Vitamin C, B1, B2 & B3

1. Water soluble vitamins Vitamin C, B1, B2 & B3

2. VITAMINC • It is water-soluble vitamin. • Most animals are able to synthesize all vitamin C they need from dietary sugars; but humans are unable. • Also, animals are able to increase synthesis of vitamin C during stress but humans’ strictly depend on dietary sources, increases risk of deficiency during stress time.

3. Natural Source of Vitamin C Guava Kiwifruit Red pepper Plum Strawberry Orange Broccoli Papaya Grapefruit Mango Lemon

4. Vitamin C L- Ascorbic Acid (Reduced Form) L-Dehydroascorbic Acid (Oxidised Form) Physiologically active forms for vitamin C RDA: Adults: 60 mg/day Children: 30 mg/day

5. Chemistry and Stability of Vitamin C • It is a weak acid and its salts called ascorbate. • Unstable in alkaline pH, high temperature, and in the presence of oxygen or metals. • The D-enantiomer of ascorbic acid shows no biological activity. • Ascorbic acid is strong reducing agent, serves as an anti-oxidant and co-factor in hydroxylation reactions. • Ascorbic acid is reversibly oxidized to L- dehydroascorbic acid and both L-ascorbic and L-dehydroascorbic acids are physiologically active forms for vitamin C.

6. Functions of Vitamin C • Antioxidant function: It helps protect against oxidation by free radicals. • Helps in detoxification and excretion of drugs : • It maintains the enzyme systems in liver that detoxify and excrete drugs and toxic pollutants. • Synthesis of collagen: The major component of connective tissue in skin, joints, muscles, bones ligaments, tendons, and cartilages. • Involved in carnitine synthesis(along with niacin and vitamin B6) which is an amino acid required in breakdown of fats for energy. • It is a cofactor in the synthesis of neurotransmittersas epinephrine , norepinephrine and serotonin.

7. Important for healthy immune function: It is essential for optimum activity of WBCs and production of chemical mediators which direct the immune response. Vitamin C seems to increase T-lymphocyte activity, phagocyte function, leukocyte mobility, and possibly antibody and interferon production. • Involved in cholesterol breakdownand excretion (cholesterol level increase if vitamin C status is impaired). • Protection of folate and vitamin E from oxidation. • Involved in control of histamine levels: When vitamin C status is poor High levels of histamine aggravate allergies, asthma, stomach ulcers, and certain psychiatric disorders.

8. Symptoms of Vitamin C Deficiency • Scurvy:Impaired connective tissue synthesis and fragility of blood vessels causes abnormal bleeding: easy bruising, subcutaneous hemorrhagic spots, inflamed and bleeding gums, joint stiffness and pain (due to bleeding into joints). • Impaired wound healing. • Build-up of keratin in hair follicles producing rough • “sandpaper skin”. • Weakness, exhaustion, fatigue (due to impaired carnitine synthesis). • Impaired immunity with increased risk of infection. • Diminished antioxidant defenses: increase risk of cancer, heart disease, stroke, cataract. Scurvy was common between Sailors, Pirates and others who were on ships for months without eating fresh fruits and vegetables.

9. People at High Risk of Vitamin C Deficiency 1. Increased physical stress (e.g. infection, fever, burns, surgery, trauma to soft tissues or bones, and chronic illnesses such as hyperthyroidism, diabetes, rheumatoid arthritis, alcoholism, and kidney failure). 2. Chronic use of drugssuch as aspirin and oral contraceptives impair vitamin C status. 3. Older people, particularly those with chronic illness, and aging. 4. Periods of rapid growth–childhood, adolescence, pregnancy, and lactation. 5. Regular cigarette smoking sharply increases breakdown and excretion of vitamin C.

