Introduction of Vitamins

1. Introduction of Vitamins

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3. Definition • Vitamins are: • Natural micronutrient organic substances. • Having specific biochemical functions in the human body (essential for health maintenance). • Obtained from animals, plants, and microorganisms. • Required in very tiny (mcgs) and balanced amounts. • Not made in the body (or not in sufficient quantity)

4. Vitamins def. cont. • Exceptions are: Provitamins • β-carotenoidscan replace Vit. A. • Tryptophan containing proteins can replace Vit.B3 (niacin). • Exposure to sunlight can replace Vitamin D. • Bacteria in the human colon synthesize Vit. K2 menaquinones, which can be absorbed. • F. Their deficiency resulted in a specific diseases.

5. Tips to Remember • They are necessary dietary factors, not produced by the body (except vitamin D3). • They function as co-factor (regulator) of metabolic reactions in the body. • Daily requirement of most vitamins is around 1 mg.

6. Classification of Vitamins • Vitamins are classified by their biological and chemicalactivity. Till now 13 vitamins are universally recognized : • 1- Fat soluble vitamins: • Vit. A (Retinol, Retinal, Retinoic acid) • Vit. D (Vit. D3: Cholecalciferol, Vit. D2: • Ergocalciferol) • C. Vit. E (α-Tocopherol) • D. Vit. K (Vit. K1: Phylloquinones,Vit. K2: Menaquinones)

7. 2-Water soluble vitamins: (A) Vit. B group B1 (Thiamin) B2 (Riboflavin) B3 (Niacin) B5 (Pantothenic acid) B6 (Pyridoxine) B9 (Folic acid) B12 (Cyanocobalamin) • (B) Vit. C :(l-Ascorbic acid) • (C) Vit. H:(Biotin)

8. Role of Vitamins in Metabolism • Vitamins have catalytic functions (co-factors) in the metabolic reactions and do not act as building substances (that is why the daily requirement is very small). • Since each vitamin has very specific function in metabolism, therefore, its deficiency will adversely affect one or more biochemical reactions in certain organs and very characteristic deficiency symptoms will appeared.

9. Cases of Vitamin Deficiency and Toxicity • (1). Avitaminosis: It is any disease caused by chronic or long- term vitamin deficiency or caused by a defect in metabolic conversion, such as tryptophan to niacin. • It leads to well defined symptoms e.g. • Xerophthalmia due to Vitamin A deficiency. • Rickets due to Vitamin D deficiency. • Pellagra due to Vitamin B3 deficiency. • Beriberi due to Vitamin B1 deficiency. • Scurvy due to Vitamin C deficiency. • (2). Hypovitaminosis: Resulted from inadequate supply of one or more vitamins. It appears in the form of well defined symptoms as skin changes, reduced vitality and low resistance to infections.

10. (3). Latent hypovitaminosis: A case of unrecognizable deficiency symptoms but immediately appeared under sudden stress or exposure to different environment. • (4). Hypovitaminosis due to Anti- vitamins: • Thiaminase in raw fish destroy Vit. B1. • Avidin in raw egg forming complex with biotin (vitamin) (biotin – avidin) prevents absorption of biotin. • Liatin in linseed oil is antagonist to Vit. B6.

11. 5. Hypervitamninosis: A case which develops only upon prolonged use of excessive amount of vitamins. EXAMPLES: Hypervitaminosis D Usually this is caused by excessive ingestion or over prescription of prescribed medications such as calcium with vit. D. Symptoms include: Polyuria Vomiting Constipation Hypertension Seizures - can be fatal Hypervitaminosis A This occurs after large over dosage of the vitamin. Symptoms include: Headache Abdominal pain Nausea or vomiting Lethargy Visual changes Impaired consciousness

12. Medicinal applications of Vitamins • Elimination of hypovitaminosis. • Treatment of some diseases. • Prophylaxis against some diseases.

