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Glutathione and Vitamin D to Prevent COVID-19: A Review

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Glutathione and Vitamin D to Prevent COVID-19: A Review

Abstract

The alarming pandemic situation of corona virus disease (COVID-19) outbreak arises due to rapid spread of Novel Corona Virus (SARSCoV-2). Impaired redox homeostasis in association with oxidative stress is found to be important biological processes that may account for increased individual susceptibility to COVID-19 infection. Glutathione (GSH) is one of the main nonprotein antioxidants in the cell which, together with its related enzymes constitute the glutathione-system. The glutathione system plays an important role in the maintenance of good health and prevention of various diseases. Several approaches have been used to enhance cellular GSH availability. Restricted diet, drug administration and nutritional supplementation shows moderate success. Regular exercise has also evolved as a new approach. Some evidences suggest that GSH and vitamin D supplementation can reduce the risk of COVID-19 infections and deaths. Present review discusses the possible roles of Glutathione and Vitamin D in preventing and reducing the risk of COVID-19 associated acute infections and severity.
Indian Journal of Natural Sciences www.tnsroindia.org.in ©IJONS
Vol.12 / Issue 69 / December / 2021 International Bimonthly (Print) ISSN: 0976 – 0997
36775
Glutathione and Vitamin D to Prevent COVID-19: A Review
Surajit Majumder1*, Deblina Dhabal2 and Soumitra Kumar Choudhuri3
1Assistant Professor, Dept. of Zoology, Bankura Sammilani College, P.O. Kenduadihi, Dist. Bankura,
PIN-722102, West Bengal, India.
2Research Assistant, Dept. of Zoology, Bankura Sammilani College, P.O. Kenduadihi, Dist. Bankura, PIN-
722102, West Bengal, India.
3Former Head and Emeritus Medical Scientist, Dept. of IVCCC, Chittaranjan National Cancer Institute, 37
S.P. Mukherjee Road, Kolkata-700026, India. Residence: CD-2, Newtown, Kolkata-700156, India.
Received: 13 Aug 2021 Revised: 16 Sep 2021 Accepted: 11 Oct 2021
*Address for Correspondence
Surajit Majumder
Assistant Professor,
Dept. of Zoology,
Bankura Sammilani College,
Kenduadihi, Bankura, West Bengal, India
Email: surajitnajumder.sm@gmail.com
This is an Open Access Journal / article distributed under the terms of the Creative Commons Attribution License
(CC BY-NC-ND 3.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the
original work is properly cited. All rights reserved.
The alarming pandemic situation of corona virus disease (COVID-19) outbreak arises due to rapid spread
of Novel Corona Virus (SARSCoV-2). Impaired redox homeostasis in association with oxidative stress is
found to be important biological processes that may account for increased individual susceptibility to
COVID-19 infection. Glutathione (GSH) is one of the main nonprotein antioxidants in the cell which,
together with its related enzymes constitute the glutathione-system. The glutathione system plays an
important role in the maintenance of good health and prevention of various diseases. Several approaches
have been used to enhance cellular GSH availability. Restricted diet, drug administration and nutritional
supplementation shows moderate success. Regular exercise has also evolved as a new approach. Some
evidences suggest that GSH and vitamin D supplementation can reduce the risk of COVID-19 infections
and deaths. Present review discusses the possible roles of Glutathione and Vitamin D in preventing and
reducing the risk of COVID-19 associated acute infections and severity.
