Cis and trans isomers of the vitamin menaquinone-7: which one is
Received: 14 November 2019 /Revised: 15 January 2020 /Accepted: 23 January 2020 /Published online: 3 February 2020
#Springer-Verlag GmbH Germany, part of Springer Nature 2020
Recently, several studies have indicated that an adequate intake of menaquinone-7 (MK-7) offers numerous health benefits.
However, the low availability of MK-7 in the diet necessitates the development of dietary supplements or functional food
products to complement natural food sources and meet the daily intake requirements. Like most biological molecules, MK-7
can exist as geometric isomers that can occur in the cis,trans,andcis/trans forms; however, only the all-trans form is biologically
significant. MK-7 is traditionally produced through bacterial fermentation, but various synthetic preparations have lately become
available. The isomer composition in the final product is influenced by numerous factors, including the methods of production
and purification, as well as particular environmental and storage conditions. The MK-7 profile obtained from the various
production methods has not yet been elucidated, and the ideal method for the synthesis of the all-trans form of the vitamin is
also debatable. Consequently, the quantification of the MK-7 profile of various products is necessary to develop an understanding
of the factors that influence the proportion of isomers that are obtained in different preparations. Several possible methods exist
for the quantification of MK-7 isomers, and of these, liquid chromatography in conjunction with mass spectrometry techniques
appears to be the most promising. Evaluation of the isomer composition is an important consideration, as only the all-trans form
sustains biological activity. Furthermore, knowledge of the prominent factors that influence the MK-7 composition may also
enable their manipulation to obtain a more favorable MK-7 profile in the final product.
Keywords Cis and trans isomers .MK-7 .Biological activity .Synthesis .Quantification
Vitamin K collectively refers to a group of fat-soluble com-
pounds that contain a 2-methyl-1, 4-naphthoquinone moiety,
but differ in the structure of a lateral isoprenoid chain at the 3-
position (Sitkowski et al. 2018;Szterketal.2018b). Vitamin
K naturally exists in two forms, phylloquinone and a series of
menaquinones, both of which play an important role in hemo-
stasis (Berenjian et al. 2015; Beulens et al. 2013; Nannapaneni
et al. 2017; Szterk et al. 2018b). The major dietary source of
phylloquinone are green vegetables, whereas menaquinones
are primarily of microbial origin and are present in certain
animal products and fermented foods such as meat, beef liver,
eggs, natto, hard cheeses, curd, and sauerkraut (Berenjian
et al. 2013; Beulens et al. 2013; Szterk et al. 2018b; Vermeer
et al. 2018).
All differences in the properties of the various forms of
vitamin K are attributable to the length and degree of satura-
tion of the isoprenoid side chain (Beulens et al. 2013; Pucaj
et al. 2011; Sitkowski et al. 2018). Phylloquinone is a single
compound with a side chain comprising four isoprenoid resi-
dues, three of which are unsaturated (Beulens et al. 2013).
Whereas, menaquinones contain side chains of varying length
and degree of saturation, and can generally be represented in
the form MK-n, where n denotes the number of unsaturated
isoprenoid units in a chain, which is usually between four and
thirteen (Beulens et al. 2013;Dainesetal.2003;Szterketal.
MK-7 is a class of menaquinones that can be synthesized
through both natural (bacterial fermentation) and chemical
means for a variety of applications, including functional foods
and dietary supplements (Berenjian et al. 2015; Southee et al.
2016; Szterk et al. 2018a; Szterk et al. 2018b; Walther et al.
2013). Lately, MK-7 has gained widespread interest in both
School of Engineering, Faculty of Science and Engineering, The
University of Waikato, Hamilton, New Zealand
Applied Microbiology and Biotechnology (2020) 104:2765–2776