Water soluble vitamins

Definition
Classification
Introduction
Types of WATER SOLUBLE vitamin
Public health significance
Dietary goals
Dietary guidelines
Vitamin C
the B Vitamins
Thiamin (Vitamin B1)
Riboflavin (Vitamin B2)
Niacin (Vitamin B3)
Pantothenic Acid
Vitamin B6
Folic Acid
Vitamin B12
Nutritional programmes in india

1. 1 WATER SOLUBLE VITAMINS Dr. Ankit Mohapatra, DEPARTMENT OF PUBLIC HEALTH DENTISTRY

2. CONTENTS Definition Classification Introduction Types of WATER SOLUBLE vitamin Public health significance Dietary goals Dietary guidelines Conclusion References 2

3. VITAMINS Vitamins may be regarded as organic compounds required in the diet in small amounts to perform specific biological functions for normal maintenance of optimum growth and health of the organism. 3

4. CLASSIFICATION 4

5. They are heterogeneous group of compounds - differ chemically. Common character – solubility in water. Easily absorbed. Not stored in the body except for Vit B12. Readily excreted in urine. Form coenzymes – biochemical reactions. Water Soluble Vitamins 5

6. Originally, vitamin B referred to a vitamin whose deficiency causes beriberi in man and polyneuritis in birds. Later, Goldberger’s researches on pellagra led to the view that vitamin B consisted of at least 2 factors : a heat-labile antiberiberi factor and comparatively heat-stable antipellagra factor. Some called the former factor as vitamin B1 and the latter as vitamin B2. 6

7. But the later researches conducted by Richard Kuhn, Conrad Elvehjem and others have established the fact that vitamin B complex, as represented by yeast, rice bran and liver extracts, contains still other factors. Vitamin B complex is known to consist of a group of at least 25 components usually named as B1, B2, B3 etc. But to prevent confusion, their chemical names are now frequently used. 7

8. FEATURES IN COMMON: All of them except lipoic acid are water-soluble. Most of them, if not all, are components of coenzymes that play vital roles in metabolism Most of these can be obtained from the same source, i.e., liver and yeast. Most of them can be synthesized by the intestinal bacteria. 8

9. 9

10. VITAMIN B 1 10

11. History. Thiamine was the first member of the vitamin B group to be identified and hence given the name vitamin B1. Thiamine was first isolated by Jansen (1949) in Holland and Adolf Windaus in Germany. On account of its curing action against beriberi, it is commonly known as antiberiberi factor. It is also known as antineuritic factor or heat-labile factor. In Europe, it is also designated aneurin . 11

12. Occurrence. In all plant and animal foods. Cereals, heart, liver and kidney are excellent sources. In cereals, the outer layers of seeds are especially rich in thiamine. In yeasts and animal tissues, (present mainly as its coenzyme, thiamine pyrophosphate (TPP).) Milk also contains thiamine, (relatively low amounts) 12

13. Structure The chemical structure of thiamine was determined in 1935 by Robert R. Williams and his associates in the United States and its chemical synthesis was achieved soon thereafter. Thiamine (C12H17N4OS) is 2,5-dimethyl-6- aminopyrimidine bonded through a methylene linkage to 4-methyl-5-hydroxyethyl-thiazole. Thus, pyrimidine and thiazole are the two moieties present in its molecule. 13

14. The pyrimidine is unique in that it is the only natural pyrimidine containing an alkyl group at C2. Also, with the possible exception of penicillin, thiamine is the only natural compound which contains a thiazole group. 14

15. THIAMINE 15

16. Properties White crystalline substance Readily soluble in water, slightly so in ethyl alcohol but insoluble in ether and chloroform. Odour resembles that of a yeast. Aqueous solution is optically inactive. Destroyed at elevated temperature, unless the Ph is low. It can stand short boiling up to 100°C. 16

17. Hence, it is only partly lost in cooking or canning processes. Long boiling or boiling with alkali destroys it. Stable in acid medium. On oxidation, it produces thiochrome , which gives fluorescence. 17

18. Metabolism The requirement of this vitamin is increased under high metabolic conditions such as fever, increased muscular activity, pregnancy and lactation and also under surgery and stress. A correlation also exists between the type of food taken and the vitamin B1 requirement. 18

19. Fats and proteins reduce while carbohydrates increase the amount of this vitamin required in the daily diet. Thiamine absorption decreases with gastrointestinal or liver disease. Raw seafoods (e.g., fishes and molluscs) contain an enzyme, thiaminase which destroys thiamine in the body. People consuming such foods may, therefore, reveal symptoms of thiamine deficiency. 19

20. If thiamine is administered in human body, a part of it is excreted or recovered in the urine and a part is converted to pyramin by the enzyme, thiaminase . Besides thiaminase , certain flavonoids of nonenzymic nature also work against thiamine. Thiamine is phosphorylated with ATP to form thiamine pyrophosphate (TPP), which is also called diphosphothiamine (DPT). 20

21. 21

22. Deficiency Vitamin B1 deficiency leads to beriberi in human beings. B1 deficiency is seen in populations consuming polished rice as staple food. The early symptoms of thiamine deficiency are loss of appetite (anorexia), weakness, constipation, nausea, mental depression, peripheral neuropathy, irritability etc. 22

23. Ptosis of the eyelids Atrophy of the optic nerve. Hoarseness due to paralysis of the laryngeal nerve Muscular atrophy and tenderness of the nerve trunks are followed by ataxia, loss of coordination, and loss of deep sensation. 23

24. 24

25. 25

26. TYPES OF BERI- BERI DRY BERIBERI Symptoms usually involve the nervous system. The child may appear plump but is pale, flabby, listless and dyspneic ; the heart beat is rapid and the liver enlarged. 26

