VITAMIN
MICRONUTRIENT PRESENTATION - HCFN 428
CARINE VIEIRA DE SOUZA
ABSTRACT

Vitamin K was discovered by Henrik Dam in 1929 through experiments performed
with chicks. Vitamin K is a fat-soluble vitamin that can be synthesized by plants and
the bacteria of the lower intestine. All the naturally occurring forms of vitamin K have
the same naphthoquinone chemical structure differing only in the third position of
the side chain. The main functions of the vitamin are the synthesis of proteins
involved in blood coagulation and bone metabolism. The main dietary sources are
green vegetables and plant oils such as collards, spinach, broccoli, soybean oil and
canola oil. There are no Recommended Dietary Allowances (RDA) or Tolerable Upper
intake level established for vitamin K. However, an Adequate Intake (AI) has been
established based on the average intake of healthy individuals. The availability of
pancreatic juices, bile and dietary fats have a direct impact on the absorption of the
vitamin that commonly is excreted in the form of bile and urine. There are various
methods of assessing vitamin K and factors that can impair the absorption of the
vitamin. Deficiency of vitamin k is related to hemorrhagic events and no case of
toxicity has been reported. Vitamin K can interact with anticoagulants drugs such as
Walfarin also known as Coumadin. Osteoporosis, atherosclerosis and the
hemorrhagic disease of the newborn are some of the diseases directly related with
vitamin K consumption. Human milk, infant formula and cow’s milk have different
vitamin K concentrations and it can vary depending on a mother’s supplementation
and milk maturation.
PURPOSE OF THE STUDY

The purpose of this presentation is to discuss
the function, chemical structure, metabolism,
absorption, excretion, storage, dietary sources,
supplementation, deficiency, toxicity, drugnutrient interaction and diseases related to
vitamin K.
HISTORICAL OVERVIEW



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Vitamin K was discovered by Henrik
Dam in Copenhagen in 1929.
Experiments were performed on chicks
dealing with a hemorrhagic disease
resembling scurvy which could not be
prevented by ascorbic acid.
It was observed a lack of a particular
antihemorrhagic factor in their diet.
Henrik Dam expanded his work to prove
that none of the existed vitamins could
prevent the hemorrhagic disease and
discovery the vitamin K, which derives
from the word “Koagulation” of the
German and Scandinavian languages.
(1,2)
Available at:
http://www.nndb.com/people/836/00012
8452/henrik-dam.jpg. Accessed October15,
2009
CHEMISTRY OF VITAMIN K

All the naturally occurring vitamin K
have the same naphthoquinone
structure.

Vitamin K is classified into two groups
according to whether they are
synthesized by plants or bacteria.

Synthesized by plants Vitamin K1
(Phylloquinone)

Synthesized by bacteria  Vitamin K2
(Menaquinone-n, MK-n)

Synthetic form  Vitamin Kз
(Menaquinone, MK-4)
(3,4)
Available at: http://3.bp.blogspot.com/_j8dEXcfxbOA/SYCX3Bu0IKI/AAAAAAAAGZM/OUj_b9uDw4/s400/Vitamin+K+3+forms.jpg. Accessed September 27, 2009.
SYNTHESIS OF VITAMIN K1
Available at: http://lipidbank.jp/image/VVK0001FT0006.gif. Accessed at October 28, 2009.
FUNCTIONS
(5)
 Vitamin
K is a fat-soluble vitamin that functions as a
coenzyme for biological synthesis of active forms of
proteins involved in:


Blood Coagulation
Bone metabolism
Available at:
http://images.medicinenet.com/images/illustrations/
blood_clot.jpg. Accessed on October 28, 2009.
BLOOD COAGULATION
http://www.milnerfenwick.com/products/ha37/i
ndex.asp?dr=300
BLOOD COAGULATION (CONT.)
Available at:
http://books.google.com/books?id=46o0PzPI07YC&pg=PA387&lpg=PA387&dq=percentage+vita
min+k+absorption&source=bl&ots=GizAfsICKN&sig=u9dcgVYzt9M0bYFh3po75wu1qUc&hl=en&e
i=DyHpSv7QFY6k8AbLi4WIDw&sa=X&oi=book_result&ct=result&resnum=9&ved=0CCgQ6AEwCA
#v=onepage&q=percentage%20vitamin%20k%20absorption&f=true. Accessed October 28, 2009.
METABOLISM



(6,7,8)
Vitamin K is responsible for the biological activation of the
plasma prothrombin (coagulation factor II) and
procoagulants factors VII, IX, and X.
Vitamin K is a cofactor required for enzymatic reactions
that converts carboxylates glutamyl residues to γcarboxyglutamyl (Gla), which is a calcium binding site.
The vitamin K modification of proteins is essential for the
calcium-binding property of prothrombin.
ABSORPTION

Vitamin K is absorbed in the jejunum
and ileum.



