Vitamins K2 and D3 Improve Long COVID, Fungal Translocation, and Inflammation: Randomized Controlled Trial
Ornina Atieh, Joviane Daher, Jared C Durieux, Marc Abboud, Danielle Labbato, Jhony Baissary, Ziad Koberssy, Kate Ailstock, Morgan Cummings, Nicholas T Funderburg, Grace A Mccomsey
Nutrients, doi:10.3390/nu17020304
Background: Long COVID (LC) is characterized by persistent symptoms at least 3 months after a SARS-COV-2 infection. LC has been associated with fungal translocation, gut dysfunction, and enhanced systemic inflammation. Currently, there is no approved treatment for this condition. The anti-inflammatory effect of vitamins K2 and D3 was shown to help attenuate the course of acute COVID-19 infection. Objective and hypothesis: This trial aims to investigate the effects of vitamins K2/D3 on LC symptoms, as well as gut and inflammatory markers, in people with established long COVID. Our hypothesis is that by attenuating systemic inflammation, vitamins K2/D3 will improve long COVID symptoms. Methods: This single-site randomized controlled study enrolled adults experiencing ≥2 moderate LC symptoms at least 3 months after a COVID-19 infection. The RECOVER Long COVID Research Index and number and type of LC symptoms were considered. Participants were randomized 2:1 to daily 240 µg K2 (pure MK-7 form) and 2000 UI vitamin D3 or standard of care (SOC) for 24 weeks. The endpoints were changes in symptomatology and in select inflammatory, metabolic, and gut biomarkers at 24 weeks. Results: We enrolled 151 participants (n = 98 received vit K2/D3 and 53 received SOC). The median age was 46 years; 71% were female and 29% were non-white. Baseline demographics were balanced between groups. At 24 weeks, the active treatment group only had a sharp increase in 25(OH) D, indicating good treatment adherence. In the vitamin K2/D3 arm, there was a 7.1% decrease in the proportion who had an LC Index ≥12 (vs. a 7.2% increase in the SOC group; p = 0.01). The average number of LC symptoms remained stable in the vitamin K2/D3 arm but increased in the SOC arm (p = 0.03). Additionally, reductions in oxidized LDL, inflammatory markers sTNF-RI and sCD163, and fungal translocation marker (1,3)β-d-glucan were observed in the vitamin K2/D3 arm compared to the SOC arm (p < 0.01) over 24 weeks. Conclusions: Vitamins K2/D3 improved the RECOVER Long COVID Index, the number of LC symptoms, and several gut and inflammatory markers. Vitamins K2/D3 provide a promising safe intervention for people suffering from long COVID.
Supplementary Materials: The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/nu17020304/s1 , Supplementary Table S1 : Symptom Resolution by Type. Supplementary Table S2 : Adverse Events Frequency by Type. Author Contributions: G.A.M. designed and supervised the study and received funding. D.L. contributed to the acquisition of data. J.C.D., O.A. and G.A.M. contributed to the analysis and interpretation of data. J.C.D. contributed to statistical analysis. M.C., K.A. and N.T.F. performed laboratory procedures. O.A., J.C.D., J.D., M.A., J.B., Z.K. and G.A.M. drafted the manuscript, and all authors contributed to the critical revision of the manuscript for important intellectual content. All authors have read and agreed to the published version of the manuscript. Conflicts of Interest: G.A.M. reports a relationship with Genentech and Pfizer that includes funding grants (paid to their institution). Also, G.A.M. served as a research consultant for Gilead, Glaxo-SmithKline, and Merck, unrelated to this study. NTF has received funding from Gilead, unrelated to this study. All other authors report no conflicts of interest.