27. 27

28. WET BERIBERI Symptoms associated with edema and effusions. Child is undernourshied , pale and edematous and has dyspnea , vomiting and tachycardia. Skin appears waxy. Urine may contain albumin and casts. 28

29. 29

30. PERNICIOUS BERIBERI Symptoms involving heart, resulting in acute. Lesions found principally in the heart, peripheral nerves, subcutaneous tissue and serous cavities. Heart is enlarged, to the right and there is fatty degeneration of the myocardium. 30

31. Generally edema of the legs, serous effusions, and venous engorgement may be seen. In the brain include vascular dilatation and hemorrhage . Finally, death ensues due to heart failure. 31

32. Treatment If beriberi occurs in breast-fed infant, both the mother and child should be treated with thiamine. In such cases, the daily dose for adults is 50 mg and for children 10 mg or more. Oral administration is effective until gastrointestinal disturbances prevent absorption. IM & IV to children with cardiac failure. 32

33. REQUIREMENTS The daily recommended dietary allowances : Men- 1.2–1.4 mg Women - 1.0 mg Pregnant and lactating mothers – 1.5 mg Infants – 0.2- 0.5 mg 33

34. VITAMIN B 2 34

35. HISTORY Riboflavin or vitamin B2 was first isolated in 1879 from milk. Since it was first isolated from milk, vitamin B2 is also known as lactoflavin . Originally, it was also known as ovoflavin ( from eggs) and hepatoflavin ( from liver). Its synthesis was done by Richard Kuhn and Paul Karrer. It is popularly called as the “yellow enzyme”. 35

36. Occurrence In nature, it occurs almost exclusively as a constituent of one of the two flavin coenzymes, namely, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). Milk, cheese, eggs, liver, kidney, heart and brewer’s yeast are excellent sources of this vitamin. Cow’s milk contains about 5 times as much riboflavin as human milk. Leafy vegetables are good sources. 36

37. Fruits and most root vegetables- moderate quantities. Whole grains, cereals and milled flour - low riboflavin content. Ordinary cooking processes do not affect the riboflavin content. Fermentation residues from alcohol manufacture probably offer the richest large supplies. 37

38. Structure Riboflavin (C17H20N4O6) belongs to a class of water-soluble pigments called lyochromes . A molecule of thiamine consists of a sugar alcohol, (D- ribitol ,) attached to a chromogenic dimethyl isoalloxazine ring at position number 9. 38

39. RIBOFLAVIN 6, 7-dimethyl-9-(1′-D-ribityl) isoalloxazine 39

40. Properties Bright orange-yellow crystalline powder. Soluble in water and ethanol but insoluble in ether and chloroform. Stable to heat and acids but is easily decomposed by alkalies and exposure to light. Aqueous solution exhibits yellow-green fluorescence. Stands ordinary cooking and canning. 40

41. On exposure to light, the ribityl residue splits off, forming a compound lumiflavin in alkaline solution and lumichrome in acidic or neutral solution. 41

42. Metabolism Riboflavin is synthesized by most bacteria, yeasts and moulds. Ashbya gossypii , an yeast, produces it in such large amount that riboflavin crystals are formed in the culture medium. The ingested riboflavin is largely passed out as such or as its coenzyme, the FMN ( flavin mononucleotide). When riboflavin is phosphorylated in the presence of an enzyme, flavokinase , it gets converted to FMN which is essential in the biosynthesis of fats. 42

43. The flavoenzymes play a key role in cell metabolism. They function in accepting hydrogen atoms from reduced pyridine nucleotides. They have been shown to participate in the enzymic oxidation of glucose, fatty acids, amino acids and purines . 43

44. Deficiency Riboflavin deficiency is usually caused by inadequate intake ( Ariboflavinosis ). Faulty absorption may contribute in patients with biliary atresia or hepatitis or in those receiving probenecid , phenothiazine or oral contraceptives. Phototherapy destroys riboflavin content. Interestingly riboflavin deficiency without deficiency of other member of the B complex is rare. 44

45. DEFICIENCY LEADS TO- Keratitis - inflammation of the cornea of the eye Conjunctivitis photophobia- An inflammation of the conjunctiva resulting in dilatation of the conjunctival blood vessels, causing the eye to appear red with a fear to light. Corneal vascularization (bloodshot eyes) Seborrheic dermatitis- A skin disorder affecting the scalp, face, and torso. Lacrimation 45

46. Keratitis 46

47. Corneal vascularization 47

48. Seborrheic dermatitis 48

49. Cheilosis Pallor at the angles of the mouth, followed by thinning and maceration of the epithelium. Superficial fissures often covered by yellow crusts develop in the angles of the mouth and extend radially into the skin for distances upto 2 cm. 49

50. CHELIOSIS 50

51. Glossitis   soreness or usually inflammation with depapillation of the dorsal surface of the tongue (loss of the lingual papillae), leaving a smooth and  erythematous  (reddened) surface. Patients suffering from pellagra and beriberi are usually also deficient in riboflavin. 51

52. GLOSSITIS 52

53. Treatment Ariboflavinosis may be prevented by a diet that contains adequate amounts of milk, eggs, leafy vegetables, and lean meats. Treatment consists in oral administration of 3-10 mg of riboflavin daily. If no response, IM of 2 mg of riboflavin in saline solution may be administered 3 times in a day. 53

54. REQUIREMENTS The minimum daily requirement varies from Children and adults- 0.6 to 1.7 mg Pregnancy and lactation women- up to 2.0 mg 54

55. VITAMIN B 3 55

56. History First isolated by Roger J. Williams in 1938 from yeast and liver concentrates. He named it as pantothenic acid . The coenzyme form of this vitamin (coenzyme A or CoA -SH) was isolated and its structure determined by Fritz A. Lipmann. 56

