Viral Enfeksiyonda K2 Kullanımı Neden Önerilmektedir?
K vitamini, kan pıhtılaşmasına yardımcı olmasının ötesinde potansiyel bir terapötik ajan (tedavi edici) olarak önem kazanmıştır. K vitamininin iki biyoaktif formu bilinmektedir; K1 vitamini (Phytonadione/phylloquinone) ve K2 vitamini (menaquinones).
Yapılan araştırmalar neticesinde K2 (menaquinones) vitamininin K1'den daha üstün bir besin takviyesi olduğu bulgusuna ulaşılmıştır. K1 esas olarak yapraklı sebzelerden elde edilirken, K2 fermente ürünlerden ve bağırsak mikrobiyotasından elde edilmektedir. Bununla birlikte, viral enfeksiyonlarda kullanılan antibiyotiklerin bağırsak florasını bozduğu da bilinmektedir. Bu, vücut için gerekli K2 vitamini sentez yeteneğini de azaltan önemli bir sorundur.
K vitamini, yağda eriyen diğer vitaminler gibi vücutta birikmediğinden bedenin ihtiyaç duyduğu kadarının günlük olarak temini elzemdir. Kemik metabolizmasında çeşitli görevleri bulunan protein üretimi için de gerekli olduğundan mutlaka günlük olarak sağlanmalıdır.
K2 vitamini vücuttaki kalsiyum metabolizmasını düzenlerken aynı zamanda diyabet metabolizmasında da aktif görev alan bir vitamindir. K2 vitamini yetersizliği; osteoporoz, kemik kırıkları ve kardiyovasküler hastalık riskini arttırır.
Yukarıda yazılanlardan da anlaşılacağı üzere çok önemli bir vitamin olan K2, ne yazık ki henüz sağlık uzmanlarınca ve otoritelerce hak ettiği ilgiyi görmemektedir.
Bu yazıda çok kısa olarak;
1-Antibiyotik yazılan her reçetede neden K2 vitamini de olması gerektiği,
2-D vitamini ve C vitamini alırken, onlarla birlikte neden K2 vitamininin de alınması gerektiği,
3-Effervesan ürün tercihinin asıl nedeni, gibi sorulara cevap bulabileceğinizi düşünüyorum.
Yakın zamanda yaşadığımız ve pek çok yakınımızı kaybetmemize neden olan pandemide en önemli desteğimiz D vitamini olmuştu. D vitamini desteği ile ilgili olumlu görüşler her geçen gün artmaktadır (Grant et al.2020). Vitamin D düzeyinin 41 ng/ml üzerinde olmasının mortaliteye karşı önemli ölçüde koruyuculuk sağladığı 611 vakalık bir çalışma ile saptanmıştır (Maghbooli et al., 2020). Yüksekliğinin koruyucu olduğunu gösteren deliller bir yana, düşüklüğünün ciddi tehlike yarattığını bildiren yayınlar da vardır (Karonova et al., 2020). Avrupa Gıda Güvenliği Otoritesinin (EFSA, 2016) minimum 25(OH)D serum seviyesine ulaşılması için günlük 25 ng/dl tavsiye etmesi, vücut için gerekli dozajın doğruluğu hakkında şüphe uyandırmaktadır.
Toplumun düşük seviyelerde olan kan düzeyleri gerçeği karşısında belirli vitaminlerin yüksek dozlardaki kullanım önerileri, hastalıklara karşı savunmasız kalmamızın veya onlara aciz durumda yakalanmamızın kaçınılmaz olduğunu göstermektedir. Bu durum, yeterli vitamin düzeyi sağlamanın, halk sağlığı açısından hastalıklara karşı çok önemli koruyucu hizmet anlamına geleceği konusunu açıklamaktadır.
Ancak yüksek düzeylerde kullanılan tek taraflı vitamin destekleri de bazı zararlı etkiler oluşturabilir. Aşağıdaki karmaşık ağda belirtildiği gibi D vitamini pek çok diğer vitamin ve hormonal düzeyle doğrudan bağlantılıdır (şekil 1). Aşırı D vitamini alımı hipervitaminoz D olarak bilinen duruma sebep olabilir.
