The direct targets of extremely low and microwave frequency range electromagnetic fields (EMFs) in producing non-thermal effects have not been clearly established. However, studies in the literature, reviewed here, provide substantial support for such direct targets.
Twenty-three studies have shown that voltage-gated calcium channels (VGCCs) produce these and other EMF effects, such that the L-type or other VGCC blockers block or greatly lower diverse EMF effects. Furthermore, the voltage-gated properties of these channels may provide biophysically plausible mechanisms for EMF biological effects. Downstream responses of such EMF exposures may be mediated through Ca2+/calmodulin stimulation of nitric oxide synthesis. Potentially, physiological/therapeutic responses may be largely as a result of nitric oxide-cGMP-protein kinase G pathway stimulation.
A well-studied example of such an apparent therapeutic response, EMF stimulation of bone growth, appears to work along this pathway. However, pathophysiological responses to EMFs may be as a result of nitric oxide-peroxynitrite-oxidative stress pathway of action. A single such well-documented example, EMF induction of DNA single-strand breaks in cells, as measured by alkaline comet assays, is reviewed here. Such single-strand breaks are known to be produced through the action of this pathway.
Data on the mechanism of EMF induction of such breaks are limited; what data are available support this proposed mechanism. Other Ca2+-mediated regulatory changes, independent of nitric oxide, may also have roles.
This article reviews, then, a substantially supported set of targets, VGCCs, whose stimulation produces non-thermal EMF responses by humans/higher animals with downstream effects involving Ca2+/calmodulin-dependent nitric oxide increases, which may explain therapeutic and pathophysiological effects.
Discussion and conclusions
How do EMFs composed of low-energy photons produce non-thermal biological changes, both pathophysiological and, in some cases, potentially therapeutic, in humans and higher animals? It may be surprising that the answer to this question has been hiding in plain sight in the scientific literature. However, in this era of highly focused and highly specialized science, few of us have the time to read the relevant literature, let alone organize the information found within it in useful and critical ways.
This study shows that:
- Twenty-three different studies have found that such EMF exposures act via activation of VGCCs, such that VGCC channel blockers can prevent responses to such exposures (Table 1). Most of the studies implicate L-type VGCCs in these responses, but there are also other studies implicating three other classes of VGCCs.
- Both extremely low frequency fields, including 50/60 cycle exposures, and microwave EMF range exposures act via activation of VGCCs. So do static electric fields, static magnetic fields and nanosecond pulses.
- Voltage-gated calcium channel stimulation leads to increased intracellular Ca2+, which can act in turn to stimulate the two calcium/calmodulin-dependent nitric oxide synthases and increase nitric oxide. It is suggested here that nitric oxide may act in therapeutic/potentially therapeutic EMF responses via its main physiological pathway, stimulating cGMP and protein kinase G. It is also suggested that nitric oxide may act in pathophysiological responses to EMF exposure, by acting as a precursor of peroxynitrite, producing both oxidative stress and free radical breakdown products.
- The interpretation in three above is supported by two specific well-documented examples of EMF effects. Electromagnetic fields stimulation of bone growth, modulated through EMF stimulation of osteoblasts, appears to involve an elevation/nitric oxide/protein kinase G pathway. In contrast to that, it seems likely that the EMF induction of single-stranded DNA breaks involves a Ca2+/elevation/nitric oxide/peroxynitrite/free radical (oxidative stress) pathway.
It may be asked why we have evidence for involvement of VGCCs in response to EMF exposure, but no similar evidence for involvement of voltage-gated sodium channels? Perhaps, the reason is that there are many important biological effects produced in increased intracellular Ca2+, including but not limited to nitric oxide elevation, but much fewer are produced by elevated Na+.
The possible role of peroxynitrite as opposed to protein kinase G in producing pathophysiological responses to EMF exposure raises the question of whether there are practical approaches to avoiding such responses? Typically peroxynitrite levels can be highly elevated when both of its precursors, nitric oxide and superoxide, are high. Consequently, agents that lower nitric oxide synthase activity and agents that raise superoxide dismutases (SODs, the enzymes that degrade superoxide) such as phenolics and other Nrf2 activators that induce SOD activity , as well as calcium channel blockers may be useful. Having said that, this is a complex area, where other approaches should be considered, as well.
Although the various EMF exposures as well as static electrical field exposures can act to change the electrical voltage-gradient across the plasma membrane and may, therefore, be expected to stimulate VGCCs through their voltage-gated properties, it may be surprising that static magnetic fields also act to activate VGCCs because static magnetic fields do not induce electrical changes on static objects. However, cells are far from static. Such phenomena as cell ruffling , may be relevant, where thin cytoplasmic sheets bounded on both sides by plasma membrane move rapidly. Such rapid movement of the electrically conducting cytoplasm, may be expected to influence the electrical charge across the plasma membrane, thus potentially stimulating the VGCCs.
Earlier modelling of electrical effects across plasma membranes of EMF exposures suggested that such electrical effects were likely to be too small to explain EMF effects at levels reported to produce biological changes (see, for example ). However, more recent and presumably more biologically plausible modelling have suggested that such electrical effects may be much more substantial [104–109] and may, therefore, act to directly stimulate VGCCs.
Direct stimulation of VGCCs by partial depolarization across the plasma membrane is suggested by the following observations discussed in this review:
- The very rapid, almost instantaneous increase in intracellular Ca2+ found in some studies following EMF exposure [8, 16, 17, 19, 21, 27]. The rapidity here means that most, if not all indirect, regulatory effects can be ruled out.
- The fact that not just L-type, but three additional classes of VGCCs are implicated in generating biological responses to EMF exposure (Table 1), suggesting that their voltage-gated properties may be a key feature in their ability to respond to EMFs.
- Most, if not all, EMF effects are blocked by VGCC channel blockers (Table 1).
- Modelling of EMF effects on living cells suggests that plasma membrane voltage changes may have key roles in such effects [104–109]. Saunders and Jefferys stated  that ‘It is well established that electric fields … or exposure to low frequency magnetic fields, will, if of sufficient magnitude, excite nerve tissue through their interactions with … voltage gated ion channels’. They further state  that this is achieved by direct effects on the electric dipole voltage sensor within the ion channel.
One question that is not answered by any of the available data is whether what is known as ‘dirty electricity’ [111–113], generated by rapid, in many cases, square wave transients in EMF exposure, also acts by stimulating VGCCs. Such dirty electricity is inherent in any digital technology because digital technology is based on the use of such square wave transients and it may, therefore, be of special concern in this digital era, but there have been no tests of such dirty electricity that determine whether VGCCs have roles in response to such fields, to my knowledge. The nanosecond pulses, which are essentially very brief, but high-intensity dirty electricity do act, at least in part, via VGCC stimulation (Table 1), suggesting that dirty electricity may do likewise. Clearly, we need direct study of this question.
The only detailed alternative to the mechanism of non-thermal EMF effects discussed here, to my knowledge, is the hypothesis of Friedman et al.  and supported by Desai et al.  where the apparent initial response to EMF exposure was proposed to be NADH oxidase activation, leading to oxidative stress and downstream regulatory effects. Although they provide some correlative evidence for a possible role of NADH oxidase , the only causal evidence is based on a presumed specific inhibitor of NADH oxidase, diphenyleneiodonium (DPI). However, DPI has been shown to be a non-specific cation channel blocker , clearly showing a lack of such specificity and suggesting that it may act, in part, as a VGCC blocker. Consequently, a causal role for NADH oxidase in responses to EMF exposure must be considered to be undocumented.
In summary, the non-thermal actions of EMFs composed of low-energy photons have been a great puzzle, because such photons are insufficiently energetic to directly influence the chemistry of cells. The current review provides support for a pathway of the biological action of ultralow frequency and microwave EMFs, nanosecond pulses and static electrical or magnetic fields: EMF activation of VGCCs leads to rapid elevation of intracellular Ca2+, nitric oxide and in some cases at least, peroxynitrite. Potentially therapeutic effects may be mediated through the Ca2+/nitric oxide/cGMP/protein kinase G pathway. Pathophysiological effects may be mediated through the Ca2+/nitric oxide/peroxynitrite pathway. Other Ca2+-mediated effects may have roles as well, as suggested by Xu et al. .
