The goal of this piece is to attempt to remediate or diminish what is discussed in the substack below, in which most of the neuroinflammatory damage and further dysfunction are induced by neutrophils. Of course, the information here is applicate to many other conditions in which NETs are abundant or produced in a dysfunctional manner, some of said conditions cited here, many more not. NETs/NETosis also play a important role and impact cancer progression in different manners.
But first things first, a little introduction. Every living organism is regulated by highly complex molecular networks, cells talking to each other, and input-output, but above all else, we are all living energy bioreactors. Life can not exist without energy, so even the most complex of cellular effects and pathways are governed by bioenergetics, but how the body creates and uses energy. Within those biological “rules”, a certain type of cells, certain immune cells, each T Helper cell has a preferred metabolism, some use sugar, others prefer fat, and some really, really love sugar, these aspects will be important later. These are a massive overlap comparing what we are about to discuss and the supplements I advise most people to take to mitigate the damage from the viral infection, but especially from the mRNA vaccine.
I will attempt to simplify the content, but the scientific literature will be linked as usual. Source for the quotation and image below.
Neutrophil Extracellular Traps (NETs) were discovered in 2004, and studies of these networked structures consisting of DNA, histones, fiber, and other antimicrobial proteins show that they can kill bacteria, viruses, fungi, and protozoa [1]. Trap them and lead them to immobility and then remove these pathogens by releasing antimicrobial proteins. This event is known as a relatively new innate immune response to infections [2–5]. Evidence suggests that in addition to participating in the innate defense against pathogenic microorganisms, NET can contribute to the pathogenesis and induction of some diseases such as rheumatoid arthritis (RA), diabetes, cystic fibrosis (CF), systemic lupus erythematosus (SLE), psoriasis (PsO) and metastatic malignancies [6]. Traces of NET have also been observed in some pathological phenomena such as periodontitis, vasculitis, thrombosis, coagulation disorders, metastasis, and atherosclerosis [7–11].
Following excessive NET formation and release of auto-antigen, plasmacytoid dendritic cells (pDCs) can recognize the exposed autoantigens leading to interferon and auto-antibody production, which are accompanied by tissue damage [12]. Therefore, regarding the pathologic role of NET formation, it has been considered more by researchers as an attractive therapeutic target [13]. In this context, the use of NET inhibitors has been investigated in various studies [14–16]. NET can also be indirectly targeted and reserved by inhibition of protein arginine deiminase 4 (PAD4), Myeloperoxidase (MPO), and neutrophilic elastase [12]. Studies in animal models of inflammation as well as human respiratory disorders showed that inhibition of MPO and neutrophilic elastase significantly reduced neutrophil-mediated inflammation [17, 18].
The creation of “extracellular traps” by neutrophils is an immune response against many types of pathogens, these “traps” are essential to clear infections but the continuous or persistent presence of them is able to both progress inflammatory damage and the worst outcome, induce autoimmunity by the mechanism which some autoantigens are trapped and exposed in these traps, and some of your immune cells are able to “pick” them up and start an immune reaction.
The complexity of NETosis is demonstrated in the image above, a rather broad illustration of the process, but you should pay closer attention to the right side of the image and the green line, ways to inhibit or mitigate NETosis. The first one is one many will prefer above (almost) everything else.
Melastoma malabathricum L. Suppresses Neutrophil Extracellular Trap Formation Induced by Synthetic Analog of Viral Double-Stranded RNA Associated with SARS-CoV-2 Infection
To search for TCM with anti-NET activity, the plant Melastoma malabathricum L. which has anticoagulant activity was partially purified by fractionation. One of the fractions inhibited poly(I:C)-induced NET formation in a dose-dependent manner. This study implicates that SARS-CoV-2 structural proteins alone are not sufficient to promote NET and platelet activation. Instead, dsRNA formed during viral replication stimulates NET formation. This study also sheds new insight into using the active components of Melastoma malabathricum L. with anti-NET activity in the battle of thromboembolic diseases associated with SARS-CoV-2 infection.
Besides a flower with very potent effects and benefit, the following is somewhat even more astonishing, and somewhat more revolting. Under certain conditions, Vitamin D can prevent edothelial dysfunction by modulating the NETosis activity , fairly overrepresented among Spike Protein-induced damage (regardless of the source of the Spike), Vitamin D3 + Omega 3 can reduce the ability of neutrophils to generate NETs therefore mitigating the damage and avoiding long-term complications in a state of continuted high glucose (Type 2 Diabetes).
