Open Access
Subscription Access
Open Access
Subscription Access
Vitamin K2 Insufficiency: Linking Acute Respiratory Distress Syndrome and Coagulopathy in Severity of COVID-19
Subscribe/Renew Journal
The recent pandemic due to Coronavirus Disease-19 (COVID-19) has been a very dreadful situation for mankind. It took a toll on every sector in the world besides the common people. Understanding the disease and its management on a fast-track was a big challenge to clinicians and researchers. The root cause of death due to COVID-19 was pneumonia and acute respiratory distress syndrome (ARDS). Several pathophysiological mechanisms involving lung damage, vascular coagulopathy and inflammation have been identified. Besides key risk factors viz. advanced age and comorbidities, insufficiency of micronutrients and vitamins is known to increase severity of the disease. Vitamin C and D supplementation was one of the components of the treatment algorithm in the management of COVID-19. Another vitamin, Vitamin K has been linked to COVID-19-associated severity. The present article reviews the scientific basis of this emerging notion and gives an overview of the types of Vitamin K– K1 and K2 with emphasis on Vitamin K2-7 and its functional benefits in reducing COVID 19-related morbidity and mortality.
Keywords
COVID-19, coronavirus, nutrient insufficiency, vitamin K2-7, ARDS, vascular coagulopathy, cardiovascular complications
Subscription
Login to verify subscription
User
Font Size
Information
- ZhonghuaLiu Xing Bing Xue Za ZhiEpidemiology Working Group for NCIP Epidemic Response, Chinese Center for Disease Control and Prevention. The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China [in Chinese]. 2020;41(02):145–151.
- Singhal T. A review of coronavirus disease-2019 (COVID-19). Indian J Pediatr 2020;87(04):281–286
- WHO1: World Health Statistics2021: A visual summary. Available from: https://www.who.int/data/stories/worldhealth-statistics-2021-a-visual-summary
- WHO 2: The true death toll of COVID-19: estimating global excess mortality. Available from: https://www.who.int/data/ stories/the-true-death-toll-of-covid-19-estimating-global-excess-mortality
- Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med. 2020;8:e21.
- Desai AP, Dirajlal-Fargo S, Durieux JC, Tribout H, Labbato D, McComsey GA. Vitamin K & D Deficiencies are independently associated with COVID-19 disease severity. Open Forum Infectious Diseases. 2021;8(10).
- Dofferhoff ASM, Piscaer I, Schurgers LJ, Visser MPJ, van den Ouweland JMW, de Jong PA, et al. Reduced vitamin K status as a potentially modifiable risk factor of severe COVID-19. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2020.
- . Janssen R, Visser MPJ, Dofferhoff ASM, Vermeer C, Janssens W, Walk J. Vitamin K metabolism as the potential missing link between lung damage and thromboembolism in Coronavirus disease 2019. The British journal of nutrition.2021;126(2):191-8
- Kudelko M, Yip TF, Hei Law GC, Lee SMY. Potential beneficial effects of Vitamin K in SARS-CoV-2 induced vascular Disease? Immuno. 2021;1(1):17-29.
- Halder M, Petsophonsakul P, Akbulut AC, Pavlic A. Vitamin K: Double bonds beyond coagulation insights into differences between Vitamin K1 and K2 in Health and Disease.2019;20(4)
- Maresz K. Growing evidence of a proven mechanism shows Vitamin K2 can impact health conditions beyond bone and cardiovascular. Integrative medicine (Encinitas, Calif). 2021;20(4):34-8.
- Mandatori D, Pelusi L, Schiavone V, Pipino C, Di Pietro N, Pandolfi A. The Dual role of Vitamin K2 in “Bone-Vascular Crosstalk”: Opposite Effects on Bone Loss and Vascular Calcification. Nutrients. 2021;13(4)
- Ravishankar B, Dound YA, Mehta DS, Ashok BK, de Souza A, Pan MH, et al. Safety assessment of menaquinone-7 for use in human nutrition. Journal of food and drug analysis.2015;23(1):99-108.
- Mehta D, de Souza A, Jadhav SS. Menaquinone-7: Wide Ranging Physiological Relevance in Muscle and Nerve Health.2021. doi: http://dx.doi.org/10.5772/intechopen.99809
- MenaquineGold: The Worlds Most Researched Natural Vitamin K2-7 that’s good for more than you thought possible. [accessed on 17th January 2022] Available from: http:// www.menaquingold.com/research.html
- Piscaer I, Wouters EFM, Vermeer C, Janssens W, Franssen FME, Janssen R. Vitamin K deficiency: the linking pin between COPD and cardiovascular diseases? Respiratory research. 2017;18(1):189.
- Piscaer I, van den Ouweland JMW, Vermeersch K, Reynaert NL, Franssen FME, Keene S, et al. Low Vitamin K Status is associated with increased elastin degradation in chronic obstructive pulmonary disease. Journal of clinical medicine.2019;8(8).
