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.

17. Calcium homeostasis
17

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.

27. References
27
 http://www.umm.edu/altmed/articles/vitamin-d-
000995.htm#ixzz2R6E5HYwi.
 Caballero B (2005). Encyclopaedia of Human
Nutrition. Second Esition. Elsevier
 Zempleni J, Rucker RB, McCormick DB, and Suttie
JW (2007) Handbook of VITAMINS. Fourth Edition.
Taylor & Francis Group.
 Bender D (2003). Nutritional Biochemistry of the
Vitamins. Second Edition. Cambridge University
Press.