Summary Diet and Health NMBU 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

All outcomes: Risk: from 0 (never) to 1 (always).

- Relative risk: risk of exposed group to get disease compared to non-exposed. No diff: RR=1
- Odds ratio: how likely it is that you’re exposed to risk factor if you have the disease
a/( a+b)
RR = Cases Non- OR in Case Control = 16
c /(c +d )
cases
Odds finding smoker among lung cancer patients 16x higher.
Exposed a b
(smoker) (80) (200)
a /c Non-exposed c d
OR = RR in Cohort = 12.
b/d (non-smoker) (20) (800)
Smokers 12x higher risk of developing lung cancer

 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)

- Role of chance (statistics)

• Statistics may be treacherous- but important to use good statistical methods
• When to reject null hypothesis and accept alternative hypothesis?
• Type I error (falsely rejecting null hypothesis)- risk is 5% when p<0.05
• Type II error (falsely rejecting alternative hypothesis)
Even when you reject null-hypothesis, you can never claim that alternative hypothesis is true.

- 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.)

 24h recall (retrospective)

Interviewed about consumed food past 24h. Standardized method, open questions.
Strengths: detailed, calculate daily energy intake
Limitation: time consuming, costly and interview error

 (Weighed) Food record/dairy (prospective)

Weighed (precise) or estimated. Record every food consumed (7 days).
Strengths: accurate, no recall bias. Limitations: costs time, underreporting, need literacy. ‘
Online: My Meal Mate. But database should be adjusted for each country.

 Duplicate diet (prospective)

Put aside duplicate portion of all foods participants have eaten for chemical analysis.

 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…

Status of essential nutrients:

• Protein and essential amino acids
 No good indices for tissue proteins
 In case of very low protein status-albumin in blood/serum is used as marker
 Protein intake can be measured in urine (Nitrogen excretion)
• Fatty acids
 Profiles in serum/plasma (often prone to variation)
 Biopsies or red blood cells may be better to measure
• Fat soluble vitamins: Vitamin A, vitamin E, vitamin D measured in blood
• Minerals: Iron, zinc and selenium

Functional Assays to measure a biological response:

• Oxidative stress • Homocysteine • Gene expression profiles • Gut bacteria
• Protein levels • Hormones • Immune response

Combination methods best (energy intake against PAL, intake fruit against biomarkers)

Need high validity and high reproducibility.

Lecture 3 Diet in Different Life Phases
(Pre)-pregnancy
<22% body fat associated with reduced ovulation (Av=28%). Minimal BW to start menstruation,
higher to restore menstrual cycle.

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.

1. Maternal status (nutrient intake and absorption)

2. Placenta function
3. Fetus (utilize nutrients)

Low birthweight associated with risk of impaired neurodevelopment and CVD & diabetes later in life.

Recommended energy intake (no ideal one)

Need weight gain during pregnancy (av 13kg, recommended 11-16kg). (Uterus, fat, fluid, baby)
For obese recommended gain 5-9kg, but needs to be lower?!
Theoretical E demand: 310kcal (1.3MJ) extra per day.
Why: Gradual rise in dietary intake during pregnancy, but calculated extra energy intake is 0,3-0.6MJ.
Because basal metabolism falls in early pregnancy (rise in last trimester).
Recommendation: increase energy intake last trimester 0.84 MJ/d.

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)

Placenta functions as lung, waste elimination of fetus and nutrient transfer.

Gives increased availability of nutrients in last part pregnancy.

Dietary intake: normal diet recommended.

Need more vitamin A/C/D/Bs and proteins.
More folate B9: neural tube (for methylation of DNA. From liver, leafy vegetables, nuts legumes)
Significantly decreases lots of lethal neural tube defects (NTDs).
Need Omega3 from fish, but watch out with fat fish due to mercury and toxins.
Infancy, lactation and childhood
Newborns need VitK shot: because passage over placenta and in breast milk is low.
For blood coagulation/clotting. Low  bleeding and blood loss.

Breast milk is best for babies. Good profile aa and FA.

Colostrum: h as proteins (colostrum), high PUFAs (Omega3&6), vitamin A.

During lactation: increased E demand 500-600kcal. Help reduce weight mother.