13. 1- Fat soluble vitamins

14. 2- Water soluble vitamins

15. 2- Water soluble vitamins

16. 1. Vitaminisation: Addition of vitamins to foods which do not necessarily contain them naturally (Addition of vitamins A and D to margarine). 2. Revitaminisation: Restoration of the original vitamin contents of food that is lost during processing. (Flour loss about 70% of its vitamin B content; Skimmed milk must be revitaminized with vitamins A and D as they removed on skimming with fat). 3. Standardization:Compensation of seasonal variations of vitamins in food (e.g. Milk must standardized due to seasonal variation of vitamin A). Cases of addition of Vitamins to food

17. 4. Enrichment:Addition of vitamins over the initial natural level e.g. in Milk and flour. 5. Stabilization of food:Some food products show change in color and taste due to oxidation by light and air. Vitamins C and E ( water and fat soluble antioxidants) are used to protect food from oxidation and thus saving its nutritional value. 6. Curing agents:Na ascorbate is used to reduce the amount of nitrite and nitrate ( food stabilizer). 7. Coloring of food products: The carotenoids (natural fat soluble pigments and pro-vitamin A) and synthetic carotenoids as: β-carotene, β-apo-8‘- carotenal, and anthaxanthin are suitable for the coloring of margarine and cheese.

18. Formulation of Vitamins Formulation of vitamins must solve the following problems: 1. Organoleptic characters 2. Providing accurate known quantities. 3. Stability. (a) by addition of stabilizer (as antioxidants) (b) synthesis of stable derivatives 4. Solubility. transformation of water-soluble vitamins into fat soluble derivatives or vice versa. 5. Administration route.

19. Vitamin- A Extremely sensitive to oxidation by oxygen or light in presence of metal, heat or moisture. A. Stabilization for oily form of vit. A was achieved by: • Ester formation as acetate or palmitate . • Dissolving in vegetable oils. • Addition of antioxidants. • Using complexing agents. B. Stabilization for water soluble derivatives : Vitamin A dry powder: • Deposit in gelatin as a carrier substance. • Use of emulsion form.

20. Vitamin B1 (Thiamine) • Inactivated at neutral or alkaline pH • Unstable in light and moisture • Oxidizable. Stable if protected from light and moisture. Optimum stability at pH 3 - 4.5. In the presence of vitamin B2 it is easily oxidized in aqueous solution to thiochrome. Thiamine.HNO3 is more stable than thiamine HCl. Protected dry preparation from humidity.

21. Vitamin B2 (Riboflavin) • Unstable in light, alkaline medium, and with reducing agents – sparingly soluble in water – unpleasant taste. • Use solubilizers e.g. nicotinamide or salicylic acid or use Sodium salt of riboflavin-5'-phosphate more water soluble. • For oral use, formulate it in coated form. • 3. In aqueous solution it acts as oxidizing agent for vitamins B1, C and folic acid.

22. Vitamin B5 (Pantothenic acid) • Very sensitive • Its Ca and Na salts are more stable in absence of moisture. • The alcohol form (Pantothenol; panthenol; Dpantothenyl alcohol) is used in aqueous preparations. Vitamin B12 (Cyanocobolamine) Stable in acidic medium but unstable at high temperature and in presence of vitamin B1, B3, vitamin C, and some heavy metals.

23. Fat Soluble Vitamins (Vitamin A and Carotenoids)

24. Vitamin A exists in animal foods in the form of retinol esterified with fatty acids (usually as retinyl palmitate). In the body retinol can be oxidized to retinal or retinoic acid which have 2 specific functions: Vitamin A and Carotenoids • Retinal plays a central role in the function of retina. • Retinoic acid helps regulate gene expression and cell development.

25. The three compounds retinol,retinal and retinoic acidare collectively referred as vitamin A. Vitamin A is carried in the blood through a retinol-binding protein (RBP). RBP is synthesize in the liver. • Carotenoids(provitamin A) exist in plant foods. • The most common type is β-carotene which can be absorbed as such or after splitting by intestinal cells into vitamin A . • A large carrot contains 15 mg of β-carotene which can supply enough vitamin A for daily requirement.

