Fat soluble vitanine. mostafa askar

3. Vitamins are micronutrients

4. VITAL+
AMINE
Nutrients
VITAMINE
µg-mg
/day

5. Vitamins are organic nutrients that are
required in small quantities for a variety of
biochemical functions and which generally
cannot be synthesized in the body and must
be supplied by the diet

6. Water
soluble
Fat soluble
• B complex
• C or Ascorbic acid
• A or Retinol
• D or Cholecalciferol
• E or Tocopherol
• K
Classification

7. • B1 - Thiamine
• B2 - Riboflavin
• B3 - Niacin
• B5 - Pantothenic acid
• B6 - Pyridoxine
• Biotin
• Folic acid
• B12- Cobalamine
Vitamin B complex
Vitamine C or Ascorbic acid
•Water soluble vitaminsVITAMINS

8. Folic acid
Vitamin B12
•Vitamins B-complexVITAMINS

9. Water soluble vitamins Fat soluble vitamins
Solubility Water soluble Fat soluble
Absorption Simple Along with lipids
Storage *No storage Stored in liver
Excretion Excreted Not excreted
Excess intake Nontoxic Toxic
Deficiency Manifests rapidly Manifests slowly
Treatment Regular dietary supply Single large dose
Difference b/w water soluble & fat soluble vitaminsVITAMINS

10. Vitamin A Vitamin D
Vitamin E Vitamin K

12. Chemistry
Sources
Daily
Requirements
Absorption,
Transport and
storage
Functions
Deficincy
Vitamin A
excess

13. • Vitamin A occurs in two forms in food
Retinoids
Retinol
Retinal
Retinoic acid
Carotenes
α- carotene
β- carotene
γ- carotene

14. RETINOL
RETINAL
RETINOIC ACID
β-ionone ring

19. One ounce
of polar
bear liver
contains
enough
vitamin A
(retinol) to
kill a
person!

20. • The daily requirement of
vitamin A is expressed as
retinol equivalents [RE]
1000 RE
MEN
800 RE
WOMEN
1RE = 1µg of retinol
= 3.3 IU of retinol

21. ABSORPTION
TRANSPORT AND
STORAGE

22. RETINA
TARGET TISSUES
ABSORPTION
TRANSPORT AND
STORAGE

23. ABSORPTION
TRANSPORT
AND
STORAGE

24. Vision : 11-cis retinal [Wald’s visual cycle]
Reproduction: Retinol
Growth and differentiation : Retinoic acid
Epithelial Integrity : Retinol
Immunity
Antioxidants :β -carotenes
Glycoprotein synthesis

25. RODS
RHODOPSIN
11-Cis
retinal
Opsin
Photoreceptor cells in the retina
Photosensitive pigment

26. Rhodopsin cycle comprises two distinct events
Bleaching of rhodopsin & generation
of nerve impulse
Regeneration of rhodopsin

30. CONES
Porphyropsin
Iodopsin
Cynopsin
Photoreceptor cells in the retina
Required for vision in daylight
and colour identification

31. Causes Inadequate intake
Impaired absorption
Impaired storage & transport
Increased excretion [RBP]
Alcoholism

32. Features Nightblindness
Xerophthalmia
Bitot spots
Keratomalacia
Infections
Hyperkeratinization of skin
Growth retardation

33. Bitot’s spot Bitot’s spot

34. KeratomalaciaXerophthalmia

35. Impaired dark
adaptation time
Decreased vitamin
A in plasma
Decreased
RBP in plasma
Normal plasma vitamin
20 to 80 µg/100ml

36. Over ingestionCauses
Bone and joint
pain
Anorexia
Hair loss
Headache
Hepatomegaly
Weight loss

37. Chemistry
Sources
Daily
Requirements
Absorption,
Transport and
storage
Functions
Deficincy
Vitamin A
excess

38. Vitamin D refers to a group of fat-
soluble secosteroids responsible for enhancing intestinal
absorption of calcium, iron,magnesium, phosphate and zinc.
In humans, the most important compounds in this group
are vitamin D3 (also known ascholecalciferol) and vitamin
D2 (ergocalciferol)

39. Name Chemical composition
Vitamin D1
molecular compound of
ergocalciferol with lumisterol, 1:1
Vitamin D2 ergocalciferol (made from ergosterol)
Vitamin D3
cholecalciferol (made from 7-
dehydrocholesterol in the skin).
Vitamin D4 22-dihydroergocalciferol
Vitamin D5
sitocalciferol (made from 7-
dehydrositosterol)
Vitamin D2
Vitamin D3
Vitamin D4
Vitamin D5