Advantages milk: VitA, Ca2+ and P for skeleton. Low cost. Clean and benefits microbiota. Enzymes and
facilitates absorption nutrients.
Immune boost: immune cells, sIgA, lactoferrin (binds iron to avoid growth pathogens), lactobacillus.
Problems: milk low in VitK, B and D. Transmission of drugs, infection or antibodies.

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

Aging: - accumulation of DNA damage

- accumulation cell damage (free radicals or waste products)
- telomere shortening (finite divisions possible)

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

Institutionalized elderly much larger risk of undernutrition.

7% elderly in community undernourished, 30% are overweight: obesity.
 disease (hypertension, diabetes, atherosclerosis, arthritis, disability).
Why: reduced BMR (basic metabolic rate) and physical activity.
Vicious cycle: disability  reduced physical activity.

Progressive loss of proteins, reduced protein synthesis. Recommended: intake 1-1.25g/kg/day.

Increase: protein, vitamin D (so Ca2+ can work) and vitamin B6/12.
vitaminB6/12 for cognitive and CVD. More Ca and VitD: bone mass. More iron: anemia.
Supplementation with vitE (antiox), chocolate and fish delays dementia: less oxidative stress to brain.
VitB6/12 (= folate) determine homocysteine levels, which is risk factor for Alzheimer’s: reduces
regional loss of gray matter and slight improvement cognition. Need high dose: not through diet.

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

Adverse: susceptible to infections.

Can increase life span in many species, but not yet
proven in humans.
Caution: caloric restriction is also protein restriction. Ok when young, not when older.

Lecture 5 Vegetarian Diet

 Various reasons for being vegetarian (health, ethical, religious).

 Different variants: total abstinence of meat/ fish to occasionally.

Ovo-vegetarian (eggs), lacto (dairy), pesco (fish but not meat)
Demi (occasionally), vegans, fruitarians (raw fruits), macrobiotic (meat ok if hunted wild)

 In general vegetarians have adequate intake of most nutrients and proteins.

Vegetarian diet is not nutritionally dense  need more variety.
o Protein: few plants offer all 8 essential aa’s and harder to digest, but together = enough.
o Fatty acids (ω-3): vegetarians slightly lower saturated fats and vegans a lot lower.
ALA: higher in vegetarians: a-linolenic acid (plants short ω-3 FA) converted to longer ω-3 FA
with low efficiency  lack ω-3 consequences for CNS development and function.
DHA: docosahexaenoic acid (from fish) lower in vegetarians.
o Lack of B12 in 30% (and omega3 fatty acids). B12 from liver, meat fish: synthesized by gut
bacteria. deficiency of B12 increases homocysteine (tHcy)  CVD or dementia?
o Lack iron. From wheat, pulses, dark green vegetables and dried fruit. Deficiency in women
and people relying on rice ipv wheat. Iron from plants less bioavailable than meat.
o Vit D sufficient in vegetarians. Lack VitD in children on vegan diet. High intake phytate from
plants may lower calcium uptake.

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?

 Health: normal growth in children (after 5 years).

1) vegetarians are lighter (less obese, caution: quickly falls in elderly),
2) reduced cardiovascular disease,
3) reduction diabetes II
4) less overall cancer. No difference in stroke.
Need to adjust for reduced alcohol and smoking in vegetarians (confounding factors):
Gives lower mortality of CVD and slight cancer protection.
(avoidance hazardous production or saturated fat)
Lecture 6 Malnutrition and deficiency
Malnutrition: insufficient / too much nutrients causes illness. $3.5 trillion
= overnutrition causes obesity, hypervitaminosis, iron toxicity. $1.4 trillion
= undernutrition: insufficient protein, energy, vit (vA, iron and iodine). $2.1 trillion
Undernutrition because of - energy and protein deficiency
- vitamin and mineral deficiency
Obesity can lead to undernutrition of certain nutrients!

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

Severity undernutrition determined by anthropometry

Children: - weight for height (low = wasting)
- height for age (low = stunting)
Adults: - BMI (mild <18.5 / MAM=moderate acute malnutrtion <17 / SAM=severe acute <16)
- skin thickness and arm circumference

Three features undernutrition in poor regions:

1) stunting (low height)
Due to lack leucine for linear bone growth and lack Ca, VitD, VitA, zinc, copper.
40% children <5yrs developing countries. In EU because weird diets.

