FAT SOLUBLE VITAMINS

2. DEFINITION
 The term vitamin, means a vital amine, was proposed by
Funk in 1911.
 Vitamins are potent organic compounds that occur in low
concentration in foods; they perform specific & vital
functions in the cells & the tissues of the body.
 They can not be synthesized by the body, so must be
supplied in the food.
 Very small amounts are needed by the body (>1 gm)

3. Vitamins
Fat soluble
vitamins
Water soluble
vitamins
•Vitamin A
•Vitamin D
•Vitamin E
•Vitamin K
•Vitamin C
•B Complexes
Thiamin (B1)
Riboflavin (B2)
Niacin (B3)
Pentothenic acid (B6)
Pyridoxine (B6)
Folic acid
Cynocobalmin (B12)
Inositol
Biotin

4. FAT SOLUBLE VITAMINS VS.
WATER SOLUBLE VITAMINS

5. Fat Soluble
Vitamins
•Need fat for absorption
•Absorbed into the lymph and carried in blood
with protein transporters = chylomicrons.
•Stored in the liver

7. VITAMIN A
 Vitamin A or Retinol was the first essential lipid
soluble substance discovered by McCollum and
Davis in 1913.
 Provitamin A activity of beta carotene was
established Moore in 1930.

8. STRUCTURE (RETINOL)

9. FORMS OF VITAMIN A:
TERMINAL ENDS OF RETINOIDS

10. THE RETINOIDS
 3 forms of vitamin A
important for health
 Retinal
 Retinoic acid
 Retinol (key player; can
be converted to other
forms)
 β-carotene (a carotenoid
or pigment) in
yellow/orange foods is a
potent provitamin A

11. CONVERSION OF CAROTENOIDS TO
RETINOIDS
 Enzymatic conversion of
carotenoids occurs in liver or
intestinal cells, forming
retinal and retinoic acid

12. CONVERSION OF CAROTENOIDS TO
RETINOIDS
 Enzymatic conversion of
carotenoids occurs in liver or
intestinal cells, forming retinal
and retinoic acid
 Provitamin A carotenoids
 Beta-carotene
 Alpha carotene
 Beta-cryptoxanthin
 Other carotenoids
 Lutein
 Lycopene
 Zeaxanthin

13.  Retinoids
 Retinyl esters broken down to free retinol in small intestine -
requires digestive enzymes (retinyl esters hydrolyses).
 these retinols are emulsifies by the action of bile salts for
integration into micelles
 These micells are uptaked by mucosal cells of the small intestine.
 The cellualar free retinol is reesterified into lymph chylomicrons and
circulated in the blood by liver through apolipoproteins.
 Carotenoids
 Absorbed intact, absorption rate much lower
 Intestinal cells can convert carotenoids to retinoids
Metabolism & Absorption

14. TRANSPORT AND STORAGE OF
VITAMIN A
 Liver stores 90% of vitamin A in the body
 Reserve is adequate for several months
 Transported via chylomicrons from intestinal
cells to the liver
 Transported from the liver to target tissue as
retinol via retinol-binding protein, which is
bound to transthyretin

15. RETINOID BINDING PROTEINS
 Target cells contain
cellular retinoid binding
proteins
 Direct retinoids to
functional sites within cells
 Protect retinoids from
degradation
 RAR, RXR receptors on
the nucleus
 Retinoid-receptor complex
binds to DNA
 Directs gene expression

17.  Vision
 Growth
 Reproduction
 Epithelial cell differentiation
 Mucus secretion

18.  Vision
 The best characterized function of vitamin A is its role in the
retina of the eye.
 Retinol, supplied to the retina, which then combines with a
protein called opsin to produce a purple pigment known as
rhodopsin.
 Rhodopsin, also known as visual purple is located in the light
sensitive rod cells of the retina, when light strikes the retina,
the rod cells are bleached as the rhodopsin splits to form
retinal & opsin.
 As this occurs, a nerve stimulus is transmitted through the
optic nerve fibers to the visual centre of the brain, where the
sensation of vision is created.