Authors : Giovanni Messina (1), Rita Polito (1), Vincenzo Monda (2), Luigi Cipolloni (1), Nunzio Di Nunno (3), Giulio Di Mizio (4), Paolo Murabito (5), Marco Carotenuto (6), Antonietta Messina (2), Daniela Pisanelli (1), Anna Valenzano (1), Giuseppe Cibelli (1), Alessia Scarinci (7), Marcellino Monda (2), Francesco Sessa (1)
- Department of Clinical and Experimental Medicine, University of Foggia, Italy
2. Department of Experimental Medicine, Section of Human Physiology and Unit of Dietetics and Sports Medicine, Università degli Studi della Campania Naples, Italy
3. Department of History, Society and Studies on Humanity, University of Salento, Lecce Italy
4. Department of Law, Forensic Medicine, Magna Graecia University of Catanzaro, Italy
5. Department of General Surgery and Medical-Surgical Specialties, University of Catania, Italy
6. Department of Mental Health, Physical and Preventive Medicine, Clinic of Child and Adolescent Neuropsychiatry, Università degli Studi della Campania Italy
7. Department of Education Sciences, Psychology and Communication, University of Bari, Italy
Background: On the 31 December 2019, the World Health Organization (WHO) was informed of a cluster of cases of pneumonia of unknown origin detected in Wuhan City, Hubei Province, China.
The infection spread first in China and then in the rest of the world, and on the 11th of March, the WHO declared that COVID-19 was a pandemic. Taking into consideration the mortality rate of COVID-19, about 5–7%, and the percentage of positive patients admitted to intensive care units being 9–11%, it should be mandatory to consider and take all necessary measures to contain the COVID-19 infection.
Moreover, given the recent evidence in different hospitals suggesting IL-6 and TNF-α inhibitor drugs as a possible therapy for COVID-19, we aimed to highlight that a dietary intervention could be useful to prevent the infection and/or to ameliorate the outcomes during therapy. Considering that the COVID-19 infection can generate a mild or highly acute respiratory syndrome with a consequent release of pro-inflammatory cytokines, including IL-6 and TNF-α, a dietary regimen modification in order to improve the levels of adiponectin could be very useful both to prevent the infection and to take care of patients, improving their outcomes.
On the 31 December 2019, the World Health Organization (WHO) was informed of a cluster of cases of pneumonia of unknown origin detected in Wuhan City, Hubei Province, China. About one month later (on 8 January 2020), the Chinese authorities declared the identification of a new type of coronavirus, informing the WHO a few days later that the outbreak was associated with exposure in a seafood market in Wuhan City.
The infection spread firstly in China and then in the rest of the world, and on the 11th of March, the WHO declared that COVID-19 was a pandemic.Coronaviruses (CoVs) belong to the subfamily Orthocoronavirinae in the family of Coronaviridae in the order Nidovirales, and this subfamily includes α-coronavirus, β-coronavirus, γ-coronavirus, and delta-coronavirus .
Coronaviruses primarily cause enzootic infections in birds and mammals and, in the last few decades, have shown to be capable of infecting humans as well . In human infections with highly virulent respiratory viruses—such as avian influenza H5N1, H7N9, Severe Acute Respiratory Syndrome (SARS) coronavirus, and Coronavirus Disease-19 (COVID-19)—immunopathogenesis caused by the overproduction of pro-inflammatory cytokines may play an essential role in disease progression and mortality .
Several recent studies have reported that COVID-19 caused the destruction of the pulmonary parenchyma, including interstitial inflammation and extensive consolidation, similarly to the previously reported coronavirus infection [4,5]. During coronavirus infection, it was observed that the lungs increased in weight, with a mild pleural effusion of clear serous fluid, named pulmonary edema, and extensive consolidation [6,7]. In some areas, there was interstitial thickening, with mild-to-moderate fibrosis, but a disproportionately sparse infiltrate of inflammatory cells (mainly histiocytes, including multinucleated forms, and lymphocytes) . A dilatation of the airspaces was observed, as was focal honeycombing fibrosis. An intra-alveolar organization of exudates was described, and the formation of granulation tissues in the small airways and airspaces was reported. These lesions were typically located in the sub-pleural region, and the cellular component mainly consisted of histiocytes, as reported in a previous paper . Xu et al. described in their case report the pathological findings of COVID-19 associated with acute respiratory distress syndrome. At the X-ray investigation, they detected a rapid progression of bilateral pneumonia.
The biopsy samples were taken from the lung; the histological examination showed bilateral diffuse alveolar damage with cellular fibromyxoid exudates .Considering that the mortality rate of COVID-19, about 5–7% , and the percentage of positive patients admitted to intensive care units being 9–11% , it should be mandatory to consider and take all necessary measures intended to contain the viral infection.
A recent study analyzed the data of 150 COVID-19 patients, with the aim of defining the clinical predictors of mortality. The results obtained from this study suggest that COVID-19 mortality might be due to virus-activated “cytokine storm syndrome”, considering that the plasma levels of IL-6 were higher in deceased patients compared to in discharged subjects .Considering that a detailed study has not been performed on the immunological response to COVID-19, the only way to discuss this thematic is to refer to previous knowledge about SARS-CoV and MERS-CoV. The first response is obtained through pattern recognition receptors (PRRs) including C-type lectin-like receptors, Toll-like receptors (TLR), NOD-like receptors (NLR), and RIG-I-like receptors (RLR). Moreover, several inflammatory factors are expressed such as IL-6 and TNF-α; moreover, the synthesis of type I interferons (IFNs) is activated, and these exert their actions against virus diffusion, accelerating macrophage phagocytosis  (Figure 1).
In the light of these considerations and the recent evidence in different hospitals suggesting IL-6 and TNF-α inhibitor drugs as a possible therapy for COVID-19, this review aims to highlight how a dietary intervention could be useful to prevent the infection and/or to ameliorate the outcome during therapy.
2. The Pivotal Role of IL-6 and TNF-α in Lung Infections
The first laboratory report about COVID-19 patients indicated several parameters that were found to be altered in blood samples; for example, D-dimer, neutrophil count, blood urea, and creatinine levels were significantly higher. In the same way, several cytokines such as IL-6 and TNF-α were overexpressed, indicating the immune status of the patients .IL-6 represents pro-inflammatory signaling produced by adipose tissue; for this reason, this endocrine cytokine could be important in regulating the host response during acute infection .
Several papers have described the essential role of IL-6 in generating a proper immune response during different kinds of viral infection in the pulmonary tract. Others link this cytokine to an exacerbation of viral disease. These latter findings support the hypothesis that IL-6 upregulation during viral infections may promote virus survival and the exacerbation of the clinical disease [16,17].
Indeed, IL-6 has a pleiotropic function, and it is produced in response to tissue damage and infection. In particular, at the pulmonary level, innate and adaptative immune cell proliferation is strongly influenced by this cytokine. After targeting its specific receptor, IL-6 starts a cascade of signaling events mainly associated with the JAK/STAT3 activation pathway, promoting the transcription of multiple downstream genes related to cellular signaling processes, including cytokines, receptors, adaptor proteins, and protein kinase .
Furthermore, it has been reported that IL-6 is an essential factor for the survival of mice with a viral infection. This cytokine promotes the optimal regulation of the T-cell response, inflammatory resolution, tissue remodeling promoting lung repair, cell migration, and the phagocytic activities of macrophages, as well as preventing virus-induced apoptosis in lung epithelial cells.
However, experimental scientific evidence also suggests potential adverse consequences that increased levels of IL-6 might have on the cellular immune response against viruses. In this context, different possible mechanisms involving this cytokine might affect viral clearance, ultimately favoring the establishment of a persistent viral state in infected hosts [18,19].
