Vitamins

Vitamins are a group of organic substances essential in small quantities for normal metabolism. They are found in minute amounts in natural foodstuffs are sometimes produced synthetically. Deficiencies of vitamins cause specific diseases disorders.

A. Characteristics:Two characteristics mark a compound to be assigned as a vitamin:

  1. It must be a vital organic dietary substance, which is neither a carbohydrate, fat, mineral nor protein, but is necessary in very small quantities to the performance of particular metabolic functions or to the prevention of an associated deficiency disease.
  2. It cannot be manufactured by the body therefore must be supplied in food.

B. Megavitamin Therapy: is the excessive intake of multivitamins to overcome a deficiency in daily requirements. Vitamins in excess of body needs will be excreted.

C. Classification of Vitamins:Vitamins are usually grouped according to their solubility:

  1. The fat-soluble group includes vitamins A, D, E & K.
  2. The water-soluble group includes vitamin C the BComplex vitamins.

I. Fat Soluble Vitamins

Absorption of fat soluble vitamins depends upon:

  • Presence of fats in the GIT.
  • Hepatic function.
  • Bile contents.

A. VitaminA (Retinol):Vitamin A is an alcohol because it has a specific function in the retina of the eye, it has been given the name Retinol. However, it is still commonly referred to as vitamin A. -carotene (pro-vitamin A) is the precursor of vitamin A.

-carotene metabolism Retinol (Vitamin A) metabolism 11-cis-retinol

RhodopsinIodopsin

(Retinal rod cell pigmentation)(Retinal cone cell pigmentation)

It is photosensitive & essential

for dark adaptation

1. Physiologic functions of vitamin A:

  • Vision: Vitamin A is necessary for the proper functioning of some inner parts of the eye that are concerned with night vision.
  • Epithelial Tissue:Vitamin A has an important role in the formation maintenance of healthy, functioning epithelial tissue, the body's 1ry barrier to infections.
  • Growth: It has been observed that vitamin A deficiency is associated with retarded growth (mechanism unknown).Vitamin A is essential for the growth of skeletal, soft tissues, bones teeth.

2. Hypovitaminosis “A”: A deficiency in vitamin A may occur for 3 basic reasons:

  • Inadequate dietary intake.
  • Poor absorption.
  • Inadequate conversion of carotene (liver orintestinal disease).

This deficiency can lead to:

  • Night blindness: a condition known as nyctalopia.
  • Xerophthalmia
  • Keratinization of epithelial cells of the cornea of the eye.
  • Keratinization of epithelial cells, these become dry, flat, & gradually harden to form scales that will peel off; leading to infection.
  • Loss of appetite.

3. Hypervitaminosis “A”: Vitamins are substances required in small amounts, too much of some vitamins can be dangerous. Since the liver has a great storage capacity for vitamin A, megadoses of this vitamin are toxic. Hypervitaminosis A is manifested by: joint pain, thickening of long bones, loss of hair, jaundice.

In children: hyperstoses (bone hypertrophy)

In adults & children:

  • Peeling of skin
  • Headache
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  • Lymph node enlargement
  • Nystagmus

4. Food sources of vitamin A:

  • Animal sources: fishliver oil, liver, kidney, milk, butter egg yolk,
  • Plant sources: are the yellow green vegetables fruit sources of carotene; e.g. carrots, sweet potatoes, apricots, spinach & cabbage.

5. Uses of vitamin A:

  • Psoriasis.
  • Acne vulgaris.
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  • Ichllryosis (dark area on the skin)
  • Night blindness.

6. Daily requirements:Vitamin A can be taken orally or IM.

  • Daily requirements in children: 1300 IU – 2600 IU
  • Daily requirements in adults: 3000 IU

Any preparation containing vitamin A should contain not less than 1,600 IU for adults and 1,000 IU for children. Additionally, it should not exceed 10,000 IU.

One IU vitamin A = the biological activity of 0.3 g of retinol or 0.6 g of carotene.

Zinc (Zn) 8-9 mg/day is essential for:

  • Maintenance of vitamin A in plasma.
  • Mobilization of vitamin A from the liver.

Administration of a small amount of vitamin E with vitamin A will increase the absorption & tissue storage of vitamin A, & protect against the oxidation of vitamin A (available as vitamin A+E).

Vitamin A does not pass the placenta.

