Tutorial on Vitamin Understanding the science, impact and issues surrounding vitamin - PowerPoint Presentation

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Tutorial on Vitamin

Understanding the science, impact and issues surrounding vitamin and

vitamin K deficiency

About the Author: Robin C Koon

Robin has a broad background in clinical pharmacy and nutraceutical and pharmaceutical manufacturing with more than 25 years experience in clinical pharmacy. Besides filling prescriptions, he has worked as a drug chain executive overseeing operations and managed care (PBM), and in retail mass market (drug chain). He is licensed with the California State Board of Pharmacy and sits on the board of the California Pharmacist Association.

His manufacturing experience includes purchasing, formulation, laboratory, R&D, sales and marketing. He has worked for various employers such as Horton & Converse Pharmacies, Thrifty-Payless Drug stores, Medco, Merck Pharmaceuticals,

Fedco Super Stores, PureTek Corporation and at Robinson Pharma Inc. His leadership and experience has helped to grow Best Formulations significantly over the past few years.

Robin C. Koon senior vice president

The Beginning: The Discovery of Vitamin K

The existence of the vitamin K group was discovered by

Henrik

Dam in 1929, while studying cholesterol metabolism in chicks; he was awarded the 1943 Nobel Prize for the discovery.Henrik Dam Date of birth: Feb. 21, 1895

Date of death: April 17, 1976Birthplace: Copenhagen, DenmarkNationality: Danish

Vitamin K, also known as

menadione, phylloquinone,

menaquinones or antihemorrhagic factor, is chemically a group of fat-soluble 2-methyl-1,4-naphthoquinone derivatives. All members of the vitamin K group of vitamins share a

methylated naphthoquinone ring structure and vary in the aliphatic side chain attached at the 3-position. The fat-soluble vitamin is carried through the body by lipids and stored in fat tissue. The "K" is derived from the German word "koagulation." Coagulation refers to the process of blood clot formation. Vitamin K is cofactor of VK-dependent carboxylation reactions in a number of biochemical pathways. Vitamin K is essential for the functioning of several proteins involved in blood clotting, bone mineralization, vascular health and cell growth. As with other lipid-soluble vitamins, a normal flow of bile and pancreatic enzymes is necessary with the presence of dietary fat to enhance absorption.

Defining Vitamin K

Broccoli, and other leafy greens, are a key source of

vitamin

K

The Two Primary Forms of Vitamin K

Vitamin

K1

Known as phylloquinone (phytonadione/phytomenadione), is probably the most important dietary source for humans. It is considered natural, being synthesized by plants, and is concentrated in leafy greens and other green vegetables. When humans or animals consume vitamin K1, their tissues convert part of it into vitamin K2. It is the trans-isomer (not cis-) form that is biologically active.

Vitamin K2

C

onsists of the menaquinone (MK) forms MK-3 through MK-14. The various forms of K2 are differentiated by having side chains lengths composed of a variable number of unsaturated

isoprenoid units; generally they are designated as MK-n, where n specifies the number of isoprenoids (side chain) attached to the

napthoquinone

ring

. There are two primary

menaquinones

being commercially sold for human nutrition:

MK-4

and

MK-7

.

MK-4 appears to be synthesized by animals (including humans) from K1 and can be commercially manufactured synthetically. MK-4 is found in a number of organs other than the liver at higher concentrations than K1. This fact, along with the existence of a unique pathway for its synthesis, suggests MK-4 has a unique biological function that has not yet been identified. MK-4 can even activate blood clotting factors, which is a role traditionally given to vitamin K1. It appears to remain active in the body only a few hours.

MK-7 is considered superior to vitamin K1 in several important areas, including better absorption, much longer bioavailability and higher efficacy levels in the body. It is made in large amounts by the bacterium

Bacillus

subtilis that ferments the Japanese condiment called natto. MK-7 stays in the circulation for longer than MK-4 in humans; a three-day half-life in the blood, compared to the one- to two-hour half-life of K1.

K2: Defining

Menaquinones

; MK-4 and MK-7

Biological Functions of Vitamin K: Coagulation and Clotting

Vitamin K is a necessary cofactor for normal clotting of blood in humans. Specifically, vitamin K is required for the liver synthesis of the coagulation proteins making the clotting factors that are necessary for blood to properly coagulate.

