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VITAMIN D – synthesis and
activation, mechanism of action, RDA
and dietary sources
VITAMIN D
INTRODUCTION
• Vitamin D is a fat-soluble vitamin that has long been known to help the
body absorb and retain calcium and phosphorus; both are critical for
building bone.
• Vitamin D is not strictly a vitamin since it can be synthesized in the skin. It
is a precursor to the hormone calcitriol.
• Only when sunlight exposure is inadequate is a dietary source needed.
• Its main function is to regulate calcium absorption and homeostasis.
• It has a role in regulating cell proliferation and differentiation.
• Over 75% of Americans are Vitamin D deficient.
• Although there are many forms of vitamin D, the two most common types
are vitamin D3 and vitamin D2.
• Vitamin D is also called as cholecalciferol,
antirachitic vitamin or sun-shine vitamin.
• Angus and coworkers isolated vitamin D and
named it as calciferol, which was later
identified as vitamin D3.
• The two main types of vitamin D are
vitamin D2 and vitamin D3.
• It is a modulator of immune response.
• Higher intakes of vitamin D maybe
beneficial as it protective against various
cancers, including prostate and
colorectal cancer.
• While increased sunlight exposure would
meet the need, it carries a risk factor of skin
cancer.
SYNTHESIS OF VITAMIN D
• Vitamin D3 (cholecalciferol) is synthesized in the skin by the reaction of 7-
dehydrocholesterol(an intermediate of cholestrol synthesis and available in
malphigian layer of epidermis) or ergostrerol with UVB radiation, present
in sunlight with an UV index of 3 or more.
• In the skin, the UV breaks the bond between position 9 and 10 of the steroid
ring.
• The ring B is opened to form the provitamin called secosterol.
• The cis double bond between 5th and 6th carbon atoms is then isomerized
to trans double bond to give vitamin D3 or cholecalciferol.
• Commercially he vitamin is
derived from the fungus called
ergot.
• The ergosterol when treated
with ultraviolet light, ergocalciferol
or vitamin D2 is produced.
• The production of vitamin D in the
skin is directly proportional to the
exposure to sunlight and inversely
proportional to the pigmentation of
the skin.
• An increase in the solar
zenith angle during november to
march shifts the wavelength of UV
to longer wavelengths which will
not produce the vitamin.
• Hence vitamin deficiency is seen in
the winter.
ACTIVATION OF VITAMIN D
• Cholecalciferol undergoes 2 hydroxylations to yield the active
metabolite, 1,25-dihydroxyvitamin D or calcitriol.
• Ergocalciferol undergoes similar hydroxylation to yield ercalcitriol.
• The cholecalciferol is first transported to the liver, where
hydroxylation at 25th position occurs, to form 25-hydroxy
cholecalciferol/calcidiol.
• In plasma, 25-HCC is bound to vitamin D binding protein (VDBP)
which is the main storage form of the vitamin, an alpha-2-globulin.
• In the kidney it is further hydroxylated at the first position.
• Thus 1,25-dihydroxy cholecalciferol (DHCC) is generated. It
contains 3 hydroxyl groups at 1, 3, 25 positions, it is also called
calcitriol.
• The calcitriol thus formed is the active of vitamin and it is
a hormone.
MECHANISM OF ACTION OF VITAMIN D
• This is facilitated by the vitamin D receptor.
• VDR is a transcription factor and member of the steroid hormone
nuclear receptor family.
• The calcitriol binds to the highly specific nuclear receptor vitamin D
receptor(VDR), which forms a heterodimeric complex with RXR that
binds to vitamin D response elements(VDRE) on DNA and modulates
the transcriptional activity of vitamin D responsive genes.
• VDRs are expressed on the cells in the brain, kidney, skin, gonads,
cardiomyocytes, vascular endothelial cells, vascular smooth muscle
cells, phagocytes and cells of the nephron.
• Vitamin D receptor may play a role in
regulating smooth muscle cell(SMC)
proliferation, thrombosis, fibrinolysis
and vessel relaxation.
• The influence of VDR activators may
reduce mortality,
cardiovascular morbidity in VDR-
activator-treated patients with
hypertension.
• Sites of action of effects of vitamin D
are :
1.Intestinal villi cells
2. Bone osteoblasts
3. Kidney distal tubular cells.
RDA –
RECOMMENDED
DAILY
ALLOWANCE
The recommended daily allowances for vitamin
D along with sufficient outdoor exposure to
sunlight are :
: 400 IU or 10
: 600 IU/day
: 600 IU or 15
1. Infants
µg/day
2. Children
3. Adult males and females
µg/day
4. Pregnancy and lactation
5. Elderly persons above the
an EAR of 400 IU/day.
age of 60
: 600 IU/day
: 800 IU/day with
In obese children, supplementation with higher
doses of vitamin D upto 800 IU/day is suggested
because vitamin D is stored in fat tissue.
DIETARY
SOURCES OF
VITAMIN D
• Fish liver oil
• Egg yolk
• Fish
• Salmon
• Red meat
• Cereals
• Milk has moderate quantity of
vitamin. Hence, fortifying
dairy products with vitamin D
is the current scenario.
• Exposure to sunlight produces vitamin D3 / cholecalciferol.
• Thus, adequate exposure to sunlight without
sunscreen before 10am and after 3pm atleast 15 minutes a day (safe
sun) is recommended.
• Vitamin D is very
significant in the
body.
