NUTRITION &

VITAMINS

SHARI BABU
DEPT. OF PHYSIOLOGICAL SCIENCES
SCHOOL OF MEDICINE, UNZA
[Link]@[Link]
 OVERVIEW

• Nutrients are the constituents of food necessary to sustain the normal

functions of the body.

• All energy is provided by three classes of macronutrients: fats, carbohydrates,

protein—and in some diets, ethanol.

• The intake of these energy-rich molecules is larger than that of the other
dietary nutrients. Therefore, they are called macronutrients.

• This lecture focuses on the kinds and amounts of macronutrients that are
needed to maintain optimal health and prevent chronic disease in adults.

• Those nutrients needed in lesser amounts, vitamins and minerals, are called
micronutrients.
ENERGY REQUIREMENT IN HUMANS

• The Estimated Energy Requirement is the average dietary energy intake

predicted to maintain an energy balance in a healthy adult of a defined age,
gender, and height whose weight and level of physical activity are consistent
with good health.

• Differences in the genetics, body composition, metabolism, and behavior of

individuals make it difficult to accurately predict a person’s caloric
requirements.

• However, some simple approximations can provide useful estimates.

• For example, sedentary adults require about 30 kcal/kg/day to maintain

body weight; moderately active adults require 35 kcal/kg/day; and very
active adults require 40 kcal/kg/day.
A. Energy content of food
• The energy content of food is calculated from the heat released by
the total combustion of food in a calorimeter.
• It is expressed in kilocalories (kcal, or Cal).
• The metabolic caloric value of different macronutrient is as follows:
• Carbohydrate: 4 kcal/g
• Protein: 4 kcal/g
• Fat: 9 kcal/g
• Alcohol: 7 kcal/g
B. How energy is used in the body

• The energy generated by metabolism of the macronutrients is used for three

energy-requiring processes that occur in the body: resting metabolic rate,
thermic effect of food, and physical activity.

1. Resting metabolic rate: It represents the energy required to carry out the
normal body functions, such as respiration, blood flow, ion transport, and
maintenance of cellular integrity.

• In an average adult, the RMR is about 1,800 kcal for men (70 kg) and 1,300
kcal for women (50 kg). From 50–70% of the daily energy expenditure in
sedentary individuals is attributable to the RMR.
2. Thermic effect of food: The production of heat by the body increases as
much as 30% above the resting level during the digestion and absorption of
food. This effect is called the thermic effect of food or diet-induced
thermogenesis.

3. Physical activity: Muscular activity provides the greatest variation in energy

expenditure. The amount of energy consumed depends on the duration and
intensity of the exercise.

• The daily expenditure of energy can be estimated by carefully recording

the type and duration of all activities.

• In general, a sedentary person requires about 30–50% more than the

resting caloric requirement for energy balance, whereas a highly active
individual may require 100% or more calories above the RMR.
• Acceptable Macronutrient Distribution Ranges (AMDR) are defined as a range
of intakes for a particular macronutrient that is associated with reduced risk
of chronic disease while providing adequate amounts of essential nutrients.

• The AMDR for adults is 45–65% of their total

calories from carbohydrates, 20–35% from fat, and
10–35% from protein.
DIETARY CARBOHYDRATES
• The primary role of dietary carbohydrate is to provide energy.
A. Classification of carbohydrates
• Carbohydrates in the diet are classified as either monosaccharides
and disaccharides (simple sugars), polysaccharides (complex
sugars), or fiber.
1. Monosaccharides: Glucose and fructose are the principal mono-
saccharides found in food. Glucose is abundant in fruits, sweet corn,
corn syrup, and honey. Free fructose is found together with free
glucose and sucrose in honey and fruits.
2. Disaccharides: The most abundant disaccharides are sucrose
(glucose + fructose), lactose (glucose + galactose), and maltose
(glucose + glucose).
• Sucrose is ordinary “table sugar,” and is abundant in molasses and maple syrup.
Lactose is the principal sugar found in milk. Maltose is a product of enzymic
digestion of polysaccharides. It is also found in significant quantities in beer and
malt liquors.

3. Polysaccharides: Complex carbohydrates are polysaccharides (most

often polymers of glucose), which do not have a sweet taste.
• Starch is an example of a complex carbohydrate that is found in abundance in
plants. Common sources include wheat and other grains, potatoes, dried peas and
beans, and vegetables.

• Glycogen another example of complex carbohydrate is found in animals.

4. Fiber: Dietary fiber is that portion of plant-derived food that
cannot be completely digested by human digestive enzymes. It has
two components:
• Soluble fiber is completely or partially fermented to short-chain fatty acids in the
large intestine. Soluble fiber delays gastric emptying and can result in a sensation
of fullness.