2) Wasting (Marasmus) = thinness / energy deficiency

Starvation, caused by low food supply or infection. Gradual thinning of body (emaciation).
Not edema (swelling of body)
 3) Kwashiorkor = protein deficiency (+ wasting) = baby 1 when new baby comes.
Protein deficiency + micronutrient deficiency (changing from breast milk to starch lacking aa)
Edema: triggered by infection. Reduced albumin in blood  water loss from blood to
interstitial. Oxidative stress compromise protein function and more water loss. Death 20%.
Rare Asia, much in Africa. Protein deficiency there 3-7%, fatality less: immunization and VitA.
Case: nutritional stress in pregnancy, because of malaria and deficiencies iron and VitA. Infant low birthweight,
infection and underfed with weaning diet of low nutrient density. Get an infection later (measles)  metabolic
illness oedema and loss of pigment  fatality.

Prevention and treatment of malnutrition

• IMPROVE NATIONAL LEADERSHIP • Exclusive breast feeding for <6 months:
• Nutritional screening in health care centre weaned babies need E dense food.
• Nutrient dense food added to regular diet • Cheap weaning food & food in school
• Adequate energy intake in mothers: restrict • Adapt to local dietary traditions
hard work

Vit A deficiency (VAD): developing countries

Retinol/B-carotene. For retina, immune system (gut and T-cels), differentiation in embryogenesis.
Retinol in animal (liver, milk, meat). Precursors B-carotene in plants.
VitA Deficiency (VAD): <0.7umol/L. Night blindness, xeropthalmia (dry + scarred cornea), blindness.
VAD leading cause of blindness in children: 0.5mil blind every year, also pregnant women.
More risk death due to infections.
Availabilty? Limited meat, only B-carotene from seasonal plants. And need fat to take up VitA.
Traditional African diet has not enough VitA. Demand Vit A higher during growth and infection.

Iron: global, mostly poor regions

Needed to bind O2 in haemoglobin. e- carrier in e- transport chain.
But excess iron is toxic: oxygen radicals.
Source Haem-iron in meat and fish haemoglobin and myoglobin (5-10% dietary intake)
Non-haem iron in cereals, legumes, dark green leafy vegetables. (Cereals 30-50% iron intake)
Recomm: women 15mg/d. Men 9mg/d. Only 0.5-2mg is absorbed from intestine. Much better
absorption form haem than non-haem iron. So haem is 5% intake but 20-30% of uptake.
Iron deficiency: Most common disorder. In pre-school children and women (before menopause).
Common in vegetarians. Vit C reduces non-heam Fe 3+ to Fe2+ for better uptake.

Iodine: global, need during pregnancy

Essential mineral to synthesize thyroid hormones to manage metabolism.
Thyroid gland secretes T3 and T4. Low  low metabolic rate: bad gluco/proteo/lipo -genesis/-lysis
Source: sea food (white fish, seaweed, shellfish) and fortified salt. Milk. Soil determines [plants].
Recomm: adults 150ug/d. Pregnant women: 220g/d and lactating 290g/d.
Iodine deficiency disorders (IDD): 100ug/L urine  Hypothyroidism.
Because iodine deficient soil EU + Africa: poverty areas far from sea. Toxin linamarin inhibits uptake.
Health: fetus death or poor CNS development. Mild: cognitive decline later on. Goitre (thick neck).
Pop: famines, refugees, hospitals, alcoholism, poverty, vegetarians, pregnancy, <5yr children, elderly.
Lecture 7 Diseases of gastrointestinal system
GI system = GI tract + digestion organs (tongue, salivary glands, pancreas, liver, gallbladder).
Function: 1) transport nutrients and water into body (digestion and absorption)
By: break down food to enable uptake. Release vitamins and minerals, reuptake water and bile.
2) remove undigested food and waste through feces

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.

Microbiota: bacteria that inhabit niche. 1013 bact

Can be commensal and/or pathogenic.
Bacterial enzymes can utilize complex carbs.

