Acharya MD, in Transfusion Medicine and Hemostasis (Third Edition), 2019 Abstract However, it is also plausible that phylloquinone is the optimal dietary form because it can be converted to MK-4 in tissues where presumably needed. Because phylloquinone is converted to MK-4 in some but not all tissues, it is highly likely that MK-4 has unique roles independent of its function as an enzyme cofactor. These observations have led to speculations that (i) some of the menaquinones may possess some functions that are not shared by phylloquinone, and (ii) there may be implications for cell proliferation and for cancer risk from variations in the supply of vitamin K. MK-4 and its isolated geranyl–geraniol side chain were also able to suppress the synthesis of prostaglandin E 2, which is a potent bone resorption catalyst. MK-4 promotes extracellular matrix formation by activating SXR to upregulate tsukushi (TSK), which plays a role in collagen accumulation. Recent studies have suggested that MK-4, in particular, has a transcriptional regulatory function. However, these studies were not designed to test the hypothesis that vitamin K forms reduce cancer incidences, hence should be considered hypothesis-generating at this time. Data from observational studies also suggest that high intakes of long-chain menaquinones may be associated with lower incidence of certain cancers. In contrast, patients at risk of hepatocellular carcinoma had lower incidence of the disease when given high doses of MK-4 compared to those not receiving MK-4. Depriving certain tumors of vitamin K, both in vitro and in vivo, seemed to inhibit their growth and metastasis. There are several functions of MK-4 that are shared by the isolated geranyl–geraniol side chain, which involve the induction of apoptosis of osteoclasts and of certain cancer cells in culture. The mechanism underlying the potential influence of vitamin K on inflammatory cytokine production is unclear, although it may be through the regulation of the transcription factor NF-κB. Most recently, vitamin K, in the forms of both phylloquinone and MK-4, has also been reported in both in vivo models and in human studies to modulate proinflammatory cytokine production independent of its role as a cofactor. Therefore, it is now thought that vitamin K may be involved in sphingolipid metabolism.
Vitamin K is thought to be involved in sphingolipid metabolism in certain bacteria by modulating serine palmitoyl transferase, and warfarin treatment decreased brain concentrations of sulfatides and galactocerebroside sulfotransferase activity in animals, which was reversible by vitamin K (either phylloquinone or MK-4). Booth, in Encyclopedia of Human Nutrition (Third Edition), 2013 Potential Non-Gla Functions of Vitamin K
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