1 The Fat-Soluble Vitamins

2 Vitamins  Defining a vitamin Essential organic substances Body cannot synthesize enough to maintain health Absence from the diet will produce deficiency signs and symptoms  Yield no energy, but facilitate energy- yielding chemical reactions  May be fat- or water-soluble  Natural versus synthetic

3 Historical Perspective  Foods found to cure illnesses Liver extract – vision problems Citrus fruits – scurvy  All vitamins have probably been discovered – TPN can support life

4 Storage of Vitamins in the Body  Fat-soluble are generally stored except vitamin K  Water-soluble are generally excreted except vitamin B12 and B6  Vitamin deficiency occurs when that vitamin is lacking in the diet and body stores are exhausted

5 Vitamin Toxicity  Toxicity of vitamin A is most likely  Unlikely to develop toxicity of any vitamin unless individual vitamin supplements are used  Balanced multivitamin and mineral supplement supplies < 2 x RDA

6 Malabsorption of Vitamins  Fat malabsorption leads to deficiencies of fat-soluble vitamins  Alcohol abuse affects absorption of some B vitamins  Intestinal diseases affect absorption of some B vitamins

7 Digestion and Absorption of Fat-Soluble Vitamins

8 Absorption of Fat-Soluble Vitamins  Adequate absorption depends of absorption of fat  40 – 90% of ingested fat-soluble vitamins absorbed (less efficient when consumed in higher quantities) Distribution of Fat-Soluble Vitamins  Transported by chylomicrons and lipoproteins  Carried to liver as remnants, then stored or redistributed

9 Vitamin A  Deficiency of vitamin A is the most common cause of non-accidental blindness, worldwide  Preformed Retinoids (retinal, retinol, retinoic acid) Found in animal products  Provitamin A Carotenoids Must be converted to retinoid form Intestinal cells can split carotene in two (molecules of retinoids) Found in plant products

10 Terminal Ends of Retinoids

11 Conversion of Carotenoids to Retinoids  Enzymatic conversion of carotenoids occurs in liver or intestinal cells, forming retinal and retinoic acid  Provitamin A carotenoids Beta-carotene Alpha carotene Beta-cryptoxanthin  Other carotenoids Lutein Lycopene Zeaxanthin

12 Absorption of Vitamin A  Retinoids Retinyl esters broken down to free retinol in small intestine - requires bile, digestive enzymes, integration into micelles Once absorbed, retinyl esters reformed in intestinal cells 90% of retinoids can be absorbed  Carotenoids Absorbed intact, absorption rate much lower Intestinal cells can convert carotenoids to retinoids

13 Transport and Storage of Vitamin A  Liver stores 90% of vitamin A in the body  Reserve is adequate for several months  Transported via chylomicrons from intestinal cells to the liver  Transported from the liver to target tissue as retinol via retinol-binding protein, which is bound to transthyretin

14 Retinoid Binding Proteins  Target cells contain cellular retinoid binding proteins Direct retinoids to functional sites within cells Protect retinoids from degradation  RAR, RXR receptors on the nucleus Retinoid-receptor complex binds to DNA Directs gene expression

15 Excretion of Vitamin A  Not readily excreted  Some lost in urine  Kidney disease and aging increase risk of toxicity because excretion is impaired

16 Functions of Vitamin A: Vision  Retinal turns visual light into nerve signals in retina of eye  Retinoic acid required for structural components of eye 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

17 The Visual Cycle

18 Functions of Vitamin A: Growth and Differentiation of Cells  Retinoic acid is necessary for cellular differentiation  Important for embryo development, gene expression  Retinoic acid influences production, structure, and function of epithelial cells that line the outside (skin) and external passages (mucus forming cells) within the body

19 Functions of Vitamin A: Immunity  Deficiency leads to decreased resistance to infections  Supplementation may decrease severity of infections in deficient person

20 Vitamin A Analogs for Acne  Topical treatment (Retin-A) Causes irritation, followed by peeling of skin Antibacterial effects  Oral treatment Regulates development of skin cells Caution regarding birth defects

21 Possible Carotenoid Functions  Prevention of cardiovascular disease Antioxidant capabilities ≥5 servings/day of fruits and vegetables  Cancer prevention Antioxidant capabilities Lung, oral, and prostate cancers Studies indicate that vitamin A-containing foods are more protective than supplements  Age-related macular degeneration  Cataracts  In general, foods rich in vitamin A and other phytochemicals are advised rather than supplements

22 Vitamin A in Foods  Preformed Liver, fish oils, fortified milk, eggs, other fortified foods Contributes ~70% of vitamin A intake for Americans  Provitamin A carotenoids Dark leafy green, yellow-orange vegetables/fruits

23 Measuring Vitamin A  International unit (IU)-crude method of measurement  Retinol activity equivalent (RAE) -current, more precise method of measurement