(5,9)
The bioavailability of the vitamin depends on
the form in which the vitamin is ingested.
It depends of a normal flow of bile and
pancreatic juice and dietary fats.
Vitamin K absorption is enhanced by
dietary fats because it is more well
absorbed when secreted into the
lymph as a component of chylomicrons
to enter the circulation rather than a
dietary source
EXCRETION
(5,10)
Vitamin K is rapidly catabolized and excreted by
the liver mainly in bile form.
 Vitamin K is also excreted in small amounts in
the urine.

 The
urinary excretion of metabolites reflects dietary
intake of vitamin K1.
STORAGE


The liver has the highest
concentration of vitamin k
due to its rapidly capacity of
accumulation.
Liver turnover occurs rapidly
so hepatic reserves
depletion can be rapidly
when dietary intake of
vitamin K is restricted or
insufficient.
(5)
DIETARY SOURCES
Green vegetables and plant
oils are the main dietary
sources of vitamin K.
 Spinach, collard, broccoli
and iceberg lettuce are the
main dietary source of
vitamin K in the diet of U.S
adults and children.

(5)
DIETARY RICH SOURCES
(11)
Food Source
Amount
Amount of Vitamin K (mcg)
Collards
1 cup (36g)
183.9
Brussels Sprouts
1 cup (88g)
155.8
Spinach
1 cup (30g)
144.9
Broccoli
1 cup (91g)
92.5
Cabbage
1 cup (89g)
67.6
Lettuce
1 cup (36g)
62.5
Asparagus
1 cup (134g)
55.7
Okra
1 cup (100g)
53
Green Peas
1 cup (145g)
36
Carrots
1 cup (128g)
16.9
Cauliflower
1 cup (107g)
16.6
Green Beans
1 cup (100g)
14.4
Tomatoes
1 cup (180g)
14.2
DIETARY RICH SOURCES (CONT.)
 Plant
Oils:
Food Source
Amount
Amount of Vitamin K
(mcg)
Soybean Oil
1 Tablespoon
25
Canola Oil
1 Tablespoon
10
Olive Oil
1 Tablespoon
8.1
Mayonnaise
1 Tablespoon
6.2
(11)
SUPPLEMENTATION

The average intake of
vitamin K from foods and
supplements for adults men
range between 93119ug/day and 8290ug/day for adult women.

No adverse effects have
been reported related to
vitamin k consumption from
supplements.
(5)
METHODS OF ASSESSMENT

(5,12)
Various indicators have been used to assess
vitamin K status in humans such as:
•
Prothrombin Time (PT)
•
•
Evaluates the ability of blood to clot properly.
INR (International Normalized Ratio)
•
Monitor the effectiveness of blood thinning drugs.
DIETARY REFERENCE INTAKE (DRI)
(5)
Data were insufficient to set a RDA for vitamin
K so an AI was developed based on healthy
adults
 An Adequate Intake for men is 120ug/day and
women is 90ug/day.
 Newborns typically receive a shot of vitamin K
to ensure they have enough.

DIETARY REFERENCE INTAKE (DRI)
Life Stage Group
MALES (mg/day)
FEMALES (mg/day)
0-6 months
2.0
2.0
7-12 months
2.5
2.5
1-3 years
30
30
4-8 years
55
55
9-13 years
60
60
14-18 years
75
75
19-30 years
120
90
31-50 years
120
90
51-70 years
120
90
>70 years
120
90
Pregnancy
≤18 years
75
19 – 50 years
90
Lactation
≤18 years
75
19 – 50 years
90
(5)
DEFICIENCY
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



(5,13,14, 15)
Vitamin K deficiency severe enough to affect blood
clotting is extremely rare in healthy individuals.
It is almost impossible to be vitamin K deficient in selfselected, nutritionally adequate diets.
Vitamin K-dependent clotting factors II, VII, IX and X
deficiency is usually an acquired clinical problem from
liver disease, malabsorption, or warfarin overdose.
Vitamin K deficiency has been associated with lipid
malabsorption syndromes because fat is necessary to
absorb fat-soluble vitamin K.
The classical sign of vitamin K deficiency is
hypoprothrombinemia, which increase prothrombin time
(PT) and in severe cases cause hemorrhagic event.
TOXICITY



