Introduction Vitamin K is a group of lipophilic, hydrophobic vitamins that are needed for the posttranslational modification of certain proteins, mostly required for blood coagulation but also involved in metabolism pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives. The naturally occurring forms of vitamin K are all fat soluble. chemistry: The naturally occurring forms of vitamin K are all fat soluble. They are stored in the liver, though not to any great extent. Stable to heat and reducing agents, they are destroyed by light, acid, alkali, oxidizing agents, and alcohol. Most supplemental forms of chlorophyll, as a vitamin K source, are water soluble. K1: phytonadione or phylloquinone (Aquamephyton): is a natural derivative from fish or plants. K2: menaquinone: fat-soluble form made by intestinal bacteria. K3: menadione: the synthetic water-soluble form tends to have a greater degree of toxicity. Figure 1: Chemical structures of vitamin K1 (phylloquinone, left structure) and vitamin K2 (menaquinones, right structure). History 1929 A series of experiments by Dam results in the discovery of vitamin K. 1931 A clotting defect is observed by McFarlane and coworkers. 1935 Dam proposes that the antihaemorrhagic vitamin in chicks is a new fat-soluble vitamin, which he calls vitamin K. 1936 Dam and associates succeed in preparing a crude plasma prothrombin fraction, and demonstrate that its activity is decreased when it is obtained from vitamin K-deficient chick plasma. 1939 Vitamin K1 is synthesised by Doisy and associates. 1940 Brikhous observes haemorrhagic conditions resulting from malabsorption syndromes or starvation, and finds that haemorrhagic disease of the newborn responds to vitamin K. 1943 Dam receives half of the Nobel prize for his discovery of vitamin K, the blood coagulation factor. 1943 Doisy receives half of the Nobel prize for his discovery of the chemical nature of vitamin K. Absorption, transport, storage and excreation of vitamin k It appears that up to 80% of dietary vitamin k as phylloquinine and menaquinone is taken up by cells that line the small intestine and is incorporated into chylomicrons. The process requires bile and pancreatic enzymes. The menaquinones synthesized by bacteria in the colon are absorbed, but the amount absorbed is likely provides only 10% of the vitamin k we need. Some vitamins k is stored in the liver and some is incorporated in the lipoproteins VLDL, LDL, and HDL for tranport throughtout the body. Mineral oil and other nonabsorbale lipids interfere with vitamin k absorption. Most vitamink excreation occurs via the bile with a small amount of excreation via the urine. Functions 1. Vitamin K acts as a cofactor in the final synthesis of proteins with a modified amino acid residue. This modified glutamic acid residue is found in bone proteins and can bind onto calcium ions to cause calcification. 2. It is also found in the blood and along ve

1. Dr. Savita Hulamani
Assistant Professor, Dept. Of Food
Processing and Nutrition, KSAWU,
Vijayapura, Karnataka, India

2. Contents
• Chemistry
• Distribution
• Functions
• Absorbtions, transport and metabolism
• Deficiency manifestations
• Nutritional requirement
• Methods of assay
• Interaction with other nutrients
• Antagonists and analogues of vitamin

3. Introduction
 Vitamin K is a group of lipophilic, hydrophobic vitamins that are needed for
the posttranslational modification of certain proteins, mostly required for
blood coagulation but also involved in metabolism pathways in bone and other
tissue.
They are 2-methyl-1,4-naphthoquinone derivatives.
The naturally occurring forms of vitamin K are all fat soluble. They are stored
in the liver, though not to any great extent. Stable to heat and reducing agents,
They are destroyed by light, acid, alkali, oxidizing agents, and alcohol.
Most supplemental forms of chlorophyll, as a vitamin K source, are water
soluble.

4. Phylloquinone or phytonadione (K1),
Menaquinone (K2),
Menadione (K3).
Forms of vitamin k

5. Figure 1: Chemical structures of vitamin K1 (phylloquinone,
left structure) and vitamin K2 (menaquinones, right structure).
Chemistry

6. 1929
A series of experiments by Dam results in the discovery of vitamin K.
1931 A clotting defect is observed by McFarlane and coworkers.
1935 Dam proposes that the antihaemorrhagic vitamin in chicks is a new fat-soluble
vitamin, which he calls vitamin K.
1936
Dam and associates succeed in preparing a crude plasma prothrombin fraction, and
demonstrate that its activity is decreased when it is obtained from vitamin K-
deficient chick plasma.
1939 Vitamin K1 is synthesised by Doisy and associates.
1940 Brikhous observes haemorrhagic conditions resulting from malabsorption syndromes
or starvation, and finds that haemorrhagic disease of the newborn responds to
vitamin K.
1943 Dam receives half of the Nobel prize for his discovery of vitamin K, the blood
coagulation factor.
1943 Doisy receives half of the Nobel prize for his discovery of the chemical nature of
vitamin K.

