nusctx-10-lecture-notes.pdf

lOMoARcPSD|47087965 NUSCTX 10 Lecture Notes Introduction To Human Nutrition (University of California, Berkeley) Scan to open on Studocu Studocu is not sponsored or endorsed by any college o...

lOMoARcPSD|47087965 NUSCTX 10 Lecture Notes Introduction To Human Nutrition (University of California, Berkeley) Scan to open on Studocu Studocu is not sponsored or endorsed by any college or university Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/1 University of California, Berkeley NUSCTX 10: Introduc琀椀on to Human Nutri琀椀on Fall 2023 Lecture 1 – Introduc琀椀on: The Modern Field of Nutri琀椀on, Health, and Chronic Disease Importance of Understanding Nutri琀椀on and Metabolism  Nutri琀椀on/metabolism-related disorders have become the most important and prevalent diseases in the world, but are no longer primarily de昀椀ciency problems Obesity is an Epidemic with Remarkably Changing Demographics  Prevalence increasing in the US and the world o Increased from 15% (1976-80) to ~33% in US adults now  Interna琀椀onal disease, not just in a昀툀uent countries  Common in youth, not just middle age and older  Associated with socio-economic status  Highly related to cardiovascular disease, diabetes mellitus, liver disease, etc. What is Obesity and Overweight?  Disorder of body fat (excess body fatness rela琀椀ve to lean 琀椀ssue)  Iden琀椀昀椀ed in prac琀椀ce usually by body weight/BMI o Body Mass Index = kg/m^2  BMI > 30 (obese)  BMI > 27 (overweight)  Criteria for obesity vary by age, sex, and ethnic group Changing Demographics of Obesity  Prevalence now higher in lower socio-economic groups in the western, developed world  Prevalence is higher in minority groups in the US  Tremendous increase in prevalence in young people  Accelera琀椀ng increase in less developed countries o Asia, South America, urban Africa, Central Europe, etc., where obesity used to be rare, obesity and related diseases are now common Diseases Associated with Overweight/Obesity  Diabetes mellitus (type 2); high blood pressure; dyslipidemia; cardiovascular disease, stroke; liver disease (NAFLD); cancers (colon, prostate, breast); gall bladder disease; reproduc琀椀ve dysfunc琀椀on (PCOS); depression; sleep/breathing disturbances; cogni琀椀ve dysfunc琀椀on (Alzheimer’s) Interest in Macronutrient Content of Diet  Easier to tell someone what type of food to eat/not eat than how much  Changes in diet composi琀椀on can be induced experimentally and tested for e昀昀ects  Di昀昀erences in diet composi琀椀on exist among popula琀椀ons, allowing epidemiologic comparisons  Changes in diet composi琀椀on have occurred in the popula琀椀on Lecture 2 – Energy Balance and Obesity Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/2  There is adap琀椀ve energy expenditure (EE)– we burn more or fewer calories each day in response to increased or decreased energy intake Implica琀椀ons of Dynamic Energy Balance Equa琀椀on  Predic琀椀on of who gains weight o E.g. Siblings with di昀昀erent energy expenditure gain weight di昀昀erently in calculable way  Treatment of obesity: why diets almost always fail o Easy to lose weight; hard part is maintenance  Alterna琀椀ves to gaining weight for achieving energy balance: healthy and unhealthy  Characteris琀椀cs of individuals with long-term maintenance of weight loss Why Do Most Diets Fail?  Human body is programmed to defend our body weight by reducing calories burned (energy expenditure) when we lose weight/reduce intake o In addi琀椀on to increasing appe琀椀te  Our bodies ac琀椀vely work against us when we try to get to a lower weight Fitness/Fatness Dis琀椀nc琀椀on  Fitness: capacity to do aerobic work  Can one person be “fat” and “昀椀t”? o E.g. Sumo wrestlers  Thin but “un昀椀t”?  Lean un昀椀t men have higher cardiovascular disease (CVD) mortality than obese 昀椀t men o “Skinny fat” Cardiorespiratory Fitness  Opera琀椀onally: exercise capacity on a treadmill  Conceptually: capacity of body to do aerobic work  Physiologic basis: o Capacity to deliver oxygen to 琀椀ssues  Cardiac output and delivery to working 琀椀ssues  Oxygen carriage (red blood cells, hemoglobin)  Oxygena琀椀on of blood (lung func琀椀on) o Capacity of 琀椀ssues to consume oxygen  Mitochondrial mass and func琀椀on of working 琀椀ssues  Energy storage and mobiliza琀椀on capacity  Capillariza琀椀on of 琀椀ssues Why Fitness Ma琀琀ers  Indirectly alters risk factors for disease (blood lipids, blood pressure, insulin sensi琀椀vity, glycemia, etc.)  Directly alters risk factors for disease (be琀琀er mitochondrial func琀椀on, perfusion of organs, etc.) Lean Tissue Burns Energy  Major determinant of Res琀椀ng Energy Expenditure is lean body mass o Burn more calories even while res琀椀ng Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/3  Exercise not only burns calories during the ac琀椀vity, but changes the composi琀椀on of your body (more muscle, less fat) Lecture 3 – Epidemic of Obesity: Health Consequences, Confounding Factors Cardiovascular Disease (CVD)  Risk factors are well known and most are associated with obesity: o High blood pressure o High cholesterol (LDL) o Dyslipidemia (high [TG], low [HDLc], dense LDL, high [apoB]) o Diabetes (glucose intolerance, impaired fas琀椀ng glucose) o (Obesity) o Clo琀 ng altera琀椀ons (dys昀椀brinolysis) o Cigare琀琀e smoking Synergis琀椀c E昀昀ects of Mul琀椀ple Risk Factors for CVD  Most people who get CVD do not have marked eleva琀椀ons in a single risk factor o Most commonly, modest increases in several risk factors present in the same individual  Synergis琀椀c risk from mul琀椀ple factors occurring together; combina琀椀on of mul琀椀ple risk factors has been considered as a separate condi琀椀on (a “syndrome”) o Syndrome: a complex of concurrent things Mul琀椀ple Risk Factor Syndrome– Di昀昀erent Names Given  Metabolic Syndrome (Syndrome Metabolique)  Syndrome X  Insulin Resistance Syndrome  Deadly Quartet  Familial Dyslipidemic Hypertension Metabolic Syndrome  At least three of the following: o Fas琀椀ng glucose ≥ 100 mg/dL o Waist circumference > 102 cm in men, > 88 cm in women o Serum triglycerides ≥ 150 mg/dL o HDL cholesterol < 40 mg/dL in men, < 50 mg/dL in women o Blood pressure ≥ 130/85 Insulin Resistance  A state (of a cell, 琀椀ssue, system, or body) in which greater-than-normal amounts of insulin are required to elicit a quan琀椀ta琀椀vely normal response  Two types of diabetes: o DM1: auto-immune disease of the pancrea琀椀c islet  Low levels or absent insulin o DM2: disease of insulin resistance and beta cell failure  High, “normal,” or low insulin levels (depending on the stage of disease)  Early disease typically having high insulin levels Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/4 Insulin Ac琀椀ons: “Anabolic” Hormone  Produced in pancreas  Muscle: increases glucose uptake and storage; increases protein synthesis and reduces protein breakdown  Fat: increases fat storage, reduces fat breakdown  Liver: increases glucose storage; decreases glucose release from liver into blood  Other 琀椀ssues: increased cell prolifera琀椀on Role of Obesity and Insulin Resistance in the Metabolic Syndrome  Obesity  insulin resistance & hyperinsulinemia  hypertension, dyslipidemia, pancrea琀椀c exhaus琀椀on/glucose intolerance, hypercoagulable state  type 2 diabetes, CVD, nonalcoholic fa琀琀y liver disease, etc. Nonalcoholic Fa琀琀y Liver Disease (NAFLD) and Nonalcoholic Steatohepa琀椀琀椀s (NASH)  30 years ago, three primary causes of liver disease and cirrhosis: o Alcohol intake, viral hepa琀椀琀椀s (A, B, C), gall bladder disease  Today, NAFLD/NASH is the leading cause of liver disease in the US o 90 million Americans with NAFLD  ~ 1/3 get NASH and ~ ¼ of NASH get cirrhosis Insulin Resistance/Hyperinsulinemia Drives Fat Synthesis in Liver  Weight-matched obese subjects without fa琀琀y liver synthesize less fat in liver than obese subjects with fa琀琀y liver  The higher the fat content of liver, the higher the liver fat synthesis rate  Higher fat synthesis correlates with lower sensi琀椀vity of muscle to uptake of glucose (glucose Rd) during insulin/glucose infusions  Higher liver fat synthesis correlates with lower hepa琀椀c insulin sensi琀椀vity index (HISI) during insulin/glucose infusions  Implica琀椀ons: bodies programmed to get fa琀琀y livers when muscle and liver become resistant to the usual ac琀椀ons of insulin on blood glucose o Insulin levels increase to control blood glucose o Higher liver fat synthesis correlates with higher blood insulin levels around the clock o Higher the fat content of liver, higher the liver fat synthesis rate o Physiology may explain why there is such an epidemic of fa琀琀y liver disease Associa琀椀ons with Obesity  Sleep apnea/breathing disturbances  Cogni琀椀ve dysfunc琀椀on (Alzheimer’s)  Polycys琀椀c Ovarian Syndrome (PCOS) o Insulin s琀椀mulate ovarian hormone produc琀椀on, disturbing normal period; fat cells convert estrogen to male hormone, causing menstrual disorders and skin problems  Liver disease (NAFLD/NASH)  Cancer– colon cancer risk factors o Used to be thought that meat/fat intake was epidemiologic correlate of colon cancer o Mul琀椀variate analysis now shows that two leading risks are obesity and sedentary lifestyle Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/5 What Type of Fat Stores Ma琀琀er  Tendency to release fa琀琀y acids into the blood stream: big fat cells and visceral fat cells release more fa琀琀y acids (are more lipoly琀椀c)  Adequacy of adipose fat storage capacity: paradoxical e昀昀ect of lipoatrophy (absence of subcutaneous body fat) and drug therapies that increase subcutaneous fat (glitazones) o Lipoatrophy: rare gene琀椀c disease with inability to store subcutaneous fat  Individuals have all the features of metabolic syndrome  Loss of subcutaneous fat with HIV-an琀椀retroviral medica琀椀ons has the same adverse metabolic consequences  Real problem may fat in non-adipose 琀椀ssues (liver, muscle, pancreas): “metasta琀椀c fat syndrome” o Glitazones:  Treat T2D and insulin resistance  S琀椀mulate adipose precursor cells to divide and di昀昀eren琀椀ate into mature adipose cells  Increase subcutaneous fat (make people fa琀琀er) but reduce size of fat cells that are present (more fat cells)  Insulin resistance and liver fat o昀琀en reduced  Fat in adipose stores under skin may not be real problem– trouble occurs when it spills into the rest of the body Is All Body Fat the Same?  