Module 9 - Fat-Soluble Vitamins_student.pdf

KIN275 Introduction to Nutrition Module 9 Fat-Soluble Vitamins Julia Totosy de Zepetnek, PhD Module 9 Learning Objectives 1. List the major physiological functions of each fatsoluble vitamin Discuss DRIs and identify major food sources Discuss major symptoms and diseases associated with deficiency a...

KIN275 Introduction to Nutrition Module 9 Fat-Soluble Vitamins Julia Totosy de Zepetnek, PhD Module 9 Learning Objectives 1. List the major physiological functions of each fatsoluble vitamin Discuss DRIs and identify major food sources Discuss major symptoms and diseases associated with deficiency and toxicity Fat-Soluble Vitamins More difficult eliminating excess (compared to water-soluble vitamins) – Don’t dissolve in watery substances Body stores extra, particularly in liver and adipose tissue – Overtime they can accumulate and cause toxicity Fat-soluble vitamins require bile and chylomicrons for absorption Remember? Decreased risk of deficiency, but increased risk of toxicity International Units (IUs) In the past, most vitamins expressed as IU Today most replaced with more precise mg or ug Food composition tables still often list IU values for fat-soluble vitamins Vitamin A & Carotenoids Classifying forms of Vitamin A 3 active forms of Vitamin A (retinoids): – Retinol = storage form of vitamin A (often stored as retinyl esters) – Retinal = vision – Retinoic Acid = cell differentiation Found in animal foods Plants contain carotenoids (e.g., betacarotene); provitamins / vitamin precursors -- the body must convert it to the active form(s) Vitamin A in the Digestive Tract Both pre-formed vitamin A and carotenoids are bound to proteins in foods – Must be released by pepsin In small intestine the released retinol and carotenoids combine with bile acids and other fat-soluble food components to form micelles – Absorption pre-formed vitA 70-90% – Pro-vitamin carotenoids not as well absorbed (and absorption decreases as intake increases) Transported from intestine in chylomicrons for delivery to body tissues (bone marrow, blood cells, spleen, muscles, kidney, liver) Vitamin A Yellow, orange, or red pigments that give these colors to fruits/vegetables Liver is main storage site (~90%); to move from liver stores to tissues, retinol must be bound to retinol binding protein (RBP) Body can make retinal and retinoic acid forms from retinol and carotenoids in diet; remember: – Retinol circulates in blood – Retinal important for vision – Retinoic acid (made from retinol or retinal) affects gene expression and is responsible for Vitamin A’s role in cell differentiation, growth, and reproduction *Note: conversion of retinol to retinal is reversible, but pathway from retinal to retinoic acid is not Vitamin A Cleaving betacarotene yields two molecules of retinal 12mg beta-carotene yields 1mg retinol Beta-carotene converted into retinal in intestinal mucosa and liver In the body, retinol (storage form) and retinal (vision) can be interconverted Once retinoic acid is formed, it cannot be converted back to retinal or retinol Vitamin A: Retinol and Retinal Vitamin A and Vision Retina (light-sensitive area in ea. eye) contains rods and cones – Rods enable adaptation to see in poorly lit environments – Cones responsible for color vision and function in well-lit environments Retinol needed for proper function (converted to retinal) Vitamin A: Retinol and Retinal Vitamin A: Retinol and Retinal If vitamin A (retinal) levels are low, body cannot re-form rhodopsin, and night blindness results Rhodopsin is composed of opsin and vitamin A (retinal) Eyes so sensitive to vitamin A levels that one injection can relieve this night blindness in minutes Vitamin A: Retinol and Retinal Takes a certain amount of time for rod cells to react to dim light [after a sudden and dramatic reduction in light intensity] Night blindness – Some retinal that splits away from rod cells is destroyed; to replace, the rods remove some retinol from bloodstream and convert it to retinal – If retinol is unavailable à night blindness (inability to see in dim light) Vitamin A: Retinoic Acid Regulating Gene Expression Differentiation: cells change in structure and function to become specialized – In bone marrow, some cells differentiate into various wbc, others to form rbc – Vitamin A affects this through its