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The Fat-Soluble Vitamins • • • • Vitamin A Vitamin D Vitamin E Vitamin K Dr. Latifah Al-Oboudi 2012 Vitamins: Essential Dietary Components • Vitamins are essential, organic compounds needed for important metabolic reactions in the body. • They are not a source of energy. Instead, they promote many energy-yielding and other reactions in the body, thereby aiding in the growth, development, and maintenance of various body tissues. Dr. Latifah Al-Oboudi 2012 •Vitamins cannot be synthesized in the body at all or are synthesized in insufficient amounts. •Vitamins A, D, E, and K are fat soluble, whereas the Bvitamins and vitamin C are water soluble. Dr. Latifah Al-Oboudi 2012 Absorption of vitamins • Fat-soluble vitamins are absorbed along with dietary fat. Thus adequate absorption depends on the efficient use of bile and pancreatic lipase in the small intestine to digest dietary fat and the adequate absorptive capacity of the intestinal mucosa. • Under optimal condition, about 40 to 90% of the fatsoluble vitamins are absorbed when they are consumed in recommended amounts. Dr. Latifah Al-Oboudi 2012 Malabsorption of vitamins • Fat malabsorption (resulting from GI tract and pancreatic disease) may cause poor absorption of fat-soluble vitamins. • In disease states that limit fat digestion, fatsoluble vitamin absorption may be compromised, thereby increasing the risk of deficiency in these individuals. Dr. Latifah Al-Oboudi 2012 Transport of vitamins • They travel by way of the lymphatic system into general circulation, carried by chylomicrons. Dr. Latifah Al-Oboudi 2012 Vitamin Toxicity • Fat –soluble vitamins are excreted less readily from the body than water-soluble vitamins and thus pose a potential threat for toxicity, especially of vitamins A and D. • Toxicities of these fat- soluble vitamins generally occur with high doses of supplements, rather than from foods Dr. Latifah Al-Oboudi 2012 Vitamin A • Vitamin A contributes to the maintenance of vision, the normal development of cells (especially mucous-forming cells), and immune function. Dr. Latifah Al-Oboudi 2012 Vitamin A • Vitamin A refers to the preformed retinoids and provitamin A carotenoids that can be converted to vitamin A activity. • Retinoids is a collective term for the biologically active forms of vitamin A because, unlike carotenoids, they do not need to be converted to become biologically active. Dr. Latifah Al-Oboudi 2012 Vitamin A • Retinoids exist in 3 forms: retinal(an aldehyde), retinol(an alcohol), and retinoic acid. • Carotenoids are yellow-orange pigmented materials in vegetables and fruits, some of which are provitamins--that is, they can be converted into vitamin A. • A plant derivative, known as beta-carotene, along with 2 other carotenoids(alpha-carotene and beta- cryptoxanthin), yields vitamin A after metabolism by the small intestine or liver. Dr. Latifah Al-Oboudi 2012 Interconversions of beta-carotene and various retinoids. Notice that the synthesis of retinoic acid is a “dead end” in metabolic terms. Dr. Latifah Al-Oboudi 2012 Dr. Latifah Al-Oboudi 2012 Vitamin A in Foods • Retinoids (preformed vitamin A) are found in foods of animal origin, such as liver, fish, fish oils, fortified milk and eggs. • A carotenoids are found mainly in dark green and yellow-orange vegetables and fruits, such as carrots, spinach and other greens, winter squash, sweet potatoes, broccoli, mangoes, cantaloupe, peaches, and apricots. Dr. Latifah Al-Oboudi 2012 Food sources of vitamin A Dr. Latifah Al-Oboudi 2012 • At one time the amounts of vitamin A were expressed in International Units (IUs). Today, there are more sensitive means for measuring nutrients. Consequently, milligram (1/1000 of a gram) and microgram (1/1,000,000 of a gram) measurements have generally replaced IUs as the units