40. Important to maintain calcium and phosphate homeostasis and bone and muscle integrity
Calcitriol stimulates absorption of calcium from GI tract and reduces loss of calcium in urine
PTH activates enzyme which converts inactive vitamin D to the active form and so can
be raised in vitamin D deficiency.
Calcitriol acts on intranuclear receptors present on most body cells
Calcitriol directly stimulates bone remodelling
Activation in liver and kidneys to CALCITRIOL

41. • Vitamin D insufficiency and deficiency common
• Implications for bone and muscle health
• Public health issue and raised awareness
• More requests for testing and cost implications in testing
and prescribing

42. Sources & Metabolism of Vitamin D
Solar UVB (280-310nm)
Endogenous
Vitamin D3
Dietary source
Vitamin D2 & D3
Oily fish, eggs,
fortified foods e.g:
 Infant formulas
 Cereals
Liver
25-Hydroxyvitamin D
(major circulating metabolite)
1,25-Dihydroxyvitamin D
Kidney
1α hydroxylase
(CYP27B1)
 PTH (+)
 ↓ P (+)
 FGF23 (-)
(7-dehydoxycholesterol)
DBP
25-hydroxylase
(CYP2R1)
24-hydroxylase
(CYP24A1)
DBP
24,25-hydroxyvitamin D
Calcitroic acid

43. Why do people become vitamin D
deficient?
• Lack of UVB sunlight exposure (90% UK too far north to
have adequate levels for 6 months of the year!)
• Small quantities in food
• Sunscreen with SPF 15+ blocks 99% vitamin D synthesis
• Possibility of many other health problems associated with
Vitamin D deficiency inc cardiovascular disease, infections,
autoimmune diseases and cancers...

44. Factors which contribute to development of Vitamin D deficiency
 Residence in Northern or Southern Latitudes
 Pigmented skin
 Sun blocking creams – Factor 8 ↓ Vit D synthesis by >95%
 Sunshine avoidance for religious or cultural reasons
 Cloud Cover & Atmospheric Pollution
 Obesity
 Genetic propensity
 An independent protective effect of meat consumption
 Low dietary Calcium & High Fibre diets

45. Roles of 1,25-Dihydroxyvitamin D in Bone Mineral Homeostasis
 Stimulates GI calcium absorption
 Promotes renal calcium re-absorption
 Stimulates GI phosphorous absorption
 Calcium homeostasis: together with PTH it mobilises calcium from skeletal
stores
 Mineralisation of the growth plate & osteoid
Normal Growth Plate Rachitic Growth Plate
Low Calcium
or
Low Phosphorous
Radiograph showing
Rachitic Changes

46. Low Calcium & High Fibre Diet and Vitamin D Status
Vitamin D Dietary Ca
 High fibre & phytic acid reduce dietary Ca intake
 Low Ca intake leads to secondary hyperparathyroidism & raised serum
1,25(OH)2D concentration
 Raised serum 1,25(OH)2D concentration degrades 25OHD to inactive
24,25-dihydroxyvitamin D, thereby depleting body stores of vitamin D
Clements et al. Nature 1987;325:62–5

47. 1 ml ~ 1mg
1 pot ~ 150 mg
~ 35 mg/slice
1 Bowl ~ 80 mg
1 oz ~ 200 mg
RNI (mg/day) in the UK
Infants up to 1 yr 525
Children 1- 3 yrs 350
Children 2-6 yrs 450
Children 7-10 yrs 550
Adolescent boys 11-18 yrs 1000
Adolescent girls 11-18 yrs 800

48. DIAGNOSIS: Severe vitamin D deficiency & low calcium intake
Pre Rx Post Rx
25(OH)D (ng/ml) <2 27.1
PTH (ng/ml)
(10-60)
593 90
Calcium (mmol/l)
(2.15 – 2.65)
1.38 2.23
Phosphate (mmol/l)
(1.0 – 1.8)
1.68 1.43
Alk Phos (I/U) 1020 592
Rx: Single orally dose 180, 000 IU Vitamin D3 + 500mg/day Ca supplement
Vitamin D Deficiency & Myopathy
 14 year old female
 Limb pains
 Difficulty walking & Climbing stairs
 Life long intolerance of dairy products
(Ca intake <300 mg/day)
 Arrived from Saudi Arabia 8 months ago
8th April 09 5th May 09

49. Life threatening Cardiomyopathy in Early Infancy
Maiya S et al .Hypocalcaemia and Vitamin D deficiency: an important, but preventable cause of life
threatening infant heart failure.Heart. 2007 Aug 9; [Epub]
 16 infants (6 South Asian, 10 Black ethnicity) admitted to GOS with Heart Failure
 Median age 5.3 months (3 weeks - 8 months);12 exclusively breast-fed
 12 needed inotropic support
 8 ventilated & 2 needed ECMO
 2 referred for cardiac transplantation
 6 suffered a cardiac arrest & 3 died!
Median (range) Reference range
Calcium (mmol/L) 1.50 (1.07 – 1.74) 2.17 – 2.44
PTH (pmol/L) 34.3 (8.9 – 102) 0.7 – 5.6
25OHD (nmol/L) 18.5 (0.00 – 46) >50
Fractional shortening (%) 10 (5-18) 28 – 45
Left ventricular end diastolic
dimension Z score 4.1 (3.1-7) -2 < +2