Produce SCFA (short-chain FA): lower pH, signalling.

Acetate, propionate, butyrate.

Two type of gastrointestinal disorders:

1) Structural GI disorders:
Bowels look
abnormal, any GI spot.
Can be acute <2wks, chronic>4wks or recurrent.
2) Functional GI disorders (FGIDs):
Structure normal, but function abnormal, like
IBS and
constipation. Gut-brain-axis important.
Problems can be with motility, secretion, inflammation,
digestion/absorption (secondary).
Plus cancers: colorectal, gastric, liver, pancreas.

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.

Inflammatory bowel disease (IBD)

Prevalence increasing in north of Western countries. Immigrants to west have increased risk.

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)

Bristol stool chart used to classify severity diarrhoea or constipation.

Rome foundation: criteria FGIDs (Frequent GI Disorders)
Rome IV replaced Rome III

New in Rome: more emphasis on gut-brain axis.

IBS = hypersensitivity to movement and metabolites of gut. Increase contractional muscle gut which
increases diarrhoea. Anxiety and stress-related.

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.

Prevalence: > 1/3 developed world.

Risk: High risk: diabetes and CVD. Obesity risk factor MetS.
Prevention: lifestyle modification, reduce stress and more physical activity
Cause: question: what kind of Carbs (sugar, starch, fiber), Proteins (red and processed meat)
and Fats (un/saturated, trans fat and cholesterol) should we eat?

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.

Unhealthy lifestyle  High risk diseases (hypertension, diabetes, hyperlipidemia, obesity)

(+ age and family history)  organ damage (heart disease, stroke, kidney disease)

Lipoproteins: chylomicron, VLDL, LDL, HDL

 Chylomicron delivers FA to organs after meal from blood  smaller and smaller  chylomicron-
reminants taken up in liver.
 Liver will produce VLDL (Very Low Density Lipoprotein) if excess fat. Elevated in MetS.
VLDL and chylomicron: deliver FA to tissue.

 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.

Seven country studies: Criticized

Saturated FA in diet increases serum LDL-cholesterol that leads to high CVD risk.

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.

Most risk CVD: Decreases risk CVD:

1) Trans fat 1) Polyunsaturated fat
2) Saturated fat 2) Monounsaturated fat
Replace saturated FA with trans fat increases risk. Reduced risk by monounsaturated.
Replace saturated FA with sugar  increased risk. Leading cause?
33% increased risk with replaced high energy refined carbohydrates.

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.

Dietary Approaches to stop hypertension (DASH):

Normal diet compared to DASH diet (rich in fruits, grains, fibers. Low in meat, fat, sweets).
Modified for salt: both either high or low amount salt.
Healthy diet + = low systolic blood pressure.
low salt= low systolic blood pressure.
Healthy diet + low salt = lower systolic blood pressure.

Cafestol and Kaveol = LDL stimulus (coffee). Need to filter in paper.

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.

HDL lowered by trans FA

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.

Normal Blood glucose control

Glucose from food in bloodstream. β-pancreas recognizes spike blood glucose and releases insulin.
Sugar recognized by membrane receptor GLUT2  close K channels  depolarization  ca2+ influx
 fusion insulin vesicle with membrane for exocytosis.
Insulin binds to insulin receptor that activates glucose receptor in cell.
 Lower blood sugar and increased energy storage, because of:
 Increased glucose uptake, glycogen storage, pyruvate synthesis and fat storage.
Insulin signals adipose cells to take up glucosefat. And in liver: glucoseglycogen. Muscle: E use.
Effect insulin is equalize glucose level blood and tissue: decrease blood sugar.
High blood glucose:
1. High blood glucose leads to insulin release from bcells of the pancreas
2. Insulin increase uptake of glucose from the blood into cells such as muscle cells.
3. Leads to storage of glucose as glycogen in the liver and fat in adipose tissue
4. Insulin stops glucose release from the liver and stops lipolysis in adipose tissue High blood
glucose =save/build for late

If blood glucose is too low after exercise:

Balance by releasing glycogen from liver to glucose by glucagon from α-pancreas cells.

