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Vitamins
Definitions:
Vitamins are organic compounds required by the
body in trace amounts to perform specific
function, and can not be synthesized by humans,
or can not be synthesized in adequate (sufficient)
quantities to meet needs.
 When present in inadequate quantities, deficiency
states results leading to disease.
 Modern views suggest that more quantities than
RDIS might be needed to prevent some chronic
diseases.

Definitions:

Provitamins are precursors of vitamins that could
be converted into vitamins inside the body e.g.
Carotenes are provitamin A.

Vitamers: These are different forms of one
vitamin e.g. Vitamin D has 2 vitamers; D2 &D3.
Common features of fat soluble
vitamins:
 Released,
absorbed and transported with
the fat in the diet.
 Not readily excreted in the urine.
 Excess of immediate need is stored in liver
or adipose tissues.
 Some cause toxicity in excess.
. Vitamin A (retenoids)
Carotenes are the provitamin A.
The different forms (vitamers) of vitamin
A used by the body are :retinol, retinal
and retinoic acid
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Sources:
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Liver, kidney, eggs milk fat and fish liver oil.
It is also present in yellow and dark green
vegetables as provitamin A Carotenes (α, β and
γ).
Requirements:
 it is expressed as retinol equivalent where 1 RE
equals 1 μg of retinol. RE equals 5 IU and the
daily requirement is about 5000 lU.
Absorption and Metabolism
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In the intestine, β-carotene is converted into
retinal. Retinyl esters also are hydrolyzed and
retinol is absorbed.
In the intestinal mucosal cells, retinol is reesterified with palmitic acid and transported in
chylomicrons to the liver, where 90% of the
body's vitamin A is stored.
Retinoic acid is absorbed directly into the portal
circulation to the liver.
When the body cells need vitamin A, retinyl
esters are hydrolyzed and free retinol combines
with a protein formed by the liver called retinol
binding protein (RBP).
RBP carries retinol to the target cells. When
retinol becomes inside the cells, it is bound by
cellular retinol binding protein (CRBP).
Functions of vitamin A:

Vision: The human retina contains
two types of receptor cells for vision;
cones and rods. Vitamin A is a
component of
visual pigments
present in cones and rods. Cone cells
are responsible for day vision and
color. Rod cells are responsible for
vision in poor light e.g. at night.
Visual cycle:
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Rhodopsin (the visual pigment of rod cells)consists
of protein called opsin bound to 11-cis retinal
(double bond at position 11 is in cis form, while other
double bonds are in trans form).
When rhodopsin is exposed to light, 11 cis retinal is
converted into all trans retinal (all double bonds are
in trans form), and dissociates from opsin.
All trans retinal changes the permeability of cell
membrane of rod cells. This allows the calcium ions
to pass out of the cell membrane. This stimulates the
nerve impulse in optic nerve. Thus the brain
perceives light.
Rhodopsin must regenerated for vision. All trans
retinal is converted back to 11-cis retinal, but this
conversion is incomplete. This can be supplied from
dietary retinol, which is oxidized to give 11 cis
retinal.
Functions of vitamin A (continue)
Vitamin A acts as a hormone. It binds to nuclear
proteins and acts on certain genes (by affecting
their transcription rate). It has the following
functions:
 Reproduction: Retinol and retinal are essential for
reproduction. They support sperm formation
(spermatogenesis) in males and maintain fetal life
in females.
 Growth: Vitamin A is essential for normal growth
and bone formation.

Functions of vitamin A (continue)
Glycoprotein synthesis, and phospholipids
synthesis in the lungs (lung surfactant) and for cell
differentiation .
 Maintenance of epithelial cells: It is essential for
normal differentiation of epithelial cells. This is
important for smoothness of skin and mucus
membranes.
 Antioxidant (anticancer) action: Retinoids and
carotinoids (Carotenes) act as antioxidants and
protect tissues from toxic effect of some oxidants
that may lead to epithelial tissue cancer
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Deficiency of vitamin A:

1- Eye: deficiency will lead to night blindness
(impaired dark adaptation) and Xeroophthalmia (dryness and roughness of cornea)
and keratomalicia..
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2-Growth retardation.

3-Skin and mucus membranes: roughness of skin
and mucus membranes of different body systems
e.g. urinary system. This leads to increased
susceptibility to infection.

4- Degeneration of testes and abortion.

5-Hydrocephalus
pressure
and
increased
intracranial
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Treatment of deficiency: the usual line of
treatment is 220 mg of retinol orally divided on
two days.

Evaluation of nutritional status: retinol level in
serum is the most widely used method, the
normal range for children is 20-90 ug/dl, in adult
it is 30-90 ug/dl, serum level higher than 100
ug/dl is an indication of toxicity.
Excess vitamin A intake
(hypervitaminosis A):
intake of more than 100000 IU/day: Occurs when
excessive vitamin A intake exceeds the capacity of
RBP.
 Free retinol will be released in blood with the
following toxic effects; Headache, nausea, bone
pain due to bony depositions (hyperostosis) and
loss of hair, dermatitis and skin itching.
 Vitamin A is teratogenic in high doses (> 15000
IU/day) if taken during the first two months of
pregnancy. It may cause congenital abnormalities
in the fetus including microcephaly, dilated
ventricles and abortion.