The formation of NETs and Neutrophil function is by itself highly glycolytic function, in simple words, it prefer and uses a lot more “sugar”, and it also generate energy by a very “potent” chemical reaction, generation tons of ROS what I sometimes refer to cellular rust, but it is much more, these are aking to cellular bombs throwed in with the “rust”. In fact, there is a substantial presence and dysfunction of NETs in diabetic patients, so once again we refer back to the only pharmaceutical drug I suggest.
Metformin. It can inhibit NETs and the promotion of pancreatic cancer in obese people, Metformin can affect the excess release of NETs regardless of glucose control, directly interfering with the metabolic process of the neutrophils.
ROS by itself can induce the formation of NETs (there are ROS depedent, and independent NETosis), so common sense dictates that NAC would have some effect on this process, by directly acting on the redox (detox) pathways, particularly present in NETosis and in SARS-CoV-2 infections, the more severe the infection the further need for redox a patient has, NAC can help mitigate both damage and presence of NETs directly, and indirectly it can modulate half a dozen pathways in whic NETosis will create and driver further damage and immune dysregulation.
Do you care to guess another drug that can inhibit NETs ? One that was vehemently vilified. Hydroxychloroquine can directly inhibit the formation of NETs, via multiple pathways, HCQ also directly acts upon Th17 cells and stop the inflammatory damage caused by the state when dysregulated. A state that I have been written and argued extensively as being the major contributor for a lot of the damage seen and chronicled all around, the same for Vitamin D, Metformin, NAC, they all may directly or indirectly act upon the aforementioned immune state.
Melatonin can aid the recovery of proper neutrophil function by directly positively afffecting glutathione pathway, especially under glutathione deficient states, which arguably are most of the states in which NETosis is abundant.
Under sepctic conditions, Vitamin C is a powerful regulator of NETosis. A more recent paper found different mechanisms by which intravenous Vitamin C impacts NETosis. The two best, for last. One of the best ways to deal with NETs would be free, easily avaible and possessing huge long-term benefits if you decide to “use it”.
Physical Exercise Promotes DNase Activity Enhancing the Capacity to Degrade Neutrophil Extracellular Traps
Blood samples were drawn in two-month intervals to assess routine laboratory parameters, cell-free DNA (cfDNA), and DNase activity. (3) Results: Prevailing CV risk factors were overweight (65.9%), a positive family history (44.9%), hypertension (32.7%) and smoking (20.4%). Performance changed by 7.8 ± 9.1% after 8 months. Comparison of baseline to 8 months revealed a decrease in cfDNA and an increase in DNase activity. This effect was driven by participants who achieved a performance gain. (4) Conclusions: Regular physical activity might improve CV health by increasing DNase activity and thereby, the capacity to lower pro-inflammatory signalling, complementing measures of primary and secondary prevention.
Aerobic Exercise Attenuates Acute Lung Injury Through NET Inhibition
And as the last.
The Physiological Ketone Body Beta-Hydroxybutyrate Potently Neutralizes APS-Associated NETosis
Conclusion: We found, for the first time to our knowledge, that the physiological ketone body beta-hydroxybutyrate inhibits both NADPH oxidase-dependent and -independent NETosis, potentially targeting multiple NETosis pathways and thereby limiting escape mechanisms. Furthermore, APS IgG-induced NETosis was highly susceptible to the effects of beta-hydroxybutyrate, laying the foundation for examining ketosis as a possible treatment paradigm. Experiments, including mouse thrombosis models, are now underway to better understand the therapeutic potential suggested by these preclinical data.
I wrote a series of Substacks that were inspired by a big Twitter thread originally written back in May 2021, among my many suggestion the major one was, and still is to this day, both the adoption of a low carbohydrate diet, and in certain cases such as severe infections, Long-Covid, long-term inflammatory states and chronic diseases adding BHB, that being Part 3 of the series. The positive effects of both a low-carb/keto diet and adding BHB are enormous, from recovering proper T Cell function, lowering overall inflammation, control of chronic diseases, and ameliorating or halting degenerative diseases of all kinds.
A last point I should add is the supplementation of BHB and its signifcant positive effects in all manner of central nervous diseases, and neurodegenerative diseases.
You can find all the correlations between the ways to deal with NETosis and my previous substack here. As a PSA, since quite a few followers after a specific one asked me to republish or rewrite some of my pieces, I plan to write them again in a simpler way, as an overall suggestion and ways to deal or heal from a myriad of situations.
Thank you for anyone who chose to support this Substack however they saw fit, helps build the work !
Hi John, thanks again for all the Info ! One question: I am searching for a good brand for Serrapeptase. I found a brand that are calling it „Serratiopeptidase“...is this the same as Serrapeptase ? Thanks a lot !
Nice to see how this ties in with the LPS = Endotoxin NETosis caused by mRNA jabs.