effect on gene expression (can turn on or off production of certain proteins that regulate functions within cells and throughout the body) Vitamin A can determine what type of cell an undifferentiated cell will become Vitamin A: Retinoic Acid Retinoic Acid Vitamin A Functions: Growth & Development Role in cell differentiation necessary for production, maturation, and maintenance of epithelial tissue – Form protective tissues that line the body (incl. skin and linings of digestive, respiratory, and reproductive tracts) Vitamin A Functions: Immune Function If microorganisms breach first barrier (epithelial cells), immune cells attack invaders Also -- plays a role in production and activity of white blood cells – Vitamin A controls gene expression that induces differentiation of immature immune system cells into mature wbc (phagocytes, lymphocytes) – Certain white blood cells produce antibodies that help destroy infectious agents (e.g., bacteria) Vitamin A Functions: Bone Growth & Development Bones constantly remodeled – Vitamin A helps produce bone cells needed for growth [required for bone remodeling] – Too much Vitamin A also results in bone loss and increased risk fracture Vitamin A Stable when heated but may be destroyed by exposure to light and oxygen Retinol activity equivalent (RAE) provides Vitamin A intake from all sources: Vitamin A Deficiency Threat to health, sight, lives of millions children in developing world Why are children more susceptible than adults? Can be caused by insufficient intakes of vitamin A, fat, protein… Not common in developed world; status depends on liver stores & protein intake Vitamin A DRI UL 18+ yrs: 3000 ug/day Toxic at extremely high doses; typically from supplements Toxicity Symptoms acute toxicity: nausea, vomiting, headache, dizziness, blurred vision, lack of muscle coordination Symptoms chronic toxicity: weight loss, muscle/joint pain, liver damage (main site of storage), visual defects, dry scaling lips, skin rashes, bone abnormalities Vitamin D “the sunshine vitamin” Vitamin D Produced in skin (Vitamin D3) from sun exposure Absorbed from diet (vitamin D2) D2: fatty fish, cod liver oil, egg yolk, butter, dietary supplements Vitamin D Classifying Forms of Vitamin D Blood levels of 25-OH vitamin D are used to determine vitamin D status Vitamin D Metabolism UVB action on 7 dehydrocholesterol to form D3 --> enters circulation (chylomicrons, lymph, liver) – can be stored in fat or go to liver – in liver, hydroxylated to 25OH-D (inactive) – circulation to kidney – hydroxylated to 1,25 dihydroxycholecalciferol (active hormone) Active Vitamin D production tightly regulates Ca and P levels via parathyroid hormone Vitamin D Calcium must be carefully regulated b/c of important role it plays in muscle contraction More in the bone-building nutrients module! Vitamin D Does not play a major role Vitamin D Other Functions of Vitamin D Regulating neuromuscular and immune function Reducing inflammation Reduce risk heart disease, cancer, diabetes, multiple sclerosis, asthma, depression – Much research is needed to clarify its role in chronic disease prevention Vitamin D Females Infants Children Males Pregnancy Lactation Those south of 33rd parallel and who are outdoors btw 10am3pm (when sunlight is more intense) often obtain enough sun exposure to synthesize vitamin D during most of the yr Those living north of 33rd parallel, angle of winter sun is such that sun’s rays must pass through more of atmosphere than at other times of yr Vitamin D Deficiency A nutrient of public health concern Many North Americans do not consume enough Vitamin D (nearly half have low blood levels); more likely to be deficient if: – – – – Darker skin tone Overweight Electronic media / games >4h/day, Drinking milk less than once/wk Elite athletes also at risk; some research suggests relationship between deficiency and injury risk Vitamin D Deficiency (Rickets) By the 17th century, some people in parts of northern Europe learned that exposing children to sunlight or giving fish liver oil prevented [or treated] rickets By 19th century, scientists learned that rickets can be prevented by sunlight exposure, vitamin D supplements, and vitamin Drich foods Vitamin D Deficiency (Rickets) While severe rickets is uncommon, recent increase in no. cases in infants / toddlers Human breast milk insufficient