of measure. However, some food and vitamin supplement labels may still display the older IU value. • Dietary vitamin A activity is currently expressed in Retinol Activity Equivalents(RAE) Dr. Latifah Al-Oboudi 2012 Dr. Latifah Al-Oboudi 2012 Vitamin A Needs • The RDA for vitamin A is 900 µg Retinol Activity Equivalents(RAE) per day for adult men and 700 µg RAE per day for adult women. Dr. Latifah Al-Oboudi 2012 Absorption, Transport, Storage, and Excretion of Vitamin A • Up to 90% of retinol is absorbed into the cells of the small intestine. • After absorption, a fatty acid is attached to retinol to form a new retinyl ester. These retinyl esters are packaged into chylomicrons before entering the lymphatic circulation. Dr. Latifah Al-Oboudi 2012 Absorption, Transport, Storage, and Excretion of Vitamin A • The provitamin A carotenoids can be enzymatically split within the intestinal cells or liver cells to form retinal or, to lesser extent, retinoic acid. • The carotenoid absorption is much lower than that of retinol. • After being absorbed in the small intestine , carotenoids can be cleaved to yield retinal, which is then converted to retinol. Dr. Latifah Al-Oboudi 2012 Absorption, Transport, Storage, and Excretion of Vitamin A • The chylomicrons deliver vitamin A to tissue for storage or cellular use. • Storage: Over 90% of the body’s vitamin A stores are found in the liver, with small amounts in adipose tissue, kidneys, bone marrow, testicles, and eyes. Normally, the liver stores enough vitamin A to last for several months to protect against vitamin A deficiency. Dr. Latifah Al-Oboudi 2012 Excretion of Vitamin A • Although vitamin A is not readily excreted by the body, some is lost in the urine. • Kidney disease increases the risk of vitamin A toxicity because this urinary route of excretion is compromised. Dr. Latifah Al-Oboudi 2012 Functions of Vitamin A ( Retinoids) • • • • Growth and Development. Cell Differentiation. Vision. Immune Function. Dr. Latifah Al-Oboudi 2012 Vitamin A deficiency Diseases • Conjunctiva: • Xerophthalmia: Dr. Latifah Al-Oboudi 2012 Vitamin A Toxicity • Preformed vitamin A can be quite toxic when taken at doses 2 to 4 times or more the RDA. • Use of vitamin A supplements is especially dangerous during pregnancy because it can lead to fetal malformations. Dr. Latifah Al-Oboudi 2012 Vitamin A Toxicity • Consuming the right amount of vitamin A is critical to overall health. Avery low (deficient) or very high (toxic)vitamin A intake (as retinoids) can produce harmful symptoms and can even lead to death. Dr. Latifah Al-Oboudi 2012 Golden rice was genetically engineered to synthesize beta-carotene. This rice was developed for use as a fortified food in areas of the world that have limited access to vitamin A-rich foods. Dr. Latifah Al-Oboudi 2012 Dr. Latifah Al-Oboudi 2012 Vitamin D • In presence of sunlight, skin cell synthesize a sufficient supply of vitamin D from a derivative of cholesterol. • Dietary source is not required if synthesis is adequate to meet needs, the vitamin is more correctly classified as a “conditional” vitamin or prohormone (a precursor of an active hormone). Dr. Latifah Al-Oboudi 2012 Vitamin D • In the absence of UV light exposure, an adequate dietary intake of vitamin D is essential to prevent the deficiency diseases rickets and osteomalacia and to provide for cellular needs. • After exposure to the sun, humans produce vitamin D₃ (cholecalciferol) from a derivative of cholesterol. • The liver and kidneys each add a hydroxyl group(-OH) to this to yield the active form of vitamin D ( 1,25 dihydroxy D₃, or calcitriol). Dr. Latifah Al-Oboudi 2012 Vitamin D₂ in foods • • • • • • The best food sources of vitamin D are: Fatty fish (e.g. sardines, mackerel, and salmon). Cod liver oil. Fortified milk. Some fortified breakfast cereals. Although