References
Aguayo-Ruiz, García-Cobián, Pascoe-González, Sánchez-Enríquez, Llamas-Covarrubias et al., 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,
doi:10.1186/s13098-020-00580-wAli, Driscoll, Walters, Limper, Carmona, Beta-Glucan Activated Human B-Lymphocytes Participate in Innate Immune Responses by Releasing Pro-Inflammatory Cytokines and Stimulating Neutrophil Chemotaxis, J. Immunol,
doi:10.4049/jimmunol.1500559Allen, Kelly, Basdeo, Kinsella, Mulready et al., A Pilot Study of the Immunological Effects of High-Dose Vitamin D in Healthy Volunteers, Mult. Scler,
doi:10.1177/1352458512442992Ancona, Alagna, Alteri, Palomba, Tonizzo et al., Gut and Airway Microbiota Dysbiosis and Their Role in COVID-19 and Long-COVID, Front. Immunol,
doi:10.3389/fimmu.2023.1080043Ao, Kikuta, Ishii, Biomolecules The Effects of Vitamin D on Immune System and Inflammatory Diseases, Biomolecules,
doi:10.3390/biom11111624Athanassiou, Mavragani, Koutsilieris Mediterr, MEDITERRANEAN JOURNAL OF RHEUMATOLOGY The Immunomodulatory Properties of Vitamin D, Mediterr. J. Rheumatol,
doi:10.31138/mjr.33.1.7Bekkering, Quintin, Joosten, Van Der Meer, Netea et al., Oxidized Low-Density Lipoprotein Induces Long-Term Proinflammatory Cytokine Production and Foam Cell Formation via Epigenetic Reprogramming of Monocytes, Arterioscler. Thromb. Vasc. Biol,
doi:10.1161/ATVBAHA.114.303887Ben-Eltriki, Hopefl, Wright, Deb, Association between Vitamin D Status and Risk of Developing Severe COVID-19 Infection: A Meta-Analysis of Observational Studies, J. Am. Nutr. Assoc,
doi:10.1080/07315724.2021.1951891Dofferhoff, Piscaer, Schurgers, Visser, Van Den Ouweland et al., Reduced Vitamin K Status as a Potentially Modifiable Risk Factor of Severe COVID-19, Clin. Infect. Dis,
doi:10.1093/cid/ciaa1258Dumas, Bernard, Poquet, Lugo-Villarino, Neyrolles, The Role of the Lung Microbiota and the Gut-Lung Axis in Respiratory Infectious Diseases, Cell Microbiol,
doi:10.1111/cmi.12966Giron, Peluso, Ding, Kenny, Zilberstein et al., Markers of Fungal Translocation Are Elevated during Post-Acute Sequelae of SARS-CoV-2 and Induce NF-KB Signaling, JCI Insight,
doi:10.1172/jci.insight.164813Goddek, Vitamin D3 and K2 and Their Potential Contribution to Reducing the COVID-19 Mortality Rate, Int. J. Infect. Dis,
doi:10.1016/j.ijid.2020.07.080Grant, Lahore, Mcdonnell, Baggerly, French et al., Evidence That Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths, Nutrients,
doi:10.3390/nu12040988Hope, Evering, Postacute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 Infection, Infect. Dis. Clin. N. Am,
doi:10.1016/j.idc.2022.02.004Janssen, Visser, Dofferhoff, Vermeer, Janssens et al., Vitamin K Metabolism as the Potential Missing Link between Lung Damage and Thromboembolism in Coronavirus Disease, Br. J. Nutr,
doi:10.1017/S0007114520003979Janus, Durieux, Hajjari, Carneiro, Mccomsey, Inflammation-Mediated Vitamin K and Vitamin D Effects on Vascular Calcifications in People with HIV on Active Antiretroviral Therapy, AIDS,
doi:10.1097/QAD.0000000000003149Lapin, Li, Englund, Katzan, Health-Related Quality of Life for Patients with Post-Acute COVID-19 Syndrome: Identification of Symptom Clusters and Predictors of Long-Term Outcomes, J. Gen. Intern. Med,
doi:10.1007/s11606-024-08688-9Linneberg, Kampmann, Israelsen, Andersen, Jørgensen et al., The Association of Low Vitamin K Status with Mortality in a Cohort of 138 Hospitalized Patients with COVID-19, Nutrients,
doi:10.3390/nu13061985Maghbooli, Ebrahimi, Shirvani, Nasiri, Pazoki et al., Vitamin D Sufficiency Reduced Risk for Morbidity and Mortality in COVID-19 Patients, Lancet,