Bu D vitamini toksikasyonu kalsiyum artışı yaparak damar vasküler yapısında çökmelere vasküler kalsinozise (damar sertliğine), böbreklerde birikerek nefrokalsinozise (böbrek taşına) neden olur. Fakat çalışmalar bu hiperkalseminin asıl nedeninin K2 vitamin eksikliği olduğunu da göstermiştir (Flore et al., 2013; Vermeer and Theuwissen, 2011).
K2 vitamini kemik yapımından sorumlu olan osteokalsin proteinini (kalsiyumu kemik dokusuna yerleştiren protein yapıdaki hormon) aktive eder. Eğer D vitamini yüksek alınır ve K2 desteği alınmazsa osteokalsin aktive olmayacağı için kalsiyum kemiklerde biriktirilemez ve kan kalsiyumu yükselir. Bu da çeşitli dokularda çökerek sağlığa zarar verir.
Sözün özü, D vitamini etkilerinin antogonisti olarak K2, vücut homeostazı için de önemlidir. Bu nedenle D vitamini ve K2 vitamininin birlikte kullanımı önerilir. Viral salgınlarda kullanılan yüksek dozajlı D vitamini ve C vitamini tedavilerinde K2 verilmesi sağlık açısından çok önemlidir.
Effervesan konusuna gelecek olursak; genelde sıvı alımı arttırılmak istendiğinden effervesan gıda takviyelerinde D vitamini ve C vitamini birlikte sunulmuştur. Fakat son açıklanan veriler ışığında bu tarz ürünlerde K2 desteğinin preperatta olup olmadığına dikkat etmek ve mümkünse Vit D ,Vit C ve Vit K2 içeren kombine ürünlerin tercih edilmesi en doğru seçenek olacaktır (Yasui et al., 2006; Dofferhoff et al., 2020).
Özellikle yaşlı hastalarda, kalp damar sağlığı problemi olanlarda veya tanı almamış risk grubundaki kişilerde D vitamini ve C vitamini preperatı verirken yanında mutlaka K2 olmalıdır. Avrupa’da artık, insülin direnci olanlara veya Tip 2 diyabet tanı hastalara hastalıklardan korunma sağlanması ve tedavi desteği amacıyla C vitamini verilirken K2 ve D vitamini içeren kombinasyon yaygın olarak tercih edilmektedir.
Diğer Referans Kaynaklar:
1. Dam H. Cholesterinstoffwechsel in Huhnereien und Huhnchen.
Biochem Zeitschr 1929;215:475–92.
2. Tsugawa N, Shiraki M. Vitamin K nutrition and bone health. Nutrients
2020;12(7):1909.
3. Oxholm Gordeladze J. Vitamin K2: a vitamin that works like a hormone, impinging on gene expression. In: Ray S (ed.). Cell
Signalling—Thermodynamics and Molecular Control [Internet], IntechOpen, 2019. Available via https://www.intechopen.com/books/
cell-signalling-thermodynamics-and-molecular-control/vitamin-k2-a-vitamin-that-works-like-a-hormone-impinging-on-gene-expression (Accessed 15 May 2021).
4. Xv F, Chen J, Duan L, Li S. Research progress on the anticancer effects of vitamin K2 (Review). Oncol Lett [Internet] 2018. Available via http://www.spandidos-publications.com/10.3892/ol.2018.8502 (Accessed 15
May 2021).
5. Schwalfenberg GK. Vitamins K1 and K2: the emerging group of vitamins required for human health. J Nutr Metab 2017;2017:1–6.
6. Berenjian A, Mahanama R, Kavanagh J, Dehghani F. Vitamin K series: current status and future prospects. Crit Rev Biotechnol 2015;35(2):199–208.
