56 Comments
Jul 26, 2022·edited Jul 26, 2022Liked by Modern Discontent

Great article, 10 out of 10. You and Brian are on a tear.

100% agree on the N protein. The N protein antibody is an indication of a broad immune response -- not really a great weapon in the fight against the virus.

If the S protein antibody is a rifle that can engage the enemy and keep him away -- the N antibody is at best a bayonet that you can use if the enemy is inside your quarters and you are running out of bullets.

What I understood through the pandemic is that the science is only beginning to lift the veil on how our immune system works and scientists use tidbits of knowledge to poke around in the dark. (This is why Warp Speed was a terrible idea and a cover the the already pre-made vaccine) This is okay since science takes time to develop, we just need to be aware of it.

But I broadly do not understand what our immunity to Sars-Cov-2 even IS.

Why, say, among the below constantly exposed people there is a diference:

- unvaccinated Adam had no covid ever

- unvaccinated Igor had only one Covid in Nov 2020 despite being out and about

- unvaccinated Bob had three Covids

- Vaccinated Charles had vaccine and no covid

- Vaccinated David had vaccines and multiple covids

What is it that is different between those persons? I am not entirely stupid and ignorant and I can observe differences betwen classes of people and how vaxed people seem to get reinfected more often. But while I have some observations and ideas that I posted on my substack, I also realize that I have much to learn.

For example: can someone get reinfected with the SAME variant as their last Covid, if we tried to infect them on purpose, say half a year after last infection, using a lab solution of their own specific virus that this person had 6 months ago.

Etc

Many questions that I do not see answered. Wondering what you think

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The issue is that a lot of this may just boil down to individual differences. We are all different, including our immune systems, so we probably should not expect each of us to respond in a similar manner. We all carry unique HLA haplotypes so our APCs present different epitopes to T cells. Some of us may be vaccinated to high heaven but produce no response (non-responders). Some people just never get sick.

Our innate immune systems are different. We each have genetic differences that affect which interleukins are released.

Then there are some of us who are older; some are younger. Some are fitter; some are fatter. Some love desserts and sugar, and some eat purely vegan. There's so many differences that are never accounted for in individuals.

Then we have exposure rates. Some people are exposed more frequently than others. Some take on higher viral loads, some take on less and don't get infected. Some people spend most of their time outdoors while most stay indoors without sunshine in a cramped office space.

In short, we are all just different. No study will ever capture the individual differences between us all. Science can only provide an average, and then we have to battle with the issue of whether the average is presentative of the whole. There's just far too many variables to deal with, and we really need to come to terms with that.

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Jul 26, 2022·edited Jul 26, 2022Liked by Modern Discontent

This concern with averages and ignoring idiosyncrasies is a root problem in "science." Individual cases MUST be understood if science is to be useful for healing.

Engineers can build bridges and buildings that ALWAYS stand, not bridges that stand "on average." It is a profound shortcoming of medical science to be unable to do that.

If all that science is ever going to do is look at averages while ignoring the outliers, it can only ever be a tool of one-size-fits-all, anti-human "treatment". This is in many cases harmful and not healing, and the poor outcomes are even blamed on the patient.

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It reminds me of when people say that people on average have fewer than two legs or two arms. Well sure, we can average it out but for the person with one leg they're not going to magically grow a stump.

The problem with medicine is that there are so many variables to consider that you really can't account for every single one. Individual-based medicine would need to get the genetic profile of an individual, get their dietary status, as well as their past behaviors, where they live, their family's prior risks, etc. The list can just go on, and medicine really has no way of finding it all out. So instead it has to work on the average to figure it out. The problem is how close to the average are individuals- it's one thing if most people may clump together but may be off by about one standard deviation. It's another if people are generally on opposite ends, and we just take them in the middle.

I think what science can do is to take outliers and understand why they are outliers. There are some people who appear to never get COVID regardless of what they do, so what makes these people somewhat impervious?

Overall, it's really a balance between what science can do and what the public should expect. Science should probably be more focused on transparency and not promising the moon when there's so much that science has yet to uncover and has yet to fix.

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Jul 27, 2022·edited Jul 27, 2022Liked by Modern Discontent

What I meant is that case studies are at least as important as randomized controlled trials.