19. Vitamin A in Vision

20. VISUAL CYCLE

21. ROLE OF RETINOL IN THE VISUAL CYCLE.
Dark Light
Lumirhodopsin
Meta-rhodopsin
Opsin+Cis-retinene Transretinene+opsin
Retinene reductase Retinene reductase
Cis-vitamin A Trans –vitamin A
Rhodopsin
Blood vitamin A

22. GROWTH AND DIFFERENTIATION OF CELLS
• Retinoic acid is necessary for cellular differentiation
• Important for embryo development, gene expression
• Retinoic acid influences production, structure, and
function of epithelial cells that line the outside (skin) and
external passages (mucus forming cells) within the body

23. GROWTH
 Required for bone growth
 An early symptom of vitamin A deficiency is loss of
appetite, followed by a cessation of growth( growth
plateau) then rapid weight loss and ultimate death.
 In vitamin A deficiency bones weak, although
thicker than normal. The cavity in the skull and
spinal column do not enlarge to make room for the
growing nervous system.

24. Function in protein synthesis and cell
differentiation
(retinol)

25.  Reproduction
In absence of vit. A (retinol), the male’s body fails to
produce sperm cells & the females body resorbs a fetus.
 Immunity
 Vitamin A (β carotene) is required to maintain the normal
health & function of epithelial layers, which
provide a first line of defense against invading
microorganisms.
 Humoral immune response (antibodies) & cellular immune
response which involves the direct killing of infected cell
are regulated by vit.A or its metabolites.

26. ROLE OF PARATHYROID HORMONE
Region Effect
Bone
It enhances the release of calcium from the large reservoir
contained in the bones.[7] Bone resorption is the normal
destruction of bone by osteoclasts, which are indirectly
stimulated by PTH. Stimulation is indirect since osteoclasts
do not have a receptor for PTH; rather, PTH binds to
osteoblasts, the cells responsible for creating bone. Binding
stimulates osteoblasts to increase their expression of RANKL
and inhibits their expression of Osteoprotegerin (OPG). OPG
binds to RANKL and blocks it from interacting with RANK, a
receptor for RANKL. The binding of RANKL to RANK
(facilitated by the decreased amount of OPG) stimulates
these osteoclast precursors to fuse, forming new osteoclasts,
which ultimately enhances bone resorption.

27. Kidney
It enhances active reabsorption of calcium and magnesium
from distal tubules and the thick ascending limb. As bone is
degraded, both calcium and phosphate are released. It also
decreases the reabsorption of phosphate, with a net loss in
plasma phosphate concentration. When the calcium:
phosphate ratio increases, more calcium is free in the
circulation.[8]
Intestine
It enhances the absorption of calcium in the intestine by
increasing the production of activated vitamin D. Vitamin D
activation occurs in the kidney. PTH up-regulates 25-
hydroxyvitamin D3 1-alpha-hydroxylase, the enzyme
responsible for 1-alpha hydroxylation of 25-hydroxy vitamin
D, converting vitamin D to its active form (1,25-dihydroxy
vitamin D). This activated form of vitamin D increases the
absorption of calcium (as Ca2+ ions) by the intestine via

28. SOURCES
 Preformed
 Liver, fish oils, fortified milk,
eggs, other fortified foods
 Provitamin A carotenoids
 Dark leafy green, yellow-orange vegetables/fruits

29. RDA FOR VITAMIN A AND ß-CAROTENE
Retinol (ug/d) β-Carotene (ug/d)
Man 600 4800
Women 600 4800
Pregnant 800 6400
Lactating 950 7600
Infant
0-6 months
6-12 months
350
350
------
2800
Children (1-6 yrs.) 400 3200
Children (7-9 yrs.) 600 4800
Boys 600 4800
Girls 600 4800

31. Signs & Symptoms of Vitamin A deficiency
 Clinical signs
 Night blindness
 Conjuctival xerosis
 Bitot’s spot
 Corneal xerosis
 Keratomalacia

32. NIGHT BLINDNESS
 When vit. A is deficient the
formation of rhodopsin is impaired
with varying degree of thickening ,
wrinkling & pigmentation (muddy
coloring) of the conjunctiva.
 The pigmentation gives the
conjunctiva a peculiar “smoky “
appearance.

