks if they are dizzy. Means insulin is too
high and blood sugar too low, but body can’t communicate that.
Diabetes Type 2
Insulin resistance and impaired β-cell function: can’t get glucose down.
In elderly and overweight people. Due to obesity, genetics, low PAL, diet. Will probs double US 2030.
Treatment: weight loss (surgery), exercise and insulin injection.
Continually rising blood glucose levels lead to overactive pancreas. Cells are starving breakdown
glycogen to glucose from liver higher blood glucose β working harder worn-out: stop insulin
production (Vicious cycle). Can be kinda asymptomatic: undiagnosed.
Flawed glucagon secretion: elevated glucagon even in fasting stage (no inhibition by insulin).
Symptoms similar:
- Excessive urination and thirst (damage filtration glomerulus in kidneys)
- Constant hunger (lack satiety insulin)
- Fatigue (little glycogen reserves)
- Weight loss (less glucose is taken up and converted to fat)
- Vision change (vascular complications eye)
- Frequent infection.
Pancreas gets worn out due to inflammation bad diet. Vicious cycle also worns out. Chronic FFA
release from adipose tissue.
Increased ox stress and influmation has effect on genes insulin and impaired growth factor signalling
to insulin.
Management DMtII
1) Diet and exercise
Avoid overweight. Conditions exaggerate each other. Reduction 5-10% improve gluc control.
2) Oral hypoglycaemic therapy
Drugs improve insulin secretion/action
3) Insulin therapy
Injections and pumps. Or maybe regeneration
Lecture 11 Obesity
Best risk assessment methods: weight, BMI, waist, waist to hip, fat (free) mass.
- Weight tracking in pop has limitation: doesn’t take height into account.
- BMI kg/m2 doesn’t take fat free mass into account and height: overestimated in tall and athlete.
Normal (18.5-24.9) Overweight (25-29.9) Obese 1 (30-34.9) Obese 2 (35-40).
- Waist obesity >102 in men >88cm in women. Waist/hip WHR >0.85 women >0.90 men.
Waist circumference: good assessment central obesity (cut-off MetS). No info on muscle mass.
WHR same, but can mask if hips are large and harder to interpret.
Hormones
Insulin(SATIETY)
• More secretion by high blood glucose or by action of GIP or GLP-1 (released after a meal)
Leptin (SATIETY)
• Secreted from adipose tissue
• Long-term regulator of food intake
• Stimulate energy expenditure via nerves
• Stimulated by insulin
• i.e. stimulated by glucose, not by fat or fructose which do not stim insulin.
Gherlin (HUNGER)
• Only known hunger factor, released when nutrition is scarce
Triggers:
•Diet (carbs)/ Alcohol/ Portion size • Physiological trauma
• Pregnancy • Smoking cessation
• Sudden change in physical activity • Endocrinological disorders
• Impaired sleep and stress • Drugs
DNA adducts: binding between mutagen and DNA creates incorrect DNA replication cancer
Dietary mutagens:
- Nitrosamines, a.o. from (processed) meat: salting, smoking, cooking colorectal
- Heterocyclic amines / polyaromatic hydrocarbons (high temp cooking: BBQ) mutation.
- Aflatoxin from asparagillus fungus: food contaminated from soil. Liver cancer in china.
2) Alcohol
Alcohol provides enhanced uptake carcinogens, liver damage, acetaldehyde byproduct (toxic) and
hormonal change in women.
No evidence that red wine is protective (confounding: different life style vodka vs red wine)
3) Obesity:
Reflux of stomach acid irritates mucosal cell oesophagus cancer
Breast cancer because estrogen from adipose tissue stimulates cell growth
Others: low grade inflammation??
Enough evidence for decreased risk: Dietary fibre
Afrika. Better from cereal grains than from F&V?
Reduces transit time in intestine: less exposure / uptake carcinogens
Dilution / binding carcinogens
Bacterial fermentation of short-chain FA apoptosis: differentiation and anti-inflammatory.
But epidemiologically: increased intake F&V marginally associated with decreased risk cancer.
Stomach cancer:
Because H. pylori. Fruit and veggies can protect infection. Salt increses risk.
Colorectal cancer:
From polyps. Years to turn into malign carcinoma. Diet difference in countries = difference cancer.
Due to obesity, alcohol, red/processed meat. Protection by fibre and calcium (milk).
Breast cancer:
2nd common. Because alcohol, weight and weight in pre/post-menopause. Risk reduced by lactation
and physical exercise.
9 specific lessons
1. Moderate, regular physical activity.
2. Life purpose.
3. Stress reduction.
4. Moderate calories intake.
5. Plant-based diet.
6. Moderate alcohol intake, especially wine.
7. Engagement in spirituality or religion.
8. Engagement in family life.
9. Engagement in social life.