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Flashcards in Fat Soluble Vitamins Deck (43)
1

Vitamins:

a. Complex organic substances required in small quantities in the diet relative to all other nutrients except the trace elements; "essential" because substance can't be synthesized at all or in adequate quantities to meet metabolic needs.

b. Vitamins have precise, specific functions in metabolism and thus help maintain normal functions of all organs.

2

Water and Fat Soluble Vitamins

a. Water soluble:
-generally not stored (except Vitamin B-12), but chronic intake affects tissue levels
-highly absorbed from dietary sources
-excreted via urine
-low toxicity.

b. Fat soluble:
-accumulated "stores" in body;
-require absorption of dietary fat and a carrier system for transport in blood
-potential for toxicity with excessive inatke.

3

Fat soluble Vitamins:

a. accumulated "stores" in body;

b. require absorption of dietary fat and a carrier system for transport in blood

c. potential for toxicity with excessive intake.

The Fat Soluble Vitamins:
Vit A
Vit D
Vit E
Vit K

4

Vitamin A Summary

VITAMIN A
a. Function: essential in photochemical basis of vision (signals in retina-->brain visual cortex); maintenance of conjunctival membranes & cornea; critical for epithelial cellular differentiation and proliferation

b. Food sources:
i. preformed Vit A (retinol/retinal): liver, dairy products, egg yolks, fish oil (e.g. cod liver oil)

ii. precursor (carotenoids e.g. beta-carotene): abundant in deep yellow/orange & green vegetables, eg. spinach, carrots, broccoli, pumpkin

c. Deficiency:
•Night blindness, xerophthalmia (extreme dryness of cornea), Bitot's spots on sclera, eventual blindness;
• Immune deficiency – dysregulation of immune response; effect depends on infectious agent & type of immune response it elicits; supplementation to correct Vit A deficiency ↓’s child mortality by 23-34%
• Abnormal epithelial morphology: epithelial, linings become flattened, dry & keratinized
• Vit A treatment of infants & children with measles associated w/ reduced morbidity & mortality; data strongest in developing countries; supportive data in U.S. children w/ low retinol levels;

d. Risk of deficiency: low intake &/or low fat intake (fat < 5% of kcal); fat malabsorption (liver disease & low bile salts; pancreatic insufficiency); protein energy malnutrition

5

Vitamin A Deficiency

1. Night blindness, xerophthalmia (extreme dryness of cornea),

2. Immune deficiency – dysregulation of immune response; effect depends on infectious agent & type of immune response it elicits; supplementation to correct Vit A deficiency ↓’s child mortality by 23-34%

3. Abnormal epithelial morphology: epithelial, linings become flattened, dry & keratinized

4. Vit A treatment of infants & children with measles associated w/ reduced morbidity & mortality; data strongest in developing countries; supportive data in U.S. children w/ low retinol levels;

6

Vitamin A function and food sources

a. Function: essential in photochemical basis of vision (signals in retina-->brain visual cortex); maintenance of conjunctival membranes & cornea; critical for epithelial cellular differentiation and proliferation

b. Food sources:

1. Preformed Vit A (retinol/retinal):
i. liver, dairy products, egg yolks, fish oil (e.g. cod liver oil)

2. Precursor (carotenoids e.g. beta-carotene):
i. abundant in deep yellow/orange & green vegetables, eg. spinach, carrots, broccoli, pumpkin

7

Toxicity and Biochemical Evaluation of Vitamin A

a. Toxicity (only w/ preformed Vit A retinol, dose dependent): vomiting, increased intracranial pressure, headache, bone pain (periosteal proliferation), bone mineral loss (↑ fractures & ↑ osteoporosis), liver damage (hepatitis, fibrosis, liver failure), death; birth defects


b. Biochemical evaluation: serum retinol (but levels remain WNL until liver stores nearly exhausted & ↓ w/ Acute Phase Reaction)

