Status Requirements and Recommended Intakes

Vitamin K status can be measured either by its concentration in plasma or by its efficacy in ensuring optimal carboxylase function, as indicated by specific carboxylated plasma proteins. Accurate assay of the very low concentrations of vitamin K that are present in plasma was a considerable analytical challenge, which was eventually solved by highperformance liquid chromatography (HPLC) followed by high-sensitivity coulometric or fluoro-metric detection. A popular method uses organic solvent extraction, a cartridge cleanup step, an HPLC separation followed by postcolumn reduction of the vitamin K quinone to the reduced quinol form by metallic zinc or other reductant, and finally fluorometric quantitation of the fluorescent quinol. A useful internal standard, not found in nature, is the homolog of phylloquinone, vitamin K1(25). With modern detectors, analysis is possible with only 0.25 ml plasma. A published 'normal' range in the United States is 0.25-2.7 nmol/l, corresponding to approximate average daily intakes of 100 mg/day in men and 80 mg/day in women. As noted earlier, the phylloquinone content of plasma has a short half-life and is strongly correlated with plasma triglycerides. It is therefore not ideal as a long-term index of status. Alternatives include functional indices such as plasma prothrombin time (increased only by severe vitamin K deficiency), PIVKA, (which is more sensitive to marginal deficiency), and ucOC (which is the most sensitive functional indicator). These functional indices are not totally specific for vitamin K deficiency, although ucOC (for which monoclonal antibodies now exist) does appear to possess reasonably good specificity. Unfortunately, the different commercial kit assays measure different epitopes of OC, which makes harmonization difficult. Urinary total Gla is sensitive to vitamin K status, but it varies with age and has not yet proved to be very useful as a status indicator. Functional indices that are based on impaired carboxylase activity affecting other Gla proteins may be developed in the future.

Most estimates of the amount of phylloquinone needed to correct clotting changes suggest that adult human requirements are between 0.5 and 1 mg/kg/day. There are no reference nutrient intakes defined for vitamin K in the United Kingdom, although a 'safe intake' for adults was set in 1991 at 1 mg/kg/day and for infants 10 mg/day. In the United States, the Food and Nutrition Board of the National Academy of Sciences has defined an Adequate Intake (AI) of phylloquinone of 90 mg/day for adult women and 120 mg/day for adult men, with proportionately smaller values for children. For infants aged 0-6 months, the AI is only 2 mg/day, and it is 2.5 mg/day at 7-12 months, thus creating a larger proportional difference between infants and older age groups than for most micronutrients.

Both phylloquinone and the menaquinones appear to be nontoxic, even in multimilligram amounts. However, menadione, the water-soluble form of vitamin K, was found to cause hemolytic anemia, hyperbilirubinemia, and kernicturus in infants when

>5 mg was given. Therefore, it is not currently used for human prophylaxis or treatment.

Since vitamin K is thought to have a wide range of functions in the body in addition to blood clotting, and some of these may have long-term health implications, research on requirements and optimal intakes, with multiple end points, is needed. Metabolic and health-related differences between the menaquinones and phylloquinone also need to be defined.

See also: Bone. Fruits and Vegetables. Infants:

Nutritional Requirements. Pregnancy: Safe Diet for Pregnancy. Vitamin A: Biochemistry and Physiological Role. Vitamin E: Physiology and Health Effects.

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