26. Conversion of Carotenoids to Retinoids • Enzymatic conversion of carotenoids occurs in liver or intestinal cells, forming two molecules of retinal and finally retinol and retinoic acids. • Provitamin A carotenoids • Beta-carotene • Alpha carotene • Beta-cryptoxanthin

27. Structure of different forms of Vitamin A 1 11 11 13 7 9 15 2 6 8 14 10 12 3 5 4 All-trans-Retinol All-trans-Retinal All-trans-Retinoic acid 11-cis-Retinal

28. Absorption of Vitamin A • Retinoids • Retinyl esters broken down to free retinol in small intestine with the help of bile and digestive enzymes. • Once absorbed, retinyl esters reformed in intestinal cells. • 90% of retinoids can be absorbed by this mode of absorption. • Carotenoids • Absorbed intact but the absorption rate is much lower. • Intestinal cells can convert carotenoids in to retinoids.

29. Source and Concentration of Vit. A and β-Carotene Foods rich in vitamin A (retinol ) Serving size μg Beef liver 100g 9100 Cod liver oil (very rich source) 10g 2550 Egg 1 whole 110 Others: kidney, dairy products, butter, fortified margarine. Foods rich in β- and other carotenoids Serving size μg Vit. A Carrot 1, large 810 Sweet potato 1, large 920 Spinach and broccoli 100mg 460 Others: red palm oil apricots, peaches, melon, pumpkin.

30. Do you know? Natural carotenoid supplements are preferable micronutrients (Why?) Answer: 1.They contain, along with β-carotene (the precursor of Vit.A), a mixture of other important carotenoids, including lutein and lycopene, which has additional health benefits e.g: Lycopene (red pigment of tomato) is a potent antioxidant and decrease the risk of prostate cancer and cataract. lutein/zeaxanthin (yellow stereoisomeric pigments in leafy vegetables) which give the yellow colour to the macula lutea in the retina. 2. Less toxic than Vit. A. lutein Lycopene

31. Functions of Vitamin A 1. Vision: Vit. A plays a central role in the transformation of light energy into nerve impulses which perceived by brain as vision. Deficiency:Night blindness

32. Role of Vitamin A in Vision • Retinal turns visual light into nerve signals in retina of eye. • Retinoic acid required for structural components (Cones and Rods) 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

33. Mechanism of Action of Retinal in Night Vision

34. Mechanism of Action of Retinal in Night Vision • Rhodopsin, is a biological pigment in photoreceptor cells of the retina that is responsible for the first events in the perception of light. It is extremely sensitive to light, enabling vision in low-light conditions. • Rhodopsin consists of the protein moiety opsin and a reversibly covalently bound cofactor,  11-cis retinal. • The process of night vision occurs via G-protein coupled receptors called opsins which contain the chromophore (A chromophore absorbs and transmits light energy)11-cis retinal.  • When struck by photon, 11-cis retinal undergoes photoisomerization to all-trans retinal which changes the conformation of the opsin GPCR leading to formation of signal cascade massages and sent to brain. • Cessation of dark current takes place.

35. 2. Skin and mucus membrane health : Vit. A promotes proper growth of skin epithelial cells and mucous membranes of the respiratory, gastrointestinal, and genitourinary tracts. Deficiency: Xerosis (mucus-secreting cells are replaced by keratin producing cells) dry skin and dry eye (xerophthalmia).