33. CONJUCTIVAL XEROSIS
 It manifests as dry patches of non-
wettable conjunctiva.
 It may be associated with various
degree of thickening, wrinkling and
pigmentation (muddy coloring) of the
conjunctiva.
 The pigmentation gives the conjunctiva
a peculiar ‘smoky’ appearance .

34. BITOT’S SPOTS
 It is more an extension of the
xerotic process.
 These spots are raised, muddy and
dry triangular patches.

35. CORNEAL XEROSIS
 When dryness spreads to the cornea there
is a dull hazy lack luster appearance.
 This is due to the keratinization which is the
result of vitamin A deficiency on all epithelial
surfaces.
 The characteristic feature is a loss of
substance (erosion) of a part or the whole of
the corneal thickness.
 If there is secondary infection there is
inflammation . The lesion only heals by
scarring.
 If properly managed the corneal changes
usually heal leaving useful vision. Corneal
xerosis may progress suddenly and rapidly
to keratomalacia.

36. KERATOMALACIA
 In this condition softening and
dissolution of the cornea occurs. if the
process is not stopped by treatment
,perforation of the cornea leads to
prolapse of the iris, extrusion of the
lens and infection of the whole eyeball
which almost invariably occurs.
 Healing results in scarring of the whole
eye and frequently in total blindness.

37. EFFECT ON REPRODUCTION
In females:
Increased abortions
Neonates born dead/weak
Deformed young: no eyeballs;
hydrocephalus
In males:
Keratinization of testicular
epithelium

38. Hyperkeratosis
Uterus with stratified
squamous epithelium with
keratinization at surface
Lung bronchus - lumen
(top) filled with purulent
exudate containing
desquamated epithelial
cells

39.  Changes in Gastrointestinal tract
Many disturbances in the GI tract, such as diarrhea
take place in the absence of vit.A.
 Failure to tooth enamel
 Loss of sense of both taste & smell

41. Acute – short-term megadose (100 x RDA);
symptoms disappear when intake stops
-GI effects
-Headaches
-Blurred vision
-Poor muscle coordination

42. Chronic – long-term megadose; possible
permanent damage
-Bone and muscle pain
-Loss of appetite
-Skin disorders
-Headache
-Dry skin
-Hair loss
-Increased liver size
-Vomiting

43.  Teratogenic (may occur with as little as 3 x RDA of
preformed vitamin A)
 Tends to produce physical defect on developing fetus as a
result of excess vitamin A intake
 Spontaneous abortion
 Birth defects

45.  Vitamin D is also known as “sunshine vitamin”
 Vitamin D is a Prohormone
 It is derived from cholesterol
 Activated by enzymes in liver and kidney
Vitamin D exists in two forms
1)D3-Cholecalciferol (animal origin)
2)D2-Ergocalciferol (Plant origin)

46. Metabolism & Absorption

47. Functions of
Vitamin D

48. (1)Regulate blood calcium level

49. Groff & Gropper, 2000
 1,25-(OH)2 D binds to
vitamin D receptor
(VDR) in nucleus
 Increase in calbindin
(Ca-binding protein)
Vitamin D affects absorption of
dietary Ca

50. 1,25-(OH)2 D3 increases activity of alkaline
phosphatase
Hydrolyses phosphate ester bonds
Releases phosphorus
Increase in phosphate carriers
Vitamin D affects absorption of
dietary Phosphorus

51. Vitamin D is able to influence differentiation
and function of the some cells
Linked to reduction of breast, colon, and
prostate cancer development
Vitamin D & cell differentiation

52.  Vitamin D creates a supersaturated Ca + Phos solution
 Causes Ca + Phos to deposit in the bones
 Strengthen bones
 Rickets is the result of low vitamin D
 Osteomalacia (soft bone) is rickets in the adult
Role in bone formation

53.  Vitamin D has other roles in the body, including
modulation of the cell growth.
 Neuromuscular & immune function reduction of
inflammation.
 Many genes encoding proteins that regulate cells
proliferation, differentiation & apoptosis are modulated in
part vitamin D.

