Presented by: Ashok ku. singh Pharm.D

CHITKARA UNIVERSITYDepartment of Pharmacy PracticeChitkara College of Pharmacy

DISORDER OF VITAMINS

Vitamins are organic substances which cannot be synthesised within the body and are

essential for maintenance of normal structure and function of cells. Thus, these substances

must be provided in the human diet. Most of the vitamins are of plant or animal origin so

that they normally enter the body as constituents of ingested plant food or animal food.

They are required in minute amounts in contrast to the relatively large amounts of essential

amino acids and fatty acids. Vitamins do not play any part in production of energy.

ETIOLOGY OF VITAMIN DEFICIENCIES : In the developing countries, multiple deficiencies of vitamins and other nutrients are common

due to generalised malnutrition of dietary origin. Chronic alcoholism is a common denominator

in many of vitamin deficiencies. A few other noteworthy features about vitamins are as under:

1. While both vitamin deficiency and excess may occur from another disease, the states of

excess and deficiency themselves also cause disease.

2. 2. Vitamins in high dose can be used as drugs.

CLASSIFICATION OF VITAMINS : Vitamins are conventionally divided into 2 groups:

a) Fat-soluble and

b) water-soluble.

a) Fat-soluble vitamins :There are 4 fat-soluble vitamins: A, D, E and K. They are absorbed from intestine in the

presence of bile salts and intact pancreatic function. Their deficiencies occur more readily

due to conditioning factors (secondary deficiency). Beside the deficiency syndromes of these

vitamins, a state of hypervitaminosis due to excess of vitamin A and D also occurs.

b) Water-soluble vitamins. This group conventionally consists of vitamin C and members of B complex group. Besides,

choline, biotin and flavonoids are new additions to this group. Water-soluble vitamins are

more readily absorbed from small intestine. Deficiency of these vitamins is mainly due to

primary (dietary) factors. Being water soluble, these vitamins are more easily lost due to

cooking or processing of food.

FAT-SOLUBLE VITAMINS :

a) Vitamin A (Retinol)

PHYSIOLOGY ::Vitamin A or retinol is a fat-soluble alcohol. It is available in diet in 2 forms: As preformed

retinol, the dietary sources of which are animal-derived foods such as yolk of eggs, butter,

whole milk, fish, liver, kidney . Retinol is stored in the liver cells and released for transport to

peripheral tissues after binding to retinol-binding protein found in blood .

LESIONS IN VITAMIN A DEFICIENCY: Nutritional deficiency of vitamin A is common in countries of South-East Asia, Africa,

Central and South America whereas malabsorption syndrome may account for conditioned

vitamin A deficiency in developed countries.

The physiologic functions of retinol are as follows:

a) Maintenance of normal vision in reduced light.

b) Maintenance of structure and function of specialised epithelium.

c) Maintenance of normal cartilaginous and bone growth.

d) Increased immunity against infections in children.

e) . Anti-proliferative effect.

Vitamin D (Calcitriol)

PHYSIOLOGY :This fat-soluble vitamin exists in 2 activated sterol forms:

Vitamin D2 or calciferol; and Vitamin D3 or cholecalciferol.

The material originally described as vitamin D1 was subsequently found to be impure

mixture of sterols. Since vitamin D2 and D3 have similar metabolism and functions, they are

therefore referred to as vitamin D.

There are 2 main sources of vitamin D:

i) Endogenous synthesis. 80% of body’s need of vitamin D is met by endogenous synthesis

from the action of ultraviolet light on 7-dehydrocholesterol widely distributed in oily

secretions of the skin. The vitamin so formed by irradiation enters the body directly through

the skin. Pigmentation of the skin reduces the beneficial effects of ultraviolet light.

. ii) Exogenous sources : The other source of vitamin D is diet such as deep sea

fish, fish oil, eggs, butter, milk, some plants and grains.

