{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:09:55Z","timestamp":1788448195431,"version":"build-2803163510"},"reference-count":49,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>COVID-19 is not only a short-term infection, as patients (pts) recovering from SARS-CoV-2 infection complain of persisting symptoms, which may lead to chronic fatigue syndrome. There is currently no evidence that nutritional supplements can assist in the recovery of pts with chronic fatigue syndrome. 1-Methylnicotinamide (1-MNA) is an endogenic substance that is produced in the liver when nicotinic acid is metabolized. 1-MNA demonstrates anti-inflammatory and anti-thrombotic properties. Therefore, we investigated whether 1-MNA supplements could improve exercise tolerance and decrease fatigue among patients recovering from SARS-CoV-2. Methods: The study population was composed of 50 pts who had recovered from symptomatic COVID-19. The selected pts were randomized into two groups: Gr 1 (NO-1-MNA)\u2014without supplementation; Gr 2 (1-MNA) with 1-MNA supplementation. At the beginning of the study (Phase 0), in both groups, a 6-minute walk test (6MWT) was carried out and fatigue assessment was performed using the Fatigue Severity Scale (FSS). Both FSS and 6MWT were repeated after 1 month. Results: A significant improvement in the mean distance covered in the 6MWT was noted at follow-up in Gr 1-MNA, compared with Gr NO-1-MNA. We also noted that in Gr 1-MNA, the 6MWT distance was significantly higher after 1 month of supplementation with 1-MNA, compared with the beginning of the study (515.18 m in Phase 0 vs. 557.8 m in Phase 1; p = 0.000034). In Gr 1-MNA, significantly more pts improved their distance in the 6MWT (23 out of 25 pts, equal to 92%), by a mean of 47 m, compared with Gr NO-1-MNA (15 of 25 pts, equal to 60%) (p = 0.0061). After one month, significantly more patients in the group without 1-MNA had severe fatigue (FSS \u2265 4) compared with the group with supplementation (Gr 1-MNA = 5 pts (20%) vs. Gr NO-1-MNA = 14pts (56%); p = 0.008). Conclusions: 1-MNA supplementation significantly improved physical performance in a 6-min walk test and reduced the percentage of patients with severe fatigue after COVID-19. The comprehensive action of 1-MNA, including anti-inflammatory and anticoagulant effects, may be beneficial for the recovery of patients with persistent symptoms of fatigue and low tolerance to exercise after COVID-19.<\/jats:p>","DOI":"10.3390\/nu14153004","type":"journal-article","created":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T01:42:13Z","timestamp":1658713333000},"page":"3004","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Use of 1-MNA to Improve Exercise Tolerance and Fatigue in Patients after COVID-19"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8805-9688","authenticated-orcid":false,"given":"Micha\u0142","family":"Chudzik","sequence":"first","affiliation":[{"name":"Medical Center, Saint Family Hospital, 90-302 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9875-7383","authenticated-orcid":false,"given":"Monika","family":"Burzy\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Social and Preventive Medicine of the Medical University of Lodz, 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5082-3641","authenticated-orcid":false,"given":"Joanna","family":"Kapusta","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiac Rehabilitation, Medical University of Lodz, 70-445 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1001\/jama.2020.12603","article-title":"Persistent symptoms in patients after acute COVID-19","volume":"324","author":"Carfi","year":"2020","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Moldofsky, H., and Patcai, J. (2011). Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study. BMC Neurol., 11.","DOI":"10.1186\/1471-2377-11-37"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1001\/archinternmed.2009.384","article-title":"Mental morbidities and chronic fatigue in severe acute respiratory syndrome survivors: Long-term follow-up","volume":"169","author":"Lam","year":"2009","journal-title":"Arch. Intern. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1001\/jama.2020.1585","article-title":"Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus\u2013infected pneumonia in Wuhan, China","volume":"323","author":"Wang","year":"2020","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"m606","DOI":"10.1136\/bmj.m606","article-title":"Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: Retrospective case series","volume":"368","author":"Xu","year":"2020","journal-title":"BMJ"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.jinf.2020.02.018","article-title":"Characteristics of COVID-19 infection in Beijing","volume":"80","author":"Tian","year":"2020","journal-title":"J. Infect."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1176\/appi.ajp.160.2.221","article-title":"Chronic fatigue syndrome: A review","volume":"160","author":"Afari","year":"2003","journal-title":"Am. J. Psychiatry."