Fat loca琀椀on: central vs. gluteo-femoral adipose, or subcutaneous vs. internal (“apple” vs. “pear” shaped obesity) o Central obesity/internal fat associated with much worse health outcomes  Cell size and number (“hypertrophic” vs. hyperplas琀椀c” obesity): big fat cells worse to have than many small fat cells Lecture 4 – Macronutrient Diges琀椀on, Absorp琀椀on, Metabolism Nutrients  Dietary chemicals that provide: o Energy: kilocalories/kilojoules  1 kcal = energy to warm 1 g of water (1º C = 4.2 kJ) o Heat: thermogenesis o Structure: tendons, cells, organs, muscles, bones o Func琀椀on: metabolic pathways that make things happen that have func琀椀onal consequences o Regulatory/signaling molecules: hormones, cytokines, adipokines  Food delivers dietary chemicals, nutrients, etc. Dietary Cons琀椀tuents  Macronutrients: protein, carbohydrates, fat/lipids, water  Micronutrients: vitamins, minerals  Fiber: complex non-diges琀椀ble carbohydrates  Phytochemicals and other cons琀椀tuents of food: trace chemicals in foods that are not 昀椀ber, macronutrients and micronutrients, but may impact health Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/6 Protein  All proteins consist of amino acids (AA) linked end-to-end  20 common AA  Some are essen琀椀al: human body cannot make them and must obtain them from diet  Some are condi琀椀onally essen琀椀al: may not be able to make su昀케cient quan琀椀琀椀es (depending on rate of growth/diet)  Some are non-essen琀椀al: our cells can synthesize them  Proteins are involved in growth, maintenance, and repair (they supply AA)  Proteins carry out most of the func琀椀ons in the body and conserved when possible o E.g. in starva琀椀on or calorie de昀椀ciency  Meat, 昀椀sh, poultry, dairy products, legumes, and grains provide high amounts of protein  4 kcal/gram as energy Carbohydrate  Simple sugars and complex carbohydrates  Simple sugars (sucrose, lactose)– most comprise of 2 a琀琀ached sugars o Sucrose = glucose + fructose o Lactose = glucose + glucose  Complex carbs (grains, beans, peas, potatoes)– slower absorp琀椀on o Certain types of complex carbs promote be琀琀er blood glucose (glycemic) control than simple sugars  4 kcal/gram as energy Fat  Family of lipids  Fats evaporate; easy to smell  Triacylglycerol (TAG) or triglyceride (TG)  Consists of fa琀琀y acids (FA) bound to glycerol  FA provide concentrated energy o 9 kcal/gram as energy  Dense energy storage without requiring water o Hydra琀椀on is more e昀케cient  Humans have a large capacity to story fat o Excess CHO or protein will be converted into fat (TG) Vitamins  Organic chemicals required in small amounts for health because our bodies cannot synthesize them  Cofactors (co-enzymes) for metabolic reac琀椀ons; precursors to signaling molecules (like hormones)  Regulate metabolism of other dietary chemicals, maintain normal growth and cell func琀椀on  Necessary for life and health  Fat-soluble or water-soluble o Fat-soluble: A, D, E, K o Water-soluble: B1, B2, B3, B5, B7, B9, B12, C Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/7 Minerals  Components of 琀椀ssues, including bones (Calcium, Ca++); and many life-suppor琀椀ng systems, such as oxygen transport enzymes (iron, Fe++/+++) and DNA structure (zinc, Zn++)  Major minerals (quan琀椀ta琀椀vely) needed in large amounts: calcium, phosphorus, magnesium, sodium, potassium, sulfur, chloride  Trace minerals needed in small amounts: iron, zinc, iodine, copper, manganese Fiber  Non-diges琀椀ble carbohydrate (not a nutrient)  Gives plants support; not usually digested  Soluble and insoluble o Soluble: absorbs cholesterol, which prevents its uptake o Insoluble: speeds transit of foods through the diges琀椀ve system Water  Solvent of living organisms  Our cells are composed of more than 70% water  Bodies typically have higher % water when young; decreases as aging occurs (less lean 琀椀ssue)  Distributes without barriers through body  Water balance 琀椀ghtly regulated  Transports nutrients and other molecules to cells/within cells  Rids body of waste materials  Regulates body temperature Diges琀椀on and Absorp琀椀on  Diges琀椀on: converts chemicals in food into molecules that can be absorbed  Absorp琀椀on: transports digested molecules from gastrointes琀椀nal tract into interior of the body  Gastrointes琀椀nal (GI) tract: hollow tube consis琀椀ng of mouth, pharynx, esophagus, stomach, small intes琀椀ne, large intes琀椀ne (colon), and anus o Topographically outside the body: epithelial surface contacts external world  Important for cancer risk  Transit 琀椀me: amount of 琀椀me it takes food to traverse the length of the GI tract  Feces: waste consis琀椀ng of unabsorbed residue (昀椀ber), bacteria, intes琀椀nal cells, water The Diges琀椀ve System  Organs of the GI tract: o Mouth, pharynx (swallows), esophagus, stomach, small intes琀椀ne, large intes琀椀ne, anus  Accessory organs: salivary glands, liver, pancreas, gallbladder  Diges琀椀ve hormones: o Stomach and duodenum secrete diges琀椀ve hormones (pep琀椀des) o Pep琀椀de hormones alter:  Acid produc琀椀on by stomach  Appe琀椀te  Use of glucose by 琀椀ssues  Water and bicarbonate release  Pancrea琀椀c enzyme secre琀椀on into small intes琀椀ne  Diges琀椀ve enzymes: Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/8 o Salivary glands, stomach, pancreas, small intes琀椀ne secrete diges琀椀ve enzymes (proteins) o Enzymes break down carbohydrates, proteins, pep琀椀des, and lipids, including TG Large Intes琀椀ne  Colon and rectum  Large intes琀椀ne absorbs water, and some vitamins and minerals  Intes琀椀nal micro昀氀ora (bacteria) are produced here o Small intes琀椀ne is sterile  Water, nutrients, fecal material may spend up to 24 hours in large intes琀椀ne Metabolism  Biological chemical reac琀椀ons catalyzed by enzymes  Metabolic pathways: series of reac琀椀ons that transform chemicals in food into products (metabolites) used for structure, energy, signaling/regula琀椀ng molecules o Reac琀椀ons create complex molecules from simple molecules  Catabolism: breaks down food chemicals (catabolizes) into smaller molecules so they can be absorbed o Smaller molecules used a昀琀er absorp琀椀on to generate energy; release energy trapped in chemical bonds o Provides simple molecules to create complex structures  Anabolism: generates complex structures from simple molecules (e.g. fat, muscle, hormones) o AA into protein, fa琀琀y acids into TG, simple sugars into glycogen (complex carbohydrate), nucleic acid bases into polynucleo琀椀des (DNA/RNA), components into new cells Lecture 5 – Carbohydrates and Insulin Resistance Dietary Carbohydrates  Basis of most modern diets o Provide > ½ of kcals consumed by Americans  Provide readily available source of energy o 4 kcal/gram  Provide variety of nutrients needed for health when consumed in “whole food” form Whole Grains vs. Re昀椀ned Grains  Whole grain products contain three key components: o Endosperm: made up primarily of starch; contains most of kernel’s protein, along with some vitamins and minerals o Bran: contains most of the 昀椀ber; good source of many vitamins and minerals o Germ: embryo where sprou琀椀ng occurs  Source of oil; rich in vitamin E  Re昀椀ned Grains o Re昀椀ning grains separates carbohydrates from many essen琀椀al nutrients found in whole, unre昀椀ned foods o May be enriched with thiamin, ribo昀氀avin, niacin, and iron; for琀椀昀椀ed with folate  Do not contain magnesium, vitamin E, and some of the B vitamins/other nutrients of whole grains Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/9 Types of Carbohydrates  Simple carbohydrates o Monosaccharide: made up of a single sugar unit o Disaccharide: made up of two sugar units  Complex carbohydrates: o Polysaccharide: made up of many sugar units Monosaccharides  Basic unit of a carbohydrate is a single sugar molecule  Three most common monosaccharides in diet: glucose, fructose, galactose Glucose  “Blood sugar”  Most important carbohydrate fuel for the body  Main circula琀椀ng sugar; provides constant source of fuel  Under 琀椀ght regulatory control to maintain blood glucose at a constant level o Produc琀椀on form liver and disposal in muscle Disaccharides  Made of two monosaccharides linked together  Sucrose (table sugar) formed by linking glucose with fructose o Only sweetener in the U.S. labeled “sugar” Making and Breaking Sugar Chains  Hydrolysis reac琀椀on breaks sugar molecules apart  Dehydra琀椀on synthesis links two sugar molecules together Complex Carbohydrates  Oligosaccharides: short chains