Fat soluble vitamins

Vitamin D, E & K
Vitamin D
 Vitamin

D
The term “Vitamin D” refers to a family of
related compounds biosynthesized from
cholesterol and ergosterol.

 Vit. D3 (cholecalciferol) is synthesized from

7-dehydrocholesterol in sun-exposed skin
and found naturally in animal products
such as eggs, fish and liver.

 Vit. D2 (ergocalciferol) is another form of

vit. D synthesized by certain fungi and is
used in many supplements.
 (Cholecalciferol) )Ergocalciferol(
VITAMIN D3 VITAMIN D2

 Synthesized in the body Found in plant life

 Naturally derived  Synthetically derived

supplement supplement
 Significantly increases  Moderately increases vitamin
vitamin D levels in the body D levels in the body

 Recommended by experts  Alternative form appropriate

for optimal bone and immune for vegetarians
support
 However, vit. D3 is the preferred form for humans
as its bioavailability is twice that of vit. D2.

 After absorption from foods or production in

the skin, vitamin D is stored as 25- hydroxy-vit.
D3 in the liver. When needed
by the body, it is then activated to 1,25-
dihydroxy vit. D3 in the kidney.

NB: A healthy liver and kidneys are essential for

optimum vit. D status.
Biosynthesis and Activation of Vit. D3

Stored in Liver
Daily Requirment = 10 μg vit. D (400 IU vit. D).
 FUNCTIONS OF VITAMIN D
1. Calcium metabolism (main function):
Vit. D regulates Ca+2 levels in the blood and
tissues. A fall in blood Ca+2  stimulate
active vit. D production  stimulate Ca+2
absorption from food + increase release of
Ca++ from bones + decrease renal excretion
of Ca+2.
2. Essential for normal bone growth during
childhood and for maintaining bone density
and strength during adulthood (as it increases
Ca+2 absorption from foods +
increases Ca+2 deposition into the
skeleton).

3. Integrated function with parathyroid hormone

in stabilization of Ca+2 level in blood.

4. Regulation of cell growth and development

(particularly WBCs and epithelial cells).
PEOPLE AT GREATER RISK OF DEVELOPING
VITAMIN D DEFICIENCY
1. Older people (> 50 years) due to:
The decrease of ability of skin to
convert 7-dehydrocholesterol to
pre-vit. D3.
2. Newborn infants:
who are absolutely breastfed require
vit. D supplements because
mother milk does not contain
significant levels of Vit. D.
3.Women after labor: the serum
concentration of vit. D and Ca+2 falls
rapidly.
5. Dark-skinned individuals may require
extra vit. D because melanin acts like
a sun-block, prolonging the time
required to generate vit. D.
6. Obese people have lower levels of the
circulating form of vitamin D, probably
because it is deposited in body fat
masses  less bioavailable vit. D.
7. Patients with chronic liver disease or
malabsorption or parathyroidectomy.
8. Vit. D is found only in animal foods.
strict vegetarian people sharply
increase the risk of deficiency if sunlight
exposure is inadequate.
 CAUSES OF VIT. D DEFICIENCY

 Decreased intake or malabsorption.

 Reduced sun exposure.

 Increased hepatic catabolism (e.g. due to

metabolizing induction drug)
Decreased endogenous synthesis (via 25-
hydroxylation in the liver and subsequent
1-hydroxylation in the kidney).
DISEASES CAUSED BY VIT. D DEFICIENCY
Vit. D deficiency causes several bone diseases:

Rickets: a childhood disease characterized

by failure of growth and deformity of long
bones.
Osteoporosis: a condition characterized by
fragile bones due to decreased bone density.
fragile bone easily fractured.
Osteomalacia: (adult version of Rickets) is a
case of softening of bones due to defective
bone mineralization and characterized by proximal
weakness and bone fragility.
 Rickets