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.bbi.2011.06.016","article-title":"Chronic fatigue syndrome, the immune system and viral infection","volume":"26","author":"Bansal","year":"2012","journal-title":"Brain Behav. Immun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1016\/j.bbi.2012.06.006","article-title":"Biomarkers for chronic fatigue","volume":"26","author":"Klimas","year":"2012","journal-title":"Brain Behav. Immun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"E7150","DOI":"10.1073\/pnas.1710519114","article-title":"Cytokine signature associated with disease severity in chronic fatigue syndrome patients","volume":"114","author":"Montoya","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","first-page":"747","article-title":"Evidence for the presence of immune dysfunction in chronic fatigue syndrome","volume":"9","author":"Natelson","year":"2002","journal-title":"Clin. Diagn Lab. Immunol."},{"key":"ref_13","first-page":"485","article-title":"Impaired microcirculation function in COVID-19 and implications for potential therapies","volume":"27","author":"Filipiak","year":"2020","journal-title":"Cardiol. J."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Jimeno-Almaz\u00e1n, A., Pallares, J.G., Buend\u00eda-Romero, A., Martinez-Cava, A., Franco-Lopez, F., Sanchez-Alcaraz Martinez, B.J., Bernal-Morel, E., and Courel-Lbanez, J. (2021). Post-COVID-19 Syndrome and the Potential Benefits of Exercise. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18105329"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/sj.bjp.0707383","article-title":"1-Methylnicotinamide (MNA), a primary metabolite of nicotinamide, exerts anti-thrombotic activity mediated by a cyclooxygenase-2\/prostacyclin pathway","volume":"152","author":"Chlopicki","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"ref_16","first-page":"109","article-title":"1-Methylnicotinamide: A potent anti-inflammatory agent of vitamin origin","volume":"55","author":"Gebicki","year":"2003","journal-title":"Pol. J. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/nchembio.1352","article-title":"Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide","volume":"9","author":"Schmeisser","year":"2013","journal-title":"Nat. Chem. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1161\/HYPERTENSIONAHA.111.183210","article-title":"Nitric oxide production and endothelium-dependent vasorelaxation ameliorated by N1-methylnicotinamide in human blood vessels","volume":"59","author":"Domagala","year":"2012","journal-title":"Hypertension"},{"key":"ref_19","first-page":"3016","article-title":"N1-methylnicotinamide is a signalling molecule produced in skeletal muscle coordinating energy metabolism","volume":"14","author":"Ottosson","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1093\/sleep\/31.11.1601","article-title":"Validation of the Fatigue Severity Scale in a Swiss Cohort","volume":"31","author":"Valko","year":"2008","journal-title":"Sleep"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1097\/MRR.0b013e3280146ec4","article-title":"The validity and reliability of the Fatigue Severity Scale in Turkish multiple sclerosis patients","volume":"30","author":"Armutlu","year":"2007","journal-title":"Int. J. Rehabil. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1111\/j.1468-1331.2006.01499.x","article-title":"Fatigue and sleep disturbance in multiple sclerosis","volume":"13","author":"Kaynak","year":"2006","journal-title":"Eur. J. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories (2002). ATS Statement: Guidelines for the six-minute walk test. Am. J. Respir. Crit. Care Med., 166, 111\u2013117.","DOI":"10.1164\/ajrccm.166.1.at1102"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"101166","DOI":"10.1016\/j.ctcp.2020.101166","article-title":"Respiratory rehabilitation in elderly patients with COVID-19: A randomized controlled study","volume":"39","author":"Liu","year":"2020","journal-title":"Complement. Ther. Clin. Pract."},{"key":"ref_25","first-page":"e13080","article-title":"The COVID-19 Sequelae: A Cross-Sectional Evaluation of Post-recovery Symptoms and the Need for Rehabilitation of COVID-19 Survivors","volume":"13","author":"Ayman","year":"2021","journal-title":"Cureus"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1136\/thoraxjnl-2020-215818","article-title":"\u2018Long-COVID\u2019: A cross-sectional study of persisting symptoms, biomarker and imaging abnormalities following hospitalisation for COVID-19","volume":"76","author":"Mandal","year":"2021","journal-title":"Thorax"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1002\/jmv.26368","article-title":"Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-sectional evaluation","volume":"93","author":"Halpin","year":"2021","journal-title":"J. Med. Virol."},{"key":"ref_28","first-page":"00542","article-title":"Persistent symptoms 3 months after a SARS-CoV-2 infection: The post-COVID-19 syndrome?","volume":"6","author":"Delbressine","year":"2020","journal-title":"ERJ Open Res."},{"key":"ref_29","first-page":"127","article-title":"1-Methylnicotinamide (MNA) prevents endothelial dysfunction in hypertriglyceridemic and diabetic rats","volume":"60","author":"Bartus","year":"2008","journal-title":"Pharmacol. Rep. PR"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1038\/s41418-020-0530-3","article-title":"COVID-19 infection: The perspectives on immune responses","volume":"27","author":"Shi","year":"2020","journal-title":"Cell Death Differ."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Przyborowski, K., Wojewoda, M., Sitek, B., Zakrzewska, A., Kij, A., Wandzel, K., Zoladz, J.A., and Chlopicki, S. (2015). Effects of 1-methylnicotinamide (MNA) on exercise capacity and endothelial response in diabetic mice. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0130908"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S1734-1140(12)70777-6","article-title":"Single bout of endurance exercise increases NNMT activity in the liver and MNA concentration in plasma","volume":"64","author":"Chlopicki","year":"2012","journal-title":"Pharmacol. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/S0735-1097(86)80293-5","article-title":"Fifteen year mortality in Coronary Drug Project patients: Long-term benefit with niacin","volume":"8","author":"Canner","year":"1986","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1513\/AnnalsATS.201703-244FR","article-title":"The Value and Application of the 6-Minute-Walk Test in Idiopathic Pulmonary Fibrosis","volume":"15","author":"Brown","year":"2018","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1097\/HCR.0000000000000517","article-title":"Using the 6-min Walk Test to Monitor Peak Oxygen Uptake Response to Cardiac Rehabilitation in Patients With Heart Failure","volume":"40","author":"Chirico","year":"2020","journal-title":"J. Cardiopulm. Rehabil. Prev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/S0140-6736(20)32656-8","article-title":"6-month consequences of COVID-19 in patients discharged from hospital: A cohort study","volume":"397","author":"Huang","year":"2021","journal-title":"Lancet"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.ijid.2020.07.014","article-title":"Silent hypoxia in patients with SARS CoV-2 infection before hospital discharge","volume":"99","author":"Fuglebjerg","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1159\/000514387","article-title":"Pulmonary Rehabilitation in Patients Recovering from COVID-19","volume":"100","author":"Zampogna","year":"2021","journal-title":"Respiration"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1097\/PHM.0000000000001549","article-title":"Feasibility and Efficacy of Cardiopulmonary Rehabilitation After COVID-19","volume":"99","author":"Hermann","year":"2020","journal-title":"Am. J. Phys. Med. Rehabil."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e2036142","DOI":"10.1001\/jamanetworkopen.2020.36142","article-title":"Respiratory and Psychophysical Sequelae Among Patients With COVID-19 Four Months After Hospital Discharge","volume":"4","author":"Bellan","year":"2021","journal-title":"JAMA Netw. Open."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e25339","DOI":"10.1097\/MD.0000000000025339","article-title":"Inspiratory muscle training for recovered COVID-19 patients after weaning from mechanical ventilation: A pilot control clinical study","volume":"100","author":"Abodonya","year":"2021","journal-title":"Medicine"},{"key":"ref_42","first-page":"633","article-title":"Functional outcome after inpatient rehabilitation in post-intensive care unit COVID-19 patients: Findings and clinical implications from a real-practice retrospective study","volume":"56","author":"Curci","year":"2020","journal-title":"Eur. J. Phys. Rehabil. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.pulmoe.2021.03.004","article-title":"Predictors of reduced 6-minute walk distance after COVID-19: A cohort study in Mexico","volume":"27","author":"Wong","year":"2021","journal-title":"Pulmonology"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Spielmanns, M., Pekacka-Egli, A.-M., Schoendorf, S., Windisch, W., and Hermann, M. (2021). Effects of a Comprehensive Pulmonary Rehabilitation in Severe Post-COVID-19 Patients. Int. J. Environ. Res. Public Health., 18.","DOI":"10.3390\/ijerph18052695"},{"key":"ref_45","first-page":"167","article-title":"Cardiopulmonary rehabilitation in post-COVID-19 patients: Case series","volume":"33","author":"Tozato","year":"2021","journal-title":"Rev. Bras. Ter. Intensiva."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e13746","DOI":"10.1111\/ijcp.13746","article-title":"Assessment and characterisation of post-COVID-19 manifestations","volume":"75","author":"Kamal","year":"2021","journal-title":"Int. J. Clin. Pract."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1136\/thoraxjnl-2020-216086","article-title":"Patient outcomes after hospitalisation with COVID-19 and implications for follow-up: Results from a prospective UK cohort","volume":"76","author":"Arnold","year":"2021","journal-title":"Thorax"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1192\/bjp.173.6.475","article-title":"Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever","volume":"173","author":"White","year":"1998","journal-title":"Br. J. Psychiatry."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"653516","DOI":"10.3389\/fmed.2021.653516","article-title":"Post-COVID-19 Syndrome: The Persistent Symptoms at the Post-viral Stage of the Disease. A Systematic Review of the Current Data","volume":"4","author":"Salamanna","year":"2021","journal-title":"Front. Med. (Lausanne)"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/15\/3004\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:54:36Z","timestamp":1760140476000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/15\/3004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,22]]},"references-count":49,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["nu14153004"],"URL":"https:\/\/doi.org\/10.3390\/nu14153004","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.07.14.21259081","asserted-by":"object"}]},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,22]]}}}