 A few sample chapters

Four sample chapters (Chapter 1, Chapter 3, Chapter 9 and Chapter 13) are enclosed.

CHAPTER 1

Concept of Nutrition, Energy Metabolism and Health

Physiological Consideration of Nutrition

Concept of Nutrition

The basic aim of food (balanced diet) is to provide nutrients in an assimilable form.

Quantities of nutrients should be sufficient to meet the body’s requirements. Body

is nourished by the nutrients. Proper nutrition is a prerequisite for a healthy life.

Active daily living (both indoor and outdoor activities) can be carried out if there is

sufficient nutrition. Lack of nutrients can disturb the functions of cells, tissues,

organs and the body as a whole. Furthermore, one of the nutrients (vitamins) acts as

coenzymes for various metabolic reactions that are essential for function of the

cells. Overnutrition is to be avoided as it may lead to obesity and toxicity.

Excessive intake of vitamin A, calcium, vitamin D, vitamin B3 and iron will have

adverse effects.

Essential nutrients of the diet

Energy Essential Vitamins Minerals Water Choline Carnitine

Sources amino acids
and fatty acids
Carbohydrate Fat Protein

Component of food-nutrients (Table 1.1)

Protein, fat and carbohydrate are called macronutrients as they are needed in

larger amounts and the intake of these three nutrients is larger than that of the other

dietary nutrients. Whereas, vitamins and minerals are called micronutrients as

these nutrients are needed in lesser amounts. Minerals can be further subdivided

into macrominerals and microminerals. If the daily requirement of minerals is

more than 100 mg, they are called macrominerals. If the daily requirement of

minerals is less than 100 mg, they are called microminerals or trace elements. Apart

from macronutrients and micronutrients water, choline and carnitine are considered

as essential nutrients. Water is essential for the survival of all living organisms and

takes part in various metabolic processes. Amount of body water depends on the

balance between water intake and water loss. Normal water intake is about 2.4 L/d

(which includes drinking water/liquid, water from solid and semisolid food and

water from the oxidation of food) and normal water loss at normal body

temperature which is about 2.3 L/d (through urine, feces, sweat, skin and lungs).

Excessive loss of water due to gastroenteritis (vomiting and diarrhea) causes

marked lowering of blood pressure, resulting in hypovolemic shock followed by

coma and even death. On the other hand, high intake of water especially after

administration of ADH causes water intoxication. Swelling of brain cells leads to

convulsion and coma followed by death. Special attention about water intake

should be paid to the infants and lactating mothers. Infants require more water due

to high ratio of surface area to volume. Adequate intake of water for infants should

not be less than 0.7 L/d. Lactating mothers require additional water intake for milk

production. Choline is a lipotropic factor and is synthesized using methyl group

donated by methionine (an essential amino acid). Carnitine is synthesized from

lysine and methionine (essential amino acids) and is essential for oxidation of fatty

acids (chapter 2). Due to defective synthesis of carnitine the body is not able to

utilize fatty acids as fuel.

Insert Table 1.1

Nutritional Requirements (minimum amount of nutrients that are essential for

physio-biochemical functions of the body):

Recommended dietary allowance (RDA) is the average daily amount of a nutrient

required by the body. RDA reflects the standard of good nutrition and ensures the

nutritional requirement of the individual. RDA maintains energy homeostasis. The

RDA of nutrients varies with different age groups, gender, weight, and during

pregnancy and lactation. Tolerable upper intake level (UL) is the maximum

average daily intake of nutrients of an individual. UL may not cause health hazard.

Above UL, the individual may have adverse health effects. Convalescence (gradual
recovery of strength of body after a disease) and growth period require additional

nutrients with high protein diet. Dietary pattern can affect the nutritional

requirements:

(1) Diet poor in vitamin C will impair absorption of iron.

(2) Protein synthesis is impaired due to lack of any essential amino acid in diet.

(3) Prolonged consumption of raw eggs causes biotin deficiency.

(4) Chronic alcoholics will suffer from deficiencies of vitamin B1 and vitamin

B6.

Nutritional and dietary requirements at different age groups and during

pregnancy and lactation

Infants (0-1 year)

The term nutrition is derived from the Latin word “Nutrire” which means to breast-

feed and nurse. Mother’s milk should be preferred than cow’s milk for first 6

months.

Advantages of mother’s milk for infants:

 It is sterile. It contains IgA, lactoferrin and lactoperoxidase. Lactoferrin is a

glycoprotein having antimicrobial activity. Human colostrum contains

maximum amount of lactoferrin followed by mother’s milk and then cow’s

milk. Lactoperoxidase catalyzes the oxidation of a number of substrates. The

oxidized products are antimicrobial and kill bacteria in milk. The low pH of
 mother’s milk also inhibits the growth of pathogens. Thus, mother’s milk

protects infants from infection.

 It protects against allergens. Reduces chances of allergic reactions in infants.

 It reduces mortality rate of infants.

 It contains lactalbumin which is easily digested compared with casein of

cow’s milk. The ratio of lactalbumin and casein in mother’s milk is 2 : 1 and

in cow’s milk is 1 : 3.

 It provides amylase and lipase. Carbohydrates and highly emulsified fat are

better digested preventing abdominal pain in infants.

 It contains high amount of docosahexaenoic acid which improves cognitive

functions as well as development of brain in infants.

 It provides 8.3% linoleic acid, whereas cow’s milk contains 1.6%.

 It provides high amount of nicotinic acid.

Note: Mother must avoid caffeine, alcohol and as far as possible antibiotics as they

are secreted into mother’s milk and could be harmful to infants.

Advantages of breast feeding for mother:

 Breast feeding is an important birth control device. Suckling reflexly through

the hypothalamus stimulates the secretion of prolactin from the anterior

pituitary. Prolactin which stimulates the formation of milk inhibits the

actions of follicle-stimulating hormone (FSH) and luteinizing hormone (LH)

on the ovaries. As a result ovulation is inhibited.

  Risk of breast cancer is less.

 Prolactin stimulates maternal behavior.

Weaning is the gradual period of introducing liquid and semisolid diet to the infant

other than breast milk from 6 months to 1 year. Weaning foods should contain

adequate amount of calories, protein, vitamin C, vitamin D, calcium, phosphorus

and iron for the maintenance of normal skeletal-muscle growth and for the

prevention of anemia. Breast milk contains low amount of the above nutrients.

Marasmus occurs in infants of poor mother below 1 year age. Infants should be

admitted to hospital for food supplement as the mortality rate is very high.

Newborn infants need a prophylactic dose of vitamin K to prevent hemorrhagic

disease. Flours of germinating cereals should be preferred as they contain high

amount of amylase.

Insert Table 1.2

Pre-school children (1-6 years)

 Adequate protein intake is needed as Kwashiorkor generally occurs in

children after 1 year of age if their diet consists mainly of carbohydrates.

 High energy intake is necessary for growth and activity.

 Oral dose of vitamin A should be given below the age of 5 to prevent

blindness.

 Additional amount of calcium, phosphorus and vitamin D is needed as ricket

occurs mostly between the age of 1 and 3 years.

 Excess fat, salt and sugar should be avoided from the beginning to decrease

desire to eat these nutrients.

 The habit of eating a balanced diet should be initiated from the age of 5-6

years.

 Soluble dietary fibers and plenty of fluid are to be started to prevent

constipation.

School Children (6-12 years)

 Continuous growth demands increased calorie intake.

 All the nutrients according to RDA should be taken.

 Nutrients in excess of RDA are not recommended.

 Special care should be considered for bone formation.

 Balanced diet is to be followed. Dietary fibers, plenty of fluids and fruits are

to be consumed.

 Regular exercise must be encouraged.

 Excess salt, sugar, saturated and trans fat should be avoided.

 Fluoridated tooth paste is recommended to prevent dental caries.

Adolescents (8-13 years in girls and 9-14 years in boys)

 Rapid growth needs adequate nutrients.

 Require more protein (about 1.5g/kg/d) compared with adults (about 1.0g/

kg/d) for the maturation of reproductive organs.

 Calcium and vitamin D are needed for building bone density. Dietary fibers,

plenty of fluids and fruits are to be consumed.

Adults (21-59 years)

 Nutritional needs as described under RDA are essential to slow age-related

progressive decline of physiological and cognitive functions.

 Adult females require more iron to compensate loss of blood during

menstruation.

 Daily exercise and active daily living will minimize the progression of life

style related diseases or disorders like Type 2 diabetes, hypertension, obesity

and atherosclerosis.

 Minimize saturated and trans fat (< 10% of total energy).

 Minimize cholesterol-rich diet (< 250 mg/ d).

 Minimize salt intake (< 4 g/d) with more potassium in the diet.

 Quit smoking as it increases synthesis of cholesterol and causes constriction

of coronary artery leading to myocardial infarction.

 Extra calcium and vitamin D are needed to prevent osteomalacia. More

fruits, vegetables and dietary fibers are to be consumed.

Elderly people (60 years and above)

 Low protein intake due to anorexia causes depletion of protein store with

aging. If protein intake is not adequate (not less than 0.8g/kg/d), elderly
 people may suffer from edema and lower resistance to infection. Positive

nitrogen balance should be maintained.

 Extra vitamin D and calcium is needed to prevent osteoporosis and fractures.

 Anti-oxidants are needed to decrease oxidative stress.

 Regular walking or non-strenuous exercise is essential to slow the progess of

aging.

 Saturated fat, trans fat and cholesterol-rich diet must be restricted to prevent

atherosclerosis.

 Soluble dietary fibers with plenty of fluid should be taken to prevent

constipation.

 Apart from RDA certain nutrients may be required in increased amounts due

to defective absorption eg, vitamin B12 and iron to prevent anemia and zinc

for wound healing.

 Tobacco smoking must be avoided as it produces ROS. It increases the

metabolic rate and aggravates insomnia.

 Alcohol consumption must be avoided to prevent loss of cognitive function.

 Stimulants coffee and tea should be avoided before night sleep to prevent

insomnia.

Pregnant women

 Additional requirement of nutrients (more than all age groups) must be

considered for the benefit of fetus. The nutritional requirements of the

 pregnant women for "feeding two" are more than those of non-pregnant

women.

 Sufficient energy is needed for the development of fetus.

 Excessive amount of vitamin A should be avoided as it may be teratogenic.

 More folate is needed to prevent abnormal fetal development.

 Adequate amount of essential fatty acids is needed for the fetal brain

development.

 Inadequate intake of iodine may cause congenital hypothyroidism of infants.

 Regular non-strenuous exercise should be advised.

 Soluble dietary fibers with plenty of fluids should be taken to prevent

constipation.

 Alcohol consumption during pregnancy must be avoided as it may cause

abnormal fetal development.

 Maternal smoking may cause miscarriage and fetal death.

Lactating mother

In lactating mothers, the nutritional requirements are higher than all age groups and

pregnant women. Adequate fluid intake and nutrients are required for the

production of milk. Undernourished mother produces less quantity of milk.

Smoking, alcohol and drugs must be avoided during lactation.

Concept of Energy Metabolism

Energy derived from food. Metabolic Rate.

The metabolism of food converts about 40% of the energy of the food to ATP and

60% of energy is dissipated as heat. Heat cannot be utilized for energy and

increases body temperature. The energy content of food is measured from the heat

released by the total combustion of food in a calorimeter and is calculated in

kilocalorie (kcal) i.e equal to 1000 calories per gram. A calorie (equal to 4.185

Joules) is the amount of heat that raises the temperature of 1gm of water from

14.5˚C to 15.5˚C.

Energy derived from the Macronutrients ("Energy Nutrients")

(kcal/g)

Fats Carbohydrate Protein

9 4 4

Food provides energy which is essential to power all body functions. Normal health

depends on the supply of optimal energy. Energy supply from food is utilized for

the storage of energy, internal heat production and external work. Energy supply is

reduced by energy expenditure of Basal Metabolic Rate (BMR). BMR is defined as

the minimum energy expenditure necessary to carry on the basic physiologic

functions of the body and the vital life processes of the body (heart rate, respiratory

rate ,etc) and to maintain metabolic functions of the tissues when a person is at rest
and is awake. BMR is thus called "metabolic cost of living". The measurement of

BMR is taken at least 12 hours after a meal in a room at a comfortable

thermoneutral temperature (about 25˚C). The subject must be at complete physical

and mental rest (standardized conditions). 1 liter of oxygen consumption used to

oxidize food releases 4.82 kcal. Oxygen consumption (ml per unit time) is

measured by a spirometer (oxygen-filled chamber with a device to absorb carbon

dioxide) and is corrected to standard temperature and pressure. Metabolic rate =

Liter of oxygen consumption per unit time x 4.82 kcal. An adequate diet must

have an energy value sufficient to provide the requirement of basal metabolism.

The BMR of men (about 60 kg) is about 1800 kcal/d and for women (about 50 kg)

is about 1400 kcal/d. Active person (agricultural workers, swimming daily for an

hour, jogging for about one hour, rowing (15 strokes/ min), blacksmith, etc) require

more calories (80-100%) above the BMR. The metabolic rate (total energy

expenditure per unit time) depends on various factors (Table 1.3) and diseases /

disorders (Table 1.4). Causes altering the metabolic rate are listed in Table 1.5.

Insert Table 1.3

Insert Table 1.4

Insert Table 1.5

Ingested food increases the metabolic rate due to specific dynamic action of food

(SDA). SDA is also called thermic effect of feeding. SDA of a food is the energy

expenditure due to digestion and absorption. SDA contributes to about 10% of total
energy expenditure. The SDA of food is exerted mainly by protein food. An

amount of protein sufficient to provide 100 kcal increases the metabolic rate of

about 30 kcal. A similar amount of carbohydrate increases it by 6kcal and a similar

amount of fat increases it by 4 kcal. Total energy expenditure = BMR + SDA +

Physical activity. Physical activity level (PAL) can be determined from total

energy expenditure and BMR. PAL= Total energy expenditure / BMR. PAL

reflects physical activity and is much higher in athletes compared with people

having sedentary life.

Energy balance depends on the balance between energy intake and energy

expenditure. Energy balance is negative when the energy expenditure is more than

the energy content of ingested food. Due to negative energy balance endogenous

stores i.e., fat, glycogen and proteins are catabolized, resulting in loss of body

weight. Energy balance is positive when the energy expenditure is less than the

energy content of ingested food. Due to positive energy balance energy is stored,

resulting in gain of body weight. However, under physiologic condition food intake

is regulated to the point where energy intake equals to energy expenditure (energy

homeostasis). Body weight depends on the balance between energy intake and

energy expenditure. Food intake increases after illness or starvation until the

individual regains the lost weight. Food intake decreases after over-feeding for

days until the individual loses body weight to the control level.
The RDA of energy intake depends on age, gender, body weight and physical

activity Energy intake for elderly person is about 1970 kcal/d, whereas energy

intake for adults is about 2600 kcal/d. The RDA of energy intake indicates the

average dietary intake that is essential to maintain energy homeostasis. Pregnant

women require additional energy for the development of fetus, placenta and

maternal tissues. ICMR recommended an additional intake of 300 kcal/d during 2nd

and 3rd trimesters. In view of sufficient milk production ICMR recommended

additional energy of 550 kcal/d during the first 6 months of lactation. Because of

loss of lean body mass and poor physical activity, energy intake of elderly people is

less than the adult.

Respiratory Quotient (RQ): The RQ is the ratio of the volume of CO2 production

to the volume of O2 consumption per unit of time.

RQ for carbohydrate:

C6H12O6 + 6O2  6CO2 + 6H2O ; RQ=6/6=1.0

(Glucose)

RQ for Fat:

CH3(CH2)14 COOH + 23O2  16CO2 + 16H2O ; RQ=16/23= 0.7

(Palmitic acid)
(more O2 is required for the formation of H2O)
RQ for Protein: As proteins are not simply oxidized to CO2 and H2O, determination

of RQ of proteins is a complex process. Generally the RQ value of protein is

around 0.82.

The amount of oxidation of carbohydrate, fat and protein can be determined from

the RQ and the urinary nitrogen excretion (metabolism of about 6.3 g of protein

produces 1.0 g of urinary nitrogen).

The RQ is reduced under the following conditions:

(i) Diabetes mellitus due to increased utilization of fat secondary to decreased

utilization of carbohydrate.

(ii) High fat diet.

(iii) Increased oxidation of ketone bodies.

Energy sources of the cells

Energy is released when a cell breaks down macronutrients and is transferred to

adenosine triphosphate (ATP). ATP consists of a molecule of adenosine and

three phosphate groups having high-energy phosphate bonds. The stored energy of

ATP is released due to hydrolysis. ATP is converted to adenosine diphosphate

(ADP), inorganic phosphate and H+ with the liberation of energy

(ATP + H2O ADP + Pi + H+ + energy). Loss of another phosphate forms

adenosine 5' monophosphate (AMP) with the release of energy. Energy is

utilized for various functions of the body such as physical activity and muscular

contraction, active transport of molecules across the membrane, synthesis of

organic molecules, regulation of body temperature, and other physiological

functions which require energy. Other high-energy phosphate compounds are

(1) Phosphoenolpyruvate which is converted to pyruvate with the formation of

ATP.