57. The chemical synthesis of this coenzyme was, however, described by Khorana in 1959. This vitamin is sometimes called as filtrate factor or the yeast factor. 57

58. Occurrence Yeast, liver and eggs are the richest sources of it. Vegetables (potatoes, sweet potatoes, cabbage, cauliflower, broccoli) and fruits (tomatoes, peanuts) and also the skimmed milk, wheat bran, whole milk and canned salmon are some of the less important sources. In most animal tissues and microorganisms, it occurs as its coenzyme. 58

59. Structure Pantothenic acid (C9H17NO5) is an amide of pantoic acid (α, γ- dihydroxy -β, β- dimethyl butyric acid) and β- alanine . Pantoyl - β- alanine 59

60. Properties Pale yellow viscous oil, Soluble in water and ethyl acetate Insoluble in chloroform. Stable to oxidizing and reducing agents Destroyed by heating in an acidic and alkaline medium (i.e., it is heat-labile). 60

61. Metabolism Pantothenic acid can be synthesized by green plants and various microorganisms ( Neurospora , Escherichia coli, Bacteria linens) but not by mammals. Hence, this must be present in the diet to serve as a starting point for coenzyme A ( CoA ). Coenzyme A is richly found in the liver and in poor quantities in adrenals. 61

62. There may be as much as 400 mg of CoA per kilo of liver. It functions in acetylation reactions. In order to be effective, CoA must be present in the form of acetyl- CoA . It may arise in many ways but the most common way of its production is that CoA , in the presence of ATP, acetate and a suitable enzyme, is converted into acetyl CoA . 62

63. The only known metabolic fate of vitamin B 3 is its participation in the formation of the biologically important coenzyme A. It functions as a thioester of carboxylic acids. 63

64. Deficiency No definite deficiency syndrome, because of the ubiquitous nature and a little amount is synthesized in the body. Its correlation with achromotrichia (premature greying of the hair) has been described in the case of man, sometimes. 64

65. REQUIREMENTS The dietary allowance dose has not been officially worked out. Yet, 5—10 mg per day of vitamin B3 has been suggested. 65

66. VITAMIN B 5 66

67. History Vitamin B5 refers to nicotinic acid and was named as pellagra preventive (PP) factor by an Austrian- American physician of the U. S. Public Health Service, Joseph Goldberger (1920) because of its curing action on pellagra (After Goldberger's death, vitamin B5 was sometimes called vitamin G in his honour). 67

68. Nicotinic acid was first recognized by Conrad Elvehjem and D. Wayne Woolley of Wisconsin University in 1937. This vitamin has a curing action against black tongue disease in dogs, it is also called as anti black tongue factor. It was first isolated by Funk in 1911. Because the name `nicotinic acid' might mislead people into thinking that tobacco is nutritious, nicotinic acid has been given the alternative official name niacin. 68

69. Occurrence Niacin is widely distributed in nature in plant and animal tissues mainly as its amide called nicotinamide (not an alkaloid nicotine of tobacco). As dietary tryptophan( α - amino acid ) can be converted, in restricted quantities, to niacin in the body, it can partially substitute for niacin. Most vegetables and fruits are poor sources of it. 69

70. Niacin is most abundantly found in yeast. Liver, lean pork, salmon, poultry and red meat are also good sources, but most cereals contain only small amounts of it. Milk and eggs, which contain very little or practically no niacin, are good pellagra-preventive foods because of their high content of tryptophan. Vegetarian’s diet lack in this vitamin. 70

71. Nicotinamide , is present as a constituent in two pyridine nucleotide coenzymes namely NAD( nicotinamide adenine dinucleotide ) and NADP(  nicotinamide adenine dinucleotide phosphate). Niacin is stable to heating and oxidation, there are only small losses in cooking. 71

72. Structure Niacin (C6H5O2N) is simplest of all the known vitamins. As it is a pyridine derivative Vitamin B5 and its amide 72

73. Properties Niacin white crystalline substance. Soluble in ethyl alcohol but less soluble in ether and benzene. Heat-stable. Nicotinamide , When pure, occurs as white needle like crystals. Soluble in water and stable in air and heat. 73

74. Metabolism The conversion of niacin to niacinamide takes place in the kidney and brain slices and also in the liver slices, if glutathione is present. Nicotinamide is synthesized by amidation of nicotinic acid adenine dinucleotide and subsequent degradation of NAD thus formed. The niacin in man and other animals is derived from the amino acid tryptophan 74

75. The conversion of tryptophan to nicotinic acid in the body takes place through a series of intermediate steps, which are 75

76. These two coenzyme forms of this vitamin, NAD and NADP, carry out 2 important functions in the tissues: (a) Oxidation of alcohols, aldehydes , amino acids and hydroxy -carboxylic acids. (b) Reduction of the flavin coenzymes. 76

77. Deficiency A deficiency of niacin causes pellagra in man. Pellagra is characterized by 3 “Ds”, namely Dermatitis of the exposed parts, Diarrhoea Dementia 77

78. 78

79. Symptoms of Pellagra High sensitivity to sunlight Aggression Dermatitis,  alopecia (hair loss),  edema  (swelling) Smooth, beefy red  glossitis  (tongue inflammation) Red skin lesions Insomnia 79

80. Weakness Mental confusion Ataxia (lack of coordination), paralysis of extremities,  peripheral neuritis (nerve damage) Diarrhea Dilated cardiomyopathy  (enlarged, weakened heart) Eventually dementia 80

