A. History: No other vitamin, with the possible exception of vitamin E, is as generally misunderstood as is vitamin C. It is ironic that the oldest therapeutically-used vitamin, urnished in 1750s in the form the lemons to British sailors to prevent scurvy, is still a subject of controversy. However, 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. It has a curing action against scurvy and hence popularly called as antiscorbutic factor.
B. 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 uptodate, is the acerola fruit (Malpighia punctifolia). The fruit yeilds 1,000–4,000 mg of ascorbic acid per 100 g of edible matter. Citrus fruits (such as orange, lemon, lime), gooseberry, pineapple, guavas, tomatoes, melons, raw cabbage and green pepper are also rich sources of it. New potatoes contain relatively large amounts. Dried legumes and cereals contain very little vitamin C. Dry seeds, in general, are devoid of it but during their sprouting, the vitamin appears. Woody tissues also lack it. Vitamin C is synthesized by most mammals, but not by primates (such as apes, man) and guinea pigs which acquire it from their diets. In animals, the vitamin occurs in tissues and various glands or organs such as liver, adrenals, thymus, corpus luteum etc. Meat contains relatively low concentration. Human milk is 3 to 4 times richer in vitamin C contents than cow's milk. Vitamin C is, however, absent from fish, fats and oils.
It is also not present in or required by microorganisms. Since this vitamin 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. The adrenal and lenses have particularly high contents of vitamin C. The infant is usually born with adequate stores of as corbic acid if the mother’s intake has been adequate; the ascorbic acid content of cord blood plasma is 2-4 times greater than that of maternal plasma. Under these conditions, the breast milk contains ca 4-7 mg/dL of ascorbic acid and is an adequate source of ascorbic acid.
The vitamin C content of some food items are presented in Table.
It is also not present in or required by microorganisms. Since this vitamin 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. The adrenal and lenses have particularly high contents of vitamin C. The infant is usually born with adequate stores of as corbic acid if the mother’s intake has been adequate; the ascorbic acid content of cord blood plasma is 2-4 times greater than that of maternal plasma. Under these conditions, the breast milk contains ca 4-7 mg/dL of ascorbic acid and is an adequate source of ascorbic acid.C. 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 (refer Fig Metabolism of vitamin C ). Although ascorbic acid is a small molecule when compared with DNA, RNA or proteins, its metabolic impact is no less considerable. The dienolic group consisting of hydroxyls on C2 and C3 with a double bond between them invests the ascorbic acid molecule with redox property.
D. Properties: Ascorbic acid is a colourless and odourless crystalline substance, slightly sour in taste and optically active. Only the L-isomer has antiscorbutic properties. It is soluble in water and alcohol but practically insoluble in chloroform, solvent ether and light petroleum. It is readily oxidized, particularly in the presence of copper and iron but not of aluminium. It is for this reason that the foods cooked in copper utensils lose ascorbic acid quickly.This vitamin is also rapidly destroyed by alkalies but is fairly stable in weak acid solutions. Therefore, baking soda has a deleterious effect but steam cooking destroys very little amount of ascorbic acid. Drying ofvegetables and also their storage results in a loss of their ascorbic acid. However, freezing has no detrimental effect on this vitamin.
Citrus fruit juices and tomato juice may be canned with but little loss of ascorbic acid. On account of its easily oxidizable nature, the ascorbic acid is a powerful reducing agent.
D. Properties: Ascorbic acid is a colourless and odourless crystalline substance, slightly sour in taste and optically active. Only the L-isomer has antiscorbutic properties. It is soluble in water and alcohol but practically insoluble in chloroform, solvent ether and light petroleum. It is readily oxidized, particularly in the presence of copper and iron but not of aluminium. It is for this reason that the foods cooked in copper utensils lose ascorbic acid quickly.This vitamin is also rapidly destroyed by alkalies but is fairly stable in weak acid solutions. Therefore, baking soda has a deleterious effect but steam cooking destroys very little amount of ascorbic acid. Drying ofvegetables and also their storage results in a loss of their ascorbic acid. However, freezing has no detrimental effect on this vitamin.