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

25 Deficiency of Vitamin A  Most susceptible populations: Preschool children with low F&V intake Urban poor Older adults Alcoholism Liver disease (limits storage) Fat malabsorption  Consequences: Night blindness Decreased mucus production Decreased immunity Bacterial invasion of the eye Conjunctival xerosis Bitot’s spots Xerophthalmia Irreversible blindness Follicular hyperkeratosis Poor growth

26 Upper Level for Vitamin A  3000 μg retinol  Hypervitaminosis A results from long- term supplement use (2 – 4 x RDA)  Toxicity  Fatal dose (12 g)

27 Toxicity of Vitamin A Acute – short-term megadose (100 x RDA); symptoms disappear when intake stops  GI effects  Headaches  Blurred vision  Poor muscle coordination

28 Toxicity of Vitamin A Chronic – long-term megadose; possible permanent damage  Bone and muscle pain  Loss of appetite  Skin disorders  Headache  Dry skin  Hair loss  Increased liver size  Vomiting

29 Toxicity of Vitamin A  Teratogenic (may occur with as little as 3 x RDA of preformed vitamin A) Tends to produce physical defect on developing fetus as a result of excess vitamin A intake Spontaneous abortion Birth defects

30 Health Effects of Vitamin A

31 Toxicity of Carotenoids  Not likely, as rate of conversion of carotenoids to retinoic acid by liver is slow and efficiency of absorption of carotenoids decreases as intake increases  Hypercarotenemia High amounts of carotenoids in the bloodstream Excessive consumption of carrots/squash/beta- carotene supplements Skin turns a yellow-orange color

32  What are the functions of vitamin A?  What are the two forms of vitamin A and in what foods can they be found?  How does vitamin A help with night vision?  What are the effects of a diet that is deficient in vitamin A?  What are the effects of a diet that is toxic in vitamin A? Content Review

33 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 diseases Rickets Osteomalacia

34 Vitamin D 3 Formation in the Skin  Sunlight converts provitamin D 3 to previtamin D 3 in skin  Previtamin D 3 converted to vitamin D 3 and released into bloodstream

35 Absorption of Vitamin D 2  ~80% of vitamin D consumed is incorporated into micelles  Absorbed in the small intestine and transported via chylomicrons  Fat malabsorption impairs vitamin D absorption

36 Metabolism, Transport, Storage and Excretion of Vitamin D  Transported from small intestine to liver in form of chylomicrons in lymphatic system  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

37 Functions of Vitamin D  Regulate blood calcium level Increased intestinal absorption of calcium from food With parathyroid hormone, releases calcium from bone  Cell differentiation Linked to reduction of breast, ovarian, colon, and prostate cancer development

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

39 Vitamin D Needs  Due to variation in sunlight exposure, no RDA set, but AI established as: 5 μg/d (200 IU/d) for adults under age μg/d ( IU/d) for older adults  Light skinned individuals can produce enough vitamin D to meet the AI from casual sun exposure  Infants are born with vitamin D, but AAP recommends supplementing breastfed infants with 5 μg (200 IU)/d until weaned to fortified infant formula

40 Vitamin D Deficiency  Rickets – poor bone mineralization in children  Osteomalacia – soft bones in adults  Vitamin D resistance – problem with synthesis of active form or defective receptor binding

41 Pharmacologic Use of Vitamin D Analogs Psoriasis  Skin disorder  Topical treatment

42 Upper Level for Vitamin D  UL = 50 μg/d (2000 IU/d)  Regular intake of 5-10x the AI can be toxic Over-absorption of calcium (hypercalcemia), increase calcium excretion Calcium deposits in kidneys, heart, and blood vessels, narrowing of pulmonary arteries and aorta, facial changes, mental retardation  Results from consuming megadoses, not excess sun exposure

43  Why is vitamin D considered a pro- hormone?  How is vitamin D metabolized?  What are the functions of vitamin D?  What are good sources (food and non- food) of vitamin D? Content Review

44 Miracle Vitamin D  Vitamin D Sources Sun exposure  80 – 100% from sun exposure  SPF 8 reduces synthesis by 97.5% Foods contain low levels  Test of fortified milk reveal little or no vitamin D  Vitamin D Deficiency >50% of older adults are deficient Various studies show 32 – 41% of middle-aged adults are deficient EXPERT OPINION

45 Miracle Vitamin D  More than bone health Intestinal absorption of calcium Potent inhibitor of cell growth Lymphocyte function Blood pressure regulation Possible roles in treatment or prevention of hypertension, MS-like disease, and diabetes EXPERT OPINION

46 Vitamin E  Tocopherols and tocotrienols  Amount absorbed is dependent on fat intake  Vitamin E structure and the R configuration

47 Absorption, Transport, Storage, and Excretion of Vitamin E  Absorption is dependent on the absorption of dietary fat  Dependent on bile and pancreatic enzyme for absorption  Incorporated into chylomicrons to the liver, then incorporated into lipoproteins  Stored in adipose tissue, liver, and muscle  Found in cell membranes  Much excreted via bile and urine