81.  PSYCHOLOGICAL SYMPTOMS OF PELLAGRA Psychosensory disturbances (impressions as being painful, annoying bright lights, odors intolerance causing nausea and vomiting, dizziness after sudden movements) Psychomotor disturbances (tense, restlessness and a desire to quarrel) Emotional disturbances 81

82. Treatment Children respond quickly to antipellagral therapy. A well-balanced diet should be augmented with 50-300 mg/day of niacin; 100 mg may be given intravenously in acute cases or in cases of poor intestinal absorption. The diet should be supplemented B complex group. Sun exposure should be avoided during the active phase The diet of the cured pellagrin should be supervised continuously to prevent recurrence. 82

83. REQUIREMENTS The recommended daily allowance of nicotinic acid is: Children - 8 and 15 mg Men - 15 and 20 mg Women - 13 and 15 mg Pregnant and lactating - up to 20 mg 83

84. VITAMIN B 6 84

85. History The name vitamin B6 was suggested by Albert Szent-Györgyi (1934) to designate substances, other than thiamine and riboflavin, which cured a dermatitis ( acrodynia ) in rats. It was, henceforth, also named as adermin or antidermatitis factor. Vitamin B6 group includes 3 compounds : pyridoxine, pyridoxal and pyridoxamine . Pyridoxine was first isolated, in 1938, from yeast and liver. 85

86. Occurrence The B6 vitamins are widely distributed in plant and animal tissues. They are especially rich in cereals, peas, carrots, potatoes, sweet potatoes, bananas, watermelons and yeasts. B6 vitamins are also found in egg yolk, salmon, chicken, fish, beaf , pork and liver. 86

87. Pyridoxine is adequately available in human and cow’s milk. Pyridoxal (PAL) and pyridoxamine (PAM) also occur as their coenzymes, namely, pyridoxal phosphate (PALP) and pyridoxamine phosphate (PAMP), respectively. 87

88. Structure All the 3 forms of vitamin B6 are derivatives of pyridine, C5H5N and differ from each other at position 4 of the ring. All the 3 forms are readily interconvertible biologically. 88

89. Properties White crystalline substance. Soluble in water and alcohol. Slightly soluble in fat solvents. Sensitive to light and ultraviolet irradition . Resistant to heat in both acidic and alkaline solutions. While pyridoxal and pyridoxamine are destroyed at high temperatures. 89

90. METABOLISM Vitamin B6 serve as growth factors to a number of bacteria. In addition, the 3 forms are converted to pyridoxal - 5-phosphate, which acts as a coenzyme in various enzymic reactions involved in amino acid metabolism such as transamination , decarboxylation and racemization and in the metabolism of glycogen and fatty acids. It is also essential in the metabolism of hydroxy amino acids, sulfurcontaining amino acids and also tryptophan. 90

91. Pyridoxal or its phosphate derivative also possibly acts as a carrier in the active transport of amino acids across cell membranes. Pyridoxine can be converted to either pyridoxal or pyridoxamine but neither of them can be changed to pyridoxine. 91

92. EXCRETION All these three can be detected in the urine after ingestion although 4-pyridoxic acid is the most important excretion product quantitatively. It is for this reason that when administered in the human body, about 90% of pyridoxine is oxidized to pyridoxic acid and excreted in human urine in this form. 92

93. B6 vitamins are also essential for the breakdown of kynurenine . If it does not happen, xanthurenic acid appears in the urine. 93

94. DEFICIENCY Seborrhoeic dermatitis-like eruption,  Atrophic glossitis  with ulceration,  Angular cheilitis ,  Conjunctivitis,  Intertrigo , Neurologic symptoms, Confusion. 94

95. nausea Vomiting However, these deficiencies are rare. In adults, the vitamin B6 deficiency is normally not found because the intestinal bacteria are capable of synthesizing vitamin B6 95

96. INTERTRIGO 96

97. A syndrome resembling vitamin B6 deficiency, has also been reported in man during the treatment of tuberculosis with high doses of the drug isoniazid . The symptoms were alleviated by the administration of pyridoxine. Thus, 50 mg of pyridoxine per day completely prevented the development of neuritis. It is believed that isoniazid forms a hydrazone complex with pyridoxal , resulting in partial activation of the vitamin. 97

98. Isoniazid , thus, is a potent antagonist of vitamin B6 . Isoniazid 98

99. Treatement Balanced diets usually contain enough pyridoxine so that deficiency is rare. For convulsions due to pyridoxine deficiency, 100 mg of vitamin should be given intramuscularly. Excessive intake may cause sensory neuropathy. 99

100. REQUIREMENTS The minimum dietary allowance of vitamin B6 is : Infants and children - 0.2 and1.2 mg Men and women - around 2.0 mg Pregnancy and lactation - 2.5 mg 100

101. VITAMIN B 7 101

102. History In 1935, Fritz Kögl , a Dutch biochemist, isolated in crystalline form from 250kg of dried egg yolks about 1 mg of a ‘bios’ factor (growth promoting factor) necessary for yeast and named it as “biotin”. Four years later, Szent-Györgyi et al conclusively proved that biotin is synonymous to the “ antiegg white injury factor” which is responsible for the cure of egg white injury, induced in rats and other animals by feeding them with raw egg white. 102

103. Occurrence Biotin has a wide range of distribution both in the animal and the vegetable kingdoms. Yeast, liver, kidney, milk and molasses are among the richest sources. Peanuts and eggs have lesser amounts. Biotin occurs in nature usually in combined state as biocytin It is a bound form of biotin, linked as a peptide with the amino acid lysine. 103

104. BIOCYTIN OR BIOTINYLLYSINE 104

105. Structure The structure of biotin (C10H16O3N2S) was worked out by Vincent du Vigneaud in 1942. Biotin has an unusual structure and consists of a fused imidazole and thiophene ring with a fatty acid side chain. Two forms of biotin can exist, allobiotin and epibiotin . 105

