The Role of Vitamin K in Humans: Implication in Aging and Age-Associated Diseases
Abstract
:1. Introduction
2. Vitamin K in Bone Health
3. Vitamin K in the Prevention and Therapy of Vascular Calcification and Cardiovascular Diseases
4. The Effects of Vitamin K on Metabolic Disorders
5. The Effect of Vitamin K on Neurodegenerative Diseases
6. The Effect of Vitamin K on Cancer
7. Correlation between Vitamin K and Pulmonary Disease
8. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
ACE-I | Angiotensin-converting enzyme inhibitor |
AD | Alzheimer’s disease |
AKT | Protein kinase B |
AMPK | Adenosine monophosphate-activated protein kinase |
Bcl-2 | B-cell lymphoma 2 |
BMC | Bone mineral content |
BMD | Bone mineral density |
CCC | Cholangiocellular carcinoma |
CHD | Coronary heart disease |
CKD | Chronic kidney disease |
CNS | Central nervous system |
cOC | Carboxylated osteocalcin |
CRP | C-reactive protein |
CV | Cardiovascular |
CVD | Cardiovascular disease |
dp-ucMGP | Dephosphorylated-uncarboxylated matrix Gla protein |
Gas6 | Growth arrest-specific protein 6 |
GGCX | Gamma-glutamyl carboxylase |
Gla | γ-carboxylated glutamic acid |
Glu | Glutamic acid |
GRP | Gla-rich protein |
HbA1c | Glycated hemoglobin |
HCC | Hepatocellular carcinoma |
HDL | High-density lipoprotein |
HIF-1α | Hypoxia-inducible factor-1α |
HOMA-IR | Homeostatic model assessment for insulin resistance |
HR | Hazard ratio |
IL | Interleukin |
JNK | C-Jun N-terminal kinase |
metS | Metabolic syndrome |
MGP | Matrix Gla protein |
MK | Menaquinone |
mTORC | Mammalian target of rapamycin complex |
NF-кB | Nuclear factor kappa-light-chain-enhancer of activated B cells |
Nrf2 | Nuclear factor erythroid 2–related factor 2 |
OA | Osteoarthritis |
OC | Osteocalcin |
OR | Odds ratio |
OS | Oxidative stress |
PCOS | Polycystic ovary syndrome |
PD | Parkinson’s disease |
PI3K | Phosphatidylinositide-3-kinase |
PK | Phylloquinone |
RCT | Randomized controlled trial |
ROS | Reactive oxygen species |
SIRT | Sirtuin |
T2D | Type 2 diabetes |
TNF-α | Tumor necrosis factor-alpha |
tOC | Total osteocalcin |
UBIAD1 | UbiA prenyltransferase domain containing 1 |
ucMGP | Uncarboxylated matrix Gla protein |
ucOC | Undercarboxylated osteocalcin |
VC | Vascular calcification |
vitD | Vitamin D |
VK | Vitamin K |
VKAs | Vitamin K antagonists |
VKDP | Vitamin K-dependent protein |
ACE-I | angiotensin-converting enzyme inhibitor |
AD | Alzheimer’s disease |
AKT | protein kinase B |
AMPK | adenosine monophosphate-activated protein kinase |
Bcl-2 | B-cell lymphoma 2 |
BMC | bone mineral content |
BMD | bone mineral density |
CCC | cholangiocellular carcinoma |
CHD | coronary heart disease |
CKD | chronic kidney disease |
CNS | central nervous system |
cOC | carboxylated osteocalcin |
CRP | C-reactive protein |
CV | cardiovascular |
CVD | cardiovascular disease |
dp-ucMGP | dephosphorylated-uncarboxylated matrix Gla protein |
Gas6 | growth arrest-specific protein 6 |
GGCX | gamma-glutamyl carboxylase |
Gla | γ-carboxylated glutamic acid |
Glu | glutamic acid |
GRP | Gla-rich protein |
HbA1c | glycated hemoglobin |
HCC | hepatocellular carcinoma |
HDL | high-density lipoprotein |
HIF-1α | hypoxia-inducible factor-1α |
HOMA-IR | homeostatic model assessment for insulin resistance |
HR | hazard ratio |
IL | interleukin |
JNK | c-Jun N-terminal kinase |
metS | metabolic syndrome |
MGP | matrix Gla protein |
MK | menaquinone |
mTORC | mammalian target of rapamycin complex |
NF-кB | nuclear factor kappa-light-chain-enhancer of activated B cells |
Nrf2 | nuclear factor erythroid 2–related factor 2 |
OA | osteoarthritis |
OC | osteocalcin |
OR | odds ratio |
OS | oxidative stress |
PCOS | polycystic ovary syndrome |
PD | Parkinson’s disease |
PI3K | phosphatidylinositide-3-kinase |
PK | phylloquinone |
RCT | randomized controlled trial |
ROS | reactive oxygen species |
SIRT | sirtuin |
T2D | type 2 diabetes |
TNF-α | tumor necrosis factor-alpha |
tOC | total osteocalcin |
UBIAD1 | UbiA prenyltransferase domain containing 1 |
ucMGP | uncarboxylated matrix Gla protein |
ucOC | undercarboxylated osteocalcin |
VC | vascular calcification |
vitD | vitamin D |
VK | vitamin K |
VKAs | vitamin K antagonists |
VKDP | vitamin K–dependent protein |
References
- Franco, R.; Navarro, G.; Martínez-Pinilla, E. Hormetic and Mitochondria-Related Mechanisms of Antioxidant Action of Phytochemicals. Antioxidants 2019, 8, 373. [Google Scholar] [CrossRef] [Green Version]
- Bjørklund, G.; Chirumbolo, S. Role of oxidative stress and antioxidants in daily nutrition and human health. Nutrition 2017, 33, 311–321. [Google Scholar] [CrossRef] [PubMed]
- Maurya, P.K.; Kumar, P.; Chandra, P. Biomarkers of oxidative stress in erythrocytes as a function of human age. World J. Methodol. 2015, 5, 216–222. [Google Scholar] [CrossRef] [Green Version]
- Rusu, M.E.; Gheldiu, A.-M.; Mocan, A.; Vlase, L.; Popa, D.-S. Anti-aging potential of tree nuts with a focus on phytochemical composition, molecular mechanisms and thermal stability of major bioactive compounds. Food Funct. 2018, 9, 2554–2575. [Google Scholar] [CrossRef] [PubMed]
- Harshman, S.; Shea, M. The Role of Vitamin K in Chronic Aging Diseases: Inflammation, Cardiovascular Disease, and Osteoarthritis. Curr. Nutr. Rep. 2016, 5, 90–98. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Braasch-Turi, M.; Crans, D.C. Synthesis of Naphthoquinone Derivatives: Menaquinones, Lipoquinones and Other Vitamin K Derivatives. Molecules 2020, 25, 4477. [Google Scholar] [CrossRef]
- Schurgers, L.; Vermeer, C. Determination of phylloquinone and menaquinones in food. Effect of food matrix on circulating vitamin K concentrations. Haemostasis 2000, 30, 298–307. [Google Scholar] [CrossRef] [PubMed]
- Turck, D.; Bresson, J.-L.; Burlingame, B.; Dean, T.; Fairweather-Tait, S.; Heinonen, M.; Hirsch-Ernst, K.I.; Mangelsdorf, I.; McArdle, H.; Naska, A.; et al. Dietary reference values for vitamin K. EFSA J. 2017, 15, e04780. [Google Scholar] [CrossRef]
- Elder, S.J.; Haytowitz, D.B.; Howe, J.; Peterson, J.W.; Booth, S.L. Vitamin K Contents of Meat, Dairy, and Fast Food in the U.S. Diet. J. Agric. Food Chem. 2006, 54, 463–467. [Google Scholar] [CrossRef]
- Melse-Boonstra, A. Bioavailability of Micronutrients from Nutrient-Dense Whole Foods: Zooming in on Dairy, Vegetables, and Fruits. Front. Nutr. 2020, 7, 101. [Google Scholar] [CrossRef] [PubMed]
- Booth, S.L. Vitamin K: Food composition and dietary intakes. Food Nutr. Res. 2012, 56, 5505. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Margier, M.; Antoine, T.; Siriaco, A.; Nowicki, M.; Halimi, C.; Maillot, M.; Georgé, S.; Reboul, E. The Presence of Pulses within a Meal can Alter Fat-Soluble Vitamin Bioavailability. Mol. Nutr. Food Res. 2019, 63, e1801323. [Google Scholar] [CrossRef] [Green Version]
- Halder, M.; Petsophonsakul, P.; Akbulut, A.C.; Pavlic, A.; Bohan, F.; Anderson, E.; Maresz, K.; Kramann, R.; Schurgers, L. Vitamin K: Double Bonds beyond Coagulation Insights into Differences between Vitamin K1 and K2 in Health and Disease. Int. J. Mol. Sci. 2019, 20, 896. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wei, F.-F.; Trenson, S.; Verhamme, P.; Vermeer, C.; Staessen, J.A. Vitamin K-Dependent Matrix Gla Protein as Multifaceted Protector of Vascular and Tissue Integrity. Hypertension 2019, 73, 1160–1169. [Google Scholar] [CrossRef]
- Gröber, U.; Reichrath, J.; Holick, M.F.; Kisters, K. Vitamin K: An old vitamin in a new perspective. Dermato Endocrinol. 2015, 6, e968490. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bender, D.; Vitamin, K. Nutritional Biochemistry of the Vitamins; Cambridge University Press: Cambridge, UK, 2003; pp. 131–147. ISBN 9780521803885. [Google Scholar]
- Simes, D.; Viegas, C.; Araújo, N.; Marreiros, C. Vitamin K as a Diet Supplement with Impact in Human Health: Current Evidence in Age-Related Diseases. Nutrients 2020, 12, 138. [Google Scholar] [CrossRef] [Green Version]
- Li, J.; Lin, J.C.; Wang, H.; Peterson, J.W.; Furie, B.C.; Furie, B.; Booth, S.L.; Volpe, J.J.; Rosenberg, P.A. Novel Role ofVitamin K in Preventing Oxidative Injury to Developing Oligodendrocytes and Neurons. J. Neurosci. 2003, 23, 5816–5826. [Google Scholar] [CrossRef] [Green Version]
- Sinbad, O.O.; Folorunsho, A.A.; Olabisi, O.L.; Ayoola, A.O.; Temitope, J. Vitamins as Antioxidants. J. Food Sci. Nutr. Res. 2019, 2, 214–235. [Google Scholar] [CrossRef]
- Rusu, M.E.; Simedrea, R.; Gheldiu, A.-M.; Mocan, A.; Vlase, L.; Popa, D.-S.; Ferreira, I.C.F.R. Benefits of tree nut consumption on aging and age-related diseases: Mechanisms of actions. Trends Food Sci. Technol. 2019, 88, 104–120. [Google Scholar] [CrossRef]
- Fusaro, M.; Gallieni, M.; Rizzo, M.A.; Stucchi, A.; Delanaye, P.; Cavalier, E.; Moysés, R.M.A.; Jorgetti, V.; Iervasi, G.; Giannini, S.; et al. Vitamin K plasma levels determination in human health. Clin. Chem. Lab. Med. 2017, 55, 789–799. [Google Scholar] [CrossRef] [PubMed]
- DiNicolantonio, J.J.; Bhutani, J.; O’Keefe, J.H. The health benefits of vitamin K. Open Hear 2015, 2, e000300. [Google Scholar] [CrossRef]
- Akbulut, A.; Pavlic, A.; Petsophonsakul, P.; Halder, M.; Maresz, K.; Kramann, R.; Schurgers, L. Vitamin K2 Needs an RDI Separate from Vitamin K1. Nutrients 2020, 12, 1852. [Google Scholar] [CrossRef] [PubMed]
