Melatonin may decrease risk for and aid treatment of COVID-19 and other RNA viral infections
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)
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.
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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treatments are complementary. All practical, effective, and safe means should
be used based on risk/benefit analysis. No treatment, vaccine, or intervention
is 100% available and effective for all current and future variants. We do not
provide medical advice. Before taking any medication, consult a qualified
physician who can provide personalized advice and details of risks and
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