containing 3-10 monosaccharides  Polysaccharides: long chains of monosaccharides o Glycogen found in animals; starch and 昀椀ber found in plants Dietary Fiber  Cannot be digested or absorbed by humans, but is important part of diges琀椀ve process/health of GI tract  Two types of 昀椀ber: o Soluble: dissolves in water  Legumes, prunes, apricots, raisins o Insoluble: doesn’t dissolve in water  Wheat bran, whole-wheat bread, broccoli  Can be added to processed foods to thicken and reduce fat and calories Lactose Intolerance  Occurs when there is not enough enzyme lactase in small intes琀椀ne to digest milk sugar lactose  Undigested lactose cannot be absorbed and passes into large intes琀椀ne  Lactose rapidly metabolized by intes琀椀nal bacteria, producing acids and gas  Symptoms include abdominal disten琀椀on, 昀氀atulence, cramping, diarrhea Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/10 Delivering Glucose to Body Cells  In order to provide steady supply of glucose to cells, concentra琀椀on of glucose in blood is regulated by liver/enzymes secreted from pancreas  Glycemic response o How quickly/how high blood glucose rises a昀琀er carbohydrates are consumed  Glycemic index: ranking of how a food a昀昀ects glycemic response  Glycemic load: food’s glycemic index mul琀椀plied by amount of available carbohydrate in a serving of the food Glycemic Index  Impact of di昀昀erent carbohydrate-containing foods on glycemic response of the body rela琀椀ve to a standard food (usually white bread or glucose) within two hours of consump琀椀on  GI 70: carbohydrate-containing food/drink causes 70% of the blood glucose response observed with the same amount of carbohydrate from pure glucose or white bread  Very low GI: < 40 o Raw apple, len琀椀ls, soy beans, cow’s milk  Low GI: 41-55 o Noodles/pasta, raw banana, chocolate  Intermediate GI: 56-70 o Brown rice, rolled oats, so昀琀 drinks  High GI: > 70 o Bread, boiled potato, white rice Metabolic Fate of Carbohydrates  Glycogen storage  Oxida琀椀on: conversion to energy o Metabolic pathway uses 6 molecules of oxygen to convert 1 molecule of glucose into 6 molecules of carbon dioxide, 6 molecules of water, and ~ 38 molecules of ATP  Very li琀琀le glucose (starches like rice, bread, pasta) is converted to fat o No storage capacity of fructose– lipogenesis (fat synthesis) Diabetes Mellitus  Type 1 diabetes: insulin no longer made in body  Type 2 diabetes: insulin present, but cells don’t respond (insulin resistance)  Gesta琀椀onal diabetes: occurs during pregnancy Insulin Resistance  Occurs in two 琀椀ssues: o Skeletal muscle:  Primary site of glucose disposal  Transport of glucose molecule into muscle requires insulin  Insulin resistance: greater secre琀椀on of insulin needed to transport glucose into muscle  Result: decreased glucose disposal; elevated blood glucose o Liver:  Site of glucose storage; releases glucose to maintain blood glucose levels Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/11  Hepa琀椀c glucose produc琀椀on (HGP) under hormonal control  A昀琀er a meal, blood glucose levels rise, resul琀椀ng in secre琀椀on of insulin  Insulin shuts down HGP  As liver becomes insulin resistant, insulin has diminishing e昀昀ect on HGP  Result: overproduc琀椀on of glucose; elevated blood glucose Glycosyla琀椀on  Glucose is “s琀椀cky” o Binds to proteins in the body– high blood glucose results in glycosylated hemoglobin and many other glycosylated proteins  Hemoglobin A1C = poor glucose control o Cataract forma琀椀on in eye– consequence of glycosyla琀椀on Diabetes Symptoms and Complica琀椀ons  Immediate symptoms: excessive thirst, frequent urina琀椀on, blurred vision, weight loss  Long-term complica琀椀ons: damage to heart, blood vessels, kidneys, eyes and nervous system o Infec琀椀ons more common in pa琀椀ents with diabetes; amputa琀椀ons may be necessary Components of Daily Energy Expenditure  Basic Metabolic Rate (BMR) o Body composi琀椀on– muscle mass is most important determinant o Energy balance– hypocaloric diet reduces metabolic rate  Thermic e昀昀ect of feeding o Fat is far less thermogenic than carbohydrate o Protein is more thermogenic than carbohydrate  Physical ac琀椀vity o Voluntary: exercise, daily ac琀椀vi琀椀es o Involuntary (昀椀dge琀椀ng): Non-Exercise Ac琀椀vity Thermogenesis (NEAT) Lecture 6 – Lipids Lipids  Chemicals of biological origin  Only marginally soluble in water  Fats and oils (triacylglycerol, aka TAG) o TAG: major form of lipid in fat (food and body)  Fats: TAG that are solid at room temperature  Oils: TAG that are liquid at room temperature  Lipids contribute texture, 昀氀avor, and aroma to food  Fats and oils: 9 kcal/gram Lipids: Fas琀椀ng/Feas琀椀ng  Feas琀椀ng: when excess energy consumed, stored as triglycerides in adipose 琀椀ssue  Fas琀椀ng: when no food has been eaten, triglycerides from adipose 琀椀ssue are broken down o Release fa琀琀y acids as energy source White (WAT) and Brown (BAT) Adipose Tissue Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/12  TAG stored as large lipid droplets in white adipocytes  Two types of WAT: visceral, subcutaneous Nature of Fa琀琀y Acids (FA)  Last carbon of FA: omega carbon  Long chain: > 12 carbon atoms o Usually solid at room temperature  Medium change: 8-12 carbon atoms o Solidify when chilled but liquid at room temperature  Short chain: 4-7 carbon atoms o Liquid at room temperature  Cis double bonds: normal (two H atoms facing each other)  Trans double bonds: natural are minor, mostly introduced by human manipula琀椀on Saturated FA  Solid at room temperature, except tropical oils  Resists rancidity  Food sources: animal fat, tropical oils  Carbons in hydrocarbon chain bound to two hydrogens  End/omega carbon has 3 H atoms  Most animal fats/tropical oils contain saturated FA  No double bonds  Single bond: two adjacent carbon atoms connected by one bond Unsaturated FA  Liquid at room temperature  Prone to rancidity  Food sources: most plant oils  One or more carbons that are not saturated with hydrogen o Contain double bonds  In naturally occurring FA, double bonds are cis o H atoms are “together” facing each other Monounsaturated FA  One double bond (cis)  Canola, olive, peanut oils Polyunsaturated FA  More than one double bond  Naturally occurring PUFA have cis double bonds Trans FA  Not found in nature in large amounts  Created by hydrogena琀椀on of oils  Raise blood cholesterol levels and increase risk of heart disease Essen琀椀al Fa琀琀y Acids (EFA) Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/13  PUFA  Mammals cannot synthesize EFA; must obtain through diet  Contribute to growth, skin integrity, fer琀椀lity, structure/func琀椀ons of cell membranes  EFA de昀椀ciency: dry scaly rash, decreased growth, suscep琀椀bility to infec琀椀on, poor wound healing o Obesity is associated with EFA de昀椀ciency  Linolenic acid: omega-3 o Canola oil, nuts, 昀椀sh oils  Linoleic acid: omega-6 o Vegetable oils, meat Lipids: Review  Not soluble in water  Trans fa琀琀y acids: created by hydrogena琀椀on of fats/oils o Raise blood cholesterol levels; increase risk of heart disease  Triglycerides (TG/TGA): major form of fat in food/body o Consist of 3 FA molecules covalently bound to glycerol molecule o Stored in adipose 琀椀ssue o WAT stores fat to undergo fa琀琀y acid oxida琀椀on (FAO) to supply energy  Visceral WAT: surrounds organs, localizes to mid-sec琀椀on o “Bad” adipose  Subcutaneous WAT: provides ~50% estrogen in non-pregnant females o “Good” fat  BAT: stores fat to burn to defend body temperature  Fats/oils: 9 kcal/gram  Length of FA chain in TAG contributes to mel琀椀ng point o Longer chains have higher mel琀椀ng points  Degree of unsatura琀椀on (double bonds) contributes to mel琀椀ng point o Double bonds decrease mel琀椀ng points  Double bonds in naturally occurring FA have cis con昀椀gura琀椀on  EFA: cannot be made by mammals; essen琀椀al for health o Omega-6: last double bond occurs within terminal 6 carbon atoms o Omega-3: last double bond occurs within terminal 3 carbon atoms  More in昀氀ammatory than omega-6 o Linoleic: omega-6 o Linolenic: omega-3 Lecture 7 – Dietary Reference Intakes (DRIs) Nutrient Reference Values (NRVs)  Benchmarks for assessing adequacy of nutrient intakes for individuals/popula琀椀ons o How much of intake of a nutrient/dietary compound is necessary for health  First set of formal NRVs: Recommended Dietary Allowances (RDAs), 1941 o Established es琀椀mated nutrient requirements/recommended intakes based on age, biological sex, for pregnancy and lacta琀椀on o Goal: promote op琀椀mal health o Problem: RDAs were single values  One value to guide them all? Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/14  Ignores heterogeneity of requirements Dietary Reference Intakes (DRIs)  Mul琀椀-琀椀ered nutrient reference value system; allowed for probabilis琀椀c assessment of nutrient (in)adequacy  Es琀椀mated Average Requirement (EAR) o Intake that meets requirement of 50% of popula琀椀on o Assessment of probability of inadequacy for groups/individuals  Recommended Dietary Allowance (RDA) o Intake that meets requirement of 97.5% of popula琀椀on o Planning individual diets with low probability of inadequacy  Adequate Intake (AI) o Intake that meets requirement of apparently healthy group o Assumed to be adequate o Set when EAR/RDA cannot be determined  Upper Limit (UL) o Value where probability of excessive intakes increase o Toxicological risk/hazard assessment framework o Does not exist for every nutrient  Es琀椀mated Energy Requirement (EER) o Average energy intake needed to maintain energy balance o Energy input = Energy output o Based on age, gender, weight, height, physical ac琀椀vity  Acceptable Macronutrient Distribu琀椀on Ranges (AMDR) o Ranges of protein, fat, carbohydrate that can be safely consumed without risking inadequate intakes/poor health outcomes; reduce risk of chronic disease  Carbohydrates: 45-60%  Fats: 20-35%  Proteins: 10-35%  DRIs currently exist for: o Energy o Macronutrients (individual amino acids) o Essen琀椀al micronutrients: vitamins, minerals, trace elements o Water o Fiber  DRIs not currently established for other food-derived bioac琀椀ve compounds Se琀 ng DRI Values  Linking intakes across nutri琀椀onal dose-response range to speci昀椀c biochemical/physiological outcomes across age, sex, physiological state groupings o Data from “healthy” popula琀椀ons o “indicator” of requirement/adequacy Chronic Disease DRIs  Many DRIs based on measures of nutrient adequacy/preven琀椀ng physiological dysfunc琀椀on o May or may not be adequate to reduce chronic disease risk  Current chronic diseases: Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/15 o Calcium/Vitamin D: Osteoporosis o Sodium/Potassium: Blood Pressure o Fiber: Cardiovascular Disease/LDL-C DRI Challenges  Es琀椀ma琀椀ng usual nutrient intakes (food + supplements) o Intake can be inaccurately reported  We rarely know an individual’s true requirement o Can only assess probability of intake mee琀椀ng/not mee琀椀ng requirement  What is a healthy popula琀椀on? o DRIs not intended for use in popula琀椀ons/persons with high rates of disease  Assump琀椀ons  Limited data Lecture 7 – Proteins and Amino Acids Sources of Protein in the Diet  Protein de昀椀ciency rare in U.S. o About 2/3 dietary protein comes from meat, poultry, seafood, eggs, dairy products  Most of world relies on plant proteins (grains, vegetables)  As country’s economy improves, propor琀椀on of animal foods in diet tends to increase o Increased animal protein consump琀椀on increases total fat/saturated fat consump琀椀on How Protein Source Impacts Diet  Animal products: protein, B vitamins, minerals such as iron, zinc, calcium o Lower in 昀椀ber; can be high in fat  Plant sources: B vitamins, iron, zinc, 昀椀ber, phytochemicals and calcium o Less absorbable forms Amino Acids  Building blocks of protein  Each contains central carbon atom bound to a hydrogen atom, amino group, acid group, and side chain  Essen琀椀al amino acids: cannot be synthesized by human body in su昀케cient amounts to meet needs o Must be included in diet  When a nonessen琀椀al amino acid is not available from the diet, it can be made in the body by transamina琀椀on Protein Structure  Amino acids are linked by pep琀椀de bonds o Bonds formed between acid group of one amino acid and nitrogen group of next  Dipep琀椀de bonds formed between two amino acids  Polypep琀椀des formed between many amino acids  Protein is made up of one or more polypep琀椀de chains folded into 3D shape  Protein shape determines func琀椀on o Connec琀椀ve 琀椀ssue: elongated proteins/collagen Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/16 o Hemoglobin: spherical o If shape of protein is altered, its func琀椀on may be disrupted Protein Turnover and Synthesis  Body con琀椀nuously synthesizes/breaks down protein– like recycling  Synthesis: transcrip琀椀on and transla琀椀on Protein Func琀椀ons  Provide structure  Enzymes speed up metabolic reac琀椀ons  Transport proteins; move substances in and out of cells  An琀椀bodies help immune system in 昀椀gh琀椀ng o昀昀 foreign bodies  Contrac琀椀le proteins help muscles move  Hormones are chemical messengers (e.g. insulin, glucagon)  Proteins help regulate 昀氀uid and acid-base balance Protein De昀椀ciency  Protein-energy malnutri琀椀on (PEM): may include only protein de昀椀ciency or protein + energy de昀椀ciency  Kwashiorkor: pure protein de昀椀ciency  Marasmus: energy and protein de昀椀ciency Dietary Protein Requirement  Determined by nitrogen balance o Intake – Output (urine, feces, sweat, etc.)  Metabolic ward studies: typically three di昀昀erent protein intakes measured over 7-10 days o Decreased energy intake increases N loss o Higher energy and/or carbohydrate intake decreases N loss  Requirement: 0.6 g x kg^-1 x d^-1  Recommended Dietary Allowance: 0.8 g x kg^-1 x d^-1 o 0.8 g/kg body weight per day o Irrespec琀椀ve of age or ac琀椀vity level  Acceptable Macronutrient Distribu琀椀on Range (ADMR): 10-35% of energy for adults  Protein needs increase during periods of growth, pregnancy, lacta琀椀on  Regular aerobic exercise increases oxida琀椀on of essen琀椀al amino acids as a fuel o May increase protein requirement for athletes o Most athletes have increased total food intake Athle琀椀c Amenorrhea  Amenorrhea: absence of menstrual period for 3+ months  Risk increases with increased volume of training  Amenorrheic women have low bone density and increased risk of osteoporosis  Mul琀椀-factorial problem, but likely strongly related to diet o Protein/calorie imbalance o Focus on high quality, low fat protein o Soy protein may be par琀椀cularly e昀昀ec琀椀ve due to its estrogen-like e昀昀ects  Many female athletes view amenorrhea as desired side e昀昀ect of training Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/17  Greatly increased risk of stress-fractures  Should never be used as a contracep琀椀ve Lecture 8 – Aging, Sarcopenia, and Physical Ac琀椀vity Sarcopenia  Age-related loss of skeletal muscle mass  Reduced energy needs, obesity  Reduced body protein reserves  Osteopenia: bone fracture risk Anabolic Resistance  Increased dietary protein requirement  Caused by: o Aging: decreased testosterone, HGH, menopause o Increased obesity, visceral fat, muscle lipid, inac琀椀vity, insulin resistance o Chronic disease: in昀氀amma琀椀on  Reduced rate of muscle and whole body protein synthesis  Accelerated muscle protein breakdown Frailty  “Shrinking” weight loss, sarcopenia o > 10 lbs. lost uninten琀椀onally in prior year)  Exhaus琀椀on: poor endurance, self-reported  Low levels of physical ac琀椀vity o Lowest 20% (males < 383 kcal/week, females < 270 kcal/week)  Low walking speed o Lowest 20%  Muscle weakness o Lowest 20% (grip strength) Training  VO2max: 10% increase  Peak power: 25% increase  Capacity of skeletal muscle to adapt to exercise is undiminished by age  Progressive resistance training: exercise during which a muscle contracts just a few 琀椀mes against a heavy load/with high tension o Load is progressively increased with training o Dis琀椀nct from endurance (aerobic exercise) training: muscles contract against li琀琀le/no resistance  E昀昀ects of strength training on spontaneous ac琀椀vity in frail, ins琀椀tu琀椀onalized men and women: increased walking speed; increased stair-climbing ability; increased spontaneous ac琀椀vity; decreased depressive symptoms  Resistance exercise: o Increases strength and func琀椀onal capacity o Increases muscle mass o Enhances nitrogen balance (reten琀椀on of protein) Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/18 o Increases levels of physical ac琀椀vity o Improves bone health; decreases risk of osteoporosis o Increases insulin ac琀椀on; decreases risk of diabetes Bone Health  Factors a昀昀ec琀椀ng bone health: gender, heredity, race, estrogen status, body type, nutri琀椀on, physical ac琀椀vity, smoking, medica琀椀ons  Osteoporosis  Stress and bone density: weight-bearing exercise can slow the loss of bone o Exercises that stress bones can arrest loss of bone density: resistance exercise, jumping, heel drops Lecture 9 – Starva琀椀on Adapta琀椀ons Basics of Body Composi琀椀on  Mostly made of water o ~60-70% in children, ~50% in adults  Cells (lean 琀椀ssue) composed of about 20% protein  Maximum carbohydrate stores in body are miniscule  Most body energy stores are in triglycerides (TG) in adipose 琀椀ssue o Also structural fat and membrane lipids in cells Lean Tissue Conserva琀椀on in Starva琀椀on  Normal protein losses = intake = 100 g protein/day = 16 g N o People generally in nitrogen balance; loss of nitrogen from body must equal intake  If you fasted for 30 days at this rate = 3 kg protein lost o Every 100 g protein = ~500 g lean 琀椀ssue (1 lb. muscle lost every day) o 15 kg (~30 lbs.) lean 琀椀ssue lost  We do not have any purely “storage proteins” in body  All proteins in lean 琀椀ssues have func琀椀ons  Loss of 40-50% LBM typically lethal o Loss of ~15 kg LBM life-threatening o Should be able to starve < 30 days How Long Can We Starve?  