Osteoporosis Osteomalacia
 GENERAL USES OF VIT. D
1- Prophylaxis and treatment of osteoporosis as
a result of calcium depletion. Treatment
require taking both calcium and vitamin D.
2- Trteatment of Osteomalacia and rickets.
3- Vitamin D also has a role in cancer prevention
(colon cancer, breast and prostate cancer).
The action of Tamoxifen (Chemotherapeutic
agent) appears to be improved with small
added doses of vitamin D.
4- Treatment of hearing loss resulted from vitamin
D deficiency that affect the function of small
bones in the ear responsible sound
transmition.
6- In combination with phosphate to treat some
metabolic diseases as Fanconi syndrome and
familial hypophosphatemia.
Fanconi syndrome: is a disorder in which
the proximal tubular function of the kidney is
impaired, resulting in decreased re- absorption of
electrolytes and nutrients back into the
bloodstream (compounds involved include
glucose, amino acids, uric acid, phosphate and
bicarbonate).
 INTERACTIONS WITH VIT. D
1. The absorption of vitamin D is improved by
calcium, choline, fats, phosphorus, vitamins A and C.

2. Drugs as Rifampin, H2 blockers, barbiturates,

heparin, cholestyramine, carbamazepine,
phenytoin, fosphenytoin, and phenobarbital
reduce serum levels of vitamin D and increase its
metabolism.

3. Overuse of mineral oil and stimulant laxatives may

deplete vitamin D.

4. Osteoporosis and hypocalcaemia can result from

prolonged use of corticosteroids. It is necessary to
take of calcium and vit. D together with
DOSAGE FORMS
Fat Soluble Vitamins
VITAMIN E
 Vitamin E
 Vit. E is a general term used for a group of compounds
(α, β, , and δ-tocopherols) having a chromanol ring and
phytyl side chain.
1
8
2 R R
7 R
3
5 4

Chromanol Group Phytyl side chain

Position of Methyl Tocopherol structure d-α -tocopherol
groups on aromatic ring Equivalent
(TE) = 1 mg = 1.5 IU
5,7,8 α-tocopherol
Recommended daily
5,8 β-tocopherol amount
7,8 γ-tocopherol = 30 IU = 20 mg
Larger doses are allowed
8 δ-tocopherol
(safe)
 The most abundant and active form of Vit. E is α-
tocopherol (α-RRR-tocopherol).
 The relative activities of tocopherols vary
considerably and thus Vit. E activity should referred to
α-tocopherol.
Vit. E form Relative Biological Activity
α-tocopherol 100%
β-tocopherol 50%
-tocopherol 10-30%
δ-tocopherol 1%

 For example, soybean oil has a higher total tocopherol

content than sunflower oil. Most of Vit. E in soya oil is δ-
tocopherol while in sunflower oil most of the Vit. E is α-
tocopherol, which gives the sunflower oil a greater level of
Vit. E activity.
 Sources of Vitamin E
 Natural sources of vitamin E (d-RRR-α-tocopherol)
Vegetable oils from seeds
(Sunflower, Cottonseed)
Lettuce.
Nuts.
Unprocessed grains.
 Synthetic sources racemic-tocopherols.
Pharmacokinetics of Vit. E
Gastrointestinal absorption of all forms of Vit. E is
equivalent.
Subsequent biological steps are sharply in
favour of the RRR form.
Cellular liver transfer protein that maintains
plasma level is specific for the RRR form of α-
tocopherol.
 Functions of Vitamin E
1. Antioxidant action:
 Tocopherols (Vit. E) interrupt free radical chain
reactions by capturing free radicals (free radical
scavanger); this imparts to them their antioxidant
properties.
 Therefore, Vit. E protects the cells, with other nutrient
(e.g. Vit. C and Selenium) against the harmful free
radicals formed during metabolism of fatty acids.
 The free hydroxyl group on the aromatic ring is
responsible for the antioxidant properties. The
hydrogen from this group is easily donated to the free
radical, resulting in a relatively stable free radical form
of the vitamin.
2. Antithrombotic action:

Vit. E slows down the action of

thrombin (a blood clotting protein)
and reduces platelet aggregation by
inhibiting thromboxanes. Although
Vit. E is a natural “blood thinner” it
does not increase risk of bleeding in
healthy people.
Uses of Vitamin E as prophylaxis and Therapy
1. Cardiovascular disease: (e.g. angina pectoris and
venous thrombosis): It inhibits oxidation of
cholesterol in LDL and VLDL particles  decrease
the risk of coronary heart disease.

