Coronavirus Pandemic Update 69: "NAC" Supplementation and COVID-19 (N-Acetylcysteine)

welcome to another medcram

covid

-19

update

, we have over 4 million total confirmed worldwide, let's at least take a look at some of these countries and although the United States tops the list in terms of total cases if we look at deaths per 1 million inhabitants we are certainly not near the top of that list, Europe is still at the top of that list in terms of Spain, the number of new cases per day is decreasing and that holds true for the number of deaths new ones per day in Spain like Well, the number of daily cases in Russia has also increased here recently and in addition to the number of deaths, and when we look at a very large country like India, we also see that the number of cases is increasing.

It doesn't look like they've peaked yet and the daily death toll is also going along with that at the moment and we're all keeping our eyes on Australia. I know they're supposed to be heading into winter there. At this point but it's still pretty hot so we'll have to see how things go once the weather starts to cool down there in Australia and they haven't had any deaths there in Australia for some time now. We have not heard from South Korea. for some time and they have been doing a tremendous job at keeping the number of new cases here at bay.

Well, today we're going to go back to medical school a little bit and we're going to talk more about our oxidative stress because I think this is really important and we've been building on this for the last week in terms of the lectures, once again we have oxygen and when you take an oxygen molecule and add an electron to it, you get one superoxide and you add another one. Two oxygen molecules and two hydrogen molecules are added to the electron, another electron molecule is obtained, a hydroxyl is obtained and finally water is obtained, so the most reduced form here is H2O or water and the most reduced form Oxidized here is also O2.

Note that when you add electrons, the protons also become active and that is why you start to see the ratio of protons to oxygen molecules increase as you go from left to right. The body's defense mechanisms are again superoxide dismutase, which converts the superoxide form here into hydrogen. peroxide and oxygen, there is also catalase that converts hydrogen peroxide into oxygen and water and finally what we are going to talk about a little more is glutathione peroxidase and I want you to realize here that glutathione peroxidase takes glutathione, which is se reduces and reduces the hydrogen peroxide and turns it into water while it itself is oxidized in this disulfide bond, that's what it's called, so the sulfide bonded to hydrogen is the reduced form and the sulfide bonded to another sulfide is the oxidized form that en in turn regenerates itself by taking the reduced form of nadp plus, which is nadph, and converting it to nadp plus through this enzyme called glutathione reductase, so there are other ways to reduce glutathione from its disulfide bond form to its sulfhydrolic group and again the reason this is important is because we have shown how superoxide can accumulate in oxidative stress environments such as diabetes, hypertension, coronary heart disease and that when you have

covid

-19 it creates a perfect storm of superoxide , why once again is it because covid-19 hits the ace? enzyme that is its receptor and therefore there is an accumulation of Angiotensin II that stimulates the production of superoxide there is also a deficiency of angiotensin-17 that inhibits the production of superoxide through a nitric oxide mediator in addition to this the covid itself- 19 attracts pmns which are neutrophils which can also cause the production of superoxide and that superoxide that's here will cause the production of hydrogen peroxide and a bunch of other hydroxy radicals which can cause oxidation and destruction of the endothelial cells and possibly even thrombosis as well that this is glutathione and, for example, those of you who are biochemically inclined will see the backbone here of an n c c n c c amino acid chain and you will notice that this here is the amino acid cysteine ​​and that's where an acetyl cysteine ​​would come from, but you can also be regenerated glutathione. for an acetyl cysteine ​​which we'll talk about in a moment, the key point I want you to see, however, is this fish.

This is really important because this fish can also bind with another form of this molecule and instead of having an S attached. to one H it can be attached to another s which would be the oxidized form here this is in the reduced form there is a hydrogen attached to this sulfur group this sulfur group can be attached to another sulfur group and that would be the oxidized form then, what does that do? With good intentions, what this means is that if you have two glutathione with this sh group and you oxidize them with hydrogen peroxide, you will join two of these glutathione into a bond that will connect them and you will release water, so look at two. reducing glutathione plus hydrogen peroxide gives you an oxidized glutathione plus water and that should sound familiar again here we have two glutathione oxidizing to a disulfide bond connected and what you get is hydrogen peroxide turning into water that's important to understand because here you have a g s h y What you are doing is connecting two independent molecules and I am going to plant a little seed in your head with this article that says that the reduction of the disulfide bond of the Von Willebrand factor by Ada MTS 13.