• Insoluble fiber passes through the digestive track largely intact. They provide bulk
and absorb water as they move through the digestive tract, easing defecation.

• Consumption of soluble fiber has now been shown to lower LDL cholesterol levels
by increasing fecal bile acid excretion and interfering with bile acid absorption.

• Also, fiber- rich diets decrease the risk for constipation, hemorrhoids, and
diverticulosis.
Requirements for carbohydrate
• Carbohydrates are not essential nutrients, because the carbon
skeletons of most amino acids can be converted into glucose.
• However, the absence of dietary carbohydrate leads to ketone body
production, and degradation of body protein whose constituent
amino acids provide carbon skeletons for gluconeogenesis.
• The RDA for carbohydrate is set at 130 g/day for adults and
children, based on the amount of glucose used by carbohydrate-
dependent tissues, such as the brain and erythrocytes.
 DIETARY FATS
A. Plasma lipids and Coronary Heart Disease (CHD)
• Plasma cholesterol may arise from the diet (animal products) or from
endogenous biosynthesis. In either case, cholesterol is transported
between the tissues in combination with protein and phospholipids as
lipoproteins.
1. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL): The
level of plasma cholesterol is not precisely regulated, but rather varies in
response to the diet.
• Elevated levels result in an increased risk for CHD. The risk increases
progressively with higher values for serum total cholesterol.
• A much stronger correlation exists between the levels of blood LDL
cholesterol and heart disease.
• In contrast, high levels of HDL cholesterol have been associated with a
decreased risk for heart disease.
B. Dietary fats and plasma lipid
• Triacylglycerols are quantitatively the most important class of
dietary fats.
• The influence of triacylglycerols on blood lipids is determined by
the chemical nature of their constituent fatty acids.
1. Saturated fat: Triacylglycerols composed primarily of fatty acids
whose hydrocarbon chains do not contain any double bonds are
referred to as saturated fats.
• Consumption of saturated fats is positively associated with
high levels of total plasma cholesterol and LDL cholesterol,
and an increased risk of CHD.
• The main sources of saturated fatty acids are dairy and meat
products and some vegetable oils, such as coconut and palm oils.
Most experts strongly advise limiting intake of saturated fats.
• Saturated fatty acids with carbon chain lengths of 14 (myristic)
and 16 (palmitic) are most potent in increasing the serum
cholesterol.
• Stearic acid (18 carbons—found in many foods including
chocolate) has little effect on blood cholesterol.
2. Monounsaturated fats: Triacylglycerols containing primarily fatty
acids with one double bond are referred to as monounsaturated fat.
• Unsaturated fatty acids are generally derived from vegetables and fish.

• When substituted for saturated fatty acids in the diet, monounsaturated

fats lower both total plasma cholesterol and LDL cholesterol but maintain
or increase HDL cholesterol.

3. Polyunsaturated fats: Triacylglycerols containing primarily fatty

acids with more than one double bond are referred to as
polyunsaturated fats. The effects of polyunsaturated fatty acids
(PUFAs) on cardiovascular disease is influenced by the location of the
double bonds within the molecule.
a. w-6 Fatty acids: These are long-chain, PUFAs, with the first double
bond beginning at the sixth bond position when starting from the
methyl end of the fatty acid molecule.
• Consumption of fats containing w-6 PUFAs, principally linoleic acid, 18:2(9,12),
obtained from vegetable oils, lowers plasma cholesterol when substituted for
saturated fats. Plasma LDL are lowered, but HDL, which protect against CHD, are
also lowered.

b.w-3 Fatty acids: These are long-chain, PUFAs, with the first double
bond beginning at the third bond position from the methyl end.
• Dietary w-3 polyunsaturated fats suppress cardiac arrhythmias, reduce serum
triacylglycerols, decrease the tendency for thrombosis, lower blood pressure, and
substantially reduce risk of cardiovascular mortality, but they have little effect on
LDL or HDL cholesterol levels.
4. Trans fatty acids: Trans fatty acids are chemically classified
as unsaturated fatty acids, but behave more like saturated
fatty acids in the body, that is, they elevate serum LDL (but
not HDL), and they increase the risk of CHD.
• Trans fatty acids do not occur naturally in plants, but occur in small
amounts in animals.