54. Fortified
 Milk
 Margarine
 Butter
 Cereal
Veal, Beef
Egg yolk
Fatty fish (salmon, sardines, herring)
Vitamin D Sources

55. RDA FOR VITAMIN D
 It can be synthesized in the body in adequate
amounts by simple exposure to sunlight.
 Under certain situations where there is minimal
exposure to sunlight, a specific recommendation of
a daily supplement of 4ooµg is made by ICMR.

56. VITAMIN D - DEFICIENCY
 Young children
 Rickets
 Failure of bones to grow properly
 Results in “bowed” legs or knock-knees,
outward bowed chest and knobs on ribs
 Protruding forehead
 Olders
 Osteomalacia: Adult form of rickets
 Softening of bones, bending of spine, and bowing of
legs
 Osteoporosis (porous bones):
 Vitamin D plays a major role along with calcium
 Loss of vitamin D activity with advancing age
 Associated with fractures  very serious for geriatrics

57. VITAMIN D TOXICITY
 Calcification of soft tissue
 Lungs, heart, blood vessels
 Hardening of arteries (calcification)
 Hypercalcemia
 Normal is ~ 10 mg/dl
 Excess blood calcium leads to stone formation in kidneys
 Lack of appetite
 Mental retardation in infants
 Excessive thirst and urination

59.  Vitamin E was first recognized in 1922 by Evans &
Bishop.
 The term vitamin E refers to a family of eight
related compounds, the tocopherols and the
tocotrienols
 The four major forms of vitamin E are designated
a, b, d, g, that have varying levels of biological
activity
 Alpha- (or α-) tocopherol is the most active form
 Termed an antioxidant

60. Metabolism & Absorption

62.  As an antioxidant,
(vitamin E acts as a peroxyl radical scavenger, preventing
the propagation of free radicals in tissues, by reacting
with them to form a tocopheryl radical, which will then
be reduced by a hydrogen donor (such as vitamin C)
and thus return to its reduced state).
 As it is fat-soluble, it is incorporated into cell
membranes, which protects them from oxidative
damage.
Act as an antioxidant

63. As an enzymatic activity regulator, for instance,
protein kinase C (PKC), which plays a role in
smooth muscle growth, can be inhibited by α-
tocopherol. α-Tocopherol has a stimulatory effect on
the dephosphorylation enzyme, protein
phosphatase 2A, which in turn, cleaves phosphate
groups from PKC, leading to its deactivation,
bringing the smooth muscle growth to a halt.
Enzymatic activities

64. Vitamin E also has an effect on gene expression.
Macrophages rich in cholesterol are found in the
atherogenetic tissue.
Gene Expression

65.  Vitamin E also plays a role in neurological
functions, and inhibition of platelet aggregation.
 Vitamin E also protects lipids and prevents the
oxidation of polyunsaturated fatty acids.

66.  Cotton seed oil, corn oil,
peanut oil and wheat germ
oil are good sources.
Green lettuce leaves have
high content.
Other good sources:
eggs, muscle meat,
liver and fish. Slide
Sources

67. RDA FOR VITAMIN E
 The requirement of vitamin E suggested by ICMR is
0.8mg/g of essential fatty acids.

69. Anemia
 Anemia is a blood disorder wherein there is a low
amount of red blood cells present in the blood.
 In research findings, there was a link with infants who
have pronounced low birth weight and vitamin E
deficient.
 This deficiency leads to hemolytic anemia, which, in
turn, triggers the degradation of the red blood cells.
 Administration of doses of vitamin E proved to be helpful
in treating these infants. They were treated with
tocopherols to help them absorb the vitamin E.

70. Poor Balance
 Vitamin E works as an antioxidant, thus deficiency
in this vitamin will result to a series of great
oxidative stress by many cells or tissues. This could
lead to damage in many parts of the body.
 Vitamin E deficiency affects the central nervous
system.
 Thus, a person greatly lacking vitamin E will
experience nerve degeneration of the hands and
feet, poor reflexes, impaired coordination, and loss
of balance.

71. Muscle Weakness
 Another symptom of vitamin E deficiency is myopathy,
wherein the muscular fibers do not function well or are
weakened.