Citrus fruit juices and tomato juice may be canned with but little loss of ascorbic acid. On account of its easily oxidizable nature, the ascorbic acid is a powerful reducing agent.E. Metabolism:Higher plants (like pea) and all known mammals except man, the primates
ContentsWATER-SOLUBLE VITAMINS 1011 and guinea pig can synthesize ascorbic acid from L-gulonolactone. The rat, for example, is resistant to scurvy. In animals, the liver and adrenals (cortical portion) are the main sites of synthesis. The biosynthesis of ascorbic acid in animals takes place according to the scheme as depicted in Fig.(Biosynthesis of vitamin C). The scheme also probably applies to the plants. Man lacks the enzyme L-gulono-oxidaseand as such is incapable of synthesizing ascorbic acid. Ascorbic acid can be readily oxidized (Fig. Metabolism of vitamin C) to dehydroascorbic acid in the presence of metal ions. Dehydroascorbic acid is a much more powerful electron donor than even ascorbic acid by virtue of its unpaired electron. It is, in fact, the free radical form of ascorbic acid.
Dehydroascorbic acid can be reduced, in the presence of H2S or cysteine, back to ascorbic acid. The reduced form (i.e., L-ascorbic acid) predominates in the plasma and also apparently in tissues
at a ratio of about 15 : 1 of the oxidized form (i.e., dehydro-L-ascorbic acid). Both of these are
biologically active and are equally potent in carrying out their metabolic functions. 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. Since the hydration reaction takes place automatically in the neutral medium, the oxidation of ascorbic acid, in other words, means its biologic inactivation. These reactions have been shown to occur in vivo in man and guinea pigs.
Dehydroascorbic acid can be reduced, in the presence of H2S or cysteine, back to ascorbic acid. The reduced form (i.e., L-ascorbic acid) predominates in the plasma and also apparently in tissuesat a ratio of about 15 : 1 of the oxidized form (i.e., dehydro-L-ascorbic acid). Both of these are
biologically active and are equally potent in carrying out their metabolic functions. 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. Since the hydration reaction takes place automatically in the neutral medium, the oxidation of ascorbic acid, in other words, means its biologic inactivation. These reactions have been shown to occur in vivo in man and guinea pigs.
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’. In fact, ascorbic acid appears to be essential to the activity of the enzyme collagen proline hydroxylase, which catalyzesthe conversion of proline to hydroxyproline. Hydroxyproline (Hyp) is found exclusively in collagenand is vital in maintaining the tertiary structure of this major vertebrate protein, i.e., collagen.
Recent researches have established the role of ascorbic acid in the conversion of folic acid to
a physiologically active form, tetrahydrofolic acid.Ascorbic acid also plays a key role in tyrosine metabolism. One of the steps in tyrosine metabolism is the oxidation of p-hydrophenylpyruvic acid to homogentisic acid. The vitamin C protects the enzyme p-hydrophenylpyruvic acid oxidase from inhibition by excess substrate. Ascorbic acid is also involved in electron transport in the microsomal fraction. However, in none of the biological oxidation systems, ascorbic acid has been shown to act as a specific coenzyme. Vitamin C is found concentrated in certain parts of human body such as brain and the white blood cells. This body “pool” amounts to roughly 1,500 mg for a man and slightly more for a woman, which is normally enough for about a month's need. However, illness or stress can substantially decrease the body's vitamin C reserves, as also can smoking, drinking, and a variety of drugs such as aspirin. 
Vitamin C plays an important role in our body's wondrous immune system. It may enhance the body's production of interferon, prostaglandins, T-lymphocytes and immunoglobulins-weapons of the body's self-defence arsenal. However, huge doses of ascorbic acid can leach calcium and other needed minerals out of the body. It can act as a diuretic and laxative.The fact that in old age the deficiency of vitamin C is frequently observed point to a possiblerole of vitamin C as an anti-ageing agent. Free radicals are the major cause of ageing. These are oxygen molecules which lose an electron in the course of circulating through the blood-stream. These highly reactive molecules try to regain chemical stability by ‘snatching’ electrons from other molecules, a process which causes much damage. While normal metabolic processes produce some free radicals, their number increases by tissue injuries from infection, toxins, reduced blood flow, excessive exercise and environmental hazards like radiation, heat, and cold. And the antioxidants like vitamins A, C and E neutralize these free radicals by ‘donating’ electrons.vitamin C (and also vitamins A and E) have long been known to be 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 (C17H98O33N14S) which leads to a tan and hyperpigmentation. Some dermatologists encourage the use of vitamin C as an anti-inflammatory agent as its topical application speeds up the skin's healing process, reducing redness and irritation caused by sun exposure. Ascorbic acid plays an important role in germination, growth, metabolism and flowering of plants (Chenoy JJ, 1962, 1967–1973). During germination, embryo axis has higher ascorbic acid content as well as higher rate of ascorbic acid utilization compared with those of the endosperm or the cotyledons. Ascorbic acid stimulates amylase, protease and RNAase activity and RNA content in various crops including gram (Cicer arietinum). Free radical content of the endosperm/cotyledon has been shown to be higher during
the initial stages of germination as compared to that in the embryo axis, suggesting an active participation of free radicals in the process of energy flow for transport of metabolites from storage organ to the embryo axis. Increase in free radical content of the embryo axis, at later stages of germination is highly suggestive of the important role of free radical in the biosynthesis of macromolecules and other cell constituents for seedling growth. Further, it was established that the ascorbic acid turnover is appreciably higher during the reproductive
phase of differentiation in many thermophobes (wheat, barley, oat), as well as in many thermophytes (maize, sesame). During the period of reproductive differentiation, the free radical content is enhanced.