10. Uses of Vitamin C in Prevention and Therapy • Enhance ability to fight infection:Vitamin C stimulates the activity and ability of WBCs to destroy bacteria and viruses. • Treatment of cold and flu: At doses of 1-2 g, it slightly increases body temp. functions of WBCs and blood histamine immune response and nasal and bronchial congestion duration and symptoms of Cold and Flu. • Helps reduce risk of cancer: particularly cancers of GIT, bladder, breast, pancreas, and uterus (antioxidant + enhancer for immune defenses against cancer and + helps detoxify carcinogenic food additives e.g. nitrates, pesticides, and other chemicals and heavy metals).

11. Large doses platelet aggregationreduce risk of blood clots.In addition, vitamin C the strength of blood vessel walls. By these mechanisms, vitamin C can protect from coronary heart disease, thrombotic stroke, and peripheral vascular disease. • Protection from heavy metals: It absorption and detoxification and excretion of heavy metals. • Improves healing of wounds and fractures in burns, trauma, and surgery. • Iron deficiency (by iron absorption from meals). • Preventing and curing Scurvy.

12. Recommended Therapeutic Doses • For scurvy, 100-250 mg once or twice daily. • For treating the common cold, 1-3 g daily. • During acute stress, 1 g (3 times daily) • For preventing sunburn, 2 g of vitamin C and 1000 IU vitamin E has been used.

13. Toxicity and Side Effects of Vitamin C • Vitamin C is generally regarded as safe in usual doses (up to 1000 mg). Dental erosion may occur from chronically chewing vitamin C tablets. • High doses of vitamin C more than 2000 mg/day may induce kidney stones, severe diarrhea, nausea, and gastritis. Large doses may precipitate hemolysis in patients with glucose 6-phosphate dehydrogenase deficiency. • Vitamin C is metabolizedto oxalic acid. Increased consumption increases the urinary concentration of oxalic acid and increases the risk of oxalate stone formation.

14. Vitamin C- Drug Interaction • Vitamin C chromium and aluminium absorption. Patients with renal failure who take (Al) compounds should avoid vitamin C in doses above the RDA. • Vitamin C can destroy dietary vitamin B12 (so, it must be taken at least 2 hours after meals). • Acidification of the urine by vitamin C could increase re- absorption of salicylates by the renal tubules, and increase plasma salicylate levels .

15. High doses of vitamin C can the response to warfarin, possibly by causing diarrhea and reducing Warfarin absorption • Aspirin increases elimination of vitamin C. It reduces tissue and leukocyte uptake of vitamin C, leaving more in the plasma to be excreted into the urine. • Estrogens can vitamin C absorption or its breakdown.

16. Vitamin B Group

17. Vitamin B Group Water Soluble Vitamins Vitamin B1 (Thiamine)

18. Vitamin B1 (Thiamine) • The 1stwater-soluble B-vitamin family to be discovered. • Since body reserve of thiamine is small (~30mg), a steady dietary supply of it is important to avoid deficiency. • Because of its central role in energy production, most of thiamine is located in the muscles. • Once thiamine absorbed, it is rapidly transformed into the active form, thiamin pyrophosphate (TPP) which acts as a coenzyme. Methyl Bridge Thiazole Ring Pyrimidine Ring Thiamin or Aneurine (Coenzyme form)

19. Daily Required amount and Sources • RDA (Recommended Dietary Allowance )is based on the number of calories in diet: • Energy requirement • Adult male: 3000 k cal. • Female: 2100 k cal • Children : 1700-2000 k cal • Daily requirement increases with high carbohydrate intake and for hard worker or athletes. Vitamin B1 requirement 1.5 mg/day 1.1 mg/day 1mg/day

20. Stability of Thiamine • Stable in crystalline form but not so in solution. • Destroyed by prolonged heat, baking soda (with heating), sulfite preservatives. • Unstable in aqueous solutions with pH > 5.0. At pH 8.0 or above, thiamine turns yellow and is destroyed by a complex series of irreversible reactions. • In strong alkaline solution with the presence of oxidizing agents, e.g. potassium ferricyanide, thiamine is converted to thiochrome, which is blue fluorescent compound and is used for fluoremetric determination of vitamin B1 in foods, pharmaceutical preparations, and biological fluids. Thiochrome