- Louka, M.; Fawzy, A.; Naiem, A.; Elseknedy, M.; Abdelhalim, A.; Abdelghany, M. Vitamin D and K signaling pathways in hepatocellular carcinoma. Gene 2017, 629, 108–116. [Google Scholar] [CrossRef]
- Kim, Y.; Keogh, J.; Clifton, P. Benefits of nut consumption on insulin resistance and cardiovascular risk factors: Multiple potential mechanisms of actions. Nutrients 2017, 9, 1271. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Paul, C.I.; Vitamin, K. Textbook of Natural Medicine, 5th ed.; Pizzorno, J.E., Murray, M.T., Eds.; Churchill Livingstone: St. Louis, MO, USA, 2020; pp. 919–947.e5. ISBN 978-0-323-52342-4. [Google Scholar]
- Vermeer, C.; Raes, J.; van’t Hoofd, C.; Knapen, M.H.J.; Xanthoulea, S. Menaquinone Content of Cheese. Nutrients 2018, 10, 446. [Google Scholar] [CrossRef] [Green Version]
- Ferland, G. Vitamin K and brain function. Semin Thromb Hemost. 2013, 39, 849–855. [Google Scholar] [CrossRef]
- Beulens, J.W.J.; Booth, S.L.; van den Heuvel, E.G.; Stoecklin, E.; Baka, A.; Vermeer, C. The role of menaquinones (vitamin K₂) in human health. Br. J. Nutr. 2013, 110, 1357–1368. [Google Scholar] [CrossRef] [Green Version]
- Ferland, G.; Vitamin, K. An emerging nutrient in brain function. Biofactors 2012, 38, 151–157. [Google Scholar] [CrossRef] [PubMed]
- Thijssen, H.; Drittij-Reijnders, M. Vitamin K status in human tissues: Tissue-specific accumulation of phylloquinone and menaquinone-4. Br. J. Nutr. 1996, 75, 121–127. [Google Scholar] [CrossRef]
- Sato, T.; Inaba, N.; Yamashita, T. MK-7 and Its Effects on Bone Quality and Strength. Nutrients 2020, 12, 965. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vermeer, C. Vitamin K: The effect on health beyond coagulation—An overview. Food Nutr. Res. 2012, 56. [Google Scholar] [CrossRef]
- Schwalfenberg, G.K. Vitamins K1 and K2: The Emerging Group of Vitamins Required for Human Health. J. Nutr. Metab. 2017, 2017, 6254836. [Google Scholar] [CrossRef]
- Ravishankar, B.; Dound, Y.A.; Mehta, D.S.; Ashok, B.K.; de Souza, A.; Pan, M.-H.; Ho, C.-T.; Badmaev, V.; Vaidya, A.D.B. Safety assessment of menaquinone-7 for use in human Nutrition. J. Food Drug Anal. 2015, 23, 99–108. [Google Scholar] [CrossRef] [Green Version]
- Huang, Z.; Wan, S.; Lu, Y.; Ning, L.; Liu, C.; Fan, S. Does vitamin K2 play a role in the prevention and treatment of osteoporosis for postmenopausal women: A meta-analysis of randomized controlled trials. Osteoporos Int. 2015, 26, 1175–1186. [Google Scholar] [CrossRef] [PubMed]
- Kirk, B.; Feehan, J.; Lombardi, G.; Duque, G. Muscle, Bone, and Fat Crosstalk: The Biological Role of Myokines, Osteokines, and Adipokines. Curr. Osteoporos Rep. 2020, 18, 388–400. [Google Scholar] [CrossRef] [PubMed]
- Hill, H.S.; Grams, J.; Walton, R.G.; Liu, J.; Moellering, D.R.; Garvey, W.T. Carboxylated and uncarboxylated forms of osteocalcin directly modulate the glucose transport system and inflammation in adipocytes. Horm. Metab. Res. 2014, 46, 341–347. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mohammad Rahimi, G.R.; Niyazi, A.; Alaee, S. The effect of exercise training on osteocalcin, adipocytokines, and insulin resistance: A systematic review and meta-analysis of randomized controlled trials. Osteoporos Int. 2021, 32, 213–224. [Google Scholar] [CrossRef]
- Tsugawa, N.; Shiraki, M. Vitamin K Nutrition and Bone Health. Nutrients 2020, 12, 1909. [Google Scholar] [CrossRef]
- Binkley, N.C.; Krueger, D.C.; Kawahara, T.N.; Engelke, J.A.; Chappell, R.J.; Suttie, J.W. A high phylloquinone intake is required to achieve maximal osteocalcin gamma-carboxylation. Am. J. Clin. Nutr. 2002, 76, 1055–1060. [Google Scholar] [CrossRef]
- Lin, X.; Brennan-Speranza, T.C.; Levinger, I.; Yeap, B.B. Undercarboxylated Osteocalcin: Experimental and Human Evidence for a Role in Glucose Homeostasis and Muscle Regulation of Insulin Sensitivity. Nutrients 2018, 10, 847. [Google Scholar] [CrossRef] [Green Version]
- Fusaro, M.; Cianciolo, G.; Brandi, M.L.; Ferrari, S.; Nickolas, T.L.; Tripepi, G.; Plebani, M.; Zaninotto, M.; Iervasi, G.; La Manna, G.; et al. Vitamin K and Osteoporosis. Nutrients 2020, 12, 3625. [Google Scholar] [CrossRef]
- Shiraki, M.; Shiraki, Y.; Aoki, C.; Miura, M. Vitamin K2 (menatetrenone) effectively prevents fractuRes. and sustains lumbar bone mineral density in osteoporosis. J. Bone Min. Res. 2000, 15, 515–521. [Google Scholar] [CrossRef] [PubMed]
- Bolton-Smith, C.; McMurdo, M.E.; Paterson, C.R.; Mole, P.A.; Harvey, J.M.; Fenton, S.T.; Prynne, C.J.; Mishra, G.D.; Shearer, M.J. Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women. J. Bone Min. Res. 2007, 22, 509–519. [Google Scholar] [CrossRef]
- Binkley, N.; Harke, J.; Krueger, D.; Engelke, J.; Vallarta-Ast, N.; Gemar, D.; Checovich, M.; Chappell, R.; Suttie, J. Vitamin K Treatment Reduces Undercarboxylated Osteocalcin but Does Not Alter Bone Turnover, Density, or Geometry in Healthy Postmenopausal North American Women. J. Bone Min. Res. 2009, 24, 983–991. [Google Scholar] [CrossRef] [PubMed]
- Rønn, S.; Harsløf, T.; Pedersen, S.; Langdahl, B. Vitamin K2 (menaquinone-7) prevents age-related deterioration of trabecular bone microarchitecture at the tibia in postmenopausal women. Eur. J. Endocrinol. 2016, 175, 541–549. [Google Scholar] [CrossRef] [Green Version]
- Iwamoto, J.; Takeda, T.; Ichimura, S. Effect of menatetrenone on bone mineral density and incidence of vertebral fractuRes. in postmenopausal women with osteoporosis: A comparison with the effect of etidronate. J. Orthop. Sci. 2001, 6, 487–492. [Google Scholar] [CrossRef]
- Purwosunu, Y.; Muharram; Rachman, I.A.; Reksoprodjo, S.; Sekizawa, A. Vitamin K 2 treatment for postmenopausal osteoporosis in Indonesia. J. Obs. Gynaecol. Res. 2006, 32, 230–234. [Google Scholar] [CrossRef]
- Knapen, M.; Schurgers, L.; Vermeer, C. Vitamin K 2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporos Int. 2007, 18, 963–972. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Booth, S.L.; Dallal, G.; Shea, M.K.; Gundberg, C.; Peterson, J.W.; Dawson-Hughes, B. Effect of Vitamin K Supplementation on Bone Loss in Elderly Men and Women. J. Clin. Endocrinol. Metab. 2008, 93, 1217–1223. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cheung, A.M.; Tile, L.; Lee, Y.; Tomlinson, G.; Hawker, G.; Scher, J.; Hu, H.; Vieth, R.; Thompson, L.; Jamal, S.; et al. Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): A randomized controlled trial. PLoS Med. 2008, 5, e196. [Google Scholar] [CrossRef]
- Hirao, M.; Hashimoto, J.; Ando, W.; Ono, T.; Yoshikawa, H. Response of serum carboxylated and undercarboxylated osteocalcin to alendronate monotherapy and combined therapy with vitamin K2 in postmenopausal women. J. Bone Min. Metab. 2008, 26, 260–264. [Google Scholar] [CrossRef]
- Tsugawa, N.; Shiraki, M.; Suhara, Y.; Kamao, M.; Ozaki, R.; Tanaka, K.; Okano, T. Low plasma phylloquinone concentration is associated with high incidence of vertebral fracture in Japanese women. J. Bone Min. Metab. 2008, 26, 79–85. [Google Scholar] [CrossRef]
- Yamauchi, M.; Yamaguchi, T.; Nawata, K.; Takaoka, S.; Sugimoto, T. Relationships between undercarboxylated osteocalcin and vitamin K intakes, bone turnover, and bone mineral density in healthy women. Clin. Nutr. 2010, 29, 761–765. [Google Scholar] [CrossRef]
- Je, S.H.; Joo, N.-S.; Choi, B.-H.; Kim, K.-M.; Kim, B.-T.; Park, S.-B.; Cho, D.-Y.; Kim, K.-N.; Lee, D.-J. Vitamin K Supplement Along with Vitamin D and Calcium Reduced Serum Concentration of Undercarboxylated Osteocalcin While Increasing Bone Mineral Density in Korean Postmenopausal Women over Sixty-Years-Old. J. Korean Med. Sci. 2011, 26, 1093–1098. [Google Scholar] [CrossRef]
- Kanellakis, S.; Moschonis, G.; Tenta, R.; Schaafsma, A.; van den Heuvel, E.; Papaioannou, N.; Lyritis, G.; Manios, Y. Changes in parameters of bone metabolism in postmenopausal women following a 12-month intervention period using dairy products enriched with calcium, vitamin D, and phylloquinone (vitamin K(1)) or menaquinone-7 (vitamin K (2)): The Postmenopausal Health Study II. Calcif. Tissue Int. 2012, 90, 251–262. [Google Scholar] [CrossRef]
- Knapen, M.; Drummen, N.; Smit, E.; Vermeer, C.; Theuwissen, E. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporos Int. 2013, 24, 2499–2507. [Google Scholar] [CrossRef] [PubMed]
- Jiang, Y.; Zhang, Z.-L.; Zhang, Z.-L.; Zhu, H.-M.; Wu, Y.-Y.; Cheng, Q.; Wu, F.-L.; Xing, X.-P.; Liu, J.-L.; Yu, W.; et al. Menatetrenone versus alfacalcidol in the treatment of Chinese postmenopausal women with osteoporosis: A multicenter, randomized, double-blinded, double-dummy, positive drug-controlled clinical trial. Clin. Interv. Aging 2014, 9, 121–127. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bultynck, C.; Munim, N.; Harrington, D.; Judd, L.; Ataklte, F.; Shah, Z.; Dockery, F. Prevalence of vitamin K deficiency in older people with hip fracture. Acta Clin. Belg. 2020, 75, 136–140. [Google Scholar] [CrossRef] [PubMed]
- Moore, A.E.; Kim, E.; Dulnoan, D.; Dolan, A.L.; Voong, K.; Ahmad, I.; Gorska, R.; Harrington, D.J.; Hampson, G. Serum vitamin K 1 (phylloquinone) is associated with fracture risk and hip strength in post-menopausal osteoporosis: A cross-sectional study. Bone 2020, 141, 115630. [Google Scholar] [CrossRef]
- Sim, M.; Lewis, J.R.; Prince, R.L.; Levinger, I.; Brennan-Speranza, T.C.; Palmer, C.; Bondonno, C.P.; Bondonno, N.P.; Devine, A.; Ward, N.C.; et al. The effects of vitamin K-rich green leafy vegetables on bone metabolism: A 4-week randomised controlled trial in middle-aged and older individuals. Bone Rep. 2020, 12, 100274. [Google Scholar] [CrossRef]