7. Kojima A, Ikehara S, Kamiya K, Kajita E, Sato Y, Kouda K, et al. Natto intake is inversely associated with osteoporotic fracture risk in postmenopausal Japanese Women. J Nutr 2020;150(3):599–605.
8. DiNicolantonio JJ, Bhutani J, O’Keefe JH. The health benefits of vitamin K. Open Heart 2015;2(1):e000300.
9. w Walther B, Chollet M. Menaquinones, bacteria, and foods: vitamin K2 in the diet. In: Gordeladze JO (ed.). Vitamin K2—Vital for Health and Wellbeing [Internet], InTech, 2017. Available via http://www.
intechopen.com/books/vitamin-k2-vital-for-health-and-wellbeing/menaquinones-bacteria-and-foods-vitamin-k2-in-the-diet (Accessed 15 May 2021).
10. Shearer MJ, Newman P. Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis. J Lipid Res 2014;55(3):345–62.
11. Halder M, Petsophonsakul P, Akbulut A, Pavlic A, Bohan F, Anderson E, et al. Vitamin K: double bonds beyond coagulation insights into differences between vitamin K1 and K2 in health and disease. IJMS 2019;20(4):896.
12. Okano T, Shimomura Y, Yamane M, Suhara Y, Kamao M, Sugiura M, et al. Conversion of phylloquinone (vitamin K1) into menaquinone-4 (vitamin K2) in mice. J Biol Chem 2008;283(17):11270–9.
13. Hirota Y, Tsugawa N, Nakagawa K, Suhara Y, Tanaka K, Uchino Y, et al. Menadione (vitamin K3) is a catabolic product of oral phylloquinone (vitamin K1) in the intestine and a circulating
precursor of tissue menaquinone-4 (vitamin K2) in rats. J Biol Chem 2013;288(46):33071–80
1. Dam H. Cholesterinstoffwechsel in Huhnereien und Huhnchen. Biochem Zeitschr 1929;215:475–92.
2. Tsugawa N, Shiraki M. Vitamin K nutrition and bone health. Nutrients 2020;12(7):1909.
3. Oxholm Gordeladze J. Vitamin K2: a vitamin that works like a hormone, impinging on gene expression. In: Ray S (ed.). Cell
Signalling—Thermodynamics and Molecular Control [Internet], IntechOpen, 2019. Available via https://www.intechopen.com/books/
cell-signalling-thermodynamics-and-molecular-control/vitamin-k2-a-vitamin-that-works-like-a-hormone-impinging-on-gene-expression (Accessed 15 May 2021).
4. Xv F, Chen J, Duan L, Li S. Research progress on the anticancer effects of vitamin K2 (Review). Oncol Lett [Internet] 2018. Available via http://
www.spandidos-publications.com/10.3892/ol.2018.8502 (Accessed 15 May 2021).
5. Schwalfenberg GK. Vitamins K1 and K2: the emerging group of vitamins required for human health. J Nutr Metab 2017;2017:1–6.
6. Berenjian A, Mahanama R, Kavanagh J, Dehghani F. Vitamin K series: current status and future prospects. Crit Rev Biotechnol 2015;35(2):199–208.
7. Kojima A, Ikehara S, Kamiya K, Kajita E, Sato Y, Kouda K, et al. Natto intake is inversely associated with osteoporotic fracture risk in postmenopausal Japanese Women. J Nutr 2020;150(3):599–605.
8. DiNicolantonio JJ, Bhutani J, O’Keefe JH. The health benefits of vitamin K. Open Heart 2015;2(1):e000300.
9. w Walther B, Chollet M. Menaquinones, bacteria, and foods: vitamin K2 in the diet. In: Gordeladze JO (ed.). Vitamin K2—Vital for Health and Wellbeing [Internet], InTech, 2017. Available via http://www.intechopen.com/books/vitamin-k2-vital-for-health-and-wellbeing/menaquinones-bacteria-and-foods-vitamin-k2-in-the-diet (Accessed 15 May 2021).
