Pleiotropic Functions of Nitric Oxide Produced by Ascorbate for the Prevention and Mitigation of COVID-19: A Revaluation of Pauling’s Vitamin C Therapy
Yamasaki et al.,
Pleiotropic Functions of Nitric Oxide Produced by Ascorbate for the Prevention and Mitigation of COVID-19: A..,
Microorganisms, doi:10.3390/microorganisms11020397 (Review)
Extensive review of vitamin C and nitric oxide focusing on the potential antiviral activity of vitamin C for SARS-CoV-2 via the production of nitric oxide. Authors note that vegetables are a major dietary source of nitrate, and that dietary vitamin C from fruits and vegetables can reduce nitrite to produce nitric oxide in the oral cavity when chewing foods.
Authors conclude that intermittent bursts of nitric oxide, for example as generated by the combination of nitrite and vitamin C, is a potential therapeutic treatment to prevent and mitigate COVID-19.
Authors also note that nitric oxide may be related to the observed lower than expected risks seen with asthma and smoking. Elevated levels of nitric oxide in the breath are used for diagnosing asthma, and smoking involves bursts of concentrated nitric oxide in cigarette smoke.
Yamasaki et al., 3 Feb 2023, Japan, peer-reviewed, 4 authors.
Contact:
yamasaki@sci.u-ryukyu.ac.jp (corresponding author).
Abstract: microorganisms
Review
Pleiotropic Functions of Nitric Oxide Produced by Ascorbate for
the Prevention and Mitigation of COVID-19: A Revaluation of
Pauling’s Vitamin C Therapy
Hideo Yamasaki *, Hideyuki Imai
, Atsuko Tanaka
and Joji M. Otaki
Faculty of Science, University of the Ryukyus, Nishihara 903-0213, Okinawa, Japan
* Correspondence: yamasaki@sci.u-ryukyu.ac.jp
Citation: Yamasaki, H.; Imai, H.;
Tanaka, A.; Otaki, J.M. Pleiotropic
Functions of Nitric Oxide Produced
by Ascorbate for the Prevention and
Mitigation of COVID-19: A
Revaluation of Pauling’s Vitamin C
Abstract: Linus Pauling, who was awarded the Nobel Prize in Chemistry, suggested that a high dose
of vitamin C (L-ascorbic acid) might work as a prevention or treatment for the common cold. Vitamin
C therapy was tested in clinical trials, but clear evidence was not found at that time. Although
Pauling’s proposal has been strongly criticized for a long time, vitamin C therapy has continued
to be tested as a treatment for a variety of diseases, including coronavirus infectious disease 2019
(COVID-19). The pathogen of COVID-19, SARS-CoV-2, belongs to the β-coronavirus lineage, which
includes human coronavirus, severe acute respiratory syndrome (SARS), and Middle East respiratory
syndrome (MERS). This review intends to shed new light on vitamin C antiviral activity that may
prevent SARS-CoV-2 infection through the chemical production of nitric oxide (NO). NO is a gaseous
free radical that is largely produced by the enzyme NO synthase (NOS) in cells. NO produced
by upper epidermal cells contributes to the inactivation of viruses and bacteria contained in air or
aerosols. In addition to enzymatic production, NO can be generated by the chemical reduction of
inorganic nitrite (NO2 − ), an alternative mechanism for NO production in living organisms. Dietary
vitamin C, largely contained in fruits and vegetables, can reduce the nitrite in saliva to produce
NO in the oral cavity when chewing foods. In the stomach, salivary nitrite can also be reduced to
NO by vitamin C secreted from the epidermal cells of the stomach. The strong acidic pH of gastric
juice facilitates the chemical reduction of salivary nitrite to produce NO. Vitamin C contributes in
multiple ways to the host innate immune system as a first-line defense mechanism against pathogens.
Highlighting chemical NO production by vitamin C, we suggest that controversies on the therapeutic
effects of vitamin C in previous clinical trials may partly be due to less appreciation of the pleiotropic
functions of vitamin C as a universal bioreductant.
Therapy. Microorganisms 2023, 11, 397.
https://doi.org/10.3390/
microorganisms11020397
Keywords: antiviral activity; COVID-19; L-ascorbic acid: Linus Pauling; nitric oxide; nitrite;
SARS-CoV-2; vitamin C
Academic Editors: Samuele Sabbatini
and Anna Gidari
Received: 16 December 2022
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