I say this with experience in software. If your software is widely used, and you have 10,000 or even just 10 reports of a bug, you have failed. A bug reported by a user should be rare (you found the common ones in testing), and then 1-3 bug reports should be sufficient to identify and fix the bug (just 1 can be enough if you can get detailed information).

In many "scientific" fields, this just does not happen. "Oh, it happened once? Coincidence!" No, not coincidence. One good report of a bug is a bug, is a bug, is a bug. Failure to act on that report is already negligence. I am most proud of my work when I get a single bug report, find it, and fix it.

Anecdotal information and case reports are undervalued, at least partly because science is manipulated and statistics afford room for "creativity." But the result is worthless, or harmful.

Outliers should always be carefully studied, more so than the average. Outliers are the jackpot.

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But the questions that I asked are very important! Bob and David from my example, for example, are prime candidates for dying in the upcoming dieoff. We need to understand why Bob and David are so unlucky if we want to keep people healthy.

So, to me, just saying "people are just different", is not good enough when facing questions that are in some ways key to understanding this pandemic and saving lives.

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Igor, you have to understand whether your hypothetical participants would not have died off in prior waves. There are so many things to consider than just what is provided in a little scenario. Why did Bob keep getting sick? Is Bob immunocompromised? Why didn't he die? Was it severe? Does Bob have a prior history of comorbidities such as obesity, cancer, smoking? Does he have a poor diet? How old is Bob? Where did Bob spend most of his years living. Is Bob married? What does Bob do for a living?

There are so many things to consider that no hypothetical will ever work unless we have an actual Bob (and David for that matter). Remember that our health tells a story about ourselves, who we are (genetics) and where we come from (well, more genetics). We are the sum of all of our experiences, and it is our sum that determines what happens.

So we can't just look at this scenario and create a simple explanation. I say people are different, you should consider what differences could be responsible in causing someone to either never get sick or to always get sick. Apply the knowledge that you see all over Substack. Collect the information and piece things together.

This is generally my concern that I am seeing- definitely not pointed at you specifically Igor. I'm seeing many people just passively absorbing the information yet not knowing what to do with or what the information means (if they can figure it out in the first place). Dig deeper than the superficial. If someone presents something, ask if it makes sense, see why it does with evidence that substantiates the claims. If not, find evidence that would refute it. But don't take the claims at face value. If we're going to argue that we are critical thinkers than we should put critical thinking to practice, not to speculate and pontificate on things to which we may not be able to fully substantiate.

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I agree in general. I am just worrying that the science is leaving people like Bob and David to fend for themselves. I wish they tried to figure that out.

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Hi Igor. I salute your work as I am sure many others do.

Unless all these people you mention have been supplementing vitamin D3 properly for months, their 25-hydroxyvitamin D levels are likely to be in the 5 to 25 ng/mL range, depending on the season, their skin colour and the degree to which they have exposed their skin to direct high elevation sunshine (no sunscreen or glass) in the past month or two. Then are are individual variations in 25-hydroxyvitamin D levels which would occur even if they all had the same skin type, ate the same food, and exposed themselves to the same amount of UV-B.

People like me who understand that almost all people who are not supplementing vitamin D3 properly (70 kg BW 5000 to 7000 IU/day) have profoundly weakened immune systems, with much greater risk of self-destructive inflammation, see the whole world totally differently from how other folks see it.

We see the whole world going to hell in a handbasket - and this was before COVID-19 - with 10 million or so doctors and many more nurses working feverishly trying to help people, the vast majority of whom has totally crapped up immune systems. With rare exception, the medical professionals are flying blind. That is why 11 million people a year die horribly from sepsis. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32989-7/fulltext . Virtually none of this terrible toll - and the tens of millions more who are seriously injured in this way - would occur if everyone supplemented vitamin D properly.

We tell a few of these doctors about vitamin D and the immune system, and most of them dismiss it as spam, or can't believe it could be true - its "too simple". So they go about their business, still clueless, and we feel like ghosts.

I have been working assiduously on this since March 2020. I collaborate with PhD researchers, MD researchers (including some Professors of Medicine) who have been doing this for decades. The proclivity of most doctors and many non-doctors not to take an interest in this is the most perplexing thing we have ever encountered.

For various reasons, it is much easier for non-medical professionals to understand this. I work in electronics and computer programming. It is real obvious to me. You are both more abstractly elevated - mathematics - and more gutsily grounded, moving heavy industrial equipment for a living (and selling, modifying and I guess repairing it too).

