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Chapter 9: The Fat-Soluble Vitamins

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(1)

Chapter 9:

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

(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

(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

(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

(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

(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

(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 51

 10-15 μg/d (400 - 600 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

(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

(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

(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

(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

(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

(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

(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

(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

(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

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