doi:10.2139/ssrn.3616008Mouchati, Durieux, Zisis, Labbato, Rodgers et al., Increase in Gut Permeability and Oxidized Ldl Is Associated with Post-Acute Sequelae of SARS-CoV-2, Front. Immunol,
doi:10.3389/fimmu.2023.1182544Proal, Vanelzakker, Aleman, Bach, Boribong et al., SARS-CoV-2 Reservoir in Post-Acute Sequelae of COVID-19 (PASC), Nat. Immunol,
doi:10.1038/s41590-023-01601-2Pugach, Pugach, Strong Correlation between Prevalence of Severe Vitamin D Deficiency and Population Mortality Rate from COVID-19 in Europe, Wien. Klin. Wochenschr,
doi:10.1007/s00508-021-01833-yQasemi, Ghavamzadeh, Faghfouri, Valizadeh, Mohammadi et al., The Effect of Vitamin D Supplementation on Flow-Mediated Dilatation, Oxidized LDL and Intracellular Adhesion Molecule 1 on Type 2 Diabetic Patients with Hypertension: A Randomized, Placebo-Controlled, Double-Blind Trial, Diabetes Metab. Syndr. Clin. Res. Rev,
doi:10.1016/j.dsx.2021.102200Radkhah, Zarezadeh, Jamilian, Ostadrahimi, The Effect of Vitamin D Supplementation on Lipid Profiles: An Umbrella Review of Meta-Analyses, Adv. Nutr,
doi:10.1016/j.advnut.2023.08.012Roumeliotis, Georgianos, Visser, Dofferhoff, Van Den Ouweland et al., Effects of Vitamin D and K on Interleukin-6 in COVID-19, Front. Nutr,
doi:10.3389/fnut.2021.761191Singh, Jain, Prakash, Thakur, Studies on the Synergistic Interplay of Vitamin D and K for Improving Bone and Cardiovascular Health, Curr. Res. Nutr. Food Sci. J,
doi:10.12944/CRNFSJ.10.3.3Sobczak, Pawliczak, Effect of Vitamin D3 Supplementation on Severe COVID-19: A Meta-Analysis of Randomized Clinical Trials, Nutrients,
doi:10.3390/nu16101402Tarkesh, Namavar, Jahromi, Hejazi, Tabatabaee, Beneficial Health Effects of Menaquinone-7 on Body Composition, Glycemic Indices, Lipid Profile, and Endocrine Markers in Polycystic Ovary Syndrome Patients, Food. Sci. Nutr,
doi:10.1002/fsn3.1837Thaweethai, Jolley, Karlson, Levitan, Levy et al., Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection, JAMA,
doi:10.1001/jama.2023.8823Woodrow, Carey, Ziauddeen, Thomas, Akrami et al., Systematic Review of the Prevalence of Long COVID, Open Forum Infect. Dis,
doi:10.1093/ofid/ofad233Zhao, Li, Hasan Rashedi, Sohouli, Rohani et al., The Effect of Vitamin K Supplementation on Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis, J. Nutr. Sci,
doi:10.1017/jns.2023.106Zisis, Durieux, Mouchati, Funderburg, Ailstock et al., Arterial Stiffness and Oxidized LDL Independently Associated With Post-Acute Sequalae of SARS-CoV-2, Pathog. Immun,
doi:10.20411/pai.v8i2.634{ 'indexed': { 'date-parts': [[2025, 1, 17]],
'date-time': '2025-01-17T05:16:10Z',
'timestamp': 1737090970013,
'version': '3.33.0'},
'reference-count': 41,
'publisher': 'MDPI AG',
'issue': '2',
'license': [ { 'start': { 'date-parts': [[2025, 1, 16]],
'date-time': '2025-01-16T00:00:00Z',
'timestamp': 1736985600000},
'content-version': 'vor',
'delay-in-days': 0,
'URL': 'https://creativecommons.org/licenses/by/4.0/'}],
'funder': [ { 'DOI': '10.13039/100012729',
'name': 'Clinical and Translational Science Collaborative (CTSC) of Northern Ohio',
'doi-asserted-by': 'publisher',
'award': ['UM1TR004528'],
'id': [{'id': '10.13039/100012729', 'id-type': 'DOI', 'asserted-by': 'publisher'}]},
{'name': 'Kimble Foundation'},
{'name': 'CanPrev Natural Health Products, Ltd., Ontario Canada'}],
'content-domain': {'domain': [], 'crossmark-restriction': False},
'abstract': '<jats:p>Background: Long COVID (LC) is characterized by persistent symptoms at least 3 months '
'after a SARS-COV-2 infection. LC has been associated with fungal translocation, gut '
'dysfunction, and enhanced systemic inflammation. Currently, there is no approved treatment '
