Vitamin E

1
Vitamin E

• Fat soluble compounds, produced by plants to
  prevent lipid peroxidation in their cell
  membranes and oil droplets
• Tocopherols (?, ß, ?, ? )
• Tocotrienols (?, ß, ?, ? )

2
Vitamin E natural compounds
3
Eight stereochemical isomers of ?-Tocopherol in
synthetic Vitamin E

• Active Inactive
• RRR- SRR-
• RSR- SSR-
• RRS- SRS-
• RSS- SSS-
• Different arrangement of methyl groups in the
  side chain starting at chromanol ring

4
Vitamin E units

• 1 IU (International Unit)
• 1 mg all rac-?-tocopheryl acetate 0.67 mg
  RRR-?-tocopherol
• 1 mg RRR-?-tocopherol 1.49 IU

5
Vitamin E activity units

• Used in food tables to calculate total intake
• ?-Tocopherol Equivalent (?-TE)
• mg ?-tocopherol
• (mg ß-tocopherol x 0.5)
• (mg ?-tocopherol x 0.1)
• (mg ?-tocotrienol x 0.3)
• mg ?-tocopherol mg ?-TE x 0.8

6
Food Sources
o
(1.49 IU/mg)
Major sources are vegetable oils, whole grains,
seeds and nuts.
7
Vitamin E Dietary Reference Intakes (2000)
8
Vitamin E Tolerable Upper Intake Levels
UL are referring to any form of supplementary of
?-tocopherol, and were set to prevent increased
tendency to hemorrhage.
9
Vitamin E Deficiency

• Very rare in normal subjects
• AVED (ataxia and vitamin E deficiency) defect
  in ?-TTP gene
• Abetalipoproteinemia (inability to produce
  chylomicrons, LDL, VLDL)
• Cystic fibrosis (defective fat absorption)
• Cholestatic liver disease

10
Vitamin E deficiency symptoms

• Primary symptom peripheral neuropathy
  (degeneration of large axons in sensory neurons)
• Ataxia
• Myopathy
• Hemolysis of RBC in vitro, using hydrogen
  peroxide, is indicative of low vitamin E status.
• Plasma level lt 600 µg/dL

11
Absorption and transport of vitamin E

• All forms are absorbed with fat in the intestine,
  esters are hydrolyzed
• Liver binds only RRR-?-tocopherol to hepatic
  ?-tocopherol transfer protein (?-TTP)
• RRR-?-tocopherol is preferentially secreted by
  liver to circulating lipoproteins (VLDL, HDL, LDL)

12
Antioxidant Function of Vitamin E

• Vitamin E is a free radical scavenger which
  halts the chain reaction of polyunsaturated fatty
  acid (PUFA) peroxidation.
• Oxidation is caused by highly reactive free
  radicals that contain one or more unpaired
  electrons and donate an electron (oxidize) to an
  electron acceptor.
• When PUFA react with free radicals, they form
  lipid radicals, which react with molecular oxygen
  to form lipid peroxyl radicals .
• When vitamin E intecepts a peroxyl radical, a
  relatively stable tocopheryl radical is formed.
  Vitamin E is regenerated by other antioxidants
  (vitamin C, ubiquinols, glutathione).

13
Vitamin E Function
Free radicals
Quenched radical
Oxidative damage
14
Therapeutic Vitamin E

• Vitamin E may play a limited but significant role
  in the prevention or alleviation of certain
  diseases
• Atherosclerosis (coronary heart disease) by
  prevention of LDL oxidation
• Cancer (prostate and lung) by prevention of DNA
  damage
• Cataract by prevention of oxidative damage to
  lens proteins
• Alzheimers disease (slower progression)
• Tardive dyskinesia (less involuntary movements)

15
Vitamin E in Cardiovascular Disease

• Animal studies strongly support the prevention of
  CVD by vitamin E
• - inhibition of LDL oxidation, of smooth
  muscle proliferation, of platelet adhesion and
  aggregation
• - promotion of prostacyclin (vasodilator) in
  endothelium
• Epidemiological studies and human intervention
  trials were inconclusive

16
Adverse effects of high doses of Vitamin E

• Increase in prothrombin time
• Interruption of blood coagulation
• Inhibition of platelet aggregation and adhesion
• Hemorrhage - sepsis and necrotizing enterocolitis
  in premature infants, hemorrhagic stroke in adults

17
Vitamin K
18
Vitamin K sources

• Food sources
• Green leafy vegetables (kale, turnip greens,
  spinach, broccoli, cabbage, lettuce), 100 450
  µg/100g
• Other vegetables and fruits (green beans, peas,
  avocados)
• Vegetable oils and margarine (50 200 µg/100g)
• Endogenous sources
• Colonic bacteria
• Human milk is very low in vitamin K (2.5 µg/L)

19
Vitamin K Dietary Reference Intakes

• Adequate Intake (AI)
• 0 - 6 mo 2 µg
• 7 - 12 mo 2.5 µg
• 1 - 3 y 30 µg
• 4 - 8 y 55 ug
• 9 13 y 60 µg
• 14 -18 y 75 µg
• male gt 18 y 120 µg
• female gt 18 y 90 µg
• No Upper Tolerable Level Intake (UL) was
  established because no adverse effects of high
  intake were observed.