Tumor necrosis factor is a cell-signaling protein (cytokine) involved in systemic inflammation, released predominately from macrophages, but it is also released from a variety of other immune cells. It has been well described that during infection with the influenza virus, the expression of TNF-α in lung epithelial cells was higher, exerting powerful anti-influenza virus activity .
In an animal model, it has been demonstrated that TNF-α plays a pivotal role in the development of pulmonary fibrosis. TNF-α signals via two receptors, TNF-RI and TNF-RII; the first receptor (TNF-RI) promotes intracellular signaling involving c-Jun N-terminal kinase (JNK) and nuclear factor (NF)-κB, while the other receptor, TNF-RII, promotes TNF-RI–dependent cell death, without directly inducing apoptosis. Although both receptors are broadly expressed, it is known that the majority of inflammatory signaling is elicited through TNF-RI .
In an in vitro model, it has been described that serine/threonine kinases can phosphorylate TNF-RI and its molecules, preventing tyrosine phosphorylation [22,23,24].In patients with COVID-19, the high serum levels of IL-6 and TNF-α are negatively correlated to T cells; contrariwise, it has been demonstrated that T cell levels were restored by reducing IL-6 and TNF-α concentrations . These findings suggested that these cytokines could represent important targets of anti-COVID-19 therapies.
3. Adiponectin Function in Lung Infections
Through the secretion of adipokines, adipose tissue participates in the regulation of several pathophysiological processes in many organs and tissues. Among the adipokines, adiponectin is the most relevant. Adiponectin is one of the most abundant circulating adipocytokines, accounting for 0.01% of total serum protein. Adiponectin is an important regulator of cytokine responses, and this effect is isoform-specific. It is involved in a wide variety of physiological processes, including energy metabolism, inflammation, and vascular physiology. These effects are mediated by two atypical, widely expressed seven-transmembrane receptors, AdipoR1 and AdipoR2 . Adiponectin has beneficial effects in cardiovascular systems and blood vessels, protecting these tissues through the inhibition of pro-inflammatory and hypertrophic responses and stimulation of endothelial cell responses .
Adiponectin circulates as three different isoforms (low molecular weight—LMW, medium molecular weight—MMW, and high molecular weight—HMW) .Infectious diseases are characterized by an increased production of adiponectin. Several papers suggest that adiponectin may be related to disease activity and/or severity in different conditions such as rheumatoid arthritis, osteoarthritis, and systemic lupus erythematosus. Since adiponectin has been found to display both pro- and anti-inflammatory activities, controversial findings have been observed regarding the role of total adiponectin in systemic autoimmune and inflammatory joint diseases. For this reason, the relative contribution of each adiponectin isoform to the inflammatory response and joint and/or tissue damage requires further study .
It is reported that adiponectin is regulated by transcription factors in adipose tissue, such as peroxisome proliferator-activated receptor-γ (PPAR-γ) . During viral infections, it has been reported that the role of the predisposition of hosts is also important, as well as their state of health and nutrition. Indeed, it is well known that white adipose tissue is considered an endocrine source of biologically active substances with local and/or systemic action, called adipokines.
The inappropriate secretion of adipokines seems to participate in the pathogenesis of obesity-related diseases, including endothelial dysfunction, inflammation, and atherosclerosis [31,32,33].The biological function of adipokines in lung diseases seems to be mainly related to the inflammatory process. In particular, the intercorrelation between adipose tissue and the lung has become evident as the involvement of adiponectin has been demonstrated in several lung diseases such as Chronic Obstructive Pulmonary Disease (COPD), emphysema, and cancer . In fact, with specific regard to COPD, a low-grade inflammatory state has been demonstrated [35,36,37].
Moreover, increasing evidence suggests that adiponectin also exerts a crucial role in the vascular endothelium, maintaining vascular homeostasis and protecting against vascular dysfunctions. Altogether, these findings support the anti-inflammatory role of adiponectin in COPD and, in general, in other lung diseases .The critical role of adiponectin in the pathophysiological conditions of the lung is also supported by the modulation of AdipoRs with the downregulation of AdipoR2. It has been described that the adiponectin oligomerization state is altered in COPD; moreover, the presence of AdipoR1 and AdipoR2, with a lower expression of AdipoR2 compared to AdipoR1, in lung tissue  has been demonstrated. The low expression of AdipoR2 could suggest a specific role of this receptor, mainly implicated in adiponectin’s effects on inflammation and oxidative stress. Mainly, it has been observed that higher levels of adiponectin are associated with a significant and specific increase in HMW adiponectin, representing the most biologically active forms. Thus, HMW adiponectin increases IL-6 secretion in human monocytes and human monocytic leukemia cell lines but does not suppress lipopolysaccharide (LPS)-induced IL-6 secretion. Byn contrast, LMW adiponectin reduces LPS-mediated IL-6 release and also stimulates IL-10 secretion .
Furthermore, several in vitro studies have demonstrated that adiponectin in the A549 adenocarcinoma human alveolar basal epithelial cell line has an essential apoptotic effect and also reduces the production of pro-inflammatory cytokines such as TNF-α, blocking NF-κB nuclear translocation [41,42].Indeed, adiponectin can reduce innate and adaptive immune cell proliferation and polarization, also blocking the production of pro-inflammatory cytokines such as TNF-α, IL-2, and IL-6, and enhancing that of anti-inflammatory cytokines such as IL-10, with a decrease in the phosphorylation of AMPK, p38, ERK1/2, and c-JNK [43,44,45,46]. Data from in vitro studies on lung cells were consistent with an anti-inflammatory function of adiponectin, and adiponectin-deficient mouse models developed lung function impairments and systemic inflammation .
The possible role of adiponectin in inflammatory pulmonary diseases, such as asthma and chronic obstructive pulmonary disease (COPD), and in critical illnesses has been the subject of recent investigations. Particularly, the HMW isoform has a specific role in pulmonary diseases and critical illnesses, even if its role should be better clarified [48,49].
An interesting study reported that systemic adiponectin concentrations in humans fall during the acute phase of lung infection: particularly, during the early phase, the pro-inflammatory state is generated by the high systemic TNF-α and IL-6 concentrations, with the subsequent inhibition of adiponectin production. Contrariwise, it has been described that the reduction in TNF-α and IL-6 factors generates a corresponding bounce-back in systemic adiponectin concentrations .
Although it is still unclear whether the modulation of systemic adiponectin or its signaling pathways has any therapeutic benefit in pulmonary or critical illnesses, it may serve as a novel therapeutic or preventative tool for these illnesses in the future. One obvious pharmaceutical treatment would be the exogenous administration of adiponectin by the inhalational or intravenous route. Although this has been tried in mouse models , the problems to be overcome prior to human administration include establishing what the biologically active molecule is and what role post-translational modifications have upon its function, and the associated difficulties in generating biologically active molecules on a large scale.
Considering the difficulty linked to the direct administration of adiponectin, in the last few years, other drugs have been used that indirectly improve adiponectin production. For example, a synthetic ligand of peroxisome proliferator-activated receptors can increase adiponectin mRNA in adipocytes, improving the production and secretion of adiponectin [52,53,54,55]. Moreover, other drugs such as fibrates can increase systemic adiponectin levels by enhancing PPAR-γ activity [56,57]. Another way to improve adiponectin levels is the use of angiotensin converting enzyme inhibitors [58,59,60]. Furthermore, it is possible to stimulate adipocyte differentiation  and the activation of PPAR .
Finally, it has been described that calcium channel blockers  and a central-acting anti-hypertensive agent  also increase systemic adiponectin concentrations . The possibility to improve the action of adiponectin through diet is intriguing; it has been described that nutritional interventions may help to regulate systemic adiponectin concentrations. In an animal model, it has been demonstrated that a diet with a high concentration of polyunsaturated fatty acids and supplemented with ω-3 can improve the plasma levels of adiponectin, increasing gene expression . On the other hand, in humans, adiponectin levels are positively associated with a healthy lifestyle and the Mediterranean diet, even if the mechanisms of action are not completely known . Finally, in light of these considerations, in COVID-19 therapy, it could be very useful to combine drug therapy with a specific diet regimen.