Hunger strikes in prison, people stranded without food, etc.: survival can be 60-90 days or more, if hydra琀椀on and electrolytes maintained  Reduce nitrogen loss to 20 g protein/day (3 g N) = 100 g lean 琀椀ssue lost/day instead of 500 g/day o Can survive starva琀椀on much longer  Normal response to starva琀椀on complex and highly e昀昀ec琀椀ve o Involves coordina琀椀on among many 琀椀ssues o Has consequences on health and disease in many contexts o Preserves lean 琀椀ssue: allows much longer survival during protein-calorie depriva琀椀on Metabolic Response to Prolonged Fas琀椀ng  Phase 1: 昀椀rst few days o Glycogen deple琀椀on Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/19 o High rate of nitrogen loss o Baseline fuel mixture maintained  Phase 2: ~7 days o Fa琀琀y acid oxida琀椀on o Ketosis o Reduced nitrogen and 琀椀ssue losses  Phase 3: 3 g N lost/day o Brain keto-adapta琀椀on o Greatly reduced nitrogen and 琀椀ssue losses o Further adapta琀椀ons: kidney, endocrine, behavioral o Brain stops using only glucose, thereby reducing need for gluconeogenesis from amino acids Role of Di昀昀erent Tissues  Liver: glycogen deple琀椀on o Reduces glucose release into blood o Lowers blood glucose, insulin levels o Increases fa琀琀y acid oxida琀椀on/ketosis o Reduces gluconeogenesis from amino acids to supply the brain  Pancreas: reduces insulin secre琀椀on  Adipose: increases fa琀琀y acid release into blood  Muscle: reduces glucose oxida琀椀on o Increases fat oxida琀椀on o Reduces protein breakdown and amino acid release  Brain: keto-adapta琀椀on (can use ketones) o Reduces glucose oxida琀椀on o Drama琀椀cally reduces amino acid use from proteins for gluconeogenesis  Kidney: conserva琀椀on of ketones  Endocrine organs: mul琀椀ple adapta琀椀ons Hormonal Consequences  Growth axis: growth factor, GH/IGF-1 o Consequences for height of popula琀椀ons  Reproduc琀椀ve system: gonadotropins, gonadal func琀椀on o Health implica琀椀ons in modern world o Timing of menarche o Aerobic athletes o Anorexia nervosa o Breast cancer  Thyroid axis: T4/T3/TSH o U琀椀lity and downside in obesity  Insulin sensi琀椀vity: therapeu琀椀c uses  Lep琀椀n secre琀椀on: primary func琀椀on Growth (Growth Factor) Axis  Soma琀椀c growth an GH/IGH-1 axis  IGF-1: ac琀椀ve hormone Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/20 o GH s琀椀mulates its synthesis by 琀椀ssues  GH secreted by pituitary gland; IGF-1 made mostly by liver o Liver decides whether we grow and make lean 琀椀ssue, more so than pituitary  Consequences for growth failure in children  Opposite e昀昀ects: over-nutri琀椀on and cancer risk Reproduc琀椀ve System  In昀氀uence of nutrient intake/body composi琀椀on on reproduc琀椀ve func琀椀on in mammals o Gonadotropin secre琀椀on by pituitary and nutri琀椀on/body composi琀椀on  Age by 昀椀rst menses in young women through history  Dura琀椀on of unopposed estrogens and breast cancer  Loss of periods in women (body weight, fat, energy intake) o Anorexia nervosa, athletes, stress fractures  Adap琀椀ve explana琀椀on (especially for females)  E昀昀ects in men (e.g. cancer, HIV infec琀椀on): therapeu琀椀c implica琀椀ons  Health implica琀椀ons in modern world: anorexia nervosa, fer琀椀lity, bone health, cancer Thyroid Axis  Major hormone in昀氀uencing energy expenditure  T3 is ac琀椀ve hormone  T4 secreted by thyroid gland  T4 to T3 conversion by peripheral 琀椀ssues o In昀氀uence of calorie intake  Hypothalamic/pituitary also respond Insulin Sensi琀椀vity: Dietary Treatment of T2DM  Rapid e昀昀ects of nega琀椀ve energy balance on liver glycogen stores reduces hepa琀椀c glucose produc琀椀on and fas琀椀ng blood glucose concentra琀椀ons within a few days  “Starva琀椀on response” and e昀昀ect on insulin resistance: implica琀椀ons for how we think about weight loss prescrip琀椀on in T2DM Lep琀椀n Secre琀椀on  Primary func琀椀on: “adipostat” vs. undernutri琀椀on defense in evolu琀椀onary history  E昀昀ects of acute starva琀椀on/carbohydrate depriva琀椀on compared to long-term weight loss on lep琀椀n levels/expression in adipose 琀椀ssue  E昀昀ects of lower lep琀椀n vs. higher lep琀椀n levels rela琀椀ve to normal levels o Dose-response curve  Therapeu琀椀c implica琀椀ons: weight loss treatment, infer琀椀lity? Lecture 9 – Starva琀椀on and Infec琀椀on Classic Forms of Starva琀椀on  Marasmus: lose weight but look healthy o No swelling; usually do well  Kwashiorkor: appear sick o Swollen belly; o昀琀en die Interac琀椀on with Infec琀椀on Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/21  Presence of infec琀椀on/in昀氀amma琀椀on alters the starva琀椀on response  Highly conserved biological program: “the acute-phase response” o Fever, low blood iron/anemia o Sleep, fa琀椀gue o Loss of appe琀椀te o Poor grooming o High metabolic rate o Change in proteins, increase in blood lipids  Lose more nitrogen (muscle 琀椀ssue) than in well-adapted “simple” starva琀椀on o Lower albumin (swelling) o More infec琀椀ons o Inability to gain lean 琀椀ssue when nutrients are provided Starva琀椀on/Infec琀椀on Combina琀椀ons in Humans  Tuberculosis: “consump琀椀on”  Cancer: common look of cancer pa琀椀ents ("cachexia”) o Di昀케culty reversing was琀椀ng by feeding  HIV/AIDS: common to have was琀椀ng early in HIV epidemic (“slim disease” in Africa) o Inability to reverse lean 琀椀ssue losses by feeding strategies o Able to increase lean 琀椀ssue only with targeted anabolic interven琀椀ons E昀昀ects of Feeding in Infec琀椀on/PCM: HIV- or Cancer- Associated Was琀椀ng  Was琀椀ng of lean 琀椀ssue very common in HIV infec琀椀on/cancer o Correlates with/possibly causes death  O昀琀en associated with men with low testosterone levels  Generally no increase in lean body mass with nutri琀椀onal interven琀椀ons o Gain only fat o Parenteral nutri琀椀on, enteral supplements, appe琀椀te s琀椀mulants  Alterna琀椀ve: anabolic therapies (growth hormone, androgens, resistance exercise +/- androgens) Stun琀椀ng in Children  Environmental Enteric Dysfunc琀椀on (EED): stun琀椀ng o Short stature, delayed development, impaired vaccine response, suscep琀椀bility to infec琀椀ons  Consequences are usually long-term/permanent o Par琀椀cularly shorter stature: lower height than gene琀椀c poten琀椀al o Neuro-cogni琀椀ve impairment (lower IQ than gene琀椀c poten琀椀al)  Causes are mul琀椀factorial o Gastrointes琀椀nal infec琀椀ons o Systemic infec琀椀ons o Poor nutri琀椀on o Bad water o Chronic in昀氀amma琀椀on  Stun琀椀ng: one of the most important interna琀椀onal public health problems that prevents people from reaching their full poten琀椀al  Major issue: how to objec琀椀vely iden琀椀fy/diagnose; how to evaluate e昀昀ec琀椀veness of interven琀椀ons Muscle Mass and Stun琀椀ng Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/22  Body weight not accurate enough; children can be normal weight but stunted o Fat mass preserved  Muscle is the largest reservoir of protein in human body o Remarkably responsive to chronic changes in nutri琀椀onal status, in昀氀amma琀椀on, intercurrent illnesses  Skeletal muscle: not deposited in sick individuals  Muscle mass in children correlates with brain development  Largest component of fat-free mass: muscle is most accurate index of general nutri琀椀onal status  Measurement of muscle mass should be a fundamental part of any assessment of stun琀椀ng  Measuring muscle mass in humans: imaging (MRI), biochemistry (crea琀椀ne pool size) Calorie Restric琀椀on (CR) Background  Reducing caloric intake without malnutri琀椀on o Typically 20-40% less than ad-libitum fed controls  Decreased age-related diseases: cancer, neurodegenera琀椀on, cardiovascular, immune dysfunc琀椀on  Extends lifespan and/or healthspan across variety of organisms: o Worms, 昀氀ies, rodents, non-human primates  40% CR extends lifespan by ~20% in mice o Would be like people living to 120 years Mechanisms of CR  Scarcity adapta琀椀ons o Turnover rates of cells/proteins  “Stress resistance” programs  Physiologic altera琀椀ons due to hormonal/metabolic signals of calorie insu昀케ciency  Less oxida琀椀ve stress/free radicals  Slowing down of metabolic rates: fewer mistakes, less damage and repair needed  None are proven, however Problems Transla琀椀ng CR Data in Animal Models into Humans  Causes of death in small laboratory animals vs. humans o Animals in the wild do not live long enough to age o “Aging genes” that evolved to control popula琀椀on size/promote popula琀椀on turnover to ensure adaptability o Most mice in laboratories die of cancer  CR reduces cell division rapidly in many cell types  Cell division mechanis琀椀cally linked to aging:  Increases “promo琀椀onal” phase of carcinogenesis  Leads to senescence of cells/琀椀ssue  Many longevity models associated with decreased growth factors and cell division rates  Might CR not really extend maximal lifespan, but just prevent premature cancer deaths?  Extrapola琀椀on to humans would be limited if this is the explana琀椀on  Body size and metabolic rate o 24 hr. fast in mice is like a week-long fast in humans  Would be di昀케cult to do or test Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/23  Alterna琀椀ve approaches to capture the bene昀椀ts without the di昀케culty?  Intermi琀琀ent fas琀椀ng?  Alternate-day fas琀椀ng?  Di昀케culty in reducing daily calorie intake and bodyweight over a life琀椀me o Ea琀椀ng less for the rest of your life as a prac琀椀cal strategy? o Non-nutri琀椀onal approaches?  