vitamin D Young children most likely to develop rickets: breastfed, dark skin, minimal sunlight exposure, little to no vitD intake Recommendation: breastfed -400IU supplement / day; formula fed -- ensure formula fortified with vitamin D Consume 400 IU/day through adolescence Vitamin D Deficiency (Osteomalacia) Adults form vitamin D deficiency “soft bones” (bend and break easily; esp. hips, spine) Normal amount collagen but lower-than-normal amount calcium – Can precipitate or exacerbate osteoporosis Highest risk: confined indoors or almost fully covered when outside (religious, cultural reasons); kidney, liver, intestinal diseases Vitamin D Deficiency (Osteoporosis) Skeletal disorder characterized by low bone strength predisposing a person to increased risk of fracture Most common sites: hip, lumbar spine, wrist More in the bonebuilding minerals module! BMJ. 2006; 333(7581): 1251–1256. Vitamin D Deficiency with Age With age, production of 7-dehydrocholesterol in skin declines, and conversion of pre-vitamin to active vitamin D in kidneys decreases – More likely to develop vitamin D deficiency Older adults also at risk for bone fractures Not uncommon for ppl w/ osteomalacia to also have osteoporosis – Associated with inadequate calcium intakes… but long-term vitD deficiency contributes to condition because calcium absorption is reduced Vitamin D Toxicity DRI UL 19 yrs: 100 ug or 4000 IU/day Does not occur from sunlight or dietary sources; can occur from supplementation 30min midday summer sun exposure: 10,000-20,000 IU Vitamin D Toxicity from supplements can cause high blood Ca2+ (hypercalcemia) – Nausea, vomiting, weakness, frequent urination Deposition of Ca2+ in soft tissues (blood vessels, kidneys), and CV damage Vitamin E (antioxidant) Vitamin E Classifying Forms of Vitamin E Many forms (8 similar compounds); only alpha-tocopherol found in humans Unlike A & D, vitamin E is not primarily stored in liver; ~90% is stored in body fat Prevents oxidation, and has synergistic action with selenium in protecting cell membranes from oxidation – May protect LDLc from oxidation Vitamin E Remember Oxidative Stress? Occurs because of an imbalance between prooxidant systems and anti-oxidant systems Vitamin E Vitamin E ROS Damage Lipids most vulnerable to oxidative stress Vitamin E Lipid Radicals Lipid + OH Lipid + H2O Hydroxyl radical takes H atom from lipids (e.g. PUFA), generates a lipid radical + water Lipid radical reacts with oxygen --> forms another lipid radical à remove H atoms from other lipids Initiates a chain reaction Vitamin E Lipid + OH Lipid + H2O Active Vit E + Lipid Inactive Vit E + Lipid Vit E donates electrons to lipid radical (or other radical species) --> Vit E no longer active --> free radical stopped from causing more damage and generating more radicals Vitamin E Inactive Vit E can be re-activated by Vitamin C Inactive Vit E + Vit C Ascorbic acid with its H atoms (reduced form of Vit C) Active Vit E + Vit C Dehydroascorbic acid without its H atoms (oxidized form of Vit C) 54 Vitamin E Vitamin E Vitamin E protects vulnerable PUFAs in cell membranes, in blood, and elsewhere by “scavenging” free radicals Vitamin E Sensitive to destruction by O2, metals, light, heat --> some lost during food processing, cooking, and storage Relatively stable at normal cooking temps; but vit E in cooking oils may be destroyed if oil is repeatedly heated too high temps (deep-frying) Vitamin E Vitamin E Deficiency Very rare in healthy people – Linked to certain diseases where fat is not properly digested or absorbed (e.g., Crohn’s, CF) – Very low fat diets may need vitamin E supplement Deficiency can cause nerve and muscle damage, loss of neuromuscular control, blindness Can also reduce functioning of immune system and cause form of anemia in preterm infants Vitamin E Toxicity DRI UL: 1000 mg/day of any form from supplemental sources Some people who have risks of blood clots etc. may take vitamin E… can reduce the risk of blood clots and therefore heart attack and sudden death …but they have to be careful; excessive vitamin E intake can cause blood thinning and can lead to fatal bleeding – Evidence of hemorrhagic stroke at doses 1500 mg/day (interferes with blood clotting) – Interferes with vitamin K [essential in blood clotting] Vitamin K “koagulation” Vitamin K Vitamin K Named for Danish word