Vitamin C plays an important role in our body's wondrous immune system. It may enhance the body's production of interferon, prostaglandins, T-lymphocytes and immunoglobulins-weapons of the body's self-defence arsenal. However, huge doses of ascorbic acid can leach calcium and other needed minerals out of the body. It can act as a diuretic and laxative.The fact that in old age the deficiency of vitamin C is frequently observed point to a possiblerole of vitamin C as an anti-ageing agent. Free radicals are the major cause of ageing. These are oxygen molecules which lose an electron in the course of circulating through the blood-stream. These highly reactive molecules try to regain chemical stability by ‘snatching’ electrons from other molecules, a process which causes much damage. While normal metabolic processes produce some free radicals, their number increases by tissue injuries from infection, toxins, reduced blood flow, excessive exercise and environmental hazards like radiation, heat, and cold. And the antioxidants like vitamins A, C and E neutralize these free radicals by ‘donating’ electrons.vitamin C (and also vitamins A and E) have long been known to be 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 (C17H98O33N14S) which leads to a tan and hyperpigmentation. Some dermatologists encourage the use of vitamin C as an anti-inflammatory agent as its topical application speeds up the skin's healing process, reducing redness and irritation caused by sun exposure. Ascorbic acid plays an important role in germination, growth, metabolism and flowering of plants (Chenoy JJ, 1962, 1967–1973). During germination, embryo axis has higher ascorbic acid content as well as higher rate of ascorbic acid utilization compared with those of the endosperm or the cotyledons. Ascorbic acid stimulates amylase, protease and RNAase activity and RNA content in various crops including gram (Cicer arietinum). Free radical content of the endosperm/cotyledon has been shown to be higher during
the initial stages of germination as compared to that in the embryo axis, suggesting an active participation of free radicals in the process of energy flow for transport of metabolites from storage organ to the embryo axis. Increase in free radical content of the embryo axis, at later stages of germination is highly suggestive of the important role of free radical in the biosynthesis of macromolecules and other cell constituents for seedling growth. Further, it was established that the ascorbic acid turnover is appreciably higher during the reproductiveF. 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. However, after a variable period of vitamin C depletion, contain vague symptoms of irritability, tachypnea (very rapid respiration), digestive disturbancesand loss of appetite appear.
The main symptoms which later develop are listed below :
The main symptoms which later develop are listed below :
- Tender bones : There is evidence of general tenderness, esp., noticeable in the legs when the infant is picked up or when the diaper is changed. The legs assume the typical “froglike position”, in which the hips and knees are semiflexed with the feet rotated outward. This may be mistaken for paralysis and is hence aptly called pseudo-paralysis.
- Edematous swellings : These develop along the shafts of the legs and in some cases a subperiosteal hemorrhage can be palpated at the end of the femur.
- Petechial hemorrhages : The capillaries become brittle and burst, thus giving rise to red and purple spots (or petechiae) over the body. Petechiae may be seen in the skin and mucous membranes. Hematuria, melena, and orbital or subdural hemorrhages may be found.
Bleeding gums :
.
