VITAMINS

Fat soluble vitamins

Dr Bilal Azakir
Faculty of Medicine
BAU

Reference:
Lippincott
Vitamins classification
 What do we need to know
Vitamin A
Vitamin D Functions Sources

Vitamin K
At the end
Vitamin E of this Metabolism Deficiency
session

Absorption Toxicity
Fat soluble Vitamins
Absorption
 Fat Soluble Vitamin
Absorption
• Form micelles in jejunum
• Clusters of lipids
• Hydrophobic groups inside
• Hydrophilic groups outside
• Absorbed by enterocytes
• Packaged into chylomicrons
• Secreted into lymph
• Carried to liver as chylomicron remnants
 Fat Malabsorption
• Leads to deficiencies of fat-soluble vitamins
• Loss of A, D, E, and K
• Abnormal bile or pancreatic secretion
• Disease or resection of intestine
• Key Causes
• Cystic fibrosis (lack of pancreatic enzymes)
• Celiac sprue
• Crohn’s disease
• Primary biliary cirrhosis
• Primary sclerosing cholangitis
VITAMIN A
 Vitamin A
• Retinol = Vitamin A
• Retinoids
– Family of structures
– Derived from vitamin A
– Important for vision, growth, epithelial tissues
– Key retinoids: retinal, retinoic acid
 Vitamin A
Dietary sources
• Found in liver
• Dark green and yellow vegetables
• Many people under-consume vitamin A
• Stored in liver (years to develop deficiency)
 Vitamin A: Structure
1. Retinol
• In Animal tissues as a retinyl ester with
long-chain fatty acids
2. Retinal and retinol can readily be
interconvert
3. Retinoic acid
• cannot be reduced in the body,
• cannot give rise to either retinal or retinol.
4. β-Carotene
• cleaved in the intestine to yield two
molecules of retinal
 Beta Carotene
• Pro-vitamin A (a carotenoid)
• Major source of vitamin A in diet
• Cleaved into retinal
• Antioxidant properties
– Similar to vitamin C, vitamin E
– Protects against free radical damage
– May reduce risk of cancers and other diseases
 Retinal
• Found in visual pigments
• Rods, cones in retina
• Rhodopsin = light-sensitive protein receptor
• Generates nerve impulses based on light
• Contains retinal
 Retinoic Acid

• Binds with receptors in nucleus

• Acts like a hormone
• Regulates/controls protein synthesis
• Important example: keratin
• Limit/control keratin production
• Retinoic acid (or similar) used in treatment of psoriasis
• Deficiency: dry skin
• Important example: mucous
• Limit/control mucous production epithelial cells
Mechanism of
action of vitamin A
Functions of vitamin A
Visual cycle
 Growth
• Decreased growth rate in children and Bone
development
 Reproduction
• Retinol and retinal are essential for normal
reproduction
• Male:
• Spermatogenesis
• Female:
• preventing fetal resorption in the female.
 Maintenance of epithelial cells
• Normal differentiation of epithelial tissues and
mucus secretion.
 Clinical indications

