Perspectives in Nutrition, 8th Edition
Chapter 12 Outline: The Fat-Soluble Vitamins
After studying this chapter, you will be able to:
1. Define the term vitamin and list 3 characteristics of vitamins as a group.
2. Classify the vitamins according to whether they are fat-soluble or water soluble.
3. List 3 important food sources for each fat-soluble vitamin.
4. List the major functions for each fat-soluble vitamin.
5. Describe the deficiency symptoms for each fat-soluble vitamin and state the conditions in which deficiencies are likely to occur.
6. Describe the toxicity symptoms caused by excess consumption of certain fat-soluble vitamins.
7. Evaluate the use of vitamin and mineral supplements with respect to their potential benefits and risks to health.
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12.1 Vitamins: Essential Dietary Components
A. General
1. Vitamins: essential, organic substances needed in small amounts in the diet
a. Fat-soluble vitamins: dissolve in organic solvents (e.g., ether, benzene)
b. Water-soluble vitamins: dissolve in water
2. Supply no energy
3. Aid in growth, development, and maintenance of body tissues
4. Essential in diet because they cannot be synthesized at all or in sufficient amounts by the body to support needs
5. Health declines when vitamins are deficient
6. Resupplying vitamins alleviates deficiency symptoms
7. Megadoses of some vitamins are useful as pharmacological agents
8. Synthetic and natural forms of vitamins generally work equally well in the body
9. Vitamins consumed in foods as part of a varied diet are more beneficial than supplements
B. Absorption of Vitamins
1. Fat-soluble vitamins are absorbed with dietary fat
a. Requirements for absorption
i. Dietary fat
ii. Bile
iii. Pancreatic lipase
iv. Absorptive capacity of intestinal cells
b. Absorption efficiency of fat-soluble vitamins is 40 - 90% when consumed in recommended amounts
2. Water-soluble vitamins are absorbed in the small intestine independent of dietary fat with 90 - 100% efficiency
C. Malabsorption of Vitamins
1. Fat malabsorption (e.g., from GI tract disease or pancreatic disease) may cause poor absorption of fat-soluble vitamins
2. Alcohol abuse and some intestinal diseases may cause malabsorption of some B-vitamins
3. Poor absorption increases vitamin requirements
D. Transport of Vitamins
1. Fat-soluble vitamins are transported through lymphatic system and delivered to bloodstream via chylomicrons and other blood lipoproteins
a. Triglycerides are removed by cells as chylomicrons circulate
b. Remnants, which include fat-soluble vitamins, are taken up by the liver and repackaged as new lipoproteins for transport or stored in adipose tissue or liver
2. Water-soluble vitamins are delivered directly to the bloodstream and distributed throughout the body
E. Storage of Vitamins in the Body
1. Except for vitamin K, fat-soluble vitamins are not readily excreted, but are stored in the liver and/or adipose tissue
2. Except for vitamins B-6 and B-12, water-soluble vitamins are excreted readily and poorly stored
3. Vitamins should be consumed daily, but deficiency symptoms do not develop for several weeks with inadequate consumption
F. Vitamin Toxicity
1. Toxicity from vitamins A and D is most likely
2. Toxicity usually results when intake exceeds 5 - 10 times DRI guidelines
3. Balanced multivitamin and mineral supplements that supply less than 2X the Daily Value are unlikely to cause toxicity
12.2 Vitamin A
A. General
1. Vitamin A (from consumption of beef liver) has been known to prevent night blindness for >3500 years
2. Vitamin A is a family of compounds
a. Preformed retinoids: biologically active form of vitamin A; three forms may be interconverted to some extent
i. Retinol
ii. Retinal
iii. Retinoic acid
b. Provitamin A carotenoids: must be converted to vitamin A
3. Carotenoids: yellow/orange pigments in fruits and vegetables; some are provitamins (converted to vitamin A)
a. Alpha-carotene
b. Beta-carotene
c. Beta-cryptoxanthin
B. Vitamin A in Foods (see Figure 12-3)
1. Sources of retinoids
a. Liver
b. Fish and fish oils
c. Fortified milk
d. Eggs
e. Margarine
2. Sources of carotenoids
a. Yellow/orange fruits and vegetables (e.g., carrots, spinach, winter squash, sweet potatoes, mangoes, cantaloupe, peaches, apricots)
b. Leafy green vegetables
c. Broccoli
3. 70% of vitamin A in typical American diet comes from animal (preformed vitamin A) sources
4. Dietary vitamin A activity is expressed in Retinol Activity Equivalents (RAE)
a. 1 RAE = 1 µg retinol
b. 1 RAE = 12 µg beta-carotene
c. 1 RAE = 24 µg alpha-carotene or beta-cryptoxanthin
5. Outdated units of measurement for vitamin A
a. International units (IU)