eggs, butter, liver, and a few brands of margarine contain some vitamin D, large servings must be eaten to obtain an appreciable amount of the vitamin. Thus, these foods are not considered a significant source. Dr. Latifah Al-Oboudi 2012 Cod liver oil was a common supplements for children in the US until 1933, when milk was first fortified with vitamin D Dr. Latifah Al-Oboudi 2012 Vitamin D₂ in foods • Most fortified foods and supplements containing vitamin D are in the form of ergocalciferol, or vitamin D₂, the same form found naturally in foods. • Ergocalciferol has vitamin D activity in humans, but in lesser amounts than provided by cholecalciferol (vitamin D₃). Dr. Latifah Al-Oboudi 2012 Food sources of vitamin D Dr. Latifah Al-Oboudi 2012 Dr. Latifah Al-Oboudi 2012 Vitamin D₃ Formation in the Skin • The synthesis of vitamin D₃ begins with a compound called 7-dehydrocholesterol, a precursor of cholesterol synthesis located in the skin. • 1 ring on the molecule undergoes a chemical transformation, forming the more stable vitamin D₃ (cholecalciferol). • This change allows vitamin D₃ to enter the bloodstream for transport to the liver and kidneys, where it undergoes hydroxylation (the addition of -OH) and subsequent conversion to its bioactive form 1,25 dihydroxy D₃ (calcitriol). Dr. Latifah Al-Oboudi 2012 Vitamin D₃ Formation in the Skin • For many individuals, sun exposure provides 80 to 100% of the vitamin D₃ required by the body. • The amount of sun exposure needed , however, depend on the time of day, the geographic location, the season of the year, one’s age, one’s skin color, and the use of sunscreen. Dr. Latifah Al-Oboudi 2012 • The production of vitamin D₃ in the skin decreases by about 70% when one reaches the age of 70. older people are advised to get small amounts of sun exposure, or to take vitamin D supplements to prevent deficiency. • The large amount of melanin (skin pigment) in dark-skinned individuals may block UV light and prevent adequate vitamin D₃ synthesis. Dr. Latifah Al-Oboudi 2012 • Scientists recommend that people expose their hands, face, and arms to UV light at least 2 or 3 times a week for 10 to 15 minutes. • Individuals with dark skin may need sun exposure of 3o minutes or more (or vitamin D supplementation). • People who do not receive enough UV light exposure to synthesize adequate amounts of vitamin D₃ should make certain that they have adequate sources of vitamin D in their diets. Dr. Latifah Al-Oboudi 2012 Vitamin D Needs • The adequate intake for vitamin D is 5µg/day (200 IU/day) for people under age 51, 10µg/day (400 IU/ day) for people between 51 and 70, and 15µg/day (600 IU/ day) for older adults. • Older adults may need 20 to 25µg/day (800 to 1000 IU/ day) from a combination of vitamin D-fortified foods and a supplement to decrease the risk of bone loss and other chronic diseases. • The daily value used on food and supplements labels is 10 µg. • Breastfed infants recommended to be given a vitamin D supplement of 5 µg/day (200 IU) until they are weaned to infant foods fortified with, or rich in, vitamin D . Dr. Latifah Al-Oboudi 2012 Absorption, Transport, Storage, and Excretion of Vitamin D • About 80% of vitamin D₂ is incorporated (along with other dietary fats) into micelles in the small intestine, absorbed, and transported to the liver by chylomicrons through the lymphatic system. Dr. Latifah Al-Oboudi 2012 Whether synthesized in the skin or obtained from dietary sources, vitamin D ultimately function as a hormone: 1,25(OH)₂ vitamin D₃ (calcitriol) Dr. Latifah Al-Oboudi 2012 Function of Vitamin D • Vitamin D has hormone like functions, which help regulate the body’s concentration of calcium and phosphorus Dr. Latifah Al-Oboudi 2012 Figure 12-13 The active vitamin D Hormone– 1,25 (OH)₂ vitamin D₃ --and parathyroid hormone interact to control blood calcium concentration. Low blood calcium is a trigger for the following actions, all of which raise blood calcium levels. 