NAC, Metformin positively impacts Long Covid

And a lot more information

As I wrote in my last substack this one will be more on the helpful side, not incredibly in-depth on its own, but I will link a lot of other things I wrote with information on each specific beneficial dynamic/effect. Also what were the odds, I found the first papers and read just the highlights at first, and now reading the entire thing, I can’t help but laugh a little, you will understand why soon.

Clinical experience with the α2A-adrenoceptor agonist, guanfacine, and N-acetylcysteine for the treatment of cognitive deficits in “Long-COVID19”

For clarification, a2A adrenoreceptor is just another name for a2A-adrenergic receptor, you can also find it named ADRA2A in other papers.

Certain regions of the brain are more predisposed to further damage, especially after an infection or injury sensitizes said region to a secondary hit, often referred to in the literature as “hit and run effect”, which SARS-CoV-2 is a master on. As we covered recently, close to 25% of Long Covid patients have Central Nervous System manifestations, and sequelae, so addressing such changes is often a way to treat the condition. In many cases of brain fog after a SARS-CoV-2 infection, the pre-frontal cortex is the one that takes “the brunt of the damage”, and per the paper itself, this region is vulnerable because it used different receptors to function (NMDA receptors), and the way it deals with the flow of calcium and potassium can weaken the connectivity, especially during stress.

During chronic stress (or low-grade long-term inflammation, among other conditions) occurs an excessive presence of calcium in the mitochondria and this activates the microglia (immune cells of the brain) to remove spines.

Here is a fairly extensive substack I wrote about the Kynurenine pathway and SARS-CoV-2, this is about KP and Long Covid, and here is one I would recommend most to read, and yes it does intersect with the current subject.

Inflammaging, SARS-CoV-2 and HSCs

In fact, after fairly extensive research on the topic, I found that such as Galectin-3, the Kynurenine metabolites and its own pathway are a double-edged sword, under very specific circumstances it has a fairly protective effect, the problem arises outside of said circumstances, or continuous, dysregulated production of them, such as under chronic infection, stress or inflammation.

In the case of PASC/Long Covid with so many secondary hits after the initial infection, creating a fairly complex case to be unsolved, almost on an individual basis, all roads lead to Rome, and as such, the many dysfunctions in the afflicted end up shifting tryptophan metabolism towards kynurenine.

I am fairly “anti-drug” and would prefer Long Covid patients to attempt other interventions before going on the drug route, but if you have tried a few combinations of supplements, consistently for a few months and saw no improvement, you should talk to your doctor on testing Guanfacine. I am fairly confident that 90% of the time the “stack” I often suggest to people will improve people’s health dramatically.

For people with long-term Long Covid/PASC that didn’t improve after 4-6 months of following, consistently the way I suggest, my “stack” or similar list of suggestions I highly advise you to get tested for autoantibodies. I will write more about this subject, I am taking my time by the sheer fact that is too depressing.

Here is more information on NAC I previously covered. NAC stopping inflammasomes (the biggest driver of disease severity and post-infection dysfunction via many mechanisms), many reasons to take NAC with Glycine, I also suggest in my “Brain Stack” to use NAC and Piracetam, and I believe many people with neurological sequelae from any sort of viral infection would improve, there are many reasons to perhaps consider Piracetam.

The second is “good news if you listened to me” rather than just straight-up good news.

Outpatient treatment of Covid-19 with metformin, ivermectin, and fluvoxamine and the development of Long Covid over 10-month follow-up

“Simple”, direct to the point, and in line with much of what I have been writing for the most part of the last 2 and a half years, that Metformin would have a myriad of positive impacts given all the metabolic and immune pathways it acts on, it also can help with gut issues, the list of positive effects of Metformin is huge. The following substack is short on size but heavy on content, scroll down and see all the referred papers, it is just a little bit of what Metformin can do. Note that Metformin also directly downregulates the Kynurenine Pathway.

For future reference, whenever you see someone, a paper, or myself citing the positive effects of Metformin, you can pretty much read it as Berberine, it is an almost 1:1, perfect analog to Metformin, with certain positive effects being found only on one, or the other. If you are American, European, or Australian, for the most part, it is just easier and probably cheaper to get Berberine over Metformin.

Metformins is associated with Reduced SARS-2 Severity

Metformin (therefore Berberine) will also positively impact Akkermansia Municiphila, the precise microbe in your gut microbiome that Omicron significantly impacts, in the long term. Some Long Covid has very low levels of Akkermansia, therefore it is self-evident the positive impact the drug or the natural supplement could end up giving.

A short guide to improving your microbiome

Tangentially related to inflammaging topic, here is a substack one about SARS-CoV-2, senescence, and mitochondrial dysfunction, with Metformin directly acting upon the pathways described in the paper analyzed. You can find even more about Metformin in this substack and how it is somewhat “central” to my whole approach in this substack, which I need to update and rewrite it.

As a reminder, there are many other things that are helpful in most circumstances related to SARS-CoV-2, I will leave some here.

Short guide on modulating Galectin-3

Breaking news ! Vitamin C works to prevent SARS-CoV-2 infection

Vitamin D enhances Type I Interferon signaling

Antimicrobial peptide LL37, Niacinamide and SARS-CoV-2

As I wrote before, this would be mostly a helpful post, and a decent starting point if you want to understand why, and how certain supplements work the way I and many others described either early on, or in the last 12 months. These are but a mere fraction of what many of these nutrients can do, one could legitimately write pages upon pages on this, but it can get confusing pretty fast.

Here is the “starting point” I suggest for most people.

600 mg NAC (N-Acetyl-Cysteine) - Depending on your level of inflammation, stress, or chronic disease you can easily up to 1200, 1800 whenever you get infected by any viral infection
Glycine - Same dosage as NAC, a literal one-to-one, together WITH NAC
Niacin (Flush) is my chosen type, but one could opt for Nicotinamide, either Mononucleotide or Riboside
Vitamin D+K2 - I personally take 10.000 IU every other day, but sometimes I stay off for a week
Metformin (or Berberine) - Starting with 500 mg and going up to 1000 mg, some go higher with Metformin close to 2000
A decent multivitamin
Vitamin C - 500 mg Every 4 hours, has synergy with almost everything
Melatonin - Each person is different, my daily dosage is 10 mg, going so far as 60 mg whenever I injure myself or get an infection, Melatonin, such as NAC+Glycine has a laundry list of positive effects.

Most people with any form of sequelae after Covid are poor absorbers or deficient in Magnesium, huge arguments about the best type, so choose whichever you prefer, with most choosing Magnesium Glycinate

I stay away from blanket suggesting people take some specific supplements, so you should test out your response towards Tryptophan, most people with inflammation, neurocognitive issues, and gut issues respond positively to Tryptophan. So I suggest you read a little and try it.

Most of the things in this list either have synergy or directly affect multiple pathways that may lead to more severe disease, but especially halt long-term consequences from multiple infections, and shortly fix them, which is precisely the goal. Halting subclinical damage, and fixing it before the inevitable next hit comes until the endemic SARS-CoV-2 becomes basically a fly without all the hidden nasty mimicry inside (getting close to that).

I wish you a good Sunday.

I appreciate the support of those who choose a paid subscription, or who decide to buy me a coffee whenever they feel like it, and everyone who shares my Substack. This work wouldn’t be possible.