Please take a look at the research articles at: https://vitamindstopscovid.info/00-evi/ . You will see everything differently. Many of the people you tell about it will ignore what you say or write, and you will feel like a ghost too - but some will listen, learn and transform their lives and medical work.

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Jul 26, 2022·edited Jul 26, 2022Liked by Modern Discontent

Why not target the membrane or envelope proteins then?

Why aren't they getting a mention?

Are they more stable to mutating?

Even if they were prone to mutating it would give more options for the immune system surely... thus less likely for the whole virus to escape it...(?)

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User Obvious below linked this post talking about the M protein:

https://hillmd.substack.com/p/why-dont-covid-vaccines-target-membrane

So that's interesting. I'll try to look further into the matter and see what I can find.

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I'll be honest and state I haven't looked at the other surface proteins. I would assume it's because it still doesn't stop the spike from sticking and entering into the cell. It really comes down to the actual functions of those proteins and whether they would be hindered if targeted by antibodies. Then if targeted does it stop many of the virus' necessary functions. I'll keep an eye on those other targets but that may require looking into those proteins and figuring out what they do more.

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Jul 27, 2022Liked by Modern Discontent

Oòoo it's dangerous to assume....

That article makes the M a great candidate! Most abundant protein... highly immunogenic... stable !!!

And surely the point of an antibody is not Just to get in the way of the bully and the defenceless dweeb.....

Doesn't it also bring in the bouncers.... to evict corona from the club.... or worse....

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So I looked at a few of the articles provided in the post I linked. I think it's interesting however I don't find the studies convincing (yet). One thing I forgot to mention is that with proteins it depends on how much of the protein is expressed on the outside of the cell. It appears that most of the M protein is not expressed on the surface.

A few of the studies show that people who have recovered from COVID have anti-M protein antibodies, but that doesn't quite tell us whether those antibodies are neutralizing, just that the M protein is immunogenic (produces an immune response against it). A few of the studies take parts of the M protein and sees the response. One suggested that the C and N terminal are targets, and one suggested that the active site may be targeted.

The main problem is that all of this hinges on the fact that targeting the M protein would be sterilizing due to its conserved nature. However, the M protein is conserved across different coronaviruses, including SARS-COV1 and human coronaviruses. Wouldn't human coronaviruses provide cross-reactive anti-M antibodies, and thus neutralize SARS-COV2? Better yet, wouldn't prior infection from SARS-COV2 provide anti-M antibodies that would neutralize the virus? Yet we are seeing many people- both vaccinated and naturally immunized getting sick again.

I think I would need to see more data so that I can piece the information together more properly.

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I think it's worth mentioning, even though the vaccines target the spike protein, "to stop the virus entering the cell," this doesn't actually stop anything. Boosted people are taking twice as long to clear the virus as the unvaccinated:

https://igorchudov.substack.com/p/study-boosted-people-slowest-to-clear

Instead of developing immunity, the vaccinated are developing tolerance for spike protein - as if it was a harmless allergen. This allows their bodies to be flooded by the toxin:

https://unglossed.substack.com/p/boosting-tolerance-igg4

All in all, it doesn't sound like this idea of "stopping the virus entering the cell" is working. :)

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Jul 26, 2022Liked by Modern Discontent

You might want to take a look at this pre-print. https://www.biorxiv.org/content/10.1101/2022.03.09.483635v1 While a priori it might seem like vaccines against internal proteins are useless, they appear to have some value in practice. Certainly more mechanistic studies are needed, but if a vaccine derived from a non-surface viral protein can A) provide some protection against severe disease and B) be non-pathogenic in and of itself, it may have some value as a therapeutic for high risk populations. My main problem with this type of vaccine is that it will be inherently non-sterilizing and might then serve as a strong selective pressure to drive faster mutation in a part of the virus that does not normally mutate so fast. It may be worth it to use only for very high risk individuals. I think not developing any more vaccines against COVID is probably the best course of action, but it's impossible to convince most other people of that. Convincing them to pursue an alternative that's less damaging than continued injections of the original S protein vaccines may be the best we can do.

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Thanks for the study! I made a comment in my footnote that targeting the N protein may reduce cytotoxic effects, but if the general idea is to halt viral replication the N protein wouldn't be the way to go.