b. Retinol equivalents (RE): overestimate contribution of carotenoids to vitamin A needs
i. For preformed vitamin A, 1 RE (3.3 IU) =1 RAE
ii. For provitamin A, assume 1 RE/2 = 1 RAE
C. Vitamin A Needs
1. RDA
a. Adult men: 900 µg
b. Adult women: 700 µg
2. DV: 5000 IU (1000 µg)
3. No DRI available for carotenoids
4. Average intake meets DRI
D. Absorption
1. Preformed vitamin A in animal foods
a. Retinol
b. Retinyl esters (attached to fatty acid); must be cleaved by action of bile and pancreatic lipase to have vitamin A activity
2. Absorption of preformed vitamin A
a. Takes place in the small intestine
b. Up to 90% efficient
3. Absorption of carotenoids
a. Takes place in small intestine
b. Absorption efficiency is lower than that of preformed vitamin A
E. Transport of Vitamin A
1. Transport of retinoids
a. After absorption, retinol is attached to a fatty acid to form a new retinyl ester and packaged into chylomicrons
b. Chylomicrons are absorbed into lymphatic vessels, which empty into the bloodstream
2. Transport of carotenoids
a. Enzymatically split in intestinal cells or liver cells to form retinal and retinoic acid
b. Retinal is converted to retinol and can become a retinyl ester to enter lymphatic circulation
c. Carotenoids can also enter bloodstream directly
3. Retinoids are released from liver into bloodstream bound to retinol-binding protein, which binds to transthyretin (prealbumin)
4. Carotenoids are released from liver into bloodstream as part of VLDL
5. Retinoids bind to specific RBPs in cells
F. Storage of Vitamin A
1. 90% of body’s vitamin A stores are in the liver (enough to last for several months)
2. Small amounts of vitamin A are stored in adipose tissue, kidneys, bone marrow, testicles, and eyes
G. Excretion of Vitamin A
1. Minor amount lost in urine
2. Kidney disease can lead to vitamin A toxicity because of impaired excretion
H. Functions of Vitamin A (Retinoids)
1. Growth and Development
a. Development of eyes, limbs, cardiovascular system, and nervous system of embryo
b. Lack of vitamin A in first trimester leads to birth defects or fetal death
c. Retinoid acid is needed for production, structure, and normal function of epithelial (mucous forming) cells in lungs, trachea, skin, GI tract, etc
2. Cell Differentiation (see Figure 12-4)
a. Retinoids bind to retinoid receptors in cell nucleus that regulate formation of mRNA and subsequent gene expression, which directs cell differentiation (process by which stem cells develop into specialized cells)
i. Retinoic acid receptor (RAR)
ii. Retinoid X receptor (RXR)
b. Especially involved in cell differentiation in the eyes
3. Vision
a. Retinal is needed in the retina to turn visual light into nerve signals to the brain
b. Rods: vision in dim light, black and white images, detection of motion
i. 11-cis-retinal binds to opsin to form rhodopsin
ii. Absorption of light catalyzes bleaching process: change in shape of 11-cis-retinal to all-trans-retinal, separates from opsin
iii. Ion permeability of photoreceptor cells
iv. Initiation of signal to nerve cells that communicate with brain’s visual center
v. With exposure to bright light, rhodopsin is completely activated and cannot respond to more light
vi. Regeneration of 11-cis-retinal from all-trans-retinal and binding with opsin restarts visual cycle
vii. Some retinal is stored and not used for each visual cycle
viii. Depletion of vitamin A pools leads to night blindness, wherein the process of dark adaptation is impaired
ix. Dark adaptation: [rhodopsin] in the eye increases in dark conditions to allow vision in the dark
c. Cones: vision in bright light, color vision
4. Immune Function
a. Increased incidence of infection is an early symptom of vitamin A deficiency
b. May be due to role of vitamin A in maintenance of epithelial cells, which form a barrier against pathogens
c. Vitamin A supplementation decreases severity of infections in vitamin A deficient children
5. Use of Vitamin A Analogs in Dermatology
a. Retin-A (topical) and Accutane (oral)
b. Used to treat acne and psoriasis or lessen damage from sun or UV exposure
c. Toxic effects are especially harmful to fetus; causes birth defects
I. Carotenoid Functions
1. Some can be converted to vitamin A
2. Reduced risk of eye disease
3. Reduced risk of cancer
4. Reduced risk of cardiovascular disease
5. Beta-carotene may act as antioxidant, especially to protect eye tissues; diets high in fruits and vegetables show more success than supplementation
6. Possible role for beta-carotene in prevention of lung cancer: although diets high in fruits and vegetables are associated with reduced risk of lung cancer, supplementation actually increases risk of lung cancer in high-risk individuals