- Hooshmand, S.; Kern, M.; Metti, D.; Shamloufard, P.; Chai, S.C.; Johnson, S.A.; Payton, M.E.; Arjmandi, B.H. The effect of two doses of dried plum on bone density and bone biomarkers in osteopenic postmenopausal women: A randomized, controlled trial. Osteoporos Int. 2016, 27, 2271–2279. [Google Scholar] [CrossRef]
- Higgs, J.; Derbyshire, E.; Styles, K. Nutrition and osteoporosis prevention for the orthopaedic surgeon: A wholefoods approach. EFORT Open Rev. 2017, 2, 300–308. [Google Scholar] [CrossRef]
- Emaus, N.; Gjesdal, C.G.; Almås, B.; Christensen, M.; Grimsgaard, A.; Berntsen, G.; Salomonsen, L.; Fønnebø, V. Vitamin K2 supplementation does not influence bone loss in early menopausal women: A randomised double-blind placebo-controlled trial. Osteoporos Int. 2010, 21, 1731–1740. [Google Scholar] [CrossRef] [PubMed]
- Feskanich, D.; Weber, P.; Willett, W.C.; Rockett, H.; Booth, S.L.; Colditz, G.A. Vitamin K intake and hip fractuRes. in women: A prospective study. Am. J. Clin. Nutr. 1999, 69, 74–79. [Google Scholar] [CrossRef] [Green Version]
- Popa, D.-S.; Rusu, M.E. Isoflavones: Vegetable Sources, Biological Activity, and Analytical Methods for Their Assessment. In Superfood and Functional Food—The Development of Superfoods and Their Roles as Medicine; Shiomi, N., Waisundara, V., Eds.; InTech: London, UK, 2017; ISBN 978-953-51-2942-4. [Google Scholar] [CrossRef] [Green Version]
- Lappe, J.; Kunz, I.; Bendik, I.; Prudence, K.; Weber, P.; Recker, R.; Heaney, R.P. Effect of a combination of genistein, polyunsaturated fatty acids and vitamins D3 and K1 on bone mineral density in postmenopausal women: A randomized, placebo-controlled, double-blind pilot study. Eur. J. Nutr. 2013, 52, 203–215. [Google Scholar] [CrossRef] [Green Version]
- Capozzi, A.; Scambia, G.; Lello, S. Calcium, vitamin D, vitamin K2, and magnesium supplementation and skeletal health. Maturitas 2020, 140, 55–63. [Google Scholar] [CrossRef]
- Goddek, S. Vitamin D3 and K2 and their potential contribution to reducing the COVID-19 mortality rate. Int. J. Infect. Dis. 2020, 99, 286–290. [Google Scholar] [CrossRef] [PubMed]
- Schröder, M.; Riksen, E.A.; He, J.; Skallerud, B.H.; Møller, M.E.; Lian, A.; Syversen, U.; Reseland, J.E. Vitamin K2 Modulates Vitamin D-Induced Mechanical Properties of Human 3D Bone Spheroids In Vitro. JBMR Plus 2020, 4, e10394. [Google Scholar] [CrossRef]
- Braam, L.; Knapen, M.; Geusens, P.; Brouns, F.; Hamulyák, K.; Gerichhausen, M.; Vermeer, C. Vitamin K1 Supplementation Retards Bone Loss in Postmenopausal Women Between 50 and 60 Years of Age. Calcif. Tissue Int. 2003, 73, 21–26. [Google Scholar] [CrossRef] [PubMed]
- Inoue, T.; Fujita, T.; Kishimoto, H.; Makino, T.; Nakamura, T.; Nakamura, T.; Sato, T.; Yamazaki, K. Randomized controlled study on the prevention of osteoporotic fractuRes. (OF study): A phase IV clinical study of 15-mg menatetrenone capsules. J. Bone Min. Metab. 2009, 27, 66–75. [Google Scholar] [CrossRef]
- Cockayne, S.; Adamson, J.; Lanham-New, S.; Shearer, M.J.; Gilbody, S.; Torgerson, D.J. Vitamin K and the Prevention of Fractures. Arch Int. Med. 2006, 166, 1256–1261. [Google Scholar] [CrossRef] [PubMed]
- Yamaguchi, M.; Weitzmann, M.N. Vitamin K2 stimulates osteoblastogenesis and suppresses osteoclastogenesis by suppressing NF-κB activation. Int. J. Mol. Med. 2011, 27, 3–14. [Google Scholar] [CrossRef] [Green Version]
- Falcone, T.D.; Kim, S.S.W.; Cortazzo, M.H. Vitamin K: Fracture Prevention and Beyond. PM&R 2011, 3, S82–S87. [Google Scholar] [CrossRef]
- Liang, J.; Lian, S.; Qian, X.; Wang, N.; Huang, H.; Yao, J.; Tang, K.; Chen, L.; Li, L.; Lin, W.; et al. Association Between Bone Mineral Density and Pancreatic β-Cell Function in Elderly Men and Postmenopausal Women. J. Endocr. Soc. 2017, 1, 1085–1094. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Azuma, K.; Inoue, S. Multiple Modes of Vitamin K Actions in Aging-Related Musculoskeletal Disorders. Int. J. Mol. Sci. 2019, 20, 2844. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shea, M.K.; Kritchevsky, S.B.; Hsu, F.-C.; Nevitt, M.; Booth, S.L.; Kwoh, C.K.; McAlindon, T.E.; Vermeer, C.; Drummen, N.; Harris, T.B.; et al. The association between vitamin K status and knee osteoarthritis featuRes. in older adults: The Health, Aging and Body Composition Study. Osteoarthr. Cart. 2015, 23, 370–378. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chin, K.-Y. The Relationship between Vitamin K and Osteoarthritis: A Review of Current Evidence. Nutrients 2020, 12, 1208. [Google Scholar] [CrossRef]
- Mozos, I.; Stoian, D.; Luca, C.T. Crosstalk between Vitamins A, B12, D, K, C, and E Status and Arterial Stiffness. Dis. Markers. 2017, 2017, 8784971. [Google Scholar] [CrossRef]
- Jaminon, A.M.G.; Dai, L.; Qureshi, A.R.; Evenepoel, P.; Ripsweden, J.; Söderberg, M.; Witasp, A.; Olauson, H.; Schurgers, L.J.; Stenvinkel, P. Matrix Gla protein is an independent predictor of both intimal and meDial. vascular calcification in chronic kidney disease. Sci. Rep. 2020, 10, 6586. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shioi, A.; Morioka, T.; Shoji, T.; Emoto, M. The Inhibitory Roles of Vitamin K in Progression of Vascular Calcification. Nutrients 2020, 12, 583. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dai, L.; Schurgers, L.J.; Shiels, P.G.; Stenvinkel, P. Early vascular ageing in chronic kidney disease: Impact of inflammation, vitamin K, senescence and genomic damage. Nephrol. Dial. Transplant. 2020, 35, ii31–ii37. [Google Scholar] [CrossRef] [Green Version]
- Simes, D.C.; Viegas, C.S.B.; Araújo, N.; Marreiros, C. Vitamin K as a Powerful Micronutrient in Aging and Age-Related Diseases: Pros and Cons from Clinical Studies. Int. J. Mol. Sci. 2019, 20, 4150. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cozzolino, M.; Fusaro, M.; Ciceri, P.; Gasperoni, L.; Cianciolo, G. The Role of Vitamin K in Vascular Calcification. Adv. Chronic Kidney Dis. 2019, 26, 437–444. [Google Scholar] [CrossRef] [PubMed]
- Dofferhoff, A.S.M.; Piscaer, I.; Schurgers, L.J.; Visser, M.P.J.; van den Ouweland, J.; de Jong, P.; Gosens, R.; Hackeng, T.; van Daal, H.; Lux, P.; et al. Reduced vitamin K status as a potentially modifiable risk factor of severe COVID-19. Clin. Infect. Dis. 2020, ciaa1258. [Google Scholar] [CrossRef] [PubMed]
- Roumeliotis, S.; Dounousi, E.; Salmas, M.; Eleftheriadis, T.; Liakopoulos, V. Vascular Calcification in Chronic Kidney Disease: The Role of Vitamin K- Dependent Matrix Gla Protein. Front. Med. 2020, 7, 154. [Google Scholar] [CrossRef]
- Shea, M.K.; Booth, S.L. Vitamin K, Vascular Calcification, and Chronic Kidney Disease: Current Evidence and Unanswered Questions. Curr. Dev. Nutr. 2019, 3, nzz077. [Google Scholar] [CrossRef]
- Geleijnse, J.M.; Vermeer, C.; Grobbee, D.E.; Schurgers, L.J.; Knapen, M.H.J.; van der Meer, I.M.; Hofman, A.; Witteman, J.C.M. Dietary Intake of Menaquinone Is Associated with a Reduced Risk of Coronary Heart Disease: The Rotterd. Am. Study J. Nutr. 2004, 134, 3100–3105. [Google Scholar] [CrossRef] [PubMed]
- Gast, G.C.M.; De Roos, N.M.; Sluijs, I.; Bots, M.L.; Beulens, J.W.J.; Geleijnse, J.M.; Witteman, J.C.; Grobbee, D.E.; Peeters, P.H.M.; Van Der Schouw, Y.T. A high menaquinone intake reduces the incidence of coronary heart disease. Nutr. Metab. Cardiovasc. Dis. 2009, 19, 504–510. [Google Scholar] [CrossRef]
- Shea, M.K.; O’Donnell, C.J.; Hoffmann, U.; Dallal, G.E.; Dawson-Hughes, B.; Ordovas, J.; Price, P.A.; Williamson, M.K.; Booth, S.L. Vitamin K supplementation and progression of coronary artery calcium in older men and women. Am. J. Clin. Nutr. 2009, 89, 1799–1807. [Google Scholar] [CrossRef]
- Schurgers, L.J.; Barreto, D.V.; Barreto, F.C.; Liabeuf, S.; Renard, C.; Magdeleyns, E.; Vermeer, C.; Choukroun, G.; Massy, Z. The circulating inactive form of matrix gla protein is a surrogate marker for vascular calcification in chronic kidney disease: A preliminary report. Clin. J. Am. Soc. Nephrol. 2010, 5, 568–575. [Google Scholar] [CrossRef] [Green Version]
- Ueland, T.; Gullestad, L.; Dahl, C.P.; Aukrust, P.; Aakhus, S.; Solberg, O.G.; Vermeer, C.; Schurgers, L.J. Undercarboxylated matrix Gla protein is associated with indices of heart failure and mortality in symptomatic aortic stenosis. J. Int. Med. 2010, 268, 483–492. [Google Scholar] [CrossRef] [PubMed]
- Schlieper, G.; Westenfeld, R.; Krüger, T.; Cranenburg, E.C.; Magdeleyns, E.J.; Brandenburg, V.M.; Djuric, Z.; Damjanovic, T.; Ketteler, M.; Vermeer, C.; et al. Circulating Nonphosphorylated Carboxylated Matrix Gla Protein Predicts Survival in ESRD. J. Am. Soc. Nephrol. 2011, 22, 387–395. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ueland, T.; Dahl, P.; Gullestad, L.; Aakhus, S.; Broch, K.; Skårdal, R.; Vermeer, C.; Aukrust, P.; Schurgers, L. Circulating levels of non-phosphorylated undercarboxylated matrix Gla protein are associated with disease severity in patients with chronic heart failure. Clin. Sci. (Lond.) 2011, 121, 119–127. [Google Scholar] [CrossRef] [Green Version]
- Westenfeld, R.; Krueger, T.; Schlieper, G.; Cranenburg, E.C.M.; Magdeleyns, E.J.; Heidenreich, S.; Holzmann, S.; Vermeer, C.; Jahnen-Dechent, W.; Ketteler, M.; et al. Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: A randomized trial. Am. J. Kidney Dis. 2012, 59, 186–195. [Google Scholar] [CrossRef] [PubMed]