The researchers make this comment, but it is specifically in regard to in vitro studies:

"As expected (Dangi et al., 2021b; Sanchez et al., 2021), sera from mice that received this spike-based vaccine prevented SARS-CoV-2 infection, even when the sera were diluted 450-fold (Figure 2B). However, sera from mice that received the nucleocapsid-based vaccine did not exert any antiviral effect in this in vitro infection assay (Figure 2B–2C). Taken together, only spike-specific antibodies can block SARS-CoV-2 infection, consistent with the widely established notion that these antibodies are protective, as they can block the first step in the SARS-CoV-2 life cycle (entry into host cells)."

The researchers don't provide much in possible mechanism with the N protein. The mice study is interesting, although it does suffer from the typical issues of using a small number of animals in the study. It's strange because one mouse appears to show nearly all clearance of the virus, so I wonder if the researchers considered this an outlier (Fig. 3). Also, the researchers provided an adenovirus-based vaccine for the N protein, but then boost the mice by exposing them to the N protein, which may confound the evidence.

I actually don't believe that targeting of the N protein will drive mutations. Generally a conserved protein suggests that the protein exists in a precarious situation- a few mutations and the protein may lose all functionality, so generally the more important the protein/epitope, the less likely it is to mutate without compensation in some way. So there's likely a good reason the N protein has not mutated to the extent that the spike does.

Overall, the N protein would be something interesting to look into, but if the attempt was to halt the infection the spike would be the best option. With the N protein you would just hope that the symptoms are attenuated, without much explanation for the possible mechanism.

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Jul 27, 2022Liked by Modern Discontent

I generally agree on those points. With most of the world having been infected and/or vaccinated at this point, the vaccines hardly even matter any more. The effect of boosters is modest, temporary, and vaccine efficacy turns negative months after the last injection. Furthermore, the effect of OAS seems to be pretty strong for those vaccinated or previously infected, although if the previously infected can make antibodies against the mutation resistant proteins (such as N) we may have a better chance of having milder symptoms upon reinfection with new variants. This leads to the question of why big pharma is rolling out a different vaccine in the fall when previous two attempts at strain-specific mRNA vaccines (against beta and omicron, see here: https://arstechnica.com/science/2022/02/monkey-study-casts-doubt-on-need-for-an-omicron-specific-booster/) failed to do any better than the original vaccine. It seems to be nothing more than a ploy to make money. How then will big pharma get approval if their new variant-specific vaccine is ineffective? I think we've already seen how that works with the approval for child vaccines.

It seems then the next three questions that covid-vaccine skeptics need to focus on are:

1) Is repeated exposure to the carrying agents (lipids) of mRNA vaccines associated with toxicity and/or cancer?

2) Do the new spike proteins have the potential to cause the same toxicity as the original?

3) Does the repeated practice of turning a wide variety of cells throughout the body into factories for highly immunogenic antigens eventually trigger autoimmune diseases?

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Jul 27, 2022Liked by Modern Discontent

Beth Mole is not an impressive study reviewer.

The Moderna Omi booster clearly induced memory response toward BA.1 spike, the effect is just hard to spot because they don't normalize for pre-booster differences in the lab monkeys https://unglossed.substack.com/p/macaque-to-the-future

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Well, to argue that the effect of OAS is strong we would need to pin down the effects of OAS. Not applying specifically to you, but I feel like OAS has kind of become the new hip lingo to use around the block although many people haven't quite provided a robust argument as to why OAS is occurring.

https://moderndiscontent.substack.com/p/open-thread-lets-talk-about-oasimmune

I remember Brian Mowrey raised questions about that study in monkeys that was pretty interesting, although I might be misremembering. I haven't quite looked into it too extensively, but it really comes down to the methodology being measured. Usually animal studies already suffer from an extremely low sample population and so even one or two animals showing something profound may heavily skew the data.

I'm curious about the LNP comment. I've grown more concerned about the inflammatory nature of them, but I also like to know which evidence people use as well.

As to 2) the answer is generally yes, it does appear to be the case. That's generally my argument. There are concerns that the structures may be different due to changes such as codon optimization, but I'd have to look up evidence to see if there were any studies such as x-ray crystallography to at least compare spike structures between the two.

https://moderndiscontent.substack.com/p/all-roads-lead-to-spike-protein

The autoimmune disease part is interesting. I think a concern may be tolerance over repeat exposure. If the spike leads to continuously inflammatory processes, the body may just give up and leave it be because the inflammatory response may be too damaging to have it keep going on. I believe that's generally the argument about tolerance, but I haven't looked into it too extensively.