20
Vitamin K Function
Vitamin K is a cofactor of ?-carboxylation of
glutamate in blood clotting factors (prothrombin
Factor II, Factors VII, IX, X) and in bone
protein osteocalcin.
21
(No Transcript)
22
ANTICOAGULANTS
Inhibit vitamin K-dependent ?-glutamyl
carboxylase
Prevent recycling of vitamin K epoxide to active
vitamin form
23
Vitamin K Deficiency

• 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).

24
Vitamin K Deficiency
GI Bleeding
Hemorrhagic disease of the newborn
25
Vitamin K Deficiency
Hemorrhagic disease of the newborn
Subdural hematoma
26
Vitamin K Deficiency or Excessive Anticoagulation
Bruising Purpura
27
Vitamin D

• A hormone or a vitamin?
• Vitamin D is photosynthesized in skin and
  converted by liver and kidneys to its active
  form. It is the most important biological
  regulator of calcium homeostasis.
• Dietary intake of vitamin D precursors is
  required when sunlight exposure is limited.

28
Acetyl-CoA
Cholesterol
Vitamin DEndogenous Production
UV exposure can be as little as 20 min 3 x per
week
29
Vitamin DEndogenous Production
30
(No Transcript)
31
(No Transcript)
32
(No Transcript)
33
(No Transcript)
34
Vitamin D units

• 1 IU 0.025 µg cholecalciferol (D3)
• 0.005 µg 25(OH)D
• 1µg cholecalciferol 40 IU
• 1µg 25(OH)D 200 IU
• AI for 0-50 y old 200 IU
• AI for 51-70y old 400 IU
• AI for gt70 y old 600 IU

35
Special considerations

• Higher vitamin D intake (25 µg/day) may be
  required with some drugs
• Glucocorticoids inhibit vitamin D dependent
  intestinal calcium absorption
• Seizure control (phenobarbital, dilantin) may
  alter vitamin D metabolism, resulting in
  osteomalacia

36
Functions of Vitamin D

• Vitamin D maintains blood calcium and phosphorus
  levels
• It enhances the efficiency of Ca and P absorption
  by promoting the synthesis of Ca and P binding
  proteins in the intestine.
• It mobilizes Ca from bones by stimulation of
  osteoclasts formation.
• It stimulates Ca reabsorption by kidneys.

37
Vitamin D deficiency

• Defective bone formation in children
• Rickets Overproduction and deficient
  calcification of osteoid tissue (bone matrix).
  Multiple skeletal abnormalities result from the
  soft bones.
• Adult bone diseases
• Osteomalacia a gradual softening and bending of
  the bones due to poor calcification of osteoid
  tissue.
• Osteopenia decreased bone density (porotic
  bones, fractures)
• Possible increase in risk of cancer (colon,
  breast, prostate)

38
Symptoms of Vitamin D deficiency

• Rickets in Children
• Squared appearance of head (frontal bossing)
• Rachitic rosary (overgrowth of rib cartilage and
  osteoid tissue)
• Pigeon breast deformity (concave breast)
• Bowing of legs or knocked knees

39
Rachitic Rosary
40
Rickets
41
Pseudofracture
42
Vitamin D Toxicity

• Most toxic of all vitamins
• Hypercalcemia (increased Ca absorption, enhanced
  bone resorption)
• Calcification of soft tissues (heart, kidneys,
  lungs, blood vessels)
• Loss of appetite
• Increased calcium excretion (hypercalciuria)
• Excessive thirst and urination
• Irritability, depression
• Upper Tolerable Intake Level (UL) 0-12 mo
  25 µg or 1000 IU
• gt1 y 50 µg or 2000 IU

43
Serum 25(OH)D

• Primary indicator of vitamin D adequacy
• Normal range 16-74 ng/ml
• Deficient children lt11 ng/ml
• African-Americans and Mexican-Americans have
  lower range due to lactose intolerance and
  melanin pigmentation.