Deuterium-labeled phylloquinone has tissue-specific conversion to menaquinone-4 among Fischer 344 male rats.

Phylloquinone (PK) is converted into menaquinone-4 (MK-4) via side chain removal-addition. Stable isotope use is an effective approach to identify the tissue location of this conversion, which is currently unknown. Following a 14-d PK-deficient diet, male Fischer 344 rats (8 mo; n = 15) were fed 1.6 mg deuterium-labeled PK (L-PK) per kg diet for 0 (control), 1 d (PK-1d), and 7 d (PK-7d). Both L-PK and deuterium-labeled MK-4 (L-MK-4) were detected in tissues in PK-1d and PK-7d, although the results varied. Whereas some tissues had an overall increase in MK-4 in response to L-PK, total brain, testes, and fat MK-4 concentrations did not. In contrast, L-MK-4 concentrations increased in all 3 tissues. The deuterium label was found only on the L-MK-4 naphthoquinone ring, confirming the need for side chain removal for the formation of MK-4. Labeled menadione (MD) was detected in urine and serum in PK-1d and PK-7d, confirming its role as an intermediate. A Caco-2 cell monolayer model was used to study the role of the enterocytes in the conversion process. Neither MK-4 nor MD was detected in Caco-2 cells treated with PK. However, when Caco-2 cells were treated with MD, MK-4 was formed. Similarly, MK-4 was formed in response to MD-treated 293T kidney cells, but not HuH7 liver cells. These data demonstrate that MK-4 is the predominant form of vitamin K in multiple tissues, but there appears to be a tissue-specific regulation for the conversion of PK to MK-4.

Vitamin K prophylaxis for premature infants: 1 mg versus 0.5 mg.

We studied babies (22 to 32 weeks gestational age) of mothers wishing to breast-feed. Group 1 received 1 mg of vitamin K and Group 2 received 0.5 mg of vitamin K. The Day 2 plasma levels of vitamin K were 1900 to 2600 times higher on average, and the Day 10 vitamin K levels 550 to 600 times higher on average, relative to normal adult plasma values, whether an initial prophylaxis dose of 0.5 mg or 1 mg was used. We conclude that 0.5 mg as the initial dose of vitamin K intramuscularly or intravenously would likely be more than adequate to prevent hemorrhagic disease of the newborn, and that 0.3 mg/per kg may be used for babies with birth weights below 1000 g. To decrease vitamin K intakes in this population, new preparations of total parenteral nutrition multivitamins are needed.

A high phylloquinone intake is required to achieve maximal osteocalcin gamma-carboxylation.

BACKGROUND: Dietary vitamin K is usually inadequate to maximize serum osteocalcin gamma-carboxylation. Phylloquinone supplementation increases osteocalcin gamma-carboxylation; however, the amount required to maximize carboxylation is not known. OBJECTIVE: This study assessed the ability of various doses of phylloquinone (vitamin K(1)) to facilitate osteocalcin gamma-carboxylation. DESIGN: Healthy adults aged 19-36 y participated in 2 substudies. In an initial dose-finding study (substudy A), 6 women and 4 men received a placebo daily for 1 wk and then phylloquinone daily for 3 wk: 500, 1000, and 2000 micro g during weeks 2, 3, and 4, respectively. Osteocalcin and undercarboxylated osteocalcin were measured at baseline and after each week of supplementation. Subsequently, to further delineate the gamma-carboxylation response of osteocalcin to various doses of vitamin K, 58 women and 42 men were randomly assigned to receive placebo or phylloquinone supplementation (250, 375, 500, and 1000 micro g/d) for 2 wk (substudy B). The percentage of undercarboxylated osteocalcin (%ucOC) was measured at baseline and weeks 1 and 2. RESULTS: In substudy A, %ucOC decreased with phylloquinone supplementation (P < 0.0001); a greater reduction was observed with 1000 and 2000 micro g than with 500 micro g (P < 0.05). In substudy B, %ucOC decreased in all supplemented groups by week 1 (P for the trend < 0.0001), which was sustained through week 2. Phylloquinone supplementation decreased %ucOC dose-dependently; %ucOC was significantly different between the 250- micro g and the placebo groups and between the 1000- and 500- micro g groups but not between the 250-, 375-, and 500- micro g groups. CONCLUSION: A daily phylloquinone intake of approximately 1000 micro g is required to maximally gamma-carboxylate circulating osteocalcin.