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Melatonin may decrease risk for and aid treatment of COVID-19 and other RNA viral infections
DiNicolantonio et al., Open Heart, doi:10.1136/openhrt-2020-001568 (Review)
DiNicolantonio et al., Melatonin may decrease risk for and aid treatment of COVID-19 and other RNA viral infections, Open Heart, doi:10.1136/openhrt-2020-001568 (Review)
Mar 2021   Source   PDF  
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Review of melatonin for COVID-19 and the result of Ramlall et al., suggesting that vitamin D, zinc, and melatonin supplementation may have general utility for the prevention and treatment of RNA virus infections, such as COVID-19 and influenza.
DiNicolantonio et al., 19 Mar 2021, peer-reviewed, 3 authors.
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Abstract: Open access Editorial James J DiNicolantonio ‍ ‍,1 Mark McCarty,2 Jorge Barroso-­Aranda3 To cite: DiNicolantonio JJ, McCarty M, Barroso-­Aranda J. Melatonin may decrease risk for and aid treatment of COVID-19 and other RNA viral infections. Open Heart 2021;8:e001568. doi:10.1136/ openhrt-2020-001568 Accepted 22 February 2021 © Author(s) (or their employer(s)) 2021. Re-­use permitted under CC BY-­NC. No commercial re-­use. See rights and permissions. Published by BMJ. 1 Department of Preventive Cardiology, Saint Luke's Mid America Heart Institute, Kansas City, Missouri, USA 2 Catalytic Longevity, Encinitas, California, USA 3 Clinica Libre de Adicciones, Tijuana, Mexico Correspondence to Dr James J DiNicolantonio; ​ jjdinicol@​gmail.​com ABSTRACT A recent retrospective study has provided evidence that COVID-19 infection may be notably less common in those using supplemental melatonin. It is suggested that this phenomenon may reflect the fact that, via induction of silent information regulator 1 (Sirt1), melatonin can upregulate K63 polyubiquitination of the mitochondrial antiviral-­signalling protein, thereby boosting virally mediated induction of type 1 interferons. Moreover, Sirt1 may enhance the antiviral efficacy of type 1 interferons by preventing hyperacetylation of high mobility group box 1 (HMGB1), enabling its retention in the nucleus, where it promotes transcription of interferon-­inducible genes. This nuclear retention of HMGB1 may also be a mediator of the anti-­inflammatory effect of melatonin therapy in COVID-19—complementing melatonin’s suppression of nuclear factor kappa B activity and upregulation of nuclear factor erythroid 2-­related factor 2. If these speculations are correct, a nutraceutical regimen including vitamin D, zinc and melatonin supplementation may have general utility for the prevention and treatment of RNA virus infections, such as COVID-19 and influenza. MELATONIN SUPPLEMENTATION MAY REDUCE RISK FOR COVID-19 A retrospective analysis of 791 intubated patients with COVID-19 has found that, after adjustment for pertinent demographics and comorbidities, those treated with melatonin had a markedly lower risk for mortality (HR: 0.131, 95% CI: 0.076 to 0.223)—suggestive of a profound anti-­inflammatory benefit.1 Such an effect might be anticipated, in light of melatonin’s ability to upregulate expression of silent information regulator 1 (Sirt1)—a deacetylase that is known to suppress the activity of the proinflammatory nuclear factor kappa B (NF-­kappaB) transcription factor— and also upregulate nuclear factor erythroid 2-­ related factor 2 (Nrf2), which promotes the transcription of a range of antioxidant proteins.2–4 Moreover, recent epidemiology suggests that melatonin usage may reduce the risk for contracting COVID-19. A recent retrospective study, examining data from 26 799 subjects in a COVID-19 registry and using propensity score matching to account for a range of covariates, found that current supplementation with melatonin was associated with a significant 28% reduction in risk for serologically detectible COVID-19 infection. Among Black Americans, this reduction in risk was a remarkable 52% (OR=0.48, 95% CI 0.31 to 0.75).5 The basis of this decrease in risk for COVID-19 is unclear, especially since Sirt1 activity, which melatonin promotes, is known to transcriptionally upregulate expression of ACE2—the cellular membrane receptor for COVID-19.6 7 MELATONIN-INDUCED SIRT1 MAY BOOST VIRALLY..
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