2. Anemia:
It functions as an antioxidant, enhancing
function and durability of RBCs and stabilizes their
membranes  decrease syndromes of hemolytic and
sickle-cell anemia.
3. Immunity:
It enhances resistance to viral and bacterial
infections and increases antibody production by
WBCs and increases phagocytosis.
4. Alzheimer’s disease (AD) and memory loss:
It can decrease progression of AD and help
maintain memory function through decreasing
oxidative damage to neurons.
5. Eye Diseases:
It inhibits oxidative damage to the lens 
inhibits developing of cataract. It also decrease
incidence of macular degeneration.

6. Rheumatic disorders and pains:

It acts as free radical scavenger and so as anti-
inflammatory and analgesic. It can decrease joint
inflammation and stiffness in osteoarthritis and
rheumatoid arthritis.
7. Protection and treatment of cancer:
Higher intakes of vitamin E decrease risk of
cancer of the skin, breast, lung, esophagus, and
stomach. It can also increase efficacy of the radiation
treatment and protects healthy cells against damage
during radiotherapy.
8. Skin Care:
It is applied topically to abrasions, wounds, or
burns  reduce scar formation and contraction, and
improve healing.
9. Hepatoprotective
10. Disorders of premature infants:
It decreases the risk of hemolytic anemia and
bronchopulmonary dysplasia (characterized
by inflammation and scarring in the lungs).
 Toxicity and side effects

 Vit. E is well-tolerated, and side effects are

rare even at higher doses (up to 2000 mg/day).

 However, in some individuals who are Vit. K

deficient, Vit. E may increase the risk for
hemorrhage or bleeding.

 People taking anticoagulant drugs should

also be cautious with high doses.

 People with diabetes should be cautious

when starting high doses of Vit. E because it
may enhance the action of insulin, but rarely.
People at greater risk of developing Vit. E deficiency
 Many people do not obtain adequate dietary Vit.
E when depends more on processed food (e.g.
refined flour and white rice lose nearly all of
original vitamin present in whole grain).

People who consume much of polyunsaturated

fatty acids (PUFAs) as in USA and Europe need
more Vit. E to protect PUFAs in their tissues from
oxidation particularly if dietary intake of Vit. E is
marginal.

Newborn and premature infants are at high risk

for deficiency due to their poor ability to absorb Vit.
E and very limited tissue reserves of Vit. E.
 Drug and Herbal Interactions with Vit. E
 It can alter the efficacy of anticoagulant.

 It increases bleeding time in patient taking herbal

preparations as Feverfew or Gingko biloba.

 Inorganic iron supplements destroy Vit. E, so

individuals taking iron should space out their doses
(e.g., iron in the morning and Vit. E in the evening).

 Large doses of Vit. A can decrease the absorption

of Vit. E.

 Alcohol and mineral oil can reduce Vit. E

absorption, and thus should be avoided in Vit. E
deficient individuals.
VITAMIN K
 VITAMIN K
 A group of compounds derived from 2-methyl-1,4-
naphthoquinone that act as antihemorrhagic factor in
birds and mammals. There are 3 forms of vitamin K:
a) Vit. K1 (Phylloquinone) found in plant
foods.
b) Vit. K2 (Menaquinone) from animal and
bacterial sources.
2-methyl-1,4- c) Synthetic Vitamin K3 (Menadione).
naphthoquinone

Vit. K1 (Phylloquinone) Vit. K2 (Menaquinone) Vit. K3 (Menadione)

Commercial infant Recommended New born: 500- 1000 μg once

formula contain 50- 125 1- 6 Months: 5 mg/day
μg/day
Daily amount
6- 12 Months: 15 mg/day
Adult: 80 mg/Kg (body weight) / day
 Sources of Vitamin K
Foods rich in Vitamin K:
Spinach, Green cabbage, Turnip, Parsley, lettuce,
beef liver, green tea (in decreasing order), etc.