50. Holick BMJ June 2008;336:1318-1319
Possible Consequences of Vitamin D Deficiency

51. Vitamin D & Innate Immunity
Adequate serum 25(OH)D
Innate immunity
 Toll like receptors recognise pathogens

  expression of VDR & CYP27B1 enzyme
25(OH)D  1,25(OH)2D
 1,25(HO)2D leads to production of
antimicrobial proteins (AMPs)
 AMPs (e.g. Cathelcidin) important role in
defence against bacterial & viral infections

52. Vitamin D Deficiency & Pneumonia
New RMCH July 2009

53. Preventing Vitamin D Deficiency
in children
DOH recommendations:
• All infants and children under 5 years should
take supplements – at least 280 IU daily
• All pregnant women should take 400IU
vitamin D supplements daily
• All breastfeeding should take 400 IU vitamin D
supplements daily

54. Preventing Vitamin D Deficiency in adults
• Fair skinned young person – needs 20-30min UVB
exposure at midday to face and forearms 3 x /wk for
healthy vitamin D levels (each exposure = 2000IU)
• Elderly and those with pigmented skin need more
frequent and longer sun exposure to achieve same
levels (2 to 10 fold!)
• Healthy adults at risk of deficiency – 400IU vitamin D
supplement daily
• Adults at high risk of deficiency e.g. South Asians, aged
over 65 years, extensive covering take 800IU vitamin D
supplement daily

57. 1. To treat vitamin D deficiency with 60,000IU per week for 12
weeks
2. To encourage patients to buy OTC supplements and share
the approximate costs with them as they may perceive the
cost to be much higher.
3. To prescribe Hux D3/Biovit D3 instead of Dekristol (cheaper
as not unlicensed)
4. To prescribe vitamin D supplement by brand
5. To prescribe Fultium D3 as maintenance therapy instead of
AdcalD3 in vitamin D deficiency

58. Chemistry
Sources
Daily
Requirements
Absorption,
Transport and
storage
Functions
Deficincy
Vitamin A
excess

59. Both structures are similar except the tocotrienol structure has double bonds on the isoprenoid units.
There are many derivatives of these structures due to the different substituents possible on
the aromatic ring at positions 5, 6, 7, and 8.
Position of methyl groups
on aromatic ring
Tocopherol structure Tocotrienol structure
5,7,8 alpha-Tocopherol alpha-Tocotrienol
5,8 beta-Tocopherol beta-Tocotrienol
7,8 tau-Tocopherol tau-Tocotrienol
8 delta-Tocopherol delta-Tocotrienol
• Vitamin A occurs in two forms in food

60. Vitamin E, a fat-soluble vitamin, is an
antioxidant vitamin involved in the
metabolism of all cells. It protects vitamin A
and essential fatty acids from oxidation in
the body cells and prevents breakdown of
body tissues.

61. • Chain-breaking antioxidant
• Protects cell membranes
• Enhances immune response
• Regulates platelet aggregation
• Regulates protein kinase C activation

62. Vegetable oils,
sunflower seeds and nuts
are the richest dietary
sources
Average daily intake is
15 I.U. in men and 11.4 I.U
in women (NHANES III)
DRI and RDA is 15 mg
alpha-tocopherol (22.5
I.U.)
Optimal vitamin E
intakes may be 100-400
I.U. per day

63. • Susceptible groups
– Patients with malabsorption syndromes
– Premature infants
– Patients on TPN
• Characterized by progressive neurological syndrome
– Gait disturbances
– Absent or altered reflexes
– Limb weakness
– Sensory loss in arms and legs
• Improved neurological function with vitamin E therapy

66. • Natural-source is a single isomer
(d-alpha-tocopherol)
• Synthetic is a mixture of eight isomers
• Natural-source has twice the bioavailability of
synthetic

67. Chemistry
Sources
Daily
Requirements
Absorption,
Transport and
storage
Functions
Deficincy
Vitamin A
excess

69. Vitamin K1
Vitamin K2
• Vitamin K1 (phylloquinon) – plant
origin
• Vitamin K2 (menaquinon) – normally
produced by bacteria in the large
intestine
• K1 a K2 are used differently in the
body
– K1 – used mainly for blood clothing
– K2 – important in non-coagulation
actions - as in metabolism and bone
mineralization, in cell growth,
metabolism of blood vessel walls
cells.
Synthetic derivatives of Vit.K

70. • Cofactor of liver microsomal carboxylase which carboxylates glutamate
residues to g-carboxyglutamate during synthesis of prothrombin and
coagulation factors VII, IX a X (posttranslation reaction).
• Carboxylated glutamate chelates Ca2+ ions, permitting the binding of
blood clotting proteins to membranes.
• Forms the binding site for Ca2+ also in other proteins – osteocalcin.