7. Absorption, transport, storage and excreation of
vitamin k
• It appears that up to 80% of dietary vitamin k as phylloquinine
and menaquinone is taken up by cells that line the small intestine
and is incorporated into chylomicrons.
• The process requires bile and pancreatic enzymes.
• The menaquinones synthesized by bacteria in the colon are
absorbed, but the amount absorbed is likely provides only 10% of
the vitamin k we need.

8. Conti….
• Some vitamins k is stored in the liver and some is incorporated in
the lipoproteins VLDL, LDL, and HDL for tranport throughtout the
body.
• Mineral oil and other nonabsorbale lipids interfere with vitamin k
absorption.
• Most vitamink excreation occurs via the bile with a small amount
of excreation via the urine.

9. • Vitamin K acts as a cofactor in the final synthesis of proteins with a
modified amino acid residue.
This modified glutamic acid residue is found in bone proteins and can bind
onto calcium ions to cause calcification.
•It is also found in the blood and along vessel walls, and along with platelet-
derived phospholipid, binds calcium, and is an integral part of the clotting
process.
• Vitamin K facilitates the action of calcium in building bone and clotting
blood.
Functions

10. •Synthesis of a protein, osteocalcin, which is found in high amounts in
bone. It allows calcium ions to bind, thus resulting in the calcification of
bone.
•Synthesis of a kidney protein that functions in the inhibition of calcium
oxalate stone formation via its ability to bind onto calcium in the
kidneys.
• Synthesis of proteins C and S. These two proteins, formed in the liver,
promote fibrinolysis and anti-coagulation. Thus, they are involved with
reducing inflammation.
Conti….

11. Liver
Prothrombin Thrombin
Thromboplastin
Fibrinogen Firin + fibrinopeptides
Fibrin aggregates
Cross linked polymer
Aggregation phase
Cross linking phase
Thrombin
Inactive
fibrinase
Activated fibrinase
Thrombin
Probable mechanism of blood coagulation
Ca2+
Ca2+

12. Interaction with other nutrients
Excess vitamin A interferes with the absorption of
vitamin K, a fat-soluble vitamin necessary for blood
clotting.

13. Antagonists of vitamin k
• The compounds namely heparin, bishydroxy-coumarin act as
anticoagulants and are antagonist to vitamin k.
• Salicylates and dicumarol are also antagonists.
• Many drugs, particularly antibiotics, cephalosporins and
anticonvulsants such as phenytoin (Dilantin) directly interfere
with vitamin K synthesis and metabolism.

14. Vitamin K may play a role in the prevention and/or
treatment of the following health conditions:
•Anticoagulant therapy
•Bone fracture
•Chronic liver disease
•Cystic fibrosis
•Hardening of the arteries
•Inflammatory bowel disease
•Liver cancer
•Pancreatic cancer
•Kidney stones
•Nausea and vomiting during pregnancy
•Osteopenia (bone loss)
•Osteoporosis (decreased bone mineral density)
•Thrombosis

15. Methods of assessment
• Prothrombin time test:
Measures the time required for blood to clot Blood sample mixed
with citric acid and put in a fibrometer. Delayed clot formation
indicates a deficiency. Unfortunately insensitive to mild deficiency
as the values do not change until the concentration of
prothrombin in the blood has declined by at least 50 percent.
• Plasma Phylloquinone:
Was found to be positively correlated with phylloquinone intake
in elderly British women, but not men. However an article by
Schurges et al. reported no correlation between FFQ and plasma
phylloquinone
• Urinary γ-carboxyglutamic acid:Urinary Gla responds to changes
in dietary vitamin K intake. Several days are required before any
change can be observed.

16. • Rich sources: Lettuce, spinach, kale, cauliflower, cabbage, egg yolk,
soybean oil, liver, kelp, alfalfa and other green plants, cow's milk, liver.
Leafy green vegetables are the single best dietary source of vitamin K
because of their high chlorophyll content.
•Good sources: cereals, legumes, milk, eggs, meat and fish
Fair sources: fruits
• Probiotic flora in intestines with a healthy ecology normally
manufacture vitamin K.
Dietary sources