106. Biotin is optically active. Biotin and thiamine are the only sulfur -containing vitamins isolated to date. 106

107. BIOTIN 107

108. Properties Biotin crystallizes as long needles. Soluble in water and ethyl alcohol But insoluble in chloroform and ether. Heat-stable Resistant to both acids and alkalies . Melting point of 230°C. 108

109. Metabolism Biotin serves as a prosthetic group for many enzymes. These biotin containing enzymes catalyze the fixation of co2 into organic molecules, thus bringing about carboxylation . The carbon dioxide is carried as a carboxyl group attached to one of the ureidonitrogen atoms of biotin, forming n- carboxybiotin complex . 109

110. N-CARBOXYBIOTIN COMPLEX 110

111. Deficiency Brawny dermatitis, Somnolence, Hallucinations, Hyperesthesia with accumulation of organic acids Egg white injury. Loss of hair, Decrease in weight Edema . 111

112. Treatment Parenteral solutions should contain biotin. Deficient patients - Oral administration of 10 mg. 112

113. REQUIREMENTS The intestinal bacteria synthesize biotin in such appreciable amounts that the amount excreted in urine exceeds the intake. That is why the RDA for this vitamin has not been established. However, about 10 mg per day of biotin is sufficient for an adult. 113

114. VITAMIN B 9 114

115. History Day, for the first time, showed the existence of this nutritional factor by demonstrating that yeast extract could cure cytopenia , a disease experimentally induced in monkeys. The potent factor was obtained from spinach leaf and this led to its nomenclature as folic acid, FA ( foliumL = leaf). The official name of this vitamin is folacin . 115

116. This is also known as liver Lactobacillus casei factor as it was isolated from liver and was shown as necessary for the growth of lactic acid bacteria. Hogan called this as vitamin Bc . 116

117. Occurrence Folic acid and its derivatives (tri- and hepta-glutamyl peptides) are widely distributed in biological world. A few important sources are liver, kidney, tuna fish, salmon, yeast, wheat, dates and spinach. Root vegetables, sweet potatoes, rice, corn, tomatoes, bananas, pork and lamb contain little folid acid. With improper cooking, folacin contents are destroyed. 117

118. Structure A molecule of folic acid consists of 3 units: glutamic acid, p- aminobenzoic acid and a derivative of the heterocyclic fused-ring compound pterin . Its molecular formula is C19H19O6N7. 118

119. VITAMIN B 9 OR FOLIC ACID 119

120. Properties Yellow crystalline substance. Slightly soluble in water Stable to heat in alkaline or neutral solutions only. Inactivated by sunlight. 120

121. Metabolism Reduction products of folic acid act as coenzymes. An enzyme, folic reductase , reduces folic acid to dihydrofolic acid (DHFA or FH2), the latter compound is further reduced by dihydrofolic reductase to 5,6,7,8-tetrahydrofolic acid (THFA or FH4). 121

122. The formation of FH4 from FA is associated with the oxidation of NADPH or NADH and requires the presence of ascorbic acid( Vit C). 122

123. Folic acid, in conjunction with ascorbic acid, also appears to be related to tyrosine metabolism. Folic acid provides protection against Alzheimer’s disease. Connelly, Peter J., et al. "A randomised double‐blind placebo‐controlled trial of folic acid supplementation of cholinesterase inhibitors in Alzheimer's disease."  International journal of geriatric psychiatry  23.2 (2008): 155-160. 123

124. Deficiency Deficiency of  folate  can occur when the body's need for folate is increased, when dietary intake of folate is inadequate, or when the body excretes (or loses) more folate than usual. Medications that interfere with the body's ability to use folate may also increase the need for this vitamin. Deficiency is more common in pregnant women, infants, children, and adolescents. 124

125. Situations increaseing the need for folate : Hemorrhage Kidney dialysis Liver disease Malabsorption , including celiac disease Pregnancy and lactation (breastfeeding) Tobacco smoking Alcohol consumption 125

126. Medications can interfere with folate utilization, including: anticonvulsant  metformin  (sometimes prescribed to control blood sugar in type 2 diabetes) 126

127. methotrexate , & sulfasalazine   - an anti-cancer drug also used to control inflammation associated with ulcerative colitis and rheumatoid arthritis. triamterene  (a diuretic) oral contraceptives 127

128. Deficiency leads to- In man- megaloblastic anemia , glossitis gastrointestinal disorders Pregnant women and infants- tropical sprue , in which there is a general deficiency in absorption of many nutrients from the small intestine. 128

129. REQUIREMENTS. The daily dietary allowance of folic acid : Infants - 0.1 mg Children - 0.2 mg Adult men and women - 0.4 mg Pregnant mothers - up to 0.8 mg Lactating women – 0.5 mg 129

130. VITAMIN B 12 130

131. History In 1926, George Minot and George William Murphy discovered that patients suffering from pernicious anemia could be cured by feeding them with about half a pound of liver a day. This landmark in medicine brought them Nobel Prize in 1934. 131

132. In 1929, Castle suggested that gastric juice contained a factor (intrinsic factor) that, together with a factor present in the food (extrinsic factor), is responsible for the cure of pernicious anemia . This anti-pernicious anemia factor (APA factor) was, later, isolated in crystalline form in 1948 independently by E. Lester Smith in England and by Edward Rickes and Karl Folkers in the United States. . 132

133. It was then named as vitamin B 12 or cyanocobalamin . It is the last B-vitamin to be isolated and is also known as Factor X or L.L.D. factor. The coenzyme form of this vitamin ( deoxyadenosyl cobalamin or cobamide coenzyme) was first isolated by Barker of California. Coenzyme B 12 has been called a “biologic Grignard reagent”. 133