(2) 1,3-Bisphosphoglycerate forms ATP from ADP.

(3) Phosphocreatine is a high-energy phosphate compound used during muscular

contraction.

Oxidative phosphorylation: Formation of ATP associated with oxidation by the

flavoprotein-cytochrome system (by the reaction between hydrogen and oxygen to

form water) is called oxidative phosphorylation. As the electrons are passed down

the electron transport chain to molecules of oxygen, energy is stored by the

formation of ATP from ADP and Pi. Uncoupling of oxidative phosphorylation

releases energy without the formation of ATP (eg, thyroid hormones).

Thermogenin (uncoupling protein): Mitochondria of brown adipose tissue in

infants contain thermogenin, which causes thermogenesis due to uncoupling

oxidative phosphorylation. Energy of oxidation is not used for the formation of

ATP, but rather resulting in oxidation of fatty acids of adipocytes and dissipating

energy as heat.

Calorigenic hormones

1. Thyroid hormones (thyroxine and triiodothyronine) increase the metabolic

rate at a very high level. The hormones increase the oxygen consumption and heat

production of metabolically active organs except the adult brain. This calorigenic

action is mainly mediated by uncoupling oxidative phosphorylation. The hormones

increase the activity of Na+- K+ ATPase, which hydrolyzes ATP to ADP with the

release of energy.

2. Epinephrine and Norepinephrine increase the metabolic rate due to cutaneous

vasoconstriction, which decreases heat loss and increases heat production. The

calorigenic action is also due to lipolysis.

3. Ghrelin secreted by the stomach and neuropeptide Y secreted by arcuate

nucleus of the hypothalamus increase the metabolic rate by stimulating food intake.

4. Growth hormone, Glucocorticoids and Glucagon increase lipolysis by

activating hormone-sensitive lipase (see lipid metabolism) and thus, can increase

the metabolic rate. The calorigenic action of glucagon is partly due to increased

deamination of amino acids in the liver. Growth hormone increases metabolic rate

in infants and children due to metabolism of new tissue formed.

Concept of Health

The cells of our body are surrounded by the extracellular fluid (ECF). Cells take up

oxygen and nutrients from ECF. The interstitial fluid of ECF is outside the blood

vessels, bathing the cells and is the actual internal environment of the cells.

Constancy of the interstitial fluid is maintained in order to have normal functions of

the cells by various physio-biochemical regulatory mechanisms. Maintenance of

constant internal environment is known as homeostasis (coined by W.B. Cannon).

Homeostatic imbalance results in disorders or diseases. The excess or deficiency of

amino acids, glucose, fatty acids, vitamins, minerals and water of the internal

environment will lead to nutritional disorders. Optimal nutrition is one of the major

determinants of health. It promotes health, improves quality of life, prevents

diseases, slows the progression of aging and degenerative diseases, and promotes

optimal growth. Various factors namely physical and mental state, poverty, chronic

infection, lack of exercise, inadequate intake of nutrients, genetic, hereditary,

educational status, type of occupation and food habits can affect health. Poor

digestion and absorption of nutrients will deteriorate health.

‘Good health is a state of complete physical, mental and social well being and not

merely the absence of disease or infirmity’ (WHO)

Physical

Normal appearance of skin, face, eye, leg, muscle mass without excess fat

deposition and posture indicates good health. Cracking, erosion and ulceration of

skin is present in Kwashiorkor; Skin becomes rough due to Vitamin A deficiency;

Dermatitis occurs due to deficiency of Niacin; Cheilosis i.e., fissures at the corners

of mouth occurs due to deficiency of Vitamin B2; Xerophthalmia, Bitots spots and

Keratomalacia of the eyes occur due to Vitamin A deficiency; Bowing of legs

occurs due to Rickets in children and deformed legs in adults due to osteomalacia;

Emaciation is predominant in Marasmus; Excess fat deposition is found in obese

individuals.

Mental

Normal mental state of human beings is essential for the maintenance of health. An

individual with an abnormal state of mind cannot take care about his/her health.

Poor memory, deterioration of personal care, hallucination, decline of intellectual

functions (due to niacin deficiency, chronic alcoholism/drug abuse) will affect

health. Paranoid personality disorder (suspiciousness, hostility, delusion of sexual

infidelity, etc) deteriorates health.

Social

Socially grouped individuals can take better care of their health compared with

isolated individuals (recluse). An individual living in a good family will have

cheerful attitude of life. Prevalence of alcoholism, smoking and drug abuse is less

in joint families. Marital tension and unemployment deteriorates health.

Genetics

Expression of DNA, transcription and translation determine the genetic make-up of

an individual. Nutrients influence the synthesis of proteins and enzymes by

influencing gene expression within the cells. Glucose increases the transcription of

glucokinase synthesis in the liver. Similarly vitamin K dependant carboxylase

increases the transcription of glutamic acid residues in the liver to form ϒ-

carboxyglutamate of prothrombin.

Hereditary

A vast number of diseases are hereditarily acquired eg, Type 2 diabetes mellitus.

Economic Status

Poverty is the major cause of malnutrition and high infant/child mortality rate. It

affects normal pregnancy. Elderly people with low economic status are more

susceptible to age-related diseases.

Educational status

Educated people are more aware and concerned about health. Regular exercise and

optimal diet promotes health. Smoking, alcohol and illicit drugs are avoided due to

awareness of their detrimental effects.

Type of occupation and Employment

Occupational hazards for eg, welders suffer from health hazards (even fibrosis of

the lungs) due to inhalation of zinc oxide.

Food habits

Excessive intake of iodine present in sea foods and seaweeds may cause

hyperthyroidism. Storage and boiling of food in brass vessels may cause adverse

effect on health due to copper toxicity characterized by anorexia and hepatitis.

Preparation of food in iron utensils causes iron toxicity characterised by

hemosiderosis (Chapter 3).

Physiological Consideration of Nutrition

During evolution the anaerobic organisms which could survive in the absence of

oxygen were transformed into multicellular organisms with highly developed

processes of oxidative phosphorylation. The life of higher animals is dependent

upon:

1. Adequate supply of oxygen to the tissues, by which cells derive energy in the

form of ATP. Constant and abundant supply of ATP, 'the energy currency of the

cells', depends on constant and abundant supply of oxygen. Every cell of the body

is an oxygen sensor i.e., senses oxygen concentration. A vast number of enzymatic

reactions utilize oxygen as a substrate. Oxygen utilization results in the formation

of highly toxic reactive oxygen species (ROS). Therefore, there must be continuous

supply of oxygen through internal respiration (oxygen consumption and carbon

dioxide production due to mitochondrial respiration) via external respiration

(exchange of oxygen and carbon dioxide occurring between alveolar air and

pulmonary capillaries).

2. Gastrointestinal system for digestion and absorption of food, liberating nutrients

into the blood.

3. Cardiovascular system to distribute nutrients and oxygen to the cells.

4. Neural and endocrine system to coordinate and integrate the functions of various

systems of the body in response to various nutrients.

Physiological studies determine the following:

1. The role of various macronutrients and micronutrients needed for the optimum

physiological functioning of every cell of the body.

2. The problems of undernutrition, malnutrition and overnutrition.

3. 'How much to eat and when to stop eating' depends on the interactions of the

hypothalamus with appetite-stimulating and appetite-inhibiting hormones as

mentioned below.

Control of Food Intake

Hunger (an intrinsic instinct of sensation to eat food) and Appetite (desire to eat

food associated with pleasant sensation) depend on the interaction of feeding center

(lateral hypothalamus) and nearby satiety center (ventromedial nucleus of

hypothalamus [Figure 1.1]). Feeding center is active all the time and initiates

hunger and appetite. But increased activity of satiety center after the ingestion of

food inhibits the feeding center, leading to cessation of eating. Whereas, inhibition

of satiety center (eg, in the morning) leads to unchecked activity of feeding center,

leading to hunger and appetite. The activity of satiety center ultimately determines

the activity of feeding center. Various factors have been proposed to explain the

activity of satiety center (Figure 1.2).

1. Glucostatic Theory: Satiety center contains cells known as glucostats

(glucoreceptors). Activity of the satiety center is determined by the level of glucose

utilization. Inability to utilize glucose eg, in case of diabetes mellitus will cause
inhibition of satiety center and will lead to unchecked activity of feeding center,

leading to polyphagia.

2. Food present in the gastrointestinal tract releases the hormone Cholecystokinin

(CCK) which in turn inhibits feeding by stimulating satiety center whereas,

Ghrelin, an appetite-stimulating hormone, secreted by the stomach will have the

opposite effect. Neuropeptide Y (NPY) secreted by the arcuate nucleus of

hypothalamus increases food intake whereas norepinephrine decreases food intake

(Note: Amphetamine discussed under drug abuse causes anorexia by releasing

norepinephrine in the hypothalamus). Leptin, an appetite-inhibiting hormone,

released from fat depots due to increased fat deposition inhibits food intake by

activating the leptin receptors of the hypothalamus, possibly in the satiety center.

The anorexigenic alpha-melanocyte stimulating hormone (α-MSH) secreted by

the arcuate nucleus of hypothalamus inhibits food intake. PYY3-36 is a peptide

hormone secreted by the small intestine and colon. It inhibits NPY release from the

arcuate nucleus and reduces food intake. The hormone adiponectin released by the

adipocytes reduces energy intake and prevents triglyceride deposition in the

adipocytes. These interactions among hormones, polypeptides and

neurotransmitters controlling food intake are complex (Figure 1.3).

3. Distension of the stomach after eating will try to terminate feeding by

stimulating satiety center.

4. Thermostatic theory: A fall in body temperature increases food intake and a

rise in body temperature (fever) decreases food intake, acting at the level of

hypothalamus.

Insert Figure 1.1

Insert Figure 1.2

Insert Figure 1.3

Insert Table 1.6

VMN

LH LH

Anterior Posterior
Pituitary Pituitary
Figure 1.1 Diagrammatic Representation of Satiety Center [Ventromedial Nucleus
of the Hypothalamus (VMN)] and Feeding Center [Lateral Hypothalamus (LH)].

-
Neuropeptide Y Fever Norepinephrin
e
- + +
FEEDING SATIETY
CENTER
- CENTER
+ Glucose
utilization

+ +
+ - Leptin
Distension of stomach CCK Ghrelin
after feeding

Initiates hunger and

appetite
Figure 1.2 Factors controlling food intake. + Stimulation ; - Inhibition.

SATIETY CENTER
?
- +
Arcuate Nucleus

NPY secretory α-MSH secretory

cells - cells

+ Hunger - Hunger
+
 + -
- +
Energy Expenditure

Leptin from adipose tissue and insulin

from pancreas

Ghrelin from
Stomach

Figure 1.3 Interaction of hormones controlling food intake. NPY and α-MSH of
the arcuate nucleus of the hypothalamus are reciprocally innervated. Leptin from
adipose tissue and insulin from pancreas inhibit NPY secretory cells and stimulate
α-MSH secretory cells. Ghrelin stimulates NPY secretory cells. Balance of these
interactions will determine food intake and energy expenditure.

Table 1.1 Macronutrients and Micronutrients.

Macronutrients Micronutrients

Carbohydrate, Protein & Fat Vitamins & Minerals

Macrominerals Microminerals/
(> 100 mg) Trace elements
(< 100mg)

Calcium Iron
Phosphorus Copper
Sodium Iodine
Potassium Zinc
 Chloride Fluoride
Magnesium Manganese
Selenium
Molybdenum
Cobalt
Sulfur
Chromium

Table 1.2 Weaning foods.

7 months - 1 to 2 spoons of fruit juices (containing vitamin C) mixed with

less sugar. Excess sugar is to be avoided in order to prevent

overweight. 1 to 2 spoons of cooked green leafy vegetable soup

(containing iron).

8 months - 2 spoons of well cooked cereal in water or milk.

2 spoons of half boiled egg yolk.

 2 spoons of boiled and mashed potato with butter or mashed

banana with milk.

9 months - Small amounts of well cooked vegetables and rice with pulses.

10-12 months - Start with small quantities and gradually increase the amounts.

Soft boiled egg, cooked vegetables, cereals, pulses and milk.

Multivitamin syrup to be given.

Table 1.3 Factors affecting the Metabolic Rate.

1. Age ( with increasing age and in young children).

2. Sex ( in male compared with female).

3. Sleep ( about 10%).

4. Height or weight or body surface (increased).

5. Daytime (because of food intake and physical activities).

 6. Exercise

7. Recent ingestion of food (because of SDA).

8. Fasting and Starvation.

9. High environment temperature.

10. Stress

11. Growth

12. Pregnancy and Lactation.

13. Tobacco smoking.

14. Caffeine

15. High circulating levels of calorigenic hormones (see below).

Table 1.4 Diseases / Disorders affecting the Metabolic Rate.

1. Hyperthyroidism (eg. Graves’ disease).

2. Hypothyroidism ( Myxedema).

3. Adrenal insufficiency (Addison’s disease).

4. Fever
 5. Protein Malnutrition (Kwashiorkor).

6. Energy Malnutrition (Marasmus).

7. Over-nutrition (Obesity).

Table 1.5 Causes of increased or decreased Metabolic Rate under some factors.

1. Exercise increases the metabolic rate due to increased secretion of glucagon as

well as due to increased sympathetic activity. Exercise increases the metabolic rate

by about 10 times or even more. Trained athletes can increase the metabolic rate

even upto 20 times.

2. Prolonged fasting and starvation decreases the metabolic rate by about 30-40%.

Decline is due to (1) decline of plasma thyroxine and triiodothyronine (2) increased

FFA and ketones due to lipolysis, resulting in inhibition of glucagon secretion. (3)

decreased sympathetic discharge.

3. Stress increases the metabolic rate due to the activation of sympatho-

adrenocortical system.

4. Fever increases the metabolic rate (1˚C rise in body temperature increases BMR

by about 10%). This is mainly due to cutaneous vasoconstriction and shivering

(involuntary muscular contraction) during the rising phase of fever (see section on

fever).

5. Severe cold exposure may increase the metabolic rate. This is due to (1)

increased hunger (2) cutaneous vasoconstriction (3) shivering (4) increased

secretion of epinephrine and norepinephrine.

Table 1.6 Some causes of Anorexia.

1. Lack of macro and micronutrients: Protein (Kwashiorkor), Thiamin (Beriberi),

Vitamin A, Biotin and Zinc.

2. Gastrointestinal diseases: Malignancy, Ulcerative colitis, Celiac disease

(mucosal cell defect), Crohn's disease (edematous inflammation of the bowel) and

abdominal pain.

3. Liver diseases.

4. Chronic infectious diseases eg, tuberculosis.

5. Miscellaneous causes: AIDS, chronic alcoholism, severe depression, physical

and mental stress, major surgery, burns, acute sepsis and malignancy in an organ of

the body.

CHAPTER 3

Micronutrients

Vitamins are micronutrients required by the body to perform cellular functions.

They cannot be synthesized by the body and must be supplied by the diet in order

to prevent deficiencies of vitamins. The precursors of vitamins in the diet are called

provitamins. For example, provitamin beta-carotene present in carrot and spinach

produces vitamin A in the body. Vitamins do not provide energy. However, some

vitamins can provide energy indirectly as they act as coenzymes for carbohydrate,

lipid and amino acid metabolism. Vitamin D can be synthesized by the skin in the
presence of sunlight and niacin can be synthesized in the body from tryptophan.

Vitamin D and niacin may not be strictly vitamins. Rather vitamin D may be

termed prohormone as it gives rise to hormone calcitriol.

Classification
Fat Soluble Water Soluble

Vitamin A B-Complex Non B-Complex

(Retinol)
Vitamin D Vitamin B1 (Thiamin) Vitamin C
(Calcitriol) Vitamin B2 (Riboflavin) (Ascorbic acid)
Vitamin E Vitamin B3 (Niacin)
(Tocopherols) Vitamin B5 (PantothenicAcid)
Vitamin K Vitamin B6 (Pyridoxine)
(Phylloquinone, Biotin
Menaquinone) Vitamin B12 (Cobalamin)
Folic acid (Pteroylglutamic acid)

Fat Soluble Vitamins

Vitamin A

Insert Figure 3.1

Physio-Biochemical role

1. Rhodopsin (visual purple) is the photosensitive pigment of the Rods

(visual receptors) and is responsible for night or dimlight vision. Vitamin

A is necessary for the synthesis of rhodopsin ( Figure 3.2).

Insert Figure 3.2

 2. Retinoic acid derived from oxidation of retinal takes part in glycoprotein

synthesis. This may explain, in part, the action of retinoic acid in

promoting growth and differentiation of tissues.

3. Carotenoids (a variety of carotenes) are cleaved by oxidation to give rise

to retinaldehyde and thus retinol. Caretenoids are antioxidants and have

anticancer property.

