Review: Improving Therapeutics for COVID-19 with Glutathione-boosting Treatments that Improve Immune Responses and Reduce the Severity of Viral Infections

Abstract

Glutathione-boosting treatments have been shown to enhance immune responses and reduce the severity of influenza, coronavirus, HIV and other viral infections. Such viral infections markedly increase the production of Reactive Oxygen Species (ROS) and deplete cysteine and critical antioxidants, including reduced glutathione (GSH). These viruses use depletion of GSH to create an oxidized environment needed for viral replication/assembly and evading the host immune system. High levels of reduced glutathione in antigen presenting cells is critical for mounting an adaptive immune response to viral infections and for avoiding inflammatory cytokine responses. SARS CoV-1 up-regulates TGF-β1, which increases ROS, depletes glutathione and lowers substrate and enzyme needed for glutathione synthesis. Demographic groups with highest susceptibility to SARS-CoV-2 infection (e.g. the elderly; diabetics and African-Americans) have lower levels of Glutathione, lower amino acid substrate and/or critical enzyme needed to synthesize glutathione. Increased susceptibility of the elderly, diabetics and African-Americans to SARS-CoV-2 may in part be due to a reduced ability to maintain high GSH and redox status during viral infection. This paper reviews a substantial body of evidence that Glutathione-boosting supplements including N-Acetyl Cysteine (NAC), Alpha Lipoic Acid (ALA) and Liposomal Reduced Glutathione have beneficial effects in combating viral disruption of redox status and immune responses in animal models and in humans. Glutathione-boosting treatments improve immune responses, as well as reduce viral replication, inflammatory cytokines and/or severity of viral infections, including HIV and even Influenza in the elderly. The potential for glutathione-boosting supplements to reduce risks of severe COVID-19 induced cytokine storms and disease in susceptible populations is addressed. Clinical trials are needed to determine if the severity of COVID-19 is reduced from onset of symptoms by: combined oral treatment with up to 2400 mg/day NAC and 1200 mg/day ALA; or with NAC, ALA and 2000 mg/day oral Liposomal Reduced Glutathione; versus a placebo control.

Vitamins and other immune-supportive elements as cofactors for passing the COVID-19 pandemic

“…In cellular proteins, glutathione acts as a barrier against reactive oxygen species (ROS) produced by several viral infections including COVID-19, but excessive production of ROS results in depletion of the defending proteins and worsening of COVID-19 patient's condition [14][15][16]. A recent study indicated that the glutathione, glutathione peroxidase activity was lower in COVID-19 patients compared to the control group as a result of increased oxidative stress [16].…”

“…Glutathione is the main defensive antioxidant synthesized from three amino acids involving cysteine, glycine, and glutamic acid. It acts as a barrier that interacts with ROS before damaging the cellular component [14]. The depletion of glutathione and other antioxidants leads to more viral spread and replication by providing a more convenient environment [17][18][19].…”

The Effectiveness of High-dose N-acetylcysteine in Severe COVID-19 Patients

“…In the literature, it is stated that NAC is given until there is clinical improvement, improvement of chest x-ray, decrease in CRP (<10 mg/dL), or improvement of hyper inflammation (Suprabawati, 2020). NAC has a mechanism of action as a "glutathione-boosting treatment" that can increase the immune response and decrease pro-inflammatory cytokines to reduce the risk of the severity of COVID-19 caused by cytokine storms in the body (Spearow, 2020). Glutathione is an antioxidant that plays a role in protecting cells from oxidative stress and is widely found in the body (Burhan et al, 2018).…”

“…Glutathione is an antioxidant widely found in the body and plays a role in protecting cells from oxidative stress (Burhan et al, 2018). Giving NAC as a "glutathione-boosting treatment" can reduce proinflammatory cytokines to reduce the risk of the severity of COVID-19 caused by cytokine storms in the body (Medicine, 2020;Nasi et al, 2020;Spearow & Copeland, 2020).…”

Vitamin C biochemistry: From scurvy to COVID-19 treatment

“…Several proven mechanisms underlying the role of vitamin C in the treatment and/or prevention of previously mentioned diseases include enhancement of the immune system, prevention of the free radical damage (antioxidant role), inhibition of the excessive activation of the immune system, and consequential prevention of tissue damage, the formation of the epithelial and endothelial barrier. Vitamin C, along with other micronutrients (zinc, selenium, magnesium, vitamin A, D, and E) [156][157][158], glutathione [159,160], and omega-3 fatty acids [161], is considered to be one of the leading antiviral co-therapy targeting SARS-CoV-2. While the positive effects of vitamin C were recognized, its mechanism of action remains unknown.…”