Vitamins

Question 1

Vitamins definition

Answer 1

organic chemicals that must be supplied by exogenous sources to achieve adequate functional amounts (exception: vitamin D)

Question 2

Which are fat soluble and water soluble vitamins?

Answer 2

fat soluble: A, D, E, K
water soluble: B and C

Question 3

What is the cause for primary and secondary deficiencies?

Answer 3

primary: due to inadequate intake
- usually not seen in countries with adequate nutrition availability

secondary: due to improper absorption, drug-nutrient interactions, or increased requirements
- pregnancy - need more
- puberty
- old age - need less and less

Question 4

PK - Absorption of fat soluble vitamins

Answer 4

• similar to fat absorption
• bile salts enhance it or are required
• reduced absorption with increased intake with vitamin E

Question 5

Transport of fat soluble vitamins

Answer 5

• vitamin E transported in blood by plasma b-lipoproteins
• vitamin A and b-carotene transported from intestine in chylomicrons via lymph
• vitamin A released into plasma as retinol bound to specific retinol binding protein (RBP)

Question 6

Storage of fat soluble vitamins

Answer 6

• vitamin A and E mainly in liver, some in muscle, kidney, adipose, lung
• Vitamin E and D mobilized slowly from adipocytes
• Vitamin K storage limited, can be depleted in 10-20 days

Question 7

What are the consequences for dosing or intake of a vitamin being fat soluble vs water soluble?

Answer 7

water soluble vitamins
- excess removed through urine

fat soluble vitamins
- excess sit in fat stores
- testing vitamins through circulation is an incomplete representation of fat soluble vit.
- need to be careful with dose escalations

Question 8

Vitamin A Source

Answer 8

• b-carotene from plants –> 15,13- dioxygenase coverts to retinal –> dehydrogenase converts to retinol (carrot, broccoli, papaya)
• retinal used in visual system - rhodorphins
• retinol from animal products (eggs, dairy, fish)

Question 9

Vitamin A RDA

Answer 9

700ug/d females
900ug/d males

Question 10

Vitamin A functions

Answer 10

1. cellular differentiation (developmental, immunity)
2. visual pigments (opsin binds retinal = rhodopsin)
3. regulation of gene expression via retinoic acid
   - all trans retinoic acids bind to RAR (retinoic acid R)
   - RAR and RXR (retinoid X R) bind to RARE (retinoic acid response elements)
   - RARE regulates gene expression

Question 11

Vitamin A deficiency

Answer 11

• leading cause of blindness in developing nations (dietary deficiency)
• increased infectious diseases (respiratory, GI)

Question 12

Pharmacologic Uses

Answer 12

• acute promyelocytic leukemia (RAR mutations, impaired differentiation of promyelocytes)
• skin conditions, acne, fine lines and blemishes

Question 13

Vitamin A Toxicity

Answer 13

• results from excessive supplementation
• acute effects of single dose of 200,000: blurred vision, vertigo, nausea
• long term toxicity: liver damage, birth defects, skin and joint damage

Question 14

Vitamin E Structure

Answer 14

• 4 tocopherols (saturated) and 4 tocotrienes (unsaturated) (a, b, gamma, sigma)
• a-tocopherol most nutritional significance
• d-a-tocopherol highest biological activity

Question 15

Vitamin E sources and RDA

Answer 15

• vegetable oils, nuts, wheat germ, apricots
• RDA: 15mg/d a-tocopherol

Question 16

Vitamin E functions

Answer 16

1. antioxidant
2. prevents destruction of membrane lipids through oxidation
3. inhibits protein kinase C (cell signalling)
4. inhibits platelet aggregation
5. enhances vasolidation
6. affects activity of immune and inflammatory cells

Question 17

Vitamin E deficiency Prevalence and Symptoms

Answer 17

prevalence
- rare in healthy adults
- chronic fat malabsorption and b-lipoprotein deficiency
- premature infants –> due to limited storage and absorption

symptoms
- anemia –> impaired erythrocyte survival
- progressive neurological disorder –> impaired balance and neuropathy

Question 18

Vitamin E Therapeutic Use

Answer 18

treatment of susceptible individuals - prevention of CV disease (vit E enhances vasodilation)

Question 19

Vitamin E PK

Answer 19

50% absorption
circulates to B-lipoprotein
storage in liver, muscle, fat

Question 20

Vitamin E toxicity

Answer 20

• limited when intake is less than 2000mg a-tocopherol a day
• can exacerbate vitamin K deficiency –> may impair clotting and lead to hemorrhage

Question 21

Vitamin E interactions

Answer 21

• anticoagulant therapry
• antiplatelet drugs
• vitamin K deficient individuals

Question 22

Vitamin K: forms, sources, RDA, PK

Answer 22

two naturally occurring forms
1. plants: phyloquinone –> vitamin K1
- green leafy vegetables
2. bacteria: menaquinone-n –> vitamin K2
- egg yolk, liver, fermented foods, microbiota

RDA: 90ug/day

PK: limited storage (10-20 days), reused by oxidation and reduction cycles

Question 23

Vitamin K epoxide cycle

Answer 23

1. vitamin K –quinone reductase–> reduced vit K hydroquinone –carboxylase–> vit K epoxide –epoxide reductase–> vit K

• carboxylase important in making y-carboxylated proteins
  
  • clotting factors: dysfunction in vit K deficiency
  • matrix gla (carboxylased glutamate) proteins : needed to stop innappropriate calcification (seen in old age diseases)

Question 24

What is the effect of warfarin on the Vit K epoxide cycle?