• Trans fatty acids are formed during the hydrogenation of liquid

vegetable oils, for example, in the manufacture of margarine and
partially hydrogenated vegetable oil.
DIETARY PROTEIN

• The protein in food provides essential amino acids. Nine of the

20 amino acids needed for the synthesis of body proteins are
essential—that is, they cannot be synthesized in humans.
• The quality of a dietary protein is a measure of its ability to
provide the essential amino acids required for tissue
maintenance.
1. Proteins from animal sources: Proteins from animal sources
(meat, poultry, milk, and fish) have a high quality because they
contain all the essential amino acids in proportions similar to
those required for synthesis of human tissue proteins.
2. Proteins from plant sources: Proteins from wheat, corn,
rice, and beans have a lower quality than do animal proteins.
However, proteins from different plant sources may be
combined in such a way that the result is equivalent in
nutritional value to animal protein.
• For example, wheat (lysine-deficient but methionine-rich) may be
combined with kidney beans (methionine-poor but lysine-rich) to
produce an improved biologic value.
Nitrogen balance
• Nitrogen balance occurs when the amount of nitrogen consumed
equals that of the nitrogen excreted in the urine, sweat, and feces.
Most healthy adults are normally in nitrogen balance.
Positive nitrogen balance: This occurs when nitrogen intake exceeds
nitrogen excretion. It is observed during situations in which tissue
growth occurs, for example, in childhood, pregnancy, or during
recovery from an emaciating illness.
Negative nitrogen balance: This occurs when nitrogen loss is greater
than nitrogen intake. It is associated with inadequate dietary protein,
lack of an essential amino acid, or during physiologic stresses, such as
trauma, burns, illness, or surgery.
• Consumption of excess protein: There is no physiologic advantage to the
consumption of more protein than the RDA.

• Protein consumed in excess of the body’s needs is deaminated, and the

resulting carbon skeletons are metabolized to provide energy or acetyl
coenzyme A for fatty acid synthesis.

• The protein-sparing effect of carbohydrate: The dietary protein

requirement is influenced by the carbohydrate content of the diet. When
the intake of carbohydrates is low, amino acids are deaminated to provide
carbon skeletons for the synthesis of glucose that is needed as a fuel by
the central nervous system.

• If carbohydrate intake is less than 130 g/day, substantial amounts of

protein are metabolized to provide precursors for gluconeogenesis.
Therefore, carbohydrate is considered to be “protein-sparing,” because
it allows amino acids to be used for repair and maintenance of tissue
protein rather than for gluconeogenesis.
VITAMINS
• Vitamins are organic nutrients/molecules that are required in small
quantities in the diet and serve specialized functions in the body such
as for normal growth, maintenance and reproduction.

• They differ from other organic food molecules in that:

• They do not enter tissue structures, unlike proteins.

• Do not undergo degradation to provide energy.

• Several B complex vitamins play an important role as coenzymes in several

biochemical reactions.

• They are not produced in the body and most of them must be
provided in the diet.
• Vitamins can basically be classified into the following two categories:

Fat-soluble vitamins
• Includes Vitamins A, D, E and K; dissolve in fats; and are absorbed with the
help of fats that are in the diet.
• They have structures which are mostly complex hydrocarbons with only a few
functional groups
• Excessive fat-soluble vitamins are stored in the liver and will not be
eliminated from the body.

Water-soluble vitamins
• Includes Vitamins B and C, and dissolve in water.
• They have more functional groups that interact with water.
• Excessive amount of water-soluble vitamins are excreted through urine and
sweat.
• Water-soluble vitamins are readily absorbed in the intestine, but
absorption of fat-soluble vitamins depends on mixed bile salt micelles.

• Water-soluble vitamins are transported in blood.

• Fat-soluble vitamins are transported either as constituents of

lipoproteins or bound to specific plasma proteins.

• Fat-soluble vitamins supplements are most effective when taken with a

fatty meal.

• Fat-soluble vitamins deficiencies are most likely in patients with fat mal-
absorption.
VITAMIN A

• The retinoids, a family of molecules that are related to retinol (vitamin A),
are essential for vision, immunity, reproduction, growth, and maintenance
of epithelial tissues.

• Retinoic acid, derived from oxidation of dietary retinol, mediates most of

the actions of the retinoids, except for vision, which depends on retinal,
the aldehyde derivative of retinol.

• Distribution of vitamin A: Liver, kidney, cream, butter, and egg yolk are
good sources of preformed vitamin A. Yellow and dark green vegetables
and fruits are good dietary sources of the carotenes, which serve as
precursors of vitamin A.
A. Structure of vitamin
Vitamin A is often used as a collective term for several related biologically
active molecules. The term retinoids includes both natural and synthetic
forms of vitamin A that may or may not show vitamin A activity.