- Dalmeijer, G.W.; van der Schouw, Y.T.; Magdeleyns, E.; Ahmed, N.; Vermeer, C.; Beulens, J.W.J. The effect of menaquinone-7 supplementation on circulating species of matrix Gla protein. Atherosclerosis 2012, 225, 397–402. [Google Scholar] [CrossRef]
- Van Den Heuvel, E.G.H.M.; Van Schoor, N.M.; Lips, P.; Magdeleyns, E.J.P.; Deeg, D.J.H.; Vermeer, C.; Den Heijer, M. Circulating uncarboxylated matrix Gla protein, a marker of vitamin K status, as a risk factor of cardiovascular disease. Maturitas 2014, 77, 137–141. [Google Scholar] [CrossRef]
- Caluwé, R.; Vandecasteele, S.; Van Vlem, B.; Vermeer, C.; De Vriese, A.S. Vitamin K2 supplementation in haemodialysis patients: A randomized dose-finding study. Nephrol. Dial. Transplant. 2014, 29, 1385–1390. [Google Scholar] [CrossRef] [PubMed]
- Liabeuf, S.; Bourron, O.; Vemeer, C.; Theuwissen, E.; Magdeleyns, E.; Aubert, C.E.; Brazier, M.; Mentaverri, R.; Hartemann, A.; Massy, Z.A. Vascular calcification in patients with type 2 diabetes: The involvement of matrix Gla protein. Cardiovasc. Diabetol. 2014, 13, 85. [Google Scholar] [CrossRef] [Green Version]
- Cheung, C.-L.; Sahni, S.; Cheung, B.M.Y.; Sing, C.-W.; Wong, I.C.K. Vitamin K intake and mortality in people with chronic kidney disease from NHANES III. Clin. Nutr. 2015, 34, 235–240. [Google Scholar] [CrossRef]
- Knapen, M.H.J.; Braam, L.A.J.L.M.; Drummen, N.E.; Bekers, O.; Hoeks, A.P.G.; Vermeer, C. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. Thromb. Haemost. 2015, 113, 1135–1144. [Google Scholar] [CrossRef]
- Kurnatowska, I.; Grzelak, P.; Masajtis-Zagajewska, A.; Kaczmarska, M.; Stefańczyk, L.; Vermeer, C.; Maresz, K.; Nowicki, M. Effect of vitamin K2 on progression of atherosclerosis and vascular calcification in nondialyzed patients with chronic kidney disease stages 3-5. Pol. Arch. Med. Wewn. 2015, 125, 631–640. [Google Scholar] [CrossRef]
- Asemi, Z.; Raygan, F.; Bahmani, F.; Rezavandi, Z.; Talari, H.R.; Rafiee, M.; Poladchang, S.; Mofrad, M.D.; Taheri, S.; Mohammadi, A.A.; et al. The effects of vitamin D, K and calcium co-supplementation on carotid intima-media thickness and metabolic status in overweight type 2 diabetic patients with CHD. Br. J. Nutr. 2016, 116, 286–293. [Google Scholar] [CrossRef] [Green Version]
- Fulton, R.L.; McMurdo, M.E.T.; Hill, A.; Abboud, R.J.; Arnold, G.P.; Struthers, A.D.; Khan, F.; Vermeer, C.; Knappen, M.H.J.; Drummen, N.E.A.; et al. Effect of Vitamin K on Vascular Health and Physical Function in Older People with Vascular DiseaseA Randomised Controlled Trial. J. Nutr. Heal Aging 2016, 20, 325–333. [Google Scholar] [CrossRef]
- Kurnatowska, I.; Grzelak, P.; Masajtis-Zagajewska, A.; Kaczmarska, M.; Stefańczyk, L.; Vermeer, C.; Maresz, K.; Nowicki, M. Plasma Desphospho-Uncarboxylated Matrix Gla Protein as a Marker of Kidney Damage and Cardiovascular Risk in Advanced Stage of Chronic Kidney Disease. Kidney Blood Press Res. 2016, 41, 231–239. [Google Scholar] [CrossRef] [PubMed]
- Sardana, M.; Vasim, I.; Varakantam, S.; Kewan, U.; Tariq, A.; Koppula, M.R.; Syed, A.A.; Beraun, M.; Drummen, N.E.A.; Vermeer, C.; et al. Inactive Matrix Gla-Protein and Arterial Stiffness in Type 2 Diabetes Mellitus. Am. J. Hypertens. 2016, 30, 196–201. [Google Scholar] [CrossRef]
- Aoun, M.; Makki, M.; Azar, H.; Matta, H.; Chelala, D.N. High Dephosphorylated-Uncarboxylated MGP in Hemodialysis patients: Risk factors and response to vitamin K2, A pre-post intervention clinical trial. BMC Nephrol. 2017, 18, 191. [Google Scholar] [CrossRef]
- Brandenburg, V.; Reinartz, S.; Kaesler, N.; Krüger, T.; Dirrichs, T.; Kramann, R.; Peeters, F.; Floege, J.; Keszei, A.; Marx, N.; et al. Slower Progress of Aortic Valve Calcification With Vitamin K Supplementation: Results From a Prospective Interventional Proof-of-Concept Study. Circulation 2017, 135, 2081–2084. [Google Scholar] [CrossRef]
- Shea, M.K.; Booth, S.L.; Weiner, D.E.; Brinkley, T.E.; Kanaya, A.M.; Murphy, R.A.; Simonsick, E.M.; Wassel, C.L.; Vermeer, C.; Kritchevsky, S.B. Circulating Vitamin K Is Inversely Associated with Incident Cardiovascular Disease Risk among Those Treated for Hypertension in the Health, Aging, and Body Composition Study (Health ABC). J. Nutr. 2017, 147, 888–895. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Puzantian, H.; Akers, S.R.; Oldland, G.; Javaid, K.; Miller, R.; Ge, Y.; Ansari, B.; Lee, J.; Suri, A.; Hasmath, Z.; et al. Circulating Dephospho-Uncarboxylated Matrix Gla-Protein Is Associated With Kidney Dysfunction and Arterial Stiffness. Am. J. Hypertens. 2018, 31, 988–994. [Google Scholar] [CrossRef] [PubMed]
- Dal Canto, E.; Beulens, J.W.J.; Elders, P.; Rutters, F.; Stehouwer, C.D.A.; Van Der Heijden, A.A.; Van Ballegooijen, A.J. The Association of Vitamin D and Vitamin K Status with Subclinical MeasuRes. of Cardiovascular Health and All-Cause Mortality in Older Adults: The Hoorn Study. J. Nutr. 2020, 150, 3171–3179. [Google Scholar] [CrossRef]
- Roumeliotis, S.; Roumeliotis, A.; Stamou, A.; Leivaditis, K.; Kantartzi, K.; Panagoutsos, S.; Liakopoulos, V. The Association of dp-ucMGP with Cardiovascular Morbidity and Decreased Renal Function in Diabetic Chronic Kidney Disease. Int. J. Mol. Sci. 2020, 21, 6035. [Google Scholar] [CrossRef]
- Shea, M.K.; Barger, K.; Booth, S.L.; Matuszek, G.; Cushman, M.; Benjamin, E.J.; Kritchevsky, S.B.; Weiner, D.E. Vitamin K status, cardiovascular disease, and all-cause mortality: A participant-level meta-analysis of 3 US cohorts. Am. J. Clin. Nutr. 2020, 111, 1170–1177. [Google Scholar] [CrossRef]
- Wessinger, C.; Hafer-Macko, C.; Ryan, A.S. Vitamin K Intake in Chronic Stroke: Implications for Dietary Recommendations. Nutrients 2020, 12, 3059. [Google Scholar] [CrossRef] [PubMed]
- Haugsgjerd, T.R.; Egeland, G.M.; Nygård, O.K.; Vinknes, K.J.; Sulo, G.; Lysne, V.; Igland, J.; Tell, G.S. Association of dietary vitamin K and risk of coronary heart disease in middle-age adults: The Hordaland Health Study Cohort. BMJ Open 2020, 10, e035953. [Google Scholar] [CrossRef] [PubMed]
- Caluwé, R.; Verbeke, F.; De Vriese, A.S. Evaluation of vitamin K status and rationale for vitamin K supplementation in dialysis patients. Nephrol. Dial. Transplant. 2020, 35, 23–33. [Google Scholar] [CrossRef]
- Liu, Y.-P.; Gu, Y.-M.; Thijs, L.; Knapen, M.H.J.; Salvi, E.; Citterio, L.; Petit, T.; Carpini, S.D.; Zhang, Z.; Jacobs, L.; et al. Inactive Matrix Gla Protein Is Causally Related to Adverse Health Outcomes: A Mendelian Randomization Study in a Flemish Population. Hypertension 2015, 65, 463–470. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fusaro, M.; D’Alessandro, C.; Noale, M.; Tripepi, G.; Plebani, M.; Veronese, N.; Iervasi, G.; Giannini, S.; Rossini, M.; Tarroni, G.; et al. Low vitamin K1 intake in haemodialysis patients. Clin. Nutr. 2017, 36, 601–607. [Google Scholar] [CrossRef]
- Riphagen, I.J.; Keyzer, C.A.; Drummen, N.E.A.; de Borst, M.H.; Beulens, J.W.J.; Gansevoort, R.T.; Geleijnse, J.M.; Muskiet, F.A.J.; Navis, G.; Visser, S.T.; et al. Prevalence and Effects of Functional Vitamin K Insufficiency: The PREVEND Study. Nutrients 2017, 9, 1334. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, S.; Guo, L.; Bu, C. Vitamin K status and cardiovascular events or mortality: A meta-analysis. Eur. J. Prev. Cardiol. 2019, 26, 549–553. [Google Scholar] [CrossRef] [PubMed]
- Chen, H.; Sheng, L.; Zhang, Y.; Cao, A.; Lai, Y.; Kunutsor, S.; Jiang, L.; Pan, A. Association of vitamin K with cardiovascular events and all-cause mortality: A systematic review and meta-analysis. Eur. J. Nutr. 2019, 58, 2195–2205. [Google Scholar] [CrossRef]
- Al-Suhaimi, E.; Al-Jafary, M. Endocrine roles of vitamin K-dependent- osteocalcin in the relation between bone metabolism and metabolic disorders. Rev. Endocr Metab. Disord. 2020, 21, 117–125. [Google Scholar] [CrossRef]
- Lacombe, J.; Al Rifai, O.; Loter, L.; Moran, T.; Turcotte, A.; Grenier-Larouche, T.; Tchernof, A.; Biertho, L.; Carpentier, A.; Prud’homme, D.; et al. Measurement of bioactive osteocalcin in humans using a novel immunoassay reveals association with glucose metabolism and β-cell function. Am. J. Physiol Endocrinol. Metab. 2020, 318, E381–E391. [Google Scholar] [CrossRef] [PubMed]
- Ho, H.-J.; Komai, M.; Shirakawa, H. Beneficial Effects of Vitamin K Status on Glycemic Regulation and Diabetes Mellitus: A Mini-Review. Nutrients 2020, 12, 2485. [Google Scholar] [CrossRef]
- Rusu, M.E.; Mocan, A.; Ferreira, I.C.F.R.; Popa, D.-S. Health Benefits of Nut Consumption in Middle-Aged and Elderly Population. Antioxidants 2019, 8, 302. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Salas-Salvadó, J.; Becerra-Tomás, N.; Papandreou, C.; Bulló, M. Dietary Patterns Emphasizing the Consumption of Plant Foods in the Management of Type 2 Diabetes: A Narrative Review. Adv. Nutr. 2019, 10, S320–S331. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Im, J.-A.; Yu, B.-P.; Jeon, J.Y.; Kim, S.-H. Relationship between osteocalcin and glucose metabolism in postmenopausal women. Clin. Chim Acta. 2008, 396, 66–69. [Google Scholar] [CrossRef] [PubMed]
- Yoshida, M.; Booth, S.L.; Meigs, J.B.; Saltzman, E.; Jacques, P.F. Phylloquinone intake, insulin sensitivity, and glycemic status in men and women. Am. J. Clin. Nutr. 2008, 88, 210–215. [Google Scholar] [CrossRef] [Green Version]