Changes in the gums, most noticeable when the teeth are erupted, arecharacterizedby bluish-purple, spongy swellings of the mucous membrane, usually over the upper incisors (in Fig )
In 1975, Prof. Olaf Skinsnes of the University of Hawaii, Honolulu, has succeeded in obtaining almost pure cultures of leprosy bacillus that afflicts human beings. This work has, however, raised the possibility of a vaccine against this dreaded scourge. As an important sidelight of his work, it appears that vitamin C tends to slow down the growth of the bacilli by inhibiting enzyme action. Vitamin C may, thus, have a minor but an important role to play in leprosy treatment.
G. Human requirements: Since vitamin C is continuously oxidized in the body, the daily requirement of this vitamin is rather high. The recommended daily dose for children is 40 mg and for men and women, 50–60 mg. Formula-fed infants should, however, receive even lower doses, i.e., 30 mg of ascorbic acid daily. Lactating mothers should take higher doses, i.e., 100 mg daily. According to a report published by the British Nutrition Foundation, the RDA for vitamin C on which most nutritionists base diets, is far too low. The 30 mg daily that is usually recommended in most countries is way below the United States at 60 mg, Germany at 75 mg and Russia at 100 mg. Ante diluvian though it sounds, the figure of 30 mg is based on the amount of vitamin C needed to prevent that scourge of seafarers, scurvy. The Nutrition Foundation believes that a more contemporary approach to vitamin C would be to consider at what level it actually promotes good health. Besides, vitamin C requirement in humans may vary with the time of day and time of year. Early autumn, for example, is when most poeple’s vitamin C levels are at their lowest.
.Changes in the gums, most noticeable when the teeth are erupted, arecharacterizedby bluish-purple, spongy swellings of the mucous membrane, usually over the upper incisors (in Fig )
- Scorbutic rosary : The costochondral junctions become prominent and appear sharp and
angular, giving rise to a beaded structure, called scorbutic rosary. The angulation of the scorbutic beads is usually sharper than that of the rachitic rosary because it is produced by a separation of epiphyses of ribs and backward displacement of sternum rather than by widening of the softened epiphyses as occurs in rickets, where the prominence of the costochondral junction is dome-shaped and semicircular. - Delayed wound healing: The wound healing is delayed or, in many cases, even does not
occur because of the failure of the cells to deposit collagen fibrils. The healed wounds may even break down. - Cessation of bone growth : The bones cease to grow. The cells of growing epiphyses continue to proliferate but no new matrix is laid down between the cells. Consequently, bones fracture easily at the point of growth because they fail to ossify. Moreover, when an already ossified bone fractures in a scorbutic individual, the osteoblasts cannot secrete a new matrix for the deposition of new bone. With the result, the fractured bone does not heal.
- “Sicca” syndrome : Swollen joints and follicular hyperkeratosis may develop, as well as the “sicca” syndrome of Sjögren, which is usually associated with collagen disorders and includes xerostomia, keratoconjunctivitis sicca, and enlargement of the salivary glands.
- Anemia : Anemia may reflect inability to utilize iron or impaired folic acid metabolism.
- Pyrexia : Low-grade fever is usually present in scorbutic children.
In 1975, Prof. Olaf Skinsnes of the University of Hawaii, Honolulu, has succeeded in obtaining almost pure cultures of leprosy bacillus that afflicts human beings. This work has, however, raised the possibility of a vaccine against this dreaded scourge. As an important sidelight of his work, it appears that vitamin C tends to slow down the growth of the bacilli by inhibiting enzyme action. Vitamin C may, thus, have a minor but an important role to play in leprosy treatment.
G. Human requirements: Since vitamin C is continuously oxidized in the body, the daily requirement of this vitamin is rather high. The recommended daily dose for children is 40 mg and for men and women, 50–60 mg. Formula-fed infants should, however, receive even lower doses, i.e., 30 mg of ascorbic acid daily. Lactating mothers should take higher doses, i.e., 100 mg daily. According to a report published by the British Nutrition Foundation, the RDA for vitamin C on which most nutritionists base diets, is far too low. The 30 mg daily that is usually recommended in most countries is way below the United States at 60 mg, Germany at 75 mg and Russia at 100 mg. Ante diluvian though it sounds, the figure of 30 mg is based on the amount of vitamin C needed to prevent that scourge of seafarers, scurvy. The Nutrition Foundation believes that a more contemporary approach to vitamin C would be to consider at what level it actually promotes good health. Besides, vitamin C requirement in humans may vary with the time of day and time of year. Early autumn, for example, is when most poeple’s vitamin C levels are at their lowest.
H. 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.
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