8

Vitamin D

Huge Summary

VITAMIN D
a. Function: functions as a hormone; maintains intracellular & extracellular Ca++ w/in physiologic range; stimulates intestinal absorption Ca++and P, renal reabsorption of Ca++ and P, mobilization of Ca++ and P from bone; innate immune function (generation of toxic radicals), cellular growth and differentiation through nuclear and plasma membrane vitamin D receptors present in many types of cells, other: active area of scientific inquiry…

b. Sources:
i. precursor (dehydrocholesterol) in skin, converted to cholecalciferol (Vit D3) by UV light;
ii. Dietary sources: a) Natural: fish liver oils, fatty fish, egg yolks; b) fortified milk & formulas D3 from animal sources, D2 ergocalciferol from plant (algae) sources; D3 activity 2-3x > D2

c. Metabolism:Absorbed via chylomicrons; Vitamin D2 or D3 hydroxylated in liver, to 25-hydroxy-cholecalciferol and then in kidney to 1,25-dihydroxy-cholecalciferol (calcitriol) = active form
Deficiency:

d. Deficient:
i. 25OH-D <20 ng/mL (<50nmol/L) Insufficient: 21-29 ng/mL (50-80 nmol/L) Sufficient: >/= 30 ng/mL (>80 nmol/L) evidence building of association of sufficiency with decreased risk chronic illnesses
ii. Rickets: (25OH-D <11ng/mL) failure of maturation of cartilage and calcification; "rachitic rosary" on ribs, bowed legs, widened metaphyses (esp at wrist), painful bones, fractures;
iii. decreased serum Ca and P, increased alk phos (+ classic triad = late findings); decreased 25(OH)Vit D & increased PTH
iv. Vit D insufficiency “New epidemic”? - Increased rates of low 25(OH)D levels - Increased indoor time, sunscreen use;
v, NHANES 42% African American women of child bearing age <15ng/mL

e. Rapidly evolving ecologic/ epidemiologic/in vitro/RCT evidence links to autoimmune diseases, neuromuscular function, heart disease, cancer incidence, and even overall mortality. Nov 2010 Institute of Medicine Report found only reliable evidence for bone health. Stay tuned as evidence base evolves.

f. Risk of deficiency: lack of adequate sunshine exposure; low dietary intake; fat malabsorption (cystic fibrosis, liver disease, prox. sm. intest disease, orlistat – intestinal lipase inhibitor); breastfed infant, esp if mother deficient (low infant stores at birth); dark skin (increasedpigmentation=decreased skin conversion; difficult to quantify); obesity (sequestered in fat); liver or renal disease (unable to activate – need calcitriol). Much recent data/discussion re whether U.S. population levels << optimal, esp in northern latitudes; also elderly, w/  outdoor exposure &  conversion.

9

Recommendation for Vitamin D

Recommendation:
Supplement (400 IU D3) to all breastfed infants until receiving at least 500 ml(16oz+)/day infant formula or milk; non-breastfed infants/children not receiving > 500 ml infant formula or Vit D fortified milk.

Other: 5-15 min unprotected sun exposure or UVB tanning (varies with pigmentation) x 2-3x/wk not recommended by American Academy of Dermatology

10

Vitamin D Function and Sources

a. Function: functions as a hormone
i. maintains intracellular & extracellular Ca++ w/in physiologic range
ii. stimulates intestinal absorption Ca++and P, renal reabsorption of Ca++ and P
iii. mobilization of Ca++ and P from bone
iv. innate immune function (generation of toxic radicals)
v. cellular growth and differentiation through nuclear and plasma membrane vitamin D receptors present in many types of cells

b. Sources:
i. precursor (dehydrocholesterol) in skin, converted to cholecalciferol (Vit D3) by UV light;

ii. Dietary sources:
a) Natural: fish liver oils, fatty fish, egg yolks;
b) fortified milk & formulas D3 from animal sources, D2 ergocalciferol from plant (algae) sources; D3 activity 2-3x > D2

11

Vitamin D Deficiency Large Summary

Deficient:
1) 25OH-D <20 ng/mL (<50nmol/L) Insufficient: 21-29 ng/mL (50-80 nmol/L) Sufficient: >/= 30 ng/mL (>80 nmol/L)
-evidence building of association of sufficiency with decreased risk chronic illnesses

2) Rickets: (25OH-D <11ng/mL) failure of maturation of cartilage and calcification; "rachitic rosary" on ribs, bowed legs, widened metaphyses (esp at wrist), painful bones, fractures;

3) decreased serum Ca and P, increased alk phos (+ classic triad = late findings); decreased 25(OH)Vit D & increased PTH

