VITAMIN

MICRONUTRIENT PRESENTATION - HCFN 428CARINE 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, drug-nutrient interaction and diseases related to vitamin K.

HISTORICAL OVERVIEW (1,2)

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.

Available at: http://www.nndb.com/people/836/000128452/henrik-dam.jpg. Accessed October15, 2009

CHEMISTRY OF VITAMIN K (3,4)

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)

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/index.asp?dr=300

BLOOD COAGULATION (CONT.)

Available at: http://books.google.com/books?id=46o0PzPI07YC&pg=PA387&lpg=PA387&dq=percentage+vitamin+k+absorption&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%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 γ-carboxyglutamyl (Gla), which is a calcium binding site.

The vitamin K modification of proteins is essential for the calcium-binding property of prothrombin.

ABSORPTION (5,9)

Vitamin K is absorbed in the jejunum and ileum.

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 (5)

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.

DIETARY SOURCES (5)

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.

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.) (11)

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

Plant Oils:

SUPPLEMENTATION (5)

The average intake of vitamin K from foods and supplements for adults men range between 93-119ug/day and 82-90ug/day for adult women.

No adverse effects have been reported related to vitamin k consumption from supplements.

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) (5)

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

DEFICIENCY (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 self-selected, 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(5,14, 15)

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

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) (16)

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.

HEPATIC METABOLISM OF VITAMIN K INABSENCE (A) AND PRESENCE OF WARFARIN (B)

Available at: http://www.schattauer.de/de/magazine/uebersicht/zeitschriften-a-z/thrombosis-and-haemostasis/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 fat-soluble 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 (17)

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.

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 (5,19)

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.

SUMMARY

Available at: http://books.google.com/books?id=46o0PzPI07YC&pg=PA387&lpg=PA387&dq=percentage+vitamin+k+absorption&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%20absorption&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.

REFERENCES1. 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 period- a cross-sectional study. Am J Clin Nutr. 1991;53:730-735.