• Dermatology
Retinoic • Psoriasis
Acid

• Dietary
Retinol supplements
 Vitamin A
Deficiency
• Visual symptoms
• Night blindness (often first sign)
• Xerophthalmia (keratinization of cornea blindness)
• Keratinization
• Skin: thickened, dry skin
• Growth failure in children
 Vitamin A
Therapy
• Measles
• Mechanism not clear
• Used in resource-limited countries
• Skin disorders
• Psoriasis
• Acne
 Acne and psoriasis
• Treated with retinoic acid or its
derivatives
• Mild cases of acne, Darier
disease
• topical application of tretinoin (all-
trans retinoic acid),
• Severe, recalcitrant, cystic acne
unresponsive to conventional
therapies
• isotretinoin (13-cis retinoic acid)
• Retinoic acid is also used in the
treatment of promyelocytic
leukemia.
 Isotretinoin
• Teratogenic : severe, disfiguring cystic acne
that is unresponsive to standard therapies.
• Prolonged treatment with isotretinoin leads to
hyperlipidemia : cardiovascular disease.
 Isotretinoin
• Accutane
• 13-cis-retinoic acid
• Effective for acne
• Highly teratogenic
• OCP and/or pregnancy test prior
to Rx
 Vitamin A
Excess
• Hypervitaminosis A
• Usually from chronic, excessive supplements
• Dry, itchy skin
• Enlarged liver
 Toxicity of retinoids
• Excessive intake
• Limit: 7.5 mg/day of retinol
• Symptoms:
• dry skin
• enlarged and cirrhotic liver
• rise in intracranial pressure
• Pregnant women: congenital malformations in
the developing fetus.
VITAMIN D
 VITAMIN D
• The D vitamins are a group of sterols that have
a hormone-like function.
• The active molecule, 1,25-
dihydroxycholecalciferol (1,25-diOH-D3)
• The most prominent actions of 1,25-diOH-D3
are to regulate the plasma levels of calcium
and phosphorus.
 Vitamin D

• Vitamin D2 is ergocalciferol
• Found in plants
• Vitamin D3 is cholecalciferol
• Found in fortified milk
• Two sources D3:
– Diet
– Sunlight (skin synthesizes D3)
 Distribution of vitamin D
• Diet
• Ergocalciferol (vitamin D2): found in plants
• cholecalciferol (vitamin D3), found in
animal tissues

• Endogenous vitamin precursor:

• 7-Dehydrocholesterol, an intermediate 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.
 Vitamin D Activation
• Vitamin D3 from sun/food inert
• No biologic activity
• Must be hydroxylated to become active
• Step 1: 25 hydroxylation
• Occurs in liver
• Constant activity
• Step 2: 1 hydroxylation
• Occurs in kidney
• Regulated by PTH
 Vitamin D Activation
• Liver: Converts to 25-OH Vitamin D (calcidiol)
• Kidney: Converts to 1,25-OH2 Vitamin D
(calcitriol)
• 1,25-OH2 Vitamin D = active form
 Vitamin D Activation
• 25-OH Vitamin D = storage form
• Constantly produced by liver
• Available for activation by kidney as needed
• Serum [25-OH VitD] best indicator vitamin D
status
• Long half-life
• Liver production not regulated
 Vitamin D and the Kidney
• Proximal tubule converts
vitamin D to active form
• Can occur independent of
kidney in sarcoidosis
• Leads to hypercalcemia
 Vitamin D Function
• GI: ↑Ca2+ and P043- absorption
• Major mechanism of clinical effects
• Raises Ca, increases bone mineralization
• Bone: ↑Ca2+ and P043- resorption
• Process of demineralizing bones
• Paradoxical effect
• Occurs at abnormally high levels
 Vitamin D Deficiency

• Poor GI absorption Ca2+ and P043-

• Hypophosphatemia
• Hypocalcemia (tetany, seizures)
• Bone: poor mineralization
• Adults: Osteomalacia
• Children: Rickets
 Clinical indications