- Kanazawa, I.; Yamaguchi, T.; Yamamoto, M.; Yamauchi, M.; Kurioka, S.; Yano, S.; Sugimoto, T. Serum Osteocalcin Level Is Associated with Glucose Metabolism and Atherosclerosis Parameters in Type 2 Diabetes Mellitus. J. Clin. Endocrinol. Metab. 2009, 94, 45–49. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kindblom, J.; Ohlsson, C.; Ljunggren, O.; Karlsson, M.; Tivesten, A.; Smith, U.; Mellström, D. Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men. J. Bone Min. Res. 2009, 24, 785–791. [Google Scholar] [CrossRef]
- Shea, M.K.; Gundberg, C.M.; Meigs, J.B.; Dallal, G.E.; Saltzman, E.; Yoshida, M.; Jacques, P.F.; Booth, S.L. Gamma-carboxylation of osteocalcin and insulin resistance in older men and women. Am. J. Clin. Nutr. 2009, 90, 1230–1235. [Google Scholar] [CrossRef] [Green Version]
- Bao, Y.; Zhou, M.; Lu, Z.; Li, H.; Wang, Y.; Sun, L.; Gao, M.; Wei, M.; Jia, W. Serum levels of osteocalcin are inversely associated with the metabolic syndrome and the severity of coronary artery disease in Chinese men. Clin. Endocrinol. (Oxf.) 2011, 75, 196–201. [Google Scholar] [CrossRef] [PubMed]
- Alfadda, A.A.; Masood, A.; Shaik, S.A.; Dekhil, H.; Goran, M. Association between Osteocalcin, Metabolic Syndrome, and Cardiovascular Risk Factors: Role of Total and Undercarboxylated Osteocalcin in Patients with Type 2 Diabetes Assim. Int. J. Endocrinol. 2013, 2013, 197519. [Google Scholar] [CrossRef] [Green Version]
- Confavreux, C.B.; Szulc, P.; Casey, R.; Varennes, A.; Goudable, J.; Chapurlat, R.D. Lower serum osteocalcin is associated with more severe metabolic syndrome in elderly men from the MINOS cohort. Eur. J. Endocrinol. 2014, 171, 275–283. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shea, M.K.; Dawson-Hughes, B.; Gundberg, C.M.; Booth, S.L. Reducing Undercarboxylated Osteocalcin With Vitamin K Supplementation Does Not Promote Lean Tissue Loss or Fat Gain Over 3 Years in Older Women and Men: A Randomized Controlled Trial. J. Bone Min. Res. 2017, 32, 243–249. [Google Scholar] [CrossRef]
- Knapen, M.H.J.; Jardon, K.M.; Vermeer, C. Vitamin K-induced effects on body fat and weight: Results from a 3-year vitamin K2 intervention study. Eur. J. Clin. Nutr. 2018, 72, 136–141. [Google Scholar] [CrossRef] [PubMed]
- Dumitru, N.; Carsote, M.; Cocolos, A.; Petrova, E.; Olaru, M.; Dumitrache, C.; Ghemigian, A. The Link Between Bone Osteocalcin and Energy Metabolism in a Group of Postmenopausal Women. Curr. Heal Sci. J. 2019, 45, 47–51. [Google Scholar] [CrossRef]
- Guney, G.; Sener-Simsek, B.; Tokmak, A.; Yucel, A.; Buyukkagnici, U.; Yilmaz, N.; Engin-Ustun, Y.; Ozgu-Erdinc, A.S. Assessment of the Relationship between Serum Vitamin D and Osteocalcin Levels with Metabolic Syndrome in Non-Osteoporotic Postmenopausal Women. Geburtshilfe Frauenheilkd. 2019, 79, 293–299. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Aguayo-Ruiz, J.I.; García-Cobián, T.A.; Pascoe-González, S.; Sánchez-Enríquez, S.; Llamas-Covarrubias, I.M.; García-Iglesias, T.; López-Quintero, A.; Llamas-Covarrubias, M.A.; Trujillo-Quiroz, J.; Rivera-Leon, E.A. Effect of supplementation with vitamins D3 and K2 on undercarboxylated osteocalcin and insulin serum levels in patients with type 2 diabetes mellitus: A randomized, double-blind, clinical trial. Diabetol. Metab. Syndr. 2020, 12, 73. [Google Scholar] [CrossRef]
- Jeannin, A.-C.; Salem, J.-E.; Massy, Z.; Aubert, E.C.; Vermeer, C.; Amouyal, C.; Phan, F.; Halbron, M.; Funck-Brentano, C.; Harteman, A.; et al. Inactive matrix gla protein plasma levels are associated with peripheral neuropathy in Type 2 diabetes. PLoS ONE. 2020, 15, e0229145. [Google Scholar] [CrossRef]
- Sakak, F.; Moslehi, N.; Niroomand, M.; Mirmiran, P. Glycemic control improvement in individuals with type 2 diabetes with vitamin K 2 supplementation: A randomized controlled trial. Eur. J. Nutr. 2020. [Google Scholar] [CrossRef]
- Bigman, G. Vitamin D metabolites, D3 and D2, and their independent associations with depression symptoms among adults in the United States. Nutr. Neurosci. 2020, 1–9. [Google Scholar] [CrossRef]
- Shahdadian, F.; Mohammadi, H.; Rouhani, M.H. Effect of Vitamin K Supplementation on Glycemic Control: A Systematic Review and Meta-Analysis of Clinical Trials. Horm. Metab. Res. 2018, 50, 227–235. [Google Scholar] [CrossRef]
- Rasekhi, H.; Karandish, M.; Jalali, M.T.; Mohammad-Shahi, M.; Zarei, M.; Saki, A.; Shahbazian, H. The effect of vitamin K1 supplementation on sensitivity and insulin resistance via osteocalcin in prediabetic women: A double-blind randomized controlled clinical trial. Eur. J. Clin. Nutr. 2015, 69, 891–895. [Google Scholar] [CrossRef]
- Manna, P.; Kalita, J. Beneficial role of vitamin K supplementation on insulin sensitivity, glucose metabolism, and the reduced risk of type 2 diabetes: A review. Nutrition 2016, 32, 732–739. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Chen, J.; Duan, L.; Li, S. Effect of Vitamin K2 on Type 2 Diabetes Mellitus: A Review. Diabetes Res. Clin. Pr. 2018, 136, 39–51. [Google Scholar] [CrossRef] [PubMed]
- Karamzad, N.; Faraji, E.; Adeli, S.; Carson-Chahhoud, K.; Azizi, S.; Gargari, P.B. Effects of MK-7 Supplementation on Glycemic Status, Anthropometric Indices and Lipid Profile in Patients with Type 2 Diabetes: A Randomized Controlled Trial. Diabetes Metab. Syndr. Obes. 2020, 13, 2239–2249. [Google Scholar] [CrossRef] [PubMed]
- Tarkesh, F.; Jahromi, N.B.; Hejazi, N.; Tabatabaee, H. Beneficial health effects of Menaquinone-7 on body composition, glycemic indices, lipid profile, and endocrine markers in polycystic ovary syndrome patients. Food Sci. Nutr. 2020, 8, 5612–5621. [Google Scholar] [CrossRef]
- Yoshida, M.; Jacques, P.; Meigs, J.; Saltzman, E.; Shea, M.; Gundberg, C.; Dawson-Hughes, B.; Dallal, G.; Booth, S. Effect of vitamin K supplementation on insulin resistance in older men and women. Diabetes Care 2008, 31, 2092–2096. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Karamzad, N.; Maleki, V.; Carson-Chahhoud, K.; Azizi, S.; Sahebkar, A.; Gargari, B.P. A systematic review on the mechanisms of vitamin K effects on the complications of diabetes and pre-diabetes. Biofactors 2020, 46, 21–37. [Google Scholar] [CrossRef]
- Dihingia, A.; Ozah, D.; Baruah, P.; Kalita, J.; Manna, P. Prophylactic role of vitamin K supplementation on vascular inflammation in type 2 diabetes by regulating the NF-κB/Nrf2 pathway via activating Gla proteins. Food Funct. 2018, 9, 450–462. [Google Scholar] [CrossRef]
- Mera, P.; Ferron, M.; Mosialou, I. Regulation of Energy Metabolism by Bone-Derived Hormones. Cold Spring Harb Perspect Med. 2018, 8, a031666. [Google Scholar] [CrossRef]
- O’Connor, E.M.; Durack, E. Osteocalcin: The extra-skeletal role of a vitamin K-dependent protein in glucose metabolism. J. Nutr. Intermed Metab. 2017, 7, 8–13. [Google Scholar] [CrossRef]
- Gundberg, C.M.; Lian, J.B.; Booth, S.L. Vitamin K-Dependent Carboxylation of Osteocalcin: Friend or Foe? Adv. Nutr. 2012, 3, 149–157. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Beulens, J.; van der, A.D.; Grobbee, D.; Sluijs, I.; Spijkerman, A.; van der Schouw, Y. Dietary Phylloquinone and Menaquinones Intakes and Risk of Type 2 Diabetes. Diabetes Care 2010, 33, 1699–1705. [Google Scholar] [CrossRef] [Green Version]
- Booth, S.; Centi, A.; Smith, S.; Gundberg, C. The role of osteocalcin in human glucose metabolism: Marker or mediator? Nat. Rev. Endocrinol. 2013, 9, 43–55. [Google Scholar] [CrossRef] [Green Version]
- Parra, M.A.; Butler, S.; McGeown, W.J.; Brown Nicholls, L.A.; Robertson, D.J. Globalising strategies to meet global challenges: The case of ageing and dementia. J. Glob Heal 2019, 9, 020310. [Google Scholar] [CrossRef] [PubMed]
- Rusu, M.E.; Georgiu, C.; Pop, A.; Mocan, A.; Kiss, B.; Vostinaru, O.; Fizesan, I.; Stefan, M.-G.; Gheldiu, A.-M.; Mates, L.; et al. Antioxidant Effects of Walnut (Juglans regia L.) Kernel and Walnut Septum Extract in a D-Galactose-Induced Aging Model and in Naturally Aged Rats. Antioxidants 2020, 9, 424. [Google Scholar] [CrossRef]
- Chauhan, A.; Chauhan, V. Beneficial Effects of Walnuts on Cognition and Brain Health. Nutrients 2020, 12, 550. [Google Scholar] [CrossRef] [Green Version]
- Carrillo, J.Á.; Arcusa, R.; Zafrilla, M.P.; Marhuenda, J. Effects of Fruit and Vegetable-Based Nutraceutical on Cognitive Function in a Healthy Population: Placebo-Controlled, Double-Blind, and Randomized Clinical Trial. Antioxidants 2021, 10, 116. [Google Scholar] [CrossRef]
- Opie, R.; Itsiopoulos, C.; Parletta, N.; Sanchez-Villegas, A.; Akbaraly, T.; Ruusunen, A.; Jacka, F. Dietary recommendations for the prevention of depression. Nutr. Neurosci. 2017, 20, 161–171. [Google Scholar] [CrossRef]
- Fernández-Sanz, P.; Ruiz-Gabarre, D.; García-Escudero, V. Modulating Effect of Diet on Alzheimer’s Disease. Diseases 2019, 7, 12. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fenech, M. Vitamins Associated with Brain Aging, Mild Cognitive Impairment, and Alzheimer Disease: Biomarkers, Epidemiological and Experimental Evidence, Plausible Mechanisms, and Knowledge Gaps. Adv. Nutr. 2017, 8, 958–970. [Google Scholar] [CrossRef] [Green Version]
- Vasefi, M.; Hudson, M.; Ghaboolian-Zare, E. Diet Associated with Inflammation and Alzheimer’s Disease. J. Alzheimers Dis. Rep. 2019, 3, 299–309. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tamadon-Nejad, S.; Ouliass, B.; Rochford, J.; Ferland, G. Vitamin K Deficiency Induced by Warfarin Is Associated With Cognitive and Behavioral Perturbations, and Alterations in Brain Sphingolipids in Rats. Front. Aging Neurosci. 2018, 10, 213. [Google Scholar] [CrossRef] [Green Version]