4. Vitamin A prevents drying of skin and eyes.

Dietary Sources of Vitamin A

Yellow and green vegetables; green leafy vegetables eg, spinach ; carrot; fruits

(papaya, mango, pumpkin, etc) ; fish, liver, egg yolk, cream and cheese. Yellow

vegetables and fruits contain the yellow pigment beta-carotene which serves as a

precursor of vitamin A. Colostrum (yellowish fluid secreted from the mammary

gland for about 2-3 days after the delivery) contains high amount of vitamin A.

Note: Thyroid hormones convert carotene to vitamin A in the liver.

RDA of Vitamin A (µg/d) at different age groups and during pregnancy and

lactation.

For infants it is about 350-400, whereas it is about 600 from school children to

elderly person. It is about 800 for pregnant woman. Excessive intake must be

avoided during pregnancy as it may cause develpmental abnormalities of the fetus.

Lactating mothers need more amount (not less than 1000) as breast milk does not

supply enough vitamin A.

Features of Vitamin A deficiency

1. From the visual cycle it is evident that an individual due to vitamin A

deficiency will suffer from night blindness known as Nyctalopia. A person

due to nyctalopia will not be able to drive any vehicle at night and will not be

able to read in poor light.

2. Increased Dark Adaptation time: Bright light causes depletion of stores of

rhodopsin in rods. If a person spends a considerable length of time in bright-

light and then moves to dim-light (eg, entering a cinema hall), he will not be

able to see anything immediately. After a few minutes rhodopsin is re-

synthesized and vision is improved. This period is called dark adaptation

time. It is markedly increased due to deficiency of vitamin A.

3. Xerophthalmia: (Xero means dry condition). The conjunctiva (mucus

membrane that lines the front of the eye and lines the inside of the eyelids)

becomes dry, thickened and wrinkled. The conjunctiva loses its normal

transparency as it gets keratinized (keratin belongs to a family of proteins

which is fibrous in nature).

4. Bitot’s spots are greyish-white triangular spots on the surface of

conjunctiva. They consist of fragments of keratinized epithelium.

5. Keratomalacia: The cornea softens. Corneal epithelium degenerates and

will get vascularized. As a result corneal opacities will develop. Corneal

opacities, necrosis, ulceration, even perforation of the cornea ultimately lead

 to blindness. Children of age group upto 5 years are most commonly

affected.

6. Metaplasia (abmormal cell growth): Vitamin A deficiency causes

metaplasia leading to keratinized stratified squamous epithelium in the

respiratory passages and in the kidney. It is suggested that vitamin A controls

gene expression and thus cellular growth and differentiation. Loss of

mucociliary epithelium of the airways causes infection of the lungs.

Desquamation of keratin and debris predisposes to renal and urinary bladder

stones.

7. Skin: Rough skin and papules termed “ goose bump rash” (raised spots) of

the skin are due to hyperkeratinization of the epithelium lining the follicles.

8. Appetite: May be reduced possibly due to keratinization of taste buds.

9. Growth: Bone growth is slow possibly due to defective synthesis of

chondroitin sulfate (which is present in ground substance of bone and

cartilage).

10. Immune system cells: Vitamin A plays a role in the differentiation of

immune system cells (humoral immunity and T cell-mediated immunity). It

also takes part in phagocytosis. Vitamin A deficiency leads to increased

susceptibility to infections. People suffering from malabsorption of fat are

susceptible to developing Vitamin A deficiency.

Insert Figure 3.3

Prevention

An individual with any sign of vitamin A deficiency, especially apperance of

xeropthalmia, must be advised to take diet rich in vitamin A. Pregnant women

should take more vitamin A to build up stores of retinol in the fetal liver. Excessive

intake of vitamin A may cause a serious problem for pregnant women as retinol

may be teratogenic. When keratomalacia is present, oral dose of retinol must be

given to prevent blindness. According to National Blindness Control Programme

oral dose of vitamin A should be given to children below the age of 5, irrespective

of vitamin A [Link] report indicates that about 250 million children

below the age of 5 suffer from subclinical deficiency. Prevention of vitamin A

deficiency is one of the main priorities (other than iron and iodine) of the WHO.

Associated zinc deficiency augments vitamin A deficiency by interfering with

mobilization of vitamin A from the liver.

Hypervitaminosis

Hypervitaminosis may occur due to excessive intake of vitamin A.

Hypervitaminosis was first recognized among arctic explorers because of eating

polar bear liver, containing high amount of vitamin [Link] is characterized by

scaly dermatitis, anorexia, headache, aching joints and muscles, alopecia, dizziness,

hepatomegaly and even cirrhosis of liver.

Vitamin D
 Insert Figure 3.4

Vitamin D refers to a group of closely related vitamins that have hormone-like

action.

Physio-Biochemical role

Active form is 1,25-dihydroxycholecalciferol which is formed by the following

reactions:

Sunlight

7-Dehydrocholesterol Skin
Vitamin D3 (cholecalciferol)

25-Hydroxylase
(Liver)

25- Hydroxycholecalciferol

1 α-Hydroxylase
(Proximal tubules of kidney)

1,25-Dihydroxycholecalciferol (calcitriol)

Increases absorption Increases reabsorption Increases mobilization

of calcium and of calcium and phosphate of calcium and phosphate
phosphate from in the kidneys and thus from the bone by activation
the intestine decreases their excretion of osteoclast cells
from the kidney

Increases plasma levels

of calcium and phosphate

Dietary Sources: Fish oil , liver and egg yolk are good sources of vitamin D.

Dietary sources are required in individuals with limited exposure to sunlight

(northern latitudes).

Requirement for vitamin D (ug/d) at different age groups and, during pregnancy

and lactation is about 10. Pregnant woman and elderly person should have an

additional requirement. After several pregnancies women are susceptible to suffer

from osteomalacia due to inadequate exposure to sunlight and low reserve of

calcium. Higher incidence of hypocalcemia and defective dental element have been

reported in infants of pregnant mothers. Older people suffer from osteomalacia due

to inadequate exposure to sunlight and also due to less formation of 7-

dehydrocholesterol in the skin.

Deficiency: Causes defective calcification of bone matrix due to failure to deliver

adequate amounts of calcium and phosphate at the site of mineralization. The

defective calcification leads to:

i. Rickets in children (mostly affect between the age of 1 and 3). Incomplete

calcification of bone results in soft and pliable [Link] bearing bones

are bent eg, bow legs or knock knees. Knock-knee (genu valgum) is an
 abnormal curving of the legs when the knees are in contact. This is due to

gap between the ankles. In future life this may lead to arthritis. Prominence

of sternum produces pigeon like chest. The process of ossification at the

epiphyses (end of long bones) takes place in an abnormal manner which can

be felt as a marked projection on the surface.

ii. Osteomalacia in adults is a form of adult rickets. Many bones become soft

and deformed. Due to progressive loss of bone matrix (osteoporosis) the

incidence of fractures is increased.

Hypervitaminosis

High level of vitamin D is toxic as increased mobilization of calcium from the bone

causes hypercalcemia which, in turn, causes calcification of tissues eg, kidneys and

arteries.

Vitamin E

Tocopherols (vitamin E) consists of 6-hydroxy chromane ring with an isoprenoid

side chain.

Insert Figure 3.5

Physio-Biochemical role

Vitamin E consists of several tocopherols of which α-tocopherol is the most active.

Vitamin E acts as an antioxidant to prevent oxidation of cell membrane by free

radicals. Vitamin E accumulates in the mitochondria and plasma memebrane to

prevent oxidation by free radicals.

Synergestic action of vitamin E and selenium: Selenium present in glutathione

peroxidase destroys free radicals and thus removes the cause of lipid peroxidation.

Vitamin E prevents lipid peroxidation. Thus vitamin E and selenium act

synergestically to prevent lipid peroxidation.

Dietary sources: Vegetable oils ( eg, sunflower oil, soyabean oil, etc) are rich

sources of vitamin E. Wheatgerm, tomatoes, carrots, leafy vegetables, nuts, seeds,

fish, liver and eggs contain significant [Link] E is destroyed by cooking

and by food processing.

Requirement of vitamin E (mg/d) in infants, pre-school children and school

children is about 4-6. Whereas adult, elderly person and pregnant women require

about 10. Lactating mothers require slightly more i.e. about 12. Requirement

increases with decreased intake of polyunsaturated fatty acids.

Deficiency of Vitamin E

Defective fat absorption leads to Vitamin E deficiency as vitamin E is dissolved in

dietary fat and incorporated into chylomicrons and absorbed during fat digestion.
Deficiency of vitamin E may also occur due to insufficient dietary intake.

Deficiency may cause increased fragility of RBCs, resulting in anemia. This may

be due to abnormal cellular membrane due to oxidative radicals. Vitamin E

deficiency causes peripheral neuropathy due to degeneration of the axons of spinal

cord and cerebellar dysfunction (eg. ataxia).

Vitamin K

Vitamin K is a derivative of napthoquinone having a isoprenoid side chain. There

are several forms of vitamin K eg, Phylloquinone (vitamin K1), menaquinone

(vitamin K2), menadione (vitamin K3). Phylloquinone is present in green leafy

vegetables. Menaquinone is synthesized by intestinal bacteria. Menadione, a

synthetic compound, is metabolized to phylloquinone.

Insert Figure 3.6

Physio-Biochemical role

1. Vitamin K is essential for the synthesis of blood clotting factors. It catalyzes

ϒ-carboxylation of glutamic acid residues on various clotting factors as

shown below. Liver synthesizes inactive precursors of clotting factor II

(Prothrombin), factor VII (Proconvertin or Stable factor), factor IX

 (Christmas factor) and factor X (Stuart-Prower factor) containing glutamic

acid residues.

Glutamic acid residues

CO2

Vitamin K dependant carboxylase

ϒ-Carboxyglutamate (Gla) of the

clotting factors (active form)

Active Gla is released into the circulation. They take part in the cascade

of clotting reactions. In brief, prothrombin binds with calcium and

platelet phospholipid and is converted to thrombin which in turn, converts

soluble fibrinogen into insoluble fibrin, resulting in clot formation.

2. Osteocalcin of the bone matrix is essential for bone mineralization and

contains Gla. Pregnant women treated with warfarin may cause bone

abnormalities of their newborn child (“ Fetal warfarin syndrome”).

Vitamin K antagonists: Coumarin derivatives dicumarol and warfarin inhibit

ϒ-Carboxyglutamate and act as anticoagulant. Furthermore dicumarol is having

chemical resemblance of vitamin K and prevents the action of vitamin K by

occupying the site of action of vitamin K in the liver (substrate competition).

Dietary Sources

Spinach, broccoli, peas, green beans, cabbage, cauliflower, egg yolk , liver,

soyabean and olive oil are rich in vitamin K. Mother’s milk contains low amount of

vitamin K and is less than cow’s [Link] K is synthesized by intestinal

bacteria. This synthesis is sufficient for the body’s requirement, provided the

intestinal absorption is normal.

Requirement of vitamin K (ug/d) in infants, pre-school and school children is

about 15-20. Adults and elderly person require about 60. Pregnant women and

lactating mothers require more i.e about 70-80.

Deficiency may be due to (i) extensive use of antibiotic and (ii) fat malabsorption.

Vitamin K is absorbed into the lymphatics in chylomicrons (therapeutic use of

menadione, being water soluble, is absorbed directly into the hepatic portal vein).

Vitamin K deficiency will lead to hypoprothrombinemia and will cause

hemorrhage due to the defect of clotting mechanism. Newborn infants are very

much vulnerable to vitamin K deficiency and may suffer from hemorrhagic

diseases due to the following reasons: (i) Vitamin K cannot cross the placental

barriers efficiently to reach the fetus. Reserve of vitamin K of the liver is low in the

fetus (ii) The intestines are sterile after birth (iii) Human milk is poor source of

vitamin K. In view of the above reasons all newborn infants should be given a

prophylactic dose of vitamin K in order to prevent hemorrhagic diseases.

Water Soluble Vitamins

Thiamin (Vitamin B1)

Thiamin was the first vitamin identified.

Insert Figure 3.7

Physio-Biochemical role

Thiamin pyrophosphate is the active form of vitamin B 1 formed by the transfer of a

pyrophosphate group from ATP to thiamin.

Thiamin diphosphotransferase
Thiamin Thiamin pyrophosphate (TPP)
[Thiamin diphosphate]
ATP AMP

TPP is the coenzyme for oxidative decarboxylation reactions.

CO2
Pyruvate Acetyl CoA
Pyruvate dehydrogenase
TPP

CO2
α-Ketoglutarate Succinyl COA
α-Ketoglutarate dehydrogenase
TPP

Thus TPP takes part in carbohydrate and amino acid metabolism. It takes part in

gluconeogenesis. TPP is coenzyme of transketolase in the hexose monophosphate

shunt pathway of glycolysis and provides NADPH for fatty acid synthesis. It

releases energy from carbohydrate.

Dietary Sources

The best sources are yeast, pulses and unrefined cereals, nuts, meat, fish, egg and

liver. Thiamin is almost absent in polished rice. Aleurone layer of food grains

contains thiamin. When the grain is boiled along with husk, aleurone layer will be

fixed with the grain. By parboiling process, thiamin is fixed in the grain. Whole

wheat bread is a good source compared with white bread. Thiamin is destroyed by

heat and sunlight. Thiaminase present in certain fishes, red cabbage, tea and coffee

destroys thiamin. Continuous chewing of betel nuts can precipitate thiamin

deficiency in individuals whose main diet is polished rice. Polyphenols and

thiaminase present in betel nuts destroy thiamin.

RDA (mg/d) of thiamin at different age groups, and during pregnancy and

lactation : Infants need about 0.3, whereas adults, elderly persons, pregnant and

lactating mothers need about 1.5. RDA at different age groups and during

pregnancy / lactation may vary as it depends on the pattern of dietary intake.

Thiamin Deficiency

Thiamin is synthesized by intestinal bacteria. Thiamin deficiency can be

precipitated by the oral administration of antibiotics which kill intestinal bacteria.

One should take B-complex tablet containing thiamin along with antibiotic.
Thiamin deficiency leads to Beriberi. It occurs mainly in areas where polished rice

and white flour are the major components of the diet.

Citric acid cycle indicates the following:

1. Thiamin deficiency results in a decreased production of ATP. Thus cellular

functions are impaired.

2. Carbohydrate utilization is impaired with the accumulation of pyruvic and

lactic acid. It is well established that all nervous tissues including brain use

blood glucose as their primary source of energy.

Most of the signs and symptoms of Beriberi are due to the above two reasons.

Adult Beriberi

Neuritic (dry form) Cardiac (wet form) Cerebral

CNS manisfestation Palpitation, edema of legs, Loss of appetite,

are mainly observed. dyspnea and enlargement nausea,vomiting,
The spinal cord and of heart. Due to impaired insomnia, depression,
peripheral nerves activity of pyruvate dehydr- loss of recent memory,
(show inflammation ogenase, accumulation of nystagmus(involuntary
with loss of sensation) lactic & pyruvic acid cause oscillation of eyeball)
are mainly involved. dilation of arterioles which and opthalmoplegia
 Neuritis is also due to causes edema of the legs & (paralysis of the eye
degeneration of myelin face as well as causes lactic muscles) are the
sheath. Muscles acidosis. characteristic features.
are weak and stiffness
of leg muscles causes
difficulty to rise from
squatting position and
the patient is unable to
walk. Edema is mostly
absent.

Infantile Beriberi

It occurs in nursing infants (usually two to six months of age) whose mothers are

suffering from thiamin deficiency. The disease is found in underdeveloped

countries among malnourished infants. It is characterized by anorexia, weight loss,

tachycardia, vomiting, diarrhea, peripheral edema (lower legs) and convulsion. In

the acute form the baby suffers from dyspnea on exertion and the baby may die of

heart failure.

Chronic alcoholics generally suffer from thiamin deficiency either due to dietary

insufficiency or due to impaired absorption of thiamin. Alcohol interferes not only

with the intestinal absorption of thiamin but also with the synthesis of TPP.

Chronic alcoholics suffer from Wernicke’s encephalopathy due to thiamin

deficiency which is characterized by nystagmus, ataxia, neuritis and

opthalmoplegia. The syndrome is known as Wernicke-Korsakoff syndrome if there

is an associated loss of memory.

Riboflavin (Vitamin B2)

Riboflavin consists of three ring cyclic structure, isoalloxazine ring attached to

sugar alcohol i.e. ribitol.

Insert Figure 3.8

Properties: It is soluble in water and heat stable. It is a fluorescent pigment and

decomposes in the presence of light. Due to its yellow color it is used as a food

color. Riboflavin is converted to inactive lumiflavin and lumichrome due to

photolysis. These inactive compounds produce unpleasant smell when milk, fish

etc are exposed to sunlight (“Sunlight flavor”).

Physio-Biochemical role

Flavin mononucleotide Flavin adenine dinucleotide

Riboflavin (FMN) (FAD)
(Active form) (Active form)

Enzymes containing riboflavin are called flavoproteins. Flavoproteins act as

electron carriers in the mitochondrial electron transport chain.