• Only occurs in children

• Deficient mineralization of growth plate
• Growth plate processes
• Chondrocytes hypertrophy/proliferate
• Vascular invasion ____ mineralization
• ↓ Vitamin D:
• Growth plate thickens without mineralization
• Clinical features
• Bone pain
• Distal forearm/knee most affected (rapid growth)
• Delayed closure fontanelles
• Bowing of femur/tibia (classic X-ray finding)
Rickets
 Clinical Indications
Osteomalacia
• Children and adults
• Occurs in areas of bone turnover
• Bone remodeling constantly occurring
• Osteoclasts clear bone
• Osteoblasts lay down new bone (“osteoid”)
• ↓ Vitamin D = ↓mineralization of newly formed bone
• Clinical features
• Bone pain/tenderness
• Fractures
• PTH levels very high
• CXR: Reduced bone density
Vitamin D in Renal Failure
 Clinical indications
• Renal osteodystrophy:
• Chronic renal failure
• decreased ability to form the active form of vitamin
Vitamin D + phosphate
• Hypoparathyroidism:
• Lack of parathyroid hormone causes hypocalcemia
and hyperphosphatemia.
• These patients may be treated with calcitriol and
calcium supplementation.
 Vitamin D
Breast Feeding
• Breast milk low in vitamin D
• Even if mother has sufficient levels
• Lower in women with dark skin
• Most infants get little sun exposure
• Exclusively breast fed infants:
supplementation
 Toxicity of vitamin D
• Vitamin D can be stored in the body and is
only slowly metabolized.
• Symptoms: loss of appetite, nausea, thirst,
and stupor.
• Enhanced calcium absorption and bone
resorption results in hypercalcemia:
deposition of calcium in many organs,
particularly the arteries and kidneys.
 Toxicity of vitamin D
• Hypervitaminosis D
– Massive consumption calcitriol
supplements
– Sarcoidosis :abnormal
collections of inflammatory
cells
– Granulomatous macrophages
express 1α-hydroxylase
• Hypercalcemia,
hypercalciuria
• Kidney stones
• Confusion
VITAMIN K
 Vitamin K
• Activates clotting factors in liv
• Vitamin K dependent factors: II, VII, IX, X, C, S
• Post-translational modification by vitamin K
 Vitamin K
• Found in green, leafy vegetables (K1 form)
• Cabbage, kale, spinach
• Also egg yolk, liver
• Also synthesized by GI bacteria (K2 form)
 VITAMIN K
• Posttranslational modification of various blood
clotting factors
• Serves as a coenzyme in the carboxylation of
certain glutamic acid residues present in these
proteins.
• Vitamin K exists in several forms:
– plants as phylloquinone (or vitamin K1)
– in intestinal bacterial flora as menaquinone (or
vitamin K2).
– Menadione: A synthetic form of vitamin K
Function of vitamin K:Formation of γ-
carboxyglutamate (Gla)
• Hepatic synthesis of
prothrombin and
blood clotting factors
II, VII, IX, and X.
• Formation of the
clotting factors
requires the vita- min
K–dependent
carboxylation of
glutamic acid residues
to Gla residues
 Function of vitamin Interaction of
prothrombin with platelets
• The Gla residues of prothrombin are good chelators of positively
charged calcium ions,
• The prothrombin–calcium complex is then able to bind to
phospholipids essential for blood clotting on the surface of platelets.
• Attachment to the platelet increases the rate at which the
proteolytic conversion of prothrombin to thrombin can occur
 Vitamin K Deficiency
• Results in bleeding (“coagulopathy”)
• Deficiency of vitamin K-dependent factors
• Dietary deficiency rare
• GI bacteria produce sufficient quantities
 Vitamin K Deficiency
Causes
• Warfarin therapy (deficient action)
• Antibiotics
• Decrease GI bacteria
• May alter warfarin dose requirement
• Newborn babies
• Sterile GI tract at birth
• Insufficient vitamin K in breast milk
• Risk of neonatal hemorrhage
• Babies given IM vitamin K at birth
 Toxicity of vitamin K
• Prolonged administration
• Hemolytic anemia and jaundice in the infant
• Toxic effects on the membrane of red blood
cells
 VITAMIN E
• Tocopherols
• Antioxidant :
• Prevention of the nonenzymic oxidation of cell
components
• Key role in protecting RBCs from oxidative damage
 Deficiency of vitamin E
• Restricted to premature infants.
• In adults
• Associated with defective lipid absorption or transport.
• Symptoms
• Sensitivity of erythrocytes to peroxide
• Appearance of abnormal cellular membranes.
• Hemolytic anemia
• Muscle weakness
 Clinical indications
• Vitamin E is not recommended for the
prevention of chronic disease, such as
coronary heart disease or cancer.
• Increased incidence of stroke.
• Very high dosages reported to inhibit vitamin
K

• least toxic of the fat-soluble vitamins, and no

toxicity has been observed at high doses
Many thanks