- Kuba K, Imai Y, Rao S, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. 2005;11:875–879
- Wrapp D, Wang N, Corbett KS, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science.2020;367:1260–1263
- Martines RB, Ritter JM, Matkovic E, Gary J, Bollweg BC, Bullock H, et al. Pathology and Pathogenesis of SARS-CoV-2 Associated with Fatal Coronavirus Disease, United States.Emerging infectious diseases. 2020;26(9):2005-15.
- Mohanty SK, Satapathy A, Naidu MM, Mukhopadhyay S, Sharma S, Barton LM, et al. Severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2) and coronavirus disease 19 (COVID-19) – anatomic pathology perspective on current knowledge. Diagnostic Pathology. 2020;15(1):103
- Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020; 395:507–13.
- Emami A, Javanmardi F, Pirbonyeh N, Akbari, A. Prevalence of underlying diseases in hospitalized patients with COVID-19: a systematic review and meta-analysis. Arch. Acad. Emerg. Med. 2020;8:35.
- Petrovic V, Radenkovic D, Radenkovic G, Djordjevic V, Banach M. Pathophysiology of Cardiovascular Complications in COVID-19. Frontiers in Physiology. 2020;11(1296).
- Guo T, Fan Y, Chen M, Wu X, Zhang L, He T, et al.Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019. 2020
- Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus– infected pneumonia in Wuhan, China. JAMA.2020;323:1061–1069. doi: 10.1001/jama.2020.1585
- Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese center for disease control and prevention. JAMA.2020;323:1239–1242. doi: 10.1001/jama.2020.2648
- Ranard LS, Fried JA, Abdalla M, Anstey DE, Givens RC, Kumaraiah D, Kodali SK, Takeda K, Karmpaliotis D, Rabbani LE, Sayer G, Kirtane AJ, Leon MB, Schwartz A, Uriel N, Masoumi A. Approach to Acute Cardiovascular Complications in COVID-19 Infection. Circ Heart Fail. 2020 Jul;13(7):e007220. doi: 10.1161/ CIRCHEARTFAILURE.120.007220.
- Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, et al. Association of Cardiac Injury with Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. JAMA Cardiol. 2020;5:802–810. doi: 10.1001/jamacardio.2020.0950
- Katneni UK, Alexaki A, Hunt RC, Schiller T, DiCuccio M, Buehler PW, et al. Coagulopathy and Thrombosis as a Result of Severe COVID-19 Infection: A Microvascular Focus. Thrombosis and haemostasis. 2020;120(12):1668-79.
- Petrovic V, Radenkovic D, Radenkovic G, Djordjevic V, Banach M.Pathophysiology of Cardiovascular Complications inCOVID-19. Frontiers in Physiology, 2020;11(1296).
- Fox SE, Akmatbekov A, Harbert JL, Li G,Brown JQ, Vander Heide RS. Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series fromNew Orleans Lancet Respir Med.2020;8(7):681-6doi:10.1016/ S2213-2600;(20):30243-5
- Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506.
- Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel corona virus pneumonia. J Thromb Haemost. 2020;18(4):844-847.
- Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-1062.
- Bourke CD, Berkley JA, Prendergast AJ. Immune dysfunction as a cause and consequence of malnutrition. Trends Immunol 2016;37:386–98
- McAuliffe S, Ray S, Fallon E, Bradfield J, Eden T, Kohlmeier M. Dietary micronutrients in the wake of COVID-19: an appraisal of evidence with a focus on high-risk groups and preventative healthcare. BMJ nutrition, prevention & health. 2020;3(1):93-9.
- Muthuvattur Pallath M, Ahirwar AK, Chandra Tripathi S, Asia P, Sakarde A, Gopal N. COVID-19 and nutritional deficiency: a review of existing knowledge. Hormone molecular biology and clinical investigation. 2021;42(1):77-85.
- D’Avolio A, Avataneo V, Manca A, Cusato J. 25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2. 2020;12(5).
- Hastie CE, Mackay DF, Ho F, Celis-Morales CA, Katikireddi SV, Niedzwiedz CL, et al. Vitamin D concentrations and COVID-19 infection in UK Biobank. Diabetes & metabolic syndrome. 2020;14(4):561-5.
- Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ (Clinical research ed). 2017;356:i6583.
- Goddek S. Vitamin D3 and K2 and their potential contribution to reducing the COVID-19 mortality rate. International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases. 2020;99:286-90
- Grant WB, Lahore H, McDonnell SL, Baggerly CA, French CB, Aliano JL, Bhattoa HP. Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths. Nutrients. 2020 Apr 2;12(4):988. doi: 10.3390/nu12040988. PMID: 32252338; PMCID: PMC7231123
- Walk J, Dofferhoff AS, van den Ouweland JM, van Daal H, Janssen R.Vitamin D – contrary to vitamin K – does not associate with clinical outcome in hospitalized COVID-19 patients. 2020.