Medica琀椀ons, hormonal altera琀椀ons, slowing metabolism (reduced protein synthesis)  Length of studies required to test longevity e昀昀ects Signaling Pathways in CR  SIR: silent informa琀椀on regulator  SIR2: NAD-dependent histone de-acetylase  Sirtuin agonist drug discovery e昀昀orts have not worked so far Summary  Many poten琀椀al mediators of CR: metabolic, hormonal, intracellular signals  Extrapola琀椀on to humans is lacking– many di昀昀erences from small animals  Prac琀椀cal di昀케cul琀椀es of life-long CR and of studying life-long CR  Capturing the bene昀椀ts of the “starva琀椀on response” remains an elusive goal Lecture 10 – Nutri琀椀on During Pregnancy Why Study Pregnancy  Pregnancy represents high energy/nitrogen demand to support growth and/or remodeling of: o Fetus; amnio琀椀c 昀氀uid; breast and uterine 琀椀ssue; blood  Pregnancy in昀氀uences micronutrient metabolism; can increase requirements  Adequate nutri琀椀on can be signi昀椀cant determinant of maternal/fetal health outcomes during pregnancy  Pregnancy can cause unique disease states in both mother and o昀昀spring o Can in昀氀uence maternal intakes and/or be mi琀椀gated by dietary modi昀椀ca琀椀on  Nausea/vomi琀椀ng (hyperemesis gravidarum)  Gesta琀椀onal diabetes and hypertension  Birth defects and cogni琀椀ve impairments  Pregnancy is a metabolic stressor; can uncover/exacerbate underlying poor health o Long-term risk of type 2 diabetes mellitus, CVD Why Pregnancy Increases Nutrient Requirements  Deposi琀椀on of 琀椀ssue and its metabolic costs o Es琀椀mated 925 g protein deposited in mother and fetus across pregnancy o Increased essen琀椀al fa琀琀y acids in all cells, especially developing fetal brain  Nutrient accre琀椀on within fetal 琀椀ssues o E.g. minerals like iron and calcium  Increased metabolic ac琀椀vity to produce raw materials of the cell o Folate needed to make DNA in fetal cells o Choline needed to make phospholipids o Iron needed to support red blood cell synthesis and turnover Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/24  Nutrient signaling to coordinate fetal development (e.g. vitamin A)  Increased nutrient excre琀椀on by mother Adapta琀椀ons in Pregnancy  Bioenerge琀椀cs o Increases in BMR: uterus, lung, heart o Synthesis cost of new 琀椀ssues  Blood o Increased blood volume, red blood cells, heart rate o Decreased plasma proteins, blood pressure  Intes琀椀nal o Slower gastric empty o Reduced intes琀椀nal mo琀椀lity o Altered absorp琀椀ve capacity for nutrients  Kidney o Increase up to 30% in size o Increased glomerular 昀椀ltra琀椀on rate  Nutrient losses  Adapta琀椀ons to selec琀椀vely retain nutrients  Liver o Reduced albumin synthesis o Altered cytochrome P-450 enzyme ac琀椀vity (detoxi昀椀ca琀椀on)  Hormonal o Natural insulin resistance o Increased estrogens and progesterone Energy and Weight Gain  Weight gain expected during nearly all pregnancies o Accre琀椀on of fetal 琀椀ssues o Altera琀椀ons in maternal 琀椀ssue weight o Fluid  Weight gain facilitated by changes in calorie intake/reduced physical ac琀椀vity  Recommended weight gain dependent on: o Baseline weight status o Trimester  Weight gain recommenda琀椀ons intended to op琀椀mize maternal and fetal/o昀昀spring outcomes  Consequences for the mother: o Excessive gesta琀椀onal weight gain may increase the risk of:  Gesta琀椀onal diabetes and hypertension  Labor and delivery complica琀椀ons (especially cesarean delivery)  Postpartum weight reten琀椀on  Poor lacta琀椀on performance  Long-term metabolic disease risk Recommended Calorie Intakes  Calorie intakes to facilitate guideline-directed gesta琀椀onal weight gain should be individualized o Based on observed rate of gain, physical ac琀椀vity levels, weight history Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/25  General calorie intake recommenda琀椀ons derived from popula琀椀on studies Calcium  Required by the body to: maintain bone density; contract muscles; excite neurons; secrete hormones  99% of all calcium in the body is in the bone  Calcium homeostasis is 琀椀ghtly regulated by absorp琀椀on, excre琀椀on, and release from bone o Adapta琀椀ons occur during pregnancy to ensure calcium homeostasis  No increased dietary requirements compared to non-pregnant mothers  Drama琀椀cally-increased calcium absorp琀椀on during 2 nd and 3rd trimester o Some reduced renal calcium excre琀椀on  Recommended calcium intakes strongly linked to reduced gesta琀椀onal hypertension risk o Supplementa琀椀on during pregnancy in areas with low (< 500 mg/d) intake of calcium consistently reduces risk  Poten琀椀ally mediated by altered placental func琀椀on/maternal vasculature to placental debris Addi琀椀onal Nutrients of Concern  Iodine: fetal neurodevelopment/o昀昀spring cogni琀椀on  Omega-3 fa琀琀y acids: fetal re琀椀nal, immune, and neurodevelopment; preterm birth risk  Iron: maternal/o昀昀spring amenia; neurodevelopment  Choline: fetal neurodevelopment/o昀昀spring cogni琀椀on  Vitamin D: gesta琀椀onal diabetes mellitus, pre-eclampsia, fetal/infant growth Public Health and Foodborne Illness  Pregnancy alters immune func琀椀on to support tolerance of the fetus and placenta o Mediated in part by progesterone levels  Increases risk of foodborne illness and spontaneous abor琀椀on, s琀椀llbirth and low birthweight o Listeria monocytogenes (10x risk): unpasteurized dairy and so昀琀 cheese, processed meats o Salmonella enterica: undercooked/unpasteurized eggs, raw sprouts, undercooked meat o Toxoplasma gondii: undercooked meats/shell昀椀sh Lecture 11 – Lipids, Blood Lipoproteins, Metabolic Syndrome, E昀昀ects of Diet Func琀椀ons of Lipids in Body  Provide major components of cell membranes o Phospholipids, cholesterol  Used by many 琀椀ssues as energy source o By far the major energy store in human body  Provides precursors for several hormones/signaling molecules in cells o Steroid hormones (e.g. estrogens, testosterone, cor琀椀sol, aldosterone) o Prostaglandins and related molecules o Fat soluble vitamins: A (re琀椀noids), D (calcium and bone), E (an琀椀-oxidant), K (blood clo琀 ng)  Myelina琀椀on of nerve 昀椀bers: allows e昀케cient electrical impulse propaga琀椀on in brain  Insula琀椀on and heat conserva琀椀on in adipose 琀椀ssue Types of Fats in Diet Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/26  Saturated: animal fats, milk products  Mono-unsaturated: e.g. olive oil  Poly-unsaturated: vegetable oils  Omega-3: oily 昀椀sh  Cholesterol-rich: meats, eggs, liver  Essen琀椀al fa琀琀y acids: e.g. linoleic, linolenic, arachidonic What Lipids do People Eat?  Typical macronutrient content of Western diet: o Energy intake = 40-60% CHO, 25-45% fat, 15% protein o Calculates to ~ 75-150 g fat/day  Recommended diet: < 30% energy (< 7% saturated; < 1% trans) o < 300 mg cholesterol/day; 昀椀sh > twice/week  Major di昀昀erences in types of dietary fat among countries and popula琀椀ons o E.g. Mediterranean (mono-unsaturated) o Milk and meat (saturated) o Fish (omega-3) o Developing countries: small % dietary energy Cholesterol  Can come from diet or be synthesized by cells in the body o Roughly about 50% comes from each source on typical Western diet o Higher cholesterol intake par琀椀ally suppresses synthesis by 琀椀ssues (especially liver) o Higher cholesterol intake reduces absorp琀椀on e昀케ciency by intes琀椀ne o Dietary cholesterol has modest e昀昀ects on blood cholesterol levels  Essen琀椀al func琀椀ons in cell membranes  Precursor for cri琀椀cal molecules  Most widely-discussed lipid in terms of risk for heart disease Blood Lipoproteins  Fats are not soluble in water: they have to be packaged in par琀椀cles called lipoproteins to be carried in blood  Lipoproteins categorized by density class o Chylomicron: transport fats/vitamins from diet to 琀椀ssue o Very-low-density lipoprotein (VLDL): transport of lipids, especially triglycerides (TG) from liver to 琀椀ssues o Low-density lipoprotein (LDL): transport of cholesterol from liver to 琀椀ssues o High-density lipoprotein (HDL): “reverse” transport of cholesterol from 琀椀ssues to liver Composi琀椀on of Lipoproteins  Transport lipids through lymph and blood  Consist of cholesterol, TG, phospholipids, fat-soluble vitamins, proteins o Apolipoproteins  Apolipoproteins: interact with enzymes/receptors in 琀椀ssues o Allow 琀椀ssue recogni琀椀on of speci昀椀c lipoproteins o Determine the func琀椀on of lipoproteins  Outer surface is hydrophilic; inner core contains hydrophobic lipids Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/27 Chylomicron  Made in enterocytes (small intes琀椀ne absorp琀椀ve cells)  Largest and least dense  ~ 1% protein  Mostly TG (of long-chain FA), some cholesterol, fat-soluble vitamins, and other lipids  Enter lymph and then blood  Deliver TG to adipose and other muscle 琀椀ssues  A chylomicron remnant results from removing TG; cholesterol remains o Remnant delivers cholesterol to liver Very-Low-Density Lipoproteins (VLDL)  Made in liver  ~ 8% protein  Mostly TG (some cholesterol)  Enter blood from liver  Deliver TG to adipose and other 琀椀ssues (including remnants that return to liver)  A昀琀er delivering TG to adipose, VLDL undergo transforma琀椀on into LDL o Can return to liver Low-Density Lipoproteins (LDL)  So-called “bad” cholesterol  Made in blood from metabolism of VLDL  High VLDL cholesterol can lead to high LDL cholesterol  ~ 20% protein  High ra琀椀o of cholesterol rela琀椀ve to TAG  Deliver cholesterol to 琀椀ssues, including liver  Bind to LDL receptors on cell surfaces  Upon receptor-binding, undergo endocytosis (engulfed into cell)  Upon endocytosis, cholesterol is distributed in membranes/converted into bile acids (liver) o Apolipoproteins are catabolized High-Density Lipoproteins (HDL)  So-called “good” proteins  Made de novo in blood (from ApoA core)  Smallest and most dense of lipoproteins  ~ 50% protein  High % cholesterol rela琀椀ve to TAG  Func琀椀on: reverse cholesterol transport? o Remove cholesterol from extrahepa琀椀c 琀椀ssues and deliver to liver (primarily) or endocrine organs  Deliver small amounts of cholesterol for steroid hormone biosynthesis  Upon receptor-binding, HDL undergo endocytosis (engulfed into cell)  Upon endocytosis, cholesterol used (hormone biosynthesis) or catabolized into bile acids (liver) o Apolipoproteins are catabolized Blood Lipoproteins and Risk of Cardiovascular Disease Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/28  Classes have di昀昀erent associa琀椀ons with risk for heart disease  VLDL-TG: general associa琀椀on with obesity, low HDL, heart disease  LDL-C: strong associa琀椀on with atherosclero琀椀c cardiovascular disease (heart a琀琀acks/strokes) o Every 1% increase in