4. ω-3 PUFAs and Lung Infections
Another important mediator involved in the immune response and influenced by nutrition are fatty acids, in particular, ω-3 PUFAs [67,68]. In fact, during bacterial and viral infections, they are able to act on immune cells and regulate diverse inflammatory processes. ω-3 PUFAs are known to have anti-inflammatory properties and play an essential role in the resolution of inflammation .
In several lung infections, the administration of PUFA can ameliorate the outcome of the patient in acute pneumonia. Sharma et al. reported in their study that the dietary supplementation of ω-3 PUFA can exert an overall beneficial effect against acute pneumonia through the upregulation of the host’s specific and nonspecific immune defenses . ω-3 polyunsaturated fatty acids (PUFA, ω-3-fatty acids), the key components of fish and flaxseed oils, are increasingly consumed by the public because of their potential health benefits and can be used clinically for the treatment of metabolic, cardiac, inflammatory, and autoimmune diseases .
However, numerous studies have shown that these compounds are immunoregulatory and immunosuppressive and thus may increase susceptibility to infection. While reports suggest that ω-3 PUFAs may have beneficial effects against extracellular pathogens, few studies have been performed on systemic viral infections in mammals. Jones and Roper described in their study that a diet rich in ω-3 PUFAs did not significantly lower survival of the vaccinia virus infection, at least with short-term (~6 week) feeding in mice .
ω-3 PUFAs are metabolized into various mediators possessing anti-inflammatory properties such as resolvins and protectins. It is known that ω-3 PUFAs can reduce NF-κB activation by preventing nuclear p65 NF-κB translocation. Furthermore, ω-3 PUFAs minimize the activation of ERK1/2 MAPK, also reducing COX-2 production. The ω-3 PUFA-derived lipid mediator could markedly attenuate influenza virus replication via the RNA export machinery. In addition, the treatment of protectin D1 with peramivir could completely stop mouse mortality .
ω-3 supplementation was previously studied in Acute Respiratory Distress Syndrome (ARDS). Singer and Shapiro suggested that the enteral administration of natural antioxidant substances could improve oxygenation and clinical outcomes in ICU patients . A systematic review performed in 2015 reported a positive effect only for patients suffering from ARDS with high mortality . A more recent meta-analysis highlighted the importance of clinical trials in order to clarify the use of ω-3 fatty acids and antioxidants in patients with ARDS to ascertain the positive effects in order to reduce the lengths of ICU stays and the numbers of days spent on ventilators .
Although the role of ω-3 supplementation in ARDS should be better clarified, its pivotal role in reducing reactive oxygen species and pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-6, and IL-8 , is well known.Therefore, ω-3 PUFAs, including protectin D1, which is a novel antiviral drug, could be considered for potential interventions for COVID-19.
5. Other Dietary Constituents and Lung Infections
As previously described, other dietary constituents can be used to improve the patients’ outcomes during lung infection, regulating the inflammatory response. Among these, antioxidants play an important role in protecting lung cells against viruses and bacteria. Viral infection leads to an increase in the intrapulmonary oxidative burden. In many diseases, the balance between oxidants and antioxidants (redox balance) is altered, with severe consequences .
The pathophysiological mechanisms by which free radicals generate various types of stress—such as oxidative, nitrative, carbonyl, inflammatory, and endoplasmic reticulum stress—lead to lung inflammation and an altered lung immune response. In this scenario, dietary antioxidants may play an important role against lung oxidative stress .
Several studies reported the protective role of the antioxidants in lung infection and in lung inflammation [78,79].In particular, vitamin C, polyphenols, and flavonoids can play a protective role in lung infections, being immune modulators and inflammatory mediators. Indeed, as reported by Carr et al., during infection, vitamin C levels may become depleted; for this reason, vitamin C supplementation can attenuate infection. Based on this evidence, these authors suggested a clinical trial with vitamin C infusion for the treatment of severe COVID-19 patients .
Among polyphenols, epigallo-catechin 3 gallate (EGCG) is the most potent ingredient in green tea and exhibits antibacterial, antiviral, antioxidative, anticancer, and chemo-preventive activities. Recently, numerous studies have investigated the protective effects of EGCG against asthma and other lung diseases such as COPD and lung pneumonia. EGCG may suppress inflammation and inflammatory cell infiltration into the lungs of asthmatic mice, and may also inhibit epithelial-mesenchymal transition EMT via the PI3K/Akt signaling pathway through upregulating the expression of phosphatase and tensin homolog (PTEN), both in vivo and in vitro .
Moreover, flavonoids can be used to attenuate lung injury in mice; it has been reported that they inhibit influenza virus and Toll-like receptor signaling, blocking NF-κB translocation .Therefore, as summarized in Table 1, supplementation with vitamin C, flavonoids, and polyphenols can be tested in COVID-19 patients, both in order to prevent viral infection and to improve patients’ outcomes.
Table 1. The principal antioxidants involved in lung infection and the immune-inflammatory response.
6. Discussion and Conclusions
During pulmonary infections, and particularly in COVID-19 patients, intracellular signaling leads to the production of pro-inflammatory cytokines, such as TNF-α and IL-6, which act in concert with chemoattractants, such as CXCL1 and CXCL2, to recruit polymorphonuclear leukocytes (PMNs) to the lungs, killing pathogens but generating fibrosis .
Another important consideration during COVID-19 infection is related to the modification of the secretory products of the upper and lower airways, which usually include mucin and pulmonary surfactant. During infection, mucin production is upregulated, with the function of preventing microbes from binding to and infecting epithelial cells .
The primary source of phospholipids (PLs) in the lung is pulmonary surfactant, synthesized and released by alveolar epithelial type II cells. The surfactant contains approximately 80–90% PLs, with fatty acid chains that can be oxidized during different challenges in the lung . The oxidation of these PLs in the lung can occur in the setting of an increased oxidative stress situation, such as infection and inflammation . The immune effects of oxidized phospholipids oxPLs during infectious diseases are inevitably dictated by the balance among activation, degradation, and scavenging. It has been shown that oxPLs are generated in the lung during several pulmonary infections, including influenza and avian influenza (H5N1), as well as SARS coronavirus, even if the mechanisms of action are not well known [87,88,89].
As reported by Imai et al., oxPL-induced inflammation is mediated by TLR4 and TRIF, driving an increase in IL-6 production . It is intriguing to consider that oxPL-dependent defects in phagocytosis and ROS generation may lead to an increased susceptibility to respiratory infections . Cholesterol is the major neutral lipid in pulmonary surfactant, in which it is thought to promote the spreading, mobility, and adsorption of surfactant films .
As previously documented, modulating adiponectin levels can be considered an important way to reduce cytokines levels; in this way, the adverse effects related to the COVID-19 infection should be attenuated. It is well described in animal models that the consumption of hyperlipidemic diets, rich in saturated fat, reduces the levels of adiponectin, while diets rich in polyunsaturated fatty acids and supplemented with ω-3 PUFA increase adiponectin levels, reducing pro-inflammatory cytokines .Innate and adaptive immune responses are influenced not only by oxPLs and cholesterol but also by the fatty acid profiles of tissues in response to pharmacological agents and diet .
Several studies performed in animal models demonstrated how ω-3 PUFA uptake into the lung tissue influences outcomes associated with infection, promoting the resolution of inflammation . In another study, ω-3 PUFAs reduced the levels of PMNs and lowered IL-6 levels in lung infections . These positive effects remain controversial; for example, Jones and Roper reported that in their experimental model, no statistically significant differences were found among the diet regimens, with and without ω-3 PUFAs, with respect to the susceptibility of mice to viral infection, morbidity, viral organ titers, recovery time, or mortality .