10. Shearer MJ, Newman P. Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis. J Lipid Res 2014;55(3):345–62.
11. Halder M, Petsophonsakul P, Akbulut A, Pavlic A, Bohan F, Anderson E, et al. Vitamin K: double bonds beyond coagulation insights into differences between vitamin K1 and K2 in health and disease. IJMS 2019;20(4):896.
12. Okano T, Shimomura Y, Yamane M, Suhara Y, Kamao M, Sugiura M, et al. Conversion of phylloquinone (vitamin K1) into menaquinone-4 (vitamin K2) in mice. J Biol Chem 2008;283(17):11270–9.
13. Hirota Y, Tsugawa N, Nakagawa K, Suhara Y, Tanaka K, Uchino Y, et al. Menadione (vitamin K3) is a catabolic product of oral phylloquinone (vitamin K1) in the intestine and a circulating precursor of tissue menaquinone-4 (vitamin K2) in rats. J Biol Chem 2013;288(46):33071–80
1. Dam H. Cholesterinstoffwechsel in Huhnereien und Huhnchen.
Biochem Zeitschr 1929;215:475–92.
2. Tsugawa N, Shiraki M. Vitamin K nutrition and bone health. Nutrients 2020;12(7):1909.
3. Oxholm Gordeladze J. Vitamin K2: a vitamin that works like a hormone, impinging on gene expression. In: Ray S (ed.). Cell Signalling—Thermodynamics and Molecular Control [Internet], IntechOpen, 2019. Available via https://www.intechopen.com/books/cell-signalling-thermodynamics-and-molecular-control/vitamin-k2-a-vitamin-that-works-like-a-hormone-impinging-on-gene-expression (Accessed 15 May 2021).
4. Xv F, Chen J, Duan L, Li S. Research progress on the anticancer effects of vitamin K2 (Review). Oncol Lett [Internet] 2018. Available via http://www.spandidos-publications.com/10.3892/ol.2018.8502 (Accessed 15 May 2021).
5. Schwalfenberg GK. Vitamins K1 and K2: the emerging group of vitamins required for human health. J Nutr Metab 2017;2017:1–6.
6. Berenjian A, Mahanama R, Kavanagh J, Dehghani F. Vitamin K series: current status and future prospects. Crit Rev Biotechnol 2015;35(2):199–208.
7. Kojima A, Ikehara S, Kamiya K, Kajita E, Sato Y, Kouda K, et al. Natto intake is inversely associated with osteoporotic fracture risk in postmenopausal Japanese Women. J Nutr 2020;150(3):599–605.
8. DiNicolantonio JJ, Bhutani J, O’Keefe JH. The health benefits of vitamin K. Open Heart 2015;2(1):e000300.
9. w Walther B, Chollet M. Menaquinones, bacteria, and foods: vitamin K2 in the diet. In: Gordeladze JO (ed.). Vitamin K2—Vital for Health and Wellbeing [Internet], InTech, 2017. Available via http://www.intechopen.com/books/vitamin-k2-vital-for-health-and-wellbeing/menaquinones-bacteria-and-foods-vitamin-k2-in-the-diet (Accessed 15 May 2021).
10. Shearer MJ, Newman P. Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis. J Lipid Res 2014;55(3):345–62.
11. Halder M, Petsophonsakul P, Akbulut A, Pavlic A, Bohan F, Anderson E, et al. Vitamin K: double bonds beyond coagulation insights into differences between vitamin K1 and K2 in health and disease. IJMS 2019;20(4):896.
12. Okano T, Shimomura Y, Yamane M, Suhara Y, Kamao M, Sugiura M, et al. Conversion of phylloquinone (vitamin K1) into menaquinone-4 (vitamin K2) in mice. J Biol Chem 2008;283(17):11270–9.
13. Hirota Y, Tsugawa N, Nakagawa K, Suhara Y, Tanaka K, Uchino Y, et al. Menadione (vitamin K3) is a catabolic product of oral phylloquinone (vitamin K1) in the intestine and a circulating precursor of tissue menaquinone-4 (vitamin K2) in rats. J Biol Chem 2013;288(46):33071–80.
