1974). The excretion products have not been extensively characterized but are known to proceed through the oxidative degradation of the phytyl side chain of phylloquinone, followed by glucuronide conjugation. Turnover in the liver is rapid and hepatic reserves are rapidly depleted when dietary intake of vitamin K is restricted (Usui et al., 1990).
The human gut contains a large amount of bacterially produced menaquinones, but their contribution to the maintenance of vitamin K status has been difficult to assess (Suttie, 1995). Although the content is extremely variable, human liver contains about 10 times as much vitamin K as a mixture of menaquinones than as phylloquinone (Shearer, 1992; Thijssen and Drittij-Reijnders, 1996; Usui et al., 1990). Absorption of these very lipophilic membrane-associated compounds from the distal bowel has been difficult to demonstrate (Ichihashi et al., 1992). Evidence of vitamin K inadequacy in normal human subjects following dietary restriction of vitamin K also suggests that this source of the vitamin is not utilized in sufficient amounts to maintain maximal γ-carboxylation of vitamin K-dependent proteins. One specific menaquinone, MK-4, appears to have a unique yet unidentified role. MK-4 can be formed from menadione (2-methyl-1,4-naphthoquinone) but is also formed in animal tissues from phylloquinone (Davidson et al., 1998; Thijssen and Drittij-Reijnders, 1994). It is present in much higher concentrations than phylloquinone in tissues such as pancreas, salivary gland, brain, and sternum, and its concentration in these tissues is to some degree dependent on phylloquinone intake.
A clinically significant vitamin K deficiency has usually been defined as a vitamin K-responsive hypoprothrombinemia and is associated with an increase in prothrombin time (PT) and, in severe cases, bleeding. Spontaneous cases have been rare and have usually been associated with various lipid malabsorption syndromes (Savage and Lindenbaum, 1983). There are numerous case reports of bleeding episodes in antibiotic-treated patients, and these have often been ascribed to an acquired vitamin K deficiency resulting from a suppression of menaquinone-synthesizing organisms. However, these reports are complicated by the possibility of general malnutrition in this patient population and by the antiplatelet action of many of the same drugs (Suttie, 1995).
Reports of experimentally induced, clinically significant vitamin K deficiencies are scant. Udall (1965) fed 10 healthy subjects a diet