• Its deficiency
causes
1.rickets in
children
2.osteomalacia
in adults
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Presentation 3.pptx

  • 1. VITAMIN D – synthesis and activation, mechanism of action, RDA and dietary sources
  • 2. VITAMIN D INTRODUCTION • Vitamin D is a fat-soluble vitamin that has long been known to help the body absorb and retain calcium and phosphorus; both are critical for building bone. • Vitamin D is not strictly a vitamin since it can be synthesized in the skin. It is a precursor to the hormone calcitriol. • Only when sunlight exposure is inadequate is a dietary source needed. • Its main function is to regulate calcium absorption and homeostasis. • It has a role in regulating cell proliferation and differentiation. • Over 75% of Americans are Vitamin D deficient. • Although there are many forms of vitamin D, the two most common types are vitamin D3 and vitamin D2.
  • 3. • Vitamin D is also called as cholecalciferol, antirachitic vitamin or sun-shine vitamin. • Angus and coworkers isolated vitamin D and named it as calciferol, which was later identified as vitamin D3. • The two main types of vitamin D are vitamin D2 and vitamin D3. • It is a modulator of immune response. • Higher intakes of vitamin D maybe beneficial as it protective against various cancers, including prostate and colorectal cancer. • While increased sunlight exposure would meet the need, it carries a risk factor of skin cancer.
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  • 5. SYNTHESIS OF VITAMIN D • Vitamin D3 (cholecalciferol) is synthesized in the skin by the reaction of 7- dehydrocholesterol(an intermediate of cholestrol synthesis and available in malphigian layer of epidermis) or ergostrerol with UVB radiation, present in sunlight with an UV index of 3 or more. • In the skin, the UV breaks the bond between position 9 and 10 of the steroid ring. • The ring B is opened to form the provitamin called secosterol. • The cis double bond between 5th and 6th carbon atoms is then isomerized to trans double bond to give vitamin D3 or cholecalciferol.
  • 6. • Commercially he vitamin is derived from the fungus called ergot. • The ergosterol when treated with ultraviolet light, ergocalciferol or vitamin D2 is produced. • The production of vitamin D in the skin is directly proportional to the exposure to sunlight and inversely proportional to the pigmentation of the skin. • An increase in the solar zenith angle during november to march shifts the wavelength of UV to longer wavelengths which will not produce the vitamin. • Hence vitamin deficiency is seen in the winter.
  • 7. ACTIVATION OF VITAMIN D • Cholecalciferol undergoes 2 hydroxylations to yield the active metabolite, 1,25-dihydroxyvitamin D or calcitriol. • Ergocalciferol undergoes similar hydroxylation to yield ercalcitriol. • The cholecalciferol is first transported to the liver, where hydroxylation at 25th position occurs, to form 25-hydroxy cholecalciferol/calcidiol. • In plasma, 25-HCC is bound to vitamin D binding protein (VDBP) which is the main storage form of the vitamin, an alpha-2-globulin. • In the kidney it is further hydroxylated at the first position. • Thus 1,25-dihydroxy cholecalciferol (DHCC) is generated. It contains 3 hydroxyl groups at 1, 3, 25 positions, it is also called calcitriol. • The calcitriol thus formed is the active of vitamin and it is a hormone.
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  • 9. MECHANISM OF ACTION OF VITAMIN D • This is facilitated by the vitamin D receptor. • VDR is a transcription factor and member of the steroid hormone nuclear receptor family. • The calcitriol binds to the highly specific nuclear receptor vitamin D receptor(VDR), which forms a heterodimeric complex with RXR that binds to vitamin D response elements(VDRE) on DNA and modulates the transcriptional activity of vitamin D responsive genes. • VDRs are expressed on the cells in the brain, kidney, skin, gonads, cardiomyocytes, vascular endothelial cells, vascular smooth muscle cells, phagocytes and cells of the nephron.
  • 10. • Vitamin D receptor may play a role in regulating smooth muscle cell(SMC) proliferation, thrombosis, fibrinolysis and vessel relaxation. • The influence of VDR activators may reduce mortality, cardiovascular morbidity in VDR- activator-treated patients with hypertension. • Sites of action of effects of vitamin D are : 1.Intestinal villi cells 2. Bone osteoblasts 3. Kidney distal tubular cells.
  • 11. RDA – RECOMMENDED DAILY ALLOWANCE The recommended daily allowances for vitamin D along with sufficient outdoor exposure to sunlight are : : 400 IU or 10 : 600 IU/day : 600 IU or 15 1. Infants µg/day 2. Children 3. Adult males and females µg/day 4. Pregnancy and lactation 5. Elderly persons above the an EAR of 400 IU/day. age of 60 : 600 IU/day : 800 IU/day with In obese children, supplementation with higher doses of vitamin D upto 800 IU/day is suggested because vitamin D is stored in fat tissue.
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  • 13. DIETARY SOURCES OF VITAMIN D • Fish liver oil • Egg yolk • Fish • Salmon • Red meat • Cereals • Milk has moderate quantity of vitamin. Hence, fortifying dairy products with vitamin D is the current scenario.
  • 14. • Exposure to sunlight produces vitamin D3 / cholecalciferol. • Thus, adequate exposure to sunlight without sunscreen before 10am and after 3pm atleast 15 minutes a day (safe sun) is recommended.
  • 15. • Vitamin D is very significant in the body. • Its deficiency causes 1.rickets in children 2.osteomalacia in adults