'for this condition. The anti-inflammatory effect of vitamins K2 and D3 was shown to help '
'attenuate the course of acute COVID-19 infection. Objective and hypothesis: This trial aims '
'to investigate the effects of vitamins K2/D3 on LC symptoms, as well as gut and inflammatory '
'markers, in people with established long COVID. Our hypothesis is that by attenuating '
'systemic inflammation, vitamins K2/D3 will improve long COVID symptoms. Methods: This '
'single-site randomized controlled study enrolled adults experiencing ≥2 moderate LC symptoms '
'at least 3 months after a COVID-19 infection. The RECOVER Long COVID Research Index and '
'number and type of LC symptoms were considered. Participants were randomized 2:1 to daily 240 '
'µg K2 (pure MK-7 form) and 2000 UI vitamin D3 or standard of care (SOC) for 24 weeks. The '
'endpoints were changes in symptomatology and in select inflammatory, metabolic, and gut '
'biomarkers at 24 weeks. Results: We enrolled 151 participants (n = 98 received vit K2/D3 and '
'53 received SOC). The median age was 46 years; 71% were female and 29% were non-white. '
'Baseline demographics were balanced between groups. At 24 weeks, the active treatment group '
'only had a sharp increase in 25(OH) D, indicating good treatment adherence. In the vitamin '
'K2/D3 arm, there was a 7.1% decrease in the proportion who had an LC Index ≥12 (vs. a 7.2% '
'increase in the SOC group; p = 0.01). The average number of LC symptoms remained stable in '
'the vitamin K2/D3 arm but increased in the SOC arm (p = 0.03). Additionally, reductions in '
'oxidized LDL, inflammatory markers sTNF-RI and sCD163, and fungal translocation marker '
'(1,3)-β-d-glucan were observed in the vitamin K2/D3 arm compared to the SOC arm (p < 0.01) '
'over 24 weeks. Conclusions: Vitamins K2/D3 improved the RECOVER Long COVID Index, the number '
'of LC symptoms, and several gut and inflammatory markers. Vitamins K2/D3 provide a promising '
'safe intervention for people suffering from long COVID.</jats:p>',
'DOI': '10.3390/nu17020304',
'type': 'journal-article',
'created': {'date-parts': [[2025, 1, 16]], 'date-time': '2025-01-16T09:55:19Z', 'timestamp': 1737021319000},
'page': '304',
'source': 'Crossref',
'is-referenced-by-count': 0,
'title': 'Vitamins K2 and D3 Improve Long COVID, Fungal Translocation, and Inflammation: Randomized '
'Controlled Trial',
'prefix': '10.3390',
'volume': '17',
'author': [ { 'ORCID': 'https://orcid.org/0009-0004-3112-8944',
'authenticated-orcid': False,
'given': 'Ornina',
'family': 'Atieh',
'sequence': 'first',
'affiliation': [ { 'name': 'School of Medicine, Case Western Reserve University, Cleveland, '
'OH 44106, USA'}]},
{ 'ORCID': 'https://orcid.org/0009-0007-9008-4066',
'authenticated-orcid': False,
'given': 'Joviane',
'family': 'Daher',
'sequence': 'additional',
'affiliation': [ { 'name': 'School of Medicine, Case Western Reserve University, Cleveland, '
'OH 44106, USA'}]},
{ 'given': 'Jared C.',
'family': 'Durieux',
'sequence': 'additional',
'affiliation': [ { 'name': 'Clinical Research Center, University Hospitals Cleveland Medical '
'Center, Cleveland, OH 44106, USA'}]},
{ 'given': 'Marc',
'family': 'Abboud',
'sequence': 'additional',
'affiliation': [{'name': 'Faculty of Medicine, Saint Joseph University, Beirut, Lebanon'}]},
{ 'given': 'Danielle',
'family': 'Labbato',
'sequence': 'additional',
'affiliation': [ { 'name': 'Clinical Research Center, University Hospitals Cleveland Medical '
'Center, Cleveland, OH 44106, USA'}]},
{ 'given': 'Jhony',
'family': 'Baissary',
'sequence': 'additional',
'affiliation': [ { 'name': 'School of Medicine, Case Western Reserve University, Cleveland, '
'OH 44106, USA'}]},
