classification of vitamin /best vitamins for women / what are the best vitamins for women? classification of vitamin a deficiency

 Vitamins

Vitamins are nonenergy yielding organic com pounds, essential for normal human metabolism, that must be supplied in small quantities in the diet. This definition excludes the inorganic essential trace minerals and essential amino acids and fatty acids which are required in much larger quantities. Other substances needed for proper growth of microorganisms or cells in culture are called ‘growth factors’. The different chemical forms and precursors of a vitamin can be called its Vitamers (analogy—isomers). The importance of vitamins as drugs is pri marily in the prevention and treatment of deficiency diseases. Some vitamins do have other empirical uses in pharmacological doses. Vitamin deficiencies occur due to inadequate intake, malabsorption, increased tissue needs, increased excretion, certain genetic abnormali ties and drugvitamin interactions. Vitamins, as a class, are overpromoted, over prescribed and overused. Myths like ‘vitamins ener gise the body’, ‘any physical illness is accom panied by vitamin deficiency’, ‘vitamin intake in normal diet is precariously marginal’, ‘vitamins are harmless’, are rampant. Vitamins are traditionally divided into two groups

(a) Fat-soluble (A, D, E, K): 

These (except vit K) are stored in the body for prolonged periods and are liable to cause cumulative tox icity after regular ingestion of large amounts. Some of them interact with specific cellular receptors analogous to hormones.

 (b) Water-soluble (B complex, C): 

These vitamins are mea gerly stored: excess is excretedwith little chance of toxicity. They act as cofactors for specific enzymes of intermediary metabolism. Chemical forms and preparations of vitamins are listed in Table 69.1.

 FAT-SOLUBLE VITAMINS

VITAMIN A 

Chemistry and source Vitamin A occurs in nature in several forms. Retinol (Vit. A1 ) is an unsaturated alcohol containing an ‘ionone’ ring. Marine fish (cod, shark, halibut) liver oils are rich sources. Appreciable amounts are present in egg yolk, milk and butter. Dehydroretinol (Vit A2 ) is present in fresh water fishes. Carotenoids are pigments found in green plants (carrot, turnip, spinach) of which β Carotene is the most important carotenoid. It is inactive as such, one mol ecule splits to provide two molecules of reti nol. Man on normal diet gets half of his vit A as retinol esters and half from carotenoids. 1 µg of retinol = 3.3 IU of vit. A activity 1 Retinol Equivalent = 6 µg of dietary caro tene (because of incomplete utiliza tion of the provitamin).

Absorption and fate Retinyl palmitate, the chief retinyl ester in diet, is hydrolysed in intestines to retinol which is absorbed by carrier transport and reesterified. Aided by bile, it passes into lacteals. Absorption is normally complete, but not in steatorrhoea, bile deficiency and from protein poor diet. Retinol ester circulates in chylomicrons and is stored in liver cells. Free retinol released by he patocytes combines with retinol binding protein (RBP a plasma globulin) and is transported to the target cells. On entering them, it gets bound to the cellular retinol binding protein (CRBP). Small amount is conjugated with glucuronic acid, excreted in bile, undergoes enterohepatic circulation. Minute quantities of water soluble metabolites are excreted in urine and faeces. In contrast to retinol, only 30% of dietary β carotene is absorbed. It is split into two molecules of retinal in the intes tinal wall; only half of this is reduced to retinol and utilized. 

 Physiological role and actions 

 (a) Visual cycle Retinal generated by revers ible oxidation of retinol is a component of the light sensitive pigment Rhodopsin which is synthesized by rods during dark adaptation. This pigment gets bleached and split into its compo nents by dim light and in the process generates a nerve impulse through a Gprotein called Transducin. Retinal so released is reutilized. A similar pigment (Iodopsin) is synthesized in the cones— responsible for vision in bright light, colour vision and primary dark adaptation. In vit. A deficiency rods are affected more than cones; irreversible structural changes with permanent night blindness occur if the deprivation is longterm. 

 (b) Epithelial tissue Vit. A promotes differentiation and maintains structural integrity of epithelia all over the body. It also promotes mucus secretion, inhibits kerati nization and improves resistance to infection. It appears to have the ability to retard development of malignancies of epithelial structures. Vit A is also required for bone growth. 

 (c) Reproduction Retinol is needed for mainte nance of spermatogenesis and foetal development.