1. Retinol: A primary alcohol, retinol is found in animal tissues as a retinyl

ester with long-chain fatty acids.

2. Retinal: This is the aldehyde derived from the oxidation of retinol. Retinal
and retinol can readily be interconverted.

3. Retinoic acid: This is the acid derived from the oxidation of retinal.
Retinoic acid cannot be reduced in the body, and, therefore, cannot give rise
to either retinal or retinol.

4. b-Carotene: Plant foods contain b-carotene, which can be oxidatively

cleaved in the intestine to yield two molecules of retinal.
B. Absorption and transport of vitamin A
1. Transport to the liver: Retinyl esters present in the diet are
hydrolyzed in the intestinal mucosa, releasing retinol and free fatty
acids.
• Retinol derived from esters and from the cleavage and reduction of
carotenes is re-esterified to long-chain fatty acids in the intestinal
mucosa and secreted as a component of chylomicrons into the
lymphatic system.
• Retinyl esters contained in chylomicron remnants are taken up by, and
stored in, the liver.

2. Release from the liver: When needed, retinol is released from

the liver and transported to extrahepatic tissues by the plasma
retinol-binding protein (RBP).
• The retinol–RBP complex attaches to specific receptors on the surface
of the cells of peripheral tissues, permitting retinol to enter.
C. Mechanism of action of vitamin A
• Retinol is oxidized to retinoic acid.
• Retinoic acid binds with high affinity to specific receptor
proteins present in the nucleus of target tissues, such as
epithelial cells.
• The activated retinoic acid–receptor complex interacts with
nuclear chromatin to regulate gene expression, resulting in
control of the production of specific proteins that mediate
several physiologic functions.
• For example, retinoids control the expression of the gene for
keratin in most epithelial tissues of the body.
D. Functions of vitamin A
• 1. Visual cycle: Rhodopsin, the visual pigment of the rod cells in the
retina, consists of 11-cis retinal specifically bound to the protein opsin.

• When rhodopsin is exposed to light, a series of photochemical

isomerization occurs, which results in the release of all-trans retinal and
opsin.

• This process triggers a nerve impulse that is transmitted by the optic

nerve to the brain.

• The brain processes the impulse into an image.

• Regeneration of rhodopsin requires isomerization of all-trans retinal back

to 11-cis retinal.

• 11-cis retinal combines with opsin to form rhodopsin, thus completing

the cycle. Similar reactions are responsible for color vision in the cone
cells.
2. Growth: Vitamin A is required for normal growth and bone
development in children.
3. Reproduction: Retinol and retinal are essential for normal
reproduction, supporting spermatogenesis in the male and
preventing fetal resorption in the female.
• Retinoic acid is inactive in maintaining reproduction and in the visual
cycle, but promotes growth and differentiation of epithelial cells.

4. Maintenance of epithelial cells: Vitamin A is essential for normal

differentiation of epithelial tissues and mucus secretion.
E. Clinical indications
• Retinol and its precursor are used as dietary supplements, whereas
various forms of retinoic acid are useful in dermatology.
• Dietary deficiency: Night blindness is one of the earliest signs of vitamin
A deficiency, making it difficult to see in dim light.
• Prolonged deficiency leads to an irreversible loss in the number of visual
cells.
• Severe vitamin A deficiency leads to xerophthalmia, a pathologic dryness
of the conjunctiva and cornea.
• Vitamin A is required for the differentiation and proliferation of the
epithelium of the conjunctiva and cornea.
• If untreated, xerophthalmia results in corneal ulceration and,
ultimately, in blindness because of the formation of opaque scar tissue.
• Keratomalacia is severe eye disorder as a result of vitamin A
deficiency.
• Normal epithelium is replaced by inappropriately keratinised
epithelium leading to opaque cornea.

• Acne and psoriasis: Dermatologic problems such as acne

and psoriasis are effectively treated with retinoic acid or its
derivatives.
G. Toxicity of retinoids
1. Vitamin A: Excessive intake of vitamin A produces a toxic
syndrome called hypervitaminosis A.
• Amounts exceeding 7.5 mg/day of retinol should be avoided.
• Early signs of chronic hypervitaminosis A are reflected in:
• the skin, which becomes dry and

• the liver, which becomes enlarged and can become cirrhotic, and

• the nervous system, where a rise in intracranial pressure may mimic the
symptoms of a brain tumor.