That is The Von Willebrand factor is actually joins and polymerizes with the help in part of disulfide bonds. By the way, this is the same thing that happens with hair, so here there are simply strands of keratin, which is the spiral structure, and a single strand of hair is basically multiple keratin. fibers and what happened is their S groups that bind them together and then what happens when you get a perm is basically a reducing agent and you break all these disulfide bonds and you put H's on them and then you bend the hair so it's like this and then you bend it What happens is that you neutralize the perming agent by putting hydrogen peroxide in the perming agents and what happens is that new disulfide bonds will form keeping the hair with its curl Better Living Through Chemistry, so if we do in fact get covid- 19 excess superoxide and hydroxy radicals and that excess superoxide can actually be taken care of through things like glutathione peroxidase.

Are there things we can do to help glutathione peroxidase be in reduced form to take care of this so we can alleviate the problem? stress caused by this oxidative stress and the answer is potentially yes enter

acetylcysteine

​​also known as Knack or NAC as you can see

acetylcysteine

​​is both an antioxidant and a disulfide breaking agent and this is why it can see very clearly the fact that Knack has sulfur bonded to hydrogen, which means it is a reducing agent and looks a lot like cysteine, its amino acid, except it has an acetyl group bonded to the nitrogen, which is why it is known as n acetyl cysteine ​​and as you can see here very clearly, Knack will do that. break these disulfide bonds and put reduced state hydrogens on them so that these strands are no longer connected, so these highly cross-linked, elastic mucus gels break down and you get reduced viscosity and that's exactly how Knack used to be used.

It used to be inhaled by people who wanted to cough up thick sputum. It was a mucolytic. The other thing Knack would do is take the Tylenol metabolite. If Tylenol overdose was a concern, this Tylenol metabolite would be here and overuse and consume all of your glutathione. What an acetyl would do is it would remove the acetyl group and you would be left with cysteine, and the cysteine ​​would recharge the glutathione and allow it to metabolize the toxic agent and prevent cell damage. and the immune response that is well known in Tylenol overdose due to liver toxicity, as can be seen here, Knack acts by replenishing hepatic glutathione, which is the main endogenous nucleophilic peptide capable of neutralizing the main metabolite of acetaminophen, which is Tylenol , now known in Europe. as paracetamol and is metabolized forming the electrophilic metabolite and apqi which is detoxified by glutathione in the case of glutathione depletion mapqi reacts with the proteins here forming adducts that can induce cellular damage or immune response and this is how liver failure and death occur , so you can see.

That Knack is a very important molecule, not only is it favorable in saving people from a Tylenol overdose, but it can also act as a mucolytic, as you can see here, but that's not all that Knack is useful, article continues talking about what glutathione is like. It is used in many different reactions in the cell and can be used up, especially in some regular types of infections like colds and tonsillitis, etc. Here it says that they conducted a review of the literature from 1980 to 2016 on the role of oxidative stress and glutathione in ear, nose and throat conditions, the authors concluded that many otorhinolaryngological conditions, such as rhinitis, allergic rhinitis, rhinosinusitis, chronic with polyps, otitis media with effusion, chronic otitis media, chronic otitis media and cholecystoma, sclerosis of the tympanic membrane, tonsillitis, Meniere's disease, laryngeal conditions and chronic cough, are associated with you .

I hypothesized that oxidative stress and glutathione depletion, both locally in affected tissues and systemic decline in glutathione levels, are also associated with common features of aging, as well as with a wide range of pathological conditions, so it seems safe to say here that glutathione could be recharged with an acetyl. cysteine, well, let's see if it really works in diseases. Here is a study that was published in 1997 and analyzed a total of 262 subjects of both sexes. This was a double-blind randomized trial that looked at over 20 different centers in Italy and they were randomly assigned to either Mire Placebo or NAC 600 milligram tablet twice a day for six months and when they looked at how many people got the H1N1 flu there was no difference In both groups they got the same amount of flu, but when they looked at which ones actually had symptomatic forms of the flu, the placebo group, 79 percent of them got symptomatic forms of the flu, while only 25 percent of the who were treated with Knack, wow, that's an absolute risk reduction of 0.5, meaning you would only need to treat two people to prevent one of them from getting flu symptoms, so they concluded that the Administration of n-acetyl cysteine ​​during winter appeared to provide significant attenuation of influenza and similar episodes, especially in high-risk elderly people, but did not prevent influenza now. infection but significantly reduced the incidence of clinically apparent diseases.