1 Parathyroid hormone (PTH) and 1,25(OH)₂ vitamin D₃ mobilize calcium from the bone. 2 PTH also a. Reduces calcium excretion by the kidneys. b. stimulates kindly synthesis of 1,25(OH)₂ vitamin D₃. 3 1,25(OH)₂ vitamin D₃ stimulates intestinal calcium absorption. Conversely, when calcium levels in the blood become too high, the hormone calcitonin responds by promoting calcium disposition in the bone (see chapter 14)/. Dr. Latifah Al-Oboudi 2012 Function of Vitamin D • Vitamin D promotes increased intestinal absorption of calcium and phosphorus from foods to maintain blood levels of these minerals. This makes calcium and phosphorus available for body cells and for incorporation into bones when there is more than needed for basic functions. Dr. Latifah Al-Oboudi 2012 Function of Vitamin D • When blood levels of calcium and phosphorus start to fall, vitamin D (with PTH from the parathyroid gland) can release calcium and phosphorus from bone into the blood to restore blood levels of these minerals. • This action can eventually weaken the bones if it continues for a prolonged period of time, it helps provide the calcium and phosphorus needed for many basic life functions. If the bones did not supply calcium and phosphorus for these functions, a person could quickly have serious, even fatal, health consequences. Thus, vitamin D preserves these important functions even if dietary intakes of these minerals are inadequate. Dr. Latifah Al-Oboudi 2012 Function of Vitamin D • Vitamin D has important functions beyond its role in maintaining calcium and phosphorus homeostasis and bone health. • Vitamin D also is involved in immune function and cellular metabolism. Dr. Latifah Al-Oboudi 2012 Function of Vitamin D • Vitamin D also may be involved in cell cycle regulation. • Additionally, vitamin D may decrease the risk of certain types of infections and autoimmune diseases, such as multiple sclerosis, through its action in the immune system and offer protection against diabetes, hypertension, and certain cancers. Dr. Latifah Al-Oboudi 2012 Vitamin D Deficiency Diseases • Vitamin D deficiency results in harmful changes in bone, a condition known as rickets in children and osteomalacia in adults. Dr. Latifah Al-Oboudi 2012 The bone deformities and bowed legs of rickets, a vitamin D deficiency disease in children. Dr. Latifah Al-Oboudi 2012 Vitamin D Toxicity • Vitamin D toxicity can occur from excessive vitamin D supplementation, causing the deposition of calcium in the kidneys, heart, and lungs. Dr. Latifah Al-Oboudi 2012 Vitamin E • The importance of vitamin E was first noted in 1922 in rats. • Vitamin E was not fully recognized as an essential nutrient in humans until the mid-1960s. • The first RDA for vitamin E was established in 1968. • Vitamin E is a family of 8 naturally occurring compounds- 4 tocopherols ( alpha, beta, gamma, delta) and 4 tocotrienols (alpha, beta, gamma, delta)—with widely varying degrees of biological activity. Dr. Latifah Al-Oboudi 2012 Vitamin E • The most active form of the vitamin E is alphatocopherol. • This is the form found in some foods and in varying amounts in vitamin supplements. • Gamma-tocopherol is a potentially beneficial form of vitamin E found in many vegetable oils. It does not have as much biological activity as alpha-tocopherol. Dr. Latifah Al-Oboudi 2012 Vitamin E in foods • Vitamin E is plentiful in plant oils(e.g., cottonseed, canola, safflower, and sunflower oils), wheat germ, asparagus, almonds, peanuts, and sunflower seeds. • Products made from the plant oils—margarine, shortenings, and salad dressings– also are good sources. Dr. Latifah Al-Oboudi 2012 Food sources of vitamin E Dr. Latifah Al-Oboudi 2012 Vitamin E in foods • Animal fats and dairy products