71. • Green leafy vegetables
• vegetable oil
• broccoli
• cereals
http://health.allrefer.com/health/nutrition.html

72. • Vitamin K serves as an
essential cofactor for a
carboxylase that catalyzes
carboxylation of glutamic
acid residues on vitamin K-
dependent proteins. These
proteins are involved in:
1) Coagulation
2) Bone Mineralization
3) Cell growth

73. Deficiencies are very rare in humans except in
newborns due to:
• insufficient gut bacteria
• poor placental transport of vitamin K
• low prothrombin synthetic capacity of
neonatal liver
Newborns routinely receive vitamin K injection
(0.5 -1 mg vitamin K) or 2 mg orally, because
human milk is very low in vitamin K (2.5 μg/L).
Bleeding episodes may occur in patients with low
vitamin K status on long-term antibiotic
treatment (loss of colonic bacteria).
Vitamin K Deficiency

74. Vitamin K - deficiency
• Deficiency is caused by fat malabsorption or by the liver
failure.
• Blood clotting disorders – dangerous in newborns, life-
threatening bleeding (hemorrhagic disease of the newborn).
• Osteoporosis due to failed carboxylation of osteokalcin and
decreased activity of osteoblasts.
• Under normal circumstances there is not a shortage, vit. K is
abundant in the diet.

75. Symptoms of Vitamin K Deficiency
• 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 hemorrhage

76. Newborns are prone to vitamin K deficiency because…
1. Vitamin K and lipids are not easily transported across the placental barrier
2. Prothrombin synthesis in the liver is an immature process in newborns,
especially when premature.
3. The neonatal gut is sterile, lacking the bacteria that is necessary in
menaquinone synthesis.
4. Breast milk is not a good source of vitamin K
Results in a hemorrhagic disease called vitamin K deficiency bleeding (VKDB)
This disease is associated with breastfeeding, maladsorption of lipids, or liver
disorders.

77. • The transformation of
liquid blood into a solid
gel
• Stops blood flow in the
damaged area
• Fibrin is the final protein
which produces a
meshwork to trap RBC
and other cells

78. • Certain clotting factors/proteins require calcium to bind for
activation
• Calcium can only bind after gamma carboxylation of specific
glutamic acid residues in these proteins
• The reduced form of vitamin K2 (vitamin KH2) acts as a cofactor for
this carboxylation reaction.
• These proteins are known as “Vitamin K dependent” proteins

79. • factor II (prothrombin)
• factor VII (proconvertin)
• factor IX (thromboplastin component)
• factor X (Stuart factor)
• protein C & protein S
• Protein Z

81. Vitamin K Cycle
Glutamic Acid
Gamma Carboxy
Glutamic Acid
Vitamin K
Vitamin K Epoxide
Vitamin KH2
Vitamin K Dependent
Carboxylase
Reductase
Epoxide
Reductase
Warfarin Inhibits

82. Vitamin K-dependent clotting factors (FII, FVII, FIX, FX, Protein C/S/Z)
Epoxide
Reductase
g -Carboxylase
(GGCX)
Warfarin inhibits the vitamin K cycle
Warfarin
Inactivation
CYP2C9
Pharmacokinetic

83. Life Stage Age Males (mcg/day) Females (mcg/day)
Infants 0-6 months 2.0 2.0
Infants 7-12 months 2.5 2.5
Children 1-3 years 30 30
Children 4-8 years 55 55
Children 9-13 years 60 60
Adolescents 14-18 years 75 75
Adults 19 years and older 120 90
Pregnancy 18 years and younger - 75
Pregnancy 19 years and older - 90
Breast-feeding 18 years and younger - 75
Breast-feeding 19 years and older - 90
As outlined by the Food and Nutrition Board (FNB) of the Institute of Medicine in the US (January 2001)

84. • Vitamin K can be given orally
• In the case of someone who improperly absorbs fat or is at high risk of bleeding,
Vitamin K can be injected under the skin
• If a drug is causing Vitamin K deficiency, the dose is altered or extra Vitamin K is given
• In people who suffer from both severe liver disorders and Vitamin K deficiency,
Vitamin K injections may be insufficient so blood transfusions may be necessary to
replenish clotting factors
• It is recommended that all newborns are given an injection of phylloquinone (Vitamin
K1) into the muscle to prevent intracranial bleeding after delivery
• Formulas for infants contain Vitamin K

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• 6. Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women’s
Health Initiative limited access dataset and meta-analysis BMJ2011;342:d2040
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87. 