- Dahlbäck B. Blood coagulation. Lancet 2000;355:1627–1632
- Al-Samkari H, Karp Leaf RS, Dzik WH, Carlson JCT, Fogerty AE, Waheed A, et al. COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection.Blood. 2020;136(4):489-500
- Speed V, Patel RK, Byrne R, Roberts LN, Arya R. A perfect storm: Root cause analysis of supra-therapeutic anticoagulation with vitamin K antagonists during the COVID-19 pandemic. Thrombosis research. 2020;192:73-4
- Williams H, Guidance for the safe switching of warfarin to direct oral anticoagulants (DOACs) for patients with nonvalvular AF and venous thromboembolism (DVT/PE) during the coronavirus pandemic. Royal College of General Practitioners and British Society of Haematology. 2020 26 March.
- Schurgers LJ, Uitto J, Reutelingsperger CP. Vitamin K-dependent carboxylation of matrix Gla-protein: A crucial switch to control ectopic mineralization. Trends Mol. Med.2013;19:217–226.
- Mithieux SM, Weiss AS. Elastin. Adv Protein Chem.2005;70:437-461.
- Ames BN. Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage. Proc Natl Acad Sci U S A. 2006;103:17589-17594
- Alperin JB. Coagulopathy caused by vitamin K deficiency in critically ill, hospitalized patients. JAMA. 1987;258(14):1916-9.
- Shea MK, O’Donnell CJ, Hoffmann U, Dallal GE, DawsonHughes B, Ordovas JM, Price PA, Williamson MK, Booth SL.Vitamin K supplementation and progression of coronary artery calcium in older men and women. Am. J. Clin. Nutr. 2009;89:1799–1807
- van Ballegooijen AJ, Pilz S, Tomaschitz A, Grübler MR, Verheyen N. The Synergistic Interplay between Vitamins D and K for Bone and Cardiovascular Health: A Narrative Review. International journal of endocrinology. 2017;2017:7454376
- Nelsestuen GL, Zytkovicz TH, Howard JB. The mode of action of vitamin K. Identification of gamma-carboxyglutamic acid as a component of prothrombin. J. Biol. Chem.1974;249:6347–6350.
- Nelsestuen GL, Suttie JW. Mode of action of vitamin K. Calcium binding properties of bovine prothrombin. Biochemistry 1972;11:4961–4964
- Pan MH, Maresz K, Lee PS, Wu JC, Ho CT, Popko J, Mehta D, Stohs SJ, Badmaev V. Inhibition of TNF-, IL-1, and IL-1 by Pretreatment of human monocyte-derived macrophages with Menaquinone-7 and cell activation with TLR Agonists In Vitro. J. Med. Food 2016;19:663–669.
- Akbulut AC, 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.
- Schurgers LJ, Teunissen KJ, Hamulyák K, Knapen MH, Vik H, Vermeer C. Vitamin K-containing dietary supplements: Comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood.2007;109:3279–3283
- Knapen MH, Drummen NE, Smit E, Vermeer C, Theuwissen E. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporosis international 2013 Sep;24(9):2499-507.
- Ronn SH, Harslof T, Oei L, Pedersen SB, Langdahl BL. The effect of vitamin MK-7 on bone mineral density and microarchitecture in postmenopausal women with osteopenia, a 3-year randomized, placebo-controlled clinical trial. Osteoporosis international 2021;32(1):185-91.
- Knapen MHJ, Jardon KM, Vermeer C. Vitamin K-induced effects on body fat and weight: results from a 3-year vitamin K2 intervention study. European journal of clinical nutrition. 2018;72(1):136-41
- Zhou J, Tan J. Vitamin K2 Supplementation for the prevention and treatment of rheumatoid arthritis: Curr Dev Nutr. 2021 Jun 7;5(Suppl 2):1334
- Lindholt JS, Frandsen NE, Fredgart MH, Øvrehus KA, Dahl JS, Møller JE, et al. Effects of menaquinone-7 supplementation in patients with aortic valve calcification: study protocol for a randomised controlled trial. 2018;8(8):e022019.
- Vossen LM, Schurgers LJ, van Varik BJ, Kietselaer BL, Vermeer C, Meeder JG, et al. Menaquinone-7 Supplementation to Reduce Vascular Calcification in Patients with Coronary Artery Disease: Rationale and Study Protocol (VitaK-CAC Trial). Nutrients. 2015;7(11):8905-15.
- Zwakenberg SR, de Jong PA, Bartstra JW, van Asperen R, Westerink J, de Valk H, et al. The effect of menaquinone-7 supplementation on vascular calcification in patients with diabetes: a randomized, double-blind, placebo-controlled trial. The American journal of clinical nutrition. 2019;110(4):88390.
- Maresz K. Proper Calcium Use: Vitamin K2 as a promoter of bone and cardiovascular Health. Integrative medicine (Encinitas, Calif). 2015;14(1):34-9.
Abstract Views: 98
PDF Views: 0