In conclusion, it is well known that general treatments are very important to enhance the host immune response against RNA viral infection. In addition, the immune response has often been shown to be weakened by inadequate nutrition in many model systems as well as in human studies. However, the nutritional status of the host, until recently, has not been considered as a contributing factor to the emergence of viral infectious diseases. The recent reports about the pathogenesis of COVID-19 suggested that one of the most important consequences of this infection is the cytokine storm syndrome , which could be strictly linked with coagulopathy, generating acute pulmonary embolism caused by in-situ thrombosis [96,97]. Therefore, a great number of clinical trials are ongoing to define a useful therapy to attenuate cytokine storms .For these reasons, an adequate ω-3 PUFA intake may be a valid strategy against viral infection.
Indeed, following the recommended intake of ω-3 PUFA, in the range of 0.5% and 2% of total calories (250 mg/day), may be important to protect against an excessive inflammatory response, also reducing IL-6 levels. This theory found important support in a recent study that demonstrated that ω-3 PUFA-derived lipid mediator protectins can suppress influenza virus replication through a mechanism that blocks the export of viral mRNA. Moreover, Imai demonstrated that this mediator can be used in combination with the antiviral peramivir, even at late time points in infection .
Nevertheless, the efficacy of ω-3 PUFAs at the clinical level is under investigation; for example, Hecker et al. described a beneficial effect for a diet regimen with ω-3 PUFAs, describing that the pro-inflammatory cytokine levels decreased after this diet regimen . The suggested positive role in the outcome and prevention of the COVID-19 infection is summarized in Figure 2.
In addition, adiponectin plays a role in lung diseases and obesity; in the development and progression of lung disease and cancer, a pathogenic role of adiponectin was defined by both in vivo and in vitro studies.
Recently, immunometabolic pathomechanisms have been identified as important factors determining and modulating lung function and disease. Particularly, adiponectin levels have been found to be greater in patients with COPD compared with in control patients, and adiponectin-deficient mice are protected from several lung diseases .
Moreover, it has been reported that adherence to the Mediterranean diet was associated with an increase in adiponectin levels, improving cardiovascular system functionality , particularly in elderly people . These findings are only apparently contradictory to the first data about the mortality rate from COVID-19 infections in the Mediterranean area (such as in Italy and Spain) .
First of all, the data have been referred only to the tested population; moreover, it is well described that the presence of several comorbidities such as hypertension, diabetes, and cardiovascular diseases severely influenced the mortality rate reported in this area .
All these comorbidities can be counteracted with a correct dietary regimen. Therefore, both adiponectin and ω-3 PUFAs appear to be attractive biomarkers for monitoring lung disease progression.
Finally, considering that the COVID-19 infection can generate a mild or highly acute respiratory syndrome with a consequent release of pro-inflammatory cytokines, including IL-6 and TNF-α, a modification of the dietary regimen in order to improve the levels of adiponectin could be very useful both to prevent the infection and to take care of the patients, improving their outcomes.
Given the similar pathway of action, it can be hypothesized that adiponectin and ω-3-PUFA could be used as real drugs to reduce inflammation, reducing both IL-6 and TNF-α levels as well as ameliorating the lung damage that occurs following coronavirus infection.
Buried in their user manuals, cell phone companies specifically instruct us that phones should not be held close to the body. Without following those instructions, we risk being exposed to levels of radiation that are deemed unsafe. At the same time, significant research is showing cell phone radiation can damage the nervous., reproductive, and immune systems. Many scientists recommend reduced exposure, especially for children who are more vulnerable.
The problem is, today’s cell phones are still new, and we won’t know the full impact for years. That means that now, we’re all part of an experiment – we have a group of heavy users taking risks and a control group taking precautions. To know which group to join, we need the facts up front.
This is a ramble, of the threads of thought which are on my mind. In time this may be edited and streamlined, but presently I feel it paints a picture that may help others. It is clear something deep is happening in the world, bigger than just COVID in my opinion. So it will start with a long article about using H2O2 and wander on from there.
Surviving the Coronavirus Disease, How Hydrogen Peroxide Works
By Paul Ebeling on April 9, 2020
Hydrogen Peroxide Has a Long History of Medical Use
Hydrogen peroxide (H2O2) consists of a water molecule (H2O) with an extra oxygen atom.
The oxygen inactivates viral pathogens by breaking down the viral structure
Additionally, our immune cells produce hydrogen peroxide. This is in part how your immune system kills infected cells. Hydrogen peroxide therapy aids aids immune cells to perform their natural function more effectively.
H202 is on the shelf at the local grocery or drug store for $1.00 a bottle.
The Big Q: Can an inexpensive and easy to administer at-home treatment treat the novel coronavirus, SARS-CoV-2?
The Big A: Dr. Thomas Levy says Yes. The remedy is hydrogen peroxide H202, aerosolized in any standard nebulizer.
It’s worth keeping in mind that while the elderly and those with underlying medical conditions are at increased risk of serious complications and death, the overall mortality rate of COVID-19 is quite low, and very similar to the flu.
A compilation of reported mortality statistics from around the world can be found in the paper,“Likelihood of Survival of Coronavirus Disease 2019,” published in The Lancet Infectious Diseases, 30 March 2020.
For the latest up to the min COVID-19 resources click here.
To perform this treatment, you need but two items: a nebulizer with a face mask that covers your mouth and nose that emits a fine mist, and common household 3% hydrogen peroxide, available at most grocery stores and pharmacies for less than $1.
However, you may choose to purchase the more expensive food grade hydrogen peroxide as it doesn’t have any stabilizers in it. Stabilizers are proprietary and companies do not need to disclose them on the label, but some can be problematic.
Typically food grade peroxide comes in concentrations higher than 3% so if you chose it your will need to dilute it down to 3% to use it.
Viruses are not “alive” they need a live host in which they can infect live cells that then replicate the viral DNA and RNA. Once a cell is infected, newly replicated viruses exit the cell and move on to the next cell to duplicate the process.
So, when they talk about “killing” a virus, they are talking about inactivating them by breaking down their structure. This is why soap works so well. Coronaviruses are held together by a lipid (fatty) coating. Soap, being amphipathic, meaning it can dissolve most molecules dissolves this fat membrane, causing the virus to fall apart and become harmless.
More specifically, the fat-like substances in soap are structurally similar to the lipids found in the virus membrane, so the soap molecules compete with and replace the fats in the membrane. In so doing, the “fatty glue” holding the virus together dissolves.
Hydrogen peroxide works in a similar way. As noted by Dr. Levy, “the way to control any viral infection is not to kill the virus; rather, the infected cells that have been turned into viral factories must be killed.”
Our immune cells actually produce hydrogen peroxide. This is in part how the immune system kills cells that have been infected with a virus. By killing the infected cell, viral reproduction is stopped. So, hydrogen peroxide therapy is in essence only aiding our immune cells to perform their natural function more effectively.
Hydrogen peroxide is also a Key redox signaling agent.
“At the low physiological levels in the nanomolar range, H2O2 is the major agent signaling through specific protein targets, which engage in metabolic regulation and stress responses to support cellular adaptation to a changing environment and stress …
Recent methodological advances permit the assessment of molecular interactions of specific ROS [reactive oxygen species] molecules with specific targets in redox signaling pathways.
Accordingly, major advances have occurred in understanding the role of these oxidants in physiology and disease, including the nervous, cardiovascular and immune systems, skeletal muscle and metabolic regulation as well as ageing and cancer.
In the past, unspecific elimination of ROS by use of low molecular mass antioxidant compounds was not successful in counteracting disease initiation and progression in clinical trials. However, controlling specific ROS-mediated signaling pathways by selective targeting offers a perspective for a future of more refined redox medicine.”
In short, hydrogen peroxide is a major ROS, but while ROS are typically thought of as “all bad,” this is a gross oversimplification.
As noted: “Steady-state physiological flux of H2O2 to specific protein targets leads to reversible oxidation, thereby altering protein activity, localization and interactions, which contributes to orchestration of various processes in cells and organs, including cell proliferation, differentiation, migration and angiogenesis. This state of low-level H2O2 maintenance and its associated physiological redox signaling is called ‘oxidative eustress.’”
Contrary to oxidative stress or oxidative distress, oxidative eustress denotes an oxidative challenge that has positive or beneficial effects and is essential in redox signaling.