21. Functions of Vitamin B1 • It act as co-enzyme (TPP)in carbohydrate metabolism (for glycolysis and Kreb’s cycle enzymes: pyruvate dehydrogenase and α-ketoglutarate dehydrogenase), which enable conversion of glucose into biological energy through oxidative decarboxylation reactions. This role is important: • To provide energy to the brain. • To improve transmission of nerve impulses by providing nerves with energy. • To increase the efficiency of the heart muscles. • For the formation of RBC’s. • 2. It act as co-enzyme for transketolase which functions in: • The pentose phosphate pathway to synthesize NADPH. • The pentose sugars: deoxyribose and ribose are involved in nucleic acids biosynthesis.

22. Thiamine Antagonists • Oxythiamine is a competitive inhibitor (Amino group in pyrimidine ring is replaced by hydroxyl group). • Neopyrithiamine (It prevents the phosphorilation of hydroxy ethyl group that is essential for activity of the vitamin B1). • Thiaminase (found in raw fish destroys vitamin B1). Causes of Thiamine Deficiency • Malnutrition. • A diet high in thiaminase-rich foods (raw freshwater fish, raw shellfish, ferns) • Foods having anti-thiamine factors (tea, coffee etc.). • Chronic consumption of alcohol

23. Diagnostic Testing for Vitamin B1 deficiency A diagnosis test for B1 deficiency can be determined by measuring transketolase levels of erythrocyte. Diseases of Vitamin B1 deficiency • Beriberi is the deficiency disease caused by lack of thiamine resulted from malnutrition, alcoholism or other causes. • There are two major types of beriberi: • Dry beriberi: affect the nervous system • Wet beriberi: affects the cardiovascular system and ends by Wernicke-Korsakoff syndrome which affect the nervous system.

25. Diseases of Vitamin B1 deficiency (BERI-BERI)

26. People at high risk of Vitamin B1 Deficiency • Heavy alcohol consumers (Alcohol reduces absorption of thiamin and interferes with its conversion to TPP). • Much consumption of coffee and black tea depletes thiamin stores in the body and hinder its absorption. • Patients having liver cirrhosis, malabsorption syndromes, diabetes, kidney disease, or hypermetabolim. • The elderly peoples with poor nutritional status and difficulties with absorption. • Folate deficiency impairsabsorption of thiamin. • Infants who are breastfed by thiamin deficient-mothers can rapidly develop life-threatening signs of thiamin deficiency.

27. Use of Thiamine in prevention and Therapy • Nerve disorders:Supplemental thiamin may be effective in inflammatory nerve disorders (such as trigeminal neuralgia) and in diabetic neuropathy. • 2. Central nervous system disorders:e.g. Alzheimer’s disease, anxiety, and depression associated with anxiety. • 3. Heart failure:Particularly in the elderly chronic heart failure that responds poorly to conventional medical therapy. • 4. Anemia:Thiamin deficiency produces an anemia resembling that of folate or vitamin B12 deficiency (with macrocytosis) that responds to thiamin. • 5. Disease caused by heavy alcohol consumption.

28. Vitamin B1- Drug Interactions • Oral contraceptives, antibiotics, sulfa drugs, and certain types of diuretics may lower thiamine levels in the body. • Vitamin B1 may intensify the effects of neuromuscular blockers that are used during some surgical procedures. • B vitamins are best absorbed as a complex, and magnesium also promotes the absorption of thiamine. Toxicity • Thiamin is virtually nontoxic. • Doses > 200mg may cause drowsiness in some people. • Rare, but severe, allergic reactions may be happened with injectable thiamin.

29. Vitamin B2 (Riboflavin)

30. Vitamin B2 (Riboflavin) • Riboflavin is defined chemically as 7,8-Dimethyl- 10-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl] benzo [g] pteridine-2,4-dioneand is a yellow to orange-yellow powder and soluble in water. • It is the precursor of phosphorylated coenzymes: FMN, FAD, and flavin coenzymes linked covalently to specific tissue proteins, at the 8- α methyl position of the isoalloxazine ring. Riboflavin is stored mainly in liver, kidney and heart as it is or as FAD (70- 90%) or FMN.