 (d) Immunity Increased susceptibility to infec tion occurs in vit A deficiency. Physiological amount of vit A appears to be required for proper antibody response, normal lym phocyte prolife ration and killer cell function.

Deficiency symptoms Since 

vit. A is stored in liver, deficiency symptoms appear only after long-term deprivation, but vit A deficiency is quite prevalent, especially among infants and children in developing countries. Manifesta tions are: 

 • Xerosis (dryness) of eye, ‘Bitot’s spots’, kerato malacia (softening of cornea), corneal opa cities, night blindness (nyctalopia) pro gressing to total blindness. 

 • Dry and rough skin with papules (phryno derma), hyperkeratinization, atrophy of sweat glands. 

 • Keratinization of bronchopulmonary epithe lium, increased susceptibility to infection. 

 • Unhealthy gastrointestinal mucosa, diarrhoea. 

 • Increased tendency to urinary stone formation due to shedding of ureteric epithelial lining which acts as a nidus. 

 • Sterility due to faulty spermatogenesis, abor tions, foetal malformations. • Growth retardation, impairment of special senses.

Therapeutic uses

 1. Prophylaxis of vit A deficiency during infancy, pregnancy, lactation, hepatobiliary diseases, steatorrhoea: 3000–5000 IU/day.

 2. Treatment of established vit A deficiency: 50,000–100,000 IU i.m or orally for 1–3 days followed by intermittent supplemental doses. 

 3. Skin diseases like acne, psoriasis, ichthyosis. Retinoic acid (see below) and 2nd or 3rd generation retinoids are used.

 Interactions  

 • Vit E promotes storage and utilization of retinol and decreases its toxicity. 

 • Regular use of liquid paraffin by carrying through with it vit A can result in deficiency. 

 • Longterm oral neomycin induces steator rhoea and interferes with vit A absorption.

 Hypervitaminosis A Regular ingestion of gross excess of retinol (100,000 IU daily for  months) has produced toxicity—nausea, vomit ing, itch ing, erythema, dermatitis, exfoliation, hair loss, bone and joint pains, loss of appetite, irritability, bleeding, increased intracranial ten sion and chronic liver disease. Excess retinol is also tera togenic in animals and man. Daily intake should not exceed 20,000 IU.

Retinoic acid (vit A acid) 

Retinoic acid has vit A activity in epithelial tissues and promotes growth, but is inactive in eye and reproductive organs. All trans retinoic acid (Tretinoin) is used topically, while 13cis retinoic acid (Isotretinoin) is given orally for acne (see Ch. 66). Unlike retinol, it is not stored but rapidly metabolized and excreted in bile and urine. The cellular retinoic acid binding protein (CRABP) is different from CRBP, is present in skin and other tissues but not in retina—this may be the reason for the inability of retinoic acid to participate in visual cycle. 

 Retinoid receptors

 Retinol and retinoic acid act through nuclear retinoid receptors which function in a manner analogous to the steroid receptors. Their activation results in modulation of protein synthesis. In the target cells (epi thelial, gonadal, fibroblast) synthesis of certain proteins is enhanced while that of other proteins is depressed—accounting for the structural and functional changes. Two distinct families of retinoid receptors, viz. Retinoic acid receptors (RARs) and Retinoid X receptors (RXRs) have been identified with differing affinities for dif ferent retinoids.

 VITAMIN E

Chemistry and source

 A number of toco pherols, of which α tocopherol is the most abundant and potent, have vit E activity. The disomer is more potent than l isomer. Wheat germ oil is the richest source, others are cereals, nuts, spinach and egg yolk. 

 1 mg of d αtocopherol is called αtocopherol equivalent = 1.49 IU of vit E. The daily requirement of vit. E is estimated at 10 mg. It is increased by high intake of polyunsaturated fats.

 Absorption and fate Vit. E is absorbed from intestine through lymph with the help of bile; it circulates in plasma in association with βlipoprotein, is stored in tissues and excreted slowly in bile and urine as metabolites.

 Physiological role and actions

 Vit E acts as anti oxidant, protecting unsaturated lipids in cell membranes, coenzyme Q, etc. from free radical oxidation damage and curbing generation of toxic peroxidation products. Feeding animals with polyunsaturated fats increases vit E require ment, while antioxidants like cystein, methionine, selenium, chromenols prevent some vit E deficiency symptoms in animals. However, vit E might be having some more specific action or a structural role in biological membranes, because other deficiency symptoms are not relieved by these unrelated antioxidants.