{ 'ORCID': 'https://orcid.org/0009-0002-6819-1926',
'authenticated-orcid': False,
'given': 'Ziad',
'family': 'Koberssy',
'sequence': 'additional',
'affiliation': [ { 'name': 'School of Medicine, Case Western Reserve University, Cleveland, '
'OH 44106, USA'}]},
{ 'given': 'Kate',
'family': 'Ailstock',
'sequence': 'additional',
'affiliation': [ { 'name': 'School of Health and Rehabilitation Sciences, Ohio State '
'University, Columbus, OH 43210, USA'}]},
{ 'given': 'Morgan',
'family': 'Cummings',
'sequence': 'additional',
'affiliation': [ { 'name': 'School of Health and Rehabilitation Sciences, Ohio State '
'University, Columbus, OH 43210, USA'}]},
{ 'given': 'Nicholas T.',
'family': 'Funderburg',
'sequence': 'additional',
'affiliation': [ { 'name': 'School of Health and Rehabilitation Sciences, Ohio State '
'University, Columbus, OH 43210, USA'}]},
{ 'ORCID': 'https://orcid.org/0000-0003-2690-8888',
'authenticated-orcid': False,
'given': 'Grace A.',
'family': 'McComsey',
'sequence': 'additional',
'affiliation': [ { 'name': 'School of Medicine, Case Western Reserve University, Cleveland, '
'OH 44106, USA'},
{ 'name': 'Clinical Research Center, University Hospitals Cleveland Medical '
'Center, Cleveland, OH 44106, USA'}]}],
'member': '1968',
'published-online': {'date-parts': [[2025, 1, 16]]},
'reference': [ { 'key': 'ref_1',
'unstructured': '(2024, October 20). COVID-19 Cases | WHO COVID-19 Dashboard. Available '
'online: https://data.who.int/dashboards/covid19/cases?n=c.'},
{ 'key': 'ref_2',
'doi-asserted-by': 'crossref',
'first-page': '379',
'DOI': '10.1016/j.idc.2022.02.004',
'article-title': 'Postacute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 '
'Infection',
'volume': '36',
'author': 'Hope',
'year': '2022',
'journal-title': 'Infect. Dis. Clin. N. Am.'},
{ 'key': 'ref_3',
'doi-asserted-by': 'crossref',
'first-page': '1934',
'DOI': '10.1001/jama.2023.8823',
'article-title': 'Development of a Definition of Postacute Sequelae of SARS-CoV-2 '
'Infection',
'volume': '329',
'author': 'Thaweethai',
'year': '2023',
'journal-title': 'JAMA'},
{ 'key': 'ref_4',
'doi-asserted-by': 'crossref',
'first-page': 'ofad233',
'DOI': '10.1093/ofid/ofad233',
'article-title': 'Systematic Review of the Prevalence of Long COVID',
'volume': '10',
'author': 'Woodrow',
'year': '2023',
'journal-title': 'Open Forum Infect. Dis.'},
{ 'key': 'ref_5',
'doi-asserted-by': 'crossref',
'first-page': '1301',
'DOI': '10.1007/s11606-024-08688-9',
'article-title': 'Health-Related Quality of Life for Patients with Post-Acute COVID-19 '
'Syndrome: Identification of Symptom Clusters and Predictors of '
'Long-Term Outcomes',
'volume': '39',
'author': 'Lapin',
'year': '2024',
'journal-title': 'J. Gen. Intern. Med.'},
{ 'key': 'ref_6',
'doi-asserted-by': 'crossref',
'first-page': '5500',
'DOI': '10.1016/j.cell.2024.07.054',
'article-title': 'Mechanisms of Long COVID and the Path toward Therapeutics',
'volume': '187',
'author': 'Peluso',
'year': '2024',
'journal-title': 'Cell'},
{ 'key': 'ref_7',
'doi-asserted-by': 'crossref',
'first-page': '1616',
'DOI': '10.1038/s41590-023-01601-2',
'article-title': 'SARS-CoV-2 Reservoir in Post-Acute Sequelae of COVID-19 (PASC)',
'volume': '24',
'author': 'Proal',
'year': '2023',
'journal-title': 'Nat. Immunol.'},
{ 'key': 'ref_8',
'doi-asserted-by': 'crossref',
'unstructured': 'Low, R.N., Low, R.J., and Akrami, A. (2023). A Review of Cytokine-Based '
'Pathophysiology of Long COVID Symptoms. Front. Med. (Lausanne), 10.',
'DOI': '10.3389/fmed.2023.1011936'},
{ 'key': 'ref_9',
'doi-asserted-by': 'crossref',
'first-page': '1',
'DOI': '10.20411/pai.v8i2.634',
'article-title': 'Arterial Stiffness and Oxidized LDL Independently Associated With '
