Perspectives in Nutrition 5 th ed. Gordon M.Wardlaw, PhD, RD, LD, CNSD PowerPoint Presentation by Dana Wu Wassmer, MS, RD

Chapter 9: The Fat-Soluble Vitamins

Vitamins Essential organic substances Yield no energy, but facilitate energy- yielding chemical reactions If absent from a diet, it will produce deficiency signs and symptoms Fat-soluble vitamins Water-soluble vitamins Preservation of vitamins in foods –exposure to light, heat, air, water, and alkaline

Fat-Soluble Vitamins Overview Dissolve in organic solvents Not readily excreted; can cause toxicity Absorbed along with fat Concern for people with fat malabsorption Transported like fat in chylomicrons, VLDL, LDL

Vitamin A Most common cause of non-accidental blindness Preformed –Retinoids (retinal, retinol, retinoic acid) –Found in animal products Proformed –Carotenoids (beta-carotene, alpha carotene,lutien, lycopene, zeaxanthin) –Must be converted to retinoid form –Intestinal cells can split carotene in two (molecules of retinoids) –Found in plant products

Terminal Ends of Retinoids H H O C OH C O C O H H Retinol Retinal Retinoic Acid

Conversion of Carotenoids to Retinoids  -Carotene 2 molecules of retinol retinal retinoic acid Enzymes in the small intestine or liver cells Oxidation

Absorption of Vitamin A Requires bile, digestive enzymes, integration into micelles Dependent on the fat in the diet 90% of retinoids can be absorbed Only ~3% of carotenoids are absorbed Intestinal cells can convert carotenoids to retinoids

Transport and Storage of Vitamin A Liver stores 90% of vitamin A in the body Reserve is adequate for several months Transported via chylomicrons to the liver Transported from the liver as retinol via retinol-binding protein to target tissue Carotenoids can be transported via VLDL Target cells contain intracellular retinol- binding proteins RAR, RXR receptors on the nucleus

Nuclear Retinoid Receptors (Fig. 9-2) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Functions of Vitamin A Retinol is needed for reproduction Retinoic acid supports growth and cell maturation Retinal is needed for night and color vision

The Visual Cycle Cones in the retina –Responsible for vision under bright lights –Translate objects to color vision Rods in the retina –Responsible for vision in dim lights –Translate objects to black and white vision

The Visual Cycle (Fig. 9-3) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Growth and Development Retinoic acid is necessary for cellular differentiation Retinoic acid triggers specific RAR and RXR receptors on the DNA for differentiation Important for embryo development, gene expression Synthesis of bone protein and enlargement of bone

Cell Health and Maintenance Epithelial cells line the outside (skin) and external passages (mucus forming cells) within the body Retinoic acid influences how epithelial cells differentiate and mature Without vitamin A, cells will deteriorate Leads to xerophthalmia (major cause of blindness) Leads to follicular hyperkeratosis (skin disorder)

The Anti-Infection Vitamin Uncertain of the action of vitamin A and resistance to disease Deficiency leads to poor mucus formation Deficiency reduces activity of some immune-system cells High-dose therapy of vitamin A increase immune response

Cancer and Carotenoids Role in cell development and immune- system Role as an antioxidant Lower risk of breast cancer with vitamin A supplements Megadose is not advise Mixed results in cancer/vitamin A studies Foods rich in vitamin A and other phytochemicals are advised

Deficiency of Vitamin A Night blindness Decrease mucus production Leading to bacterial invasion in the eye –Conjunctival xerosis –Bitot’s spots –xerophthalmia Irreversible blindness

Deficiency of Vitamin A Follicular hyperkeratosis Keratin protects the inner layers of skin and maintains moisture Kertinized cells replaces the normal epithelial cells in the underlying skin layers Hair follicles become plugged Bumpy, rough, and dry skin

Prevention of Deficiency Establish an adequate liver store in weaned infants Deficiency occurs most often after baby has been weaned Providing a megadose of vitamin A to at risk population may be helpful

Cancer Prevention Some studies report positive benefit from taking vitamin A (retinoids) No longer-term studies on human has been done Role in cell differentiation Role in inhibition of proliferation Possible role in programmed cell death Carotenoid lycopene may protect against prostate cancer

Cardiovascular Prevention Carotenoids’ antioxidant capacity No definitive conclusions Many recommend 5-A-Day