31. Isoalloxazine moiety Riboflavin phosphate Ribose moiety Riboflavin = Vitamin B2 Flavin adenine dinucleotide (FAD)

32. Required Daily Amount and Sources RDA is an average of 1.5 mg/ day Mushrooms Yoghurt Milk – Egg Calf liver Mature Soya beans Spinach

33. Stability of Riboflavin • Riboflavin and its coenzymes are sensitive to alkali and acid but in the presence of light or UV light. • Riboflavin is photodegraded to yield lumiflavin (7,8,10- trimethylisoalloxazine) under alkaline conditions and to lumichrome (7,8-dimethylalloxazine) under acidic conditions, and these products are biologically inactive . • Therefore, phototherapy of neonatal jaundice and of certain skin disorders may promote systemic riboflavin deficiency.

34. Functions of Vitamin B2 • 1. Energy production: • The active forms of riboflavin are the phosphorylated coenzymes FMN and FAD which play central roles in about 150 oxidation-reductions reactions and are involved in: • Metabolism of carbohydrates, fat, and protein. • Production of adenosine triphosphate (ATP) through cellular respiration in mitochondria. • Activation of vitamin B12, folate, vitamin B6 and the conversion of tryptophan to niacin. • 2. Antioxidant action: • Riboflavin is a cofactor of glutathione reductase. This enzyme helps in recycle of oxidized glutathione, which plays a key role in maintaining proper function and preventing oxidative stress in human cells including erythrocytes.

35. Causes of Riboflavin Deficiency • Malnutrition. • Health conditions which affect intestinal absorption. • Increase of vitamin excretion from the body. Diagnostic testing for vitamin B2 Deficiency A positive diagnostic test of serum riboflavin is by measuring glutathione reductase levels of erythrocytes.

36. Symptoms of vitamin B2 deficiency (Ariboflavinosis) • Red, scaly, painful, and itchy patches on sensitive skin (around nose, ears, mouth, labia majora (female), and the scrotum (male). • Painful fissures and cracks form at the angles of the mouth (angular stomatitis) and on the lips (cheilosis),usually associated with bacterial and fungal infection. The tongue and throat become purplish and painful. • Mouth ulcers Red, scaly, painful skin Mouth ulcers Cheilosis angular stomatitis

37. Redness, burning, excessive tearing of eye. • Anemia with decreased production of red blood cells. • Deficiency of riboflavin typically produces symptoms of vitamin B6 and niacin deficiency. Anemia Symptoms of niacin deficiency Redness, burning, tearing of eyes

38. People at high risk of vitamin B2 deficiency • Children, and adolescent, athletes, as well as during pregnancy and lactation (cases with a high-energy output) need additional vitamin B2. • People under high stress • Diabetics may have low level of riboflavin as a result of increased urinary excretion. • The elderly people (nutritional inadequacy and problems with absorption) • Patients administering thyroid hormones, oral contraceptives, phenothiazines, barbiturates, probenacid, and Tricyclic antidepressant.

39. Use of Vitamin B2 in Prevention and Therapy • Detoxification: Riboflavin helps liver to detoxify pesticides, chemicals, and other environmental toxins. • Increasing the antioxidant capacity throughout the body and especially for lens of the eye. • Ample intake of riboflavin help decrease the incidence of cataracts. • As a cofactor of glutathione reductase, riboflavin with vitamin C increase body's level of glutathione (antioxidant). • Ample riboflavin intake maintains healthy skin and mucous membranes. • It may be beneficial in stomatitis, cheilosis, and skin eruptions and rashes.

40. Vitamin B2 – Drug interaction • Probenecid (anti-gout) and propantheline bromide (antipeptic ulcers) both delays and impairs its absorption. • Phenothiazines (antipsychotic drugs) increase the excretion of riboflavin, thus lowering serum levels. • Oral contraceptives may also decrease its serum levels. • Riboflavin interferes with the absorption and effectiveness of anti-malarial (ex. chloroquine), tetracycline antibiotics and sulfa-containing drugs.