• Pregnant women particularly should not ingest excessive

quantities of vitamin A because of its potential for causing
congenital malformations in the developing fetus.
VITAMIN D
• The active form of vitamin D, 1,25-dihydroxycholecalciferol
(1,25-diOH-D3), also know as calcitriol have hormone like
function. Normally formed in the kidneys.
• It binds to intracellular receptor proteins.
• The 1,25-diOH-D3–receptor complex interacts with DNA in the
nucleus of target cells in a manner similar to that of vitamin A,
and either selectively stimulates gene expression or specifically
represses gene transcription.
• The most prominent actions of calcitriol are to regulate the
plasma levels of calcium and phosphorus.
A. Distribution of vitamin D
• Diet: Ergocalciferol (vitamin D ), found in plants, and cholecalciferol
2

(vitamin D ), found in animal tissues, are sources of pre- formed

3

vitamin D activity.
• Vitamin D occurs naturally in fatty fish, liver, and egg yolk. Milk,
unless it is artificially fortified, is not a good source of the vitamin.
• Endogenous vitamin precursor: 7-Dehydrocholesterol, an inter-
mediate in cholesterol synthesis, is converted to cholecalciferol in
the dermis and epidermis of humans exposed to sunlight.
• Preformed vitamin D is a dietary requirement only in individuals
with limited exposure to sunlight.
C. Function of vitamin D
• Calcitriol maintains adequate plasma levels of calcium by: 1)
increasing uptake of calcium by the intestine, 2) minimizing loss of
calcium by the kidney, and 3) stimulating resorption of bone when
necessary.

• Effect of vitamin D on the intestine: Calcitriolstimulates intestinal

absorption of calcium and phosphate.
• Calcitriol binds to a cytosolic receptor. The calcitriol–receptor complex then
moves to the nucleus where it selectively interacts with the cellular DNA.

• As a result, calcium uptake is enhanced by an increased synthesis of a

specific calcium-binding protein.

• Effect of vitamin D on bone: Calcitriolstimulates the mobilization of

calcium and phosphate from bone. The result is an increase in
plasma calcium and phosphate.
D. Clinical indications
1. Nutritional rickets: Vitamin D deficiency causes a net de-
mineralization of bone, resulting in rickets in children and
osteomalacia in adults.
• Rickets is characterized by the continued formation of the collagen
matrix of bone, but incomplete mineralization, resulting in soft,
pliable bones.
• In osteomalacia, demineralization of pre-existing bones increases
their susceptibility to fracture.
• Insufficient exposure to daylight and/or deficiencies in vitamin D
consumption occur predominantly in infants and the elderly.
2. Renal osteodystrophy: Chronic renal failure results in decreased
ability to form the active form of vitamin D. Supplementation with
calcitriol is an effective therapy.

E. Toxicity of vitamin D
• Like all fat-soluble vitamins, vitamin D can be stored in the body and
is only slowly metabolized.
• High doses (100,000 IU for weeks or months) can cause loss of appetite,
nausea, thirst, and stupor. Enhanced calcium absorption and bone
resorption results in hypercalcemia, which can lead to deposition of
calcium in many organs, particularly the arteries and kidneys.
VITAMIN K
• The principal role of vitamin K is in the post-translational modification
of various blood clotting factors, in which it serves as a coenzyme in the
carboxylation of certain glutamic acid residues present in these
proteins.

• Vitamin K exists in several forms, for example, in plants as phyllo-

quinone (or vitamin K ), and in intestinal bacterial flora as menaquinone
1

(or vitamin K ). A synthetic form of vitamin K, menadione, is available.

2

• Vitamin K is found in cabbage, kale, spinach, egg yolk, and liver. There is
also extensive synthesis of the vitamin by the bacteria in the gut.
A. Function of vitamin K
1. Formation of g-carboxyglutamate (Gla): Vitamin K is required in the
hepatic synthesis of prothrombin and blood clotting factors II, VII, IX, and X.
• These proteins are synthesized as inactive precursor molecules. Formation of the
clotting factors requires the vitamin K–dependent carboxylation of glutamic acid
residues.

• This forms a mature clotting factor that is capable of subsequent activation.

• The carboxylation is sensitive to inhibition by dicumarol, an anti- coagulant and by

warfarin, a synthetic analog of vitamin K.

2. Interaction of prothrombin with platelets: The Gla residues of

prothrombin can bind to calcium ions.
• The prothrombin–calcium complex is then able to bind to phospholipids essential
for blood clotting on the surface of platelets.
B. Clinical indications
1. Deficiency of vitamin K: A true vitamin K deficiency is unusual
because adequate amounts are generally produced by intestinal
bacteria or obtained from the diet.
• If the bacterial population in the gut is decreased, for example, by
antibiotics, this can lead to hypoprothrombinemia.

