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Nutrients
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Vitamin K Intake and Human Health
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Vitamin K Intake and Human Health

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Micronutrients and Human Health".

Deadline for manuscript submissions: closed (28 February 2020) | Viewed by 61034

Special Issue Editor

Prof. Michio Komai

E-Mail Website
Guest Editor
Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
Interests: zinc; vitamin K; biotin; functional food components; intestinal morphology; taste physiology; appetite regulation

Special Issue Information

Dear Colleagues,

All vitamin K (VK) analogs are active as a cofactor for the post-translational formation of Gla-proteins (Clotting factors, osteocalcin (bone Gla-protein), matrix Gla-protein (MGP), and so on). However, of the VK analogs, menaquinone-4 (MK-4) has specific activities for various important physiological functions. Most of the menaquinone analogs (MK-n = vitamin K2) are synthesized by microorganisms, but many researchers have reported that MK-4 is unique in being synthesized by the conversion of orally ingested VK1 or menaquinones (VK2) by endogenous enzymatic action in the major tissues of germfree rats and mice which lack their intestinal microbiota. Therefore, future studies must be undertaken to clarify the important role of MK-4 existence in the tissues, as well as comparative studies using vitamin K1 against MK-4 because orally ingested VK1 (or MK-n) is partially converted into MK-4 in each tissue. Studies on unique functions of MK-4, such as bone formation activity that is dependent or independent on osteocalcin, and the mechanism of anti-cancer, anti-atherosclerosis, anti-diabetes, anti-inflammation activities must be included; furthermore, studies on functions through the binding to the nuclear steroid X receptor (SXR or PXR), and on the direct effect of MK-4 on steroid hormone (testosterone) synthesis in the testis or brain must be added to this issue.

Dr. Michio Komai
Guest Editor

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Keywords

  • Vitamin K (VK)
  • Phylloquinone (VK1)
  • Menaquinones (MK-n=VK2)
  • Gla-proteins
  • Bleeding in infancy
  • Bone formation
  • SXR (or PXR)
  • Anti-cancer
  • Anti-inflammation
  • Testosterone biosynthesis

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Published Papers (5 papers)