Here's another paper that was published in 2010 that shows that the same substance Knack actually inhibited viral replication and reduced these inflammatory cytokines, these pro-inflammatory molecules and the recommendation was that therefore antioxidants like Knack represent a possible option of additional treatment that could be considered in the event of an influenza A virus

pandemic

. Now here is a meta-analysis looking at the effects of n-acetylcysteine ​​treatment on acute respiratory distress syndrome of all types. This was a meta-analysis again in 2017. Now remember that the definition of ARD had changed and therefore the number of trials here may be a bit heterogeneous, but what they found was that there was a statistically significant difference in the duration of stay in the ICU although there was no difference in duration. 30-day mortality or short-term mortality and are left saying that the number of trials included in patients with additional small trials are necessary to provide sufficient evidence of the effectiveness of knack in ards, but as part of their criteria and as their basis say here that the scavenging of reactive oxygen species by antioxidants has been applied in clinical practice and that Knack is the most commonly used antioxidant.

Another key finding is that no serious adverse reactions were observed in the patients who were included. Here is another article about this one published in 2018 titled an acetyl cysteine ​​improves oxidative stress and inflammatory response in patients with community acquired pneumonia and what they did here was look for different levels of oxidative stress and what they found was that these levels oxidative stress were similar between the two. groups before treatment, but that plasma levels of MDA and tumor necrosis factor alpha decreased more in the NAT group than in the no-mac group, including total antioxidant capacity again here they said that no ability-related adverse effects were observed Of course, this is for the community. non-acquired pneumonia 19.

It may be that oxidative stress plays a more important role in kova 19 than in community-acquired pneumonia; in fact, it could play a big role because, as we have shown before, this oxidative stress can lead to von Willebrand Factor hypercoagulable state thrombosis, there may be another frontthat an acetyl is opening here with kova 19 in the sense that an acetyl cysteine ​​can not only affect the oxidative stress aspect of Cova 19 but also the hypercoagulable state that is established by excess von Willebrand factor here we have this article which was published in 2013 showing that n-acetylcysteine ​​can have an effect on coagulation factors in plasma samples from healthy subjects.

They concluded that they were able to demonstrate a significant decrease in the activity of coagulation factors. 2 7 9 and 10 with the addition of acetyl cysteine, this would mean that the patient's blood would be more liquid or less able to clot. This article was published in 2006 and discusses the effects of n-acetyl cysteine ​​on blood clotting and platelet function in patients. underwent open repair of an abdominal aortic aneurysm and what they concluded was that Knack has an anticoagulant and platelet-inhibiting property in patients undergoing major vascular surgery, this abnormal hemostatic activity should be considered when Knack is administered to patients at increased risk of bleeding and the articles keep appearing.

This one published two years ago said that they had previously shown that diabetes exacerbates induced strokes. brain injury and that this correlates with brain methogloxal to glutathione status again our friend glutathione brain injury was reversed by an acetyl cysteine ​​here we tested whether the prothrombolic phenotype observed in the systemic circulation and brain during diabetes was associated with an increase of protein glycation and if Knack was able to reverse this, so what they did was give Knack and this is what they showed, they said collectively, these results show that the blood and brain of diabetics become progressively more susceptible to platelet activation and thrombosis.

I would have to assume that this could be due to the The same process of oxidative stress in the neck administered after the establishment of diabetes may offer protection against stroke risk by altering both systemic and vascular thrombotic responses by enhancing the clearance of platelet gsh and gsh-dependent mg, as well as correcting the levels of antioxidants such as superoxide dismutase 1. and glutathione peroxidase, both are enzymes that are specifically analyzed here in our videos and now the best article so far, this one published just three years ago, remember what we said about oxidative stress in Covet 19. We thought oxidative stress was causing endothelial stress. damage and that that endothelial damage was causing the release of Von Willebrand factors that were cross-linking and allowing thrombosis and hypoxemia to occur perhaps in Covid-19.

Well, here is an article titled Potent thrombolytic effect of an acetyl cysteine ​​on arterial thrombi. Let me just say that Circulation is a very prestigious journal, it's certainly peer reviewed and what they're saying here is that the cross-linking of platelets during arterial thrombosis involves the multimers of von Willebrand factor, therefore the proteolysis which means the breakdown of the von Willebrand factor appears promising for disaggregating platelet-rich thrombi. and restore vessel patency in acute thrombotic disorders such as ischemic stroke, acute coronary syndrome or acute limb ischemia. Knack or an acetyl cysteine ​​can reduce intracane disulfide bonds. Remember what we said, that an acetyl cysteine ​​can actually cleave these SS bonds well. a place where it could help in terms of breaking these clots into large polymeric proteins.

