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Vitamin d
1. UNIVERSITY PUTRA MALAYSIA
FACULTY OF MEDICINE AND HEALTH SCIENCES
DEPARTMENT OF NUTRITION SCIENCES
VITAMIN D
MICRONUTRIENTS IN HEALTH AND DISEASE
By
Mohammed Ellulu
2. Introduction
Vitamin D is represented by:
1. cholecalciferol (vitamin D3)
2. ergocalciferols (vitamin D2) (in plant, fungi, yeast)
they are structurally similar, derived from the UV irradiation
of provitamin D sterols.
Vitamin D3 is produced by the action of sunlight on
7-dehydrocholesterol in the skin.
2
3. Structural differences of D2 and D3
3
In C-17 side chain, vitamin D2 has double bond and
additional methyl group.
4. Human activation
4
1. Endogenous or dietary origin of vitamin D will be
hydroxylated in the liver at carbon 25 to yield 25-
hydroxyvitamin D [25(OH)D].
2. This compound circulates in the blood and,
3. In the kidney, hydroxylation at the α-position of
carbon 1 to generate 1α,25-dihydroxyvitamin D
[1α,25(OH)2D].
5. The active form
5
The dihydroxylated vitamin D2 and D3 metabolites
are the active hormones.
6. Dietary sources
6
The proportion of vitamin D obtained from the diet
is very small compared with that synthesized in skin
in response to sunlight.
Fish-liver oils,
Fatty fish as sardines,
Eggs and dairy products,
Cereals, vegetables and fruit contain no vitamin D,
Meat and poultry contribute insignificant amounts.
7. Cutaneous synthesis
7
Vitamin D3 is synthesized in the skin from 7-
dehydrocholesterol (provitamin D3).
Provitamin D3 is converted photochemically to
previtamin D3, which converted to vitamin D3 by a
temperature-dependent process (non enzymatic).
The waveband of solar radiation responsible for the
conversion of the provitamin to the previtamin is
that between 290 and 315 nm, known as the UV-B
band (less than 290 does not reach the earth).
8. Factors affecting vitamin D3 production
8
1- Ageing
The skin becomes progressively thinner. The epidermal
concentration of 7-dehydrocholesterol decreases.
Young adults produce 3 times more than elderly.
2- Degree of skin pigmentation
Skin pigmentation is a limiting factor for previtamin
D3 synthesis because melanin competes with 7-
dehydrocholesterol in absorbing UV-B radiation.
3- Use of sunscreens
9. Intestinal absorption and transport
9
Vitamin D is incorporated into chylomicrons, when
released, the chylomicrons convey the vitamin in the
mesenteric lymph to the systemic circulation.
In the lymph, an appreciable amount of the vitamin
D in the chylomicrons is transferred to the DBP.
After lipolysis of the chylomicrons, the vitamin D
remaining on the chylomicron remnants, and also the
vitamin D bound to protein, is initially taken up by
the liver.
10. Calcium and phosphate homeostasis
10
1α,25-Dihydroxyvitamin D restores low plasma
concentrations of Ca2+ and Pi to normal by action at the
three major targets; intestine, bone, kidney.
a) stimulates the intestinal absorption of Ca2+ and Pi by
independent mechanisms,
b) stimulates the transport of Ca2+ (accompanied by Pi)
from the bone fluid compartment to the extracellular
fluid compartment,
c) facilitates the renal reabsorption of Ca2+. These
three mechanisms provide calcium for bone
mineralization and prevent hypocalcaemic tetany.
11. 11
1α,25-Dihydroxyvitamin D3 regulates the synthesis
of two classes of calcium-binding proteins
(calbindins) found in mammalian intestine and
kidney.
An intestinal protein (calbindin-D9k) binds two
calcium ions per molecule,
A renal protein (calbindin-D28k) binds five to six
calcium ions per molecule.
Calcium and phosphate homeostasis
12. Intestinal calcium absorption
12
Calcium is present in foods and dietary supplements as
relatively insoluble salts.
Calcium is absorbed only in ionized form, it must be
released from the salts (mostly acidic medium).
On reaching the alkaline environment of the small
intestine, some of the Ca2+ complex with minerals or
other specific dietary constituents, thereby limiting
calcium bioavailability.
Calcium absorption takes place by the translocation of
luminal Ca2+ through the enterocytes (transcellular
route) and between adjacent enterocytes via the tight
junctions (paracellular route).
13. The calbindin-based diffusional-active
transport model13
This transcellular pathway is a complex process
involving three steps:
(1) entry by movement of Ca2+ from lumen through
the brush-border membrane of the enterocyte,
(2) intracellular diffusion,
(3) extrusion from the cell across the basolateral
membrane. The major action of vitamin D in
regulating this process is on the steps involved in
Ca2+ movement beyond brush-border entry.
14. Intestinal phosphate absorption
14
Dietary phosphorus is a mixture of inorganic and
organic phosphorus.
Phosphorus in meat and fish exists largely in the
form of phosphoproteins and phospholipids
(enzymatic hydrolysis).
80% of phosphorus in grains is found as phytic acid
(bioavailability reduced).
Milk protein (casein) is highly phosphorylated.