41. Assay of Vitamin B2 Lumiflavin method: Riboflavin solution or biological sample is irradiated in alkaline medium to yielded a chloroform- soluble lumiflavin, measured by fluoremetry.

42. VITAMIN B3 (NIACIN & NIACINAMIDE)

43. Vitamin B3 (Niacin & Niacinamide) • Two main forms of Vitamin B3 are found in foods: nicotinic acid (niacin) and nicotinamide (niacinamide). • Niacin can be partially satisfied by intake of tryptophan, which is converted by the liver into niacin. • 60 mg of tryptophan can be converted into about 1mg of niacin. • Dietary requirements for niacin are described in terms of niacin equivalents (NEs): • 1NE = 60mg of tryptophan = 1mg of niacin RDA: 13- 20 mg/day

44. Sources of Vitamin B3 Nicotinic acid or Niacin Nicotinamide or Niacinamide Prawns Cow’s milk Meat Fish Sheep liver Rice bran Groundnuts Chilgozas Turnip Beet greens Bran Yeast

45. Pharmacokinetics of Vitamin B3 Absorption: At low concentration by active transportation. At high concentration by passive diffusion. Transportation: Both Nicotinic acid and Nicotinamide bind to plasma proteins for transportation. Biosynthesis: The liver can synthesize Niacin from the essential amino acid Tryptophan, but the synthesis is extremely slow and requires vitamin B1, B2, and B6 (60 mg of Tryptophan 1mg of niacin). Bacteria in the gut may also perform the conversion but are inefficient.

46. Functions of Vitamin B3 • It acts as a co-enzyme in oxidation reduction reactions: • Catabolic Rxn: in form of NAD+/NADH • Anabolic Rxn: in form of NADP+/NADPH • Therefore, it is required for functions of >200 enzymes dealing with the biosynthesis of several compounds e.g. fatty acids, steroids andcatabolism of fuel molecules for energy. • 2. DNA replication and repair: • It is vital for synthesis of DNA-bound nuclear proteins (histones)

47. 3. Antioxidant functions: It plays an important role in antioxidant systems, particularly in the liver. 4. Blood sugar regulation: It is a component of the glucose tolerance factor (GTF), which together with insulin, helps to control blood glucose. 5. Fat and cholesterol metabolism: It lowers levels of total and LDL cholesterol in the blood, while increasing levels of HDL cholesterol (the healthy, protective form of cholesterol).

48. Vitamin B3 Deficiency Diseases • 1. Milder deficiency of niacin (as well as tryptophan) can cause: • Glossitis (inflammation of the tongue leading to purplish discoloration) • Dermatitis around the mouth and rashes • Fatigue • Irritability • Poor appetite • Indigestion • Weight loss • Headache Dermatitis around mouth Glossitis Fatigue Poor appetite Indigestion Headache

49. 2. Severe deficiency leads to Pellagra: Characterized by • Inflamed mouth (painful swollen tongue and fissured lips) and GIT. • Diarrhea • Dermatitis in the exposed skin of hands, face, neck (Casal’s necklace) • Dementia and mental disorders • Death. • It is very rare now, except in alcoholics, strict vegetarians, and people with very poor nutrition (or niacin or tryptophan- deficient food e.g corn). • Death. Dermatitis of exposed skin Mental disorders Inflamed mouth Diarrhea

50. People at high risk of vitamin B3 deficiency • People with very poor nutrition (or niacin or tryptophan- deficient food e.g corn). • People with deficiencies in vitamin B6 or riboflavin (conversion of tryptophan to niacin is reduced niacin stores in the body is reduced). • People with inflammatory bowel disease and other digestive disorders malabsorption of niacin. • Heavy alcohol consumption interferes with absorption and metabolism of niacin. • People under high stress, chronic illnesses, liver disease.