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Review

16 pages, 744 KiB  
Review
Beneficial Effects of Vitamin K Status on Glycemic Regulation and Diabetes Mellitus: A Mini-Review
by Hsin-Jung Ho, Michio Komai and Hitoshi Shirakawa
Nutrients 2020, 12(8), 2485; https://doi.org/10.3390/nu12082485 - 18 Aug 2020
Cited by 21 | Viewed by 8714
Abstract
Type 2 diabetes mellitus is a chronic disease that is characterized by hyperglycemia, insulin resistance, and dysfunctional insulin secretion. Glycemic control remains a crucial contributor to the progression of type 2 diabetes mellitus as well as the prevention or delay in the onset [...] Read more.
Type 2 diabetes mellitus is a chronic disease that is characterized by hyperglycemia, insulin resistance, and dysfunctional insulin secretion. Glycemic control remains a crucial contributor to the progression of type 2 diabetes mellitus as well as the prevention or delay in the onset of diabetes-related complications. Vitamin K is a fat-soluble vitamin that plays an important role in the regulation of the glycemic status. Supplementation of vitamin K may reduce the risk of diabetes mellitus and improve insulin sensitivity. This mini-review summarizes the recent insights into the beneficial effects of vitamin K and its possible mechanism of action on insulin sensitivity and glycemic status, thereby suppressing the progression of diabetes mellitus. Full article
(This article belongs to the Special Issue Vitamin K Intake and Human Health)
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16 pages, 1200 KiB  
Review
Vitamin K Nutrition and Bone Health
by Naoko Tsugawa and Masataka Shiraki
Nutrients 2020, 12(7), 1909; https://doi.org/10.3390/nu12071909 - 27 Jun 2020
Cited by 54 | Viewed by 10619
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Vitamin K Intake and Human Health)
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9 pages, 1358 KiB  
Review
MK-7 and Its Effects on Bone Quality and Strength
by Toshiro Sato, Naoko Inaba and Takatoshi Yamashita
Nutrients 2020, 12(4), 965; https://doi.org/10.3390/nu12040965 - 31 Mar 2020
Cited by 37 | Viewed by 13613
Abstract
Vitamin K acts as a cofactor and is required for post-translational γ-carboxylation of vitamin K-dependent proteins (VKDP). The current recommended daily intake (RDI) of vitamin K in most countries has been established based on normal coagulation requirements. Vitamin K1 and menaquinone (MK)-4 has [...] Read more.
Vitamin K acts as a cofactor and is required for post-translational γ-carboxylation of vitamin K-dependent proteins (VKDP). The current recommended daily intake (RDI) of vitamin K in most countries has been established based on normal coagulation requirements. Vitamin K1 and menaquinone (MK)-4 has been shown to decrease osteocalcin (OC) γ-carboxylation at RDI levels. Among the several vitamin K homologs, only MK-7 (vitamin K2) can promote γ-carboxylation of extrahepatic VKDPs, OC, and the matrix Gla protein at a nutritional dose around RDI. MK-7 has higher efficacy due to its higher bioavailability and longer half-life than other vitamin K homologs. As vitamin K1, MK-4, and MK-7 have distinct bioactivities, their RDIs should be established based on their relative activities. MK-7 increases bone mineral density and promotes bone quality and strength. Collagen production, and thus, bone quality may be affected by MK-7 or MK-4 converted from MK-7. In this review, we comprehensively discuss the various properties of MK-7. Full article
(This article belongs to the Special Issue Vitamin K Intake and Human Health)
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13 pages, 506 KiB  
Review
Vitamin K Deficiency Bleeding in Infancy
by Shunsuke Araki and Akira Shirahata
Nutrients 2020, 12(3), 780; https://doi.org/10.3390/nu12030780 - 16 Mar 2020
Cited by 70 | Viewed by 15957
Abstract
Vitamin K is essential for the synthesis of few coagulation factors. Infants can easily develop vitamin K deficiency owing to poor placental transfer, low vitamin K content in breast milk, and poor intestinal absorption due to immature gut flora and malabsorption. Vitamin K [...] Read more.
Vitamin K is essential for the synthesis of few coagulation factors. Infants can easily develop vitamin K deficiency owing to poor placental transfer, low vitamin K content in breast milk, and poor intestinal absorption due to immature gut flora and malabsorption. Vitamin K deficiency bleeding (VKDB) in infancy is classified according to the time of presentation: early (within 24 h), classic (within 1 week after birth), and late (between 2 week and 6 months of age). VKDB in infancy, particularly late-onset VKDB, can be life-threatening. Therefore, all infants, including newborn infants, should receive vitamin K prophylaxis. Exclusive breastfeeding and cholestasis are closely associated with this deficiency and result in late-onset VKDB. Intramuscular prophylactic injections reduce the incidence of early-onset, classic, and late-onset VKDB. However, the prophylaxis strategy has recently been inclined toward oral administration because it is easier, safer, and cheaper to administer than intramuscular injection. Several epidemiological studies have shown that vitamin K oral administration is effective in the prevention of VKDB in infancy; however, the success of oral prophylaxis depends on the protocol regimen and parent compliance. Further national surveillance and studies are warranted to reveal the optimal prophylaxis regimen in term and preterm infants. Full article
(This article belongs to the Special Issue Vitamin K Intake and Human Health)
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13 pages, 253 KiB  
Review
The Inhibitory Roles of Vitamin K in Progression of Vascular Calcification
by Atsushi Shioi, Tomoaki Morioka, Tetsuo Shoji and Masanori Emoto
Nutrients 2020, 12(2), 583; https://doi.org/10.3390/nu12020583 - 23 Feb 2020
Cited by 62 | Viewed by 11419
Abstract
Vitamin K is a fat-soluble vitamin that is indispensable for the activation of vitamin K-dependent proteins (VKDPs) and may be implicated in cardiovascular disease (CVD). Vascular calcification is intimately associated with CV events and mortality and is a chronic inflammatory process in which [...] Read more.
Vitamin K is a fat-soluble vitamin that is indispensable for the activation of vitamin K-dependent proteins (VKDPs) and may be implicated in cardiovascular disease (CVD). Vascular calcification is intimately associated with CV events and mortality and is a chronic inflammatory process in which activated macrophages promote osteoblastic differentiation of vascular smooth muscle cells (VSMCs) through the production of proinflammatory cytokines such as IL-1β, IL-6, TNF-α, and oncostatin M (OSM) in both intimal and medial layers of arterial walls. This process may be mainly mediated through NF-κB signaling pathway. Vitamin K has been demonstrated to exert anti-inflammatory effects through antagonizing NF-κB signaling in both in vitro and in vivo studies, suggesting that vitamin K may prevent vascular calcification via anti-inflammatory mechanisms. Matrix Gla protein (MGP) is a major inhibitor of soft tissue calcification and contributes to preventing both intimal and medial vascular calcification. Vitamin K may also inhibit progression of vascular calcification by enhancing the activity of MGP through facilitating its γ-carboxylation. In support of this hypothesis, the procalcific effects of warfarin, an antagonist of vitamin K, on arterial calcification have been demonstrated in several clinical studies. Among the inactive MGP forms, dephospho-uncarboxylated MGP (dp-ucMGP) may be regarded as the most useful biomarker of not only vitamin K deficiency, but also vascular calcification and CVD. There have been several studies showing the association of circulating levels of dp-ucMGP with vitamin K intake, vascular calcification, mortality, and CVD. However, additional larger prospective studies including randomized controlled trials are necessary to confirm the beneficial effects of vitamin K supplementation on CV health. Full article
(This article belongs to the Special Issue Vitamin K Intake and Human Health)
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