Age-Related Macular Degeneration Leading cause of legal blindness among Americans over the age of 65 Changes in the macula (for detail vision) Carotenoids lutein and zeaxanthin found in high amounts in healthy macula Risk lowered with high intakes of carotenoids

Vitamin A and Your Skin Topical treatment and oral drug Decreases sebum secretion Accutane (oral) and Retin-A (topical) Can induce toxicity symptoms Must limit sun exposure Not recommended for pregnant women Use only under supervision of a physician

Sources of Vitamin A Preformed –Liver, fish oils, fortified milk, eggs –Contributes to half of all the vitamin A intake Proformed –Dark leafy green, yellow-orange vegetables/fruits –Contributes to half of all the vitamin A intake

Vitamin A from the Food Guide Pyramid (Fig. 9-5) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Measuring Vitamin A International unit (IU)-crude method of measurement Retinol activity equivalent (RAE) - current, more precise method of measurement 1 ug of retinol = 1 RAE = 3.3 IU =12 ug beta-carotene = 24 ug of other provitamin A

RDA for Vitamin A for Adults 900 REA for men 700 REA for women Average intake meets RDA Much stored in the liver Vitamin A supplements are unnecessary No separate RDA for carotenoids

Who is at Risk For Deficiency Breast fed infants Preschooler with poor vegetable intake Urban poor Elderly Alcoholics and people with liver disease Individual with fat malabsorption HIV, AIDS

Toxicity of Vitamin A Hypervitaminosis A Result of long-term supplement use (3-10x >RDA) Acute Ingestion of LARGE dose(s) of vitamin A (within a short period) Result in intestinal upset, headache, blurred vision, muscular incoordination Symptoms disappear when supplements are stopped

Toxicity of Vitamin A Chronic Large intake of vitamin A over a long period Bone/muscle pain, loss of appetite, skin disorders, headache, dry skin, hair loss, increased liver size, vomiting Discontinue supplement is recommended Possible permanent damage

Toxicity of Vitamin A Teratogenic Tends to produce physical defect on developing fetus as a result of excess vitamin A intake Spontaneous abortion, birth defects May occur with as little as 3 x RDA of preformed vitamin A Upper Level for Vitamin A 3000ug for adults Fatal dose - 12 g of vitamin A can be fatal

Effects of Vitamin A (Fig. 9-6) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Toxicity of Carotenoids Hypercarotenemia High amounts of carotenoids in the bloodstream Excessive consumption of carrots/squash/beta-carotene supplements Skin turns a yellow-orange color

Vitamin D Prohormone Derived from cholesterol Synthesis from sun exposure Insufficient sun exposure makes this a vitamin Activated by enzymes in liver and kidneys Deficiency can cause diseases

Vitamin D Synthesis (Fig. 9-7) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Absorption of Vitamin D ~80% of vitamin D consumed is incorporated into micelles Absorbed in the small intestine and transported via chylomicrons Transported through the lymphatic system

Metabolism and Storage of Vitamin D Activation by the liver and the kidneys Stored in fat tissue Activate vitamin D when calcium is inadequate Excretion of vitamin D mainly via bile

Functions of Vitamin D Regulate blood calcium level (Fig. 9-8) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Vitamin D and Cell Differentiation Calcitriol is able to influence differentiation and function of the some cells Linked to reduction of breast, colon, and prostate cancer development

Role in Bone Formation Calcitriol creates a supersaturated Ca + Phos solution Causes Ca + Phos to deposit in the bones Strengthen bones Rickets is the result of low vitamin D Osteomalacia (soft bone) is rickets in the adult

Food Sources of Vitamin D Fatty fish (salmon, herring) Fortified milk Some fortified cereal

The Adequate Intake (AI) for Vitamin D 5 ug/d (200 IU/day) for adults under age ug/day ( IU/day) for older Americans Light skinned individuals can produce enough vitamin D to meet the AI from casual sun exposure Infant are born with enough vitamin D to last ~9 months of age.