Irrespective of the source of vitamin D, it must be converted to its active metabolites

LESIONS IN VITAMIN D DEFICIENCY : Deficiency of vitamin D may result from:

i) reduced endogenous synthesis due to inadequate exposure to sunlight;

ii) dietary deficiency of vitamin D;

iii) malabsorption of lipids due to lack of bile salts such as in intrahepatic biliary obstruction,

pancreatic insufficiency and malabsorption syndrome;

iv) derangements of vitamin D metabolism as occur in kidney disorders (chronic renal

failure, nephrotic syndrome, uraemia), liver disorders and genetic disorders; and

v) resistance of end-organ to respond to vitamin D.

Vitamin E (αα αα α-Tocopherol)

PHYSIOLOGY :Out of many naturally-occurring tocoferols and tocotrienols, α-tocopherol is biologically the

most active fat soluble compound for humans. Vitamin E is found in most of the ordinary

foods such as vegetables, grains, nuts and oils. It is absorbed from the intestine and

transported in blood in the form of chylomicrons. It is stored in fat depots, liver and muscle .

The main physiologic functions of vitamin E are as under:

1. Anti-oxidant activity

2. . Scavenger of free radicals

3. Inhibits prostaglandin synthesis

4. Activates protein kinase C and phospholipase A2.

LESIONS IN VITAMIN E DEFICIENCY: The deficiency of vitamin E is mainly by conditioning disorders affecting its absorption and

transport such as abetalipoproteinaemia, intra- and extrahepatic biliary cholestasis, cystic

fibrosis of the pancreas and malabsorption syndrome. Low birth weight neonates, due to

physiologic immaturity of the liver and bowel, may also develop vitamin E deficiency .

Lesions of vitamin E deficiency are as follows:

1. Neurons with long axons develop degeneration in the posterior columns of spinal cord.

2. Peripheral nerves may also develop myelin degeneration in the axons.

3. Skeletal muscles may develop denervation.

4. Retinal pigmentary degeneration may occur.

5. Red blood cells deficient in vitamin E such as in premature infants have reduced lifespan.

6. In experimental animals, vitamin E deficiency can produce sterility in both male and female

animals.

Vitamin K

PHYSIOLOGY : Vitamin K (K for Koagulations in Danish) exists in nature in 2 forms:

Vitamin K1 or phylloquinone, obtained from exogenous dietary sources such as most green

leafy vegetables; and

Vitamin K2 or menaquinone, produced endogenously by normal intestinal flora.

Phylloquinone can be converted into menaquinone in some organs.

The main physiologic function of vitamin K is in hepatic microsomal carboxylation reaction for

vitamin K dependent coagulation factors

LESIONS IN VITAMIN K DEFICIENCY :

Since vitamin K is necessary for the manufacture of prothrombin, its deficiency leads of

hypoprothrombinaemia . Estimation of plasma prothrombin, thus,

affords a simple in vitro test for determining whether there is deficiency of vitamin K. The

conditions which may bring about vitamin K deficiency are as follows:

1. Haemorrhagic disease of newborn

2. Biliary obstruction

3. Due to malabsorption syndrome

4. Due to anticoagulant therapy

5. Due to antibiotic therapy

6. Diffuse liver disease.

WATER-SOLUBLE VITAMINS

Vitamin C (Ascorbic Acid)

PHYSIOLOGY :Vitamin C exists in natural sources as L-ascorbic acid closely related to glucose. The major

sources of vitamin C are citrus fruits such as orange, lemon, grape fruit and some fresh

vegetables like tomatoes and potatoes. It is present in small amounts in meat and milk. The

vitamin is easily destroyed by heating so that boiled or pasteurised milk may lack vitamin C.

