Multiple Dietary Vitamin K Forms Are Converted to Tissue Menaquinone-4 in Mice

Abstract

Background “Vitamin K” is a family of structurally-related quinones, phylloquinone (PK) and the menaquinones (MKn), that share a common naphthoquinone ring but vary in sidechain length (n) and saturation. Dietary PK is a biosynthetic precursor to tissue menaquinone-4 (MK4), but little is known about the absorption and metabolism of dietary MKn. Objective To characterize absorption and metabolism of dietary MKn relative to PK. Methods In the 4-week diet study, 10-wk old male and female C57BL/6 mice were pair-fed a vitamin K deficient diet (control) or a diet supplemented with 5.0 μmol/kg total PK, MK4, and/or MK9 (separately and in combination). In the 1-week stable isotope study, 12-wk old mice were pair-fed diets containing 2.2 μmol/kg PK (unlabeled control), 2H7PK, 13C11MK4, 2H7MK7, or 2H7MK9. Vitamin K tissue content was quantified by HPLC and/or LC-MS, and concentrations were compared by sex and diet group using 2-factor ANOVA. Results Regardless of the form(s) of vitamin K provided in the feed, tissue MK4 concentrations did not differ across equimolar supplemented groups in kidney, adipose, reproductive organ, bone, and pancreas, in either males or females in the diet study (all P > 0.05). Isotopic labeling confirmed the naphthoquinone ring of MK4 in tissues originated from the administered dietary PK or MKn. Despite equimolar supplementation, accumulation of the administered dietary form differed across diet groups in small intestinal segments (all P < 0.002) and liver (P < 0.001). Female mice had greater total vitamin K than males in every tissue examined (P < 0.05). Conclusion Dietary PK, MK4, MK7, and MK9 all served as precursors to tissue MK4 in mice. This study expands our understanding of vitamin K metabolism and supports a common conversion mechanism of all dietary vitamin K forms to MK4. Further investigation of the metabolism and physiological roles of MK4 that may be independent of classical vitamin K function are warranted.

Vitamin K Status and Cognitive Function in Adults with Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort

“…Menaquinones (vitamin K2) are found in some meat and dairy products and fermented foods because they are bacterially synthesized. There are multiple menaquinone forms, which, with phylloquinone, are converted to menaquinone-4 in brain tissue ( 24 ). Menaquinone-4 is the primary form of vitamin K in the human brain ( 25 ) but is not typically detected in circulation.…”

Dietary Vitamin K1 intake is associated with lower long-term fracture-related hospitalization risk: the Perth longitudinal study of ageing women

“…36 Furthermore, when considering Vitamin K metabolism, recent evidence suggests that dietary Vitamin K1 and K2 (MK4, MK7, and MK9) all served as precursors to tissue MK4 in mice. 37 At least in mice models, perhaps the form of dietary Vitamin K ( e.g. PK or MK) may be less relevant, warranting investigation in humans.…”

Naturally occurring UBIAD1 mutations differentially affect menaquinone biosynthesis and vitamin K‐dependent carboxylation

“…Studies have shown that MK-4 is synthesized locally in different tissues by UBIAD1 using the precursor menadione, which is converted from dietary K vitamins during intestinal absorption and circulated to targeted tissues [25][26][27]61,62]. Additionally, extrahepatic VKD proteins are carboxylated locally in different tissues [63], which differ in vitamin K uptake and utilization [64,65]. These tissues also have different abundances of vitamin K recycling enzymes [66].…”