Keywords: SARSCoV-2, COVID-19, Glutathione, Vitamin D
INTRODUCTION
The novel corona virus SARSCoV-2 (COVID-19) continues to spread throughout the world, affecting more and more
people; majority of people have asymptomatic, mild, or moderate disease, and only 14% patients developed severe
ABSTRACT
REVIEW ARTICLE
Indian Journal of Natural Sciences www.tnsroindia.org.in ©IJONS
Vol.12 / Issue 69 / December / 2021 International Bimonthly (Print) ISSN: 0976 – 0997
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and 5% developed critical illness [1]. Higher rates of death and serious illness from COVID-19 infection among older
people and those having comorbidities suggest the role of age and disease-related biological processes leads
individuals to be more sensitive to environmental stress factors, including infectious agents like corona virus
SARSCoV-2 [2]. SARSCoV-2, with its minute virion size (50-200 nm diameter) enters into the human body by using
its spike protein (ACE2) and protease (TMPRSS2) and binds to cellular receptor (ACE2) and then starts rapid
multiplication in the lung tissue leading to breathing difficulty and death [3]. For its rapid growth the virus attacks
the immune system, overpowers the defense mechanism and creates the so called ‘cytokine storm’ [4]. Severe
oxidative stress caused by various factors leads to destruction of the phase II detoxification pathway, the major
component of body’s Innate Immune System. The function of this detoxification system is governed by GSH
(reduced form) and some related enzymes [5, 6]. The thiol compound GSH -glutamyl cysteine glycine, a
ubiquitous tripeptide) is the major antioxidant that controls various biological processes, e.g., removal of free
radicals, mitochondrial activity, apoptosis, immune response and even antiviral action. The cellular GSH level also
keeps varying with age, sex and other disease features of the body [7]. Several studies indicate that higher levels of
GSH may improve an individual’s responsiveness to viral infections [2]. Recent reports disclose that Vitamin D plays
a role in reducing the risk of COVID-19 and other acute respiratory tract infections and severity. Studies also suggest
that vitamin D plays important role in reducing the risk of acute pneumonia. These include direct inhibition with
viral replication or with anti-inflammatory or immunomodulatory ways [8]. Herein we will discuss the crucial role of
Glutathione and Vitamin D, their inter-relation and feasibility to prevent and treat COVID-19 pathogenesis.
Glutathione and COVID 19
Glutathione (GSH) plays the role of ‘master antioxidant’ in all tissues [9]. Extracellular GSH uptake, regeneration
from the oxidized form (GSSG) and de novo synthesis control the intracellular GSH balance. In cytosol, GSH synthesis
takes place in two ATP-dependent reactions which are catalyzed by glutamate-cysteine ligase (GCL) and glutathione
synthase (GS). GSH exists in reduced (GSH) and oxidized (GSSG) states. In the reduced state, the thiol group of
cysteine is capable of donating a reducing equivalent to other unstable molecules, for example ROS. After donating
an electron, GSH itself becomes reactive, and then it readily reacts with another reactive GSH to form glutathione
disulfide (GSSG). Such a reaction is possible due to the presence of relatively high concentration of glutathione in
cells (up to 5 mM in the liver). Glutathione reductase (GR) catalyzes the regeneration reaction of GSH from GSSG in
the GSH redox cycle [9]. Studies including ours indicate that cellular GSH deficiency which is caused by increased
depletion or decreased biosynthesis, results into oxidative stress, viral attack, immune dysfunction and cancer [10-
12]. Recent biomedical literature also emphasizes that GSH deficiency is the most accepted explanation of higher
COVID-19 infection among aged population and in persons suffering from comorbidity (diseases like diabetes,
cardiac or pulmonary diseases) [13]. GSH deficiency can also promote the increased activation of von Willebrand
Factor and leads to coagulopathy in COVID-19 patients [2].