 Deficiency symptoms Experimental vit E defi ciency in animals produces recurrent abortion, degenerative changes in spinal cord, skeletal muscles and heart, and haemolytic anaemia. No clear-cut vit E deficiency syn drome has been described in humans, but vit E deficiency has been implicated in certain neuromuscular diseases in children, neurologi cal defects in hepatobiliary disease and some cases of haemolytic anaemia. 

 Therapeutic uses 

 1. Primary vit E deficiency does not occur clini cally. Supplemental doses (10–30 mg/ day) may be given to patients at risk (see above). 

 2. G-6-PD deficiency—prolonged treatment with 100 mg/day increases survival time of erythrocytes. 

 3. Acanthocytosis—100 mg /week i.m: norma lizes oxidative fragility of erythrocytes. 4. The risk of retrolental fibroplasia in premature infants exposed to high oxygen concentra tions can be reduced by 100 mg/kg/day oral vitamin E. 5. Alongwith vit A to enhance its absorption and storage, and in hypervitaminosis A to reduce its toxicity. 6. Large doses (400–600 mg/day) have been reported to afford symptomatic improvement in intermittent claudication, fibrocystic breast disease and nocturnal muscle cramps.

For its antioxidant property, vit E has been promoted for recurrent abortion, sterility, menopausal syndrome, toxaemia of pregnancy, atherosclerosis, ischaemic heart disease, cancer prevention, several skin diseases, prevention of neurodegenerative disorders, postherpetic neu ra lgia, scleroderma and many other con ditions, but without convincing evidence of benefit.

 Toxicity Even large doses of vit E for long periods have not produced any significant toxic ity, but creatinuria and impaired wound healing have been reported; abdominal cramps, loose motions and lethargy have been described as side effects of vit. E. Vit E can interfere with iron therapy.

Antioxidant vitamins (vit E, β carotene, vit C) in prevention of cardiovascular disease and cancer

Antioxidants are believed to quench free radicals. Free radicals are atoms or molecules with ‘singlet’, i.e. unpaired electron which makes them highly reactive. Oxidative free radicals are generated by metabolic reactions, and create a chain reaction leading to membrane lipid peroxidation, DNA damage, etc. Free radical oxidation has been implicated in atherosclerosis (oxidized LDL is more atherogenic), cancers, neurodegenerative diseases and inflammatory bowel diseases. Many endogenous and dietary compounds like super oxide dismutase, ferritin, transferrin, ceruloplasmin, α tocopherol, β carotene and ascorbic acid have antioxidant and free radical scavenging properties. On this theoretical basis supported by some epidemiological 

observations, cohort studies and prospective trials β carotene, vit C and especially vit E have been claimed to protect against atherosclerosis leading to coronary artery disease as well as many types of cancers (lung, breast, mouth, skin, esophagus, stomach, etc.). As a result, vit E and others are being aggressively promoted and many physicians are prescribing them for prophylaxis of these conditions. Learning from mass media, people on their own also are consuming antioxidants on a large scale. However, the evidence of a beneficial effect is highly equivocal. Several large observational studies (involv ing tens of thousands of subjects) and their meta analysis have failed to demonstrate any benefit of antioxidant vitamins in terms of cardiovascular event/cancer prevention in well nourished population. On the other hand, there is some indication of increased risk of CHF with >400 mg/day α tocopherol and increased risk of hip fracture among postmenopausal women with high dose of vit A. Therefore, it would be well advised to adopt a healthy lifestyle, viz. eating sufficient fruits and vegetables, doing regular exercise, avoiding overweight and smoking, rather than consuming antioxidant medications. A large number of antioxidant proprietary preparations (ANTOXID, CAROFIT, GLACE, VITOXID, REVOX, CARNITOR, CARNIVIT-E, etc.) containing widely variable amounts of βcarotene, vit A acetate, vit E, vit C, selenium, zinc, copper, manganese, carnitine (a substance synthesized in liver and kidney, and involved in intracel lular transport of longchain fatty acids) are briskly promoted and consumed, but with no credible evidence of benefit, and may be some potential harm.