LDL-C = 2% increase in heart a琀琀acks  HDL: inverse rela琀椀on to heart disease o High levels are good o Inverse rela琀椀on to VLDL-TG (free C exchanges from HDL to VLDL) o High TG causes low HDL E昀昀ects of Dietary Cons琀椀tuents on Blood Lipids  Saturated fats: raise LDL-C; raise VLDL-TG  Mono-unsaturated fats (e.g. olive oil): tend to reduce LDL-C and VLDL-TG  Omega-3 fa琀琀y acids (昀椀sh oils): reduce VLDL-TG  Trans-fa琀琀y acids: worsen LDL-C  Cholesterol: increase blood LDL-C (modest impact)  Carbohydrates: tend to increase VLDL-TG, reduce HDL-C o Anyone with high VLDL-TG will have lower HDL-C (CEPT) Carbohydrate-Induced Hypertriglyceridemia (CHO-induced HPTG)  Common with some high CHO diets  Even small change in CHO content o E.g. from 35/50% to 25/60% fat/CHO intake  Greater the increase CHO, the greater % subjects are a昀昀ected and higher TG levels seen  Essen琀椀ally a dose-dependent e昀昀ect of dietary CHO on blood TG  High VLDL-TG lowers HDL-C  If allow weight loss– TG nearly normalizes  If no weight loss is allowed– HPTG is persistent o Only par琀椀al normaliza琀椀on  If exercise– modest increase TG only  If complex CHO intake– modest increase TG  If replace fat with protein– modest increase  if induce high CHO slowly– modest increase  if high sugar intake– high TG more likely E昀昀ects of Simple Sugars  greater e昀昀ect on TG if sugars are > 50% of dietary CHO  even change from 60/40% to 40/60% complex/simple sugars will alter TGs  Fiber or whole food intake– results in reduced e昀昀ect  Fructose is par琀椀cularly casual (makes it worse at any level of CHO) Lecture 12 – Simple Sugars or Surplus Carbohydrate Intake, Fa琀琀y Liver Disease and Metabolic Health Hierarchy of Fuel Selec琀椀on in Humans  Macronutrients compete for oxida琀椀on in 琀椀ssues and in the whole body  When both CHO and fat are present, CHO is selected for oxida琀椀on Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/29 o CHO s琀椀mulates insulin– combina琀椀on inhibits oxida琀椀on of fa琀琀y acids by 琀椀ssues (muscle, liver) and increases oxida琀椀on of CHO o Spares fat from being oxidized o Result is accrual of fat in body  Ethanol converted to acetate  Acetate directly converted to acetyl-CoA and oxidized by mitochondria in 琀椀ssues  Fuel oxida琀椀on hierarchy: acetate (ethanol)  carbohydrate  fats Conversion of CHO to Fat  All organisms can convert CHO to fat or make new fat from other sources o Process: de novo lipogenesis (DNL)  Very ac琀椀ve in some organisms o E.g. grain-fed cows or pigs; mice on high-CHO diet; honey bees o Plants and algae (poten琀椀al basis of biofuels)  Occurs in liver and fat cells (adipose) in mammals  Not very ac琀椀ve in most humans being under most dietary circumstances Surplus CHO or Simple Sugars in Body  Not primarily converted to fat (only a few grams)  CHO gets burned instead of dietary fat, even a昀琀er overnight fas琀椀ng (“spares” fat) o Occurs by liver releasing more glucose even while fas琀椀ng  Net e昀昀ect: extra CHO will add to body fat, but not by being directly converted to body fat  Inhibitors of new fat synthesis (DNL) will therefore not be e昀昀ec琀椀ve for preven琀椀ng obesity Dietary Fructose  Fructose: greatest change in U.S. diet over past 40 years  Represents ~8% of calories in diet of young people  Now about same average intake from fructose as saturated fat intake in American diet  Par琀椀cularly from sweetened drinks (high-fructose corn syrup) and sweetened foods o Fructose tastes sweeter than glucose o Sucrose = equal parts glucose and fructose o High-fructose corn syrup = 55% fructose, 45% glucose  Intake of sugar in so昀琀 drinks can represent 20% or more of calories in certain groups E昀昀ects of Long-Term Fructose Intake  Increased visceral fat  Increased post-prandial triglyceride levels  Increased hepa琀椀c fat synthesis  Worse insulin sensi琀椀vity o Modifying factors (weight loss, etc.) o Interac琀椀on with exercise CHO-Induced Blood Triglycerides (HPTG): E昀昀ects of Simple Sugars  Greater e昀昀ect on TG if sugars >50% of CHO  Even 60/40% to 40/60% complex/simple sugar will alter TGs  Fiber or whole food intake– reduced e昀昀ect  Fructose par琀椀cularly causal Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/30 Nonalcoholic Fa琀琀y Liver Disease (NAFLD) and Nonalcoholic Steatohepa琀椀琀椀s (NASH)  30 years ago, three primary causes of liver disease and cirrhosis: alcohol intake, viral hepa琀椀琀椀s (A, B, C), gall bladder disease  Today, NAFLD/NASH leading cause of liver disease in U.S.; threatens to cause cirrhosis epidemic o 90 million Americans with NAFLD  ~ 1/3 get NASH, ~ 1/4 of NASH get cirrhosis o Understanding of causes, iden琀椀fying who will progress, and how to slow progression are uncertain Insulin Resistance/Hyperinsulinemia Drives Fat Synthesis in NAFLD Liver  Weight-matched obese subjects without fa琀琀y liver synthesize less fat in liver than obese subjects with fa琀琀y liver o Higher the fat content of the liver, higher the liver fat synthesis rate  Higher liver fat synthesis correlates with lower sensi琀椀vity of muscle to uptake of glucose (glucose Rd) during insulin/glucose infusions o Higher liver fat synthesis correlates with lower hepa琀椀c insulin sensi琀椀vity index (HISI) during insulin/glucose infusions  Higher liver fat synthesis correlates with higher blood insulin levels around the clock o Higher liver fat synthesis correlates with higher blood glucose levels around the clock Why is NAFLD so Common?  Flows out of our insulin resistance/metabolic syndrome program due to di昀昀eren琀椀al sensi琀椀vity of some pathways compared to others to insulin  Obesity/sedentary lifestyle reduces e昀昀ec琀椀veness of insulin on macronutrient metabolism in major 琀椀ssues (muscle, liver adipose) = insulin resistance  Blood insulin concentra琀椀ons increase as a compensa琀椀on = pancrea琀椀c beta cell secre琀椀on  High insulin and glucose levels around the clock s琀椀mulate the liver to do lipogenesis (make/store more fat) o Liver lipogenesis s琀椀ll sensi琀椀ve to the normal s琀椀mulatory e昀昀ects of insulin  Liver remains sensi琀椀ve to increased lipogenesis e昀昀ects but is resistant to reduced glucose produc琀椀on e昀昀ects of insulin = di昀昀eren琀椀al insulin resistance for di昀昀erent pathways  Elevated synthesis and storage of fat in liver appears to be natural outcome of insulin resistance syndrome– is very common Summary and Conclusions  Intake of simple sugars has increased drama琀椀cally over past genera琀椀on, especially of fructose o Now about as many calories as saturated fat in average U.S. diet– o昀琀en in liquid form  Adverse e昀昀ects on metabolic health of excess simple sugars and fructose intake o Fa琀琀y liver o Resistance to insulin ac琀椀ons o Altered fat distribu琀椀on o Hypertriglyceridemia  Restric琀椀ng sugar intake reduces fa琀琀y liver, synthesis of fat in liver, and blood LDL cholesterol in obese adolescents Lecture 13 – Fat-Soluble Vitamins: A, D, E, and K Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/31 Fat-Soluble Vitamins  Stored in 琀椀ssues  Remain in adipose and liver  Func琀椀on: hormones, blood clo琀 ng, an琀椀oxidants  Absorbed by lympha琀椀c system with fats (chylomicrons)  Not required daily  High doses can be toxic Absorp琀椀on and Diges琀椀on of Fat-Soluble Vitamins  Require bile acids and diges琀椀ve enzymes for absorp琀椀on  Gut bacteria produce li琀琀le vitamin K  Small intes琀椀ne absorbs fat-soluble vitamins similarly to fat absorp琀椀on o Packaged into chylomicrons Vitamin A: Re琀椀nol  Re琀椀noids: compounds that support physiological func琀椀ons of vitamin A  Re琀椀nal: cofactor in visual cycle o All-trans-re琀椀nal metabolite o 11-cis-re琀椀nal: cofactor in vision o Nyctalopia: night blindness  Re琀椀noic acid (RA): regulates expression of hundreds of genes to control cell func琀椀on o Vitamin A via RA is essen琀椀al for all vertebrate reproduc琀椀on and life o Severe vitamin A de昀椀ciency (re琀椀noic acid de昀椀ciency) causes xerophthalmia and blindness; testes degenera琀椀on Vitamin D: Sunlight  Calcitriol regulates gene expression and e昀昀ects on cell func琀椀on  No need for dietary vitamin D with adequate exposure to sunlight  Dietary need depends on skin pigmenta琀椀on, sunlight exposure (intensity, 琀椀me, and skin surface area), BMI, and other (pregnancy, lacta琀椀on)  Worldwide vitamin D status: ~7% de昀椀ciency; 37-88% insu昀케cient  Vitamin D insu昀케ciency o Causes: medica琀椀ons and supplements; malabsorp琀椀on; obesity o Consequences: mental; infec琀椀ons; lung disease; autoimmune disease; cancer; type 2 diabetes; metabolic syndrome Vitamin K  Cofactor in enzymes that ac琀椀vate proteins required for: o Blood clo琀 ng o Blood vessel repair o Modula琀椀ng bone density o Preven琀椀ng so昀琀-琀椀ssue calci昀椀ca琀椀on  Mechanism of vitamin K ac琀椀on: enables enzymes that ac琀椀vate target proteins/enzymes to bind calcium Vitamin E Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/32  Most potent lipid-soluble an琀椀oxidant known  Protects polyunsaturated fa琀琀y acids from oxida琀椀ve damage  Protects membranes and LDL from oxida琀椀ve damage Status of Fat-Soluble Vitamin Needs  Vitamin A: probably adequate in most North American and European popula琀椀ons  Vitamin D: inadequate levels may be common  Vitamin D: no evidence of decrease in CVD mortality  Vitamin K: probably adequate Lecture 14 – Water-Soluble Vitamins Micronutrients  Vitamins and minerals (trace metals)  Recogni琀椀on of the need for more than macromolecules in the diet about 120 years ago Water-Soluble Vitamins  B complex plus vitamin C  Required in diet (niacin can be synthesized)  Act as enzyme cofactors (catalysts)  De昀椀ciencies used to be common– rare today because of mixed diets/enrichment of food supply o People on poor diets o昀琀en de昀椀cient in mul琀椀ple vitamins– single de昀椀ciencies rarer  “Natural vitamins”: 琀椀ssue or food forms are o昀琀en less bio-available than “synthe琀椀c” vitamins o Synthe琀椀c vitamins usually transport forms  RDAs usually based on amounts that prevent clinical de昀椀ciency symptoms  Losses in food prepara琀椀on, storage, cooking  Not stored in body– large doses of some vitamins can be toxic  In future, RDIs may be based on reduc琀椀on of chronic disease risk (hypertension, cancer, etc.) Vitamin C (Ascorbic Acid)  Required by primates (including humans) and guinea pigs  Func琀椀ons: forma琀椀on of collagen (framework of bone, skin, gums); an琀椀oxidant; immune func琀椀on; hormone and neurotransmi琀琀er synthesis  De昀椀ciency: Scurvy, loss of appe琀椀te, retarded wound healing, bleeding gums/capillaries  Good sources: fruit juices, fruit, spinach, asparagus  RDA: 75 mg women, 90 mg men o Doses above 200 mg excreted in urine/not absorbed in gut o UL: 2 gm.  