In the present study we postulated that Knack could cleave Von Willebrand factor multimers within occlusive thrombi, leading to their dissolution and arterial recanalization, which means opening them. The arteries once again, so what exactly did they find? Knack administration promotes the lysis of arterial thrombi. These are the same type of thrombi that could be acting in covid-19 in the pulmonary vasculature and in other places they also discovered that the thrombolytic effects. The ability is mainly found in the Von Willebrand factor and that if administered with a gp2b3a inhibitor such as integralin, which is another medication, it actually improves its thrombolytic effect even more that this is not accompanied by a significant worsening of the results of the hemorrhagic stroke, suggesting that it exerts a thrombolytic effect without significantly affecting normal hemostasis, we provide evidence that Knack is an effective and safe alternative to currently available antithrombotic agents to restore vessel patency.

It's fascinating and hair is another paper that was actually just published earlier this year again that shows the same thing that inhibits acetyl cysteine. thrombosis in a mirror model of myeloproliferative neoplasia here is another paper published in 2011 showing that Knack reduces the size and activity of von Willebrand factor, you guessed it, in human plasma and in mice and here you can see in the journal of clinical research these long Von Willebrand factor multimers and you can see in the control the number of strings versus Knack, so it basically cuts these things off, so you may wonder how come no one has talked about acetyl cysteine ​​before.

Well, here's a review that was done last month. On April 14 they titled acetylcysteine ​​a rapid review of the evidence on efficacy in the treatment of covid-19 and they do a very good review in which they look at the ability for acute respiratory disorders, but again, this is before we really understood that maybe covid-19. It's not just a respiratory disorder, but perhaps it's also a vascular disorder that causes thrombosis, which causes a lot of the hypoxemia, so they looked at Knack in terms of acute respiratory disorders and the verdict they came back with was that the evidence of clinical trials for use The usefulness of the ability as an antioxidant in influenza and other acute viral respiratory tract infections is very limited and therefore it is difficult to draw concrete conclusions without further evidence from trials, so they review the data here in terms of its antioxidant properties, but it doesn't really touch on Knack at all and its ability to break those disulfide bonds and break up and thrombolyze some of these clots that we're seeing and it's well referenced, so when I went to Clinicaltrials.gov To see if something was being done, I found only one study. a study of acetyl cysteine ​​in patients with covid-19 infection and if you look here, they are actually giving it to patients who have severe disease, which I was very happy to see that they were trying to enroll 86 participants, it was a study not randomized. trial and it was a phase two study of an acetyl cysteine ​​in severely or critically ill patients with refractory covid-19 infection and they are not misleading people because they are giving six grams a day of acetyl cysteine ​​intravenously and they are we are going to give it lasting up to three weeks or until discharge from the hospital, admission to a critical care unit, intubation, toxicity or death.

Let's look at our hypothesis one more time so that we have SARS Cub 2 binding to the ace2 receptor putting it out of action, so it has reduced ace2 as a result of its angiotensin II increasing and its angiotensin 1 7 decreasing, which causes an increase in superoxide, that increase in superoxide causes oxidative stress, which causes endothelial cell dysfunction, which increases the amount. from von Willebrand factor released from the subendothelial space and causing thrombosis and potentially it is the thrombosis that causes hypoxemia and other things in the pulmonary system, so the nice thing about acetyl cysteine ​​is that it could act here to reduce oxidative stress and it can potentially act here to reduce the amount of Von Willebrand fat vector monomers and polymers that bind together and form these clots and the thrombosis associated with them again, we have no evidence that this works in covid-19 because we haven't done it trials, but if we connect the dots it looks promising and more importantly in a number of studies where they gave Knack they didn't see any serious adverse outcomes so the question I have is did people take Knack via oral as a preventative, could this prevent severe forms? of covid-19, as we saw with influenza A, did not reduce the number of infections but it did reduce the severity of the infections.

The next question is: if given in high enough doses intravenously in the hospital, can it prevent patients from progressing to intubation and admission to intensive care if you think these videos are useful please give us a thumbs up, subscribe, pass them and visit us at medcram.com thank you for joining us abroad