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2. Vitamin K Structure, Source, Cycle, Metabolism

Vitamin K is the term used to name a family of fat-soluble compounds, which although differ in origin and/or function, share a common 2-methyl-1,4-naphthoquinone ring, but differ in the (lipophilic) side chains linked at the 3-position. The three main forms are vitamin PK or phylloquinone (PK), vitamin K2 or menaquinones (MKn) and vitamin K3 or menadione. These three forms can be differentiated by the 3-position: PK has an isoprenoid side chain, whereas the MK form possesses a phytyl side chain and is characterized by a variable number of connected isoprenoid units (MKn), and menadione has no side chain and is a synthetic analogue [].

2. Vitamin K Structure, Source, Cycle, Metabolism

The sources of vitamin K are different depending on the vitamers. PK can be found mainly in green leafy vegetables (e.g., kale), vegetables in the Brassica genus (e.g., Brussels sprouts, broccoli), fruits (e.g., avocado, kiwi, and green grapes), herbs (e.g., cilantro, parsley), and green and herbal teas. Other dietary sources are plant oils such as soybean, canola, and olive oils [].

4. Vitamin K Recommended Intake, Deficiency, and Assessment

The recommended daily intake (RDI) or adequate intake (AI) of vitamin K is aimed at ensuring normal blood coagulation []. There is some variability of these recommended target values across various organizations. The National Academy of Medicine in the US stated the AI of vitamin PK at 120 μg/day for adult men and 90 μg/day for adult women []. The World Health Organization and the Food and Agriculture Organization recommended dosages for vitamin PK at 65 μg/day for men and 55 μg/day for women, based on a calculated requirement of 1 μg/day/kg body weight []. Finally, the European Commission has established a recommended daily allowance (RDA) for vitamin K at 75 μg/day []. In 2012, the Italian LARN (Reference Assumption Levels for Nutrients and Energy), proposed by the Human Nutrition Italian Society (SINU) suggested an intake of vitamin K stratified for age (140 or 170 μg/day for 18–59 and >60 years old, respectively) [].

2. Vitamin K Structure, Source, Cycle, Metabolism

Vitamin K acts as a cofactor for a single microsomal enzyme, namely carboxyglutamyl carboxylase (GGCX) which catalyzes the carboxylation (and thereby activation) of vitamin-K-dependent proteins (VKDPs) []. Vitamin-K-dependent carboxylase catalyzes the posttranslational γ-carboxylation of glutamic acid (Glu) residues, placed in vitamin K-dependent proteins (also known as Gla proteins), to γ-carboxylated glutamic acid (Gla) residues. Among the Gla protein family, 17 different members have been recongnized: S prothrombin, factor VII, factor IX, factor X, protein C, protein S and protein Z belonging to the coagulative cascade; (matrix Gla protein,(MGP), Osteocalcin (OC), growth arrest-specific protein 6 (Gas6), Gla-rich protein (GRP) playing a role in modulating bone and vascular mineralization; periostin and periostin-like factor, two proline-rich Gla proteins, and two transmembrane Gla proteins. Vitamin K was previously considered only an essential factor for blood coagulation [].

2. Vitamin K Structure, Source, Cycle, Metabolism

The involvement of vitamin K in bone metabolism does not occur exclusively by the γ-carboxylation reaction. MK4, binds to the nuclear receptor, steroid, and xenobiotic receptor (SXR) and its murine ortholog, pregnane X receptor (PXR), a nuclear receptor whose primary function is to regulate the expression of genes encoding enzymes involved in steroid metabolism and detoxification of xenobiotics and various drugs [,,]. Vitamin PK is not able to activate SXR directly, suggesting vitamin PK potentially contribute to this mechanism of action after being converted into MK-4 [] ().