'Post-Acute Sequalae of SARS-CoV-2',
'volume': '8',
'author': 'Zisis',
'year': '2023',
'journal-title': 'Pathog. Immun.'},
{ 'key': 'ref_10',
'doi-asserted-by': 'crossref',
'first-page': '1731',
'DOI': '10.1161/ATVBAHA.114.303887',
'article-title': 'Oxidized Low-Density Lipoprotein Induces Long-Term Proinflammatory '
'Cytokine Production and Foam Cell Formation via Epigenetic '
'Reprogramming of Monocytes',
'volume': '34',
'author': 'Bekkering',
'year': '2014',
'journal-title': 'Arterioscler. Thromb. Vasc. Biol.'},
{ 'key': 'ref_11',
'doi-asserted-by': 'crossref',
'unstructured': 'Dumas, A., Bernard, L., Poquet, Y., Lugo-Villarino, G., and Neyrolles, '
'O. (2018). The Role of the Lung Microbiota and the Gut-Lung Axis in '
'Respiratory Infectious Diseases. Cell Microbiol., 20.',
'DOI': '10.1111/cmi.12966'},
{ 'key': 'ref_12',
'doi-asserted-by': 'crossref',
'unstructured': 'Ancona, G., Alagna, L., Alteri, C., Palomba, E., Tonizzo, A., Pastena, '
'A., Muscatello, A., Gori, A., and Bandera, A. (2023). Gut and Airway '
'Microbiota Dysbiosis and Their Role in COVID-19 and Long-COVID. Front. '
'Immunol., 14.',
'DOI': '10.3389/fimmu.2023.1080043'},
{ 'key': 'ref_13',
'doi-asserted-by': 'crossref',
'first-page': 'e164813',
'DOI': '10.1172/jci.insight.164813',
'article-title': 'Markers of Fungal Translocation Are Elevated during Post-Acute Sequelae '
'of SARS-CoV-2 and Induce NF-ΚB Signaling',
'volume': '7',
'author': 'Giron',
'year': '2022',
'journal-title': 'JCI Insight'},
{ 'key': 'ref_14',
'doi-asserted-by': 'crossref',
'unstructured': 'Mouchati, C., Durieux, J.C., Zisis, S.N., Labbato, D., Rodgers, M.A., '
'Ailstock, K., Reinert, B.L., Funderburg, N.T., and McComsey, G.A. '
'(2023). Increase in Gut Permeability and Oxidized Ldl Is Associated with '
'Post-Acute Sequelae of SARS-CoV-2. Front. Immunol., 14.',
'DOI': '10.3389/fimmu.2023.1182544'},
{ 'key': 'ref_15',
'doi-asserted-by': 'crossref',
'unstructured': 'Grant, W.B., Lahore, H., Mcdonnell, S.L., Baggerly, C.A., French, C.B., '
'Aliano, J.L., and Bhattoa, H.P. (2020). Evidence That Vitamin D '
'Supplementation Could Reduce Risk of Influenza and COVID-19 Infections '
'and Deaths. Nutrients, 12.',
'DOI': '10.20944/preprints202003.0235.v2'},
{ 'key': 'ref_16',
'doi-asserted-by': 'crossref',
'first-page': '286',
'DOI': '10.1016/j.ijid.2020.07.080',
'article-title': 'Vitamin D3 and K2 and Their Potential Contribution to Reducing the '
'COVID-19 Mortality Rate',
'volume': '99',
'author': 'Goddek',
'year': '2020',
'journal-title': 'Int. J. Infect. Dis.'},
{ 'key': 'ref_17',
'doi-asserted-by': 'crossref',
'unstructured': 'Ao, T., Kikuta, J., and Ishii, M. (2021). Biomolecules The Effects of '
'Vitamin D on Immune System and Inflammatory Diseases. Biomolecules, 11.',
'DOI': '10.3390/biom11111624'},
{ 'key': 'ref_18',
'doi-asserted-by': 'crossref',
'first-page': '881',
'DOI': '10.2310/JIM.0b013e31821b8755',
'article-title': 'Correspondence: Cynthia Aranow 350 Community Drive Manhasset, NY 11030',
'volume': '59',
'author': 'Aranow',
'year': '2011',
'journal-title': 'J. Investig. Med.'},
{ 'key': 'ref_19',
'doi-asserted-by': 'crossref',
'first-page': '7',
'DOI': '10.31138/mjr.33.1.7',
'article-title': 'MEDITERRANEAN JOURNAL OF RHEUMATOLOGY The Immunomodulatory Properties '
'of Vitamin D',
'volume': '33',
'author': 'Athanassiou',
'year': '2022',
'journal-title': 'Mediterr. J. Rheumatol.'},
{ 'key': 'ref_20',
'doi-asserted-by': 'crossref',
'first-page': '1797',
'DOI': '10.1177/1352458512442992',
'article-title': 'A Pilot Study of the Immunological Effects of High-Dose Vitamin D in '
'Healthy Volunteers',
'volume': '18',
'author': 'Allen',
'year': '2012',