72. Sight Problems
 Vitamin E deficiency may also lead to vision problems.
One of the symptoms is retinal thinning or degeneration,
where the inner lining of the eye is damaged and begins
to become thinner.
 People with an vitamin E deficiency may also experience
blurred vision and difficulty seeing at night.

73.  Clinical vitamin E deficiency that is alleviated by vitamin E
administration is seen in individuals with chronic
malabsorption syndrome, premature infants and patients on
total parenteral nutrition (TPN).
 Conditions that interfere with normal digestion, absorption or
transport of fat have been associated with low serum levels of
vitamin E. Serum vitamin E concentrations can be less than
20% of normal in individuals with malabsorption syndromes
such as celiac disease, cystic fibrosis and biliary atresia.
 Patients with abetalipoproteinemia (an inherited disorder
marked by absence of lipoproteins in the blood and low levels
of chylomicrons) frequently have very low serum vitamin E
concentrations, below measurable levels.
Malabsorption Syndrome

74.  A progressive neurological syndrome can develop due
to long term, severe vitamin E deficiency
 It is characterized by gait disturbances, absent or altered
reflexes, limb weakness and sensory loss in the arms
and legs.
 Symptoms of neurological dysfunction develop within 18-
24 months in children with vitamin E deficiency but
symptoms in vitamin E-deficient adults usually require
10-20 years of fat and vitamin E malabsorption..
Neurological Syndrome

75.  Newborn infants, especially those that are premature,
are susceptible to vitamin E deficiency due to
inadequate body stores, impaired absorption and
reduced transport capacity in the blood due to low LDL
levels at birth.
 Plasma vitamin E levels are frequently low in patients on
total parenteral nutrition as the major source of vitamin
E in the parenteral solution is the fat emulsion, which
provides primarily g- and d-tocopherols that are much
less biologically active forms of tocopherol.
 Thus, alpha-tocopherol supplementation is required
for patients on total parenteral nutrition.
Premature Infants

76.  There is extensive evidence implicating oxidative
damage in the development of degenerative
diseases and conditions. A number of studies have
evaluated the role of vitamin E, alone or in
combination with other antioxidants, in preventing
or minimizing oxidative damage associated with
development of cancer, coronary heart disease,
cataracts and Alzheimer’s disease.
Protective role in disease prevention

77. Vitamin E - Toxicity
 Diarrhea
 Nausea
 Skin irritation
 Burning upon urination
 Depletion of the mineral copper.
 Development of kidney stones due to oxalate
formation or hemochromatosis or other diseases
related to excessive iron accumulation.

78. Vitamin K was first discovered in 1934 by a
Danish scientist named Dam.

79. There are 3 forms of Vitamin K
 Vitamin K1= principle natural dietary source of Vitamin K
found in green leafy vegetables also called phylloquinone
 Vitamin K2= sources include chicken, egg yolk, butter,
certain cheeses, and fermented soybeans also; this form
includes bacteria produced by the intestine also called
menquinone
 Vitamin K3= used in animal feed and cat and dog food also
referred to as meadione
water soluble form
Forms of vitamin K
•Vitamin K was first discovered in 1934
by a Danish scientist named Dam.

80.  Dietary vitamin K, mainly as phylloquinone, is absorbed
chemically unchanged from the proximal intestine after
solubilisation into mixed micelles composed of bile salts
and the products of pancreatic lipolysis (10).
 Within the intestinal mucosa the vitamin is incorporated
into chylomicrons, is secreted into the lymph, and enters
the blood via the lacteals (11, 12).
Metabolism, Absorption

82.  Aids in blood clotting (primary function)
 Assist body in the absorption of calcium
 Prevents atherosclerosis-hardening of arteries which
inhibits the flow of blood around the body
 Lowers risk of Alzheimer’s and kidney stones
Metabolic/Biochemical Functions

83.  Primary function of Vitamin K
 Initiates the healing process by slowing and
stopping the bleeding
 Given to patients before surgery to prevent
excessive bleeding
 Vitamin K is the coenzyme to Vitamin K-
dependent coagulation proteins in the blood
coagulation cascade known as factors II, VII, IX,
and X
Aids in blood clotting