Low blood glucose:

1. Low blood sugar causes a-cells in the pancreas to release glucagon
2. Glucagon causes the liver to release glucose
3. Causes the pancrease to produce less insulin
= spend storage. Make energy avialable

Diabetes type I and II

Type I: no insulin so no key to get glucose into cell
Type II: insulin resistance. Most keys won’t fit, so compensating with producing more insulin which
wears out β-cells pancreas  lower levels of insulin.

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).

Insulin receptor due to many different genetic defects:

- Less InsR on surface (transport/synthesis)
- Flawed downstream signalling

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.

Diagnosis: high blood glucose: FBG >7mmol/L. 2h plasma glucose >11.1.

Haemoglobin in red blood cells is glycosylated: HbA1C.

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.

VAT (apple) worse than SAT (pear)

More visceral fat is high risk CVD.
Vat: bigger adipocytes, more inflammatory,
less lipid storage capacity and insulin
resitance.

Fat / fat free mass with DXA scan or MRI.

Hormones
Insulin(SATIETY)
• More secretion by high blood glucose or by action of GIP or GLP-1 (released after a meal)

CCK: Cholecystokinin (SATIETY)

• Acts on brain to stimulate bile and pancreatic juice + intestinal motility

PYY: Peptide YY (SATIETY)

• signals precence of food in the lumen

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

Evolution: storing fat is important

- Buffer for starvation, seasonal access and E for brain
- Reproduction and sexual selection
- Adaption to cold climate
- Immune function
 - Growth
Genetic deficiency of leptin or excess ghrelin.
Populations migrating to Western diet more 19x prone: used to hunger period and used to convert
more calories into fat and low fat metabolism, needed for plant diet.
Western lifestyle: eat more and move less.

Triggers:
•Diet (carbs)/ Alcohol/ Portion size • Physiological trauma
• Pregnancy • Smoking cessation
• Sudden change in physical activity • Endocrinological disorders
• Impaired sleep and stress • Drugs

Food intake control system not designed for excessive intake.

Over-eating leads eventually to disturbance: leptin (satiety) resistance
Eat too much  too much leptin produced  stop responding: higher blood levels leptin.
Lecture 12 Diet and Cancer
Lecture 12 & 13 Diet and Cancer

Bad diet: meat, meat products, salt, obesity, alcohol.

Good diet: dietary fibre, fruit and vegetables.

Inflammation causes cancer:

ROS (reactive oxygen species)  promotes mutations  tumor initiation
Gives growth factors, reduces apoptosis and supports metastasis.

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.

Enough evidence for carcinogens:

1) Meat
Consistent findings that meat increases risk of colorectal cancer with 10-20%.
High processed meat (sausages) = convincing. Red meat: still probably carcinogenic.

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.

Hypothesis: plant-based diet reduces risk cancer (bioactive molec: phytochemicals).

Phytochemicals  dampen chronic inflammation and oxidative stress  reduce risk cancer.

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.

Walter Willett’s 4 paradigm(shifts)

1. Dietary mutagens important for cancer  NOT SO IIMPORTANT
2. Type of FA important  NOPE
3. Fruits and veggies reduce cancer drastically  NO only minor
4. Obesity is most important contributor to cancer  YES

Recommendations to reduced cancer

▪ Be as lean as possible
▪ Integrain physical activity in everyday life
▪ Limit consumption of energy-dense foods. Avoid sugary drinks.
▪ Eat mostly foods of plant origin (to reduce obesity)
▪ Limit intake of red meat and avoid processed meat
▪ Limit alcoholic drinks
▪ Limit consumption of salt
▪ Aim to meet nutritional needs through diet alone
Highest priorities:
• Developed countries: 1) prevent smoking, 2) reduce prevalence of overweight/obesity and 3)
reduce consumption of alcohol.
• Developing countries; diet-related cancer prevention recommendations need to be considered in
the context of the diets and lifestyle of each population.
Lecture 14 Dietary recommendations

Sustainability is becoming part of dietary guideline.

Blue zones-What do they have in common

• Family – put ahead of other concerns
• Less smoking
• Semi-vegetarianism – majority of food derived from plants
• Constant moderate physical activity
• Social engagement –integrated into their communities
• Legumes – commonly consumed

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.