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Looking at it more, the researchers probably made the egregious mistake of vaccination then providing the N protein. Unless their argument is that this should be the approach they take with humans, I don't find such a methodology to be proper. For one, the presentation of the N protein itself should elicit an immune response, so why provide the adenoviral vector? They're essentially providing heterologous vaccines (DNA-based then a protein vaccine) which really messes with their data. So we don't even know if the adenoviral vector alone provided any immune response- there's no data in regards to that.

I haven't gone through the supplemental data, but now I really wish they did not keep giving N protein to their mice.

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Reading your article now, very interesting. I recall that they tried to make N-based vaccines and it ended up very badly among test animals

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Jul 26, 2022Liked by Modern Discontent

So, as both of you, and many others, have pointed out repeatedly, "traditional" vaccines stimulate antibodies to the antigen presented by the vaccine. (They also present lots of other toxic substances). And that the mRNA jabs stimulate production of the antigen itself (the spike) and the person recurring or becomes a faculty for, in this instance, the most toxic element which becomes produced all over the body.

That said all of the traditional vaccines produce infection, which escapes on to the community. The two everyone wants to call out as success, the polio and smallpox vaccines, cause community infection.

Just sayin

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That's another fault of individual differences as well. Live vaccines must be given at such a dose that the person given it doesn't have the virus overcome their own barriers before they can mount a proper adaptive immune response. The only problem is figuring how what each person's sub-transmissible dose is. That's far too difficult, and again a consequence of using a standard which may cause those with weaker immune systems to become ill.

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Was it against COVID or another coronavirus? I'd like to see studies on that. It's well-known that animal studies with spike antibodies with seasonal coronaviruses lead to ADE.

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There's a large literature on influenza and COVID-19 seasonality. Most of it written in ignorance of the importance of good (50 ng/mL or more) 25-hydroxyvitamin D - which is needed for proper immune system function. Without sufficient supplementation, most people have 1/10 to 1/2 of this: https://vitamindstopscovid.info/00-evi/ .

There is a lot of confused and confusing stuff written in such research articles, for instance: ", , , winter, where low humidity outdoors and high humidity/warmth indoors may create environments conducive to viral spread,"

It is important to distinguish between relative and absolute humidity. Only relative humidity matters, because this is what affects the degree to which aerosol droplets of water containing viruses evaporate into smaller particles, including perhaps a single virus with a handful of water molecules surrounding it in a single layer. (I recall this - sorry, I don't have a reference.) Such small particles with viable viruses can float in the air for hours - much longer than any droplet of water.

In winter there is less moisture in the air, in general, in absolute terms - so the absolute humidity is lower. However, the relative humidity is high - often close to 100%. In summer, the relative humidity is often very low, and only in a handful of tropical or sub-tropical areas does it get close to 100%.

I believe that winter indoors and in-vehicle conditions probably do drive transmission of influenza and SARS-C0V-2. The air is heated (hotter than indoors and in in-vehicle in summer - assuming air conditioning is used in summer) and so the relative humidity is very low. According to my limited understanding of the research on respiratory viral distribution in aerosols, this would increase viral transmission.

Most transmission occurs indoors, but I am not convinced that the supposedly greater proportion of time people spend indoors in winter makes much difference.

Please see: https://nutritionmatters.substack.com/p/covid-19-seasonality-is-primarily for a review on the research into influenza and COVID-19 seasonality. It is easy to see that the primary mechanism is seasonal changes in 25-hydroxyvitamin D, causing 24 hours a day, population-wide, changes in immune system function, with winter and spring being the low-ebb, with consequently greater disease severity, average rates of viral shedding and so greater transmission. All the overall transmission R0 has to do is get above 1.0 and the disease spreads.

See the second blue graph there - UK COVID-19 hospitalisation numbers from March 2020 to about the end of 2021. This is a better measure of disease prevalence than PCR test numbers, since testing rates vary over time.