FMN dependent enzymes: eg, amino acid oxidase

Amino acid Imino acid

 FMN FMNH2

FAD dependent enzymes: eg, succinate dehydrogenase

Succinate Fumarate

FAD FADH2

Dietary sources: Milk, meat, cheese, yeast, liver, fish, eggs, whole cereals and

green leafy vegetables and broccoli are dietary sources. Germination of cereals

increases the content of riboflavin.

RDA (mg/d) of riboflavin at different age groups, and during pregnancy and

lactation : For infants it is about 0.3, whereas other age groups and during

pregnancy / lactation it varies from 1.4 to 1.6

Deficiency of Riboflavin: Changes observed clinically are dermatitis, cheilosis

(fissures at the corners of mouth) and glossitis (tongue appears purplish known as

“magenta tongue"), angular stomatitis (inflammation at the corners of mouth),

photophobia (discomfort of the eye due to exposure of light) and seborrhea

(excessive secretion by the sebaceous glands, especially of the nose). Riboflavin

deficient subjects are resistant to malaria, the cause of which is not known.

Niacin

Niacin is a derivative of pyridine, having carboxylic acid.

Insert Figure 3.9

Niacin
(Nicotinic acid) Nicotinamide Nictoinamide
Nicotinamide adenine ATP-ADP adenine
Tryptophan dinucleotide dinucleotide
Pyridoxal (NAD+) phosphate
Phosphate [Active Form] (NADP+)
Riboflavin [Active Form]

Note: Tryptophan in lactalbumin can be converted readily to niacin derivatives.

Physio-Biochemical role

Niacin and nicotinamide are precursors of coenzymes NAD+ and NADP+ which

take part in oxidation and reduction reactions. NAD+ and NADP+ play an important

role as coenzymes to many dehydrogenase enzymes eg, lactate dehydrogenase,

pyruvate dehydrogenase, malate dehydrogenase, etc and take part in carbohydrate,

amino acid and lipid metabolism. It also takes part in gluconeogenesis.

Dietary Sources: Legumes, peanuts, liver, milk, egg, fish and lean meat are dietary

sources. Niacin, to a certain extent, can be obtained from the metabolism of

tryptophan (pyridoxial phosphate is involved in the synthesis of tryptophan). Diet

low in essential amino acid tryptophan and pyridoxine (vitamin B 6) will aggravate

deficiency of niacin. Niacin in cereals (especially bran) cannot be utilized as niacin

is bound as niacytin. Deficiency of niacin may occur in India among people whose

main diet cereal is Jowar (Sorghum vulgare) as leucine present in Jowar can inhibit

the synthesis of NAD+ from tryptophan. Isoniazid prevents the conversion of

tryptophan to NAD+ by inhibiting pyridoxal phosphate.

RDA (mg/d) of niacin at different age groups, and during pregnancy and

lactation: For infants it is about 0.5 and for other groups it is about 15. Pregnant

woman and lactating mothers need more than 15.

Deficiency of Niacin: Causes Pellagra which is characterized by:

1. Dermatitis: Skin exposed to sunlight will look like severe sunburn. Butterfly

like pattern of dermatitis distribution occurs over the face. Rash forms a ring

around the neck (“Casal’s necklace”) [Figure 3.10].

2. Dementia: Deterioration of higher intellectual functions, poor memory and

deterioration of personal care.

3. Delirium: Mental disturbances, disorientation, hallucination and extreme

excitement.

4. Depressive psychosis: May be due to reduced synthesis of serotonin from

tryptophan.

5. Diarrhea

Note: Hartnup disease causes defective intestinal absorption and impaired

reabsorption of tryptophan from renal tubules, leading to deficiency of niacin.

Insert Figure 3.10

Hypervitaminosis
Excessive intake of Niacin may cause liver damage.

Clinical importance

Due to inhibition of lipolysis in adipose tissue, it causes hypocholesterolemia and

hypolipidemia.

Pantothenic acid

Pantothenic acid is formed by combination of pantoic acid and β-alanine.

Physio-Biochemical role

Pantothenic acid is a part of coenzyme A. In brief CoA takes part in fatty acid

synthesis, fatty acid oxidation, cholesterol synthesis and synthesis of steroid

hormones. ACP takes part in fatty acid synthesis and contains pantothenic acid.

Dietary sources: Yeast, liver, eggs, whole grain cereals, meat, etc.

Daily dietary intake for children and adults is about 4-6 mg. Infants require about

1.5 mg/d.

Deficiency of pantothenic acid is rare as it is widely distributed in foods and

synthesized by intestinal bacteria. The name pantothenic acid is derived from the

Greek meaning “from everywhere”. “Burning foot syndrome” (burning and

lightning pain of lower extremities) has been ascribed to the deficiency of

pantothenic acid. Deficiency may cause muscle spasm and insomnia. Impaired

steroidogenesis decreases secretion of adrenal cortex hormones and serum

cholesterol level. Deficiency can interfere with fatty acid synthesis.

Pyridoxine (Vitamin B6)

The following are three pyridine derivatives having vitamin B6 activities.

i. Pyridoxine

ii. Pyridoxal Pyridoxal Phosphate (active form)

iii. Pyridoxamine

Insert Figure 3.11

Physio-Biochemical role

Pyridoxal phosphate takes part in the following biochemical reactions:

a) Transaminase reaction

b) Deamination

c) Decarboxylation

Pyridoxal phosphate
Histidine Histamine + CO2

Pyridoxal phosphate
Glutamate GABA + CO2

d) Glycogenolysis: Phosphorylase requires pyridoxal phosphate and breaks

down glycogen to glucose-1-phosphate.

e) Pyridoxal phosphate acts as a coenzyme for the condensation of glycine and

succinyl CoA to form δ-aminolevulinic acid (ALA) which forms heme via

porphobilinogen and protoporphyrin IX.

Dietary Sources
Liver, banana, egg yolk, wheat, corn, yeast and green leafy vegetables are good

sources of vitamin B6.

RDA (mg/d) of vitamin B6 at different age groups, and during pregnancy and

lactation : For infants it is about 0.3-0.4, for adults, elderly persons, pregnant

woman and lactating mothers it varies from 2.0 to 2.5.

Deficiency of vitamin B6

It may occur in alcoholics due to the hydrolysis of phosphate. Isoniazid, a drug

used for the treatment of tuberculosis, can cause B6 deficiency by converting

pyridoxal phosphate into an inactive derivative. Deficiency especially in children,

may lead to neurological symptoms like hyperirritability and convulsion due to

decreased formation of GABA. Deficiency causes microcytic hypochromic anemia

due to diminished synthesis of heme as pyridoxal phosphate is essential for the

synthesis of heme via ALA. Deficiency can cause hypersensitivity of steroid

hormones as pyridoxal phosphate can remove the hormone-receptor complex from

DNA binding to terminate the action of steroid hormones like cortisol, androgens,

estrogens, [Link] has been reported prolonged use of oral contraceptives may cause

B6 deficiency.

Biotin

An imidazole ring combined with a thiophene ring.

 Insert Figure 3.12

Physio-Biochemical role

Biotin is a coenzyme in carboxylation reaction (biotin dependent enzymes are

acetyl CoA carboxylase, pyruvate carboxylase and propionyl CoA carboxylase).

Biotin takes part in gluconeogenesis and fatty acid synthesis. It induces the

synthesis of glucokinase and pyruvate kinase (enzymes of glycolysis) as well as

phosphoenol pyruvate carboxykinase (key enzyme of gluconeogenesis). Because of

increased synthesis of glycolytic enzymes, biotin administration may improve

glucose tolerance in diabetes mellitus.

Dietary Sources: Liver, soyabeans, yeast, egg yolk, tomatoes, milk and meat.

Requirement of Biotin : Dietary intake should be between 100µg and 200 µg/d.

Biotin deficiency: Biotin deficiency is rare as it is present in almost all foods. The

best sources are liver, soyabeans, yeast, milk and egg yolk. Moreover a large

amount of biotin can be synthesized by intestinal bacteria. Prolonged consumption

of raw eggs can cause biotin deficiency. Egg white contains heat- labile protein

avidin which tightly combines with biotin and thus prevents absorption of biotin

from the intestine. Avidin is denatured by boiling and cannot bind biotin.

Prolonged use of oral antibiotics and prolonged consumption of raw eggs can cause

biotin deficiency characterised by depression, dermatitis, glossitis, loss of apetite,

muscle pain, nausea, loss of hair (alopecia) and rash around the eyes and mouth.

Hyperglycemia may occur due to reduced synthesis of glucokinase. As biotin is a

coenzyme necessary for the conversion of acetyl CoA to malonyl CoA, biotin

deficiency interferes with fatty acid synthesis.

Vitamin B12

Structure and Properties: Vitamin B12 (cobalamin) has a complex corrin

structure. It has the most complex structure of any vitamin known. Four pyrrole

rings with a cobalt ion at the center is called a corrin ring. Cobalt is held in the

center of the corrin ring by four bonds from the nitrogens of the pyrrole groups.

The commercial preparation for oral use is cyanocobalamin (cyanide is added to

cobalamin ring to get stable crystals and has no physiological function). Vitamin

B12 is a red crystalline substance which is water soluble and heat stable.

HC CH

HC CH
N
H
Pyrrole

Physio-Biochemical role

1. Methyl group bound to cobalamin (methylcobalamin) is transferred to

homocysteine to form [Link] removes methyl group from

methyltetrahydrofolate to form tetrahydrofolate (active folate).

Tetrahydrofolate takes part in the synthesis of purine, pyrimidine and nucleic

acid (Figure 3.13).

 Insert Figure 3.13

2. Fatty acids are converted to methylmalonyl CoA. Vitamin B 12 converts

methylmalonyl CoA to succinyl CoA of citric acid cycle and thus takes part

in gluconeogenesis (Figure 3.14).

Insert Figure 3.14

3. Vitamin B12 takes part in the synthesis of choline. Choline ultimately

synthesizes acetylcholine.

Intrinsic factor of the stomach is essential for the absorption of Vitamin B12

which is transported to the tissues as well as is stored in the liver (Figure 3.15).

Insert Figure 3.15

Dietary Sources: Is found only in food from animals and absent in vegetables.

Richest source is found in liver, milk and curd (curd contains more Vitamin B12

than milk as lactobacillus can synthesize Vitamin B 12). Egg, fish and meat also

contain good amount. Vitamin B12 is synthesized by intestinal bacteria.

RDA of vitamin B12 (µg/d) at different age groups, and during pregnancy and

lactation. Infants need about 0.3, whereas other age groups and pregnant and

lactating mothers need about 2.0 to 3.0.

Deficiency

Lack of intrinsic factor (due to autoimmune destruction of gastric parietal cells or

after total gastrectomy) causes deficiency of vitamin B12.

 Deficiency of Vitamin B12

Neurological disorders Pernicious anemia

Caused by the degeneration of Macrocytic megaloblastic anemia is the
spinal cord. The degeneration characteristic feature. Deficiency of
may be due to defective tetrahydrofolate leads to impairment of
methylation of arginine residue synthesis of purine and pyrimidine and
of myelin protein and also may thus leads to impaired DNA synthesis.
be due to deficiency of Prevents division of immature R.B.C
methionine resulting in (pronormoblast / early normoblast)
accumulation of fatty acid in
myelin sheath. This
degeneration of spinal cord is Formation of large Large modified
known as “subacute combined sized [Link] normoblastic
degeneration of the spinal (macrocytes) series resulting
cord” characterized by in formation of
paresthesia (pricking and megaloblasts in
burning sensation), muscular
Elderly people may have atrophic gastritis and may suffer the bone
from B 12marrow.
deficiency due
weakness and impairment of
sense of position
to defective and ataxia.
absorption. Strict vegetarians of low economic group who cannot

afford milk or curd are likely to suffer from vitamin B 12 deficiency. In the stomach

vitamin B12 binds to a protein cobalophilin. In the duodenum cobalophilin is

hydrolyzed and releases vitamin B12 to bind to intrinsic factor. Thus, pancreatic

disease can cause B12 deficiency as cobalophilin cannot be hydrolyzed.

Methylmalonic aciduria and Homocystinuria

Due to deficiency of B12 methylmalonyl-CoA accumulates as it cannot be converted

to succinyl CoA. It is hydrolyzed to methylmalonic acid, which is excreted in the

urine. Homocystinuria also occurs as homocysteine is not converted to methionine.

 Folic acid / Folate (Pteroylglutamic acid)

Structure: Folic acid consists of the base pteridine which is attached to para

aminobenzoic acid (PABA) to form pteroic acid. Pteroic acid is attached to

glutamic acid to form pteroylglutamic acid i.e folic acid. Pteridine + PABA =

Pteroic acid + glutamic acid = Folic acid

Properties

It is insoluble in water and is destroyed when exposed to light.

Physio-Biochemical Role

Tetrahydrolate is the active form of folic acid / folate and is a carrier of activated

one-carbon units. It takes part in amino acid and nucleotide metabolism (Figure

3.16).

Insert Figure 3.16

Tetrahydrofolate takes part in conversion of one amino acid to another :

Histidine Formiminoglutamic acid (Figlu) Glutamic acid

Tetrahydrofolate

+ Glycine + Methylenetetrahydrofolate

Serine
Catabolism of serine and glycine forms methyltetrahydrofolate via methylene

tetrahydrofolate which in turn forms methionine (Figure 3.17).

Insert Figure 3.17

Dietary Sources

Mammals are unable to synthesize a pteridine [Link] obtain folic acid from the

diet. Folic acid can be synthesized by intestinal bacteria. Folic acid is found in

green leafy vegetables, whole grain cereals, liver, egg and yeast.

RDA of folic acid (µg/d) at different age groups, and during pregnancy and

lactation : Infants need about 25-30 and other age groups need about 100. Pregnant

women and lactating mothers need about 300-400.

Interaction between folic acid and Vitamin B12

Methionine synthase is the key enzyme for the functions of folate and B 12. In B12

deficiency when methionine synthase activity is impaired, uptake of folate into the

tissues is impaired from the circulating methyl tetrahydrofolate (folate is trapped as

methyl tetrahydrofolate). B12 deficiency, therefore, causes simultaneous folate

deficiency. Both tetrahydrofolate and vitamin B12 are concerned with the

conversion of homocysteine to methionine. Both promote DNA synthesis. Like

vitamin B12, folic acid deficiency causes macrocytic megaloblastic anemia.

However, folic acid deficiency will not cause any neurological disorder. Thus

administration of folic acid in patients suffering from vitamin B 12 deficiency will

correct anemia, but not neurologic disorder (for unknown reason it may aggravate

neurological disorder).

Folic acid Deficiency Vitamin B12 Deficiency

1. Presence of macrocytic 1. Presence of macrocytic

megaloblastic anemia megaloblastic anemia

2. Absence of neurological 2. Presence of neurological

disorder disorder

3. Abscence of methylmalonic 3. Presence of methylmalonic

aciduria aciduria

4. Presence of Figlu in the 4. Figlu test may be positive

urine after administration in some cases
of histidine (Figlu test)

Clinical Implication

1. Pregnant woman should take adequate amount of folate (not less than 400

µg/d) in order to prevent abnormal fetal development eg, spina bifida (the baby

is born with the spinal cord and its covering exposed through a gap in the

backbone).

2. Due to hyperlipidemia and hypercholesterolemia, cardiovascular diseases

(hypertension and ischemic heart disease) have been correlated with folate

deficiency.
 Vitamin C (Ascorbic acid)

The formula of vitamin C is C6H8O6. The structure closely resembles simple sugar.

O=C
HO-C O
HO-C
H-C
HO-C-H
CH2OH

Properties

Vitamin C is a white substance which is soluble in water and is easily destroyed by

heat. It is a moderately strong acid. It is stable in the crystalline state but in solution

is readily oxidized by atmospheric oxygen. The oxidized form is dehydroascorbic

acid which is readily reduced to reform ascorbic acid. This property of easily

reversible oxidation and reduction occurs in the tissues. Vitamin C is a strong

reducing agent. The reducing property depends on the double-bonded carbons.

Physio-Biochemical role

Vitamin C can be synthesized from glucose by all the species except primates,

including humans, monkeys and guinea pigs. Primates cannot synthesize vitamin C

due to the lack of gulonolactone oxidase (Figure 3.18). To prevent its deficiency
human beings must consume vitamin C containing diets. Vitamin C takes part in

the following biochemical and physiological functions:

1. It is required in the synthesis of intercellular cement substance of capillaries.

2. It is required for hydroxylation of proline, collagen synthesis and connective

tissue formation.

3. It takes part in bile acid formation.

4. It takes part in intracellular electron transfer.

5. It takes part in the synthesis of epinephrine and norepinephrine from

tyrosine.

6. It increases the absorption of iron from the intestine as it is a reducing agent

and converts ferric form to ferrous form which can be absorbed from the

intestine.

7. Like vitamin E and β-carotene, it acts as an antioxidant. It is able to

inactivate toxic oxygen free radicals (radical-trapping antioxidant).

8. Adrenal cortex contains large amount of vitamin C. ACTH administration

causes depletion of vitamin C, indicating that vitamin C may have some role

in steroidogenesis.