84.  Aids in the prevention and treatment of osteoporosis and the loss of
bone density
 Vitamin K activates a protein called osteo-calcin which is
responsible for building and maintaining strong bone tissue
 Vitamin K’s role is enhanced when taken with Vitamin D and
magnesium which helps maintain healthy bones
Assists in absorbing of Ca

85.  Atherosclerosis is the hardening of arteries which inhibits the
flow of blood around the body
 Excessive calcium in the arteries contributes to a build-up of
calcium deposits on the artery walls making them thick
 Vitamin K pumps calcium out of arteries and redirects it to the
bones where it mostly needed to prevent osteoporosis
Prevents Atherosclerosis

86.  Excessive calcium deposits could interfere with the
workings of other parts of your body when built up in the
tissues known as calcification
 Individuals with Alzheimer’s have an abnormal calcium
metabolism in their brain
 Vitamin K helps regulate and restricts calcium deposits
Lowers risk of Alzheimer’s

87. Vitamin K1 produced by plants and algae
 Broccoli, kale, chard; plant oils like canola and
soybean
Hydrogenated soybean oil has ineffective K
Vitamin K2 produced by bacteria in gut
 Food Sources: fermented soybean (Natto); dairy
products, egg yolk
Vitamin K Sources

88. RDA FOR VITAMIN K
 Adult-2µg/kg/body wt
-1µg/kg from food
 Infants(0-1yr) :-12-20µg/day
 Children:-
1-3yrs 15-30µg/day
4-6yrs 20-40µg/day
7-10yrs 30-60µg/day
 Adolescents:-
11-18yrs 15-100µg/day
 Adult:- 70-140µg/day
 Pregnancy:- 200µg/day
 Lactation:- 150µg/day

90. Symptoms of Vitamin K deficiency are:-
 Bruising from bleeding into the skin
 Nosebleeds
 Bleeding gums
 Bleeding in stomach
 Blood in urine
 Blood in stool
 Tarry black stool
 Extremely heavy menstrual bleeding
 In infants, may result in intracranial haemorrhage

91.  The symptoms include RBC hemolysis, jaundice
and brain damage.
 High intake of vitamin K can reduce the
effectiveness of anti coagulant medication used to prevent
the blood from clotting.
Vitamin K - Toxicity

92. RECENT ADVANCES IN THE USE OF VITAMIN A (RETINOIDS) IN THE
PREVENTION AND TREATMENT OF CANCER.
Department of Biochemistry and Molecular Biology, Marshall
University School of Medicine, Huntington, West Virginia
25754, USA. niles@marshall.edu
2000 Nov-Dec
Source

93.  Vitamin A, its physiologic metabolites, and synthetic
derivatives (retinoids) have been shown to have protective
effects against the development of certain types of cancer.
 In addition, pharmacologic amounts of retinoids have been
used with some success in the treatment of a few human
tumors.
 The chemoprevention effect of retinoids is most likely
exerted at the tumor-promotion phase of carcinogenesis.
Retinoids block tumor promotion by inhibiting proliferation,
inducing apoptosis, inducing differentiation, or a
combination of these actions.
ABSTRACT

94. CONT…….
 Clinically, isotretinoin (13-cis-retinoic acid) significantly
decreases the incidence of second primary tumors in
patients with head-and-neck cancer and reduces
appearance of non-melanoma skin cancer in patients with
xeroderma pigmentosum. Retinoic acid has proved to be an
effective treatment for promyelocytic leukemia.
 However, retinoid resistance limits its use as a single agent.
Clinical trials are in progress to determine the efficacy of
retinoids in treating other types of cancer such as
neuroblastoma and breast carcinoma.
 The development of receptor-selective retinoids and
selective inhibitors of retinoid metabolism may lead to
further use of retinoids in both chemoprevention and
treatment of cancer.

95. ADVANCES FOR BREAST CANCER PATIENTS
THE LATEST RESEARCH HELPS TURN THOUSANDS OF
BREAST CANCER PATIENTS INTO BREAST CANCER
SURVIVORS.
BY ALICE PARK WEDNESDAY, FEB. 27, 2008
 A provocative study this year by Canadian researchers found
that women with breast cancer who were deficient in bone-
building vitamin D had twice the risk of having their cancer
recur or progress over 10 years compared with women who
had sufficient levels of the vitamin; the D-deficient patients
also had a 73% greater risk of dying from their disease.
 Current guidelines recommend 200 IU of vitamin D each day
for women up to age 50, and progressively more for older
women.