It is readily absorbed from the small intestine and is stored in many tissues, most abundantly

in adrenal cortex. The physiologic functions of vitamin C are due to its ability to carry out

oxidation-reduction reactions:

L-Ascorbic Acid Dehydro L-Ascorbic acid + 2H+ + 2e

LESIONS IN VITAMIN C DEFICIENCY :Vitamin C deficiency in the food or as a conditioned deficiency results in scurvy. The

lesions and clinical manifestations of scurvy are seen more commonly at two peak ages: in

early childhood and in the very aged. These are as under :

1. Haemorrhagic diathesis

2. Skeletal lesions

3. Delayed wound healing

4. Anaemia

5. Lesions in teeth and gums

6. Skin rash

VITAMIN B COMPLEX The term vitamin B was originally coined for a substance capable of curing beriberi (B from

beriberi). Now, vitamin B complex is commonly used for a group of essential compounds

which are biochemically unrelated but occur together in certain foods such as green leafy

vegetables, cereals, yeast, liver and milk .

The principal members of vitamin B complex are thiamine (vitamin B1), riboflavin (vitamin

B2), niacin/nicotinic acid (vitamin B3), pantothenic acid (vitamin B5), pyridoxine (vitamin

B6), folate (folic acid), cyanocobalamin (vitamin B12) and biotin. There is no definite

evidence that any clinical disorder results from deficiency of pantothenic acid (vitamin B5).

METALS AND TRACE ELEMENTSSeveral minerals in trace amounts are essential for health since they form components of

enzymes and cofactors for metabolic functions. Besides calcium and phosphorus required for

vitamin D manufacture, others include: iron, copper, iodine, zinc, selenium, manganese,

nickel, chromium, molybdenum, fluorine. However, out of these, the dietary deficiency of first

five trace elements is associated with deficiency states which are discussed in detail in

respective chapters later. These are as under

: i) Iron: Microcytic hypochromic anaemia.

ii) Calcium: reduced bone mass, osteoporosis.

iii) Phosphorous: Rickets, osteomalacia.

iv) Copper: Muscle weakness, neurologic defect, anaemia, growth retardation.

iv) Copper: Muscle weakness, neurologic defect, anaemia, growth retardation.

v) Iodine: Goitre and hyperthyroidism, cretinism.

vi) Zinc: Growth retardation, infertility, alopecia.

vii)Selenium: Cardiomyopathy, muscle degeneration.

viii) Fluoride: Dental caries.

ix) Manganese: Impaired growth and skeletal development.

x) Molybdenum: Severe neurological abnormalities

DIET AND CANCERBefore closing the discussion of nutritional pathology, it is worthwhile to sum up relationship of

these factors to carcinogenesis discussed in previoius chapter. There are three possible

mechanisms on which the story of this relationship can be built up:

1. Dietary content of exogenous carcinogens:

i) The most important example in this mechanism comes from naturally-occurring carcinogen

aflatoxin which is strongly associated with high incidence of hepatocellular carcinoma in those

consuming grain contaminated with mould, Aspergillus flavus.

ii) Artificial sweeteners (e.g. saccharine cyclomates), food additives and pesticide contamination

of food are implicated as carcinogens derived from diet.

2. Endogenous synthesis of carcinogens or promoters

i) In the context of etiology of gastric carcinoma, nitrites, nitrates and amines from the

digested food are transformed in the body to carcinogens—nitrosamines and nitrosamides.

ii) In the etiology of colon cancer, low fibre intake and high animal-derived fats are

implicated. High fat diet results in rise in the level of bile acids and their intermediate

metabolites produced by intestinal bacteria which act as carcinogens. The low fibre diet, on the

other hand, does not provide adequate protection to the mucosa and reduces the stool bulk and

thus increases the time the stools remain in the colon.

iii) In the etiology of breast cancer, epidemiologic studies have implicated the role of animal

proteins, fats and obesity with as yet unsubstantiated evidence.

3. Inadequate protective factors: As already mentioned, some components of diet such as

vitamin C, A, E, selenium, and β -carotenes have protective role against cancer. These

substances in normal amounts in the body act as antioxidants and protect the cells against

free radical injury but their role of supplementation in diet as prevention against cancer is

unproven.