Vitamins Flashcards
DRI
Daily Reference Intakes
EAR
Estimated Average Requirement: daily nutrient intake estimated to meet req of 50% of healthy individuals in specific group
RDA/RDI
Recommended Daily Allowance/ intake:
Average Daily nutrient intake level estimated to meet the req of nearly all healthy individuals in a specific life stage or gender group = EAR*2 standard deviations
AI
Adequate intake: used when RDA is unknown
UL
Upper limit: in supplements: to pose no risks
Macronutrients
Proteins, Carbs, Fats. 56:130:14 g/d (RD/AI adults)
Micronutrients
Vitamins, minerals, trace elements
Individual RDA/AI
Vitamins def
Organic chem supplied exogenously to reach adequate functional amounts
Only non-exogenous vitamin
vitamin D
Fat-soluble vitamins
ADEK
Water soluble vitamins
C and B
Primary vs secondary vitamin deficiency
Primary: inadequate intake
Secondary: absorption and/or drug-nutrient interaction issues, increased requirements
Absorption of Fat-soluble vitamins + examples
bile salts enhance or are required, ex beta-carotene, vit A precursor
Reduced absorption with increased intake like Vit E
Transport of fat-soluble vitamins
vit E transported in blood by plasma beta-lipoproteins
Vit A and beta-carotene transported from intestine in chylomicrons via lymph
Vit A released into the plasma as retinol bound to RBP (ret binding protein)
Storage of fat-soluble vitamins
A and E mainly in liver, some in muscle, kidney, adipose tissue and lung
E mobilized slowly from adipocytes
vit K storage limited, depleted in 10-20 days
Vitamin A conversion pathway
beta-carotene –> retinal –> retinol (vit A)
beta-carotene vs retinols and retinals
Beta-carotene from plants, less easily absorbed than retinal and retinols
Retinols from animal products, like fish and dairy
RDA vitamin A
700 ug/d females
900 ug/d males
about 1 cup raw carrot
vitamin A functions
- cellular differentiation - immunity development
- visual pigments - opsin binds retinal = rhodopsin
- Regulation of gene expression via retinoic acid
all-trans retinoic acid binds to RAR, RAR+RXR binds RARE
RAR- retinoic acid receptor RXR = retinoid X receptor
Vitamin A deficiency
- leading cause of blindness in developing nations = dietary deficiency
- increase infectious diseases, resp, GI
Vit A: pharma uses
- skin conditions, acne, fine lines, blemishes
- acute promyelocytic leukemia (RAR mutations, impaired diff of promyelocytes (PCL302))
Vitamin A toxicity: reason, acute effects, long-term toxicity
- Results from excess supplementations
- Acute effects of 1 dose 200 000 mcg: blurred vision, vertigo, nausea
- Long-term toxicity: liver damage, birth defects, skin + joint damage
Vitamin E; 2 types, how many subtypes each has
Four tocopherols, and four tocotrienols (alpha, beta, gamma, delta), sat vs unsat side chain
Vit E with highest nutrient significance, where found
Alpha-tocopherol- greatest nutritional significance
plant source: veggie oils, wheat ger,
Vitamin E: highest bio activity
d-alpha-tocopherol
RDA of Vit E
RDA 15 mg/d, alpha-tocopherol
100 ml canola oil, 15 tbsp wheat germ
Vitamin E functions
- antioxidant
- prevents lipid oxidative damage
- inhibits PKC, cell signalling
- inhibits platelet aggregation
- enhance vasodilation
- Affects activity of immune + inflammatory cells
Prevalence of vitamin E deficiency
Rare in healthy adults
Reason for vit E deficiency
- chronic fat malabsorption or beta-lipoprotein deficiency
- premature infants - limited storage, absorption
Symptoms of vit E deficiency
- Anemia - reduced erythrocyte survival
- Progressive neurological disorder - impaired balance + neuropathy
Vit E: absorption, circulation, storage
- 50% absorption
- Circulates bound to beta-lipoprotein
- Storage: liver, muscle and fat
Therapeutic use/prevention
Treatment of susceptible individuals - preventing CVD
Range of vit E toxicity
Limited, when >2000 mg alpha-tocopherol/day
Toxicity of vitamin E
- May exacerbate a vitamin K deficiency
- Possiblity of impaired blood clotting - hemorrhage
Vitamin E downreagulates these drugs:
Anticoagulant therapy, antiplatelet drugs, vitamin K deficient individuals
These drugs downregulate vitamin E absorption :
cholestryamine
colestipol
isoniazid
mineral oil
phenobarbital
phenytoin
carbamazepine
Natural occurring vitamin K
plants: phylloquinone K1
bacteria: menaquinone-n K2
dietary sources of vitamin K
K1: green leafy veggies
K2: egg yolk, fermented food, microbiota
RDA vitamin K
90 mcg, 1/2 cup cooked kale - 530 ug
Vitamin K epoxide cycle
Vit K –> Reduced vitamin K, Hydroquinone –> Vitamin K epoxide –> vit K
Enzyme quinone reductase
vitamin K –> reduced vit K, Hydroquinone
Carboxylase
HYdroquinone –> vit K epoxide
also produces gamma -carboxylated proteins
clotting factors
matrix gla proteins MGP
what does matrix gla protein do?