2. Deficiency of vitamin K in the newborn: Newborns have sterile

intestines and so initially lack the bacteria that synthesize vitamin
K.
• Because human milk provides only about one fifth of the daily
requirement for vitamin K, it is recommended that all
newborns receive a single intramuscular dose of vitamin K as
prophylaxis against hemorrhagic disease.
C. Toxicity of Vitamin K
• Prolonged administration of large doses of synthetic vitamin K
(menadione) can produce hemolytic anemia and jaundice in the
infant, due to toxic effects on the membrane of red blood cells;
therefore, it is no longer used to treat vitamin K deficiency.
VITAMIN E
• The E vitamins consist of eight naturally occurring tocopherols, of
which a-tocopherol is the most active.
• The primary function of vitamin E is as an antioxidant in prevention
of the non-enzymic oxidation of cell components, for example,
polyunsaturated fatty acids, by molecular oxygen and free radicals.
• Vegetable oils are rich sources of vitamin E, whereas liver and eggs
contain moderate amounts. The vitamin E requirement increases
as the intake of polyunsaturated fatty acid increases.
A. Deficiency of Vitamin E
• Vitamin E deficiency is almost entirely restricted to premature infants.

• When observed in adults, it is usually associated with defective lipid

absorption or transport.

• The signs of human vitamin E deficiency include sensitivity of

erythrocytes to peroxide, and the appearance of abnormal cellular
membranes.

B. Toxicity of vitamin E
• Vitamin E is the least toxic of the fat-soluble vitamins, and no toxicity has
been observed at doses of 300 mg/day.
 FOLIC ACID
• Folic acid (or folate), which plays a key role in one-carbon
metabolism, is essential for the biosynthesis of several
compounds.
• Sources of folate include liver, kidney, dark green leafy
vegetables, meats, fish, whole grains, fortified grains and
cereals, legumes, and citrus fruits

A. Function of folic acid

• Tetrahydrofolate (reduced folate) receives one-carbon
fragments from donors such as serine, glycine, and histidine and
transfers them to intermediates in the synthesis of amino acids,
purines, and thymidine monophosphate (TMP)—a pyrimidine
found in DNA.
B. Nutritional anemias
• Nutritional anemias—those caused by inadequate intake of one or
more essential nutrients—can be classified according to the size of
the red blood cells or mean corpuscular volume observed in the
individual.
• Microcytic anemia, caused by lack of iron, is the most common
form of nutritional anemia.
• The second major category of nutritional anemia, macrocytic,
results from a deficiency in folic acid or vitamin B . 12

• These macrocytic anemias are commonly called megaloblastic because a

deficiency of folic acid or vitamin B 12 causes accumulation of large, immature red
cell precursors, known as megaloblasts, in the bone marrow and the blood.
• Folate and anemia: Inadequate serum levels of folate can be
caused by
• increased demand (for example, pregnancy and lactation),

• poor absorption caused by pathology of the small intestine,

• alcoholism, or

• treatment with drugs that are dihydrofolate reductase inhibitors, for

example, methotrexate.

• A primary result of folic acid deficiency is megaloblastic

anemia, caused by diminished synthesis of purines and TMP,
which leads to an inability of cells (including red cell
precursors) to make DNA and, therefore, they cannot divide.
• Folate and neural tube defects in the fetus: Spina bifida and
anencephaly are the most common neural tube defects.
• Folic acid supplementation before conception and during the first
trimester has been shown to significantly reduce the defects.
• Therefore, all women of childbearing age are advised to consume 0.4
mg/day of folic acid.
• Adequate folate nutrition must occur at the time of conception
because critical folate-dependent development occurs in the first
weeks of fetal life — at a time when many women are not yet aware of
their pregnancy.
• However, there is an association of high-dose supplementation with
folic acid (>0.8 mg/day) and an increased risk of cancer. Thus,
supplementation is not recommended for most middle-aged or older
adults.
 COBALAMIN (VITAMIN B 12)

• Vitamin B is required in humans for two essential enzymatic

12

reactions:
• the re-methylation of homocysteine to methionine and

• the isomerization of methylmalonyl CoA that is produced during the

degradation of some amino acids (isoleucine, valine, threonine, and
methionine), and fatty acids with odd numbers of carbon atoms.

• When the vitamin is deficient, unusual fatty acids accumulate

and become incorporated into cell membranes, including those
of the nervous system.
• This may account for some of the neurologic manifestations of
vitamin B12 deficiency.
• It is involved in DNA synthesis.
• Vitamin B12 is synthesized only by microorganisms; it is not
present in plants.

• Animals obtain the vitamin preformed from their natural

bacterial flora or by eating foods derived from other animals.

