Vitamin K

Question 1

What are the forms of Vitamin K?

Answer 1

Phylloquinone (Vitamin K1^3) and Menaquinone-7 (MK-7) (Vitamin K2^2)

Question 2

What are the sources of Phylloquinone?

Answer 2

Plant foods -> richest sources are leafy green vegetables and plant oils

Question 3

What are the sources of Menaquinones?

Answer 3

other foods -> fermented foods, dairy products & meats

Question 4

What is the dietary intake for vitamin K?

Answer 4

insufficient evidence to derive EAR values and derivation of AI values for the entire population
- higher requirement of vitamin K for adult men, then adult women

Question 5

What are other sources of vitamin K?

Answer 5

Supplemental forms: Phylloqiunone (K1), Menaqiunone, e.g., MK-4, MK-7 (K2)

Other Sources: Intestinal anaerobic bacteria synthesized, but not in sufficient amounts

Question 6

How are fats digested and absorbed in our body?

Answer 6

Require emulsification with bile salts for effectiveness -> In the stomach, GI water and fats tend to separate, and the enzymes can’t get to the fat. When the fat enter the small intestine, the gallbladder secretes bile, which can emulsify the fats from large globules to smaller globules, which are then exposed to enzymes for digestion more efficiently
Passively diffuse into enterocytes and form chylomicrons, which enters the lymphatic system

Question 7

How is vitamin K digested?

Answer 7

no breakdown required b/c not bound to protein
Through the action of bile and digestive enzymes, micelle formation

Question 8

How is vitamin K absorbed?

Answer 8

Differs depending on sources:
1. phylloquinones and menaquinones from diet
- Mainly jejunum
- incorporated into micelles
- passive diffusion of micelle content into enterocytes -> some through receptor mediated uptake
- vitamin K in enterocyte: packaged into chylomicrons

**2. Menaquinones from bacterial synthesis **
- ileum and colon
- passive diffusion; process less well understood
absorption capacity greatly differs among individuals (insufficient)

Question 9

How can absorption be enhanced?

Answer 9

bile salts
dietary fats -> better consumed with other fats
pancreatic enzymes -> release lipase; promotes vitamin K absorption

Question 10

How can absorption be impaired?

Answer 10

fat malabsorption disorders
impaired secretion of bile
impaired secretion of pancreatic enzymes

Question 11

How is the transport of Vitamin K from the Intestine to Other tissues?

Answer 11

Upon absorption, passes through the brush border membrane -> release of vitamin K in chylomicrons from enterocytes

Transport to extrahepatic tissues in chylomicrons

delivered through the lymphatic system; drain circulating in the bloodstream

In the liver: repackaging or metabolism

transport from the liver to other tissues:
-> packaged in VLDL
-> phylloquinone (main form) and menaquinones
-> transported to extrahepatic tissues

Question 12

How are chylomicrons transported?

Answer 12

leave the intestinal mucosal cell via exocytosis
-> Enter the lacteal to lymphatic circulation
-> enter the bloodstream via the thoracic duct (near the heart) at a very slow rate
remaining vitamin K to the liver in chylomicron remnants

Question 13

How is vitamin K stored in the body?

Answer 13

Stored in the cell membrane

Overall low body storage: ~50-100 mg and smaller than that of vitamin B12

Although liver receives most newly absorbed vitamin K, the liver does not store vitamin K
Rpaid metabolism of vitamin K in liver -> either packaging into VLDL for transport to other tissues or degradation/oxidation for exertion

Question 14

How is vitamin K metabolized?

Answer 14

Phylloquinone: almost completely metabolized and oxidation of side chain and conjugation with glucuronic acid -> become water-soluble

Menaquinone: little is known

Question 15

How is vitamin K excreted?

Answer 15

Conjugated metabolites excreted with bile in feces and urine

Question 16

Does vitamin K have a tolerable upper level (UL)?

Answer 16

No toxicity (for benefit) reported from high doses of vitamin K

Question 17

What biochemical roles is vitamin K essential for?