inhibition of innapropriate calcification/mineralization when not in skeletal tissue, both MGP + K need carboxylation to properly work
Epoxide reductase
Vitamin K epoxide –> vitamin K, recycling step
Vit K epoxide enzymes inhibited by warfarin
Quinone reductase, Epoxide reductase, if want low clotting, anticoagulation
Calcification in bone vs prevention of calcification in arteries
in bone - vitamin K, but prevent calc. in arteries - MGP, still need preventing surplus of K
Vitamin K functions
Coagulation, calcium-binding of some proteins, bone mineralization, cellular growth and regulation
Vitamin K dependent clotting factors where, coenzyme for what, conversions?
Synthesized in the liver, coenzymes for the gamma-carboxylation of glutamin acid residues
result in conversion to gamma-carboxyglutamic acid
Vit K storage, recycling
Limited storage 10-20 days
reused by oxidation/red cycle
What produces Vit K deficiency
Malabsorption
Administration of antagonist warfarin
chronic use cephalosporin antibiotics
Vit K deficiency symptoms
Increased prothrombin time - bleeding, hemorrhagic disease of the newborn
first evident in GI bleeding
Therapeutic uses of vit K
increase biosynthesis of liver clotting factors
prevention of hemorrhagic disease of newborn
antidote for anticoagulant toxicity
Vitamin D, how is it different
not a true vitamin - can be synthesized by body
Derivation of vit D
from cholesterol
D2 from plants - ergocalciferol
D3 from animals - cholecalciferol
Vitamin D regulation of gene transcription
calcitriol + VDR complex in nucleus
Complex binds with RXR to form heterodimer
binds to vitamin D responsive elements
Change in gene transcription
(bone related genes, 24 hydroxylase, p21, TGFbeta2 and others)
Vitamin D synthesis in body
7-dehydrocholesterol + UVB in skin converted to
Cholecalciferol vit D in liver converted to
Calcidiol 25-hydroxyvitamin D3 in kidney conv to
Calcitriol 1,25 dihydroxyvitamin D
^^ active form - bone + small intestine
Vitamin D actions
- increase calcium absorption from gut
- increase bone mineralization
- regulation of immune function
When lack of UVB Toronto and Edmonton to make it D
Latitude 43.6 N - Toronto: Nov-Feb
Latitude 53 N - Edmonton - Oct-March
Vitamin D insufficiency definition
Conservative <40 nmol/L lack of 25 (OH)-D, the calcidiol in the kidney- easier, higher to measure in blood
No stimulation of PTH when < 80 nmol/L
Vitamin D deficiency in children
Rickets: Insufficiency or mutations in VDR
Vit D deficiency in adults
Osteomalactia: rare, decrease in bone mineral [], bone pain and soft bones
Toxicity of vitamin D from what
from chronic high dose supplementation
higher potential with supplemented calcitriol
Reason for adverse effect of vit D
Adverse effects from elevated blood calcium levels
Symptoms of vit D toxicity
Fatigue, headache, diarrhea, hypercalcemia
demineralization of bone and calcification of organs such as heart, kidneys, lungs, blood vessels and skin, growth arrest
too low - low mineralization
too much - remove mineralization as well
Vitamin D bioregulation when low Ca++
Low ca –> parathyroid gland–> increase PTD –> increase Ca++ reabsorption and PO4 excretion in kidneys
Increase calcitriol from kidney–> Ca++ reabsorption from intestine
PTH –> Higher CA++ PO4+ release from bone
Result normal Ca++
What does PTH do?
Stimulate hydroxylases
Normal range calcium extracellular
2.2-2.7 mM
Hypocalcemia: symptoms
<2.05 mM
Symptoms;
related to increased neuromuscular irritability
numbness, tingling in fingers, toes
muscle cramps, tetany, convulsions
irritability, impaired mental capacity
Laryngospasm, bronchospasm, cardiac arrest
Hypocalcemia: causes
Hypoparathyroidism
Vitamin D deficiency
Vitamin D resistance
Hypercalcemia symptoms
> 2.96 mM
Symptoms:
Decreased neuromuscular activity
Lethargy, lack of concentration, sleepiness
Headache, muscle weakness
Vomiting, diarrhea, polyuria, nocturia
Hypercalcemia Causes
Hyperparathyroidism
Malignancies
Ectopic vitamin D production
Vitamin D therapy
Ergocalciferol vitamin D2
Calciferol
Drisdol (ergocalciferol) 25 hydroxyvitamin D2
Calcitriol 1.25 dihydroxyvitamin D3
Considerations for therapy with vitamin D
Time to reach equilibrium
Fat malabsorption, hepatobiliary disease or renal disease
Drug interactions with vitamin D
Anticonvulsants: inhibit hydroxylation in liver
Glucocorticoids: inhibit actions of vitamin D at the VDR