• Cobalamin is present in appreciable amounts in liver, whole milk,

eggs, oysters, fresh shrimp, pork, and chicken.

A Clinical indications for vitamin B 12

• In contrast to other water-soluble vitamins, significant amounts

(4–5 mg) of vitamin B 12 are stored in the body.

• As a result, it may take several years for the clinical symptoms of

B12 deficiency to develop in individuals who have had a partial or
total gastrectomy and can no longer absorb the vitamin.
• Pernicious anemia: Vitamin B12 deficiency is rarely a result of an absence of the
vitamin in the diet.

• A severe malabsorption of vitamin B 12 leads to pernicious anemia.

• This disease is most commonly a result of an autoimmune destruction of the

gastric parietal cells that are responsible for the synthesis of a glycoprotein
called intrinsic factor.

• Normally, vitamin B 12 obtained from the diet binds to intrinsic factor in the
intestine.

• The cobalamin–intrinsic factor complex travels through the gut and eventually
binds to specific receptors on the surface of mucosal cells of the ileum.

• The bound cobalamin is transported into the mucosal cell and, subsequently,
into the general circulation, where it is carried by B 12-binding proteins.

• Patients with cobalamin deficiency are usually anemic, but later in the
development of the disease they show neuropsychiatric symptoms.

• The disease is treated by giving high-dose B12 orally, or intramuscular (IM)

injection of cyanocobalamin.
 PYRIDOXINE (VITAMIN B ) 6

• Vitamin B6 is a collective term for pyridoxine, pyridoxal, and

pyridoxamine, all derivatives of pyridine.

• They differ only in the nature of the functional group attached

to the ring.

• Pyridoxine occurs primarily in plants, whereas pyridoxal and

pyridoxamine are found in foods obtained from animals.

• All three compounds can serve as precursors of the biologically

active coenzyme, pyridoxal phosphate.

• Pyridoxal phosphate functions as a coenzyme for a large number

of enzymes, particularly those that catalyze reactions involving
amino acids.
• Sources include pork, meats, whole grains and cereals, legumes,
and green, leafy vegetables.
• Dietary deficiencies in pyridoxine are rare but have been observed
in new-born infants fed formulas low in B , in women taking oral
6

contraceptives, and in alcoholics.

• The classic clinical syndrome for vitamin B deficiency is a dermatitis-like
6

eruption, glossitis with ulceration, angular cheilitis, conjunctivitis,

intertrigo, and neurologic symptoms like, confusion, and neuropathy (due
to impaired sphingosine synthesis) and sideroblastic anemia (due to
impaired heme synthesis).
• Toxicity of pyridoxine: Pyridoxine is the only water-soluble
vitamin with significant toxicity.
• Neurologic symptoms (sensory neuropathy) occur at intakes
above 200 mg/day, an amount more than 100 times the RDA.
• Substantial improvement, but not complete recovery, occurs
when the vitamin is discontinued.
 THIAMINE (VITAMIN B 1)

• Thiamine pyrophosphate is the biologically active form of the vitamin,

formed by the transfer of a pyrophosphate group from ATP to thiamine.

• It is important in transmission of nerve impulses by acting as a

phosphate donor for phosphorylation of the nerve membrane sodium
transport channel.

• It acts as a coenzyme in many metabolic reactions.

• Sources of thiamin include peas, pork, liver, legumes, whole grains and
fortified grain products such as cereal, and enriched products like bread,
pasta and rice.
A. Clinical indications for thiamine
• The oxidative decarboxylation of pyruvate and a-ketoglutarate, which
plays a key role in energy metabolism of most cells, is particularly
important in tissues of the nervous system.

• In thiamine deficiency, the activity of these two dehydrogenase-catalyzed

reactions is decreased, resulting in a decreased production of ATP and,
thus, impaired cellular function.

• Beriberi: Signs of infantile beriberi include tachycardia, vomiting,

convulsions, and, if not treated, death.
• The deficiency syndrome can have a rapid onset in nursing infants whose mothers
are deficient in thiamine.

• Adult beriberi is characterized by dry skin, irritability, disordered thinking, and

progressive paralysis. When this is coupled with edema, the disease is called wet
beriberi.
• Wernicke-Korsakoff syndrome: Seen in chronic alcoholism, due to dietary
insufficiency or impaired intestinal absorption of the vitamin.
• Wernicke- Korsakoff syndrome—a thiamine deficiency state is
characterized by apathy, loss of memory, ataxia, and a rhythmic to-and-
fro motion of the eyeballs (nystagmus).