B. Vitamin D (Calciferol):Vitamin D is unique among the vitamins in two respects:

  • It occurs naturally in only a few common foods(mainly fish oil a little in egg milk).
  • It can be formed in the body by exposure of the skin to UV rays either from the sun or a lamp.

7-hydroxy ergosterol UV / activation in the liverCholicalciferol (vitamin D3) (natural)

ErgosterolUVCalciferol (vitamin D2) (synthetic)

Cholicalciferol is 100 times as active as ergocalciferol.

1. Physiologic function of vitamin D:Vitamin D has hormonelike (para-hormone) functions closely inter-balanced with the parathyroid hormone in calcium phosphorus metabolism.

  • Absorption of calcium phosphorus from the small intestine.
  • Calcification: Vitamin D works with calcium phosphorus in the calcification aspect of bone formation. It increases the mobilization of Ca++ from blood to bones.
  • Increases tubular reabsorption of Ca++.

2. Hypovitaminosis "'D": can happen due to inadequate exposure to sunlight (UV) &/or dietary deficiency. This can lead to:

  • Rickets (in children): a disease directly related to impaired metabolism of Ca & P, due to vitamin D deficiency. Characteristic clinical manifestations of rickets result from failure of calcification of growing bones. Several deformities of bones develop e.g. softening of cranial bones, bowed thighs & knockknees.
  • Osteomalacia (soft bones): in adults.
  • Hypo-parathyrodism:in adults.

3. Hypervitaminosis "'D":ingestion of excessive quantities of vitamin D can produce toxicity. Symptoms of vitamin D toxicity are:

  • Calcification of soft tissues such as lungs & kidney (kidney stones).
  • Hyper-calcemia (increased Ca++ levels in blood).

  • Bone fragility.
  • Increased digitalis toxicity.
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  • Mental retardation.
  • MI.

4. Food sources of vitamin "D": The 2 basic food sources are yeast fish liver oils. The main food sources are those to which vitamin Dhas been added or produced by irradiation, especially milk.

Vitamin D is completely absorbed from the GIT. Absorption depends on hepatic & biliary functions. Drugs that increase hepatic microsomal enzymes (anti-coagulants, barbiturates, rifampicin & anti-depressants) lead to increased elimination of vitamin D and may cause its deficiency.

5. Uses of vitamin D:

  • Anti-rickettic:in children (it promotes calcification of organic matrix of bone structure).
  • Treatment of hypo-parathyrodism.

6. Daily requirements:400 IU / day.

One IU vitamin D = 0.025 g vitamin D2.

Lasix (frusemide) is contraindicated in vitamin D deficiency as lasix itself is a hypo-calcemic agent.

C. Vitamin E (-Tocopherol):is known as the antisterility vitamin, but it has been demonstrated to have this effect only in the rat not in man.

1. Physiologic function of vitamin E:because of its reducing properties,Vitamin E protects the body against peroxides that can destroy capillary walls & RBCs; it has several physiologic functions including:

  • Anemia: The evidence of the role of vitamin E in erythrocyte protection has led to further inquiry into possible relationship between this vitamin blood disorders.
  • Muscular System: Vitamin E plays a role in the normal development of muscles.
  • Vascular System: Vitamin E is necessary for normal resistance of erythrocytes to hemolysis.

2. Hypovitaminosis “E”:

  • Deficiency anemia.
  • Muscular dystrophy.
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  • Male sterility.
  • Habitual abortions in females.

3. Hypervitaminosis “E”: Vitamin E is a safe drug that can be given in large doses.

4. Food sources of vitamin E:Richest sources are vegetables seed oils. Others: milk, eggs, meat, fish.

5. Uses of vitamin E: Vitamin E is used to increases absorption of vitamin A. Additionally, because of its reducing properties, it is used in commercial products (oily solutions) to prevent spoilage, & is added to therapeutic forms of vitamin A to prevent oxidation.

6. Daily requirements:5 – 10 IU

Vitamin E is carried in the plasma by -lipoproteins. It is incompatible with minerals e.g. Fe3+ & Ca2+

D. Vitamin K:is a group of fat-soluble vitamins that promote blood clotting. It is synthesized by the normal intestinal bacteria so that an adequate supply is generally present.

It is a naphtoquinon derivative that exists in 3 forms:

  • Vitamin K1 (phytoquinon):of plant origin.
  • Vitamin K2 (menaquinon):of bacterial origin (in the GIT).
  • Vitamin K3 (menadion):Synthetic, waer soluble (inactive).