96.  (Many doctors feel that's too low, however, and say 800 IU
daily is better, while the government says taking up to 2,000
IU a day is safe).
 Still, oncologists are not comfortable prescribing supplements
for breast cancer patients. It is unclear how much vitamin D
adults really need or whether supplements would have any
benefit for women already diagnosed with cancer.
 Further, most supplements do not contain the vitamin's most
potent form, D-3, which is what the body naturally produces
when skin is exposed to ultraviolet sunlight. It's also worth
noting that women in the Canadian study who had the
highest levels of vitamin D also had worse survival rates,
which suggests that there may be a limit to the vitamin's
value or a dose-specific benefit.

97. Department of Pediatrics, UZ Gasthuisberg,
Herestraat 49, 3000, Leuven, Belgium.
2006 Jul;165(7):429-34. Epub 2006 Feb 21.
Recent advances in vitamin E metabolism and
deficiency.
Ephrem Eggermont
Source

98.  Alpha-, beta-, gamma- and delta-tocopherol are present in
many foods and are, in the absence of fat malabsorption,
well absorbed from the gut.
 Their anti-oxidant property is well known and protects
arteries and capillaries as well as blood lipids and nervous
tissues against oxidative stress.
 In contrast to beta-, gamma- and delta-tocopherol, alpha-
tocopherol is preferentially conserved by the discriminating
action of the liver. Alpha-tocopherol transfer protein, which
also maintains plasma alpha-tocopherol concentration within
a range of 20 to 40 μm.
 In the circulation, alpha-tocopherol, in association with the
transfer-protein, is assembled into the very low-density
lipoprotein and low-density lipoprotein particles and released
for use by the peripheral tissues.
ABSTRACT

99.  Recent data suggest that alpha-tocopherol is not only an
anti-oxidant but also a regulator of gene expression through
its binding to nuclear receptors.
 The precise mechanism of regulating gene expression,
however, is still unknown.
 The four tocopherols are ultimately degraded by omega-
oxidation and subsequent beta-oxidations followed by the
elimination of the metabolites in the bile and in the urine.
 Patients with a defect of the alpha-tocopherol transfer
protein are unable to maintain their alpha-tocopherol
reserves and progressively lose tendon reflexes and have
signs and symptoms of spinocerebellar ataxia while plasma
vitamin E level drops below 2 μg/ml.
CONT…….

100. THE PHYSIOLOGY OF VITAMIN K NUTRITURE AND VITAMIN
K-DEPENDENT PROTEIN FUNCTION IN ATHEROSCLEROSIS.
BERKNER KL, RUNGE KW.
 Department of Molecular Cardiology, Lerner Research
Institute, Cleveland Clinic Lerner College of Medicine at
Case Western Reserve University, Cleveland, OH 44195,
USA. berknek@ccf.org
 2004 Dec;2(12):2118-32
Source

101.  Recent advances in the discovery of new functions for
vitamin K-dependent (VKD) proteins and in defining vitamin
K nutriture have led to a substantial revision in our
understanding of vitamin K physiology.
 The only unequivocal function for vitamin K is as a cofactor
for the carboxylation of VKD proteins which renders them
active.
 While vitamin K was originally associated only with hepatic
VKD proteins that participate in hemostasis, VKD proteins
are now known to be present in virtually every tissue and to
be important to bone mineralization, arterial calcification,
apoptosis, phagocytosis, growth control, chemotaxis, and
signal transduction action.
Abstract

102.  The advances in defining VKD protein function and
vitamin K nutriture are described, as is the potential
impact of VKD proteins on atherosclerosis.
 Many of the VKD proteins contribute to atherogenesis.
 Recent studies suggest involvement in arterial
calcification, which may be influenced by dietary levels of
vitamin K and by anticoagulant drugs such as warfarin
that antagonize vitamin K action.
CONT…….