4) Vit D insufficiency “New epidemic”? - Increased rates of low 25(OH)D levels - Increased indoor time, sunscreen use;

5) NHANES 42% African American women of child bearing age <15ng/mL

12

VITAMIN E
Summary

a. Function: antioxidant, free radical scavenger; cell membrane stabilizer

b. Food sources: polyunsaturated vegetable oils, wheat germ

c. Deficiency: neurologic degeneration: with loss of reflexes (DTR's), spinocerebellar ataxia, neuropathy, ophthalmoplegia; incoordination, loss of vibration and position sense; hemolytic anemia

d. Situations with risk of deficiency: prematurity, fat malabsorption syndromes, short gut syndrome, C.F.

e. Toxicity: low; coagulopathy (very large doses inhibit Vit K dependent factors);
i. Megadoses for protection against heart disease and/or cancer not supported by most current literature (see refs)

13

Vitamin E Deficiency

Deficiency: Neurologic Degeneration:
i. with loss of reflexes (DTR's),
ii. spinocerebellar ataxia
iii. neuropathy
iv. ophthalmoplegia
v. incoordination, loss of vibration and position sense; hemolytic anemia

d. Situations with risk of deficiency: prematurity, fat malabsorption syndromes

14

VITAMIN K
Summary

a. Function: essential for carboxylation of coagulation proteins (Factors II (prothrombin), VII, IX, X)

b. Sources: leafy vegetables, fruits, seeds; synthesized by intestinal bacteria

c. Deficiency: prolonged coagulation times; hemorrhagic disease of newborn: bleeding into skin (purpura), gi tract, CNS

d. Risk of deficiency: newborns (poor placental transport, sterile gut, low clotting factors); late (2-12 wk), esp. breastfed infants (breast milk relatively low) or fat malabsorption syndromes, chronic antibiotic use.

e. Recommendation: All newborns should receive single IM dose of 0.5-1.0 mg (adequacy of oral doses presently not defined)

15

Function and Deficiency of Vitamin K

Function: essential for carboxylation of coagulation proteins (Factors II (prothrombin), VII, IX, X)

Deficiency: prolonged coagulation times; hemorrhagic disease of newborn: bleeding into skin (purpura), gi tract, CNS

16

Vitamin Definition

a. Complex organic substances required in small quantities in the diet relative to all other nutrients except the trace elements; "essential" because substance can't be synthesized at all or in adequate quantities to meet metabolic needs.
i. Our body cannot make vitamins!

b. Vitamins have precise, specific functions in metabolism and thus help maintain normal functions of all organs.

17

Water vs Fat Soluble Vitamins

There is more possibility of fat soluble vitamin toxicity due to storing in body

a. Water soluble:
i. generally not stored (except Vitamin B-12 in the muscle), but chronic intake affects tissue levels
ii. highly absorbed from dietary sources;
iii. excreted via urine;
iv. low toxicity.

b. Fat soluble:
i. accumulated "stores" in body
ii. require absorption of dietary fat and a carrier system for transport in blood
-need a carrier in blood due to hydrophobic nature
iii. potential for toxicity with excessive intake.

18

Vitamin A Function

Function
1. Photochemical for vision
i. retinal signaling

2. Maintenance of conjunctiva and cornea

19

Vitamin A sources

Two major ones

1. Preformed retinyl palmitate from animal sources
i. Liver, dairy, egg yolk, fish oil

2. Precursor Beta-carotene
i. Deep yellow and green vegetables
ii. Spinach, carrots, broccoli,
pumpkin

20

Vitamin A Deficiency

a. EYES: xerophthalmia (corneal dryness) Bitot’s Spots, night blindness total blindness

b. EPITHELIUM:
linings flat, dry,
and keratinized

c. Immune Impairment
i. Dysregulation
ii. Effect depends on infectious agent
iii. Treatment of Deficiency decreases all cause child mortality 23-34% in developing world
iv. Vit A treatment with measles reduces morbidity and mortality
- including in US when retinol level is low

21

What does lack/deficiency of Vitamin A due to the immune system?

a. Immune deficiency – dysregulation of immune response; effect depends on infectious agent & type of immune response it elicits; supplementation to correct Vit A deficiency ↓’s child mortality by 23-34%

b. Vit A treatment of infants & children with measles associated w/ reduced morbidity & mortality
i. data strongest in developing countries; supportive data in U.S. children w/ low retinol levels