134. Occurrence Vitamin B 12 is found only in animals. The chief source is liver, although it is also present in milk, meat, eggs, fish, oysters and clams. Animal tissues contain it in varying amounts. Under certain dietary conditions, vitamin B 12 may be synthesized by the intestinal microorganisms. 134

135. Cyanocobalamin is not present in plant foods, however, it occurs in foods bound to proteins and is apparently split off by proteolytic enzymes. 135

136. Animals and plants are unable to synthesize vitamin B 12 . Cyanocobalamin is unique in this context, as it appears to be synthesized only by microorganisms especially anaerobic bacteria. However, a process of producing vitamin B 12 from waste products was developed, in 1977, by the department of Chemical Engineering of the Indian Institute of Technology, Chennai. 136

137. Structure The structure of vitamin B 12 , has been established, in 1957, by Dorothy Crowfoot Hodgkin (Nobel Laureate, 1964). A unique feature of this vitamin is the presence, of an atom of a heavy metal cobalt in the trivalent state in its molecule. No other cobalt containing organic compound has been found in nature. 137

138. Structure of vitamin B 12 or Cyanocobalamin 138

139. Many compounds with vitamin B 12 activity have been isolated from natural sources. Cyanocobalamin is the most common form also written as vitamin B 12 a. In other forms, cyanide ion is replaced by hydroxyl ion in hydroxocobalamin (vitamin B 12 b ), & nitrite ion in nitrocobalamin (vitamin B 12 c ) etc. B 12 b and B 12 c can be converted to vitamin B 12 a by treatment with cyanide. 139

140. Properties Deep red crystalline substance. Soluble in water, alcohol and acetone. Not soluble in chloroform. Levorotatory. Stable to heat in neutral solutions. Destroyed by heat in acidic or alkaline solutions. 140

141. Metabolism Vitamin B 12 is converted to coenzyme B 12 by extracts from microorganisms supplemented with ATP. 141

142. Vitamin B 12 is also needed for the biosynthesis of methyl groups. Also functions in protein synthesis and in the activation of SH enzymes( sulphydryl  ). Cyanocobalamin also affects myelin formation. 142

143. DEFICIENCY A nutritional deficiency of this vitamin is usually not observed on account of its widespread nature in foodstuffs. Most cases of deficiency are from failure to absorb the vitamin. Deficiency may be observed in individuals who abstain from all animal products including milk and eggs, i.e., those who are strict vegetarians. 143

144. Crohn's disease,  Celiac disease Chronic alcoholism  Vegan diet Adult pernicious anaemia (characterized by R.B.Cs. becoming abnormally large and fewer in number).  Graves' disease  Lupus Atrophic gastritis 144

145. 145 CROHN'S DISEASE

146. 146

147. 147

148. REQUIREMENTS The recommended daily allowance of vitamin B 12 is Children - 2 to 4 μg Men and women - 5 μg Pregnant and lactating mothers - 8 μg and 6μg 148

149. TREATMENT The excessive secretion of methylmalonic acid in the urine is a reliable and sensitive index of vitamin B12 deficiency. The physiologic need for vitamin B12 is 1-5 μg /24 hr, as hematologic responses have been observed in these small doses. If there is evidence of neurologic involvement, 1 mg should be injected IM daily for a minimum of 2 weeks. Maintenance therapy is necessary throughout patient’s life. 149

150. VITAMIN C 150

151. History It is the oldest therapeutically-used vitamin. Furnished in 1750s in the form the lemons to British sailors to prevent scurvy. In 1928, Albert G. Szent-Györgyi isolated this crystalline vitamin from the paprika plant and named it hexuronic acid. Later in 1932, C. Glen King and W.A. Waugh in United States isolated this from lemon juice. It was synthesized by Reichstein in 1933. It is also called cevitamin . 151

152. Occurrence In general, ascorbic acid is not as widely distributed as other vitamins. Among plants, it is present in all fresh fruits and vegetables. The richest source of vitamin C, known upto date, is the acerola fruit ( Malpighia punctifolia ). This fruit yeilds 1,000–4,000 mg of ascorbic acid per 100 g of edible matter. 152

153. RICH SOURCES Citrus fruits Gooseberry, Pineapple, Guavas, Tomatoes, Melons, Raw cabbage Green pepper New potatoes Vitamin C is absent from fish, fats and oils. 153

154. Vitamin C is a good reducing agent, it is lost under oxidizing conditions like aeration and heating. Thus, many cooked and canned foods contain little ascorbic acid. It is also found in the combined form as ascorbigen . Vitamin C is found concentrated in certain parts of human body such as brain and the white blood cells. 154

155. Ascorbic acid content of cord blood plasma is 2-4 times greater than that of maternal plasma. Under these conditions, the breast milk contains 4-7 mg/ dL of ascorbic acid and is an adequate source of ascorbic acid. This the reason human milk is 3 to 4 times richer in vitamin C contents than cow's milk. 155

156. Vitamin C content of some fruits and vegetables 156

157. Structure The structure of ascorbic acid (C6H8O6) was established mainly by Haworth. It is a derivative of a hexose called L- gulose . Chemically, it is 1-threo-2,4,5, 6-pentoxyhexen-2- carboxylic acid lactone . Although ascorbic acid is a small molecule when compared with DNA, RNA or proteins, its metabolic impact is no less considerable. 157

158. The dienolic group consisting of hydroxyls on C2 and C3 with a double bond between them invests the ascorbic acid molecule with redox property. 158

