Vitamin K

Overview

Vitamin K is fat-soluble and has an important role in making prothrombin and other proteins that help with blood clotting. Injections of vitamin K may be given before or after surgery to prevent hemorrhaging. Patients at risk of excessive bleeding because of liver disease, jaundice, malabsorption, or prolonged use of aspirin or antibiotics may also receive injections. Vitamin K has been used to treat heavy menstrual bleeding. It has also been used with vitamin C to treat morning sickness.

This vitamin is not readily transferred from mother to child. Without the intestinal bacteria necessary to synthesize vitamin K, newborns are at increased risk for hemorrhage. In these cases, newborns are often given vitamin K injections. Additionally, premature babies are at high risk for brain hemorrhage. Vitamin K supplements are often given to women at high risk of delivering prematurely. Women taking anti-epileptic drugs during pregnancy are often given supplements of vitamin K as their babies are at particular risk for deficiency. In the early 1990s, researchers reported a possible increase in risk for childhood cancers in children who were given vitamin K injections at birth. Results of recent studies, however, have been inconclusive. Some research suggests that oral supplements in three doses of 1 to 2 mg may be an acceptable alternative to injections.

Vitamin K inhibits the formation of calcium oxalate stones by synthesizing urinary proteins essential to kidney function. Vegetarians, whose diets are often high in vitamin K, have a low incidence of kidney stones.

Vitamin K is necessary for the conversion of osteocalcin, a protein that regulates the function of calcium in bone turnover and mineralization, to its active form. Vitamin K supplements may improve bone mineralization in postmenopausal women by increasing blood levels of osteocalcin and also by lowering the amount calcium excreted in the urine. Research suggests that vitamin K intakes much higher than the current recommendations improve biochemical markers of bone formation as well as bone density. Large supplemental doses of vitamin K have been useful in the treatment of osteoporosis. Low levels of vitamin K have been found in those with osteoporosis. In a Japanese study published in 1997, researchers found that, in a group of postmenopausal and peri-menopausal women with menopausal symptoms receiving hormone replacement therapy, those with reduced bone mineral density had lower levels of vitamin K1 and K2 than those with normal bone mineral density. Low levels of vitamin K have also been found in men with osteoporosis. A 1998 study suggested that vitamin K supplementation improves bone health in female elite athletes with amenorrhea. A 1998 study from the University of Pittsburgh suggests a synthetic form of vitamin K may stop liver cancer cell growth.

Dietary Sources

• Chlorophyll
• Green tea
• Turnip greens
• Broccoli
• Spinach
• Cabbage
• Asparagus
• Dark green lettuce

Freezing foods may destroy vitamin K. However, heating does not affect it.

Constituents/Composition

Vitamin K occurs in three forms. Vitamin K1 (phylloquinone) is made by plants and is considered the preferred form; vitamin K2 (menaquinone) is made by animals, birds, and by bacteria in the intestinal tract; and vitamin K3 (menaphthone or menadione) is synthetic.

Commercial Preparations

• Supplemental vitamin K is available in both natural and synthetic forms.
• Supplements of fat-soluble chlorophyll are an excellent source of K1.
• The water-soluble chlorophyll form of vitamin K is commonly sold in stores. Because this form cannot be absorbed in the gastrointestinal tract, its use is limited to the treatment of skin wounds.
• K1 and K3 are available in multivitamin complexes, and as 5-mg tablets.
• K1 injections are found in 2 mg/ml in 0.5-ml amps, and in 10 mg/ml in 1-ml ampules, and 2.5-ml and 5-ml vials.

Therapeutic Uses

• Helps prevent hemorrhage in surgical patients.
• Reduces risk of excessive bleeding in those with liver disease, jaundice, malabsorption and kidney disease.
• Reduces excessive bleeding in those on long-term aspirin or antibiotic therapy.
• Treats heavy menstrual bleeding.
• Used with vitamin C to treat morning sickness.
• Is a preventive measure for hemorrhage in newborns.
• May prevent calcium oxalate stones in the kidney.
• Supplements may improve bone mineralization.
• Large supplemental doses have been used to treat osteoporosis.
• A vitamin K analog, K compound 5, may stop liver cancer growth.
• Some forms (water-soluble chlorophyll) helps to control body, fecal, and urinary odor.
• Water-soluble forms are used in the treatment of skin wounds.

Dosage Ranges and Duration of Administration

Recommended dietary allowances (RDAs) are as follows.

• Neonates to 6 months: 5 mcg
• Infants 6 to 12 months:10 mcg
• Children 1 to 3 years: 15 mcg
• Children 4 to 6 years: 20 mcg
• Children 7 to 10 years: 30 mcg
• Men: 80 mcg
• Women: 65 mcg
• Pregnancy: 65 mcg
• Lactation: 65 mcg

Three doses are recommended to prevent neonatal hemorrhage: 1 to 2 mg, the first given at the first feeding, the second at two to four weeks, and the third at eight weeks.

Side Effects/Toxicology

Natural vitamin K is rarely toxic. However, large amounts of menadione, a synthetic form of vitamin K, may cause liver damage and hemolytic anemia. Intravenous injection of vitamin K can cause flushing, sweats, chest pain, and constricted breathing. Hemolysis, jaundice, and hyperbilirubinemia have been observed in newborns after the administration of vitamin K. Pain, swelling, and eczema may result from intramuscular injections.

Warnings/Contraindications/Precautions

• Vitamin K can interfere with the action of anticoagulants such as warfarin or coumadin.
• X rays and radiation can raise vitamin K requirements.
• Vitamin K is excreted in breast milk, and crosses the placenta. Use with caution in women who are pregnant or breast-feeding in conditions where there is concern for excess vitamin K.

Interactions

Omeprazole

In a crossover design clinical study, 13 healthy volunteers were maintained on a vitamin K1-restricted diet for 35 days and were randomly assigned to take omeprazole (40 mg/day) either during the first period of study or starting on day 15 until the end of the study (Paiva et al. 1998). The bacterial overgrowth induced by omeprazole included vitamin K2 (menaquinone)-synthesizing bacteria that served as a source of vitamin K. However, these bacteria were unable to restore vitamin K status to normal.

Phenytoin

Phenytoin interferes with vitamin K metabolism (Keith et al. 1983). Clotting defects may occur in neonates born to mothers receiving anticonvulsant drugs (Solomon et al. 1977). Some researchers recommend supplementing with vitamin K in pregnant women on epileptic therapy four weeks before the expected date of delivery (Nulman et al. 1999). Other researchers have not found justification for giving vitamin K to all pregnant women on anticonvulsant therapy throughout the last trimester of pregnancy (Hey 1999).

Warfarin

Vitamin K can decrease the anticoagulant effect of warfarin by interfering with the production of vitamin K-dependent clotting factors (Bell et al. 1972; Hines Burnham et al. 2000). Oral vitamin K1 (phytonadione) is used to correct excessive anticoagulation in patients on warfarin therapy who do not have serious bleeding (Weibert et al. 1997). A prospective open label clinical study with 62 warfarin-treated patients that had elevated INR values found that vitamin K1 (1 mg po) was a safe, reliable, and economical means of reducing the INR in these patients (Crowther et al. 1998). A consistent dietary intake of vitamin K is important to maintain vitamin K status and avoid a potential warfarin-vitamin K interaction (Booth et al. 1997; Booth and Centurelli 1999). Patients should avoid drastic changes in dietary habits while on warfarin therapy. Individuals taking warfarin may require more intensive monitoring of vitamin K status and INR values.

References

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