7. Lutein and zeaxanthin may protect against age-related macular degeneration (leads to deterioration of central vision)
8. Lycopene may protect against prostate cancer
9. Beta-carotene and lycopene may reduce risk of CVD, possibly by inhibiting oxidation of LDL and cholesterol synthesis and increasing LDL receptor activity in cells
10. In all cases, diets high in carotenoid-rich fruits and vegetables are recommended rather than carotenoid supplements
J. Vitamin A Deficiency Diseases
1. Low risk for deficiency in North America, but vitamin A deficiency is a major public health problem in developing countries
2. Leading cause of non-accidental blindness worldwide
3. At-risk populations in North America
a. Poverty
b. Older adults
c. Alcoholism or liver disease (limits vitamin A storage)
d. Severe fat malabsorption
e. Premature infants (low stores of vitamin A)
4. Effects on eyes
a. Slowed regeneration of rhodophsin by rods in the retina leads to night blindness
b. Deterioration of mucous-forming cells leads to xerophthalmia: progression of eye disease leading to blindness, including
i. Conjunctival xerosis: dryness
ii. Bitot’s spots: hardened epithelial cells on the eye
iii. Keratomalacia: softening of the cornea
iv. Scarring
c. Follicular hyperkeratosis: keratinized cells replace normal epithelial cells, leading to dry, roughened skin
d. Impaired growth in children
K. Vitamin A Toxicity (hypervitaminosis A)
1. Occurs with chronic intake (usually from supplements) of 5 - 10 times RDA for retinoids
2. UL: 3000 µg of retinoids (no UL for carotenoids)
3. Types of hypervitaminonis A
a. Acute:1 very large dose or several large doses over a few days (100 x RDA)
i. GI tract upset
ii. Headache
iii. Blurred vision
iv. Poor muscle coordination
v. Fatality for extremely large doses (e.g., 500 mg for children or 10 g for adults)
b. Chronic: repeated intakes of at least 10 x RDA; most symptoms disappear after supplementation ceases, but permanent damage may occur to the liver, bones, and eyes
i. Joint pain
ii. Loss of appetite
iii. Skin disorders
iv. Headache
v. Reduced bone minerals
vi. Liver damage
vii. Double vision
viii. Hemorrhage
ix. Coma
c. Teratogenic: toxic doses during pregnancy, usually from vitamin A analogs used to treat skin conditions, but also possible from food sources (e.g., liver, fortified breakfast cereals); pregnant women should limit intake of vitamin A to 100% DV
i. Birth defects, especially of head and neck, where neural crest cells form in first trimester
ii. Spontaneous abortion
4. Consuming excessive carotenoids does not lead to toxicity; may turn skin to yellow/orange color (hypercarotenemia)
12.3 Vitamin D
A. General
1. In 1918, cod liver oil (source of vitamin D) was discovered as cure for rickets
2. In the presence of sunlight, skin cells can synthesize sufficient vitamin D, which makes vitamin D a “conditional vitamin” or prohormone (precursor to active hormone)
a. Skin produces vitamin D3 (cholecalciferol) from a derivative of cholesterol
b. Liver and kidneys add hydroxyl group to cholecalciferol to yield active vitamin D (1,25 dihydroxy D3, or calcitriol)
B. Vitamin D2 (Ergocalciferol) in Foods
1. High sources
a. Fatty fish (e.g., sardines, mackerel, salmon) and fish oils (e.g., cod liver oil)
b. Fortified milk [10 µg (400 IU)/quart]
c. Fortified breakfast cereals
d. Supplements
2. Low sources
a. Eggs
b. Butter
c. Liver
d. Some brands of margarine
3. Ergocalciferol (D3) has vitamin D activity in humans, but not as much as cholecalciferol (D2)
C. Vitamin D3 Formation in the Skin
1. Occurs in the liver and kidneys
2. This process provides 80 - 100% of vitamin D requirements for some people
3. Required sun exposure varies by
a. Time of day
b. Geographic location
c. Season
d. Age: skin production decreases by 70% by age 70
e. Skin color: melanin blocks UV light and prevents adequate D3 synthesis
f. Use of sunscreen > SPF 8
4. Expose hands, face, and arms to UV light at least 2 - 3 times per week for 10 - 15 minutes (longer for dark-skinned individuals)
5. Prolonged skin exposure is unlikely to cause toxicity because excess previtamin D3 in the skin is rapidly degraded
D. Vitamin D Needs
1. AI
a. Adult men and women up to age 51: 5 µg (200 IU)
b. Adults ages 51 - 70: 10 µg (400 IU)
c. Adults ages 71+: 15 µg (600 IU); may need 20 - 25 µg from fortified foods and supplements to decrease bone loss and other chronic diseases
2. DV: 10 µg
3. Full-term infants are born with a supply of vitamin D, but American Academy of Pediatrics recommends 5 µg (200 IU)/d supplements until weaned to good food sources of vitamin D
E. Absorption of Vitamin D
1. 80% of vitamin D2 is incorporated with dietary fats into micelles in the small intestine