The Studies: What they tells us
The most relevant study is 1 that was done earlier this year in the Journal of Hospital Infection. They studies 0.5% hydrogen peroxide, 6X weaker than the 3% typically used, and found that it killed human coronaviruses and SARS corona viruses and MERS.
Another study, published in the American Journal of Infection Control in Y 2009, assessed the efficacy of vaporized hydrogen peroxide against viruses on various surfaces, finding exposure to hydrogen peroxide vapor at a concentration of 10 parts per million resulted in 99% inactivation after 2.5 mins.
And a Y 2014 study in the Journal of Hospital Infection found hydrogen peroxide vapor eliminated an array of viruses on stainless steel, including human adenovirus 1, transmissible gastroenteritis coronavirus of pigs (TGEV, a SARS-CoV surrogate), avian influenza virus and swine influenza virus.
According to the authors, “Hydrogen peroxide vapor was virucidal against feline calicivirus, adenovirus, TGEV and avian influenza virus at the lowest vaporized volume tested (25 mL).” Vaporized hydrogen peroxide was found to completely inactivate a range of exotic animal viruses in a Y 1997 study as well.
Hydrogen peroxide’s ability to inactivate dangerous infectious viruses has also been highlighted in vaccine science. As noted in a Y 2016 study in the Vaccine journal, 3% hydrogen peroxide completely and irreversibly inactivated the rabies virus within 2 hrs, thus reducing time and cost of the inactivation process required for the making of a rabies vaccine, which contains inactivated rabies virus.
The most convenient to receive H202 is to inhale its mist, using a nebulizer a small, handheld device that converts liquid into a very fine mist.
The microscopic mist, similar to smoke or vapor, can be comfortably inhaled deep into the nostrils, sinuses and lungs. While nebulizers have routinely been used by asthmatics to deliver medication into their lungs, this delivery system affects not only the lungs but your entire body.
As noted in the Y 2002 review article, “Pulmonary Drug Delivery Systems: Recent Developments and Prospects,” “Targeting drug delivery into the lungs has become one of the most important aspects of systemic … drug delivery systems.“
In the case of respiratory infections, the nebulizer has the added advantage of delivering the hydrogen peroxide right to the areas most affected by respiratory viruses: the sinuses, throat, bronchial tract and lungs.
Dr. Levy writes: “Effective hydrogen peroxide nebulization quite literally, ‘chops the head off of the snake,’ and the virus present elsewhere in the body can then readily be mopped up when the new virus influx has been terminated,”
It should be kept in mind that hydrogen peroxide kills pathogens very readily upon contact in an open wound. It should, therefore, be understandable why putting a fine mist of hydrogen peroxide in all the areas of maximal viral replication promptly puts the body on a pathway to rapid healing.”
Hydrogen Peroxide Protocol
To prevent an infection from taking hold, begin treatment at 1st signs of symptoms. Commercially available 3% hydrogen peroxide is fine for this purpose, and can be used without dilution.
If the undiluted solution stings or burns your nose, you can dilute it up to 50% with pure water. Even lower concentrations can be used, although the antiviral effects will be reduced at lower concentrations.
If already presenting with runny nose or sore throat, Dr. Levy recommends using the nebulizer for 10 to 15 mins 4X a day until the symptoms are relieved. You can also nebulized hydrogen peroxide for prevention and maintenance, which may be advisable during flu season, or while the COVID-19 pandemic is in full swing.
He notes: “As it is a completely non-toxic therapy, nebulization can be administered as often as desired. If done on a daily basis at least once, a very positive impact on bowel and gut function will often be realized as killing the chronic pathogen colonization present in most noses and throats stops the 24/7 swallowing of these pathogens and their associated toxins.
If daily prevention is not a practical option, the effectiveness of this treatment is optimized when somebody sneezes in your face or you finally get off of the plane after a trans-Atlantic flight. Do not wait for initial symptoms. Just nebulize at your 1st opportunity.”
Eat healthy, Be healthy, Live lively
ChooseLife : In Mid February I ordered and started using a Nebulizer with 1.5% H2O2 – http://chooselife.co.uk/index.php/2020/02/28/bill-munro-vs-the-coronavirus/
The Dr is bullish in his convictions, however there are associated risks to taking H2O2, perhaps mild or moderate, but they should be discussed, to best inform the reader.
Oxidative Stress may lead to the following :
Oxygen is crucial to life; however, when we use oxygen our bodies constantly produce free radicals. Free radicals are chemically unstable molecules or atoms. They also make other molecules or atoms in the body very unstable, thus damaging proteins, cell membranes, and even DNA structure. This is a process which can lead to permanent damage to cells and tissues resulting in infection, mental decline, depressed immunity system, joint disease, and heart disease. Free radicals are also considered to play an important role in the aging process.
Catalase is constantly in battle against the effect of free radicals to the body. It transforms harmful superoxide radicals into hydrogen peroxide which later breaks down into water and oxygen.
The enzyme Catalase is a key buffer for these dangers, Grey hair may be an indication of inhibited (or low) Catalase production, here are Vegetarian/Vegan food sources:
Vegetarian Sources of Catalase
Written by Don Amerman
Catalase — found throughout nature in the cells of organisms that grow in the presence of oxygen — is an enzyme with potent antioxidant properties. The enzyme facilitates the breakdown of hydrogen peroxide into its harmless components — water and oxygen. Without catalase, the hydrogen peroxide that your body produces during the metabolic process would build up to toxic levels. Catalase occurs naturally in a wide array of plant-based foods, ensuring its availability to vegetarians and vegans.
Age-Related Decline in Catalase
The cells in your body can produce catalase as well as other antioxidant enzymes, such as glutathione peroxidase and superoxide dismutase, or SOD. These enzymes help to neutralize free radicals, according to the authors of “Biology: A Human Emphasis.” Free radicals are atoms or molecules with unpaired electrons that are the byproduct of human biological reactions such as metabolism. Scientists cite free radicals as causative factors in disease and aging-related cell damage. As you age, your body gradually produces less catalase, which results in a buildup of free radicals and an increase in the damage they can cause. To help supplement your body’s declining output of catalase, consume foods that are rich in this vital enzyme.
Garlic, Onions and Their Kin
Nutritionists give members of the allium plant family, which encompasses garlic, leeks, onions and shallots, high praise for their antioxidant properties. Among the cellular antioxidants naturally occurring in allium vegetables is catalase. In a study related to the catalase in allium family members, a team of Hungarian and Romanian researchers evaluated the effects of water stress on the level and activity of catalase and other antioxidant enzymes in these plants. They found that allium plants subjected to water deprivation had increased catalase levels and activity, according to an article published in a 2007 issue of “Plant, Soil and Environment.”
Cruciferous vegetables, including broccoli, cabbage, kale and collard and turnip greens, are rich in catalase. Eating plenty of these green leafy vegetables also stimulates your body’s production of catalase. Researchers at Alabama A&M University conducted an animal study to determine what, if any, anticancer effects could be observed in laboratory rats that were fed a diet of these vegetables. As part of this study, they measured the level of catalase in test animals and found that those fed cruciferous vegetables had sharply higher amounts of catalase in their livers than those animals that were not fed these vegetables. Results of this study were published in a 2012 issue of “International Journal of Cancer Research.”
Wheat sprouts contain high levels of catalase, according to a study by molecular biology researchers at Italy’s University of Perugia. In an article published in the July 2004 issue of the “Journal of Clinical Gastroenterology,” they note that the antioxidant activity of catalase and peroxidase in wheat sprouts is extremely strong. Other vegetarian sources of catalase include apricots, avocados, carrots, cherries, cucumbers, parsnips, potatoes, radishes, spinach and zucchini.
ChooseLife : Parallel to this, is the issues reported of bronchial constriction. This would lead to the thinking that Magnesium Sulphate may be a solid companion to H2O2.
Effect of magnesium sulfate on bronchoconstriction in the lung periphery.