Answer 24

• inhibits quinone reductase and epoxide reductase
• acts as vitamin K antagonist: impairs clotting factor function

Question 25

Vitamin K functions

Answer 25

- coagulation (vit K dependent clotting factors are synthesized in the liver --> acts as a coenzyme for y-carboxylation of glutamic acid into y-carboxyglutamic acid) - calcium binding function of some proteins - roles in bone mineralization and cellular growth and regulation

Question 26

Vitamin K deficiency causes and symptoms

Answer 26

deficiency - malabsorption (insufficient fat absorption) - vitamin K antagonist (warfarin) - chronic use of cephalosporin antibiotics symptoms - increased prothrombin time (PTT) - bleeding will appear in GI tract first - hemorrhagic disease of newborn

Question 27

Vitamin K therapeutics

Answer 27

- increase biosynthesis of clotting factors by liver - prevent hemorrhagic disease of newborn - antidote for anticoagulant toxicity

Question 28

Vitamin D Sources

Answer 28

- not true vitamin --> can be synthesized by body - derived from cholesterol - D2 (ergocalciferol) from plants - D3 (cholecalciferol) from animals

Question 29

Vitamin D synthesis in the body

Answer 29

7-dihydrocholesterol --(UVB from sun in skin)-->cholecalciferol D3 --(liver)--> 25-hydroxyvitamin D3 --(kidney)--> 1,25-dihydroxyvitamin D3 (active form)

Question 30

Vitamin D regulation of gene transcription

Answer 30

1. calcitriol forms complex with vitamin D receptor (VDR) in nucleus 2. complex binds with retinoic acid X receptor (RXR) to form heterodimer 3. heterodimer binds to vitamin D responsive elements (VDRE) 4. changes in gene transcription (bone related genes, p21, 24-hydroxylase, TGFB2 and more)

Question 31

Vitamin D actions

Answer 31

- increase calcium absorption from gut - increase bone mineralization - regulation of immune function

Question 32

Vitamin D deficiency Causes and Outcomes

Answer 32

- insufficient UVB to generate vitamin D occurs during nov-feb in toronto - conservative estimates for insufficiency are <40nmol/L - but thee is no stimulation of PTH at <80nmol/L - at <25nmol/L one is deficient: bone loss in children - rickets: insufficiency or mutations in VDR in adults - osteomalacia - decrease in bone mineral content: bones are more pliable and don't fracture as much - less weight bearing - bone pain and soft bones: bowing of legs

Question 33

Vitamin D toxicity causes and consequences

Answer 33

- can occur due to chronic high dose supplementation (esp. calcitriol) adverse effects from elevated blood calcium levels - generalized symptoms: fatigue, headache, diarrhea, hypercalcemia disruption in mineralization system: - demineralization of bone - calcification of organs such as heart, kidney, lungs, BVs and skin - growth arrest

Question 34

Hypocalcemia - range, symptoms, causes

Answer 34

range: <2.05mM (2.2-2.7 is normal) symptoms: related to increased neuromuscular irritability - numbness/tingling in toes and fingers - muscle cramps, tetany, convulsions - irritability, impaured mental capacity - laryngospasm, bronchospasm, cardiac arrest common causes - hypoparathyroidism (PTH deficiency) - vitamin D deficiency - vitamin D resistance

Question 35

Hypercalcemia - range, symptoms, causes

Answer 35

range: >2.9mM (normal is 2.2-2.7) symptoms: related to decreased neuromuscular activity - lethargy, lack of concentration, sleep - headache, muscle weakness - vomiting, diarrhea, polyuria, nocturia common cause - hyperparathyroidism - malignancies (ex. increased 1-hydroxylase) - ectopic vitamin D production

Question 36

Vitamin D therapy and considerations

Answer 36

1. drisdol (ergocalciferol) 25-hydroxyvitamin D2 2. calciferol 3. calcitriol 1,25-hydroxyvitamin D3 considerations - time to reach equilibrium - fat malabsorption - hepatobiliary disease - renal disease

Question 37

Drug interactions with vitamin D

Answer 37

anticonvulsants: inhibit hydroxylation in liver glucorticoids: inhibit actions of vitamin D at VDR