14. Simes DC, Viegas CSB, Araújo N, Marreiros C. Vitamin K as a diet supplement with impact in human health: current evidence in age-related diseases. Nutrients 2020;12(1):138.
15. Ayombil F, Camire RM. Insights into vitamin K-dependent carboxylation: home field advantage. Haematologica 2020;105(8): 1996–8.
16. Akbari S, Rasouli-Ghahroudi AA. Vitamin K and bone metabolism: a review of the latest evidence in preclinical studies. BioMed Rese Int 2018;2018:1–8.
17. Liu S, Li S, Shen G, Sukumar N, Krezel AM, Li W. Structural basis of antagonizing the vitamin K catalytic cycle for anticoagulation. Science 2021;371(6524):eabc5667.
18. Jones DA, Wright P, Alizadeh MA, Fhadil S, Rathod KS, Guttmann O, et al. The use of novel oral anti-coagulant’s (NOAC) compared to vitamin K antagonists (Warfarin) in patients with left ventricular thrombus after acute myocardial infarction (AMI). Eur Heart J Cardiovasc Pharmacother 2020; pvaa096; doi:10.1093/ehjcvp/pvaa096
19. Akbulut AC, Pavlic A, Petsophonsakul P, Halder M, Maresz K, Kramann R, et al. Vitamin K2 needs an RDI separate from vitamin K1. Nutrients 2020;12(6):1852.
20. Braasch-Turi M, Crans DC. Synthesis of naphthoquinone derivatives: menaquinones, lipoquinones and other vitamin K derivatives. Molecules 2020;25(19):4477.
21. Song J, Liu H, Wang L, Dai J, Liu Y, Liu H, et al. Enhanced production of vitamin K2 from Bacillus subtilis (natto) by mutation and optimization of the fermentation medium. Braz Arch Biol Technol 2014;57(4):606–12.
22. Wu WJ, Ahn BY. Statistical optimization of medium components by response surface methodology to enhance menaquinone-7 (vitamin K2) production by Bacillus subtilis. J Microbiol Biotechnol 2018;28(6):902–8.
23. Ren L, Peng C, Hu X, Han Y, Huang H. Microbial production of vitamin K2: current status and future prospects. Biotechnol Adv 2020;39:107453.
24. Bøe CA, Holo H. Engineering Lactococcus lactis for increased vitamin K2 production. Front Bioeng Biotechnol 2020;8:191.
25. Kamao M, Suhara Y, Tsugawa N, Uwano M, Yamaguchi N, Uenishi K, et al. Vitamin K content of foods and dietary vitamin K intake in Japanese young women. J Nutr Sci Vitaminol 2007;53(6):464–70.
26. Walther B, Karl JP, Booth SL, Boyaval P. Menaquinones, bacteria, and the food supply: the relevance of dairy and fermented food products to vitamin K requirements. Adv Nutr 2013;4(4):463–73.
27. Geleijnse JM, Vermeer C, Grobbee DE, Schurgers LJ, Knapen MHJ, van der Meer IM, et al. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the rotterdam study. J Nutr 2004;134(11):3100–5.
28. McCann JC, Ames BN. Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging? Am J Clin Nutr 2009;90(4):889–907.
29. Tutusaus A, Marí M, Ortiz-Pérez JT, Nicolaes GAF, Morales A, García 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(10):2186.
30. Jagannath VA, Thaker V, Chang AB, Price AI. Vitamin K supplementation for cystic fibrosis. Cochrane Database Syst Rev [Internet] 2020; doi:10.1002/14651858.CD008482.pub6 (Accessed 17 May 2021).
31. Katayama T, Yokoyama N, Hirofumi H, Kataoka A, Watanabe Y, Kozuma K. Blood coagulation status after transcatheter aortic valve implantation between the patients with vitamin K antagonist and direct oral anticoagulants. Eur Heart J 2020;41(Supplement_2):ehaa946.1992.