48 Functions of Vitamin E  Antioxidant Vitamin E is able to donate electron to oxidizing agent Protects the cell from attack by free radicals Peroxyl-radical from fat breakdown Protects PUFAs within the cell membrane and plasma lipoproteins Prevents the alteration of cell’s DNA and risk for cancer development  Redox agent – can undergo oxidation or reduction

49 Vitamin E, An Antioxidant

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

51 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

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

53 Vitamin E in Foods  Plant oils  Wheat germ  Asparagus  Peanuts  Margarine  Nuts and seeds  Actual amount is dependent on harvesting, processing, storage and cooking

54 Vitamin E Needs  RDA = 15 mg/d for women and men (22 IU of natural source or 33 IU of synthetic form)  Average intake ~ 2/3 RDA 1 mg d--tocopherol = 0.45 IU (synthetic source) 1 mg d--tocopherol = 0.67 IU (natural sources)

55 Vitamin E Deficiency  Rare  Consequences of deficiency Hemolytic anemia Nervous system damage  Susceptible populations Premature infants People with fat malabsorption People on very low-fat diets Smokers (destruction of vitamin E in lungs)

56 Upper Level for Vitamin E  Supplements up to 800 IU is probably harmless  Upper Level is 1,000 mg/d of any form of supplemental alpha-tocopherol  Upper Level is 1500 IU (natural sources) or 1100 IU (synthetic forms)  Inhibit vitamin K metabolism and anticoagulants  Possible impact on prostate health

57  What are the functions of vitamin E?  What is an antioxidant?  What are some of the signs of vitamin E deficiency?  Can vitamin E be toxic? Why/not?  What is glutathione peroxidase and what is its role with vitamin E? Content Review

58 Vitamin K (“Koagulation”)  Phylloquinone (K 1 ) from plant sources  Menaquinones (K 2 ) from fish oils, meats, and intestinal bacteria

59 Absorption, Transport, Storage & Excretion of Vitamin K  Absorption requires bile and pancreatic enzymes Up to 80% of dietary vitamin K is absorbed in small intestine ~10% of menaquinones synthesized by intestinal bacteria is absorbed in colon  Incorporated into chylomicrons and delivered to liver via lymphatic system  Stored in the liver and incorporated into lipoproteins  Excretion is primarily via bile

60 Functions of Vitamin K: Coagulation

61 Functions of Vitamin K  Calcium-binding potential  Gla proteins  Formation of osteocalcin  Low intake is associated with increased risk for hip fractures

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

63 Vitamin K Needs  AI = 90 μg/d for women, 120 μg/d for men  Daily Value = 80 μg/d  AI achieved by most people

64 Vitamin K Deficiency  Antibiotics Destroy intestinal bacteria Inhibit vitamin K synthesis and absorption Potential for excessive bleeding  Excess vitamins A and E interferes with vitamin K  Newborns are injected with vitamin K (breast milk is a poor source)

65 Content Review  What are the functions of vitamin K?  Is vitamin K truly essential? Why or why not?  What are some good food sources of vitamin K?

66 Nutrient Supplements  Product intended to supplement the diet that contains one of the following: Vitamin Mineral Herb or other botanical Amino acid Dietary substance to supplement the diet  $17 billion/year industry in United States  Little regulation by FDA NUTRITION FOCUS

67 Nutrient Supplements  Structure or function claims  Reasons claimed for use Reduce susceptibility to health problems Prevent heart attacks Prevent cancer Reduce stress Increase energy  Little evidence supports benefit of daily multivitamin and mineral supplement NUTRITION FOCUS

68 Nutrient Supplements  Rationale to recommend supplement use North Americans unwilling to change food habits Risk for birth defects with folate deficiency Older adults at risk for vitamin B 12 deficiency  Rationale for obtaining nutrients from food Phytochemicals Fiber Bulkiness of calcium Low absorption of magnesium, zinc, and copper Megadoses present risk for toxicity Drug-nutrient interactions NUTRITION FOCUS

69 Nutrient Supplements  People most likely to need supplements Women of childbearing age – folic acid Women with excessive menstrual bleeding – iron People with low energy intakes – MVI Strict vegans – iron, calcium, zinc, vitamin B12 Newborns – vitamin K Older infants – fluoride Limited milk intake and restricted sun exposure – vitamin D People with lactose maldigestion or intolerance – calcium Older adults – vitamin B12 People with diets low in plant oils – vitamin E People with fat malabsorption – fat-soluble vitamins Drug-nutrient interactions Picky eaters Smokers and alcohol abusers NUTRITION FOCUS

70 Nutrient Supplements  Choosing a supplement Nationally-recognized brand ~100% Daily Values for nutrients  Take with or just after meals  Exercise caution to prevent overdose  Avoid unnecessary ingredients NUTRITION FOCUS