Endogenous GSH progressively decreases with age and thus cells in elderly people (particularly in lung tissue) are
more susceptible to oxidative damage caused by environmental factors and viral attack. Evidences disclose that the
effect of glutathione deficiency, as seen in many chronic diseases, causes severe oxidative damage in COVID-19
patients [13, 14]. Oxidative damage thereby exacerbates inflammation in lung and airways leading to acute
respiratory distress syndrome (ARDS), multiorgan failure and death [15]. Levels of cellular GSH is higher in female
population than in males that may be the reason of prevalence of COVID-19 attack more in males [16]. Recent clinical
findings also disclose that patients with moderate-to-severe SARSCoV-2 infection have higher levels of ROS, greater
ROS/GSH ratio and lower levels of GSH than patients with mild illness [17]. Thus corona virus (SARSCoV-2) cannot
actively replicate in patients having higher levels of cellular GSH; the lower viral load is manifested by milder
clinical symptoms [15, 17, 16]. Ample evidences thus support the proposition that GSH may be a promising drug for
etiological treatment of SARSCoV-2 infections [14, 18, 19]. Evidences also disclose that GSH inhibits replication of
viruses at different stages of the viral life cycle, and this antiviral property of GSH may prevent increased viral loads
and the cytokine storm [2]. Studies disclosed that following a 6-month preventive administration of N-acetylcysteine
(NAC, glutathione precursor), there was significant reduction in the incidence of clinically apparent influenza and
Surajit Majumder
et al.,
Indian Journal of Natural Sciences www.tnsroindia.org.in ©IJONS
Vol.12 / Issue 69 / December / 2021 International Bimonthly (Print) ISSN: 0976 – 0997
36777
influenza-like episodes, especially in elderly high-risk individuals. COVID-19 patients have lower level of cellular
GSH compared to healthy individuals and therefore, GSH replenishment may usher a new era of an effective
therapy [20].
Vitamin D and COVID 19
Vitamin D is a steroid hormone which is produced endogenously with the effect of solar radiation on human skin. It
can also be obtained from exogenous food sources or dietary supplements [21]. Studies substantiated a potential link
between vitamin D deficiency and various diseases, including systemic infection [22, 23, 24]. Some recent reviews
hypothesized that insufficient vitamin D level may hamper respiratory immune function which in turn increases the
risk of COVID-19 severity and mortality [8]. Vitamin D may be involved in maintaining the cell junctions, and gap
junctions, increasing cellular immunity by decreasing the cytokine storm; these are achieved by influencing
interferon γ and tumor necrosis factor α [25] and regulating adaptive immunity through inhibiting T helper cell type
1 responses and stimulating of T cells induction [26]. Several in vitro studies substantiated that vitamin D plays an
important role in local ‘respiratory homeostasis’ either by stimulating the exhibition of antimicrobial peptides or by
directly inhibiting the replication of respiratory viruses [27]. Vitamin D insufficiency can, therefore, be involved in
ARDS (Acute Respiratory Distress Syndrome) which is noticed in severely ill COVID-19 patients [8]. Studies also
suggest that deficiency of vitamin D can promote the renin-angiotensin system (RAS), which may result into chronic
cardiovascular disease (CVD) and reduced lung function [28]. People with such comorbidities possess higher risk of
severe illness in case of COVID-19 [8].
Relation between Glutathione and Vitamin D
Several studies indicated that greater the GSH levels, greater the level of active vitamin D [2]. Reports disclose in
T2D patients, lower levels of L-cysteine (a rate-limiting precursor of GSH) and GSH correlated with lower vitamin D
binding protein (VDBP) and Vitamin D levels [29]. L-cysteine supplementation is known to improve GSH status
through upregulation of the expression of VDBP, Vitamin D 25-hydroxylase, and vitamin D receptor, thereby
increasing vitamin D (VD) levels and decreasing inflammatory biomarkers in diabetic rats [30]. Recent study [31]
also suggests that the deficiency of GSH in association with increased oxidative stress epigenetically alters Vitamin D
regulatory genes which lead to suppressed gene expression which in turn decreases VD biosynthesis, ultimately
leading to a secondary deficiency of vitamin D. Replenishment of GSH by L-cysteine treatment beneficially altered
epigenetic enzymes methyl transferases and increased the expression of vitamin D metabolism genes. Hence we may
conclude GSH is essential for controlling endogenous vitamin D biosynthesis and can be used in the treatment of
vitamin D deficiency [31].