'journal-title': 'Mult. Scler.'},
{ 'key': 'ref_21',
'doi-asserted-by': 'crossref',
'unstructured': 'Roumeliotis, S., Georgianos, P.I., Visser, M.P.J., Dofferhoff, A.S.M., '
'van den Ouweland, J.M.W., van Daal, H., Kramers, C., Schurgers, L.J., '
'Janssen, R., and Walk, J. (2022). Effects of Vitamin D and K on '
'Interleukin-6 in COVID-19. Front. Nutr., 8.',
'DOI': '10.3389/fnut.2021.761191'},
{ 'key': 'ref_22',
'doi-asserted-by': 'crossref',
'first-page': '191',
'DOI': '10.1017/S0007114520003979',
'article-title': 'Vitamin K Metabolism as the Potential Missing Link between Lung Damage '
'and Thromboembolism in Coronavirus Disease 2019',
'volume': '126',
'author': 'Janssen',
'year': '2021',
'journal-title': 'Br. J. Nutr.'},
{ 'key': 'ref_23',
'first-page': '679',
'article-title': 'Association between Vitamin D Status and Risk of Developing Severe '
'COVID-19 Infection: A Meta-Analysis of Observational Studies',
'volume': '41',
'author': 'Hopefl',
'year': '2021',
'journal-title': 'J. Am. Nutr. Assoc.'},
{ 'key': 'ref_24',
'doi-asserted-by': 'crossref',
'first-page': '403',
'DOI': '10.1007/s00508-021-01833-y',
'article-title': 'Strong Correlation between Prevalence of Severe Vitamin D Deficiency '
'and Population Mortality Rate from COVID-19 in Europe',
'volume': '133',
'author': 'Pugach',
'year': '2021',
'journal-title': 'Wien. Klin. Wochenschr.'},
{ 'key': 'ref_25',
'doi-asserted-by': 'crossref',
'unstructured': 'Linneberg, A., Kampmann, F.B., Israelsen, S.B., Andersen, L.R., '
'Jørgensen, H.L., Sandholt, H., Rye Jørgensen, N., Thysen, S.M., '
'Benfield, T., and Liakopoulos, V. (2021). The Association of Low Vitamin '
'K Status with Mortality in a Cohort of 138 Hospitalized Patients with '
'COVID-19. Nutrients, 13.',
'DOI': '10.3390/nu13061985'},
{ 'key': 'ref_26',
'doi-asserted-by': 'crossref',
'first-page': 'E4039',
'DOI': '10.1093/cid/ciaa1258',
'article-title': 'Reduced Vitamin K Status as a Potentially Modifiable Risk Factor of '
'Severe COVID-19',
'volume': '73',
'author': 'Dofferhoff',
'year': '2021',
'journal-title': 'Clin. Infect. Dis.'},
{ 'key': 'ref_27',
'doi-asserted-by': 'crossref',
'unstructured': 'Maghbooli, Z., Ebrahimi, M., Shirvani, A., Nasiri, M., Pazoki, M., '
'Kafan, S., Moradi Tabriz, H., Hadadi, A., Montazeri, M., and Ali '
'Sahraian, M. (2020). Vitamin D Sufficiency Reduced Risk for Morbidity '
'and Mortality in COVID-19 Patients. Lancet, preprints.',
'DOI': '10.2139/ssrn.3616008'},
{ 'key': 'ref_28',
'doi-asserted-by': 'crossref',
'unstructured': 'Sobczak, M., and Pawliczak, R. (2024). Effect of Vitamin D3 '
'Supplementation on Severe COVID-19: A Meta-Analysis of Randomized '
'Clinical Trials. Nutrients, 16.',
'DOI': '10.3390/nu16101402'},
{ 'key': 'ref_29',
'unstructured': '(2024, October 22). National Institutes of Health Vitamin D Sheet for '
'Health Professionals, Available online: '
'https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/#change.'},
{ 'key': 'ref_30',
'doi-asserted-by': 'crossref',
'first-page': '163',
'DOI': '10.1016/j.bonr.2018.04.004',
'article-title': 'Vitamin D and Muscle',
'volume': '8',
'author': 'Gunton',
'year': '2018',
'journal-title': 'Bone Rep.'},
{ 'key': 'ref_31',
'doi-asserted-by': 'crossref',
'first-page': '1443',
'DOI': '10.1001/jamainternmed.2024.5726',
'article-title': 'Vitamin K2 in Managing Nocturnal Leg Cramps: A Randomized Clinical '
'Trial',
'volume': '184',
'author': 'Tan',
'year': '2024',
'journal-title': 'JAMA Intern. Med.'},
{ 'key': 'ref_32',
'unstructured': '(2024, October 21). Long COVID Basics | COVID-19 | CDC, Available '
'online: https://www.cdc.gov/covid/long-term-effects/index.html.'},
{ 'key': 'ref_33',
'doi-asserted-by': 'crossref',