(5)
No evidence and adverse affects have
been reported of high intakes of
vitamin K from foods or supplements
in healthy individuals.
Data was insufficient to set a
Tolerable Upper Intake Level (UL).
In the absence of a UL extra caution
may be warranted in consuming levels
above the recommended intake.
FACTORS AFFECTING VITAMIN K REQUIREMENT

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Drug-Nutrient Interactions
Nutrient-Nutrient Interactions
Bioavailability
Antibiotics can alter the production of vitamin K by gut
bacteria
Alcohol intake
Liver disorders
Diarrhea and vomiting
Cystic Fibrosis
Gastrointestinal diseases
(5,14, 15)
DRUG-NUTRIENT INTERACTION



(5)
Individuals taking anticoagulant (anticlotting) medications
such as Warfarin, also known as Coumadin, need to keep
a consistent intake of vitamin K.
Anticoagulants are designed to make the blood coagulate
more slowly by decreasing the activity of vitamin K and
prolonging the time it takes to form blood clots.
If vitamin K consumption increases suddenly, it can
override the effect of the drug enabling the blood to clot
too quickly.
COUMADIN (WARFARIN)

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Patients taking Coumadin should maintain a
consistent intake of vitamin K rich foods.
Mechanism of Action: Warfarin is a vitamin k antagonist which interferes
with the enzymes responsible for metabolizing vitamin K in the liver
By inhibiting the supply of vitamin K to the liver, Warfarin slow the
production of clotting factors and prevent the formation and propagation
of thrombus.
Absorption: Coumadin binds to plasma proteins, mainly albumin and it is
absorbed very rapidly in the stomach and small intestine.
Genetic variations influence the absorption of Coumadin.
Elimination: The Coumadin end-product metabolized by the liver is
excreted by the kidneys.
The most common indicator for Coumadin adequacy is the International
Normalized Ratio (INR) which should range between 2.0-3.0 or 2.5-3.5.
Coumadin dose requirements is influenced by age, genetics, concurrent
medications and co-morbidities and diet.
It is important to provide an individualized diet education and perform a
detailed diet assessment in patients taking Coumadin.
(16)
HEPATIC METABOLISM OF VITAMIN K IN
ABSENCE (A) AND PRESENCE OF WARFARIN (B)
Available at: http://www.schattauer.de/de/magazine/uebersicht/zeitschriften-a-z/thrombosis-andhaemostasis/contents/archiv/issue/727/manuscript/10312.html. Accessed October 25, 2009.
NUTRIENT-NUTRIENT INTERACTION


(5)
Elevated intakes of vitamin E can create opposite
effects of vitamin K.
Vitamin E supplements, taken in large doses, can
reduce absorption of vitamin K since both are fatsoluble vitamins.
VITAMIN K INTAKE AND CHRONIC DISEASE (5,15)







Osteoporosis
Hemorrhagic Disease of the Newborn
Biliary Obstruction
Liver Disease
Malabsorption Syndrome
Atherosclerosis
Cardiovascular Disease
VITAMIN K AND OSTEOPOROSIS




Vitamin K is important for bone formation
and it should be included in an adequate
diet.
Higher intakes of potassium and vitamin K
among vegetarians may also help to
protect bone health but does not
necessarily protect against osteoporosis
despite lower animal protein content.
Osteocalcin and matrix GLA protein are
vitamin K-dependent and it is associated
with the prevention of chronic diseases.
Low dietary intake of vitamin K is
associated with a decrease in bone
mineral density and an increased risk of
fractures.
(17)
HEMORRHAGIC DISEASE OF THE NEWBORN
(HDNB) (18)





Hemorrhagic Disease of the Newborn (HDNB) is the
condition associate with the increased chances of
bleeding during the first few weeks of life.
Vitamin K is routinely administered to prevent the
hemorrhagic disease of the newborn.
Vitamin K is poorly transported across the placenta
putting newborns at risk for vitamin K deficiency.
Plasma clotting factors are low at the time of birth.
In the United States and Canada, HDNB is prevented by
injections or orally administered dosages of vitamin K at
birth.
HUMAN MILK AND VITAMIN K



Human milk contains insufficient amounts
of vitamin K needed to meet the
recommendations of infants aged < 6
months
It does not contain as much vitamin K as
infant formula and cow’s milk.
It is localized in the colostrum and fat
globules.
(5,19)
SUMMARY
Available at:
http://books.google.com/books?id=46o0PzPI07YC&pg=PA387&lpg=PA387&dq=percentage+vitamin+k+absorptio
n&source=bl&ots=GizAfsICKN&sig=u9dcgVYzt9M0bYFh3po75wu1qUc&hl=en&ei=DyHpSv7QFY6k8AbLi4WIDw&sa
=X&oi=book_result&ct=result&resnum=9&ved=0CCgQ6AEwCA#v=onepage&q=percentage%20vitamin%20k%20ab
sorption&f=true. Accessed on October 28, 2009.
SUMMARY