Magnesium sulfate has been shown to be effective clinically as a bronchodilator, but its mechanism of action is unknown. We used a wedged bronchoscope technique to study the ability of MgSO4 at clinically relevant concentrations to attenuate hypocapnia-, acetylcholine- (ACh), and dry air-induced bronchoconstriction in the canine lung periphery. Control experiments demonstrated that consecutive challenges of either hypocapnia or ACh resulted in greater collateral system resistance (Rcs) after the second challenge compared with the first. Intravenous infusion of MgSO4 diminished the maximum response to a second hypocapnic challenge (Rcs = 1.59 +/- 0.29 cmH2O.ml-1.s prechallenge vs. 1.12 +/- 0.20 postchallenge) but had no effect on either ACh- or dry air-induced bronchoconstriction. Serum magnesium levels before MgSO4 administration were 1.59 +/- 0.04 meq/l and rose to 6.20 +/- 0.13 during the infusion. Previous studies demonstrated that nifedipine, like MgSO4 in this study, attenuates hypocapnia-induced bronchoconstriction in the canine lung periphery but has no effect on ACh- or dry air-induced bronchoconstriction. We conclude that these results are consistent with the idea that, like nifedipine, magnesium acts in the airway as a voltage-sensitive calcium channel blocker.
ChooseLife : Magnesium is also an Electron reducing agent, hence it may donate Electron potential to the free Oxygen released as Catalase supports the body to reduce H2O2 into H2O and 0xygen.
This links to this information, as I see this Disease as an Electron Crisis :
[QUOTE][…] reduced compounds such as glucose and fatty acids are oxidized, thereby releasing energy. This energy is transferred to NAD++ by reduction to NADH, as part of beta oxidation, glycolysis, and the citric acid cycle. In eukaryotes the electrons carried by the NADH that is produced in the cytoplasm are transferred into the mitochondrion (to reduce mitochondrial NAD++) by mitochondrial shuttles, such as the malate-aspartate shuttle. The mitochondrial NADH is then oxidized in turn by the electron transport chain, which pumps protons across a membrane and generates ATP through oxidative phosphorylation.[/QUOTE]
From Wikipedia article FADH2:
[QUOTE]FAD can exist in four different redox states, which are the flavin-N(5)-oxide, quinone, semiquinone, and hydroquinone. FAD is converted between these states by accepting or donating electrons. FAD, in its fully oxidized form, or quinone form, accepts two electrons and two protons to become FADH22 (hydroquinone form). The semiquinone (FADH) can be formed by either reduction of FAD or oxidation of FADH22 by accepting or donating one electron and one proton, respectively.[/QUOTE]
“Chloroquine was shown to inhibit quinone reductase 2 , a structural neighbour of UDP-N-acetylglucosamine 2-epimerases that are involved in the biosynthesis of sialic acids. The sialic acids are acidic monosaccharides found at the extremity of sugar chains present on cell”
ChooseLife : This links together the researchers and testing of hydroxychloroquine. Is this not an Electron cascade crisis? Or a pH crisis which manifests into/from Electron deficiency? Whether this is from a Virus, or 5G, the results are the same, the treatments are the same in need… Though the overlap in effects from the Virus and the reported dangers of 5G are startling, to say the least. It is no wonder getting sunlight, or Vitamin D (Protons) is postulated often as a key player in this illness crisis.
This would make sense that Zinc with chloroquine is showing great promise in tests, as Zinc again is an Electron donor, like Magnesium…
Here it is worth also noting that Johanna Budwig contributed huge research and understanding of Electron dynamics, and stated very vigorously that it is Flax Seeds which have the highest level of Electron surplus, she found in her research that taking high levels of Flaxseed Oil, mixed with Quark (1 part Flaxseed Oil, 2 parts Quark, making it water soluble) was the most efficient mechanism possible to re-invogorate the human ‘Electron Cloud’
Interestingly, in her booklet:
Dr Budwig relayed:
I often take very sick cancer patients away from hospital where they are said to have only a few days left to live, or perhaps only a few hours. This is mostly accompanied by very good results. The very first thing which these patients and their families tell me is that, in the hospital, it was said that they could no longer urinate or produce bowel movements. They suffered from dry coughing without being able to bring up any mucous.
Every- thing was blocked. It greatly encourages them when suddenly, in all these symptoms, the surface-active fats with their wealth of electrons, start reactivating the vital functions and the patient immediately begins to feel better. It is very interesting to ask how this sudden change is possible. It has to do with the reaction patterns, with the character of electrons. I will return to these electrons later. In the last two years I have come to be very fond of them. A friend of my work in Paris wrote to me how wonderful it is that you have discovered the original birthplace of the electrons in seed oils to be the sun. That’s how these connections are made!
ChooseLife : As soon as I heard about COVID, and the chief symptom of dry cough, I though about the Budwig book and that paragraph above shouted at me. Flax (ALA) I knew was a key supportive element, yet at that stage I did not see the larger context.
Further to this, a new to air youtuber – Ava Green, has become viral, after relating her experiences with Diamox and the alignment of it’s usage and the COVID symptoms : Almost High Altitude Sickness
Pulmonary Edema, Diamox (acetylzolamide) increases Urine pH, relieving this issue:
However, Pulmonary Edema is usually characterised as symptomatic of ‘Productive Cough’ or ‘Wet Cough’ not ‘Dry Cough’. Countless reports I have seen suggest quite the opposite, that the pneumonia/illness type is a very sticky mucus laiden lungs when scanned, hence a dry cough.
So, this drug may hold potential, chiefly via the increasing of urine pH, but has a multitude of nasty potential side effects, a diet with 75% fruit and vegetables is shown to raise Urine pH similarly in 3days, without the nasty side effects, in fact the other effects of this shift in diet, if green foods based, are multitude in potential positives. Mental health may be supported with the richer Magnesium this form of eating may bring (Mental Health Reviews – Magnesium).
This form of eating 75% Fruit and Vegetables, with a strong Alkaline influence (lots of leafy greens especially), if coupled with high Flax intake via a Budwig mix, is shown scientifically to elevate Metabolic and Respiratory status away from Acid and towards neutral (the author does not believe an Alkaline state is any more healthful than acidic, it is the balance which gives the reactive force, and allows the body to extract the electromagnetic energies in foods which in turn release their stored nutrients).
Altitude sickness style illness is what this Dr from New York claims he is seeing:
This Doctor, who is leading a COVID ICU, does it not sound like the symptoms you may expect to see if the 5G side effects are correct, Oxygen oscillation acceleration making uptake into the bloodstream troublesome, as the spin of Electrons become too fast to bind with Hemoglobin? It certainly seems that way to me. New York is a 5G pilot city, London, Wuhan. The Doctor says the effects are like how he envisages one would encounter if someone without acclimitisation were dropped at the top of Mount Everest…
This reflection, or speculation, of Altitude Sickness, reminded me of when I saw a documentary of Westerners climbing Mount Everest, in the Documentary I was struck that a much older Gurkha was carrying the Westerners very considerable Luggage, yet was able to smoke ceaselessly! This aligns to the statistics that are showing that a disproportionately low number of Smokers are being admitted to Hospital with COVID, are the smokers already attuned to Hypoxia like conditions and their biochemistry has been attuned coping mechanisms, like the Gurkha in Nepal? Of course he was acclimitised, but it was still staggering his body could cope in those conditions, when the younger, very fit, climber was struggling in the lower oxygen environment.
80% of those needing Ventillation in New York are dying, what if this is because 5G is in almost all the Hospitals in New York? Making the Oxygen Electrons spin too fast, forcefully adding more oxygen may only increase this damage, in those with Electron buffering insufficiency needed to take this sped up Oxygen into Hemoglobin? This paper supports this idea:
COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the
Porphyrin to Inhibit Human Heme Metabolism
The novel coronavirus pneumonia (COVID-19) is an infectious acute respiratory infection caused by the novel coronavirus. The virus is a positive-strand RNA virus with high homology to bat coronavirus.
In this study, conserved domain analysis, homology modeling, and molecular docking were used to compare the biological roles of certain proteins of the novel coronavirus. The results showed the ORF8 and surface glycoprotein could bind to the porphyrin, respectively. At the same time, orf1ab, ORF10, and ORF3a proteins could coordinate attack the heme on the 1-beta chain of hemoglobin to dissociate the iron to form the porphyrin.
