MK-4

INTRODUCTIONRABIA MEHMOOD & NIAESH JAWED

CHEMISTRY (MENAQUINONE-4)Vitamin K2 is part of a family of structurally similar fat-soluble, 2-

methyl-1,4-naphthoquinones derivatives that include phylloquinone (K1), menaquinones (K2), and menadione (K3) that

are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways

in bone and other tissue.

These vitamin K2 homologs are called menaquinones, and are characterized by the number of isoprenoid residues in their side chains. Menaquinone-4 (abbreviated MK-4) has four isoprene residues in its side

chain.

Chemistry Vitamin K family are naphthoquinone derivatives . Phylloquinone and menaquinones, both have a long isoprenoid side chain. The length of the side chain differs. Phylloquinone have a 20 C side chain ,

whereas menaquinones have a 30 C side chain. The isoprenoid chain makes these vitamin hydrophobic or lipophilic. The synthetic vitamin K

(menadione, menadiol diacetate) have only hydrogen in place of isoprenoid side chain that makes these vitamin water-soluble.

SAR• naphthoquinone core is the structural motif

responsible for the neuroprotective activity and found that amine substitution at the 2 carbon greatly enhanced the protective activity. The further addition of a benzyl group to the 2 amine improved the safety index of the compound by completely abolishing any in vitro neurotoxicity, and chloro substitution at the meta position of the aromatic ring further improved the protective potency of the compound.

KINETICS & DYNAMICSAYEHSA IRSHAD BAJWA

MECHANISM OF ACTION

• The mechanism of action of vitamin K2 is similar to vitamin K1. K vitamins play an essential role as cofactor for the enzyme γ-glutamyl carboxylase, which is involved in carboxylation of the vitamin K-dependent proteins – specifically, the conversion of peptide-bound glutamic acid (Glu) to γ-carboxy glutamic acid (Gla).

PHARMACOKINETICS ABSORPTION:

Absorption occurs in the upper small intestine .

The absorption of vitamin K2 require bile salts.

Transported from the mucosal cells to the liver by binding to chylomicrons .

STORAGE:

Vitamin K is stored in liver. Also present in significant amount in spleen and skeletal muscle

TRANSPORT:

Vitamin K released to the blood stream and transported in the blood by associating with beta-lipoproteins (LDL )

SOURCES & INDICATIONNATASHA NADIR

DIETARY SOURCES:It includes: Animal foodEx. meat, Egg yolk, and milk. Fermented food.1.Animal origin. 2.Plant origin.Ex. cheese and other fermented milk products.

SUPPLEMENT: MK-4 in supplement form is synthetic ,typically made from an extract of plant Nicotiana tabacum.

DAILY RECOMMENDATION: Men and women : 70 – 140 mcg. Children : 35 – 75mcg

SOURCES & RECOMMENDATION

INDICATIONS (MENAQUINONE-4)

Vitamin K2 supports the development

and maintenance of

bones and teeth by

enhancing calcium and phosphorus

absorption and use.

Vitamin K2 is essential for

correct calcium metabolism: It keeps calcium

where it belongs - in the bones and out of the blood

vessels

higher dietary intake of

vitamin K2, especially the MK-4 fraction, is associated

with a reduced risk of coronary

calcification (plaque build-

up) and mortality

(death) from coronary heart

disease.

Research suggests that

vitamin K2 supplementation has a greater

effect in reducing the

risk of coronary calcification

and mortality from coronary heart disease compared to vitamin K1.

Protecting Bone and Arterial Health with Vitamin K2

OTHER INDICTAIONSHINA AHMED

OTHER BENEFITS OF VIT K2:A N T I - I N F L A M M A T O R Y

vitamin K's anti-inflammatory action. As the body ages, levels of the inflammation-promoting cytokine interleukin-6 (IL-6) increase. Once IL-6 becomes out of balance with the other cytokines, inflammation accelerates. It has been observed that people with arthritis, Alzheimer's disease, and atherosclerosis have higher levels of IL-6 and are almost twice as likely to develop mobility-related disabilities.