- Rusu, M.E.; Fizesan, I.; Pop, A.; Mocan, A.; Gheldiu, A.-M.; Babota, M.; Vodnar, D.C.; Jurj, A.; Berindan-Neagoe, I.; Vlase, L.; et al. Walnut (Juglans regia L.) Septum: Assessment of Bioactive Molecules and In Vitro Biological Effects. Molecules 2020, 25, 2187. [Google Scholar] [CrossRef]
- Mohajeri, M.; Troesch, B.; Weber, P. Inadequate supply of vitamins and DHA in the elderly: Implications for brain aging and Alzheimer-type dementia. Nutrition 2015, 31, 261–275. [Google Scholar] [CrossRef] [Green Version]
- Grimm, M.O.W.; Mett, J.; Hartmann, T. The Impact of Vitamin E and Other Fat-Soluble Vitamins on Alzheimer’s Disease. Int. J. Mol. Sci. 2016, 17, 1785. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Machado-Fragua, M.; Hoogendijk, E.; Struijk, E.; Rodriguez-Artalejo, F.; Lopez-Garcia, E.; Beulens, J.; van Ballegooijen, A. High dephospho-uncarboxylated matrix Gla protein concentrations, a plasma biomarker of vitamin K, in relation to frailty: The Longitudinal Aging Study Amsterdam. Eur. J. Nutr. 2020, 59, 1243–1251. [Google Scholar] [CrossRef]
- Presse, N.; Shatenstein, B.; Kergoat, M.; Ferland, G. Low Vitamin K Intakes in Community-Dwelling Elders at an Early Stage of Alzheimer’s Disease. J. Am. Diet. Assoc. 2008, 108, 2095–2099. [Google Scholar] [CrossRef] [PubMed]
- Alisi, L.; Cao, R.; De Angelis, C.; Cafolla, A.; Caramia, F.; Cartocci, G.; Librando, A.; Fiorelli, M. The Relationships Between Vitamin K and Cognition: A Review of Current Evidence. Front. Neurol. 2019, 10, 239. [Google Scholar] [CrossRef]
- McCann, A.; Jeffery, I.B.; Ouliass, B.; Ferland, G.; Fu, X.; Booth, S.L.; Tran, T.T.; O’Toole, P.; O’Connor, E. Exploratory analysis of covariation of microbiota-derived vitamin K and cognition in older adults. Am. J. Clin. Nutr. 2019, 110, 1404–1415. [Google Scholar] [CrossRef]
- Thane, C.W.; Bates, C.J.; Shearer, M.J.; Unadkat, N.; Harrington, D.J.; Paul, A.A.; Prentice, A.; Bolton-Smith, C. Plasma phylloquinone (vitamin K1) concentration and its relationship to intake in a national sample of British elderly people. Br. J. Nutr. 2002, 87, 615–622. [Google Scholar] [CrossRef] [Green Version]
- Tanprasertsuk, J.; Ferland, G.; Johnson, M.A.; Poon, L.W.; Scott, T.M.; Barbey, K.; Barger, K.; Wang, X.-D.; Johnson, E.J. Concentrations of Circulating Phylloquinone, but Not Cerebral Menaquinone-4, Are Positively Correlated with a Wide Range of Cognitive Measures: Exploratory Findings in Centenarians. J. Nutr. 2020, 150, 82–90. [Google Scholar] [CrossRef]
- Presse, N.; Belleville, S.; Gaudreau, P.; Greenwood, C.E.; Kergoat, M.-J.; Morais, J.A.; Payette, H.; Shatenstein, B.; Ferland, G. Vitamin K status and cognitive function in healthy older adults. Neurobiol. Aging 2013, 34, 2777–2783. [Google Scholar] [CrossRef]
- Morris, M.C.; Wang, Y.; Barnes, L.L.; Bennett, D.A.; Dawson-Hughes, B.; Booth, S.L. Nutrients and bioactives in green leafy vegetables and cognitive decline. Neurology 2018, 90, e214–e222. [Google Scholar] [CrossRef] [PubMed]
- Chouet, J.; Ferland, G.; Féart, C.; Rolland, Y.; Presse, N.; Boucher, K.; Barberger-Gateau, P.; Beauchet, O.; Annweiler, C. Dietary Vitamin K Intake Is Associated with Cognition and Behaviour among Geriatric Patients: The CLIP Study. Nutrients 2015, 7, 6739–6750. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lasemi, R.; Kundi, M.; Moghadam, N.B.; Moshammer, H.; Hainfellner, J.A. Vitamin K2 in multiple sclerosis patients. Wien Klin Wochenschr. 2018, 130, 307–313. [Google Scholar] [CrossRef] [Green Version]
- Sanchez, J.M.S.; DePaula-Silva, A.B.; Libbey, J.E.; Fujinami, R.S. Role of diet in regulating the gut microbiota and multiple sclerosis. Clin. Immunol. 2020, 108379. [Google Scholar] [CrossRef] [PubMed]
- Yu, Y.-X.; Yu, X.-D.; Cheng, Q.-Z.; Tang, L.; Shen, M.-Q. The association of serum vitamin K2 levels with Parkinson’s disease: From basic case-control study to big data mining analysis. Aging (Albany NY) 2020, 12, 16410–16419. [Google Scholar] [CrossRef]
- Soutif-Veillon, A.; Ferland, G.; Rolland, Y.; Presse, N.; Boucher, K.; Féart, C.; Annweiler, C. Increased dietary vitamin K intake is associated with less severe subjective memory complaint among older adults. Maturitas 2016, 93, 131–136. [Google Scholar] [CrossRef]
- Annweiler, C.; Denis, S.; Duval, G.; Ferland, G.; Bartha, R.; Beauchet, O. Use of Vitamin K Antagonists and Brain Volumetry in Older Adults: Preliminary Results From the GAIT Study. J. Am. Geriatr. Soc. 2015, 63, 2199–2202. [Google Scholar] [CrossRef]
- Brangier, A.; Ferland, G.; Rolland, Y.; Gautier, J.; Féart, C.; Annweiler, C. Vitamin K Antagonists and Cognitive Decline in Older Adults: A 24-Month Follow-Up. Nutrients 2018, 10, 666. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lin, X.; Onda, D.-A.; Yang, C.-H.; Lewis, J.R.; Levinger, I.; Loh, K. Roles of bone-derived hormones in type 2 diabetes and cardiovascular pathophysiology. Mol. Metab. 2020, 40, 101040. [Google Scholar] [CrossRef]
- Oury, F.; Khrimian, L.; Denny, C.A.; Gardin, A.; Chamouni, A.; Goeden, N.; Huang, Y.; Lee, H.; Srinivas, P.; Gao, X.-B.; et al. Maternal and Offspring Pools of Osteocalcin Influence Brain Development and Functions. Cell 2013, 155, 228–241. [Google Scholar] [CrossRef] [Green Version]
- Battafarano, G.; Rossi, M.; Marampon, F.; Minisola, S.; Del Fattore, A. Bone Control of Muscle Function. Int. J. Mol. Sci. 2020, 21, 1178. [Google Scholar] [CrossRef] [Green Version]
- Bhatti, G.K.; Reddy, A.P.; Reddy, P.H.; Bhatti, J. Lifestyle Modifications and Nutritional Interventions in Aging-Associated Cognitive Decline and Alzheimer’s Disease. Front. Aging Neurosci. 2020, 11, 369. [Google Scholar] [CrossRef]
- Sinyor, B.; Mineo, J.; Ochner, C. Alzheimer’s Disease, Inflammation, and the Role of Antioxidants. J. Alzheimers Dis. Rep. 2020, 4, 175–183. [Google Scholar] [CrossRef]
- Wagenaar, L.J. Vitamin K2 and Macular Degeneration. European Patent Application. EP 3 106 158 A1. Bulletin 2016;51. Available online: https://patentimages.storage.googleapis.com/4d/f9/ab/0d84c163c6b0d4/EP3106158A1.pdf (accessed on 2 April 2021).
- Nimptsch, K.; Rohrmann, S.; Linseisen, J. Dietary intake of vitamin K and risk of prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg). Am. J. Clin. Nutr. 2008, 87, 985–992. [Google Scholar] [CrossRef] [PubMed]
- Chen, G.; Wang, F.; Trachootham, D.; Huang, P. Preferential killing of cancer cells with mitochondrial dysfunction by natural compounds. Mitochondrion 2010, 10, 614–625. [Google Scholar] [CrossRef] [Green Version]
- Ivanova, D.; Zhelev, Z.; Getsov, P.; Nikolova, B.; Aoki, I.; Higashi, T.; Bakalova, R. Vitamin K: Redox-modulation, prevention of mitochondrial dysfunction and anticancer effect. Redox Biol. 2018, 16, 352–358. [Google Scholar] [CrossRef]
- Dasari, S.; Ali, S.M.; Zheng, G.; Chen, A.; Dontaraju, S.; Bosland, M.C.; Kajdacsy-Balla, A.; Munirathinam, G. Vitamin K and its analogs: Potential avenues for prostate cancer management. Oncotarget 2017, 8, 57782–57799. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dahlberg, S.; Ede, J.; Schött, U. Vitamin K and cancer. Scand. J. Clin. Lab. Invest. 2017, 77, 555–567. [Google Scholar] [CrossRef] [PubMed]
- Wellington, K.; Hlatshwayo, V.; Kolesnikova, N.; Saha, S.; Kaur, M.; Motadi, L. Anticancer activities of vitamin K3 analogues. Invest. N. Drugs 2020, 38, 378–391. [Google Scholar] [CrossRef]
- Fizeșan, I.; Rusu, M.E.; Georgiu, C.; Pop, A.; Ștefan, M.-G.; Muntean, D.M.; Mirel, S.; Vostinaru, O.; Kiss, B.; Popa, D.-S. Antitussive, Antioxidant, and Anti-Inflammatory Effects of a Walnut (Juglans regia L.) Septum Extract Rich in Bioactive Compounds. Antioxidants 2021, 10, 119. [Google Scholar] [CrossRef]
- Vita, M.F.; Nagachar, N.; Avramidis, D.; Delwar, Z.M.; Cruz, M.; Siden, A.; Paulsson, K.; Yakisich, J.S. Pankiller effect of prolonged exposure to menadione on glioma cells: Potentiation by vitamin C. Invest. N. Drugs 2011, 29, 1314–1320. [Google Scholar] [CrossRef] [Green Version]
- He, T.; Hatem, E.; Vernis, L.; Lei, M.; Huang, M.-E. PRX1 knockdown potentiates vitamin K3 toxicity in cancer cells: A potential new therapeutic perspective for an old drug. J. Exp Clin. Cancer Res. 2015, 34, 152. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Miyazawa, S.; Moriya, S.; Kokuba, H.; Hino, H.; Takano, N.; Miyazawa, K. Vitamin K 2 induces non-apoptotic cell death along with autophagosome formation in breast cancer cell lines. Breast Cancer. 2020, 27, 225–235. [Google Scholar] [CrossRef]
- Dasari, S.; Samy, A.; Kajdacsy-Balla, A.; Bosland, M.; Munirathinam, G. Vitamin K2, a menaquinone present in dairy products targets castration-resistant prostate cancer cell-line by activating apoptosis signaling. Food Chem. Toxicol. 2018, 115, 218–227. [Google Scholar] [CrossRef]
- Samykutty, A.; Shetty, A.V.; Dakshinamoorthy, G.; Kalyanasundaram, R.; Zheng, G.; Chen, A.; Bosland, M.C.; Kajdacsy-Balla, A.; Gnanasekar, M. Vitamin K2, a naturally occurring menaquinone, exerts therapeutic effects on both hormone-dependent and hormone-independent prostate cancer cells. Evid. Based Complement. Altern. Med. 2013, 2013, 287358. [Google Scholar] [CrossRef]
