Stable isotope studies into the kinetics and bioavailablity of vitamin K₁ in humans

Jones, Kerry S. (2007). Stable isotope studies into the kinetics and bioavailablity of vitamin K₁ in humans. PhD thesis The Open University.



In Britain, vitamin K1 (phylloquinone) is the primary form of vitamin K in the human diet and blood. Evidence is accumulating for roles of vitamin K1 beyond established functions in blood coagulation, particularly in bone metabolism. To aid the determination of recommended intakes vitamin K1 kinetics and bioavailability were investigated in adult volunteers using stable isotopes.

Methods to measure reliably and accurately the isotopic enrichment of plasma vitamin K1 using gas chromatography mass spectrometry (GCMS) were developed. Two stable isotope labelled forms of vitamin K1 (13C and ring-D4) measured simultaneously disposal kinetics of intravenous doses and absolute absorption of 4 μg oral doses in ten lean, healthy volunteers (1 male and 9 female), aged 22 - 31 y. Isotopic data were fitted to a 2-compartment model with input and output from the sampled (blood plasma) pool, and exchange between it and a remote compartment. Mean half-times for vitamin K1 disappearance were 0.2 and 2.7 h and mean absolute absorption of oral doses was 13%.

A three-way crossover measured vitamin K1 bioavailability in twelve lean, healthy volunteers (7 male and 5 female) aged 22 - 49 y. Each volunteer consumed 20 μg of capsulated 13C-labelled vitamin K1 with one of three test-meals representing convenience, cosmopolitan or animal-oriented diets and balanced for fat, protein and carbohydrate but containing vitamin K1 in different components. Blood was sampled over 8 h. Relative bioavailability was greater from the convenience meal (relative bioavaiiability = 1.00), in which most vitamin K1 was in oils and fats not intact vegetables, compared to either the cosmopolitan (0.46) or animal-oriented (0.29) meals.

These studies demonstrate that stable isotope-based methods successfully measure vitamin K1 bioavaiiability and metabolism and their potential for use in establishing recommended dietary intakes.

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