Vitamin K is a term used to represent multiple compounds derived from plants (phylloquinone, PK) and bacteria (menaquinones, MKn). Menaquinone-4 (MK4) is present in human tissues, but the existing literature does not fully explain how these diet derived molecules are absorbed and metabolized into MK-4. Ellis and colleagues conducted a study to characterize the relative absorption and metabolism of diet derived MKn and PK, and they report their results in the April 2022 issue of The Journal of Nutrition.

Male and female mice were pair fed a vitamin K deficient diet (control), or a diet containing 5.0 µmol/kg PK, MK4, and MK9 either as individual molecules or in combination. Tissue concentrations of MK4 were determined after 4 weeks of consuming the experimental diets. A second study was conducted (1-week) using 2.2 µmol/kg stable isotope labeled 2H7PK, 13C11MK4, 2H7MK7 or 2H7MK9 to determine the impact of source on tissue concentrations of MK4 in pair-fed male and female mice.

Tissue MK4 concentrations were similar for mice receiving equimolar amounts of the vitamin K forms, regardless of the source provided. The napthoquinone ring present in tissue MK4 was derived from dietary PK or MKn. Accumulation of the dietary form differed across diet groups in the intestine and liver. Also, female mice had higher total amounts of vitamin K than males in all tissues analyzed. These observations led the authors to conclude that all of the dietary forms of vitamin K provided were equally able to serve as tissue MK4 precursors in mice. They suggest more work is required to determine if there are other functions and roles of MK4 beyond its role as vitamin K.

In an editorial, Shearer provides a description of the history behind the discoveries that led to our understanding of vitamin K absorption and metabolism prior to the work conducted by Ellis and colleagues. Shearer indicates the work by Ellis and colleagues provides us greater understanding of the absorption, metabolism, and tissue distributions of vitamin K vitamers but more work is needed to identify the physiologic purpose of the MK4 biosynthetic pathway. Shearer concludes that current improvements in analytical techniques will permit us to conduct the human studies needed to explore the importance of MK4 biosynthesis in vitamin K requirements.


Jessie L Ellis, Xueyan Fu, J Philip Karl, Christopher J Hernandez, Joel B Mason, Russell A DeBose-Boyd, Sarah L Booth, Multiple Dietary Vitamin K Forms Are Converted to Tissue Menaquinone-4 in Mice, The Journal of Nutrition, Volume 152, Issue 4, April 2022, Pages 981–993,

Martin J Shearer, The Biosynthesis of Menaquinone-4: How a Historic Biochemical Pathway Is Changing Our Understanding of Vitamin K Nutrition, The Journal of Nutrition, Volume 152, Issue 4, April 2022, Pages 917–919,

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