22

Risk of Vitamin A deficiency

a. low intake &/or low fat intake (fat < 5% of kcal); fat malabsorption (liver disease & low bile salts; pancreatic insufficiency); protein energy malnutrition

b. Poor diet in colored veggies, low meat/dairy
i. autistic child with severely restricted diet

c. Fat malabsorption
i. liver disease, low bile salts
ii. pancreatic insufficiency

23

Vitamin A Toxicity (too much vit)

a. Toxicity (only w/ preformed Vit A retinol, dose dependent): vomiting, increased intracranial pressure, headache, bone pain (periosteal proliferation), bone mineral loss (↑ fractures & ↑ osteoporosis), liver damage (hepatitis, fibrosis, liver failure), death; birth defects
i. Vomit, increased ICP, headaches
ii. bone pain, osteopenia
iii. liver damage and fibrosis


b. Will NOT get toxicity with precursor beta-carotene

c. Only get toxicity with preformed vitamin A (retinyl palmitate)
i. direct Vit A consumption

24

Lab tests for Vitamin A

a. Serum retinol level
i. remains normal until liver stores exhausted
ii. late finding after Vit A has been decreasing for a long time

b. decreased with inflammation
i. negative acute phase reactant

25

Another look at biochemical testing for Vitamin A

Biochemical evaluation: serum retinol (but levels remain WNL until liver stores nearly exhausted & ↓ w/ Acute Phase Reaction)

26

Risk of Vitamin A Deficiency

a. Low Vit A intake

b. Diet poor in colored vegs, meat/dairy
e.g. autistic child with severely restricted diet

c. Protein Energy Malnutrition

d. Very Low fat intake (<5% of kcal)

e. Fat malabsorption
i. Liver disease, low bile salts
ii. Pancreatic insufficiency

27

Vitamin A Toxicity Summary

a. NOT precursor beta-carotene
i. Only with preformed Vit A (retinyl palmitate)e.g. cod liver oil

b. Symptoms
i. Vomiting, increased ICP, headache
ii. bone pain, osteopenia/porosis
iii. liver damage hepatitisfibrosisfailure
death
iv. birth defects e.g. isotretinoin (Accutane)

28

Vit A – Laboratory Testing

Serum Retinol level:
a. Remains normal until liver stores exhausted

b. Decreased with inflammation
i. Negative Acute Phase Reactant

29

Vitamin D - Function

Hormone
a. Plasma membrane and nuclear receptors in a range of tissues
i. Vit D will act on membrane and cytoplasm receptors

b. Maintains intra/extracellular Ca++
i. Intestinal absorption Ca and Phos, renal reabsorption, and mobilization from bone

c. Immune function –
i. Innate: antimicrobial peptide generation (cathelicidin and defensins) in macrophages
ii. Adaptive: modulation of cytokines

d. Regulates cell growth and differentiation

30

Vit D - Sources

a. Conversion in skin
i. UVB light---> Dehydrocholesterol---> Cholecalciferol D3 in skin

b. Dietary
i. Fish liver oils, fatty fish, egg yolks
ii. Fortified milk and formula

c. Sources
i. Plant algae, yeast+UV D2 ergocalciferol
ii. Animal D3 cholecalciferol more potent? larger AUC than D2, similar peak plasma 25OH

31

Vit D - Metabolism

a. Absorption – chylomicrons
i. Requires fat absorption

b. Hydroxylation: First hydroxylation happens in the liver, the 2nd hydroxylation happens in the Kidney (then active)
i. D2 or D3 +OH in liver
-25 OH Vit D –level reflects body stores
ii. 25 OH Vit D hydroxylated in kidney to active form 1,25 OH Vit D (Calcitriol)

32

Vit D - Deficiency

a. Definition IOM Standard:
i. Deficiency 25OH Vit D <20 ng/mL
-Laboratory Specific alternate cutoffs may be inconsistent
-IOM
Insufficiency 20-30 ng/mL
Sufficient >30 ng/mL

b. Classical Syndrome
i. Childhood rickets -

33

Emerging Associations with Vit D insufficiency or deficiency:

a. Mostly epidemiologic / in vitro

b. Few RCT’s to prove causation / treatment effect – stay tuned
i. Autoimmune Disorders (e.g. MS)
ii. Neuromuscular function
iii. Cardiovascular Disease
iv. Cancer incidence
v. Overall Mortality

c. IOM report Nov 2010 did not find adequate evidence (1100+pages)