contain little vitamin E. • The vitamin E content of a food depends on harvesting, processing, storage, and cooking because vitamin E is highly susceptible to destruction by oxygen, metals, light, and deep-fat frying. Thus, foods that are highly processed and/or deep-fried are usually poor sources of vitamin E. Dr. Latifah Al-Oboudi 2012 Vitamin E needs • The RDA for vitamin E is 15 mg/day of alphatocopherol for both men and women. • The 15-mg allotment is equivalent to 22 IU of a natural source and 33 IU of a synthetic source of vitamin E . • Adults consume, on average, only two-thirds of the RDA for vitamin E each day. Dr. Latifah Al-Oboudi 2012 Absorption, Transport, Storage, and Excretion of Vitamin E • Absorption can vary from 20 to 70% of dietary intake. Vitamin E must be incorporated into micelles in the small intestine, a process dependent on bile and pancreatic enzymes. • Once taken up by the intestinal cells, vitamin E is incorporated into chylomicrons for transport by the lymph and eventually the blood. Dr. Latifah Al-Oboudi 2012 Absorption, Transport, Storage, and Excretion of Vitamin E • As chylomicrons are broken down, most of the vitamin E is carried to the liver as chylomicron remnants. A small amount is carried directly to other tissues. • The liver repackages the vitamin E from the chylomicron remnants with other lipoproteins (VLDL, LDL, and HDL) for delivery to body tissues. • Vitamin E carried by these lipoproteins. • Vitamin E does not accumulate in the liver; instead, most of the vitamin E in the body is localized in adipose tissue. Dr. Latifah Al-Oboudi 2012 Excretion of Vitamin E • Vitamin E can be excreted via the bile, urine, and skin. • However, because vitamin E absorption is often low, most vitamin E is excreted via the small amount of bile that exits the body in the feces. Dr. Latifah Al-Oboudi 2012 Function of Vitamin E • Vitamin E is an antioxidant that stops chain reactions caused by free radicals that can potentially damage cells. Vitamin E acts primarily in lipid-rich areas of the body, where free radicals can initiate a chain of reactions known as peroxidation. Dr. Latifah Al-Oboudi 2012 Function of Vitamin E • Lipid peroxidation reactions break apart fatty acids and create free radicals called lipid peroxyl radicals (also called reactive oxygen species because they contain oxygen radicals). • The chain of reactions continues to break apart fatty acids until 2 free radicals pair and stabilize each other. However, many lipid peroxyl radicals may be produced through these reactions before stabilization occurs. Dr. Latifah Al-Oboudi 2012 Function of Vitamin E • Vitamin E is one of the most effective mechanisms for stopping lipid peroxidation chain reaction in the body. By donating hydrogen to lipid radicals, vitamin E stops the chain of oxidation reaction, which protects the lipids in the body. For example, recall that cell membranes are composed of a phospholipid bilayer Dr. Latifah Al-Oboudi 2012 Fat-soluble vitamin E can donate an electron to stop free radical chain reaction. If not interrupted, these reactions cause extensive damage to cell membranes Dr. Latifah Al-Oboudi 2012 Function of Vitamin E • To vitamin E, the body has various other antioxidant compounds, such as glutathione peroxidase, catalase, and superoxide dismutase, to protect against oxidative damage. Dr. Latifah Al-Oboudi 2012 The body does not rely solely on vitamin E for antioxidant protection. Such protection is a team effort, utilizing a number of nutrients, metabolites, and enzyme systems. Dr. Latifah Al-Oboudi 2012 Vitamin E Deficiency • Overt vitamin E deficiency is rare in humans. • Vitamin E deficiency is characterized by the premature breakdown of red blood cells(hemolysis) and the development of hemolytic anemia. • Vitamin E deficiency also can impair immune function and cause