Vitamin K function as a coenzyme during the synthesis of biologically active
proteins involved in blood coagulation and bone metabolism.
Recommended Dietary Intake (RDI) and Tolerable Upper Intake Levels (UL)
have not been established for vitamin K because of the lack of data.
Adequate Intake (AI) has been established based on the dietary intake of
healthy individuals; the recommendation for men is 120ug/day and for
women 90ug/day.
Vitamin K can be synthesize naturally by the bacteria in the intestinal tract
or it can be found in green, leafy vegetables such as spinach and broccoli,
some fruits, vegetables and nuts.
REFERENCES
1.
Almquist HJ, Mecchi E, Klose AA. CCXLIV. Estimation of the antihaemorrhagic vitamin. Biochem J. 1938;32:1897-1903.
2.
Dam H. The antihaemorrhagic vitamin of the chick. Biochem J. 1935;29:1273-1285.
3.
Kindberg C, Suttie JW, Uchida K, Hirauchi K, Nakao, H. Menaquinone production and utilization in germ-free rats after
inoculation with specific organisms. J Nutr. 1987;117:1032-1035.
4.
Binkley SB, MacCorquodale DW, Thayer SA, Doisy EA. The isolation of vitamin K1. J Biol Chem. 1939;130:219-234.
5.
Institute of Medicine and Food and Nutrition Board (2001).DRI Dietary reference intakes for vitamin A, vitamin k,
arsenic, baron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc.
Washington D.C.: National Academy Press.
6.
Stenflo J. Vitamin K and the biosynthesis of prothrombin. J Biol Chem. 1974;249:5527-5535
7.
Suttie JW. The metabolic role of vitamin k. Fed Proc. 1980;39:2730-2725.
8.
Haroon Y, Bacon DS, Sadowski JA. Liquid-chromatographic determination of vitamin K, in plasma, with fluorometric
detection. Clin Chem. 1986;32:1925-1929.
9.
Gijsbers BL, Jie KS, Vermeer C. Effect of food composition on vitamin K absorption in human volunteers. Br J Nutr. 1996;76:223-
229.
10.
Harrington DJ, Booth SL, Card DJ, Shearer MJ. Excretion of the urinary 5C- and 7C-aglycone metabolites of vitamin k by young
adults responds to changes in dietary phylloquinone and dihydrophylloquinone intakes. J Nutr. 2007;137:1763-1768.
11.
USDA National Nutrient Database for Standard Reference. 2009. Available at: http://www.nal.usda.gov/fnic/foodcomp/search.
Accessed October 15, 2009.
REFERENCES
12.
Couris R, Tataronis G, McCloskey W, Oertel L, Dallal G, Dwer J, Blumberg JB. Dietary vitamin K variability affects international
normalized ratio (INR) coagulation indices. Int J Vitam Nutr Res. 2006;76:65-74.
13.
Weston BW, Monahan PE. Familial deficiency of vitamin K-dependent clotting factors. Haemophilia. 2008;14:1209-1213.
14.
Krasinski SD, Russell RM, Furie BC, Kruger SF, Jacques PF, Furie B. The prevalence of vitamin k deficiency in chronic
gastrointestinal disorders. Am J Clin Nutr. 1985;41:639-643.
15.
Rashid M, Durie P, Andrew M, Kalnins D, Shin J, Corey M, Tullis E, Pencharz PB. Prevalence of vitamin K deficiency in cystic
fibrosis. Am J Clin Nutr. 1999;70:378-382.
16.
Kamali F, Pirmohamed M. The future prospects of pharmacogenetics in oral anticoagulation therapy. Br J Clin Pharmacol.
2006;61:746-751.
17.
Brooth SL, Broe KL, Gagnon DR, Tucker KL, Hannan MT, McLean RR, Dawnson-Hughes B, Wilson PWF, Cupples LA, Kiel DP.
Vitamin k intake and bone mineral density in women and men. Am J Clin Nutr. 2003;77:512-516.
18.
Flood VH, Galderisi FC, Lowas SR, Kendrick A, Boshkov LK. Hemorrhagic disease of the newborn despite vitamin k prophylaxis at
birth. Ped Blood and Cancer. 2009;50:1075-1077.
19.
Canfield LM, Hopkinson JM, Lima AF, Silva B, Garza C. Vitamin K in colostrum and mature human milk over the lactation perioda cross-sectional study. Am J Clin Nutr. 1991;53:730-735.