1. Physiologic functions of vitamin K:The major function of vitamin K is to increase the hepatic synthesis of prothrombin. Prothrombin is an essential factor in blood coagulation.

2. Hypovitaminosis “K”:

  • Rarely occurs is manifested by increased prothrombin time, and hemorrhagic tendencies.
  • Excessive use of oral antibiotics can inhibit the normal GIT flora responsible for synthesis of vitamin K and might lead to its deficiency.

3. Hypervitaminosis “K”:

  • In infants: hemorrhagic anemia, kernicterus, & increased bilirubin.
  • In adults: decreased liver functions leading to jaundice.
  • Caumarine (dicaumarol) is the antidote for vitamin K toxicity.

4. Food sources of vitamin K:Green leafy vegetables (cabbage, spinach), cheese, egg yolk liver.

5. Daily requirements:No requirement for vitamin K is stated sinceadequate amount is usually ensured through intestinal bacteria the body requires vitamin K in very small amounts.

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II. Water Soluble Vitamins

A. Vitamin C (Ascorbic Acid):

1. Physiological functions of vitamin C:

  • Building maintaining bone matrix, cartilage, collagen connective tissue. Its deficiency has long been associated with the hemorrhagic disease "'Scurvy".
  • Vitamin C helps in the absorption of iron from the GIT.
  • It is important in oxidation – reduction (redox) reactions in the body & for cellular respiration.

2. Deficiency of vitamin C:Scurvy is the nutritional disease associated directly with vitamin C deficiency. Tissue deterioration changes of hemorrhagic origin take place. The skin becomes dry, rough has a brown color. Hemorrhages occur in the gums, muscle tissue & in the cavities of joints, causing infants in particular to lie, in the “pithed frog” position. Lesions in teeth, bones & blood vessels.

3. Vitamin C toxicity:

  • Increased stone formation in the urinary tract.
  • Diarrhea
  • Ingestion of 10 gm daily of vitamin C followed by rapid withdrawal causes frank symptoms of scurvy. Similarly, scurvy develops in newborns to mothers who suddenly stop ingesting large daily doses of vitamin C.

4. Food sources of vitamin C:Citrus fruits tomatoes are well known sources of vitamin C.Other sources include cabbage, potatoes as well as green yellow vegetables.

5. Uses of vitamin C

  • Wound healing: The important role of vitamin C in cementing supportive tissue makes it an important agent in wound healing. This has evident importance for vitamin C therapy in surgery or burns especially where extensive tissue regeneration is involved.
  • Fevers & infections: infections, especially bacterial infections, decrease tissue stores of vitamin C, additional intake is required to help maintain resistance to infection.
  • Reaction to Stress: Any body stress such as fracture, general illness shock requires vitamin C.
  • Treatment of mega-hemoglobinemia: because of its reducing properties.
  • Antidote for alcohol overdosage: as it activates the alcohol dehydrogenase enzyme which is essential for alcohol metabolism.

6. Daily requirements:

  • Children: > 20 mg / day
  • Adults:> 150 mg / day

Women have higher vitamin C levels than men.

Smoking reduces vitamin C levels in blood.

Vitamin C (like other reducing agents e.g. ampicillins) gives false positive results with clintest. The test depends on the reduction of CuSO4 by glucose in urine. Thus, the testape method can be used instead.

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B. Vitamin B1 (Thiamine): is the anti-beriberi factor & is an essential co-enzyme in carbohydrate metabolism (2 carbo atom metabolism, getting rid of pyruvic acid). If Thiamine is not present in sufficient amounts, clinical effects will be reflected in the GI, CV, & nervous system.

1. Deficiency of vitamin B1:causes beriberi. The disease results from the consumption of white wheat, polished rice & alcoholics. The 2 general types of beriberi are infantile adult. It is characterized by convulsive disorders, respiratory difficulties & GI problems (constipation & vomiting). Symptoms include:

  • Peripheral neuritis
  • Mental disorders
  • Fatigue
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  • Decreased conc. of HCl
  • Tachycardia
  • Cardiac hypertrophy
/
  • Cardiac failure

2. Toxicity of vitamin B1: because vitamin B1 is very safe, toxicity is not marked.

3. Food sources of thiamine:beef, liver, whole or enriched grains, bran, yeast, eggs fish. However, vitamin B1 is thermolabile.