34

Vit D – Risk for Deficiency

a. Low Sun exposure (NE winter)
i. Dark Pigmentation

b. Low dietary intake

c. Fat Malabsorption

d. Breastfed Infant supplement

e. Obesity
i. Fat sequestration, sedentary

f. Liver or Renal Disease (X-OH)
i. Need Calcitriol Rx supplementation

35

Vit D - Supplementation

a. Breastfed Infants
i. 400IU D3 per day by 2 months
ii. Until 500ml/d (>16oz) formula or milk
-Or formula fed taking <500ml/day

b. Children: AAP recs 400IU/d
i. IOM: E.A.R 400IU, RDA 600 IU/d for children
ii. 5-15 min sun (pigment)
-Dermatologist Academy and IOM prefer oral

c. Adults – recommendations vary
i. Institute of Medicine 600IU per day 18-70yrs
-800IU/day >70 years
-Some experts have recommended higher dosing 800-1000IU per day
-To Maintain 25OH D >30ng/mL, but evidence lacking

36

Vit D - Toxicity

a. Findings
i. Hypercalcemia
ii. Vomiting, seizures, nephrocalcinosis, vascular and soft tissue calcinosis

b. Risk
i. Sarcoidosis (granulomas activate D)
ii. >10,000 IU/d for wks in child or during pregnancy
iii. 50-100,000 IU daily in adult >3wks

37

Vitamin E – Function & Sources

a. Function: antioxidant, scavenges free radicals, stabilizes cell membranes

b. Sources: Polyunsaturated fat rich vegetable oils (e.g. sunflower), corn, nuts, wheat germ

38

Vit E – Deficiency

a. Neurologic Degeneration IRREVERSIBLE
i. Loss of reflexes (DTRs)
ii. Loss of coordination
iii. Loss of vibration and position sense
iv. Spinocerebellar ataxia
v. Neuropathy
vi. Ophthalmoplegia

b. Hemolytic Anemia

c. Risk:
i. malnurishment
ii. prematurity
iii. fat malbsorption / short gut

39

Vit E – Toxicity

a. Relatively Low

b. Coagulopathy
i. Very large doses inhibit Vit K dependent clotting factors

c. Literature does not support megadoses for CVD/cancer protection

40

Vit K – Function and Sources

a. Function – carboxylation of clotting factor proteins (II prothrombin, VII, IX, X)

b. Sources – leafy greens, brocolli, fruits, seeds, beef liver
i. Synthesis by Intestinal Bacteria

41

Vitamin K - Deficiency

a. Findings:
i. prolonged coagulation time
ii. Hemorrhagic disease of the newborn
-Purpura, GI bleeds, CNS bleeds

b. Risk:
i. Newborns – poor placental transport
-2-12 wks breastfed untreated
ii. Fat Malabsorption
iii. Chronic Antibiotics

c. Prevention:
i. all Newborns 0.5-1.0mg IM once
ii. Adequate oral dosing has not been defined

42

Summary of Deficiency Findings

Vitamin A
i. Finding: Eyes, epithelium, infections
ii. Risk for def: Poor or extreme low fat diet

Vitamin D
i. Finding:Rickets, Osteopenia/malacia, possibly more?
ii. Risk for def: Low sun, dark pigment, obesity, breastfeeding, liver/kidney dz

Vitamin E
i. Finding: Neurologic, anemia
ii. Risk for def: prematurity

Vitamin K
i. Finding: Impaired clotting
ii. Risk for def: Newborn, antibiotics, poor diet

43

Vitamin D Deficiency

Definition IOM Standard:
i. Deficiency 25 OH Vit D <20 ng/mL
-Laboratory Specific alternate cutoffs may be inconsistent
ii. IOM
-Insufficiency 20-30 ng/mL
-Sufficient >30 ng/mL

b. Classical Syndrome
1. Childhood rickets -failure of calcification, wide metaphyses: wrists, ‘rosary’, bone pain, bowed legs, fractures

2. Adult Osteoperosis