36. Xerophthalmia Dry Skin Stages of xerophthalmia: (Early signs of xerophthalmia include dry conjunctiva and night blindness). The first occurrence of Conjunctival xerosis (glistening white plaques formed of thickened epithelium, usually triangular) Corneal xerosis (haziness or a granular pebbly dryness of the cornea) Corneal ulceration (keratomalacia) dryness of conjunctiva and later of cornea. CEWG, 2006

37. 3. Immune system. Vit.A increases resistance to infection by: • Maintaining the integrity of the skin epithelial cells and mucous membrane barriersagainst bacteria, viruses, and parasites. • Enhancing antibody production. • Increasing number and activity of macrophages, T cells and natural killer (NK) cells and enhance production of tumor necrosis factor-alpha (TNF- α). • Deficiency: Impaired Immunity (frequent infections, especially in respiratory system). In countries where children are not immunized, infectious disease like measles have relatively higher fatality rates.

38. 4. Hormone synthesis. Vit. A is required for synthesis of steroid hormones (corticosteroids, androgens and estrogens) and production of human growth hormone (GH). 5. Reproduction. Vit. A maintains sperm count and sperm motility in males. In females, deficiency is associated with infertility and spontaneous abortion. 6. Cell growth and development. 7. Formation of red blood cells. Vit. A plays an important role in mobilizing iron stores to build new red blood cells.

39. Uses of Vitamin A in Prevention & Therapy • Treatment of Night blindness. • Treatment of Skin /scalp Disorders: e.g Psoriasis, Acne vulgaris, Dandruff, Eczema, Premature aging of skin • Help in treatment of ear infections, conjunctivitis, bronchitis, pneumonia, and infectious diarrheal disease. • Cancer treatment: large doses of retinoic acid may reduce growth and recurrence of certain forms of skin cancer.

40. 5. Cosmetics: Vitamin A derivatives are used as anti-aging, being absorbed through the skin and increases the rate of skin turnover, and a temporary increase in collagen giving a more youthful appearance. • 6. Gastric ulcers: Vit. A maintain gastric mucus production and reduce stress ulceration in traumatized or burned patients. • 7. Combination of iron + Vit. A may be effective than iron alone in treating iron-deficiency anemia.

41. Some Products of Synthetic Retenoids (orally or topically) 13-cis-Retinoic acid (Tretinoin or Accutane) Used in treatment of acne Acitretin Etretinate Used in treatment of psoriasis

42. PEOPLE AT GREATER RISK OF DEVELOPING VITAMIN A DEFICIENCY Consumers of alcoholic beverage are liable to vitamin A deficiency . Patients taking some medications (birth control pills, methotrexate, drugs sequestering bile acids e.g. cholestyramine or chitosan). Chronically ill people or recovering from surgery. Patients under cancer treatment (radiation and chemotherapy). Cases that may impair Vit. A balance (chronic diarrhea, cystic fibrosis, and kidney or liver disease).

43. Infants and children are more susceptible than adults to vitamin A toxicity. Vitamin A is a teratogen and high doses (more than 10000 μg retinol) may produce birth defects, even with exposure for 1week in early pregnancy. Pregnant women should avoid excess intake of vitamin A from supplements and from vitamin A- rich foods, such as liver (100 g contains nearly 10000 μg retinol). Daily dose should not exceed 2500 μg during pregnancy or better replaced by cartenoids (their conversion to Vit. A in the body is tightly regulated, thus carotenes do not produce vitamin A toxicity). Vitamin A Toxicity

44. Signs and Symptoms of Vitamin A toxicity • Bone pain and joint swelling. • Nausea , vomitting and diarrhoea. • Dry skin and lips. • Hair loss. • Headache and blurred vision. • Enlargement of the liver and spleen. • Reduced thyroid activity. • High blood calcium

45. Drug interactions with Vitamin A 1. Other retinoid medications has higher risk of cumulative toxicity with Vit. A supplement. 2. Use of mineral oil impairs absorption of all fat soluble vitamins, including A. 3. Cholesterol-lowering drugs (e.g. cholestyramine) and Aluminium-containing antacids inhibit absorption of Vit. A. 4. Alcohol, barbiturates, caffeine, cortisone, tobacco, and very high levels of vitamin E deplete Vit. A. 5. Over use of alcohol and Vit. A together increase the possibility of liver damage.

46. THANX