Vitamin K Medical uses, Side effects and Deficiency

Vitamin K

Vitamin K is a group of structurally similar, fat-soluble vitamins found in foods and in dietary supplements. The human body requires this vitamin for complete synthesis of certain proteins that are needed for blood coagulation (K from Koagulation, German for “coagulation”) or for controlling binding of calcium in bones and other tissues. The vitamin K-related modification of the proteins allows them to bind calcium ions, which they cannot do otherwise. Without this vitamin, blood coagulation is seriously impaired, and uncontrolled bleeding occurs. Preliminary clinical research indicates that deficiency of this vitamin may weaken bones, potentially leading to osteoporosis, and may promote calcification of arteries and other soft tissues.

Chemically, the vitamin K family comprises 2-methyl-1,4-naphthoquinone (3-) derivatives. It includes two natural vitamers: vitamin K1 and vitamin K2. Vitamin K2, in turn, consists of a number of related chemical subtypes, with differing lengths of carbon side chains made of isoprenoid groups of atoms.

Vitamin K1, also known as phylloquinone, is made by plants, and is found in highest amounts in green leafy vegetables because it is directly involved in photosynthesis. It may be thought of as the plant form of vitamin K. It is active as a vitamin in animals and performs the classic functions of vitamin K, including its activity in the production of blood-clotting proteins. Animals may also convert it to vitamin K2.

Bacteria in the gut flora can also convert K1 into vitamin K2 (menaquinone). In addition, bacteria typically lengthen the isoprenoid side chain of vitamin K2 to produce a range of vitamin K2 forms, most notably the MK-7 to MK-11 homologues of vitamin K2. All forms of K2 other than MK-4 can only be produced by bacteria, which use these during anaerobic respiration. The MK-7 and other bacterially derived forms of vitamin K2 exhibit vitamin K activity in animals, but MK-7’s extra utility over MK-4, if any, is unclear and is a matter of investigation.

Because a synthetic form of vitamin K, vitamin K3 (menadione), may be toxic by interfering with the function of glutathione, it is no longer used to treat vitamin K deficiency.

Vitamin K Medical uses

Warfarin overdose and coumarin poisoning

This vitamin is one of the treatments for bleeding events caused by overdose of the anticoagulant drug warfarin (Coumadin®). It can be administered by mouth, intravenously, or subcutaneously. It is also used in situations when a patient’s INR is greater than 10 and there is no active bleeding.

It is also part of the suggested treatment regime for poisoning by rodenticide (coumarin poisoning). Its treatment may only be necessary in people who deliberately have consumed large amounts of rodenticide or have consumed an unknown amount of rodenticide. Patients should be given oral Vitamin K1 to prevent the negative effects of rodenticide poisoning. Oral Vitamin K1 is preferred over other routes of administration because it has less side effects.

deficiency bleeding in newborns

Vitamin K is given as an injection to newborns to prevent Vitamin K deficiency bleeding. The blood clotting factors of newborn babies are roughly 30–60% that of adult values; this may be due to the reduced synthesis of precursor proteins and the sterility of their guts. Human milk contains 1–4 μg/L of vitamin K1, while formula-derived milk can contain up to 100 μg/L in supplemented formulas. Vitamin K2 concentrations in human milk appear to be much lower than those of vitamin K1. Occurrence of vitamin K deficiency bleeding in the first week of the infant’s life is estimated at 0.25–1.7%, with a prevalence of 2–10 cases per 100,000 births. Premature babies have even lower levels of the vitamin, so they are at a higher risk from this deficiency.

Bleeding in infants due to vitamin K deficiency can be severe, leading to hospitalization, blood transfusions, brain damage, and death. Supplementation can prevent most cases of vitamin K deficiency bleeding in the newborn. Intramuscular administration is more effective in preventing late vitamin K deficiency bleeding than oral administration.

Osteoporosis

There is no good evidence that its supplementation benefits the bone health of postmenopausal women.

Cardiovascular health

Adequate intake of this vitamin is associated with the inhibition of arterial calcification and stiffening, but there have been few interventional studies and no good evidence that its supplementation is of any benefit in the primary prevention of cardiovascular disease.

One 10-year population study, the Rotterdam Study, did show a clear and significant inverse relationship between the highest intake levels of menaquinone (mainly MK-4 from eggs and meat, and MK-8 and MK-9 from cheese) and cardiovascular disease and all-cause mortality in older men and women.

Cancer

Vitamin K has been promoted in supplement form with claims it can slow tumor growth; however, no good medical evidence supports such claims.

Vitamin K Side effects

Although allergic reaction from supplementation is possible, no known toxicity is associated with high doses of the phylloquinone (vitamin K1) or menaquinone (vitamin K2) forms of vitamin K, so no tolerable upper intake level (UL) has been set. Specifically vitamin K1 has been associated with severe adverse reactions such as bronchospasm and cardiac arrest when given intravenously as opposed to orally.

Blood clotting (coagulation) studies in humans using 45 mg per day of vitamin K2 (as MK-4) and even up to 135 mg per day (45 mg three times daily) of K2 (as MK-4), showed no increase in blood clot risk. Even doses in rats as high as 250 mg/kg, body weight did not alter the tendency for blood-clot formation to occur.

Unlike the safe natural forms of vitamin K1 and vitamin K2 and their various isomers, a synthetic form of vitamin K, vitamin K3 (menadione), is demonstrably toxic at high levels. The U.S. FDA has banned this form from over-the-counter sale in the United States because large doses have been shown to cause allergic reactions, hemolytic anemia, and cytotoxicity in liver cells.

Interactions

Phylloquinone (K1) or menaquinone (K2) are capable of reversing the anticoagulant activity of the anticoagulant warfarin (tradename Coumadin). Warfarin works by blocking recycling of this vitamin, so that the body and tissues have lower levels of active vitamin K, and thus a deficiency of this vitamin.

Supplemental vitamin K (for which oral dosing is often more active than injectable dosing in human adults) reverses the vitamin K deficiency caused by warfarin, and therefore reduces the intended anticoagulant action of warfarin and related drugs. Sometimes small amounts of this vitamin are given orally to patients taking warfarin so that the action of the drug is more predictable. The proper anticoagulant action of the drug is a function of vitamin K intake and drug dose, and due to differing absorption must be individualized for each patient. The action of warfarin and vitamin K both require two to five days after dosing to have maximum effect, and neither warfarin nor vitamin K shows much effect in the first 24 hours after they are given.

The newer anticoagulants apixaban, dabigatran and rivaroxaban have different mechanisms of action that do not interact with this vitamin, and may be taken with supplemental vitamin K.

Absorption and dietary need

Previous theory held that dietary deficiency is extremely rare unless the small intestine was heavily damaged, resulting in malabsorption of the molecule. Another at-risk group for deficiency were those subject to decreased production of K2 by normal intestinal microbiota, as seen in broad-spectrum antibiotic use. Taking broad-spectrum antibiotics can reduce this vitamin production in the gut by nearly 74% in people compared with those not taking these antibiotics. Diets low in this vitamin also decrease the body’s vitamin K concentration. Those with chronic kidney disease are at risk for vitamin deficiency, as well as vitamin D deficiency, and particularly those with the apoE4 genotype. Additionally, the elderly have a reduction in vitamin K2.

Reference: Wikipedia

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