Answer 17

Required to catalyze the carboxylation of glutamic acid residues in Gla proteins that allows the high-affinity binding of Ca2+ ions

Blood coagulation
Bone mineralization and bone organization
Protection of soft tissues from calcification
Memory formation
Transport of thyroxine (T4) and retinol in blood and into cerebral spinal fluid

Question 18

Why is Gla protein important?

Answer 18

Binds to Ca2+, which then reacts with either cell components like phospholipids to affect blood clotting and bone mineralization, among other processes

Question 19

How is vitamin K involved in blood coagulation?

Answer 19

Gla proteins involved in coagulation: thrombin, prothrombin, factor VII, factor IX, factor X and other

Question 20

What is the effect of anti-coagulants?

Answer 20

Impaired reduction of vitamin K -> impaired gamma-carboxylation reactions

Vitamin K antagonists = pharmacological anticoagulants (e.g., warfarin)
-> drugs to reduce thrombotic events and thereby the occurrence or reoccurrence of heart attacks
-> interfere with the vitamin K cycle
-> Warfarin inhibits the activity of quinone reductase which interrupts the formation of gamma-carboxylation, inhibiting the formation of gla protein

For patients taking pharmacological anticoagulants -> maintain adequate vitamin K status

Question 21

How is vitamin K involved in bone health?

Answer 21

Osteocalcin (Bone Gla Protein, BGLAP)
- secreted by osteoblasts during bone formation
- involved in bone mineralization and memory function

Matrix Gla Protein (MGP)
- found in bone, dentine and cartilage
- associated with bone extracellular matrix proteins
- appears to promote bone calcification
- inhibitors of calcification of soft tissue (protects soft tissues from calcification)

Question 22

What are additional functions & emerging research?

Answer 22

Transport protein
- Transthyretin (prealbumin)
- Function: carries thyroxine (T4) and retinol in blood and into the cerebral spinal fluid

Gla proteins involved in cellular mechanisms
- Implicated in cell proliferation, migration and apoptosis
- Implicated in inflammation

Question 23

Vitamin K health implications

Answer 23

1. Prevention of cardiovascular disease
2. Glucose control & prevention of type 2 diabetes
3. Prevention of osteoporosis
4. Cancer prevention or treatment

Question 24

Vitamin K deficiency

Answer 24

Symptoms: Impaired blood clotting (hemorrhage)
Rarely occurs in healthy adults

Question 25

Suboptimal Status

Answer 25

Higher prevalence of suboptimal status than deficiency
1. Impaired bone metabolism
- diminished bone mineral density
- increased fracture rates
2. Cardiovascular health
- cardiovascular disease risk
- inflammation
- arterial calcification

Question 26

Vulnerable population groups/risk factors for deficiency

Answer 26

Vitamin K deficiency most likely occurs in newborns
Why are newborn infants at risk for deficiency?
1. Low stored at birth due to poor placental transfer of vitamin K
2. Low levels of vitamin K in the breast milk
3. ‘Clean-gut’ = low gut synthesis of vitamin K

Individuals at risk of developing suboptimal
vitamin K status and vitamin K deficiency:
- Low dietary vitamin K intake
- Older adults
- Chronic treatment with antibiotics
- Fat malabsorptive disorders: cystic fibrosis,
obstructive jaundice (blocking flow of bile from liver), inflammatory bowel disease, intestinal bypass surgery, chronic pancreatitis (inflammation of pancreas), liver diseases

Question 27

Population-based Prevention Strategy

Answer 27

National prevention strategy -> intramuscular injection for newborns

3 methods of vitamin K1 administration:
* Intramuscular
* Oral (for infants whose parents
refuse intramuscular injection)
* Intravenous

*preferred method in North America due to
its efficacy and high compliance rate

Yet, not a complete protection, especially in
breastfed infants with low vitamin K intake;
additional doses to high‐risk infants

Question 28

Nutrient-Nutrient Interactions

Answer 28

Vitamin A and E = antagonists of vitamin K

Vitamin E:
- inhibition of phylloquinone metabolism
- increase in hepatic oxidation and excretion of all forms of vitamin K

Excess intake of vitamins A and E
- impair vitamin K absorption