Who is at Risk for Deficiency? Elderly (staying indoors) People living in the northern climate People with fat malabsorption need sun exposure Vitamin D resistance –Resistance to the action of vitamin D –May be due to lack of calcitriol synthesis or inability to bind to nuclear receptor –Requires large doses of calcitriol

Vitamin D as a Medicine Type II (age-related) osteoporosis Loss of bone mass Limited ability to absorb vitamin D or produce calcitriol ug vitamin D/ day plus calcium decrease bone fracture Risk for hypercalcemia Psoriasis Skin disorder Topical treatment

Toxicity Warning Vitamin D can be very toxic Regular intake of 5-10x the AI can be toxic Result from excess supplementation (not from sun exposure or milk consumption) Sign and symptoms: over absorption of calcium (hypercalcemia), increase calcium excretion Calcium deposits in kidneys, heart, and blood vessels Mental retardation in infants

Vitamin E Tocopherols and tocotrienols Amount absorbed is dependent on fat intake –Incorporated into micelles –Requires bile and fat digesting enzymes Transported via chylomicrons to the liver Transported via VLDL, LDL, HDL from the liver Found concentrated in areas where fat is found Excreted via bile and urine (much in feces due to limited absorption)

Redox Agent Vitamin E is able to donate electron to oxidizing agent Protect the cell from attack by free radicals Peroxyl-radical scavenger Protects PUFAs within the cell membrane and plasma lipoproteins Prevents the alteration of cell’s DNA and risk for cancer development

Vitamin E, An Antioxidant (Fig. 9-10) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Free Radicals Production is normal result of cell metabolism and immune function Destructive to cells; set off a chain reaction Lipid peroxidation More vitamin E is found in the lungs Smoking causes significant oxidative damage

Protection From Oxidative Damage Glutathione peroxidase –A selenium containing enzyme –Helps breakdown peroxidized fatty acids (that tends to form free radical) –Lessen the burden of vitamin E Superoxide dismutase and catalase –Reacts with peroxide and single oxygen (free radicals) –Reduce free radical activity

The Antioxidant System (Fig. 9-11) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

The More The Better? Vitamin E is only one of many antioxidant It is likely that the combination of antioxidant is more effective Diversify your antioxidant intake with a balanced and varied diet Megadose of one antioxidant may interfere with the action of another

Other Functions of Vitamin E Protects the double bonds in saturated fat Role in iron metabolism Inhibits LDL oxidation Inhibits protein kinase C activity Enhance release of prostacyclin Maintenance of nervous tissue and immune function No specific role in metabolic reaction

Food Sources of Vitamin E Plant oils Wheat germ Asparagus Peanuts Margarine Nuts and seeds Actual amount is dependent on harvesting, processing, storage and cooking

RDA for Vitamin E 15 mg/day for women and men (=22 IU of natural source or 33 IU of synthetic form) Average intake meets RDA 1 mg d-  -tocopherol = 0.45 IU (synthetic source) 1 mg d-  -tocopherol = 0.67 IU (natural sources)

Deficiency of Vitamin E Hemolytic anemia Peripheral neuropathy Maldigestion of fat Insufficient bile production Rare

Who is at Risk for Deficiency? Premature infants People with fat malabsorption –Cystic fibrosis, celiac disease, liver disease Low selenium intake

Toxicity of Vitamin E Supplements up to 800 IU is probably harmless Upper Level is 1,000 mg/day of any form of supplementary alpha-tocopherol Upper Level is 1500 IU (natural sources) or 1100 IU (synthetic forms) Inhibit vitamin K metabolism and anticoagulants

Vitamin K (“Koagulation”) Phylloquinone (K 1 ) and menaquinones (K 2 ) 40%-80% of dietary vitamin K is absorbed Absorption requires bile and pancreatic enzymes Menaquinones are synthesized by the bacteria in the colon and are absorbed Role in the coagulation process Calcium-binding potential Formation of osteocalcin

Vitamin K and the Coagulation Process (Fig. 9-13) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Drugs and Vitamin K Anticoagulant –Lessens vitamin K reactivation –Lessens blood clotting process –Monitor vitamin K intake Antibiotics –Destroy intestinal bacteria –Inhibits vitamin K synthesis and absorption –Potential for excessive bleeding

Food Sources of Vitamin K Liver Green leafy vegetables Broccoli Peas Green beans Resistant to cooking losses Limited vitamin K stored in the body

Adequate Intake for Vitamin K 90 ug/day for women 120 ug/day for men RDA met by most Excess vitamins A and E interferes with vitamin K Newborns are injected with vitamin K(breast milk is a poor source) Toxicity unlikely; readily excreted