4. Uses of vitamin B1: Vitamin B1 is useful in the treatment of

  • Beriberi.
  • Peripheral neuritis in diabetic patients.
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  • Neuralgia (nerve inflammation).
  • Mental disorders.

Vitamin B1 may be administered orally, or by subcutaneous or IM injection.

5. Daily requirements:

  • Adults:> 0.6 mg (4.5 mg)
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  • Children:> 0.4 mg

C. Vitamin B2 (Riboflavin): is a yellowgreen fluorescent pigment that is found in milk. It is an important factor in protein metabolism (it acts as a proton carrier).

1. Vitamin B2deficiency:

  • Riboflavin deficiency chiefly causes tissue inflammation breakdown.
  • Wounds become easily aggravated.
  • Lips nose crack easily (chelosis – cracks in the corner of the mouth)
  • Glossitis (inflammation of the tongue)
  • Seborrheic dermatitis (scaly, greasy eruption of the skin), Keratitis
  • Photophobia due to corneal vascularization.
  • Toxicity of the embryo in pregnants.
  • Riboflavin deficiencies seldom occur alone, they are especially likely to occur in conjunction with deficiencies of other B vitamins & protein.

2. Food sources of riboflavin:Most important food sources are milk. Other good sources are liver, kidney some vegetables. It is absorbed from the upper GIT.

3. Daily requirements:

  • Adults:> 1 mg
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  • Children:> 0.6 mg

Vitamin B1 may be administered orally, or by subcutaneous or IM injection. It is never given alone but rather in combination with other B vitamins.

D. Vitamin B3 (Niacin, Nicotinic Acid)

  • Vitamin B3 occurs either as Nicotinic acid or Nicotinamide.

Nicotinic acidNicotinamide

1. Physiological functions of vitamin B3:

  • Niacin is an important factorin the metabolism of proteins, fats glucose. It acts as a H+ carrier co-enzyme and for the production of ATP (in the respiratory chain).
  • Niacin and riboflavin are closely interrelated in cell metabolism. And if one of these vitamins is deficient, the other is usually deficient as well.

2. Vitamin B3 deficiency:

  • The disease associated with niacin deficiency is “pellagra” which is characterized by a typical dermatitis & often has fatal effects on the nervous system.
  • The deficiency is manifested as:
  • Weakness, lassitude,
  • GIT effects including anorexia & indigestion.
  • If deficiency continues, the skin nervous system will be affected. The skin areas exposed to sunlight develop a dark, scaly dermatitis (photosensitivity). Neuritis, confusion, apathy, schizophrenia disorientation also develop.

3. Vitamin B3toxicity:

  • Flushing
  • Vasodilatation
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  • Hepatotoxicity
  • GIT irritation & ulceration

Other side effects of vitamin B3 include:

  • Hyperuricemia
  • Glucose intolerance (hyperglycemia)

4. Uses of vitamin B3:

  • Treatment of pellagra.
  • Nicotinic acid (but not nicotinamide) in doses of > 3 gm / day, is hypocholesterolemic.

5. Food sources of niacin:Meat is the major source of niacin.Peanuts, beans peas are good sources.

6. Daily requirements:

  • Adults:> 6 mg – 45 mg
  • Children:> 4 mg

60 mg of tryptophan = 1 mg of nicotinic acid (niacine).

N.B: When vasodilatation is contraindicated we can use nicotinamide instead of nicotinic acid.

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E. Vitamin B6(Pyridoxine):

1. Physiological functions of vitamin B6:

  • Vitamin B6acts as a coenzyme in protein (amino acid) metabolism (in decarboxylation & transamination).
  • It is essential for the production of GABA (gamma-amino-butyric-acid) in the brain which is the main neurotransmitter inhibitor to prevent convulsions.

Serotonin (5HT) decarboxy. Tryptophan Pyridoxal 6 phosphate coenzymeNicotenic acid

2.Pyridoxine deficiency:Since pyridoxine plays an important role in several metabolic activities, it's deficiency may cause the following problems:

  • Anemia:Hypochromic, microcytic anemia has been observed in several patients even in the presence of high serum iron levels.
  • Central Nervous System Disturbances: epileptic convulsions & peripheral neuritis.
  • PregnancyEstrogen-progesterone Oral Contraceptivesdeplete vitamin B6 & thus require additional vitamin B6.
  • INH, Hydralazine & Penicillamine: decrease the tryptophan metabolism & lead to vitamin B6 deficiency.