CONCLUSION
Considering very high rate of serious illness and mortality due to COVID-19 in senior people and those with
comorbidity, identification of effective drugs for the treatment and prevention is the need of the hour. Reduction in
oxidative stress may be an effective approach to prevent and treat COVID-19 patients. Most of the cofactors (aging,
diabetes, hypertension, cardiovascular disease) of COVID-19 are found to be associated with low levels of cellular
GSH [20]. Glutathione is also involved in maintaining Vitamin D level as we already discussed. Hence, we propose
that the increase of cellular GSH may prove to be a new approach to treat COVID-19. Patients should consume lot of
pure vegetables, fruits, dairy products containing high amount of GSH. Examples of some GSH containing
vegetables are mushrooms, asparagus, avocado, cabbage, brussel sprouts, spinach, broccoli, garlic, onions, tomatoes,
cucumber, almonds, walnuts etc. Exercise should be included in the daily routine of COVID-19 patients as yoga and
exercise reduces oxidative stress and increases cellular GSH level. N-acetyl cysteine i.e., oral GSH precursor, may
represent a novel treatment approach for reducing cytokine storm syndrome, oxidative stress and respiratory
distress in severe COVID-19 cases.
Surajit Majumder
et al.,
Indian Journal of Natural Sciences www.tnsroindia.org.in ©IJONS
Vol.12 / Issue 69 / December / 2021 International Bimonthly (Print) ISSN: 0976 – 0997
36778
REFERENCES
1. Wu Z, Mc Googan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19)
outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and
Prevention, JAMA, 2020, 323(13): 1239-1242.
2. Polonikov A, Endogenous deficiency of glutathione as the most likely cause of serious manifestations and death
in COVID-19 patients, ACS Infectious Diseases, 2020, 6(7): 1558-1562.
3. Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2
receptor: molecular mechanisms and potential therapeutic target, Intensive Care Med., 3, 2020.
https://doi:10.1007/s00134-020-05985-9.
4. Tisoncik J.R, Korth M.J, Simmons C.P, Farrar J, Martin T.R, Katze M.G, Into the eye of the cytokine storm,
Microbiol Mol Biol Rev., 2012, 76: 16-32. https://doi: 10.1128/MMBR.05015-11.
5. Forman H.J, Zhang H, Rinna A, Glutathione: overview of its protective roles, measurement and biosynthesis,
Mol. Aspects Med., 2009, 30(1-2): 1-12.
6. Pizzorno J, Glutathione! Integr. Med. (Encinitas), 2014, 13(1): 8-12.
7. Sastre J, Federico VP, Viña J. Glutathione, oxidative stress and aging, AGE 19, 1996, 129-139.
https://doi.org/10.1007/BF02434082.
8. Ali N. Role of vitamin D in preventing of COVID-19 infection, progression and severity. Journal of Infection and
Public Health, 2020, 13(10): 1373-1380.
9. Flora D, Grassi C, Carati L. Attenuation of influenza-like symptomatology and improvement of cell-mediated
immunity with long-term N-acetylcysteine treatment, European Respiratory Journal, 1997, 10(7): 1535-1541.
10. Banerjee K, Biswas MK, Choudhuri SK. A newly synthesized Nickel chelate can selectively target and overcome
multidrug resistance in cancer through redox imbalance both in vivo and in vitro, J. Biol. Inorg. Chem., 2017,
22(8): 1223-1249.
11. Banerjee K, Ganguly A, Chakraborty P, Sarkar A, Singh S, Chatterjee M, Bhattacharya S, Choudhuri SK. ROS and
RNS induced apoptosis through p53 and iNOS mediated pathway by a dibasic hydroxamic acid molecule in
leukemia cells, European Journal of Pharmaceutical Sciences, 2014, 52: 146-164.
12. Basu S, Ganguly A, Chakraborty P, Sen R, Banerjee K, Chatterjee M, Efferth T, Choudhuri SK. Targeting the
mitochondrial pathway to induce apoptosis/necrosis through ROS by a newly developed Schiff’s base to
overcome MDR in cancer, Biochimie, 2012, 94: 166-183.
13. Townsend DM, Tew KD, Tapiero H. The importance of glutathione in human disease, Biomed. Pharmacology,
2003, 57: 145-155.
14. Silvagno F, Vernone A, Pescarmona GP. The role of glutathione in protecting against the severe inflammatory
response triggered by COVID-19. Antioxidants (Basel), 2020, 9(7): 624.
15. McGuinness AJ, Sapey E. Oxidative stress in COPD: Sources, markers, and potential mechanisms, J. Clin. Med.,
2017, 6(2): 21.