9. It is suggested that high dose increases resistance to common cold and

improves immune function.

Insert Figure 3.18

Dietary sources

Citrus fruits (orange, lemon, guava, amla), tomatoes, broccoli and green leafy

vegetables are good sources of vitamin C. Among all these, amla contains large

amount of vitamin C. Outer covering of citrus fruits contains bioflavonoids which

is an antioxidant as well as anti-inflammatory and also enhances immunity.

RDA of vitamin C (mg/d) at different age groups, and during pregnancy and

lactation : Infants should have 25 and other age group including pregnant woman

need about 50. Lactating mothers need more than 50 as breast milk contains less

amount of vitamin C

Deficiency of vitamin C causes Scurvy characterized by

1. Gum bleeding from tender swollen gums.

2. Capillaries are fragile. Tendency to bleed under minor pressure, resulting in

subcutaneous hemorrhage.

3. Delayed wound healing.

4. Painful swelling of joints due to hemorrhage.

The signs from 1. to 4. are due to defective collagen formation and brittle

intercellular cement substance.

5. Dimorphic anemia

Microcytic hypochromic anemia Macrocytic normochromic

occurs due to deficient iron anemia can occur as vitamin
 absorption. Hemorrhage also C can reduce folic acid to
contributes. tetrahydrofolic acid

Macrominerals

Calcium

Physio-Biochemical role

1. Ionic form (Ca2+) takes part in blood coagulation, vasoconstriction, muscular

contraction, nerve impulse transmission, hormone action, neurotransmitter

action, endocytosis, exocytosis, cellular motility and glycogen metabolism.

2. Found as calcium crystals in bone and teeth. Calcium takes part in

mineralization of bone i.e. deposition of inorganic minerals in organic matrix

of bone, leading to the formation of bone and teeth.

Regulation

Regulated by Vitamin D, parathyroid hormone (PTH) and calcitonin of thyroid

gland. 1,25 Dihydroxycholecalciferol increases absorption of dietary calcium from

the intestine. PTH increases plasma calcium level. Calcitonin decreases plasma

calcium by inhibiting bone resorption.

Calcium deficiency is rare due to the actions of PTH (Figure 3.19).

Insert Figure 3.19

Dietary sources
Milk and milk products are the best sources of calcium. Calcium content of cow’s

milk is more than that of mother’s milk. Egg yolk, leafy green vegetables soya

beans and fish contains some amount of calcium.

RDA of calcium or phosphorus (mg/d) at different age groups, and during

pregnancy and lactation: Different age groups from infants to adults require about

400-600. Elderly persons require about 800. Pregnant woman and lactating mothers

require about 1000

Calcium deficiency

1. Low ionized calcium due to impaired secretion of PTH causes Tetany,

which is characterized by neuromuscular hyperexcitability leading to spasm

of skeletal muscle, especially the muscles of extremities and larynx. Spasm

of larynx causes obstruction of the airway, resulting in death due to asphyxia

(lack of O2 and excess of CO2 in the blood).

2. Rickets in children and osteomalacia in adults due to defective calcification

of bone matrix (see vitamin D).

3. Osteoporosis in older people, especially women, leads to bone fracture.

Osteoporosis i.e. loss of bone mass (loss of both matrix and minerals) is due

to increased osteoclastic activity. Osteoclasts cause bone resorption by

eroding and absorbing formed bone (whereas osteoblasts are the cells

concerned with bone formation). Loss of bone matrix due to osteoporosis

causes increased incidence of fractures. Fractures are common in the distal

 forearm known as Colles’ fracture, hip and vertebrae. Fracture of vertebrae

causes kyphosis characterized by hunching of the back due to compression of

the vertebrae and outward curvature of the spine. Osteoporosis is more

common in elderly women, especially after menopause due to the deficiency

of estrogen. Normally estrogen inhibits osteoclastic function by increasing

apoptosis of osteoclasts. Decreased absorption of calcium in elderly woman

aggravates osteoporosis. Osteoporosis is also common in Cushing’s

syndrome as excessive glucocorticoid secretion leads to loss of bone mass by

inhibiting bone formation and stimulating bone resorption. Parathyroid

hormone and thyroid hormones cause osteoporosis due to increased bone

resorption and decreased bone mass. Low plasma concentration of insulin,

androgen and calcitonin cause decreased bone formation leading to

osteoporosis. Increased intake of calcium and vitamin D with moderate

exercise will slow the progression of osteoporosis.

Calcium Toxicity

Excess calcium may be deposited in the kidney, resulting in stone formation and

may cause constipation.

Phosphorus
Physio-Biochemical role

Phosphorus occurs as hydroxyapatite in the bone (about 80% of total body

phosphorus present in the bone) and as phospholipids. Phosphate is a constituent of

ATP, creatine phosphate, cAMP, 2,3-diphosphoglycerate and many proteins.

Phosphorylation and dephosphorylation of proteins take part in various cell

functions. Phosphate crystals along with calcium take part in bone formation.

Phosphates buffers are involved in the acid base regulation of blood. Phosphorus is

a component of DNA and RNA. In contrast to plasma calcium level, PTH

decreases plasma phosphate by increasing phosphate excretion in the urine.

Dietary sources: Phosphate is present in milk, nuts, cereals, meat, poultry and

phosphate food additives.

Deficiency Symptoms

Include anorexia, muscle weakness, bone pain and rickets in children or

ostemalacia in adults. Phosphorus deficiency occurs in patients with Fanconi’s

syndrome. Fanconi’s syndrome (autosomal dominant disorder) is a disorder of

proximal convoluted renal tubule leading to deficient phosphate reabsorption and

consequently large amount of urinary excretion of phosphate as well as large

amount of amino acids and glucose.

 Sodium, Potassium and Chloride

Physio-Biochemical role

(i) These three minerals take part in the regulation of acid base balance,

maintain the osmolarity of intracellular and extracellular fluids and water

balance.

(ii) Sodium is the principal cation of extracellular fluid, whereas potassium is

the principal cation of intracellular fluid. Chloride is found mainly in the

extracellular fluid.

(iii) Na+ influx and K+ efflux are responsible for the generation of action

potential of nerves, skeletal and cardiac muscles. Thereby they take part

in the transmission of nerve impulse and contraction of skeletal and

cardiac muscles. Furthermore, Na+K+ATPase of the plasma memebrane

removes three Na+ from the cell and takes two K+ into the cell due to the

hydrolysis of ATP. Various hormones, eg, thyroid hormones, insulin and

aldosterone increase the activity of Na+K+ATPase.

(iv) Chloride forms hydrochloric acid of the stomach. Chloride is also

concerned with chloride shift of R.B.C. and takes part in the transport of

carbon dioxide into the lungs.

Dietary sources
An individual consumes about 8-10 g of salt daily in food and salt added at the

table. Dietary sources of potassium are banana, apple, beans, potato, nuts, meat,

fish and poultry. Coconut water is a good source of potassium.

Recommended intake of sodium is about 2g/d and of potassium is about 3g/d.

Deficiency

It may occur due to vomiting and diarrhea. Salt intake should be restricted to

prevent hypertension. Insulin causes potassium to enter inside the cells, resulting in

hypokalemia. Bartter syndrome is an inherited condition of hyperkalemia and

hypovolemia.

Magnesium

It activates many enzymes eg, hexokinase, fructokinase, adenylyl cyclase, etc. It

takes part in glycolysis. It enhances the condensation of chromatin in the regulation

of gene expression. It is a constitutent of bones and teeth and about 60% of total

body magnesium is present in bone. It is essential for the secretion of PTH.

Dietary sources are cereals, pulses, nuts, leafy vegetables, fish and chicken.

Requirement for infant is about 60 mg/d. School children need about 200 mg/d.

Adults, elderly person, pregnant women and lactating mothers need about 400

mg/d.

Deficiency is produced by malnutrition. Deficiency causes hypocalcemia and

hypokalemia. Hypocalcemia occurs due to the effect of magnesium depletion on

PTH. Hypokalemia occurs due to excessive potassium excretion.

Microminerals

Iron

Physio-Biochemical role

Ferrous form is incorporated into protoporphyrin for hemoglobin synthesis. Iron is

an important constituent of cytochromes which are concerned with internal

respiration and energy production. It is required for intracellular electron transport.

Dietary Sources

Leafy vegetables, pulses, beans, meat and liver are the dietary sources. Jaggery is

also a good source of iron, whereas milk and fruits are poor sources of iron. Ferrous

iron is only absorbed from the intestine. Diets rich in vitamin C increase absorption

of iron by converting ferric to ferrous form, whereas phytate (present in cereals)

and oxalates (in leafy vegetables) inhibits absorption of iron by forming insoluble

iron salts.

RDA of iron (mg/d) at different age groups, and during pregnancy and

lactation: Infants need about 8. Adult female and elderly person requirement is

about 20. Pregnant women and lactating mothers require about 30.

Iron deficiency anemia

Is the most common type of anemia in India and is characterized by microcytic

hypochromic anemia.

Causes
(i) Dietary deficiency of Iron

(ii) Chronic blood loss due to hookworm infection in rural areas where sanitation

is poor, bleeding piles and hemorrhage due to peptic ulcer.

(iii) Poor dietary habits of elderly people.

(iv) Repeated pregnancy as blood loss occurs at parturition.

Note: Adult female requires more iron to compensate loss of blood during

menstruation. Menstruation causes average loss of 20 mg of iron per month.

Symptoms

Tiredness, fatigue, dyspnea on exertion, impaired work performance, pale

conjunctiva, spooning of nails (koilonychia), glossitis and angular stomatitis are

common features. Premature labor may occur.

Prevention

Iron deficiency anemia can be prevented by iron containing diet as mentioned

above along with diets containing vitamin C. Repeated pregnancy should be

avoided. During pregnancy, mother’s food must contain surplus quantities of iron

as the fetus is dependent on the iron reserve of the mother. This demand rises as

pregnancy progresses and is greatest in the second half of pregnancy. Sanitation

should be improved in order to prevent hookworm infection.

Diagnostic criteria of Iron deficiency anemia:

Anemia occurs when there is a reduction in the number of circulating RBCs or a

decrease in the content of hemoglobin or both (Normal average RBC count is 5.5
million/cumm in adult males and 4.8 million/cumm in adult females. Normal

average hemoglobin is 15.5 gm % in adult males and 14 gm % in adult females).

Microcytic: Size of RBC is less than normal [average diameter of normal RBC is

7.3 µ. MCV (mean corpuscular volume) i.e the volume of individual RBC is less

than normal in microcytic anemia (normal MCV is about 85 cubic micron)].

Hypochromic: Normal color of RBC is pink or orange color due to the presence of

hemoglobin. In hypochromic anemia pink color is very less due to low content of

hemoglobin. [MCH (mean corpuscular hemoglobin) i.e. amount of hemoglobin per

RBC is less than normal in hypochromic anemia (normal MCH is about 30 pg)].

[MCHC (mean corpuscular hemoglobin concentration i.e. amount of hemoglobin

per unit volume of RBC is less than normal (normal MCHC is about 35%)].

Low serum iron is below 50 µg/100 ml. Low serum iron-binding capacity is below

250 µg/100 ml.

Toxicity due to excess iron intake

Iron is stored in liver, spleen and bone marrow in the form of hemosiderin.

Hemosiderin is an aggregation of ferritin (iron-binding protein). Hemosiderosis

(excessive deposition of hemosiderin) due to repeated blood transfusion or

excessive iron intake damages tissues characterized by pigmentation of skin,

bronze diabetes (due to deposition of hemosiderin in the pancreas) and cirrhosis of

the liver. South African Bantu people prepare food in iron utensils and may suffer

from hemosiderosis.
 Copper

Physio-Biochemical role

Copper is a component of coenzymes in electron transport chain and is essential for

various biochemical reactions. The following important enzymes contain copper:

(i) Cytochrome Oxidase Essential for internal respiration. Involved in

the electron transport chain and formation of ATP.

(ii) Tyrosinase Essential for the formation of melanin.

(iii) Lysyl oxidase Essential for the maintenance of elasticity of elastin.

(iv) ALA synthase Essential for heme synthesis.

(v) Monoamine oxidase Inactivates catecholamines.

(vi) Dopamine β-hydroxylase Converts dopamine to norepinephrine.

(vii) Copper / Zinc Superoxide dismutase Prevents oxidative damage by

converting superoxide ion to hydrogen peroxide.

Ceruloplasmin is a globulin of plasma which binds six atoms of copper and

oxidizes ferrous form to ferric form which is incorporated into transferrin.

Transferrin transports iron to the bone marrow for the synthesis of heme.

Dietary sources

Green leafy vegetables (eg, spinach), cereals, nuts, bran, liver, meat, egg and fish

are dietary sources of copper. Copper content is less in milk.

Requirement for copper (ug/d) in adults, elderly person, pregnant women and

lactating mother is about 1000. Infants and school children require less (200-400

ug/d) to prevent copper toxicity.

Copper deficiencies

1. Copper is essential for heme synthesis. Copper deficiency will result in

microcytic hypochromic anemia like iron deficiency anemia. Deficiency

is common in infants getting only milk.

2. Copper deficiency causes weakening of the walls of the blood vessels as

copper is essential for maintenance of elasticity of the blood vessels.

3. Copper deficiency causes hypopigmentation of skin and hair due to lack

of formation of melanin.

Copper toxicity

1. Wilson’s disease is a genetic disease (autosomal recessive disorder) which

causes low plasma ceruloplasmin. As a result more copper is delivered and

deposited in various organs eg, liver and brain. Deposition of copper will

cause degeneration of liver and lenticular nucleus of basal ganglia of the

brain (hepatolenticular degeneration) and thus will lead to liver cirrhosis and

serious neurological symptoms like defective movement, slurred speech,

muscle spasm etc.

 2. Menkes’ Syndrome is also a genetic disease (X-linked copper deficiency)

which is fatal in infants. Here also ceruloplasmin is low. Signs and

symptoms are mental retardation due to defective myelination, fragile

abnormal (kinky) hair, convulsion due to neurodegeneration of the brain, etc.

Death usually occurs before 3 years of age.

3. Excess copper enhances oxidation of proteins and lipids and enhances the

production of free radicals. Therefore it is necessary to have normal amount

of copper in the diet.

4. Storage and boiling of food and water in brass vessels causes accumulation

of copper in the liver. Infants usually suffer from copper toxicity

characterized by abdominal distension, anorexia, hepatitis, jaundice and even

cirrhosis of the liver.

Iodine

Total body contains about 25 mg of Iodine. It is stored mainly in the thyroid gland

(about 80%). Rest is stored in salivary glands, gastric mucosa, choroid plexus of

the eyes and lactating mammary glands. Ingested iodine is converted to iodide and

absorbed from the intestine. Thyroid secretes 80µg daily as iodine in thyroid

hormones. Iodide takes part in the synthesis of thyroid hormones. This trace

element is a scarce component of soil and therefore there is little in the food. It is

present in sea foods (especially sea fish) and seaweeds. Iodine is lacking in the
mountain areas due to constant erosion of soil. Such areas are called goiterous belts

like Himalayan region and Alps. It is low in the soil of frequently flooded areas.

Requirement of iodine (ug/d) for infants is about 40 and for adults is about 150.

Pregnant women and lactating mothers require more than adults to prevent

congenital hypothyroidism and cretinism.

Goiter

(a) Iodine deficiency (b) Cabbage (c) Pendred’s Syndrome (d) Congenital
hypothyroidism

(a) Iodine deficiency goiter: Goiter means enlargement of thyroid gland (Figure

3.20). Iodine is essential for the synthesis of thyroid hormones i.e. T3

(triiodothyronine) and T4 (tetraiodothyronine or thyroxine). Iodine deficiency

(when dietary iodine intake falls below 50 µg/d) hampers the synthesis of T3 and

T4. Normally secretion of thyroid hormones is controlled by TSH (thyroid

stimulating hormone or thyrotropin) of the anterior pituitary. TSH stimulates the

secretion of thyroid hormones (by increasing the various steps of synthesis) and

is subject to negative feedback control by high circulating level of thyroid

hormone acting on the anterior pitutitary. High level of thyroid hormone inhibits

the secretion of TSH from the anterior pituitary (negative feedback). Thus TSH

stimulates the secretion of thyroid hormones which in turn inhibits the secretion
 of TSH (Figure 3.21). A balance of this feedback is maintained by appropriate

adjustment in order to have normal secretion of thyroid hormones. Low thyroid

hormones due to iodine deficiency will lead to unchecked excessive secretion of

TSH. Thyroid hypertrophies (increase in size of thyroid cells) due to excessive

secretion of TSH leads to an enlargement of thyroid gland.

(b) Cabbage Goiter: Vegetables of the brassicaceae family for eg, cabbage and

turnip contain progoitrin which is converted to antithyroid agent i.e. goitrin.

Goitrin inhibits the synthesis of thyroid hormones and causes enlargement of

thyroid gland . Mechanisms same as iodine deficiency goiter.