Spinach Green cabbage Turnip

Parsley Beef liver Green tea

 Structure Activity Relationship
1. Activity is maximum when:
 Ring A and Ring B are aromatic. 1
 Ring A is not substituted.
2
 Methyl group at C-2. A B
 3
Unsaturation of phytyl side chain
at C-3. 4

2. Activity is decreased when:

 Alkyl group larger than Methyl at C-2.
 Hydroxyl group at C-3.
 Hydroxylation or saturation or cis-configuration
of the phytyl side chain at C-3.
Activity not affected:
if positions 1 and 4 are substituted with OH, O-Ac, NH2,
OCH3, OC2H5, C=O
 Metabolism of Vit. K
1. 70% of Vit. K3 (menadione) excreted in urine in 24 h
in the form of sulphate, phosphate and glucuronic
acid conjugate.

2. Small % excreted in faces as glucuronic acid

conjugate.

3. Vit K2 and K3 undergo slower metabolism to

shorten the side chain to 5- 7 carbons carboxylate.
Symptoms of Vit. K deficiency
1. Uncontrolled internal bleeding.
2. Cartilage calcification and malformation of
developing bone.
3. Deposition of insoluble calcium salts in the arterial
vessel walls.
The basic factors needed to prevent vitamin K
deficiency:
a) Normal diet containing the Vit. K.
b) Presence of bile in the intestine.
c) Normal intestinal uptake or absorption.
d) Normal liver i.e. no interference with Vit. K
metabolism or use of Vit. K antagonists
therapeutically or accidently.
e) Heavy alcohol consumption impairs the
liver’s ability to produce vitamin K-
dependent coagulation factors and impair
recycling of vitamin K.
People at greater risk of developing Vit. K deficiency
 Newborn infants exclusively breastfed are
susceptible to abnormal bleeding due to Vit. K
deficiency.

 Breast milk contains very little Vit. K and the

immature liver of the newborn does not synthesize the
Vit. K-dependent clotting factors efficiently.

 Also, because the newborn’s colon is sterile for the

first few days after birth, no bacterial synthesis of Vit. K
occurs in the colon.

To reduce the risk of Vit. K deficiency, most babies

receive intramuscular vitamin K at birth.
 Symptoms of Vit. K Toxicity
 Vitamins K1 and K2 are non-toxic in large doses.
 Vitamin K3 (the synthetic one) is toxic in doses
three time more than the usual dose.

Toxicity manifestations:
Hyperbilirubinemia.
Severe Jaundice.
Anemia.

Drug Interaction with Vitamin K

1. Antibiotics: Prevent absorption and kill normal
bacterial flora.
2. Anticonvulsants e.g. Phenytoin : Affect Vit K
metabolism.
 Functions of Vitamin K
Vit. K is involved as a cofactor in the carboxylation of
certain glutamate residues of proteins to form -
carboxyglutamate residues (Gla-residues). Gla-residues
are usually involved in binding calcium and are
essential for the following biological activities:

1. Blood coagulation
Several proteins promote coagulation (prothrombin,
VII, IX, X) while others slow it down (proteins C and
S). Thus, activity of vitamin K balances the two
opposing sides of coagulation system in blood.
2. Bone metabolism
• Bone Gla-protein (Osteocalcin): Regulate
incorporation of calcium Phosphate into bones.
• Matrix GLA protein (MGP): Clearance of extracellular
Calcium to protect against soft tissue calcification.
 3. Bile acid sequestrants (Cholestyramine) and
Aspirin: Affect absorption.

4. Weight Loss Products (Chitosan, Orlistat, and

olestra): Affect absorption as they prevent
absorption of fats.

5. Mineral oil laxatives: Affect absorption.

6. X-rays and Radiation: Deplete vitamin K levels

and raise vitamin K requirements.
THANX