16. Elokda AS, Nielsen DH. Effects of exercise training on the glutathione antioxidant system, Eur. J. Cardiovasc.
Prev. Rehabil., 2007, 14(5): 630-7. https://doi.org/10.1097/HJR.0b013e 32828622d7.
17. Minich DM, Brown BI. A Review of Dietary (Phyto) Nutrients for Glutathione Support., Nutrients, 2019, 11(9):
2073-2093.
18. Aarón J, Méndez R, Ester R, Puc M. N-acetylcysteine as a potential treatment for novel coronavirus disease 2019,
Future Microbiol., 2020, 15: 959-962.
19. Horowitz RI, Freeman PR, Bruzzese J. Efficacy of glutathione therapy in relieving dyspnea associated with
COVID-19 pneumonia: A report of 2 cases Respiratory Medicine Case Reports, 2020, 30: 101063.
20. Choudhuri SK. Glutathione Enrichment as a Possible Prevention and Treatment for COVID-19, Int. J. of Pharma
Sci. and Scientific Res., 2020, 6(4): 65-66.
21. Holick MF. The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and prevention, Reviews in
Endocrine and Metabolic Disorders, 2017, 18(2): 153-165.
Surajit Majumder
et al.,
Indian Journal of Natural Sciences www.tnsroindia.org.in ©IJONS
Vol.12 / Issue 69 / December / 2021 International Bimonthly (Print) ISSN: 0976 – 0997
36779
22. Dankers W, Colin EM, Hamburg JP, Lubberts E. Vitamin D in autoimmunity: molecular mechanisms and
therapeutic potential, Frontiers in Immunology, 2017, 7: 697.
23. Infante M, Ricordi C, Sanchez J, Clare-Salzler MJ, Padilla N, Fuenmayor V, et al. Influence of vitamin D on islet
autoimmunity and beta-cell function in type 1 diabetes, Nutrients, 2019, 11(9): 2185.
24. Yun-Fang Z, Luo BA, Qin LL. The association between vitamin D deficiency and community-acquired
pneumonia: A meta-analysis of observational studies, Medicine (Balti.), 2019, 98(38).
25. Nobrega A. IMPORTÂNCIA DA VITAMINA D EM COVID-19, Revista Ibero-Americana de Humanidades,
Ciências e Educação, 2021, 7(7): 1060-1081.
26. Cantorna MT, Snyder L, Lin YD, Yang L. Vitamin D and 1, 25 (OH) 2D regulation of T cells, Nutrients, 2015, 7(4):
3011-3021.
27. Zdrenghea MT, Makrinioti H, Bagacean C, Bush A, Johnston SL, Stanciu LA. Vitamin D modulation of innate
immune responses to respiratory viral infections, Reviews in Medical Virology, 2017, 27(1): e1909.
28. Shi Y, Liu T, Yao L, Xing Y, Zhao X, Fu J, Xue X. Chronic vitamin D deficiency induces lung fibrosis through
activation of the renin-angiotensin system, Scientific Reports, 2017, 7(1): 1-10. https://doi: 10.1038/s41598-017-
03474-6.
29. Jain SK, Kahlon G, Bass P, Levine SN, Warden C. Can L-cysteine and vitamin D rescue vitamin D and vitamin D
binding protein levels in blood plasma of African American type 2 diabetic patients? 2015, 23(8): 688-693.
30. Jain SK, Marie PK, Warden C, Micinski D. L‐cysteine supplementation upregulates glutathione (GSH) and
vitamin D binding protein (VDBP) in hepatocytes cultured in high glucose and in vivo in liver, and increases
blood levels of GSH, VDBP, and 25‐hydroxy‐vitamin D in Zucker diabetic fatty rats, Molecular Nutrition & Food
Research, 2016, 60(5): 1090-1098. https://doi.org/10.1002/mnfr.201500667.
31. Parsanathan R, Jain SK. Glutathione deficiency induces epigenetic alterations of vitamin D metabolism genes in
the livers of high-fat diet-fed obese mice, Scientific Reports, 2019, 9(1): 1-11.
Surajit Majumder
et al.,
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