Megadoses (gm quan琀椀琀椀es) cause intes琀椀nal discomfort Folate  Coenzyme func琀椀ons: synthesis of nucleo琀椀des involved in RNA/DNA synthesis, DNA repair o Amino acid metabolism including homocysteine conversion to methionine  Also requires B12 o Methyla琀椀on pathways involved in gene regula琀椀on  Folate de昀椀ciency: macrocy琀椀c (megaloblas琀椀c) anemia o Caused by severe folate de昀椀ciency Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/33 o Results in fewer but enlarged red blood cells o Shows common symptoms of anemia: weakness, fa琀椀gue, di昀케culty concentra琀椀ng, irritability, headache, shortness of breath  Poor folate status associated with increased cancer risk  An琀椀folate drugs commonly used to treat various cancers o First cure of childhood leukemia  Concerns that folate for琀椀昀椀ca琀椀on may accelerate growth rate of preexis琀椀ng tumors  Sources of folate: o For琀椀昀椀ca琀椀on to minimize birth defects: enriched breads, 昀氀ours, pasta, grain products o Liver, spinach, len琀椀ls, oatmeal, asparagus, green leafy vegetables o Enriched juices o Heat-sensi琀椀ve; can be leached out in cooking liquid Vitamin B12  De昀椀ciency causes pernicious anemia and demyelina琀椀on of spinal cord o Sub-acute combined disease o La琀琀er is irreversible unless treated promptly  Func琀椀ons: o Coenzyme for amino acid catabolism o Maintains myelin sheath of nerve 昀椀bers o Metabolism of amino acids homocysteine  Acts together with folate  De昀椀ciency– pernicious anemia o Megaloblas琀椀c anemia (same as folate de昀椀ciency) o Causes secondary folate de昀椀ciency and defec琀椀ve DNA synthesis in blood/other cells o Autoimmune disease– destroys parietal cells of stomach  Cannot absorb B12 o Can take 5-15 years before symptoms develop  Treated by IM injec琀椀on of B12 o Elderly o昀琀en cannot absorb food B12 due to loss of stomach acid and Heliobacter infec琀椀on  Sources: available exclusively from animal sources, algae, bacteria o Normal diets (except vegan) contain B12 o Vegans may obtain vitamin B12 from for琀椀昀椀ed foods/supplements Vascular Disease  Folate/vitamin B12 are required for the metabolism of the amino acid homocysteine  Low folate/vitamin B12 intake increases level of plasma homocysteine  High plasma homocysteine levels associated with greater cardiovascular/cerebrovascular disease risk Niacin– Vitamin B3  Two forms: nico琀椀namide and nico琀椀nic acid  Coenzymes (NAD, NADP) assis琀椀ng with metabolism of carbohydrates, proteins, fats  Can be made from amino acid tryptophan  Good sources: meat, 昀椀sh, poultry, enriched bread products  Toxicity can result from supplements Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/34  Essen琀椀al amino acid tryptophan can reduce need for niacin o Can be converted to niacin  About 1 mg niacin derived from 60 mg tryptophan o Corn (maize) protein has low levels of tryptophan  Niacin in corn covalently bound to protein; only released under basic condi琀椀ons (limewater treatment) o Co昀昀ee contains high levels of niacin Niacin De昀椀ciency: Pellagra  Severe niacin de昀椀ciency  Symptoms: diarrhea, derma琀椀琀椀s, demen琀椀a, death  Usually in people consuming low protein, corn-based diets  Common in certain parts of the world Vitamin B6  Pyridoxine  Group of three related compounds  Coenzyme for over 100 enzymes in amino acid metabolism  Required to remove nitrogen and from amino acids (transamina琀椀on)  Cofactor for phosphorylase in muscle o Required glycogen breakdown  Cofactor for 昀椀rst enzyme in heme biosynthesis  De昀椀ciency: derma琀椀琀椀s, anemia (microcy琀椀c, impaired heme synthesis), convulsions (impaired neurotransmi琀琀er synthesis from amino acids)  Good sources: enriched cereals, meat, 昀椀sh, poultry, starchy vegetables  Toxic in high doses– neuropathy (nerve damage)  RDA: 1.3 mg  UL: 100 mg Vitamin B1  Coenzyme thiamin pyrophosphate required for metabolism of carbohydrate and branched-chain amino acids; produc琀椀on of DNA/RNA  Thiamin triphosphate has func琀椀on in brain  Good sources: whole grains, enriched foods, pork products  RDA: 1.1 mg adult female, 1.2 mg adult male  De昀椀ciency: Beriberi o First seen with advent of polished rice o Raw 昀椀sh contains enzyme that destroys thiamin o Symptoms: damage to nervous system, heart  Muscle weakness and was琀椀ng, edema  Common in alcoholics (encephalopathy) Vitamin B2  Aribo昀氀avinosis: ribo昀氀avin de昀椀ciency o Sore throat, swollen mucous membranes, derma琀椀琀椀s, stunted growth  Component of two coenzymes: FMN, FAD o Involved in oxida琀椀on-reduc琀椀on reac琀椀ons in metabolism Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/35  Part of an琀椀oxidant enzyme glutathione peroxidase  Good sources: milk, enriched foods, meat  Light sensi琀椀ve (use opaque milk cartons)  RDA: 1.1 mg women, 1.3 mg men Bio琀椀n  Part of coenzymes involved in metabolism of carbohydrates, fat, proteins  Important for gluconeogenesis and fa琀琀y acid synthesis  Bio琀椀n content has been determined for very few foods o Very high in egg yolk  De昀椀ciency only seen with large consump琀椀on of raw egg whites over 琀椀me (avidin)  Symptoms: nausea, cramps, lethargy, hair thinning, hair color loss, red rashes  AI: 30 mg (synthesized by gut bacteria) Pantothenic Acid  Component of coenzymes for fa琀琀y acid metabolism (CoA– coenzyme A)  Required for synthesizing cholesterol, steroids  Good sources: chicken, beef, egg yolk, potatoes, oat cereals, tomato products  No toxicity from excess pantothenic acid  De昀椀ciencies very rare– numbness, fa琀椀gue, muscle cramps, depression  AI: 5 mg Lecture 15 – Muscle Biology and the Physiology of Exercise and Sport in Health Two Types of Exercise  Strength/power ac琀椀vi琀椀es (resistance exercise) o Dura琀椀on seconds (e.g. sprints, li昀琀ing, jumping) = bursts o Relates to increase in muscle mass/neuromuscular func琀椀on  E.g. muscle 昀椀ber recruitment  Neuromuscular func琀椀on occurs in response to resistance exercise before any changes in muscle mass are observed o Power athletes have large muscle mass; fat is variable o Power ac琀椀vi琀椀es highly dependent on e昀昀ort; di昀케cult to assess clinically o Actually do not have to breathe during pure power ac琀椀vity  Purely anaerobic genera琀椀on of ATP  E.g. do not need to breathe in 100 meter dash o Capacity to maintain muscle contrac琀椀ons without oxygen in昀氀uenced by ATP “reserves” in muscle (e.g. crea琀椀ne-phosphate)  Aerobic ac琀椀vi琀椀es (endurance exercise; “cardio”) o Dura琀椀on longer than seconds o Intensity less than maximum capacity for aerobic work o Training: cardiovascular adapta琀椀ons  Muscle blood 昀氀ow  Hematologic changes  Oxygen uptake and exchange  Mitochondrial func琀椀on and mass  Capacity for lactate removal/recovery from anaerobiosis Downloaded by Lyrics Channel ([email protected])  lOMoARcPSD|47087965 Annabel Hou/36 o Consequence is improved “昀椀tness” (oxygen use) o Endurance/aerobic athletes: typically “lean”  Low fat mass; variable but typically not hypertrophied muscle mass o Aerobic 昀椀tness highly dependent on e昀昀ort; di昀케cult to assess clinically o Numerous associated metabolic altera琀椀ons with 昀椀tness:  Improved insulin-mediated glucose u琀椀liza琀椀on  Reduced blood TG, higher HDLc  Altered clo琀 ng factors  Lower res琀椀ng pulse  Reduced body fat; reduced weight; higher ra琀椀o lean body: fat mass; reduced visceral fat mass Di昀昀erent Sports Involve Di昀昀erent Types of Exercise  Some sports involve only one, some both types of exercise  American football: almost all power/resistance o Many players are not 昀椀t o Poor recovery from anaerobic state can cause fa琀椀gue, reduce performance  Baseball: pure power (most ac琀椀vi琀椀es < 1 sec-8 sec) o Many players can’t run out triples (=90 yards, < 12 sec)  Basketball: combina琀椀on; remarkable power o昀琀en  Soccer: combina琀椀on; very high level of aerobic 昀椀tness required  Golf: power; low level aerobic o Walking is part of game  Swimming: sprints vs. distance di昀昀er  Tennis: both  Sumo, boxing, wrestling: both  Bicycling: both; mostly excep琀椀onally-high aerobic 昀椀tness Training for Two Types of Exercise  Training: classic observa琀椀ons (work ac琀椀vi琀椀es, habits, etc.)  Aerobic training: > 20-30 minutes sustained aerobic ac琀椀vity; > 3 琀椀mes/week o Intermi琀琀ent ac琀椀vity is not the same o Prog