- Xv, F.; Chen, J.; Duan, L.; Li, S. Research progress on the anticancer effects of vitamin K2 (Review). Oncol. Lett. 2018, 15, 8926–8934. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Glick, D.; Barth, S.; Macleod, K.F. Autophagy: Cellular and molecular mechanisms. J. Pathol. 2010, 221, 3–12. [Google Scholar] [CrossRef] [Green Version]
- Yokoyama, T.; Miyazawa, K.; Naito, M.; Toyotake, J.; Tauchi, T.; Itoh, M.; Yuo, A.; Hayashi, Y.; Georgescu, M.-M.; Kondo, Y.; et al. Vitamin K2 induces autophagy and apoptosis simultaneously in leukemia cells. Autophagy 2008, 4, 629–640. [Google Scholar] [CrossRef]
- Enomoto, M.; Tsuchida, A.; Miyazawa, K.; Yokoyama, T.; Kawakita, H.; Tokita, H.; Naito, M.; Itoh, M.; Ohyashiki, K.; Aoki, T. Vitamin K2-induced cell growth inhibition via autophagy formation in cholangiocellular carcinoma cell lines. Int. J. Mol. Med. 2007, 20, 801–808. [Google Scholar] [CrossRef]
- Tokita, H.; Tsuchida, A.; Miyazawa, K.; Ohyashiki, K.; Katayanagi, S.; Sudo, H.; Enomoto, M.; Takagi, Y.; Aoki, T. Vitamin K2-induced antitumor effects via cell-cycle arrest and apoptosis in gastric cancer cell lines. Int. J. Mol. Med. 2006, 17, 235–243. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Otsuka, M.; Kato, N.; Shao, R.-X.; Hoshida, Y.; Ijichi, H.; Koike, Y.; Taniguchi, H.; Moriyama, M.; Shiratori, Y.; Kawabe, T.; et al. Vitamin K2 Inhibits the Growth and Invasiveness of Hepatocellular Carcinoma Cells via Protein Kinase a Activation. Hepatology 2004, 40, 243–251. [Google Scholar] [CrossRef] [PubMed]
- Jinghe, X.; Mizuta, T.; Ozaki, I. Vitamin K and hepatocellular carcinoma: The basic and clinic. World J. Clin. Cases. 2015, 3, 757–764. [Google Scholar] [CrossRef] [PubMed]
- Yoshiji, H.; Noguchi, R.; Toyohara, M.; Ikenaka, Y.; Kitade, M.; Kaji, K.; Yamazaki, M.; Yamao, J.; Mitoro, A.; Sawai, M.; et al. Combination of vitamin K2 and angiotensin-converting enzyme inhibitor ameliorates cumulative recurrence of hepatocellular carcinoma. J. Hepatol. 2009, 51, 315–321. [Google Scholar] [CrossRef] [PubMed]
- Duan, F.; Yu, Y.; Guan, R.; Xu, Z.; Liang, H.; Hong, L. Vitamin K2 Induces Mitochondria-Related Apoptosis in Human Bladder Cancer Cells via ROS and JNK/p38 MAPK Signal Pathways. PLoS ONE 2016, 11, e0161886. [Google Scholar] [CrossRef]
- Duan, F.; Mei, C.; Yang, L.; Zheng, J.; Lu, H.; Xia, Y.; Hsu, S.; Liang, H.; Hong, L. Vitamin K2 promotes PI3K/AKT/HIF-1α-mediated glycolysis that leads to AMPK-dependent autophagic cell death in bladder cancer cells. Sci. Rep. 2020, 10, 7714. [Google Scholar] [CrossRef]
- Muñoz-Esparza, N.C.; Latorre-Moratalla, M.L.; Comas-Basté, O.; Toro-Funes, N.; Veciana-Nogués, M.T.; Vidal-Carou, M.C. Polyamines in Food. Front. Nutr. 2019, 6, 108. [Google Scholar] [CrossRef]
- Minois, N.; Carmona-Gutierrez, D.; Madeo, F. Polyamines in aging and disease. Aging (Albany NY) 2011, 3, 716–732. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Orlando, A.; Linsalata, M.; Tutino, V.; D’Attoma, B.; Notarnicola, M.; Russo, F. Vitamin K1 Exerts Antiproliferative Effects and Induces Apoptosis in Three Differently Graded Human Colon Cancer Cell Lines. Biomed. Res. Int. 2015, 2015, 296721. [Google Scholar] [CrossRef]
- Russo, I.; Caroppo, F.; Alaibac, M. Vitamins and Melanoma. Cancers 2015, 7, 1371–1387. [Google Scholar] [CrossRef]
- Beaudin, S.; Kokabee, L.; Welsh, J. Divergent effects of vitamins K1 and K2 on triple negative breast cancer cells. Oncotarget 2019, 10, 2292–2305. [Google Scholar] [CrossRef] [Green Version]
- Wang, K.; Wu, Q.; Li, Z.; Reger, M.K.; Xiong, Y.; Zhong, G.; Li, Q.; Zhang, X.; Li, H.; Foukakis, T.; et al. Vitamin K intake and breast cancer incidence and death: Results from a prospective cohort study. Clin. Nutr. 2020. [Google Scholar] [CrossRef]
- Lo, J.; Park, Y.; Sinha, R.; Sandler, D. Association between meat consumption and risk of breast cancer: Findings from the Sister Study. Int. J. Cancer. 2019, 146, 2156–2165. [Google Scholar] [CrossRef]
- Sant, M.; Allemani, C.; Sieri, S.; Krogh, V.; Menard, S.; Tagliabue, E.; Nardini, E.; Micheli, A.; Crosignani, P.; Muti, P.; et al. Salad vegetables dietary pattern protects against HER-2-positive breast cancer: A prospective Italian study. Int. J. Cancer. 2007, 121, 911–914. [Google Scholar] [CrossRef]
- George, S.; Ballard-Barbash, R.; Shikany, J.; Caan, B.; Freudenheim, J.; Kroenke, C.; Vitolins, M.; Beresford, S.; Neuhouser, M. Better postdiagnosis diet quality is associated with reduced risk of death among postmenopausal women with invasive breast cancer in the Women’s Health Initiative. Cancer Epidemiol. Biomarkers Prev. 2014, 23, 575–583. [Google Scholar] [CrossRef] [Green Version]
- Nimptsch, K.; Rohrmann, S.; Kaaks, R.; Linseisen, J. Dietary vitamin K intake in relation to cancer incidence and mortality: Results from the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg). Am. J. Clin. Nutr. 2010, 91, 1348–1358. [Google Scholar] [CrossRef] [Green Version]
- Matsubara, K.; Kayashima, T.; Mori, M.; Yoshida, H.; Mizushina, Y. Inhibitory effects of vitamin K3 on DNA polymerase and angiogenesis. Int. J. Mol. Med. 2008, 22, 381–387. [Google Scholar] [CrossRef] [Green Version]
- Juanola-Falgarona, M.; Salas-Salvadó, J.; Martínez-González, M.; Corella, D.; Estruch, R.; Ros, E.; Fitó, M.; Arós, F.; Gómez-Gracia, E.; Fiol, M.; et al. Dietary Intake of Vitamin K Is Inversely Associated with Mortality Risk. J. Nutr. 2014, 144, 743–750. [Google Scholar] [CrossRef] [PubMed]
- Shen, T.; Bimali, M.; Faramawi, M.; Orloff, M.S. Consumption of Vitamin K and Vitamin A Are Associated With Reduced Risk of Developing Emphysema: NHANES 2007–2016. Front. Nutr. 2020, 7, 47. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- ten Kate, M.; van der Meer, J. Protein S deficiency: A clinical perspective. Haemophilia 2008, 14, 1222–1228. [Google Scholar] [CrossRef]
- Zagórska, A.; Través, P.; Lew, E.; Dransfield, I.; Lemke, G. Diversification of TAM. receptor function. Nat. Immunol. 2014, 15, 920–928. [Google Scholar] [CrossRef] [Green Version]
- Tutusaus, A.; Marí, M.; Ortiz-Pérez, J.; Nicolaes, G.; Morales, A.; de Frutos, P. Role of Vitamin K-Dependent Factors Protein S and GAS6 and TAM. Receptors in SARS-CoV-2 Infection and COVID-19-Associated Immunothrombosis. Cells 2020, 9, 2186. [Google Scholar] [CrossRef]
- Baicus, C.; Stoichitoiu, L.E.; Pinte, L.; Badea, C. Anticoagulant Protein S in COVID-19: The Low Activity Level Is Probably Secondary. Am. J. Ther. 2021, 28, e139–e140. [Google Scholar] [CrossRef] [PubMed]
- Janssen, R.; Visser, M.P.J.; Dofferhoff, A.S.M.; Vermeer, C.; Janssens, W.; Walk, J. Vitamin K metabolism as the potential missing link between lung damage and thromboembolism in Coronavirus disease 2019. Br. J. Nutr. 2020, 1–8. [Google Scholar] [CrossRef]
Food Category | Food Source | VK2 * |
---|---|---|
Fermented foods | Natto Sauerkraut | 850–1000 (90% MK-7, 8% MK-8) 5.5 (31% MK-6, 23% MK-9, 17% MK-5 and -8) |
Hard cheeses | 50–80 (15–67% MK-9, 6–22% MK-4, 6–22% MK-8) | |
Soft cheeses | 30–60 (20–70% MK-9, 6–20% MK-4, 6–20% MK-8) | |
Eggs | Yolk | 15–30 (MK-4) |
Meats | Pork, beef, chicken | 1.4–10 (MK-4) |
Author, Year, Country [Ref.] | Subjects (W:M) Age (Mean ± SD) | Design (Length) | Intervention Exposure | Findings |
---|---|---|---|---|
Shiraki et al. 2000 Japan [44] | 241 PMO 67.2 y | prospective 2 y | 45 mg/d MK-4 vs. control | ↓ ucOC (p < 0.0001) ↑ cOC (p = 0.0081) ↓ fracture risk (p = 0.0273) |
Iwamoto et al. 2001 Japan [48] | 72 PMO 65.3 y | prospective 2 y | 45 mg/d MK-4 + Ca vs. Ca | ↓ vertebral fractures (p < 0.0001) ↑ BMD (forearm) (p < 0.0001) |
Purwosunu et al. 2006 Indonesia [49] | 63 PMO 60.8 y | RCT 48 w | 45 mg/d MK-4 + Ca vs. Ca | ↓ ucOC (p ˂ 0.01) ↑ BMD (lumbar) (p < 0.05) |
Bolton-Smith et al. 2007 UK [45] | 244 healthy W 68.2 y | RCT 2 y | 200 μg/d VK1 + 10 μg/d vitD3 + Ca vs. placebo | ↓ ucOC (p < 0.001) ↑ BMD (ultradistal radius) (p < 0.01) |
Knapen et al. 2007 Netherlands [50] | 325 PMW 66.0 y | RCT 3 y | 45 mg/d MK-4 vs. placebo | ↑ BMC (p < 0.05) and bone strength (femoral neck) |
Booth et al. 2008 USA [51] | 452 (267:185) 68.4 y | RCT 3 y | 500 μg/d PK vs. control | ↓ ucOC (p ˂ 0.0001) |
Cheung et al. 2008 Canada [52] | 400 PMOa 59.1 y | RCT 2–4 y | 5 mg/d VK1 vs. placebo | ↓ fracture risk (p = 0.04) |
Hirao et al. 2008 Japan [53] | 44 PMW 68.4 y | prospective 1 y | 45 mg/d VK2 + 5 mg/d alendronate vs. 5 mg/d alendronate | ↓ ucOC (p = 0.014) ↓ ucOC:cOC (p = 0.007) ↑ BMD (femoral neck) (p = 0.03) |
Tsugawa et al. 2008 Japan [54] | 379 W 63.0 y | prospective 3 y | high VK1 vs. low VK1 | ↓ vertebral fracture risk (p < 0.001) |
Binkley et al. 2009 USA [46] | 381 PMW 62.5 y | RCT 1 y | 1 mg/d VK1 or 45 mg/d MK-4 vs. placebo | ↓ ucOC (p < 0.001) for both VK1 and MK-4 groups |
Yamauchi et al. 2010 Japan [55] | 221 healthy W 60.8 ± 9.5 y | cross-sectional | 260±85 μg/d VK | ↓ ucOC (p < 0.0001) ↑ BMD (lumbar) (p = 0.015) |
Je et al. 2011 Korea [56] | 78 PMW 67.8 y | RCT 6 mo | 45 mg/d MK-4 + vitD + Ca vs. vitD + Ca | ↓ ucOC (p = 0.008) ↑ BMD (lumbar) (p = 0.049) |
Kanellakis et al. 2012 Greece [57] | 173 PMW 62.0 y | RCT 12 mo | 100 μg PK or MK-7 + vitD + Ca vs. control | ↓ ucOC (p = 0.001) * ↑ BMD (lumbar) (p < 0.05) * |
Knapen et al. 2013 Netherlands [58] | 244 PMW 60.0 y | RCT 3 y | 180 μg/d MK-7 vs. placebo | ↓ ucOC (p < 0.001) ↑ BMD (lumbar spine, femoral neck), bone strength (p < 0.05) |
Jiang et al. 2014 China [59] | 213 PMW 64.4 y | RCT 1 y | 45 mg/d MK-4 + Ca vs. Ca | ↓ ucOC (p < 0.001) ↑ BMD (lumbar) (p < 0.001) |