Phosphate absorption takes place mainly in the
jejunum by an energy-dependent transcellular route.
15. Vitamin D action on bone
15
1α,25(OH)2D3 is required for normal development and
mineralization of bone, and for bone remodelling.
The effect of 1α,25(OH)2D3 on bone is indirect, being
attributable to the increased availability of calcium and
phosphate for incorporation into bone that results from
the increased intestinal absorption.
Rickets can be cured in vitamin D-deficient rats by
increasing the calcium and phosphorus content of the
diet or by maintaining normal circulating concentrations
of these minerals through infusion.
16. Vitamin D action on bone
16
A major physiological function of 1α,25(OH)2D3 in
calcium homeostasis is stimulation of bone resorption,
which refers to localized bone dissolution by osteoclasts
with resultant net calcium movement from bone to
blood.
The hormone acts by increasing the expression of
proteins essential to the resorptive process, proteins such
as carbonic anhydrase.
The hormone also inhibits bone formation by decreasing
alkaline phosphatase activity and collagen synthesis in
osteoblasts and increasing the synthesis of osteocalcin,
a potent inhibitor of mineralization.
18. Phosphate homeostasis
18
Unlike calcium, dietary phosphate usually exceeds the
body’s nutritional requirement, therefore a major component
of phosphate homeostasis is renal excretion. A diet that is
low in phosphorus is likely to be low also in calcium, which
complicates the picture of phosphate homeostasis.
A lowering of plasma phosphate will stimulate the kidney to
release 1α,25(OH)2D3, which elicits rapid and long-term
responses in the kidney, leading to increased renal
reabsorption of phosphate.
The 1α,25(OH)2D3 will also increase the intestinal
absorption of phosphate and calcium. The parathyroids will
not be stimulated to produce PTH.
19. Effects of vitamin D on insulin secretion
19
1α,25-Dihydroxyvitamin D3 is considered to be a
modulator of insulin secretion;
Because…. vitamin D deficiency in rats is associated
with marked impairment of insulin secretion and the
insulin-secreting β-cells of the pancreas contain the
vitamin D-regulated protein calbindin-D28k.
20. Vitamin D-related diseases
20
Rickets
The classic vitamin D deficiency disease in children.
The disease is characterized by bow legs or knocks
knees, curvature of the spine, and pelvic and
thoracic bone deformities.
These deformities result from the mechanical stresses
of body weight and muscular activity applied to the
soft uncalcified bone.
21. Vitamin D-related diseases
21
Osteomalacia
In adults, when the skeleton is fully developed,
vitamin D is still necessary for the continuous
remodelling of bone.
During prolonged vitamin D deficiency, the newly
formed, uncalcified bone tissue gradually takes the
place of the older bone tissue and the weakened
bone structure is easily prone to fracture.
22. Toxicity
22
Hypervitaminosis D results from the excessive
consumption of vitamin D supplements, and not from
the consumption of usual diets.
Toxic concentrations of vitamin D have not resulted
from unlimited exposure to sunshine.
Vitamin D toxicity is due primarily to the
hypercalcaemia caused by the increased intestinal
absorption of calcium, together with increased
resorption of bone.
23. Possible Interactions with Vitamin D
23
Vitamin D levels may be increased by the following
medications:
Estrogen: Hormone replacement therapy appears to
increase vitamin D levels in the blood; this may have a
beneficial effect on calcium and bone metabolism. In
addition, use of vitamin D supplements in conjunction
with estrogen increases bone mass more than ERT alone.
Isoniazid (INH): INH, a medication used to treat
tuberculosis, may raise blood levels of vitamin D.
Thiazide: Diuretics in this class increase the activity of
vitamin D and can lead to inappropriately high calcium
levels in the blood.
24. Possible Interactions with Vitamin D
24
Vitamin D levels may be decreased, or its absorption may be
reduced, by the following medications:
Antacids: Taking antacids for long periods of time may alter
the levels, metabolism, and availability of vitamin D.
Calcium channel blockers (as verapamil ): used to treat high
(bp) and heart conditions, may decrease the production of
vitamin D by the body.
Cholestyramine: cholesterol-lowering medication, known as a
bile acid sequestrant, interferes with the absorption of
vitamin D (as well as other fat-soluble vitamins).
Phenobarbital (anticonvulsant): may accelerate the body's
use of vitamin D.
25. Possible Interactions with Vitamin D
25
Weight loss products:
Orlistat, a medication used for weight loss, and
Olestra, a substance added to certain food products,
The both intended to bind to fat and prevent the
absorption of fat and the associated calories.
Because of their effects on fat, orlistat and olestra may
also prevent the absorption of fat-soluble vitamins such
as vitamin D.
In addition, multivitamins with fat soluble vitamins will
be prescribed with orlistat to the regimen.
26. Dietary requirement
26
The dietary requirement for vitamin D depends upon
the amount of vitamin synthesized by solar irradiation
of the skin.
Exposing hands, arms and face on a clear summer day
for 10–15 min, two to three times a week, should yield
sufficient cutaneous production of vitamin D to meet
daily needs.
To maintain satisfactory plasma 25(OH)D levels without
any input from skin irradiation, an oral input in the
region of 10–15 μg of vitamin D per day would be
required.