(c) Pendred’s Syndrome is an inherited disorder caused by mutation of pendrin

gene present on chromosome 7 and inhibits the secretion of thyroid hormones

from the thyroid gland, resulting in the development of goiter.

(d) Congenital hypothyroidism may be due to maternal iodine deficiency or due to

maternal antithyroid antibodies which cross the placenta. The secretion of

thyroid hormones is inhibited and causes the development of goiter in children.

During pregnancy iodine deficiency induces cerebral dysfunction of children,

leading to cretinism.

Mechanisms of goiter under (b), (c) and (d) are same as iodine deficiency goiter.

Insert Figure 3.20

Insert Figure 3.21

Iodine Toxicity occurs due to excessive intake of iodized salt or sea foods and

seaweeds. Near the sea areas cow or buffalo milk may contain high amount of

iodine due to iodine-enriched cattle feed. Excessive intake of iodine causes iodine-

induced hyperthyroidism due to excesssive secretion of thyroid hormones.

Prevention

About 1 billion people throughout the world used to suffer from iodine deficiency

disorder. It was very much common in India. The government programme of

addition of iodine in common salt has prevented the incidence of goiter. Goiter has

almost disappeared due to use of iodized salt.

Zinc

Zinc is a component of metalloenzyme Zinc / Copper Superoxide dismutase (Zn

/CuSOD), carbonic anhydrase, alcohol dehydrogenase and alkaline phosphatase.

Physio-Biochemical role

(i) Required by protein kinases which regulate gene expression.

(ii) Essential for spermatogenesis.

(iii) Being component of carbonic anhydrase takes part in the transport of

carbon dioxide.

(iv) Plays a role in immune function.

(v) Essential for taste sensation, growth and wound healing.

(vi) Takes part in protein digestion as it is a component of peptidases.

 (vii) Essential for the activities of the enzyme lactate dehydrogenase as it

contains zinc.

Dietary sources are meat, liver, cheese, nuts, beans, wheat bran and oatmeal.

Oysters contain high amount of zinc. Colostrum, compared with milk, contains

high amount of zinc.

Requirement of zinc (mg/d) at different age groups (except infant and pre-school

children) and during pregnancy and lactation is about 15. Infants and pre-school

children require about 4.

Zinc deficiency: It causes poor wound healing, impaired taste sensation,

alopecia,”flaky paint” rash of lower extremities, dermatitis, growth retardation,

hypogonadism, sexual immaturity and impaired immune function. Poor zinc

absorption due to an inherited recessive condition causes acrodermatitis

enteropathica characterised by eczematous skin on the hands, feet and other parts

of the body and chronic diarrhea.

Toxicity

Inhalation of zinc oxide fumes by welders causes toxicity characterized by nausea,

vomiting, headache and even fibrosis of the lungs. Excessive zinc causes irritation

of gastrointestinal tract and vomiting.

Fluorine

Fluoride forms calcium fluroapatite in teeth and bones and increases hardness of

the bones and teeth. It prevents dental caries as it increases enamel resistance to
acid. High level of fluoride intake (due to water intake from deep wells) may cause

discoloration and surface irregularities of teeth, anorexia and loss of body weight.

Excessive intake of fluoride may cause sclerosis of bone, hypercalcification of

ligaments and vertebrae. It may cause genu valgum (knock-knee) characterized by

curving of legs at the knees. Fluoride deficiency increases the incidence of dental

caries. Fluoridated tooth paste may prevent dental caries.

Requirement of fluoride (mg/d) for adults is about 2-4.

Manganese

It activates many enzymes eg, pyruvate carboxylase, arginase and mitochondrial

superoxide dismutase. It is essential for the synthesis of glycoproteins and

chondroitin sulfate. It is essential for urea formation, fatty acid synthesis and

release of insulin.

Dietary sources: Present in almost all foods, especially tea leaves, nuts and ginger.

Requirement for manganese (mg/d) for infants, pre-school children and school

children is about 0.5-1.5 and for adults, elderly person, pregnant women and

lactating mothers is about 2.5.

Deficiency may lead to defective formation of bone and cartilage due to lack of

chondroitin sulfate. Deficiency may be more common in infants due to low

concentration of manganese present in mother’s milk.

Selenium
It is present inside the cells as selenocysteine and selenomethionine. It is a

constitutent of glutathione peroxidase which serves to protect cell membrane. It is a

synergistic antioxidant with Vitamin E. Deiodinase enzyme (which causes

deiodination of thyroxine i.e. tetraiodothyronine to triiodothyronin) contain

selenium. Selenium is essential for the motility of sperm and immune function. It

prevents chromosome breakage.

Dietary Sources

It is present in plants and cereal grains (especially jowar and bajra) depending on

soil content. Bengal gram is a good source of selenium. Meat, chicken, egg yolk

and garlic contain selenium.

Requirement (ug/d) for infants, pre-school children and school children is about

15-20. Adults, elderly person, pregnant women and lactating mothers require about

60.

Deficiency

Keshan’s disease causes cardiomyopathy resulting in enlargement of the heart and

heart failure. It occurs in certain areas of China due to deficiency of selenium in the

soil.

Toxicity (Selenosis)

High intake of selenium causes brittle hair and nails, skin infection and garlic smell

of breath due to expiration of dimethyl selinide.

 Sulfur

Is present as chondroitin sulfates in cartilage and bone and is present in keratin of

hair and nail. Glutathione, thiamin and biotin contain sulfur group. Bile salts also

contains sulfur group. Sulfur containing amino acids (cysteine and methionine)

constitute body proteins. It is also component of insulin. Dietary sources are fish,

eggs, liver, poultry, cheese and beans.

Cobalt

Nutritional importance of cobalt is due to its presence in vitamin [Link] it takes

part in erythropoiesis.

Chromium

Enhances biotin synthesis by intestinal bacteria. Chromium deficiency causes

insulin resistance as chromium facilitates the binding of insulin to its receptor of

peripheral cells and potentiates the actions of insulin. It is present in yeast and

wine.

Molybdenum

Is a constituent of xanthine oxidase. Xanthine oxidase takes part in conversion of

purine bases to uric acid.

Insert Table 3.1

Insert Table 3.2

H3C CH3 CH3 CH3
CH2OH

Vitamin A (Retinol)
Figure 3.1 Structure of Vitamin A.

Various intermediates
RETINAL + SCOTOPSIN=RHODOPSIN
( Photorhodopsin,
Bathorhodopsin,
Lumirhodopsin, etc.)

Metarhodopsin

RETINAL(aldehyde of
Vitamin A)
 RETINAL + SCOTOPSIN (protein) Reductase

RETINOL(Vitamin A)

β-carotene

Figure 3.2 Visual cycle, showing role of Vitamin A in the synthesis of rhodopsin.

Xerophthalmia

Bitot’s spot

Keratomalacia

Figure 3.3 Pathological changes of the eye due to vitamin A deficiency.

 OH

CH2

HO OH
Figure 3.4 Structure of 1,25-dihydroxycholecalciferol (calcitriol).

CH3
HO

H3C O CH3

CH3

Figure 3.5 Structure of α-Tocopherol.

 O
CH3

R
O

Figure 3.6 Structure of vitamin K.

 NH2

CH3

N N

N CH2CH2OH
S

Figure 3.7 Structure of Thiamin.

H3C N N O

Isoalloxazine
H3C N NH

CH2
 H C OH

H C OH Ribitol

H C OH

CH2OH

Figure 3.8 Structure of Riboflavin.

COOH
 N

Figure 3.9 Structure of Nicotinic acid.

Rash on the face

Rash around the neck

Figure 3.10 Deficiency of niacin causes dermatitis over the face and around the
neck. Rash forms characteristic ring-like structure (like necklace) around the neck.

CH2OH
HOH2C OH

N CH3
H

Figure 3.11 Structure of Pyridoxine.

 O

Imidazole ring
HN NH

S C O
Thiophene ring
O
Figure 3.12 Structure of Biotin.

Homocysteine

Methyltetrahydrofolate

Methionine synthase VitaminB12 (Methylcobalamin)

Tetrahydrofolate (active folate)

Methionine Synthesis
 Purine Nucleic acid Pyrimidine

Figure 3.13 Formation of methionine and active folate is catalyzed by vitamin B12 -
dependent enzyme methionine synthase.

Fatty acids

Methylmalonyl CoA
Vitamin B12
Methylmalonyl-CoA mutase (Deoxyadenosyl cobalamin)

Succinyl CoA

Citric acid cycle

 Gluconeogenesis

Figure 3.14 Vitamin B12-dependent methylmalonyl-CoA takes part in

gluconeogenesis.

Intrinsic factor (glycoprotein) secreted by parietal cell of stomach

Binds to VitaminB12 in the intestine

Vitamin B12-Intrinsic factor Complex

 Binds to specific receptors of the mucosa cells of the intestine (ileum)

Absorbed into the blood

VitaminB12 is bound with transcobalamin I, B12 binding plasma protein,

and is transported to the tissues. Transcobalamin II is the storage form.

Figure 3.15 Role of intrinsic factor in the absorption of Vitamin B12.

Folic acid
+
NADPH + H

Folate reductase
+
NADP

Dihydrofolic acid

+
NADPH + H

Folate reductase
 +
NADP

Tetrahydrofolic acid (active form)

Amino acid synthesis Purine synthesis Thymidine synthesis

Essential for DNA synthesis

Figure 3.16 Formation of active folate is catalysed by folate reductase which

reduces folic acid to dihydrofolic acid and ultimately to tetrahydrofolic acid.

Serine Glycine

Methylene tetrahydrofolate

Methylene tetrahydrofolate
reductase

Methyl tetrahydrofolate *
 Methionine synthase

Methionine

Figure 3.17 Methylene tetrahydrofolate reductase and methionine synthase

catalyzes serine and glycine to methionine.* The form in which folate is taken up
by the tissues.

Glucose1-PO4 UDP (Uridine diphosphate) glucose

UDP glucuronic acid

Glucuronidase

Glucuronate
+
NADPH + H
 +
NADP

Gulonate

Gulonolactone

Oxidation Gulunolactone oxidase

Ascorbate

Figure 3.18 Synthesis of ascorbic acid.

Low ionized calcium concentration due to inadequate intake or due to defective

absorption of calcium from the intestine

Stimulates the secretion of PTH

 PTH increases the PTH stimulates production PTH stimulates bone
reabsorption of of calcitriol from the kidney resorption by stimulating
calcium from the which in turn increases osteoclasts and mobilizes
renal distal tubule intestinal absorption of calcium from bone into
of calcium the blood

Increases Plasma calcium level

Figure 3.19 Actions of PTH.

Figure 3.20 Goiter. Massive swelling of the neck due to the enlargement of thyroid
gland.
 Hypothalamus

Thyrotropin releasing hormone (TRH)

Anterior Pituitary

Thyrotropin (TSH)

Thyroid gland

Figure 3.21 Feedback control of Thyroid hormones. Solid lines indicates

stimulation. Dashed lines indicate inhibition.
Table 3.1 Antioxidants.
1. Vitamin C and E, provitamin β-carotene, selenium and phenolic compounds
present in whole grains, soyabeans, apples and walnuts are antioxidants as they can
inactivate oxygen free radicals.
2. Tomatoes are good antioxidants as they contain vitamin C as well as carotenoid
lycopene.
3. Melatonin is present in vegetables, fruits, flowers, seeds, walnuts and a variety of
herbs and is a potent free radical scavenger (hydroxyl radical, hydrogen peroxide
etc.).
Table 3.2 Clinical signs under various conditions.

1. Glossitis (Red / magenta tongue) is present due to deficiencies of biotin,

riboflavin and iron.
2. Peripheral neuropathy is the feature of the deficiencies of vitamin B 12,
thiamin and vitamin E.
3. Edema is present due to the deficiencies of protein (kwashiorkor), liver
disease due to alcoholism and thiamin.
4. Dermatitis occurs due to the deficiencies of riboflavin, niacin, biotin, zinc,
kwashiorkor and essential fatty acids.
5. Microcytic hypochromic and normoblastic anemia is caused by the
deficiencies of iron, copper, pyridoxine and vitamin C.
6. Macrocytic megaloblastic anemia is caused by the deficiencies of vitamin
B12 and folic acid.
7. Hemorrhagic diseases occur due to the deficiencies of vitamin K, vitamin E
and vitamin C.

CHAPTER 9

Poor Maintenance of Food Hygiene and Food Safety

Food Spoilage
Food spoilage is due to deterioration of food from the normal condition.

Discoloration, bad odor and unpleasant smell and taste of food indicate food

spoilage. Humidity, moisture, environmental high temperature (thermophilic),

oxidizing enzymes, anaerobic condition, accumulation of toxic chemicals, food

processing and insect infestation are mainly responsible for causing food spoilage.

Causes

i) Toxic glycoalkaloids solanine and chacomine cause browning of apples and

potatoes. Due to consumption of alkaloid one can suffer from diarrhea,

vomiting and abdominal pain. Excessive accumulation of toxins such as

linamarin in cassava (fleshy tuberous edible roots) can cause food

[Link] substances present in soil and thus in food eg, cadmium can

cause food spoilage and can cause renal damage. Toxins are present in many

foods for example, amygdalin in almonds and durrin in sorghum.

ii) Bacteria Clostridium botulinum causes botulism, a severe form of food

poisoning. It is due to ingestion of toxin produced by this anaerobic bacteria

in preserved food (in canned vegetables, fish and meat, bacteria grow under

anaerobic condition). Cans are inflated and show bubbles on opening,

exhibiting sign of food spoilage. Symptoms are vomiting, diarrhea, dryness

of mouth, difficulty in swallowing and breathing, and blurring of vision.

Even death may occur due to paralysis of respiratory muscles leading to

respiratory failure.
iii) Food exposed to the outside environment favors the growth of bacteria.

Bacteria can cause food spoilage characterized by bad odor and unpleasant

smell.

iv) Psicrophilic bacteria is capable of growth and reproduction in cold

temperature ranging from 15°C to 10°C and can cause food spoilage.

v) Storage of food grains (rice, wheat, etc) in humid and moist conditions

causes food spoilage. Water within or around the stored food is a good

medium for the growth of bacteria and fungus. Growth of fungus Aspergillus

flavus and [Link] produce aflatoxin which is carcinogenic and

hepatotoxic. Production of toxic ergotoxin due to fungal growth causes

constriction of peripheral blood vessels, resulting in painful sensation of the

legs. Post harvest spoilage of stored food occurs due to ochratoxin A, a

fungal toxin. Fungi such as Aspergillus grow in stored cereals, beans, pulses,

etc and produce nephrotoxic ochratoxin A. Post harvest spoilage of stored

food in humid conditions also occurs due to microbial toxin.

vi) Many weeds for example, crotalaria grows along with cereals and millets.

Weed seeds contain toxic pyrrolizidine alkaloids and may be contaminated

with the food grains. As a result human suffers from pain in the epigastrium.

vii) Food processing and packaging techniques may cause the formation of

toxic acrylamide resulting in food spoilage.

 viii) Due to storage of fruits and vegetables in lead-soldered cans, or due to

burning of discarded battery cases near the agriculture lands, lead may be

deposited on the food and can cause food spoilage. Ingestion of lead

contaminated food will cause anemia due to the inhibition of δ-

aminolevulinic acid dehydrase (ALAD).

ix) PAH (Polycyclic aromatic hydrocarbons) formed during barbequing or

grilling meat is carcinogenic. Meat after barbequing or grilling should not be

stored.

x) Methyl mercury compounds may be present in fish in contaminated water

(eg, due to burning of fossil fuels near the river). Ingestion of mercury

contaminated fish may cause mercury poisoning characterized by

impairment of hearing, ataxia, etc.

xi) Arsenic poisoning can occur due to food cooked only with ground water.

When ingested in large amounts , arsenic causes the symptoms of nausea,

vomiting, diarrhea, convulsions and even coma.

Food Adulteration

Food is adulterated if it meets any of the following criteria:

a) It contains any deleterious substance which may be detrimental to health.

 b) It contains adulterant added to foods to increase quantity and to reduce

manufacturing cost. Cheaper substance is added wholly or in part (economic

adulteration).

c) It is obtained from diseased animals.

d) It is packed after cooking under unhygienic condition.

e) It contains excessive coloring substance or excessive preservative. Prohibited

coloring substance and preservative may be added.

Examples of Food adulteration

1) Epidemic dropsy (edema): Mustard oil may be adulterated with argemone oil.

Argemone seeds (seeds of the poppy weed) derived from a wild plant are

similar to mustard seeds and contain the alkaloid sanguinarine. Adulteration

causes excessive accumulation of fluid in the extravascular space (edema).

Argemone seeds can be identified from mustard seeds. Argemone seeds on

pressing are white inside, whereas mustard seeds on pressing are yellow

inside. Sanguinarine prevents the oxidation of pyruvic acid. Accumulation of

pyruvic acid causes dilation of capillaries. Fluid comes out of the capillaries

causing [Link], diarrhea and fever are other clinical features.