The attack will cause less and less hemoglobin that can carry oxygen and carbon dioxide. The lung cells have extremely intense poisoning and inflammatory due to the inability to exchange carbon dioxide and oxygen frequently, which eventually results in ground-glass-like lung images.
The mechanism also interfered with the normal heme anabolic pathway of the human body, is expected to result in human disease. According to the validation analysis of these finds, chloroquine could prevent orf1ab, ORF3a, and ORF10 to attack the heme to form the porphyrin, and inhibit the binding of ORF8 and surface glycoproteins to porphyrins to a certain extent, effectively relieve the symptoms of respiratory distress. Favipiravir could inhibit the envelope protein and ORF7a protein bind to porphyrin, prevent the virus from entering host cells, and catching free porphyrins. Because the novel coronavirus is dependent on porphyrins, it may originate
from an ancient virus. Therefore, this research is of high value to contemporary biological experiments, disease prevention, and clinical treatment.
ChooseLife :This could be seen as supporting the 5G hypothesis, it does to me, ALARM BELLS ARE RINGING. Chloroquine is suggested again, and links the Electron issue, covered early in this ramble.
This leads me to this research paper:
Cellular Response to Cigarette Smoke and Oxidants
Adapting to Survive
The gaseous and soluble phases of cigarette smoke are sources of oxidants that contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD). Chronic oxidative stress of cigarette smoking induces mucus secretion and inhibits cystic fibrosis transmembrane conductance regulator function. The increased mucus viscosity renders the airways susceptible to bacterial infections, a hallmark of chronic bronchitis. Furthermore, lungs chronically exposed to the toxic mixture of oxidants in cigarette smoke show signs of endoplasmic reticulum stress, unfolded protein response, altered ceramide metabolism, and apoptosis. Fortunately, the respiratory tract has developed effective adaptive cellular mechanisms to limit oxidant damage. Numerous antioxidant enzymes and glutathione-dependent detoxification systems are increased in healthy smokers. The regulation of the antioxidant response is largely dependent on the nuclear factor erythroid 2–related factor-2 (Nrf2) pathway. However, patients with COPD have defective Nrf2 responses. Novel therapies such as 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) to correct defective Nrf2-dependent cellular response may hold promise for patients with COPD.
ChooseLife : So, we could see the above as suggesting that healthy smokers bodies may be acclimitised to this Hypoxia type state? Like the old Nepalese Smoker being better able to cope not only with thin air, but also smoke constantly in that environment, the similarities seem stark, however the dry unproductive cough symptom is a key differentiator to HAPE symptoms.
This research area, led me to the following research, when checking into Bronchial dilation (debating in my mind if Magnesium Sulphate is contraidicatd by the above video/Doctor):
CT Features of Coronavirus Disease 2019 (COVID-19) Pneumonia in 62 Patients in Wuhan, China
A decreased lymphocyte count and an increased high-sensitivity C-reactive protein level were the most common laboratory findings.
Read More: https://www.ajronline.org/doi/full/10.2214/AJR.20.22975
Omega3 is known to support lymphocyte production :
Effect of ω-3 polyunsaturated fatty acid-supplemented parenteral nutrition on inflammatory and immune function in postoperative patients with gastrointestinal malignancy
A meta-analysis of randomized control trials in China
In this study, lymphocyte count was significantly higher in ω-3 groups than the control groups. Omega-3 PUFAs improve the body’s defense system by the proliferation of lymphocytes, and the meta-analysis result also confirmed that the incidence of infectious complications in ω-3 groups was significantly lower than the control group.
This again says to me Metabolic Acidosis is encountered, the Lyposomes/Endosome Cargo carriers and waste removal system appears to become compromised, this is symptomtic of Cellular pH failure, as the lower pH terrain will always result in slower arrival of nutrient cargo as the Endosomes slow, and the waste removal systems slow affecting C-reactive protein as the paper above reports finding most often. Why would Sodium Bicarbonate, Magnesium Hydoxide and the like (high pH substances) not be a first line defence in these dynamics? I cannot understand why not, but a Doctor I am not!
Why does it affect Afro-Carribeans more? We’ve seen that COVID is seen to affect C-reactive protein in a very high number of cases, what if we overlay Omega 3 to this dynamic?
Relationship of Omega-3 Fatty Acids on C-Reactive Protein and Homocysteine in Haitian and African Americans with and without Type 2 Diabetes
Omega-3 fatty acids (n-3) may be protective of cardiovascular risk factors for vulnerable populations. The purpose of this study was to assess the association between n-3 with, C-reactive protein (CRP), and homocysteine (HCY) in Black minorities with and without type 2 diabetes.
African Americans had higher waist circumferences and C-reactive protein and consumed more calories as compared to Haitian Americans. Omega 3 fatty acid intake per calorie did not differ between these ethnicities, yet African Americans with low n-3 intake were three times more likely to have high C-reactive protein as compared to their counterparts [OR=3. 32 (1. 11, 9. 26) p=0.031].
Consumption of n-3 may be protective of cardiovascular risk factors such as C-reactive protein and homocysteine for certain ethnicities. Prospective studies are needed to confirm these results.
How about Magnesium, and C-Reactive Protein?
Dietary magnesium and C-reactive protein levels.
Most Americans consume magnesium at levels below the RDA. Individuals with intakes below the RDA are more likely to have elevated CRP, which may contribute to cardiovascular disease risk.
ChooseLife Notes : None of this should be construed as medical advice, or advice at all. this is just my reflections on Biological Ionisation as it relates to our current situation. The science supports that pH is very, very important, I dearly hope readers may understand this and seek to make informed choices. This period has seen a galvanising of my own diet, and my daughters, to ensure if we are infected/injured by the condition classified as COVID19 (et al) our bodies are the least likely to succumb to the worst effects some people suffer sadly.
I wish you all every wellness. May we come through this brighter and with more positive spirit than we had before, my love to you all.
Well Wishes, Rich Fosh
Coronavirus Data and thoughts which led me here = http://chooselife.co.uk/index.php/category/coronavirus/
Sixty percent of cases of clinical depression are considered to be treatment-resistant depression (TRD). Magnesium-deficiency causes N-methyl-d-aspartate (NMDA) coupled calcium channels to be biased towards opening, causing neuronal injury and neurological dysfunction, which may appear to humans as major depression.
Oral administration of magnesium to animals led to anti-depressant-like effects that were comparable to those of strong anti-depressant drugs. Cerebral spinal fluid (CSF) magnesium has been found low in treatment-resistant suicidal depression and in patients that have attempted suicide. Brain magnesium has been found low in TRD using phosphorous nuclear magnetic resonance spectroscopy, an accurate means for measuring brain magnesium.
Blood and CSF magnesium do not appear well correlated with major depression. Although the first report of magnesium treatment for agitated depression was published in 1921 showing success in 220 out of 250 cases, and there are modern case reports showing rapid terminating of TRD, only a few modern clinical trials were found.
A 2008 randomized clinical trial showed that magnesium was as effective as the tricyclic anti-depressant imipramine in treating depression in diabetics and without any of the side effects of imipramine.
Intravenous and oral magnesium in specific protocols have been reported to rapidly terminate TRD safely and without side effects.
Magnesium has been largely removed from processed foods, potentially harming the brain.
Calcium, glutamate and aspartate are common food additives that may worsen affective disorders.
We hypothesize that – when taken together – there is more than sufficient evidence to implicate inadequate dietary magnesium as the main cause of TRD, and that physicians should prescribe magnesium for TRD. Since inadequate brain magnesium appears to reduce serotonin levels, and since anti-depressants have been shown to have the action of raising brain magnesium, we further hypothesize that magnesium treatment will be found beneficial for nearly all depressives, not only TRD.
Source : https://www.ncbi.nlm.nih.gov/pubmed/19944540
Related (and updated to include this study) : Magnesium Mental Health Reviews