RDI: 10 µg/day
400 lU/day
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The synthesis of provitamin D3 and Vitamin D3 are selfcontrolled processes since further absorption of UV light
causes isomerizations of these compounds to yield inactive
products.
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In human system, the production of Vitamin D3 in skin is
important, since nutritional supply of Vitamin D3 as well as
Vitamin D2 is limited.
the sources of dietary vitamin D are limited primarily to
liver, eggs, butter, fortified milk and fatty fish.
Conversion of 7-dehydrocholesterol to previtamin D3 is
decreased to less than half in elderly people.
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From skin Vitamin D3 enters to circulation where all
Vitamin D compounds are mainly bound to Vitamin D
binding protein (DBP).
Dietary Vitamin D2 and D3 enter the circulation in the
chylomicrons.
In the body, both Vitamin D2 and D3 undergo similar
activation processes, which are prerequisite for their
biological activity.
Pathways of vitamin D activation and
inactivation:
Regulation of activation and inactivation
of vitamin D
Functions of vitamin D
Vitamin D plays an important role in
calcium and phosphate homeostasis
 It helps to increase serum calcium
and phosphate by:
1- Increasing intestinal absorption.
2- Decreasing renal excretion.
3- Increasing bone resorption.

Functions of vitamin D not related
to calcium homeostasis:
Beside its very well known function in calcium and
phosphate metabolism ,Vit. D receptors are found
in many tissues , thus it can exert its effects on
them.Examples:
A- Vit. D stimulate synthesis of non-collagenous
bone matrix proteins, e.g. osteocalcin ,osteopontin
B- It is possibly needed for the regulation of
differentiation and proliferation of various cells
including immuno regulatory cells, epidermal cells
and malignant tumor cells.
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Functions of vitamin D not related to
calcium homeostasis (continue):
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It was found that vitamin D causes arrest of cell in
G1 phase and induces apoptosis.
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It promotes monocyte differentiation and inhibits
lymphocyte proliferation and secretion of cytokines,
such as IL-2, interferon-γ and IL-12.
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Vit. D analogues are tried therapeutically eg.
treatment of psoriasis (vit D induces differentiation
and inhibits proliferation in keratinocytes).
Functions of vitamin D not related to
calcium homeostasis (continue):
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In several different types of cancer
cells Vitamin D has been shown to
have anti-proliferative effects.
 Vit
D and Ca deficiency are
associated with incidence of
colon and breast cancers.
 In vitro studies show vitamin D
analogues inhibit the
proliferation of these cells.
Deficiency of vitamin D:
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Causes demineralization of bones, resulting in
rickets in children and osteomalacia in adults ,
and is usually characterized by low serum calcium
and
phosphate,
and
increased
alkaline
phosphatase and parathyroid hormone levels.
Rickets is characterized by the continued
formation of the collagen matrix of bone , but
incomplete mineralization, resulting in soft ,
pliable bones.
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In osteomalacia demineralization of preexisting
bones increases their susceptibility to fracture.
Inability to activate to activate the vitamin in
chronic renal failure, results in renal rickets( renal
osteodystrophy)
Vitamin D Nutritional Status
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Vitamin D nutritional status can be
evaluated by measuring plasma levels of 25
OH D3 and 1 α,25 (OH)2 D3.
Serum level of 25 OH D3 represent an index
of vitamin store, while 1 α,25 (OH)2 D3 is
less reliable.
The acceptable level for adult is 20 ng/ml
for 25 OH D3 and 20-40 pg/ml for 1 α,25
(OH)2 D3.
Certain drugs as anticonvulsants used for
long
time
may
lead
to
rickets
or
osteomalacia.
Excess vitamin D (overdose or
hypervitaminosis D):
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The most toxic of the vitamins.
High doses can cause loss of appetite ,
nausea, thirst, and stupor.
Also
causes
increased
calcium
absorption
and
bone
resorption
resulting in hypercalceamia.
This leads to abnormal calcification of
tissues and deposition of calcium and
phosphate in different systems e.g.
urinary
system
causing
stone
formation.

Vitamin E (tocopherols)
Structure: there are four types of tocopherols α , β, γ and δ.
All of them contain tocol ring. The most active form is α
tocopherol (as antioxidant). , β, γ and δ tocopherols differ
from α tocnopherol in number and position of - CH3
groups attached to the tocol ring.
Sources:

green leafy plants and seed oils are the
best sources. The richest sources for
human are salad oils, margarines derived
from
soybean,
peanut,
corn
and
safflower oils. Animal sources containing
the highest amount include eggs, liver,
and muscle meats.
Requirements:
11-15 mg/day
Absorption and Transport
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absorption requires bile salts and pancreatic
esterase enzyme.
The
vitamin
is
incorporated
in
the
chylomicrons.
Most of the absorbed vitamin is deposited
initially in the liver and then distributed to
the adipose tissues.
In serum, two thirds of the vitamin is
transported bound to LDL with the rest
carried by the other lipoproteins.
In both the cardiac and hepatocyte
cytoplasm there is specific carrier protein
that
carries
the
vitamin
into
the
mitochondria.
Function of Vitamin E
vitamin E acts as antioxidant; it
prevents non-enzymatic oxidation of
cell
components
(e.g.
polyunsaturated fatty acids, DNA and
cell membranes) by molecular oxygen
or free radicals. By this function
vitamin E can prevent or decrease the
oxidation of LDL, and maintain
membrane integrity.
 Therefore ,The vitamin is found in all
cell membranes, the greatest amount
is found in adipose tissue.
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Deficiency: Occurs usually in premature
infant, in people with fat malabsorption
or biliary obstruction. Deficiency leads
to hemolysis of RBCs and anemia: due
to lack of protection against peroxides
and also leads to muscle breakdown.
It was found that people with
cardiovascular diseases and cancer
have lower levels of serum vitamin E
compared to the healthy people.
Signs, symptoms and treatment of
deficiency:
 they
are
not
specific
including
hemolytic
anemia,
myopathy,
weakness, ataxia, impaired reflexes,
ophthalmoplegia,
retinopathy.
In
severe deficiency, permanent damage
to nerve tissues takes place.
 Deficiency states may be corrected
with oral intake of 0.2-2.0 g/day.

Toxicity
 Toxicity
of vitamin E is not
observed up to more than 2000
mg/day. But doses of more than
100 mg/day can prevent the
activation of vitamin K, so it
should
be
avoided
during
anticoagulant therapy.
Use and effect of large doses: certain
rare inborn error of metabolism
respond to high doses of vitamin E e.g.
glucose-6-phosphate
dehydrogenase
deficiency,
glutathione
peroxidase
deficiency.
 Vitamin E is relatively non toxic even in
very high doses. But very high doses
for long period may impair immune
function and may interfere with
arachidonic acid and prostaglandin
metabolism.

Evaluation of nutritional status:
the best method is measuring vitamin E
level in blood, normal values are 0.5-1.2
mg/dl.
 Vitamin E mobilizes from the liver bound
to VLDL therefore hypolipidemic
patients will have lower serum levels.
 There is some evidence that a ratio of
serum tocopherol to total lipid is a
better indicator of nutritional state.
 A value below 0.8 mg tocopherol/g of
total serum lipid is considered deficient
in adult and children
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Vitamin K
Structure: There are three forms
(vitamers) of vitamin K: K1, k2 and
K3
The difference between KI and k2 lies in the
side chain R.
K3 is synthetic vitamin and has no R side
chain.
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Sources:
The main source of vitamin K is the
intestinal bacteria. They produce
Vitamin K2 (menaquinones).
Vitamin K1 (phylloquinones) is of
plant origin (green leafy vegetables,
olive, soybean and cauliflower)
It is also found in egg yolk and liver.
Vitamin K3 is synthetic, , water
soluble and more potent than vitamin
K1 and K2.
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Absorption and storage: vitamin K is
absorbed from the intestine in the
chylomicrons , and transported to the
liver, and from liver to the tissues
incorporated in VLDL. High doses of
other fat soluble vitamins decrease
vitamin K absorption.
Tissue store of the vitamin is less than
the store of other fat soluble vitamins.
Vitamin K localizes in various cellular
membranes, particularly in the golgi and
smooth microsomal membrane fractions.
Vitamin K1 is rapidly metabolized to
more polar metabolites and excreted in
the urine and bile.
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Importance of vitamin K:
Synthesis of some blood clotting factors
in liver: prothrombin, and factors II,
VII, IX and X.
These proteins are formed in the liver as
inactive precursors containing glutamic
acid residues. Carboxylation of these
glutamic acid residues converting them
into γ- carboxy gtutamate converts the
molecules into active form.
It also helps in activation of protein S,
protein C and osteocalcin and GLa
protein (which are the calcium binding
protein in bones.)
This carboxylation is done by the
enzyme glutamyl γ-carboxylase which
requires vitamin K as coenzyme.
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Deficiency of vitamin K is not common
because intestinal bacteria synthesize it.
The Deficiency leads to impairment of
blood clotting. Deficiency takes place in
certain condition such as :
-new born infant because of very low
activity of intestinal bacterial flora and
also because the vitamin does not cross
the placental membrane efficiently.
-Long use of antibiotics as they kill
intestinal bacteria.
-Chronic liver diseases, as liver is the
site for prothrombin synthesis as well as
for the formation of bile salts which are
essential for vitamin K absorption.
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Requirement:
No
RNI
,
but
recommended amount is 70-140
mg/day for adult .It is recommended
that all newborns receive a single
intramuscular dose as prophylaxis.
Toxicity can take place only if very
large
dose
is
taken
daily
for
prolonged period. It can cause
hemolytic anemia and jaundice ,
especially in infants.
Evaluation
of
nutritional
status:
vitamin K deficiency is evaluated by
measuring the plasma concentration
of one of the vitamin K-dependent
clotting factors,or prothrombin time.