2) Lathyrism: Occurs due to adulteration of pulses with seeds of Lathyrus

sativus (a kind of chick pea similar to pulses). Neurotoxin present in Lathyrus

sativus causes paralysis of lower limbs and thus causes serious health problem.
 Neurotoxin inactivates lysyl oxidase and inhibits cross-linkage of collagen

fibers and thus produces abnormalities of bone, joints and large blood vessels.

3) Excessive intake of additive/preservative/ packaged food (equivalent to

food adulteration). Pulses, fruits and vegetables are adulterated with the toxic

coloring agents so that they may look fresh. An individual suffering from

hypertension should not consume packaged frozen meat or fish containing

high sodium chloride for prolonged periods. Prolonged use of monosodium

glutamate, a food additive used especially in the Chinese food, causes

symptom like palpitation. Boric acid or sulfites may be used as additive.

Prolonged use of boric acid may cause kidney damage. Sulfite may aggravate

asthma.

4) Oleomargarine or lard is added to butter.

5) Alum is added to low quality flour, making expensive flour.

6) Chinese milk scandal: In China milk was contaminated with melamine.

Melamine is a white crystalline compound made by heating Cynamide and

used in making plastics. As a result of the contamination many children died.

7) Mogdad is leafy tropical weedy shrub whose seeds have been used as an

adulterant for coffee. Similarly coffee may be adulterated with Chicory

powder, having a large amount of caramel.

8) Chilli powder may be adulterated with brick powder

 (Identification: When put in water, brick powder will settle faster compared to

chilli powder).

9) Turmeric powder or pulses may be adulterated with metanil yellow

(Identification: Instant appearance of violet colour after adding drops of HCl

in a test tube, indicating the presence of metanil powder).

10) Milk may be adulterated with urea/tap or polluted water.

11) Pure ghee or butter may be adulterated with vanaspati.

12) Powdered beechnut husk aromatized with cinnamic aldehyde sold as

powdered cinnamon.

13) Tinopal (bleaching agent) may be added to rice noodles to make noodles

whiter.

14) Alcohol may be adultered with methanol. Methanol is an organic solvent used

in paints. Methanol is very toxic and may cause blindness and even death.

15) Although calcium carbide banned for ripening fruits by prevention of food

adulteration act (under section 44A), recent raids found use of calcium carbide

as a source of acetylene gas to ripen mangoes. Acetylene gas can damage liver

and kidney.

16) Yellow lentils may be adulterated with toxic colouring agent tartrazine, known

to cause asthma attacks and brain damage.

17) Leptospirosis (Weil’s disease) : Wheat or rice lying on the floor of the

factories may be contaminated by rat’s urine which may contain Leptospira

 bacteria. This may lead to fatal disease known as Leptospirosis characterized

by hepatitis, renal tubular necrosis, hemorrhagic conjunctivitis and even

meningitis.

Food-borne and water-borne diseases

Food-borne diseases

Food-borne viruses Food-borne bacteria Food-borne parasites

[Link] A virus 1. Clostridium botulinum 1. Protozoa
[Link] 2. Bacillus cereus a. Giardia intestinalis
[Link] 3. Staphylococcus aureus b. Entamoeba histolytica
[Link] 4. Clostridium perfringens c. Toxoplasma gondii
[Link] flu influenza 5. Escherichia coli 2. Trematodes
 virus (H5N1) 6. Campylobacter jejuni [Link] sinensis
[Link] flu influenza 7. Listeria monocytogenes (liver fluke)
virus (H1N1) 8. Salmonella species [Link] buski
7. Zika virus (eg, S. typhimurium, (intestinal fluke)
S. enteritidis) [Link]
9. Vibrio cholerae westermani (lung fluke)
[Link] parahemolyticus 3. Nematodes
[Link] enterocolitica a. Ascaris lumbricoides
12. Shigella dysenteriae (round worm)
[Link] vermicularis
(thread worm)
4. Cestodes
a. Taenia solium
(pork tapeworm)
b. Taenia saginata
(beef tapeworm)
c. Echinococcus
granulosus/ Taenia
echinococcus
(dog tapeworm)

Clostridium botulinum
(Described under food spoilage)

Bacillus cereus

Soil and dust are the sources of bacteria. Spores are heat resistant. Consumption of

contaminated milk, cereals, vegetables, meat and poultry produces enterotoxin in

the small intestine and, causes diarrhea and abdominal pain.

Staphylococcus aureus
Skin wound infection of hand, nose and throat infections may be caused by S.

aureus. Poor handling practices and exposed nose infection transfer the bacteria to

food. Consumption of contaminated food produces heat stable toxin, which in turn

produces enterocolitis characterized by nausea, vomiting, diarrhea and abdominal

colic pain. Even certain percentage of healthy individuals carries S. aureus in nose

and throat, and thus may transmit the bacteria, and can cause food poisoning.

Escherichia coli

Human and animals (cattle, sheep and pigs) feces are the sources of E. coli,

Consumption of contaminated food (undercooked beef, salad and raw milk) causes

intermittent gastroenteritis (diarrhea and abdominal pain), hemorrhagic colitis

(presence of blood in the stool) and urinary tract infection with fever. E. coli is

killed by cooking. According to the central pollution control board, the number of

fecal bacteria is very high in the Yamuna River. Foods obtained by farming along

the Yamuna banks contain excessive amount of fecal bacteria, including E. coli.

Clostridium perfringens

Soil and animal feces are the sources of C. perfringens. Consumption of

contaminated food (meat, precooked food and poultry) produces enterotoxin in the

large intestine which causes abdominal pain and diarrhea.

Campylobacter jejuni

Domestic animals and birds shed C. jejuni in their feces. Contaminated

undercooked food of animal origin, unpasteurized milk and water cause fever,
abdominal pain and watery foul smelling diarrhea (sometimes with blood and

mucus).

Listeria monocytogenes

It occurs as a saprophyte in soil, water and sewage. Human infection results from

contact with infected animals (mammals, ticks, fish, etc), inhalation of

contaminated dust and consumption of contaminated food (milk, cheese, meat and

vegetables). Immune compromised individuals (neonates, pregnant women and

elderly persons) are highly vulnerable to infection. Fever, watery diarrhea and pain

in joints and muscles are the common symptoms. Infection in pregnant woman may

lead to abortion or stillbirth. It may cause meningitis and septicaemia.

Salmonella species (eg, S. typhimurium and [Link])

Droppings of rats, lizards, poultry and other animals cause food contamination.

Human carriers also do occur. Sources of salmonella food poisoning are

undercooked poultry, milk, egg, meat, raw fruit and raw salad. Proper cooking

destroys the bacteria. Fever, diarrhea, nausea, vomiting and abdominal pain are the

common symptoms.

Vibrio cholerae

Described in detail under water-borne diseases. Contamination of food by flies and

hands and consumption of shell fish causes cholera.

Vibrio parahemolyticus

It inhabits costal and estuarine waters. It is found in fishes, shellfish, shrimps, crabs

and oysters. Consumption of infected fishes causes gastroenteritis.

Yersinia enterocolitica

It has been isolated from a wide range of domestic animals such as cats, dogs and

pigs. Consumption of undercooked pork and raw milk causes gastroenteritis with

fever and ileitis which may mimic appendicitis.

Shigella dysenteriae (Bacillary dysentery)

Worldwide endemic: Outbreaks occurs in crowded population with poor sanitation

due to natural catastrophes. Spread may occur by infected food or flies and contact

through unwashed hand after defecation. The bacteria causes inflammation of the

large bowel. Fever, diarrhea, colicky abdominal pain, tenesmus (continuous and

frequent desire to defecate with little fecal matter), purulent exudate and blood in

stools with little fecal material are the common symptoms.

Giardia intestinalis (Giardia lamblia)

Geographical distribution is worldwide but more common in the tropics. Mode of

infection in man is by ingesting cysts present in contaminated food or water. After

ingestion the cyst hatches out trophozoites which multiply in enormous numbers in

the duodenum and jejunum. They often localize in the biliary tract or gallbladder to

avoid the acidity of duodenun.

Clinical features: Enteritis, diarrhea, steatorrhea due to malabsorption of fat and

Inflammation of gallbladder, Flatulence and Abdominal distension.

Entamoeba histolytica

Geographical distribution is worldwide but more common in the tropics than in the

temperate zones. The mode of infection is fecal contamination of cysts in

vegetables, food and drinking water which causes amoebiasis. Eating of uncooked

vegetables and fruits especially causes ameobiasis.

Clinical features (i) Amoebic dysentery characterized by the intermittent passage of

blood and mucus in the stool. (ii) Thickening of the bowel wall rendering it

palpable due to ulceration. (iii) Lesion of liver: The trophozoites of E. histolytica

carried to the liver by the portal vein from the large intestine causes hepatitis and

even liver abscess characterized by pain of the upper part of right abdomen and

fever.

Toxoplasma gondii

Geographical distribution : Worldwide.

Mode of infection: (i) Congenital toxoplasmosis: Fetus is infected in uterus through

placental route of the infected mother. Infection may lead to abortion or stillborn. If

the fetus survives there may be hydrocephalous (enlargement of the head due to

increase cerebrospinal fluid within the ventricles of the brain) or microcephali

(smallness of the head due to underdeveloped brain) or blindness (ii) Acquired:

Ingestion of raw inadequately cooked infected meat, cow’s milk and egg. Humans

may be affected by ingestion of cysts discharged in the feces of infected cat.

Clinical features: Fever, enlarged lymph node, rashes of skin, hepatitis, retinitis

leading to blindness, pneumonia and neurological disorders for eg

encephalomyelitis (demyelination of the ascending or descending tracts of the

spinal cord and brain).

Clonorchis sinensis (Liver fluke)

Geographical distribution: A parasite of far east. The endemic areas include China,

Japan, Korea, Taiwan and Vietnam.

Mode of infection: Eating inadequately cooked or pickled fish. Habitat  fish

eating mammals eg cat. The adult worm lives in the biliary tract of the liver. It

infects the bile duct and the gall bladder.

Clinical features: Anorexia, abdominal pain, diarrhea, recurrent jaundice (as it

infects the bile ducts of man) and hepatomegaly are the commonest symptoms.

Fasciolopsis buski (Giant intestinal fluke)

Geographical distribution: It is an Asiatic trematode. Common in China, Malaysia,

Bengal, Assam and other Oriental regions.

Principal reservoirs of infection for man is the pigs

Mode of infection: Eating infected (encysted cercariae) water plants as raw

foodstuff. Site of localization is small intestine.

Clinical features are asthenia (weakenss or loss of strength), anasarca (edema of

legs and trunks), anemia, fever, abdominal pain and intestinal obstruction.

Paragonimus westermani (Lung Fluke)

Geographical distribution: Japan, Korea, India (Bengal, Assam and South India)

and Nepal.

Principal reservoir: Domestic and wild carnivora that feed on crustaceans.

Habitat: Adult worms live in lungs of humans.

Mode of infection: Eating of raw or improperly cooked flesh of an infected crab or

crayfish. “Drunken crab”(raw crab meat soaked in alcohol is a popular delicacy in

China).

Clinical features: Cough with recurring attacks of hemoptysis (coughing up of

blood) are the characteristic symptoms.

Ascaris lumbricoides (Round worm)

Geographical distribution: Worldwide but more prevalent in the tropics such as

India, China and South-East Asia.

Habitat: The adult worm lives in the lumen of the small intestine of humans and is

the largest intestinal nematode.

Mode of infection: Eating raw vegetables cultivated on soil infected by human

excreta and contaminated with Ascaris egg. Infection also may occur by drinking

contaminated water. Eggs may be transmitted to the mouth by dirty fingers.

Clinical features: (i) Large number of adult round worms may cause intestinal

obstruction, especially in children. (ii) The body fluids of round worm when

absorbed may cause allergic manifestations such as urticaria, conjunctivitis,

irritation of the respiratory tract etc. (iii) It may cause protein malnutrition by

preventing the absorption of amino acids from the intestine. (iv) Lungs: Larvae

penetrate intestinal mucosa, pass through portal circulation to liver and enter inside

the lungs via right heart. Pneumonia characterized by fever, cough and difficulty in

breathing is caused by the presence of larvae inside the lungs (Loeffler’s

syndrome).

Enterobius vermicularis (Thread worm)

Geographical distribution: Worldwide.

Habitat: Adult worms (gravid females) live in the caecum and appendix.

Mode of infection: By ingestion of contaminated food and drink with ova. The

movement of worms and laying eggs around the anus causes intense itching. Eggs

present in the fingers due to scratching of anus are transmitted in the food or drink

or directly into the mouth (especially in children).

Clinical features: Presence of ova causes pruritis and eczematous condition around

the anus, bedwetting due to nocturnal enuresis (involuntary micturation) and even

appendicitis are the common symptoms.

Taenia solium (Pork tapeworm)

Geographical distribution: World wide. Causes cysticercosis.

Habitat: Adult worm lives in the small intestine. The larvae penetrate the intestinal

mucosa and are carried to many parts of the body forming cysticerci.

Mode of infection: Eating insufficiently cooked pork containing cysticercus

cellulosae.

Clinical features: Vague abdominal discomfort, indigestion and diarrhea are the

common symptoms. Palpable nodules in the subcutaneous tissue and muscles are

due to the presence of cysticerci. Presence of cysticerci in the brain leads to

epileptic attack.

Taenia saginata (Beef tapeworm)

All the features are same as Taenia solium. Only difference about mode of

infection i.e., infection is due to eating of insufficiently cooked beef containing

cysticercus bovis.

Echinococcus granulosus / Taenia echinococcus

(Dog tapeworm, the hydatid worm)

Geographical distribution : Worldwide.

Habitat : Humans harbor the larval form in the small intestine.

Mode of infection: Due to ingestion of the eggs present in the dog’s feces by

humans. It occurs by (i) by allowing the dog to take food from the same plate. (ii)

by eating uncooked food contaminated with infected dog feces. (ii) by handling and

fondling of the dog.

Clinical features: Disease (Echinococcosis or Hydatid disease) remains silent for

many years. After many years, disease is detected due to pressure effect of hydatid

cyst or due to the rupture of cyst. The larval forms enter the liver via small

intestine, lungs, brain or any site of the body and form hydatid cyst in the liver,

lungs, and brain and thus damage the various organs.

The pressure symptoms will vary according to the site of cyst. Rupture of cyst

causes severe allergic reactions including fever and urticaria or even anaphylactic

reaction as the fluid of the hydatid cyst is highly toxic and contains antigen.

Hepatitis A Virus (HAV)

Severe food-borne / water borne disease is caused by Hepatitis A virus (belong to

picornavirus group of enteroviruses). It is transmitted by oral-fecal route. Infected

person excrete virus in the feces for up to 14 days before the onset of illness. The

virus may be shed in the feces for 7 to 14 days thereafter i.e., after the onset of

symptoms. Food or water becomes contaminated with feces of infected individuals.

Shellfish, oysters and raw mussels are also cause of outbreaks. Infection spreads

via intestine to liver.

Clinical features: Anorexia, fever, nausea, vomiting, abdominal pain (Right upper

abdomen due to stretching of peritoneum over the enlarged liver), tender liver and

jaundice. Diagnosis is based on detection of IgM antibody.

Norovirus (Calicivirus)

Food or water becomes contaminated with feces of infected patients (virus may be

shed for about upto 7 days after the illness). Shellfish eaters are common sufferers

as shellfish beds are contaminated with human feces from sewage. It is

characterized by gastroenteritis (nausea, vomiting and diarrhea).

Astrovirus

Infants less than 1 year are most susceptible. Contaminated food may causes

outbreaks in creches and schools. Diarrhea is the common symptom.

Rotavirus

Food and water are contaminated and causes infantile gastroenteritis characterized

by fever, vomiting and diarrhea.

Avian flu influenza virus (H5NI)

Bird flu can infect humans who have no immunity against it. Apart from people

working with poultry, consumption of undercooked infected poultry meat or eggs

can cause infection. Avian flu epidemic first occurred in Hong Kong. Afterwards it

has been reported in Asia, Africa, Europe the Pacific, Indonesia and Vietnam. Bird

flu may pose a pandemic threat. Birds who have recovered from the infection may

continue to shed the virus in the feces for about 10 days.

Clinical features: Diarrhea, cough, dyspnea, sore throat, high fever and headache

are the common symptoms. Death may occur due to pneumonia, sepsis and organ

failure.

Swine flu influenza A virus (H1N1)

In 2009 swine flu outbreaks occur in USA. Consumption of undercooked infected

pork can cause infection. It is a contagious respiratory disease caused by the virus,

which also enters the body through inhalation of droplets from mouth or nose.

Immuno-compromised individuals, cancer patients, diabetic patients, AIDS

patients are more at risk.

Clinical features: Fever, chills, sore throat, cough, body ache, head ache, fatigue,

nausea, vomiting and diarrhea. Death may occur due to electrolyte imbalance as a

result of dehydration, pneumonia and respiratory failure.

