Vitamin K effects in human health: new insights beyond bone and cardiovascular health

Fusaro, Maria; Gallieni, Maurizio; Porta, Camillo; Nickolas, Thomas L.; Khairallah, Pascale

doi:10.1007/s40620-019-00685-0

Cited by 52 publications

(62 citation statements)

References 112 publications

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“…Here, we identify that A. muciniphila -mediated orchestration of communal menaquinone (i.e., vitamin K2) pools in the gut may represent an alternative mechanism by which this keystone species impacts cancer treatment outcomes. From the perspective of human biology, vitamin K2 (dietary-derived or absorbed via microbial biosynthesis in the gut) acts as a ligand of the nuclear pregnane X receptor (also known as the steroid and xenobiotic sensing nuclear receptor, SXR, or NR1I2) and performs critical roles in blood coagulation, bone metabolism, and regulation of blood calcium levels and soft tissue calcification 34 . Interestingly, vitamin K2 is also a prospective anti-cancer agent that can target castrate-resistant PC in vitro 35 , inhibit both androgen-dependent and androgen-independent tumor growth in mice 36 , and is inversely associated with PC based on dietary intake results from a large European prospective study 37 .…”

Section: Discussionmentioning

confidence: 99%

Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients

Daisley¹,

Chanyi²,

Abdur-Rashid³

et al. 2020

Nat Commun

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Abiraterone acetate (AA) is an inhibitor of androgen biosynthesis, though this cannot fully explain its efficacy against androgen-independent prostate cancer. Here, we demonstrate that androgen deprivation therapy depletes androgen-utilizing Corynebacterium spp. in prostate cancer patients and that oral AA further enriches for the health-associated commensal, Akkermansia muciniphila. Functional inferencing elucidates a coinciding increase in bacterial biosynthesis of vitamin K2 (an inhibitor of androgen dependent and independent tumor growth). These results are highly reproducible in a host-free gut model, excluding the possibility of immune involvement. Further investigation reveals that AA is metabolized by bacteria in vitro and that breakdown components selectively impact growth. We conclude that A. muciniphila is a key regulator of AA-mediated restructuring of microbial communities, and that this species may affect treatment response in castrate-resistant cohorts. Ongoing initiatives aimed at modulating the colonic microbiota of cancer patients may consider targeted delivery of poorly absorbed selective bacterial growth agents.

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Section: Discussionmentioning

confidence: 99%

Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients

Daisley¹,

Chanyi²,

Abdur-Rashid³

et al. 2020

Nat Commun

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“…Phosphorylation was essential for the secretion of MGP into blood stream and requires phosphate. Vitamin K deficiency leads to a decrease in the levels of the phosphorylated carboxylated MGP (p-cMGP) and a rise in the levels of dephosphorylated undercarboxylated MGP (dp-ucMGP) [ 82 ], especially in patients with stage 5 chronic kidney disease. Further clarification of the role of vitamin K deficiency on the pathogenesis of various diseases such as osteoporosis, osteoarthrosis, or vascular calcification will be required in view of MGP metabolism.…”

Section: The Role Of Mgp (Matrix Gla Protein) In Bone Healthmentioning

confidence: 99%

Vitamin K Nutrition and Bone Health

Tsugawa

Shiraki²

2020

Nutrients

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Vitamin K is essential for blood coagulation and plays an important role in extrahepatic metabolism, such as in bone and blood vessels, and in energy metabolism. This review discusses the assessment of vitamin K sufficiency and the role of vitamin K in bone health. To elucidate the exact role of vitamin K in other organs, accurate tools for assessing vitamin K deficiency or insufficiency are crucial. Undercarboxylated vitamin K-dependent protein levels can be measured to evaluate tissue-specific vitamin K deficiency/insufficiency. Vitamin K has genomic action through steroid and xenobiotic receptor (SXR); however, the importance of this action requires further study. Recent studies have revealed that the bone-specific, vitamin K-dependent protein osteocalcin has a close relationship with energy metabolism through insulin sensitivity. Among the organs that produce vitamin K-dependent proteins, bone has attracted the most attention, as vitamin K deficiency has been consistently associated with bone fractures. Although vitamin K treatment addresses vitamin K deficiency and is believed to promote bone health, the corresponding findings on fracture risk reduction are conflicting. We also discuss the similarity of other vitamin supplementations on fracture risk. Future clinical studies are needed to further elucidate the effect of vitamin K on fracture risk.

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“…More than 15 types of vitamin-K-Dependent Proteins (VKDPs) were identified until now. The most studied VKDPs are the following—several proteins affecting coagulation (protein C, S, M, Z, factors VII, IX, X, and prothrombin), bone Gla protein (BGP, or osteocalcin), matrix Gla protein (MGP), Gas6 (Growth Arrest-Specific 6 Protein), GRP (Gla Rich Protein), and periostin [ 13 ]. Vitamin K acts at least in two ways.…”

Section: Vitamin K a Family Of Vitamers: Types Status And Vitammentioning

confidence: 99%

“…Vitamin K acts at least in two ways. First, as the coenzyme of a carboxylase, determining the carboxylation of glutamic acid residues with a resulting formation of the amino acid γ-carboxy-glutamic acid (Gla: active form) [ 13 , 14 ]. Second, as a ligand of the steroid and xenobiotic receptor (SXR) and pregnane X receptor (PXR, murine ortholog) [ 15 ].…”

Section: Vitamin K a Family Of Vitamers: Types Status And Vitammentioning

confidence: 99%

“…Cardiovascular disease, strongly associated with vascular calcification, is the leading cause of death in end-stage kidney disease. Vascular calcification is inhibited by the vitamin-K-dependent protein MGP (matrix γ-carboxy-glutamic acid protein), which requires serine phosphorylation for its activation, beyond the gamma-carboxylation [ 13 ] ( Figure 1 ). Thus, assessing the role of vitamin K in the complex setting of KT is of interest.…”

Section: Vitamin K a Family Of Vitamers: Types Status And Vitammentioning

confidence: 99%

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Vitamin K and Kidney Transplantation

Fusaro

Cosmai

Evenepoel³

et al. 2020

Nutrients

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The assessment of the vitamin K status and its effects on clinical outcomes in kidney transplantation (KT) patients has sparked interest, but it is still largely unfulfilled. In part, this is due to difficulties in laboratory measurements of vitamin K, especially K2 vitamers. Vitamin K status is currently best assessed by measuring undercarboxylated vitamin-K-dependent proteins. The relative contribution of vitamin K1 and K2 to the health status of the general population and CKD (chronic kidney disease) patients, including KT patients, is also poorly studied. Through a complete and first review of the existing literature, we summarize the current knowledge of vitamin K pathophysiology and its potential role in preventing KT complications and improving organ survival. A specific focus is placed on cardiovascular complications, bone fractures, and the relationship between vitamin K and cancer. Vitamin K deficiency could determine adverse outcomes, and KT patients should be better studied for vitamin K assessment and modalities of effective therapeutic approaches.

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Vitamin K effects in human health: new insights beyond bone and cardiovascular health

Cited by 52 publications

References 112 publications

Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients

Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients

Vitamin K Nutrition and Bone Health

Vitamin K and Kidney Transplantation

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