3. Food sources of pyridoxine:Yeast, wheat, corn, liver kidney are good sources of vitamin B6.

There is evidence that intestinal bacteria produce this vitamin, but the full extent of this source & the degree to which it is utilized by the body are not yet determined.

N.B:Vitamin B6is contraindicated with L-dopa as it increases its metabolism through increasing the synthesis of the decarboxylase enzyme, which converts L-dopa to dopamine in the peripheral tissues before entering the brain.

Pyridoxal is more stable than pyridoxine.

F. Pantothenic Acid (Panthenol):

  • Pantothenic acid is available in all forms of living things & throughout body tissues.
  • Intestinal bacteria synthesize considerable amounts of pantothenic acid. This, together with its widespread natural occurrence, makes deficiency unlikely.
  • Pantothenic acid plays a vital coenzyme role in overall body metabolism. It is converted to co-enzyme A which is essential for the synthesis of acetylcholine & in fatty acid metabolism.

1. Food sources of pantothenic acid:Yeast, liver kidney are rich sources, followed by egg, especially the yolk, leafy vegetables & skimmed milk.

2. Uses of pantothenic acid:

  • It is used locally to aid wound healing.
  • It can be given IM to aid motility of the intestine after surgical operations i.e. to guard against post-operative paralytic ileus.

G. Vitamin B12(Cyanocobolamin):In 1948 vitamin B12 was discovered was shown to have control over the bloodforming defects neurologic problems involved in pernicious anemia.

1. Physiologic function of vitamin B12:

  • Haematopoiesis:A well-established role of vitamin B12 is it participation in the formation of RBCs, therefore, in the control of pernicious anemia.
  • Maintenance of the myelin sheath of the nervous tissue: its deficiency leads to neurologic signs.
  • Production & normal growth of epithelial cells: in the GIT mucosa, cervix, vagina & tongue.

2. Deficiency of vitamin B12:Leads to perinaceous anemia (macrocytic &/or megaloplastic anemia), which affects all highly proliferating cells & is characterized by:

  • RBCs large sized
  • WBCs with polysegmented nucleus
  • Platelets are giant
  • Bone marrow with large cells

3. Uses of vitamin B12:

  • Treatment of perinaceous anemia (Addison’s perinaceous anemia) which is a disease resulting from the vitamin B12deficiency. This deficiency can be either due to low vitamin B12levels, or defective vitamin B12absorption due to deficiency of the GIT intrinsic factor.*Symptoms include peripheral neuritis, gastric mucosal atrophy, glotitis, achlorohydria (lack of HCl secretions), & megaloplastic anemia.
  • The drug of choice for the treatment of perinaceous anemia is vitamin B12given by IM or subcutaneous injection (oral B12 is of no value as it will not be absorbed due to lack of intrinsic factor). Folic acid should not be given as it can mask the symptoms of perinaceous anemia.
  • Vitamin B12injection is available as 100 mg or 1000 mg/ml e.g. depovit (1000 mg B12 + Zn acetate + tannic acid suspension)
  • Sprue:Like folic acid, vitamin B12was effective in treating sprue. However, it seems most effective when used in conjunction with folic acid.

4. Food sources of vitamin B12:Vitamin B12 is supplied almost entirely by animal foods where it is stored in organ meat. The richest sources are liver, kidney, meat, milk, eggs cheese. 1ml of liver extract = 10 mg of vitamin B12.

It is the only nutrient that needs a gastric secretion (intrinsic factor) to be absorbed from the GIT. The intrinsic factor is glycoprotein in nature & is secreted by the parital cells of the stomach (that secrete HCl).

This glycoprotein forms a complex with vitamin B12. The ilial cells take up the formed complex transporting it to the blood where plasma -globine transfer it to cobolamine II.

Intestinal bacteria also synthesizes some vitamin B12 although the amount supplied is not known.

* Shilling test is used to differentiate whether the cause of perinaceous anemia is vitamin B12defficiency or deficiency in both vitamin B12the intrensic factor. Radioactive (Co57 or Co58) vitamin B12is given orally. If perinaceous anemia is due to both (intrensic factor & vitamin B12deficiency) then vitamin B12will not be absorbed & Co appears in the feaces in large amounts. If Co appears in the urine (i.e. vitamin B12was absorbed) then the anemia was due to defficiency in vitamin B12only.