'first-page': '102200',
'DOI': '10.1016/j.dsx.2021.102200',
'article-title': 'The Effect of Vitamin D Supplementation on Flow-Mediated Dilatation, '
'Oxidized LDL and Intracellular Adhesion Molecule 1 on Type 2 Diabetic '
'Patients with Hypertension: A Randomized, Placebo-Controlled, '
'Double-Blind Trial',
'volume': '15',
'author': 'Qasemi',
'year': '2021',
'journal-title': 'Diabetes Metab. Syndr. Clin. Res. Rev.'},
{ 'key': 'ref_34',
'doi-asserted-by': 'crossref',
'first-page': '840',
'DOI': '10.12944/CRNFSJ.10.3.3',
'article-title': 'Studies on the Synergistic Interplay of Vitamin D and K for Improving '
'Bone and Cardiovascular Health',
'volume': '10',
'author': 'Singh',
'year': '2022',
'journal-title': 'Curr. Res. Nutr. Food Sci. J.'},
{ 'key': 'ref_35',
'doi-asserted-by': 'crossref',
'first-page': '647',
'DOI': '10.1097/QAD.0000000000003149',
'article-title': 'Inflammation-Mediated Vitamin K and Vitamin D Effects on Vascular '
'Calcifications in People with HIV on Active Antiretroviral Therapy',
'volume': '36',
'author': 'Janus',
'year': '2022',
'journal-title': 'AIDS'},
{ 'key': 'ref_36',
'doi-asserted-by': 'crossref',
'first-page': '5318',
'DOI': '10.4049/jimmunol.1500559',
'article-title': 'Beta-Glucan Activated Human B-Lymphocytes Participate in Innate Immune '
'Responses by Releasing Pro-Inflammatory Cytokines and Stimulating '
'Neutrophil Chemotaxis',
'volume': '195',
'author': 'Ali',
'year': '2015',
'journal-title': 'J. Immunol.'},
{ 'key': 'ref_37',
'doi-asserted-by': 'crossref',
'first-page': '123100',
'DOI': '10.1016/j.lfs.2024.123100',
'article-title': 'Gastrointestinal Manifestations of Long COVID',
'volume': '357',
'author': 'King',
'year': '2024',
'journal-title': 'Life Sci.'},
{ 'key': 'ref_38',
'doi-asserted-by': 'crossref',
'first-page': 'e3',
'DOI': '10.1017/jns.2023.106',
'article-title': 'The Effect of Vitamin K Supplementation on Cardiovascular Risk Factors: '
'A Systematic Review and Meta-Analysis',
'volume': '13',
'author': 'Zhao',
'year': '2024',
'journal-title': 'J. Nutr. Sci.'},
{ 'key': 'ref_39',
'doi-asserted-by': 'crossref',
'first-page': '1479',
'DOI': '10.1016/j.advnut.2023.08.012',
'article-title': 'The Effect of Vitamin D Supplementation on Lipid Profiles: An Umbrella '
'Review of Meta-Analyses',
'volume': '14',
'author': 'Radkhah',
'year': '2023',
'journal-title': 'Adv. Nutr.'},
{ 'key': 'ref_40',
'doi-asserted-by': 'crossref',
'first-page': '5612',
'DOI': '10.1002/fsn3.1837',
'article-title': 'Beneficial Health Effects of Menaquinone-7 on Body Composition, '
'Glycemic Indices, Lipid Profile, and Endocrine Markers in Polycystic '
'Ovary Syndrome Patients',
'volume': '8',
'author': 'Tarkesh',
'year': '2020',
'journal-title': 'Food. Sci. Nutr.'},
{ 'key': 'ref_41',
'first-page': '1',
'article-title': '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',
'volume': '12',
'year': '2020',
'journal-title': 'Diabetol. Metab. Syndr.'}],
'container-title': 'Nutrients',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://www.mdpi.com/2072-6643/17/2/304/pdf',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2025, 1, 16]],
'date-time': '2025-01-16T10:26:45Z',
'timestamp': 1737023205000},
'score': 1,
'resource': {'primary': {'URL': 'https://www.mdpi.com/2072-6643/17/2/304'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2025, 1, 16]]},
'references-count': 41,
'journal-issue': {'issue': '2', 'published-online': {'date-parts': [[2025, 1]]}},
'alternative-id': ['nu17020304'],
'URL': 'http://dx.doi.org/10.3390/nu17020304',
'relation': {},
'ISSN': ['2072-6643'],
'subject': [],
'container-title-short': 'Nutrients',
'published': {'date-parts': [[2025, 1, 16]]}}