D I A B E T E S

The second highest concentration of vitamin K in the body is in the pancreas, which plays a major role in blood sugar and insulin regulation. In animal studies, Japanese researchers found that when they induced vitamin K deficiency, the test animals developed Type II diabetes.

V I R A L C I R R H O S I S - R E L A T E D L I V E R C A N C E R

Japanese researchers have recently discovered that vitamin K2 may play a significant role in prevention of liver cancer caused by viral cirrhosis.

A N T I O X I D A N T

Research has indicated that vitamin K has antioxidant activity comparable to vitamin E. Animal studies have demonstrated complete hepatic (liver) protection from induced oxidative stress using vitamin K, and was found to be 80% as effective as vitamin E in preventing oxidation.

A L Z H E I M E R ' SAbout 25% of the population have a genetic predisposition for developing Alzheimer's disease - they carry the E4 form of the lipoprotein. Interestingly, people who carry this gene have been found to have low levels of vitamin K. Calcification and the development of lesions in blood vessels that feed the brain tissues are believed to be a component of Alzheimer's development. Further research may reveal high-dose vitamin K therapy to be preventive.

MENAQUINONE-4 DEFICIENCY

NABA ABBAS

DEFICIENCY (MENAQUINONE-4)It is very rare and occurs when there is an inability to absorb the vitamin from the

intestinal tract.

Vitamin K deficiency can also occur after prolonged treatment with oral antibiotics. 

Deficiency is often the result of impaired absorption rather than not getting enough in the diet.

Prolonged use of antibiotics can also cause a low level of this vitamin because they destroy some of the bacteria in the gut that help to produce vitamin K.

Newborns are at risk for vitamin K deficiency. This is because their digestive tracts contain no vitamin K-producing bacteria.

Vitamin K deficiency in adults is rare. When it occurs, it is found in people with diseases that prevent the absorption of fat. These diseases include cystic fibrosis, celiac disease,

and cholestasis sometimes.

Menstrual bleeding, gum bleeding, nose bleeding, and easy bruising.

Bleeding within the digestive tract and blood in the urine.

Issues related to problematic blood clotting or bleeding, hemorrhaging.

Cartilage calcification.

Uncontrollable bleeding at surgical or puncture sites.

Brain bleeding in newborns.

Lack of Vitamin K2 causes calcium to fail to be deposited in bones where it belongs and to be deposited instead in arteries, aorta, soft tissues including muscle, breast, kidneys and in heel spurs

SYMPTOMS OF VIT K2 DEFICIENCY

TOXICITY & INTERACTIONS

HIRA KHAN

TOXICITY OF VITAMIN K2 (MENAQUINONE-4)

There is no documented case of

toxicity for menaquino

ne

The European

Food Safety Authority’s

safety assessment

of menaquinone concluded

that low doses of

menaquinone presented

no safety concerns.

It is often postulate

d that excessive vitamin K

may result in

over coagulation, i.e.

increased thrombosi

s risk.

Despite this, it is critical

to demonstrate that a high intake of

menaquinones does not

increase thrombosis risk. It was shown in rats that

thrombosis risk is not

increased at doses up to

250 mg/kg of MK-4.

The thrombosis

risk may only occur in

individuals using

coumarin-based oral

anticoagulants, for whom

dietary supplementa

tion with vitamin K

can influence the stability

of the international normalised

ratio.

Toxic effects of vit A and

D are exacerbat

ed in presence of vit K or

E deficiency.

In new born

theres a risk of

hemolysis in

jaundice.

mineral oil can decrease the absorption of

orally-administered

Vitamin K.

Vitamin K can reduce the effects

of oral anti coagulants like

warfarin.

Orlistat and mineral oil can decrease the absorption of

orally-administered

Vitamin K.

INTERACTIONS OF VIT K WITH DRUGS AND FOOD