17. • A clinically significant vitamin K deficiency, as manifest by uncontrolled
bleeding, is rare. Those cases which do develop are usually associated with
malabsorption diseases.
•Infancy: Hemorrhagic disease of the newborn has been related to Vitamin
K deficiency. This is due to poor transport across the placenta: especially
with premature infants. Also, because of the relatively sterile infant gut, the
ability to make vitamin K is impaired. The practice of supplementing
pregnant women with vitamin K and providing vitamin K to newborn
infants has significantly reduced the risk of deficiencies among infants,
especially those who are breast-fed.
• Easy bleeding in children: especially spontaneous nose bleeds.
• Osteoporosis: A deficiency of vitamin K leads to impaired bone
mineralization due to inadequate osteocalcin levels.
Deficiency

18. Toxicity
 No toxicities have been reported or suspected as being associated
with natural vitamin K.
 Large doses of Menadione, the synthetic derivative, may produce
hemolytic anemia and jaundice in the infant. Most toxicity is
associated with IV use and may be related to allergies to various
preservatives or incipients.
 Synthetic vitamin K toxicity: flushing, sweating, chest constriction,
hemolytic anemia, kernicterus in infants.

19. 0-6 months: 2 micrograms
7-12 months: 2.5 micrograms
1-3 years: 30 micrograms
4-8 years: 55 micrograms
9-13 years: 60 micrograms
14-18 years: 75 micrograms
Males, 19 years and older: 120 micrograms
Females, 19 years and older: 90 micrograms
Pregnant or lactating females, 18 years and younger: 75 micrograms
Pregnant or lactating females, 19 years and older: 90 micrograms
Recommended dietary allowances

20. Supplementation of vitamin K in pregnant women receiving
anticonvulsant therapy prevents neonatal vitamin K
deficiency
• OBJECTIVE: Extra vitamin K administered to pregnant women on
a regimen of enzyme-inducing anticonvulsant therapy will not
decrease the frequency of symptoms of vitamin K deficiency in
their neonates.
• STUDY DESIGN: A multicenter case-control study was performed
on 16 pregnant women on anticonvulsant therapy who received
10 mg of vitamin K1 daily from 36 weeks of pregnancy onward.
Concentrations of PIVKA-II (protein induced by vitamin K absence
for factor II) and of vitamin K1 were determined in cord blood
and compared with those in 20 controls.
Cornelissen et.al
(2006)

21. • RESULTS: In none of 17 cord samples was PIVKA-II
detectable, compared with 13 of 20 in controls (chi 2, p <
0.001). Median cord vitamin K1 level was 530 pg/ml
compared with below detection limit in most controls.
• CONCLUSIONS: Antenatal vitamin K1 treatment decreases
the frequency of vitamin K deficiency in neonates of
mothers on anticonvulsant therapy

22. Current concepts and controversies in the use
of vitamin K.
• Vitamin K is a fat-soluble vitamin crucial to the production of
many proteins involved with the coagulation process.
• It is integral in the synthesis of coagulants (factors II, VII, IX and
X) and anticoagulants (proteins C and S).
• It is generally recognised that routine administration of vitamin K
(phytomenadione) shortly after birth will prevent major neonatal
morbidity and mortality related to haemorrhage.
Gaston et.al(2007)

23. Conti…
• Vitamin K supplementation during pregnancy is also
recommended if mothers are on anticonvulsant therapy or
prolonged treatment with certain antibiotics. These medications,
if ingested by pregnant women, predispose the neonate to a
bleeding tendency caused by vitamin K deficiency.
• Vitamin K treatment of pregnant mothers before premature
delivery has also been suggested to reduce the incidence of severe
intracranial haemorrhage (ICH) in premature neonates.

24. Maternal antenatal administration of vitamin K1 results in
increasing the activities of vitamin K-dependent coagulation
factors in umbilical blood and in decreasing the incidence
rate of periventricular-intraventricular hemorrhage in
premature infants.
Objective: To determine the umbilical blood activity levels of vitamin K-
dependent coagulation factors II, VII, IX and X; to investigate the change
in activities of these factors in premature infants' umbilical blood after
prenatal administration of vitamin K1 to the mothers; and to study the
prophylactic effects on PIVH after maternal antenatal supplemental
vitamin K1.
Wang et.al
(2007)

25. METHODS
•Pregnant women in preterm labor at less than 35 weeks of
gestation were randomly selected to receive antenatal vitamin
K1 10 mg per day injection intramuscularly or intravenously for
2-7 days (vitamin K1 group, n = 40), or no such treatment
(control group, n = 50).
•At the same period, cord blood samples were collected from
thirty full-term neonates to compare the factor levels with those
of premature infants.
• Intracranial ultrasound was performed by the same
sonographer to determine the presence and severity of PIVH.

26. CONCLUSIONS
Administration of vitamin K1 to pregnant women at less than 35
weeks' gestation age may result in improved coagulation and may
reduce the incidence as well as the severity degree of PIVH.