neurological changes in the spinal cord and peripheral nervous system. Dr. Latifah Al-Oboudi 2012 Vitamin E Toxicity • Toxicity from megadose therapy inhibits vitamin K activity and, in turn, increases the risk of hemorrhage. Dr. Latifah Al-Oboudi 2012 Vitamin K • The discovery of vitamin K centered on its role in blood clotting. Dr. Latifah Al-Oboudi 2012 Vitamin K • Vitamin K contributes to the body’s bloodclotting ability by facilitating the conversion of precursor proteins, such as prothrombin, to active clotting factors that promote blood coagulation. Dr. Latifah Al-Oboudi 2012 Vitamin K Sources • About 10% of the vitamin K absorbed each day comes from bacterial synthesis in the colon. • The remainder comes from dietary sources, green leafy vegetables (e.g., Kale, turnip greens, parsley, salad greens, cabbage, and spinach), broccoli, peas, and green beans are the best sources. • Vegetable oils, such as soy and canola, also are good sources. • Vitamin K can be destroyed by exposure to light. Dr. Latifah Al-Oboudi 2012 Food sources of vitamin K Dr. Latifah Al-Oboudi 2012 Vitamin K Needs • For women, the adequate intake for vitamin K is 90µg/day; for men, it is 120µg/day. • The daily value for vitamin K is 80µg/day. Dr. Latifah Al-Oboudi 2012 Absorption, Transport, Storage, and Excretion of Vitamin K • Approximately 80% of dietary vitamin K as phylloquinone and menaquinone is taken up by the small intestine and incorporated into chylomicrons. This process requires bile and pancreatic enzymes. • The menquinones synthesized by bacteria in the colon also are absorbed, but provide only 10% of the vitamin K we need. • Vitamin K can be incorporated into the lipoproteins VLDL and LDL for transport throughout the body or for storage in the liver. Dr. Latifah Al-Oboudi 2012 Excretion of Vitamin K • Most vitamin K excretion occurs via the bile that passes out of the body in the feces, with a small amount of excretion via the urine. Dr. Latifah Al-Oboudi 2012 Function of Vitamin K • Vitamin K is needed for the synthesis of bloodclotting factors by the liver and the conversion of preprothrombin to the active blood-clotting factor called prothrombin. Dr. Latifah Al-Oboudi 2012 Forming a blood clot requires the participation of vitamin K in both the intrinsic and extrinsic blood-clotting pathways. Vitamin K specifically imparts calciumbinding capacity to the proteins in these pathways, as in the conversion of preprothrombin to prothrombin, an active clotting factor. Dr. Latifah Al-Oboudi 2012 Function of Vitamin K • Vitamin K also may play a role in bone metabolism. • Vitamin K also may help protect the body from inflammation, thereby providing protection against cardiovascular disease and osteoporosis. Dr. Latifah Al-Oboudi 2012 Vitamin K deficiency • A deficiency of vitamin K is rare, but it can occur with prolonged use of antibiotics that disrupt vitamin K synthesis or with impaired fat absorption. • Vitamin K deficiency also can occur in newborns. Newborn infants are given vitamin K injections within 6 hours of delivery to prevent this possible vitamin K deficiency. Dr. Latifah Al-Oboudi 2012 Vitamin K Toxicity • To date, no upper level has been set for vitamin K. • Although vitamin K can be stored in the liver and bone, it is more readily excreted than other fat-soluble vitamins. • Can cause hemolytic anemia. Dr. Latifah Al-Oboudi 2012 Dr. Latifah Al-Oboudi 2012 Dietary supplements: Healthful or Harmful? Dr. Latifah Al-Oboudi 2012 Which food provide very little vitamin A? a. Mango b. Spinach c. Banana d. Liver Dr. Latifah Al-Oboudi 2012 Vitamin D deficiency in children results in a condition called-------a. osteomalacia b. Berberi c. Rickets d. xerophthalmia Dr. Latifah Al-Oboudi 2012 Which vitamin aids in blood clotting? a. Vitamin A b. Vitamin D c. Vitamin E d. Vitamin K Dr. Latifah Al-Oboudi 2012