Rønn et al. 2016 Denmark [47] | 148 PMOa 67.5 y | RCT 1 y | 375 µg/d MK-7 vs. placebo | ↓ ucOC (p < 0.05) ↓ ucOC:cOC (p < 0.05) ↑ bone structure (tibia) (p < 0.05) |
Bultynck et al. 2020 UK [60] | 62 (42:20) 80.0 ± 9.6 y | Prospective | ↑ serum VK | ↓ hip fracture risk |
Moore et al. 2020 UK [61] | 374 PMO 68.7 y | cross-sectional | ↑ serum VK1 | ↓ fracture risk (p = 0.04) |
Sim et al. 2020 Australia [62] | 30 (10:20) 61.8 ± 9.9 y | RCT 12 w | 136.7 μg/d VK | ↓ ucOC and ucOC:tOC (p ≤ 0.01) |
Author, Year, Country (Ref.) | Subjects (W:M) Age (Mean ± SD) | Design (Length) | Intervention Exposure | Findings |
---|---|---|---|---|
Geleijnse et al. 2004 Netherlands [90] | 4807 (2971:1836) 67.5 y | 7 y | Q1 ˂ 21.6 μg/d VK2 Q2 21.6–32.7μg/d VK2 Q3 ˃ 32.7 μg/d VK2 | ↓ CHD mortality: RR = 0.43 (95% CI: 0.24–0.77, p = 0.005) Q3 vs. Q1 ↓ AC: OR = 0.48 (95% CI: 0.32–0.71, p ˂ 0.001) Q3 vs. Q1 |
Gast et al. 2009 Netherlands [91] | 16,057 W 57.0 ± 6.0 y | Longitudinal 8.1 y | 211.7μg/d VK1 29.1μg/d VK2 | ↓ CHD risk for 10 μg VK2: HR = 0.91 (95% CI: 0.85–1.00, p = 0.04) |
Shea et al. 2009 USA [92] | 388 (235:153) 68 y | RCT 3 y | 500 μg/d VK1 vs. control | ↓progression of CAC |
Schurgers et al. 2010 France [93] | 107 (43:64) 67 ± 13 y | 18 mo | VK levels dp-ucMGP | ↓ VK levels ↑ dp-ucMGP levels with CKD stage |
Ueland et al. 2010 Norway [94] | 147 (66:81) 74.0 ± 10 y | 20 mo | VK levels dp-ucMGP | ↓ VK levels ↑ dp-ucMGP in symptomatic AS |
Schlieper et al. 2011 Serbia [95] | 188 (89:99) 58 ± 15 y | Follow-up, 1104 days | VK levels dp-ucMGP dp-cMGP | ↓ dp-cMGP ↑ CV: HR = 2.7 (95% CI: 1.2–6.2, p = 0.015) ↑ All-cause: HR = 2.16 (95% CI: 1.1–4.3, p = 0.027) |
Ueland et al. 2011 Norway [96] | 179 (39:140) 56 y | 2.9 y | VK levels dp-ucMGP | ↓ VK levels; ↑ dp-ucMGP ↑ heart failure: HR=5.62 (95% CI: 2.05–15.46, p = 0.001) |
Westenfeld et al. 2011 Germany [97] | 103 (48:55) ˃ 60.5 y | RCT 6 w | G1–45 µg/d MK-7 G2–135 µg/d MK-7 G3–360 µg/d MK-7 | ↓ dp-ucMGP by 77–93% G2 and G3 vs. control |
Dalmeijer et al. 2012 Netherlands [98] | 60 (36:24) 59.5 y | RCT 12 w | G1–180 μg/d MK-7 G2–360 μg/d MK-7 | ↓ dp-ucMGP by 31% G1 and 46% G2 vs. placebo |
van den Heuvel et al. 2013 Netherlands [99] | 577 (322:255) 59.9 ± 2.9 y | Follow-up 5.6 y | VK levels dp-ucMGP | ↓ VK levels; ↑ dp-ucMGP ↑ CVD: HR=2.69 (95% CI: 1.09–6.62, p = 0.032) |
Caluwé et al. 2014 Norway [100] | 165 (83:82) 70.8 y | RCT 8 w | 360, 720 or 1080 μg MK-7 thrice weekly | ↓ dp-ucMGP by 17–33–46% |
Liabeuf et al. 2014 France [101] | 198 (40:158) 64 ± 8 y | Cross-sectional | VK levels dp-ucMGP | ↓ VK levels; ↑ dp-ucMGP ↑ PAC: OR = 1.88 (95% CI: 1.14–3.11, p = 0.014) |
Cheung et al. 2015 USA [102] | 3401 (2245:1156) 61.9 y | Follow-up 13.3 y | ↑ VK daily intake | ↓ CVD mortality: HR = 0.78 (95% CI: 0.64–0.95, p = 0.016) |
Knapen et al. 2015 Norway [103] | 244 PMW 59.5 ± 3.3 y | RCT 3 y | 180 µg/d MK-7 vs. placebo | ↓ Stiffness Index β: −0.67 ± 2.78 vs. +0.15 ± 2.51, p = 0.018 ↓ cfPWV: −0.36 ± 1.48 m/s vs. +0.021 ± 1.22 m/s, p = 0.040 |
Kurnatowska et al. 2015 Poland [104] | 42 (20:22) 58 y | RCT 270 days | 90 μg/d MK-7 + 10 μg/d vitD vs. control | ↑ CAC ↓dp-ucMGP |
Asemi et al. 2016 Iran [105] | 66 (31:35) 65.5 y | RCT 12 w | 180 µg/d MK-7 + 10 µg/d vitD + 1 g/d Ca vs. placebo | ↓ levels of left CIMT (p = 0.02) ↓ insulin (−0.9 vs. +2.6, p = 0.01) ↓ HOMA-IR (−0.4 vs. +0.7, p = 0.01) |
Fulton et al. 2016 UK [106] | 80 (36:44) 77 ± 5 y | RCT 6 mo | 100 µg MK-7 vs. placebo | ↓dp-ucMGP (p < 0.001) |
Kurnatowska et al. 2016 Poland [107] | 38 (17:21) 58.6 y | RCT 9 mo | 90 μg/d MK-7 + 10 μg/d vitD vs. control | ↓dp-ucMGP by 10.7% |
Sardana et al. 2016 USA [108] | 66 (6:60) T2D 62 ± 2 y | Cross-sectional | VK levels dp-ucMGP | ↓ VK levels; ↑ dp-ucMGP ↑ cfPWV (β = 0.40, p = 0.011) |
Aoun et al. 2017 Lebanon [109] | 50 (20:30) 71.5 y | RCT 4 w | 360 μg/d MK-7 | ↓ dp-ucMGP by 86% |
Brandenburg et al. 2017 Germany [110] | 99 (18:81) 69.1 y | RCT 1 y | 2 mg/d VK1 vs. placebo | ↓ progression of AVC (10.0% vs. 22.0%) |
Shea et al. 2017 USA [111] | 1061 (615:446) 74 ± 5 y | Follow-up 12.1 y | VK1 levels dp-ucMGP | ↑ CVD risk in HBP patients (n = 489): HR = 2.94 (95% CI: 1.4–6.13, p ˂ 0.01) |
Puzantian et al. 2018 USA [112] | 137 (8:129) 59.6 y | VK levels dp-ucMGP | ↓ VK levels; ↑ dp-ucMGP ↑ cfPWV (β = 0.21; p = 0.019) | |
Dal Canto et al. 2020 Netherlands [113] | 601 (303:298) 70 ± 6 y | Follow-up 7 and 17 y | ↓ VK levels ↓ vitD levels | ↑ LVMI: β = 5.9 g/m2.7 (95% CI: 1.8–10.0 g/2.7) ↑ All-cause mortality: HR = 1.64 (95% CI: 1.12–2.39, p = 0.011) |
Roumeliotis et al. 2020 Greece [114] | 66 (31:35) diabetic CKD 68.5 ± 8.6 y | Follow-up 7 y | VK levels dp-ucMGP | ↓ VK levels; ↑ dp-ucMGP ↑ CVD mortality: HR = 2.82 (95% CI: 1.07–7.49, p = 0.037) |
Shea et al. 2020 USA [115] | 3891 (2154:1737) 65 ± 11 y | Follow-up 13 y | ↓ VK1 levels | ↑ CVD risk: HR = 1.12 (95% CI, 0.94–1.33) ↑ All-cause mortality |
Wessinger et al. 2020 USA [116] | 60 (11:49) chronic stroke 61.7 ± 7.2 y | Cross-sectional | VK dietary intake | Among stroke survivors, 82% reported consuming below the Dietary Reference Intake for VK |
Author, Year, Country [Ref.] | Subjects (W:M) Age (Mean ± SD) | Design (Length) | Intervention Investigations | Findings |
---|---|---|---|---|
Im et al. 2008 South Korea [129] | 339 PMW T2D 57.2 y | Biochemical and hormonal parameters for (1) NG; (2) IGF; (3) T2D groups | ↓ OC in (3) vs. (1) (p < 0.005) OC levels—inversely correlated with FG (r = −0.195, p < 0.001), HbA1c (r = −0.219, p < 0.001), FI (r = −0.131, p < 0.016), HOMA-IR (r = −0.163, p < 0.003) | |
Yoshida et al. 2008 USA [130] | 355 (213:142) 68 y | RCT 36 mo | 500 μg/d PK vs. control | ↓ HOMA-IR (p-adjusted < 0.01) and ↓ plasma insulin (p-adjusted < 0.04)—only for men ↓% ucOC (p < 0.001) for both men and women |
Kanazawa et al. 2009 Japan [131] | 329 (149:179) 65.8 y | Biochemical and hormonal parameters | Negative correlation between OC and FG and HbA1c (for all: p < 0.05),% fat, baPWV and IMT in men (p < 0.05) Positive correlation between OC and total adiponectin in PMF (p < 0.001) | |
Kindblom et al. 2009 Sweden [132] | 1010 M 857 non-T2D 153 T2D 75.3 ± 3.2 y | MrOS Sweden study | Biochemical and hormonal parameters | ↓ OC in T2D (−21.7%, p < 0.001) vs. non-T2D Plasma OC—inversely correlated with BMI, fat mass, and plasma glucose (p < 0.001) |
Shea et al. 2009 USA [133] | 348 (206:142) non-T2D 68 y | Cross sectional 3 y | OC levels (tOC, ucOC, cOC) and HOMA-IR | ↑ cOC and tOC were associated with ↓ HOMA-IR (p = 0.006 and p = 0.02, respectively) |
Bao et al. 2011 China [134] | 181 M 76 non-metS 105 metS 64.9 ± 10.7 y | Biochemical and hormonal parameters | ↓ OC in MetS vs. non-MetS (p < 0.001); OC was independently associated with metS (OR = 0.060, 95% CI: 0.005–0.651) | |
Alfadda et al. 2013 Saudi Arabia [135] | 203 T2D ± MetS 52.5 ± 9.6 y | Cross-sectional | Biochemical and hormonal parameters | ↓ tOC (p = 0.01) and ucOC (p = 0.03) in metS vs. non-metS. Positive correlation between ucOC and HDL-C (p = 0.023). Negative correlation between tOC and HbA1c (p = 0.01) and serum TGs (p = 0.049. |
Confraveux et al. 2014 France [136] | 798 M 65.3 ± 7 y | MINOS study | Biochemical and hormonal parameters | Negative correlation between OC and glycemia (p < 0.0001) |
Shea et al. 2017 USA [137] | 401 (237:164) 69 ± 6 y | RCT 3 y | 500 μg/d PK (+Ca and vitD) vs. control (Ca and vitD) | ↓ ucOC (p < 0.001) |
Knapen et al. 2018 Netherlands [138] | 214 PMW 60 y | RCT 3 y | 180 µg/d MK-7 vs. placebo | ↑ cOC (p < 0.0001) ↓ ucOC (p < 0.0001) |
Dumitru et al. 2019 Romania [139] | 146 PMW T2D 62.1 y | Cross sectional 30 mo | Biochemical and hormonal parameters in T2D group vs. control | ↓ tOC (p < 0.05) in T2D group Negative correlation between tOC and HbA1c, BMI, TGs (for all: p < 0.05), and HDL-C (p = 0.001) |
Guney et al. 2019 Turkey [140] | 191 PMW metS 56 y | cross-sectional | Biochemical and hormonal parameters in metS group vs. control | ↓ OC (p < 0.001) in metS group Positive correlation between vitD and OC (r = 0.198; p = 0.008) Negative correlation between OC and hs-CRP (p = 0.003), HOMA-IR (p = 0.048), and HbA1c (p = 0.001) |
Aguayo-Ruiz et al. 2020 Mexico [141] | 40 (24:16) T2D 56 y | RCT 3 mo | (1) 100 µg/d K2 (2) 100 µg/d K2+vit D3 (3) vit D3 | (1): ↓ glycemia (p = 0.002) ↑ cOC (p < 0.041) (2): ↓ glycemia (p = 0.002) |
Jeannin et al. 2020 France [142] | 198 (40:158) T2D 64 ± 8.4 y | Cohort | NDS, dp-ucMGP in plasma | ↑ peripheral NDS (15.7%) correlated with dp-ucMGP (r = 0.51, p < 0.0001) |
Sakak et al. 2020 Iran [143] | 68 (42:26) T2D 57.6 y | RCT 12 w | 360 μg MK-7 vs. placebo | ↓ FPG (p-adjusted = 0.031) ↓ HbA1c (p-adjusted = 0.004) ↓ HOMA-IR (p = 0.019) vs. baseline |
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Popa, D.-S.; Bigman, G.; Rusu, M.E. The Role of Vitamin K in Humans: Implication in Aging and Age-Associated Diseases. Antioxidants 2021, 10, 566. https://doi.org/10.3390/antiox10040566
Popa D-S, Bigman G, Rusu ME. The Role of Vitamin K in Humans: Implication in Aging and Age-Associated Diseases. Antioxidants. 2021; 10(4):566. https://doi.org/10.3390/antiox10040566
Chicago/Turabian StylePopa, Daniela-Saveta, Galya Bigman, and Marius Emil Rusu. 2021. "The Role of Vitamin K in Humans: Implication in Aging and Age-Associated Diseases" Antioxidants 10, no. 4: 566. https://doi.org/10.3390/antiox10040566