159. 159

160. PROPERTIES Colourless and odourless crystalline substance Slightly sour in taste Optically active Soluble in water and alcohol Practically insoluble in chloroform, solvent ether and light petroleum Readily oxidized(presence of copper and iron) It is for this reason that the foods cooked in copper utensils lose ascorbic acid quickly 160

161. Rapidly destroyed by alkalies Fairly stable in weak acid solutions Drying and storage (loss of vit c) Oxidizable in nature ( powerfull reducing agent) 161

162. Metabolism Man lacks the enzyme L- gulono - oxidase and as such is incapable of synthesizing ascorbic acid. Ascorbic acid can be readily oxidized to dehydroascorbic acid in the presence of metal ions. Dehydroascorbic acid is a powerful electron donor than even ascorbic acid by virtue of its unpaired electron. In fact, it is the free radical form of ascorbic acid. Dehydroascorbic acid can be reduced, in the presence of H2S or cysteine , back to ascorbic acid. 162

163. When dehydro -L-ascorbic acid is hydrated, 2,3-diketo-L-gulonic acid is formed which is biologically inactive and cannot be converted back to either of the active forms in the body. Dehydro -L-ascorbic acid & L-ascorbic acid are biologically active and are equally potent in carrying out their metabolic functions 163

164. Metabolism of vitamin C 164

165. Ascorbic acid functions in a number of enzymatic activities. A major function of ascorbic acid is the formation of tissue collagen or ‘intracellular cement substance’. Recent researches have established the role of ascorbic acid in the conversion of folic acid to a physiologically active form, tetrahydrofolic acid. It plays a key role in tyrosine metabolism. 165

166. Vitamin C (and also vitamins A and E) are beneficial for the skin. While vitamins A and E work by exfoliating the skin's surface cells, vitamin C works from the inside by boosting collagen production and repair. It also inhibits the excess production of melanin which leads to a tan and hyperpigmentation . 166

167. Deficiency Avitaminosis C leads to scurvy, which may occur at any stage but is rare in the newborn infant. The majority of cases appear in infants 6-24 months (mo) of age. Breast-fed infants are protected as the breast milk contains adequate amounts of vitamin C. Clinical manifestations require time to develop. 167

168. VITAMIN C DEPLETION Irritability, Tachypnea (very rapid respiration), Digestive disturbances Loss of appetite 168

169. MAIN SYMPTOMS Tender bones Edematous swellings Petechial hemorrhages (capillaries become brittle and burst, thus giving rise to red and purple spots over the body.) Bleeding gums Gingivitis Cessation of bone growth 169

170. Petechial hemorrhages 170

171. Scorbutic rosary(the costochondral junctions become prominent and appear sharp and angular, giving rise to a beaded structure) Delayed wound healing Sicca ” syndrome (the “ sicca ” syndrome of Sjögren , which is usually associated with collagen disorders and includes xerostomia , keratoconjunctivitis sicca , and enlargement of the salivary glands) 171

172. Scorbutic rosary 172

173. SICCA SYNDROME 173

174. Anemia Pyrexia Dry and splitting hair Bachelor scurvy (Elderly bachelors and widowers who have to cook their own foods). 174

175. SCRUVY A disease caused by prolonged severe dietary deficiency of ascorbic acid. In which the breakdown of intercellular cement substances leads to capillary haemorrhages and defective growth of fibroblasts, osteoblasts , and odontoblasts results in impaired synthesis of collagen, osteoid , and dentine. Characterized by haemorrhagic gingivitis affecting especially the interdental papillae (in the absence of teeth, the gums are normal), 175

176. Also characterized by subperiosteal haemorrhages, bone lesions (including the corner fraction sign, a ground-glass appearance, and trabecular atrophy) seen on radiography, perifollicular haemorrhages, and frequently petechial haemorrhages (especially on the feet). Sudden death may occur as a result of cerebral or myocardial haemorrhage. Megaloblastic anaemia, usually due to concomitant iron and/or folate deficiency, is usual. International nomenclature of diseases. Vol. IV Metabolic, nutritional, and endocrine disorders. Geneva, World Health Organization, 1991, p. 283. 176

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178. Clinical manifestations The following symptoms and signs may occur: · Tiredness and weakness Swollen gums which bleed easily at the base of the teeth Haemorrhages in the skin Nosebleeds, Blood in the urine or faeces, Splinter haemorrhages below the fingernails or subperiosteal haemorrhages 178

179. Delayed healing of wounds Anaemia. Cardiac failure. 179

180. Swelling and bleeding of the gums frequently found in certain regions and may be due to vitamin C deficiency. Subclinical vitamin C deficiency may also result in the slow healing of wounds or ulcers. Patients who are to undergo surgery should be given vitamin C if they may be deficient. Vitamin C deficiency may also contribute to anaemia in pregnancy. 180

181. Barlow's disease Scurvy sometimes occurs in infants, usually aged two to 12 months, who are bottle-fed with inferior brands of processed milk. During the processing of the milk, the vitamin C is frequently destroyed by heat. Good brands of processed milk are fortified with vita`min C to prevent scurvy 181

182. The first sign of infantile scurvy is usually painful limbs. The infant cries when the limbs are moved or even touched. The child usually lies with the legs bent at the knees and hips, widely separated from each other and externally rotated, in what has been termed the "frog-leg position". Bruising of the body may be seen. 182

183. Swellings may be felt, especially in the legs. Haemorrhages may occur from any of the sites mentioned above, but bleeding does not take place from the gums unless the child has teeth. 183

184. 184

185. Diagnosis Capillary fragility test The cuff of sphygmomanometer is placed around the arm. It is inflated to a pressure approximately midway between the subject's systolic and diastolic pressure (perhaps 100 mm Hg) and left in place for four to six minutes In a positive test, numerous small red spots appear in the skin below the cuff; these are petechial haemorrhages arising from capillary fragility 185

