Vitamins Flashcards
Vitamins definition
organic chemicals that must be supplied by exogenous sources to achieve adequate functional amounts (exception: vitamin D)
Which are fat soluble and water soluble vitamins?
fat soluble: A, D, E, K
water soluble: B and C
What is the cause for primary and secondary deficiencies?
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
PK - Absorption of fat soluble vitamins
- similar to fat absorption
- bile salts enhance it or are required
- reduced absorption with increased intake with vitamin E
Transport of fat soluble vitamins
- 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)
Storage of fat soluble vitamins
- 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
What are the consequences for dosing or intake of a vitamin being fat soluble vs water soluble?
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
Vitamin A Source
- 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)
Vitamin A RDA
700ug/d females
900ug/d males
Vitamin A functions
- cellular differentiation (developmental, immunity)
- visual pigments (opsin binds retinal = rhodopsin)
- 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
Vitamin A deficiency
- leading cause of blindness in developing nations (dietary deficiency)
- increased infectious diseases (respiratory, GI)
Pharmacologic Uses
- acute promyelocytic leukemia (RAR mutations, impaired differentiation of promyelocytes)
- skin conditions, acne, fine lines and blemishes
Vitamin A Toxicity
- 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
Vitamin E Structure
- 4 tocopherols (saturated) and 4 tocotrienes (unsaturated) (a, b, gamma, sigma)
- a-tocopherol most nutritional significance
- d-a-tocopherol highest biological activity
Vitamin E sources and RDA
- vegetable oils, nuts, wheat germ, apricots
- RDA: 15mg/d a-tocopherol
Vitamin E functions
- antioxidant
- prevents destruction of membrane lipids through oxidation
- inhibits protein kinase C (cell signalling)
- inhibits platelet aggregation
- enhances vasolidation
- affects activity of immune and inflammatory cells
Vitamin E deficiency Prevalence and Symptoms
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
Vitamin E Therapeutic Use
treatment of susceptible individuals - prevention of CV disease (vit E enhances vasodilation)
Vitamin E PK
50% absorption
circulates to B-lipoprotein
storage in liver, muscle, fat
Vitamin E toxicity
- limited when intake is less than 2000mg a-tocopherol a day
- can exacerbate vitamin K deficiency –> may impair clotting and lead to hemorrhage
Vitamin E interactions
- anticoagulant therapry
- antiplatelet drugs
- vitamin K deficient individuals
Vitamin K: forms, sources, RDA, PK
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
Vitamin K epoxide cycle
- 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)
What is the effect of warfarin on the Vit K epoxide cycle?
- inhibits quinone reductase and epoxide reductase
- acts as vitamin K antagonist: impairs clotting factor function
Vitamin K functions
- 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
Vitamin K deficiency causes and symptoms
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
Vitamin K therapeutics
- increase biosynthesis of clotting factors by liver
- prevent hemorrhagic disease of newborn
- antidote for anticoagulant toxicity
Vitamin D Sources
- not true vitamin –> can be synthesized by body
- derived from cholesterol
- D2 (ergocalciferol) from plants
- D3 (cholecalciferol) from animals
Vitamin D synthesis in the body
7-dihydrocholesterol –(UVB from sun in skin)–>cholecalciferol D3 –(liver)–> 25-hydroxyvitamin D3 –(kidney)–> 1,25-dihydroxyvitamin D3 (active form)
Vitamin D regulation of gene transcription
- calcitriol forms complex with vitamin D receptor (VDR) in nucleus
- complex binds with retinoic acid X receptor (RXR) to form heterodimer
- heterodimer binds to vitamin D responsive elements (VDRE)
- changes in gene transcription (bone related genes, p21, 24-hydroxylase, TGFB2 and more)
Vitamin D actions
- increase calcium absorption from gut
- increase bone mineralization
- regulation of immune function
Vitamin D deficiency Causes and Outcomes
- 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
Vitamin D toxicity causes and consequences
- 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
Hypocalcemia - range, symptoms, causes
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
Hypercalcemia - range, symptoms, causes
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
Vitamin D therapy and considerations
- drisdol (ergocalciferol) 25-hydroxyvitamin D2
- calciferol
- calcitriol 1,25-hydroxyvitamin D3
considerations
- time to reach equilibrium
- fat malabsorption
- hepatobiliary disease
- renal disease
Drug interactions with vitamin D
anticonvulsants: inhibit hydroxylation in liver
glucorticoids: inhibit actions of vitamin D at VDR