These factors are:

factor II (prothrombin)factor VII (proconvertin)factor IX (thromboplastin component)

factor X (Stuart factor). The mechanism by which vitamin K promotes formation in the liver of clotting factors II, VII, IX and X is not fully understood.

Other anticoagulation clotting factors that depend on vitamin K are proteins C, S and Z. Deficiency of vitamin K or disturbances of liver function (for example, severe liver failure) may lead to deficiencies of these clotting factors, causing excess bleeding.

Biological Functions of Vitamin K: Bone Health

For calcium/bone health, vitamin K has a key function primarily as an essential co-factor for the enzyme gamma-

glutamyl

-carboxylase (GGCX), responsible for gamma-carboxylation (synthesis) of vitamin K-dependent proteins. Two of these involved in calcium and bone metabolism are osteocalcin and matrix Gla-protein (MGP). Vitamin K plays a critical role in maintaining healthy bone density by facilitating the transport of calcium from the bloodstream into the bone.

Vitamin K helps maintain healthy bone density

Biological Functions of Vitamin K: Cardiovascular Systems

Vitamin K is required by calcium-regulating proteins in the arteries (vascular system). MGP is a vitamin K-dependent protein and must be

carboxylated

to function properly; poor vitamin K blood levels result in synthesis of uncarboxylated MGP (ucMGP). Since MGP is a potent local inhibitor of arterial calcification, MGP is important in relation to the health of the entire cardiovascular system. Without adequate vitamin K, calcium in the blood can bind to the arterial wall resulting in calcification. Arterial calcification has also been found to decrease bone mineralization (bone loss), often called the “calcification paradox.” It is observed mainly in patients with osteoporosis and chronic kidney disease.

MGP, a Vitamin K dependent protein, is key to the entire

cardiovascular

system

What Causes Vitamin K Deficiency?

Under normal conditions, vitamin K is moderately well absorbed (40 percent to 70 percent) from the jejunum and ileum, but very poorly in the colon. Vitamin K deficiency is rare, but can result from lack of vitamin K in the diet or from intestinal disorders that impair fat absorption, reducing absorption.

Deficiency may occur in patients with

biliary obstruction or other conditions limiting absorption of vitamin K, such as celiac disease, ulcerative colitis, sprue, regional enteritis, cystic fibrosis and intestinal resection, and in patients receiving drugs that may affect liver function or intestinal flora. Gastrointestinal disorders can limit absorption ofvitamin K

Certain Drugs can cause Deficiencies…

Vitamin K deficiency can develop in people who take certain drugs, including anticoagulants, as vitamin K’s pro-clotting actions can work against this type of medicine.

Warfarin

and other 4-hydroxycoumarin derivatives are antagonists of vitamin K action and are effective antithrombotic agents. Vitamin K blocks the conversion of KO (vitamin K-epoxide) into K by inhibiting the enzyme KO reductase. A patient who is treated with Warfarin or other 4-hydroxycoumarin derivatives should refrain from taking vitamin K, without consultation with his doctor or pharmacist. However, vitamin K does not counteract the anticoagulant effect of heparin. The use of broad spectrum antibiotics, quinidine

, quinine and high-dose salicylates may also increase requirements for vitamin K.

Warfarin

is one of many antagonists of vitamin K

Vitamin K Deficiencies in Newborns

Newborns are prone to vitamin K deficiency because only small amounts of vitamin K cross the placenta and because, during the first few days after birth, their intestines do not contain bacteria to produce vitamin K.

The deficiency can cause hemorrhagic disease of the newborn (

hypoprothrombinemia), characterized by a tendency to bleed.A vitamin K injection is usually administered to newborns to protect them from this issue. Breast-fed infants who have not received this injection at birth are especially susceptible to deficiency because breast milk contains only small amounts of vitamin K.

Symptoms of Vitamin K Deficiency

The main symptom of vitamin K deficiency is bleeding (hemorrhage)—the delayed, slowed or inability for the flowing blood to clot.

Having a liver disorder also increases the risk of bleeding because proteins that help blood clot (clotting factors) are made in the liver.

One routine test used to check this is the Prothrombin time (PT) or International Normalized Ratio (INR) test, which measures the time required for blood to clot. A result showing a delayed clot formation may indicate a deficiency of vitamin K.

The blood-clotting process can be slowed or unable to happen with a vitamin K deficiency

Recommended Daily Allowance (RDA)

Tutorial on Vitamin

Understanding the science, impact and issues surrounding vitamin K and

v

itamin K deficiency

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