• The neurologic consequences of Wernicke's syndrome are treatable with

thiamine supplementation.
 RIBOFLAVIN (VITAMIN B 2)

• The two biologically active forms are flavin mononucleotide (FMN) and
flavin adenine dinucleotide (FAD), formed by the transfer of an adenosine
monophosphate moiety from ATP to FMN.

• FMN and FAD are bound tightly—sometimes covalently—to flavoenzymes

that catalyze the oxidation or reduction of a substrate.

• Sources include liver, eggs, dark green vegetables, legumes, whole and
enriched grain products, and milk.

• Riboflavin deficiency is not associated with a major human disease,

although it frequently accompanies other vitamin deficiencies.

• Deficiency symptoms include dermatitis, stomatitis (painful red tongue

with sore throat), cheilosis (fissuring at the corners of the mouth), and
glossitis (the tongue appearing smooth and purplish). Eyes can be itchy,
watery and sensitive to light.
 NIACIN (VITAMIN B ) 3

• Niacin, or nicotinic acid, forms a biologically active coenzyme known as

nicotinamide adenine dinucleotide (NAD ) and its phosphorylated
+

derivative, nicotinamide adenine dinucleotide phosphate (NADP ). +

• Nicotinamide also occurs in the diet. Sources include liver, fish, poultry,
meat, peanuts, whole and enriched grain products.

• NAD and NADP serve as coenzymes in oxidation-reduction reactions in

+ +

which the coenzyme undergoes reduction. The reduced forms of NAD +

and NADP are NADH and NADPH, respectively.

+
Clinical indications for niacin
• Deficiency of niacin: A deficiency of niacin causes pellagra, a
disease involving the skin, gastrointestinal tract, and CNS.
• The symptoms of pellagra progress through the three Ds: dermatitis,
diarrhea, dementia—and, if untreated, death.

• Treatment of hyperlipidemia: Niacin strongly inhibits lipolysis

in adipose tissue.
• The liver normally uses these circulating fatty acids as a major
precursor for triacylglycerol synthesis.
• Thus, niacin causes a decrease in liver triacylglycerol synthesis,
which is required for VLDL production. LDL is derived from VLDL in
the plasma.
• Therefore, niacin is particularly useful in the treatment
hyperlipoproteinemia, in which both VLDL and LDL are elevated.
 BIOTIN

• Biotin is a coenzyme in carboxylation reactions, in which it serves as a

carrier of activated carbon dioxide.

• Biotin deficiency does not occur naturally because the vitamin is widely
distributed in food.

• Sources of Biotin include liver, kidney, egg yolk, milk, most fresh
vegetables, yeast breads and cereals. Biotin is also made by intestinal
bacteria.

• However, the addition of raw egg white to the diet as a source of protein
induces symptoms of biotin deficiency, namely, dermatitis, glossitis, loss
of appetite, and nausea.

• Raw egg white contains a glycoprotein, avidin, which tightly binds biotin
and prevents its absorption from the intestine.
 PANTOTHENIC ACID

• Pantothenic acid is a component of coenzyme A (CoA), which functions in the

transfer of acyl groups.

• CoA contains a thiol group that carries acyl compounds. Examples of such
structures are succinyl CoA, fatty acyl CoA, and acetyl CoA.

• Pantothenic acid is also a component of the acyl carrier protein (ACP) domain
of fatty acid synthase.

• Eggs, liver, and yeast are the most important sources of pantothenic acid,
although the vitamin is widely distributed.

• Pantothenic acid deficiency is not well characterized in humans.

 ASCORBIC ACID (VITAMIN C)

• The active form of vitamin C is ascorbic acid.

• The main function of ascorbate is as a reducing agent in several different

reactions.

• Vitamin C has a well-documented role as a coenzyme in hydroxylation

reactions, for example, hydroxylation of prolyl and lysyl residues of
collagen.

• Vitamin C is, therefore, required for the maintenance of normal

connective tissue, as well as for wound healing.

• Vitamin C also facilitates the absorption of dietary iron from the intestine.

• The best sources of Vitamin C are citrus fruits, such as orange, kiwi fruit,
grapefruit, sweet red pepper.
• Vitamin C works with vitamin E as an antioxidant, and plays a crucial
role in neutralizing free radicals throughout the body.
Deficiency of ascorbic acid
• A deficiency of ascorbic acid results in scurvy, a disease character-
ized by sore and spongy gums, loose teeth, fragile blood vessels,
swollen joints, and anemia.
• Many of the deficiency symptoms can be explained by a deficiency
in the hydroxylation of collagen, resulting in defective connective
tissue.