32. Al-Suhaimi EA, Al-Jafary MA. Endocrine roles of vitamin K-dependent- osteocalcin in the relation between bone metabolism and metabolic disorders. Rev Endocr Metab Disord 2020;21(1): 117–25
1. Dam H. Cholesterinstoffwechsel in Huhnereien und Huhnchen. Biochem Zeitschr 1929;215:475–92.
2. Tsugawa N, Shiraki M. Vitamin K nutrition and bone health. Nutrients 2020;12(7):1909.
3. Oxholm Gordeladze J. Vitamin K2: a vitamin that works like a hormone, impinging on gene expression. In: Ray S (ed.). Cell Signalling—Thermodynamics and Molecular Control [Internet], IntechOpen, 2019. Available via https://www.intechopen.com/books/cell-signalling-thermodynamics-and-molecular-control/vitamin-k2-a-vitamin-that-works-like-a-hormone-impinging-on-gene-expression (Accessed 15 May 2021).
4. Xv F, Chen J, Duan L, Li S. Research progress on the anticancer effects of vitamin K2 (Review). Oncol Lett [Internet] 2018. Available via http://www.spandidos-publications.com/10.3892/ol.2018.8502 (Accessed 15 May 2021).
5. Schwalfenberg GK. Vitamins K1 and K2: the emerging group of vitamins required for human health. J Nutr Metab 2017;2017:1–6.6. Berenjian A, Mahanama R, Kavanagh J, Dehghani F. Vitamin K series: current status and future prospects. Crit Rev Biotechnol 2015;35(2):199–208.
7. Kojima A, Ikehara S, Kamiya K, Kajita E, Sato Y, Kouda K, et al. Natto intake is inversely associated with osteoporotic fracture risk in postmenopausal Japanese Women. J Nutr 2020;150(3):599–605.
8. DiNicolantonio JJ, Bhutani J, O’Keefe JH. The health benefits of vitamin K. Open Heart 2015;2(1):e000300.
9. w Walther B, Chollet M. Menaquinones, bacteria, and foods: vitamin K2 in the diet. In: Gordeladze JO (ed.). Vitamin K2—Vital for Health and Wellbeing [Internet], InTech, 2017. Available via http://www.intechopen.com/books/vitamin-k2-vital-for-health-and-wellbeing/menaquinones-bacteria-and-foods-vitamin-k2-in-the-diet (Accessed 15 May 2021).
10. Shearer MJ, Newman P. Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis. J Lipid Res 2014;55(3):345–62.
11. Halder M, Petsophonsakul P, Akbulut A, Pavlic A, Bohan F, Anderson E, et al. Vitamin K: double bonds beyond coagulation insights into differences between vitamin K1 and K2 in health and disease. IJMS 2019;20(4):896.
12. Okano T, Shimomura Y, Yamane M, Suhara Y, Kamao M, Sugiura M, et al. Conversion of phylloquinone (vitamin K1) into menaquinone-4 (vitamin K2) in mice. J Biol Chem 2008;283(17):11270–9.
13. Hirota Y, Tsugawa N, Nakagawa K, Suhara Y, Tanaka K, Uchino Y, et al. Menadione (vitamin K3) is a catabolic product of oral phylloquinone (vitamin K1) in the intestine and a circulating precursor of tissue menaquinone-4 (vitamin K2) in rats. J Biol Chem 2013;288(46):33071–80.
14. Simes DC, Viegas CSB, Araújo N, Marreiros C. Vitamin K as a diet supplement with impact in human health: current evidence in age-related diseases. Nutrients 2020;12(1):138.
15. Ayombil F, Camire RM. Insights into vitamin K-dependent carboxylation: home field advantage. Haematologica 2020;105(8): 1996–8.
16. Akbari S, Rasouli-Ghahroudi AA. Vitamin K and bone metabolism: a review of the latest evidence in preclinical studies. BioMed Rese Int 2018;2018:1–8.