Zika virus is transmitted by Aegypti mosquitoes which also transmit dengue and

Chikungunya. They bite during the day. They cause fever, headache, muscle and

joint pain, skin rashes and redness of eyes. They may cause Guillain-Barre´

Syndrome and fetal malformations (calcification of certain areas of brain, dilation

of the ventricular system, etc). They are transmitted by mosquito bite, blood

transfusion, sexual transmission and from mother to child.

Water-borne diseases
(1) Vibrio cholerae causes cholera in the valleys of Ganges and other great

rivers of far east. Epidemics occur following large religious festivals.

Infected drinking water, ingestion of shellfish and contamination of food by

flies or by hands causes cholera. Bacteria is passed out in the stool or vomit

of the patient. Severe “rice-water” type of diarrhea, vomiting and abdominal

pain are the common symptoms. The excessive loss of fluid and electrolytes

leads to intense dehydration. The B.P. falls, the pulse becomes rapid and

feeble and the urine output decreases. The skin becomes cold and the eyes

are sunken. Death occurs due to circulatory failure unless fluid and

electrolytes are replaced.

(2) ‘Superbug’ in drinking water

NDM-1 gene hosts [Link] of the intestine NDM-1 makes bacteria highly

resistant to antibodies. The bacteria can lead to severe dysentery, septicemia

and urinary tract infection. It has been found in the drinking water of India,

Pakistan and Bangladesh. It has been reported also in developed countries.

(3) Campylobacter jejuni

(4) Giardia intestinalis

(5) Entamoeba histolytica

(6) Ascaris lumbricoides Described under food-borne diseases

(7) Enterobius vermicularis

(8) Hepatitis A virus

(9) Noroviruses

Vulnerable individuals to food-borne and water-borne diseases

Chronic food-borne and water-borne diseases can cause malnutrition.

Imuno-compromized individuals are more susceptible to severe food-borne or

water-borne infections. Immune system of neonates, infants and children are not

well developed. Pregnant women because of down regulation of immunity suffer

more from severe illness. As immune function deteriorates with aging process,

elderly person suffer easily. Children with protein malnutrition are adversely

affected. Transplant patients having immunosuppresant drugs and AIDS patients

are also adversely affected due to downregulation of immunity.

Prevention Strategies for food-borne and water-borne diseases

Whenever there is outbreak of infection, one must take the following preventive

measures:

(1) Hand washing with soap after the use of lavatory. Standard of personal

hygiene must be improved by education. Good hygiene will prevent the

spread of infection.

(2) Vaccination for a specific disease, if available, must be done where there is

endemic, epidemic or pandemic infection.

(3) Food and water are to be protected from contamination by flies, cockroaches,

rats and lizards.

(4) One should observe personal cleanliness and elementary hygiene while

taking meals.

(5) Water supplies should be protected from fecal pollution.

(6) Salads and fruits must be washed thoroughly.

(7) One should not take any undercooked food. Food must be cooked properly.

(8) Purified water must be taken (potable water).

(9) Carrier, if possible, should be detected and isolated.

(10) Habitat of the vector should be destroyed.

(11) Poultry infected with avian influenza virus must be destroyed in order to

prevent pandemic threat.

(12) It will be safe to bury or burn infective discharge, soiled clothing and stools

of infected patients at a designated disposal point.

Nausea and Vomiting

Nausea refers to the sensation or desire to vomit. Irritation of the mucosa of bowel

causes activation of vomiting center in the medulla which via visceral reflexes

causes vomiting. Due to reverse peristalsis contents are emptied into the stomach.

Vomiting ultimately refers to the forceful ejection of the gastric contents through
the mouth due to increased intra-abdominal and intra-thoracic pressure.

Simultaneous closure of the glottis prevents aspiration of the contents into the

trachea.

Causes of nausea and vomiting: Few examples are given below:

 Enteritis (Either due to bacterial infection{especially Staphylococcus aureus,

Salmonella species and Vibrio cholerae }or due to viral infection especially

Hepatitis A virus, Norovirus and Rotavirus)

 Inflammatory diseases eg, Hepatitis

 Psychological causes eg’s Anorexia nervosa and Bullemia nervosa (Induced

vomiting).

 Uremia

 Pregnancy

 Toxins liberated due to hepatic failure

 Excess consumption of alcohol

Complications of Vomiting:

Dehydration, Malnutrition, Metabolic alkalosis (Figure 9.1), Hypokalemia,

Hypochloremia, Hyperaldosteronism and Hematemesis due to mucosal tear of

the stomach.

Diarrhea and nutrition

Diarrhea is termed when fecal output is liquid or loose or watery with the increased

frequency of bowel movement. Fecal output may be mixed with blood or mucus. There

may be purulent exudate and blood in stool with little fecal material.

Diseases causing diarrhea are given below:

A. Due to parasites: (1) Giardia intestinalis (ii) Entamoeba histolytica (iii)

Clonorchis sinensis (liver fluke) (iv) Taenia solium (Pork tapeworm) (iv) Taenia

saginata (Beef Tapeworm). Giardia causes diarrhea with steatorrhea. Stools are

greasy and yellowish color due to malabsorption of fat. Entamoeba histolytica

causes intermittent blood and mucus diarrhea.

B. Due to bacterial infections : (1) Clostridium botulinum (ii) Clostridium

perfringens (iii) Staphylococcus aureus (iv) Escherichia coli (v) Campylobacter

jejuni (vi) Listeria monocytogenes (vi) Salmonella enteridis (vii) Salmonella

typhimurium (viii) Vibrio cholerae (ix) Vibrio parahemolyticus (x) Yersinia

enterocolitica (xi) Shigella dysenteriae (xii) NDM-1 gene host E. coli (xiii)

Bacillus cereus.

(1) E. coli causes intermittent blood (due to hemorrhagic colitis) and mucus

diarrhea.

(2) Purulent exhudative and blood of the stools with little fecal material occurs

due to Shigella dysenteriae. Other symptoms are colicky abdominal pain ,

fever and tenesmus.

(3) Typical rice-water diarrhea occurs due to Vibrio cholera.

 (4) Watery foul smelling diarrhea with blood and mucus occurs due to

Campylobacter jejuni.

(5) NDM-1 gene host E. coli causes antibiotic resistant severe diarrhea.

(6) Diarrhea is mostly accompanied by abdominal pain.

C. Due to viruses: (1) Hepatitis A virus (2) Noroviruses (3) Astrovirus (4) Rotavirus

(5) Avian flu influenza virus (H5N1).

(Causes of A. to C. are described under food-borne and water-borne diseases.)

D. Miscellaneous Causes

(1) Lactose intolerance is due to the deficiency of enzyme lactase. Lactose cannot be

hydrolyzed to glucose and galactose. As a result, non-absorbed lactose increases

intraluminal osmotic pressure which holds water and causes diarrhea (osmotic

diarrhea), Lactose passes into the colon, where it is fermented by bacteria,

causing, flatulence and discomfort.

(2) Celiac disease prevents the absorption of macro and micronutrients due to

abnormal mucosa of the intestine having finger-like villi. It leads to severe

diarrhea and malnutrition.

(3) Endocrine disorders causing abnormal intestinal mobility eg, Diabetic diarrhea

(due to autonomic neuropathy), hyperthyroidism and adrenal insufficiency.

(4) Inadequate absorptive surface due to surgical removal of the intestine (due to

malignancy). The defect of digestion and absorption of macro and micronutrients

will cause diarrhea with bulky fecal material and malnutrition.

Prevention

Prevention of diarrheal diseases due to bacterial infections, parasites and viruses has

been discussed under food-borne and water-borne diseases.

Management

A fluid or semi fluid diet without any dietary fiber should be given. Dehydration and

electrolytes deficiencies must be corrected by either oral administration or intravenous

administration of electrolytes (sodium, potassium and chloride) and dextrose or glucose,

depending on the severity of diarrhea. If there is associated vomiting, intravenous

therapy must be started to prevent hypovolemic shock. Diarrhea should be controlled by

the administration of specific antibiotics against bacterial infections or specific drugs for

protozoal infections (eg, amoebiasis, giardiasis, etc) or drugs for other parasitic diseases

as prescribed by the physician. Oral rehydration therapy is recommended to correct

dehydration. In addition to oral rehydration therapy, coconut water, buttermilk, barley

water, pulses water, cereal water, etc may be given depending on liking of the patient.

-
Cl Na K+ H+
 H2O pCO2 due to
inhibition of
respiration

E.C.F Volume

Angiotensin II H+ renal secretion

-
Aldosterone HCO3 renal
reabsorption

Na+ reabsorption
Metabolic alkalosis

Figure 9.1 Causes of metabolic alkalosis due to vomiting

CHAPTER 13

Nutritional Supplements, Exercise

and Diets for Mental Disorders
Mental disorder is mainly due to disturbances of emotion i.e. disturbance of

cognition , conation and affect . Normal individual will have a balance between

these three aspects of emotion. A mental illness may be due to mood, behavioral,

biological and psychological dysfunction. Mood is a state of mind or feeling with

sustained and pervasive emotional response.

Recent evidence indicates that nutritional therapies play an important role to reduce

and even to prevent the severity of mental illnesses. In view of the severe toxic side

effects of antidepressant drugs, nutritional therapies may act as prophylaxis for the

prevention of mental disorders.

Anxiety disorder, major depression, bipolar disorder, schizophrenia and obsessive

compulsive disorder (OCD) are the common mental disorders. These disorders are

known to be due to deficiencies of neurotransmitters of the brain such as serotonin,

norepinephrine, dopamine and GABA. The amino acids tryptophan, phenylalanine,

tyrosine, glutamate, glycine and methionine are converted to neurotransmitters as

shown below:

(i) Norepinephrine and dopamine are formed by hydroxylation and decarboxylation

of the amino acid tyrosine.

Phenylalanine Tyrosine Dopa

Vitamin B6
Dopamine

Ascorbate
 Norepinephrine

(ii) Tryptophan 5-hydroxytryptophan Serotonin

(5-hydroxytryptamine)

(iii) Glutamate GABA

(iv) Methionine is converted to S-adenosylmethionine (SAM)

Methionine + ATP SAM + pi + ppi

It has been suggested that SAM facilitates the synthesis of neurotransmitters of the

brain. SAM provides methyl groups in the body. Methyl group is transferred to the

amino group of epinephrine.

(v) Glycine (an inhibitory transmitter) can be synthesized from glutamate and

choline. Choline is synthesized using methyl group donated by methionine.

(vi) Taurine is an endproduct of cysteine.

Role of vitamins
(i) Tryptophan takes part in the formation of active form of niacin . Deficiency of

niacin causes dementia, delirium and depressive psychosis. These symptoms of

niacin deficiency may be due to reduced synthesis of serotonin from tryptophan.

(ii) Vitamin B12 takes part in the formation of methionine from homocysteine.

(iii) Vitamin B6 is a cofactor for the conversion of DOPA to dopamine.

(iv) Vitamin C is a cofactor for the conversion of dopamine to norepinephrine.

Role of omega-3-fatty acids: Eicosapentaenoic acid (EPA) and docosahexaenoic

acid (DHA) are two omega-3 fatty acids found in fish oil. EPA can be converted to

prostaglandins and leukotrienes that are essential for fluidity and renewal of the

[Link] neural tissues have high levels of omega-3- fatty acids. They may

maintain volume of the cerebral cortex and improve mental function. Brain cells

require omega-3-fatty acids in order to stabilize mood and emotions.

Anxiety disorder: Characterized by tachycardia, sweating, tremor, restlessness,

fearful facial expressions, dry mouth, dysfunction of cognition (eg, poor

concentration and distraction), affective symptoms like unpleasant fearfulness,

sense of apprehension, irritability, insomnia, etc. It may lead to panic disorder i.e.

an acute intense episode of anxiety. Anxiety disorder may be due to deficiency of

GABA or due to the deficiencies of norepinephrine, serotonin and dopamine.

Administration of glutamate, phenylalanine/ tyrosine and tryptophan may alleviate

anxiety disorder.
Major Depression: Characterized by melancholy, anxiety, anorexia, loss of

interest in all activities and enjoyment, social withdrawal, helplessness, extreme

dejection, loss of vigor and energy, and loss of motivation. Daily supplements of

tryptophan, tyrosine, glutamate and methionine may lead to recovery from major

depression. It has been suggested that daily supplement of EPA (about 2g) can be

helpful in treating patients suffering from major depression. Daily administration of

vitamin B12 (about 0.4 mg), folic acid (about 0.8 mg) and magnesium (about 300

mg) are essential to stimulate elevation of mood in depressed patients.

Bipolar mood disorder: Characterized by recurrent episodes of mania and

depression. Severe mood elevation, talkativeness, flight of ideas and grandiosity are

the characteristic features of mania. There may be episodes of hypomania and

depression. Mood stabilizing agent lithium is recommended for the prophylaxis and

treatment of bipolar disorder. Excess lithium causes adverse side effects such as

nausea, tremors of hand and foot, dulled personality, excessive thirst, increased

urination, weight gain, lethargy, loss of memory, loss of emotions, mental

confusion and delirium. Drug toxicity can become life threatening. It is essential to

get blood level of lithium checked occasionally in order to ensure that the toxic

effects are not present. Lithium orotate is less toxic compared to lithium carbonate.

Lower dose of lithium orotate along with dietary intake of lithium can stabilize the

central nervous system and can help the patients by reducing depressive and manic

symptoms of bipolar disorder. Foods rich in lithium are dairy products including
natural milk, eggs, tomatoes, cucumbers, potatoes, lemons, spices, crude salts, rock

salts and grains.

Vanadium is a trace element present in our diet. Elevated vanadium level of bipolar

patients causes depression and mania. Lowering level of vanadium may improve

bipolar syndrome. Lithium may antagonise and lower vanadium level. Vitamin C

detoxifies vanadium and protects the body from toxic effect of vanadium. It has

been suggested that a single 3 g of vitamin C decreases symptoms of bipolar

patients. Studies indicate that excess acetylcholine receptors of bipolar patients

contribute to the genesis of depression and mania. Studies have also shown that

taurine prevents the effects of excess acetylcholine. Clinical trials indicate that 1 to

2 g of omega-3-fatty acid daily reduces depressive and manic symptoms.

Deficiencies of amino acids (phenylalanine / tyrosine, tryptophan, methionine /

choline and cysteine / taurine) and vitamins (B12, folate, B6 and ascorbate may

aggravate bipolar syndrome.

The combination of micronutrients as mentioned above, omega-3 fatty acid and

dietary intake of lithium will reduce the symptoms of bipolar patients.

Schizophrenia is characterized by auditory hallucination, delusions, thought

blocking, speech disorders, wrong perception of reality and paranoia, lack of

relation between thoughts and feelings. An impaired synthesis of serotonin in the

brain, glycine deficiency and omega-3 deficiencies have been suggested in the

pathogenesis of schizophrenia.
Obsessive-compulsive disorder (OCD) is characterized by (i) obsession of

contamination with dirt and excreta, etc followed by compulsion i.e washing of

hands or the whole body repeatedly many times a day. (ii) multiple doubts

regarding the locking of doors and counting of money, etc. Checking repeatedly

about the doubts is the compulsion.

Low serotonin level of the brain has been implicated for the cause of OCD.

Normally serotonin released from the serotonergic neurons enters inside the

neurons by an active reuptake mechanism. This reuptake decreases the serotonin

level. Selective serotonin reuptake inhibitor (SSRI) seratraline hydrochloride

inhibits CNS neuronal uptake and increases serotonin level and thus can treat OCD.

Dose more than 100mg/d of serotonin produces side effects such as dry mouth,

nausea, tremor and dizziness. However, dietary intake of tryptophan increases

serotonin level and reduces the symptoms of OCD.

Exercise: Increases brain derived neurotrophic factor (BDNF) which stimulates the

growth of new neurons and synapses. BDNF is active in the cerebral cortex and

improves mental functions. Exercise prevents the decline of loss of volume of

cerebral cortex and thus prevents the decline of intellectual and mental functions. It

is well documented that exercise increases the liberation of norepinephrine which

will try to rectify anxiety disorder. Exercise increases β - endorphin level which

will stimulate elevation of mood. Exercise increases blood circulation of the brain

and stimulates function of the limbic system which improves motivation and mood.
Exercise improves cognitive function and distracts the mind that draws away from

negative thought, anxiety and depression.

Apart from exercise, yoga, meditation and pranayama will be useful to alleviate

mood. Pranayama (deep inspiration through one nostril and hold breath for few

seconds followed by deep expiration through another nostril) for about 15 minutes

daily will provide oxygen to the brain and will support the functions of neurons as

every cell is an oxygen sensor.

Foods: Patients suffering from mental illness should take diets rich in tryptophan.

α- lactalbumin of milk, fish, chicken, cottage cheese, nuts, cheese, eggs and beans

contain high amount of tryptophan. Ripe bananas contain serotonin, dopamine and

norepinephrine. As mentioned above foods rich in lithium will be useful.

Bright light: Exposure to bright light is very essential to reduce symtoms of mental

illness. Impulse from the retina projects to the serotonergic fibers originated from

the raphe nucleus of the midbrain and releases serotonin (known as “happy

hormone”).