186. Ascorbic acid levels can be determined in blood plasma or in white blood cells. These levels provide evidence of body reserves of vitamin C. If the level of ascorbic acid in either the blood plasma or the white blood cells is within the normal range, the condition almost certainly is not scurvy. In infantile scurvy X-ray examination will reveal periosteal haemorrhages 186

187. Treatment Scurvy is prevented by a diet rich in ascorbic acid; citrus fruits and juices are excellent sources. The administration of orange juice or tomato juice daily will quickly produce healing but ascorbic acid is preferable. The daily therapeutic dose is 100-200 mg or more, orally or parenterally . 187

188. Increased intake of vitamin C with meals can have a manifest effect on the absorption of iron. In many iron deficient populations, increasing vitamin C intake will help reduce the incidence and severity of iron deficiency anaemia. 188

189. REQUIREMENTS 189

190. PUBLIC HEALTH SIGNIFICANCE Some groups of patients are at higher risk for vitamin deficiency and suboptimal vitamin status. Many physicians may be unaware of common food sources of vitamins or unsure which vitamins they should recommend for their patients. Vitamin excess is possible with supplementation. 190

191. Special attention should be paid to folate (folic acid) intake during pregnancy, in order to avoid birth defects. Some conditions warrant an increase in vitamin C intake, such as exposure to cigarette smoke, environmental stress, growth, and sickness. 191

192. DIETARY GOALS Maintenance of a state of positive health and optimal performance in populations at large by maintaining ideal body weight. Ensuring adequate nutritional status for pregnant women and lactating mothers. Improvement of birth weights and promotion of growth of infants, children and adolescents to achieve their full genetic potential. 192

193. Achievement of adequacy in all nutrients and prevention of deficiency diseases. Prevention of chronic diet-related disorders. Maintenance of the health of the elderly and increasing the life expectancy. 193

194. DIETARY GUIDELINES Eat variety of foods to ensure a balanced diet. Ensure provision of extra food and healthcare to pregnant and lactating women. Promote exclusive breastfeeding for six months and encourage breastfeeding till two years or as long as one can. Feed home based semi solid foods to the infant after six months. 194

195. Ensure adequate and appropriate diets for children and adolescents, both in health and sickness. Eat plenty of vegetables and fruits. Ensure moderate use of edible oils and animal foods and very less use of ghee/ butter/ vanaspati . Avoid overeating to prevent overweight and obesity. Exercise regularly and be physically active to maintain ideal body weight. 195

196. Restrict salt intake to minimum. Ensure the use of safe and clean foods. Adopt right pre-cooking processes and appropriate cooking methods. Drink plenty of water and take beverages in moderation. 196

197. Minimize the use of processed foods rich in salt, sugar and fats. Include micronutrient-rich foods in the diets of elderly people to enable them to be fit and active. 197

198. N utritional programmes in india Ministry of Rural Development Applied nutrition programme (1963 Odisha , later extended to UP and TN) Ministry of Social Welfare Integrated child development services scheme (Oct.2,1975, in 33 CD Blocks under 5 th Five Year Plan) Balwadi nutrition programme (1970 under the department of social welfare ) Special nutrition programme (1970 by Ministry of Social Welfare)

199. Ministry of Health and Family Welfare National nutritional anemia prophylaxis programme (4 th 5-year plan in 1970 by the Ministry of Health and Family Welfare ) National prophylaxis programme for prevention of blindness due to vitamin A deficiency. (1970 as a centrally sponsored scheme by Ministry of H&FW, GoI .) 199

200. National iodine deficiency disorder control programme . (National Goitre Control Programme launched in 1962, at the end of 2 nd 5-year plan by Ministry of H&FW , GoI .) Ministry of Education Mid-day meal programme Started in Tamilnadu . Also known as School lunch programme . Programme in operation since 1961 under Ministry of Education. 200

201. Weekly Iron and Folic acid Supplementation (WIFS ) programme (July 22, 2013), Ministry of Health and Family Welfare under National Rural Health Mission(NRHM). 201

202. CONCLUSION Water-soluble vitamins include the vitamin B-complex and vitamin C, and are essential nutrients needed daily by the body in very small quantities. The B-complex vitamins can be found in a variety of enriched foods like cereal grains and breads, as well as other foods such as meat, poultry, eggs, fish milk, legumes, and fresh vegetables. 202

203. Vegans should be conscious of vitamin B 12 intake because it is not present in plant foods. Over consumption of the watersoluble vitamins is generally not a problem in India, especially if the nutrients are obtained through food. Large amounts of vitamin B-complex and vitamin C supplements and multivitamins are not recommended. 203

204. REFERENCES Gerald F. Combs Jr. The Vitamins, 4th Edition Pamela C. Champe , ‎Richard A. Harvey, ‎Denise R. Ferrier. Biochemistry. 2005 Evans PR. Infantile scurvy: the centenary of Barlow’s disease. British Medical Journal, 1983, 287:1862-1863. Vitamins: a brief guide. https://www.dsm.com/content/dam/dsm/cworld/en_US/documents/vitamins-a-brief-guide-booklet.pdf 204

205. http://www.unhcr.org/4cbef0599.pdf http://www.fao.org/3/a-y2809e.pdf http://extension.colostate.edu/docs/pubs/foodnut/09312.pdf National Institute of Nutrition. Dietary Guidelines for Indians- A Manual. Hyderabad. 2011. World Health Organization. Diet, Nutrition and the Prevention of Chronic Diseases. Report of a WHO Study Group, WHO Technical Report Series No. 797, WHO, Geneva, 1990. 205

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