koagulation Essential for blood clotting (coagulation) – Without it you would bleed to death from a single cut Phylloquione (K1): plant sources Menaquinones (K2): animal sources and synthesized by our intestinal bacteria Menadione (K3): synthetic form Vitamin K Functions: Blood Clotting (K1) Blood clotting requires: inactive clotting factors and platelets (cell fragments) Fibrin (protein) traps blood cells forming a mesh Vitamin K Functions: Bone Health (K2) Shown to play a role in bone health via stim of bone formation and inhib of bone breakdown Regulates body calcium; prevents deposition of calcium in soft tissues (e.g., blood vessels) – May also prevent arterial calcification [associated with atherosclerosis] …K2 may also promote insulin sensitivity, suppress cancer progression, improve cognitive performance… more research is needed Vitamin K Unlike A,D,E… body uses K rapidly, so constant supply is necessary – Vitamin K produced in bacteria in GI tract contributes to needs, but not well absorbed and alone is not enough to meet needs Vitamin K Vitamin K Deficiency (K1) In adults, vitamin K deficiency is rare; usually occurs in people with fat malabsorption problems (e.g., CF) Bruising, hemorrhage due to: – Impaired fat absorption (pancreatic disorder) – Action of drug inhibitors (antibiotics kill microflora that produce endogenous vitamin K, anticoagulant drugs inhibit vitamin K absorption) Vitamin K Deficiency (K1) Vitamin K poorly absorbed across the placenta Breastmilk has little vitamin K Newborns: digestive tract is sterile – no bacteria – blood clotting is inhibited at birth Common to give vitamin K injection within 6hrs of birth to last infant until gut microflora are established (a few weeks) Vitamin K Deficiency (K2) Can cause increased blood vessel calcification – Common in patients with chronic renal disease Increased risk of bone fracture More research needed on dosing effects and safety of vitamin K for bone health Overview: Vitamin Deficiencies Scurvy Rickets Night Blindness Beriberi Pellagra Heart Disease Anemia Bone Fractures Supplements? Health Canada Approval Process (Vitamin Supplements) Summary of Vitamins Organic compounds Play numerous roles in body; each vitamin usually has more than one function – Regulate variety of body processes Includes water-soluble thiamin, riboflavin, niacin, biotin, pantothenic acid, folate, vitamin B6, B12, C Includes fat-soluble vitamins A, D, E, K Summary of Vitamins Vitamin deficiency disorders generally result from inadequate diets or conditions that increase body’s requirement for vitamins Most commonly eaten foods do not contain toxic levels of vitamins – Toxicity occurs in people who take megadoses of vitamins Bioavailability dependent on a variety of factors Summary of Vitamin A (retinol, retinal, retinoic acid) Vitamin A family includes retinol, retinal, retinoic acid (and precursor beta-carotene) Involved in vision, cell differentiation, immune function Dietary sources: fortified milk and eggs; provitamin A carotenoids plentiful in dark green and orange fruits and vegetables Deficiency: contributes to night blindness and weakened immunity Excess: toxic; can cause liver damage, visual defects, bone abnormalities Summary of Vitamin D (calciferol) Both a hormone and a vitamin Calciferol present in both plant (ergocalciferol) and animal (cholecalciferol) sources Exposure to sunlight enables human skin to synthesize precursor of vitamin from cholesterollike substance – Body can convert it to active form in kidneys Deficiency (infants): rickets Deficiency (adults): osteomalacia Excess: body deposits calcium in soft tissue Summary of Vitamin E (alpha-tocopherol) Alpha-tocopherol is most active form Functions primarily as anti-oxidant Plant oils and products made from them are generally rich sources High doses may be detrimental to health Summary of Vitamin K (phylloquione & menaquinone) Family of compounds that includes phylloquinone (K1), menaquinone (K2), menadione (K3) – K1 essential for blood-clotting (green leafy vegetables [kale, spinach] – K2 important for healthy bone formation (liver, beef, egg yolks) Inadequate consumption can cause uncontrollable bleeding Babies usually born with low vitamin K stores; require injection of vitamin K soon after birth END Fat Soluble Vitamins! 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