17. Liu S, Li S, Shen G, Sukumar N, Krezel AM, Li W. Structural basis of antagonizing the vitamin K catalytic cycle for anticoagulation. Science 2021;371(6524):eabc5667.
18. Jones DA, Wright P, Alizadeh MA, Fhadil S, Rathod KS, Guttmann O, et al. The use of novel oral anti-coagulant’s (NOAC) compared to vitamin K antagonists (Warfarin) in patients with left ventricular thrombus after acute myocardial infarction (AMI). Eur Heart J Cardiovasc Pharmacother 2020; pvaa096; doi:10.1093/ehjcvp/pvaa096
19. Akbulut AC, Pavlic A, Petsophonsakul P, Halder M, Maresz K, Kramann R, et al. Vitamin K2 needs an RDI separate from vitamin K1. Nutrients 2020;12(6):1852.
20. Braasch-Turi M, Crans DC. Synthesis of naphthoquinone derivatives: menaquinones, lipoquinones and other vitamin K derivatives. Molecules 2020;25(19):4477.
21. Song J, Liu H, Wang L, Dai J, Liu Y, Liu H, et al. Enhanced production of vitamin K2 from Bacillus subtilis (natto) by mutation and optimization of the fermentation medium. Braz Arch Biol Technol 2014;57(4):606–12.
22. Wu WJ, Ahn BY. Statistical optimization of medium components by response surface methodology to enhance menaquinone-7 (vitamin K2) production by Bacillus subtilis. J Microbiol Biotechnol 2018;28(6):902–8.
23. Ren L, Peng C, Hu X, Han Y, Huang H. Microbial production of vitamin K2: current status and future prospects. Biotechnol Adv 2020;39:107453.
24. Bøe CA, Holo H. Engineering Lactococcus lactis for increased vitamin K2 production. Front Bioeng Biotechnol 2020;8:191.
25. Kamao M, Suhara Y, Tsugawa N, Uwano M, Yamaguchi N, Uenishi K, et al. Vitamin K content of foods and dietary vitamin K intake in Japanese young women. J Nutr Sci Vitaminol 2007;53(6):464–70.
26. Walther B, Karl JP, Booth SL, Boyaval P. Menaquinones, bacteria, and the food supply: the relevance of dairy and fermented food products to vitamin K requirements. Adv Nutr 2013;4(4):463–73.
27. Geleijnse JM, Vermeer C, Grobbee DE, Schurgers LJ, Knapen MHJ, van der Meer IM, et al. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the rotterdam study. J Nutr 2004;134(11):3100–5.
28. McCann JC, Ames BN. Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging? Am J Clin Nutr 2009;90(4):889–907.
29. Tutusaus A, Marí M, Ortiz-Pérez JT, Nicolaes GAF, Morales A, García 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(10):2186.
30. Jagannath VA, Thaker V, Chang AB, Price AI. Vitamin K supplementation for cystic fibrosis. Cochrane Database Syst Rev [Internet] 2020; doi:10.1002/14651858.CD008482.pub6 (Accessed 17 May 2021).
31. Katayama T, Yokoyama N, Hirofumi H, Kataoka A, Watanabe Y, Kozuma K. Blood coagulation status after transcatheter aortic valve implantation between the patients with vitamin K antagonist and direct oral anticoagulants. Eur Heart J 2020;41(Supplement_2):ehaa946.1992.
32. Al-Suhaimi EA, Al-Jafary MA. Endocrine roles of vitamin K-dependent- osteocalcin in the relation between bone metabolism and metabolic disorders. Rev Endocr Metab Disord 2020;21(1): 117–25
1. Dam H. Cholesterinstoffwechsel in Huhnereien und Huhnchen. Biochem Zeitschr 1929;215:475–92.
2. Tsugawa N, Shiraki M. Vitamin K nutrition and bone health. Nutrients 2020;12(7):1909.
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