In the summer of 2020, the original variant was dying out - by the end of August only 795 patients remained in hospital. If nothing had changed, the numbers would have kept falling exponentially. There had been 19,617 in hospital 4.7 months before. This is a rate of decline to 4% (1/25) in 4.5 months. The hospitalisation numbers had been halving every month for at least 4 months. In another 3 months, the numbers might have dropped to 50. This was to some small extent due to the virus running out of people to infect in the most vulnerable populations - the elderly, the Asians (from Pakistan, India and Bangladesh) who have terribly low vitamin D levels and who tend have lots of contact with other people by being in nursing homes or being in service jobs.

However, two things happened. Firstly, 25-hydroxyvitamin D levels started falling - see the curved lines in the 1st blue graph. Secondly, the Alpha variant arrived, which was more transmissible. Vaccines played no role in this decline - they were introduced at the end of 2020. So the seasonal decline ended.in late September.

We see a similar decline (2nd blue graph) occurring in the summer of 2021. The quasi-vaccines were probably affecting the outcome somewhat. There were few lockdowns over summer, as far as I know. Immunity from infection was spreading, at least in the segments of society most likely to be infected and hospitalised (those with low vitamin D - see the bar graph which follows to see how much worse Asians and other ethnic minorities were in this regard than people with white skin).

Looking at the figures (put the computer cursor over the graphs) for 2021: https://coronavirus.data.gov.uk/details/healthcare, the peak number in hospital was 38,849 on 2021 January 21st. By June 3rd this had dropped to 942. This is 1/41.2 of the peak, over 4.3 months: Every month the numbers were about 0.42 of those of the month before. If nothing had changed, this would have continued and the COVID-19 pandemic would have been well and truly over in a few months.

Vitamin D levels kept rising, which should have hastened the decline. As far as I know, lockdowns and social distancing were eased, which favoured growth in hospitalizations. The big change can be seen here: https://covariants.org/per-country In the UK, the Delta variant rapidly displaced the Alpha variant because it was more transmissible. It may also have been more virulent - causing more harm to those infected.

So we see two clear examples of seasonal decline in hospitalisation = COVID-19 transmission multiplied by average case severity, in the summer of 2020 and 2021. Both declines were ended by new variants - and the declines would have ended later anyway, as 25-hydroxyvitamin D levels started falling in September.

In the summer of 2022, with 25-hydroxyvitamin D levels rising again, we see hospital numbers more than tripled in the past 5.3 weeks, from 5001 on June 2 to 17,019 on July 14th. The rise would have been greater if 25-hydroxyvitamin D levels were not rising. The cause is BA.4 and BA.5 (violet and pale blue at the right - see them labeled in the USA graph in the middle of https://nutritionmatters.substack.com/p/how-are-we-to-recover-from-the-corruption) which are much more transmissible than the BA.2 and BA.1 which they displaced. This is in all the circumstances of many people being quasi-vaccinated, the immunity from this fading, boosters maybe helping for a while and/or, perhaps, BA.4 and BA.5 somehow replicating better in people with such quasi-vaccine induced immunity, plus their ability to escape immunity acquired from prior variants.

So the seasonal pattern of COVID-19 declining in summer in the UK is clear in 2020 and 2021, but completely overridden now because of the new variants.

Some measure of the transmissibility of BA.4 and BA.5 can be found in Australia. Here, seropositivity was apparently 17% in February and 46% in mid-June. https://www.theguardian.com/world/2022/jul/27/almost-50-of-australians-had-a-recent-covid-infection-in-mid-june-blood-donor-survey-suggests This was in blood donors, which is not a proper sample of the population, but it shows that the almost entirely vaccinated donors were being infected at a very high rate, even though February is probably the peak time for 25-hydroxyvitamin D and levels would have been above average until about May.

The situation in the USA is much messier due to being not so far from the equator as the UK, so the variation in 25-hydroxyvitamin D is not so extreme.

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So many review articles I've seen on seasonality such as the Moryama, et. al. piece are usually very technical in their argument. I wanted to truncate it extensively since the argument for seasonality can't be made until we deal with making the virus endemic, and that may require having a situation in which population-wide immunity serves to be generally inhospitable to the virus. I left out things such as bottlenecks since that would be going into the weeds and make the article even longer.

So I have no doubt that Vitamin D may be playing a role as well as other factors in driving seasonality. I'm not sure how much the Vitamin D hammer can be pushed, but I would assume by now most people may be supplementing as well as going outdoors. It really is amazing that, at least for us in the Northern Hemisphere, we are right in the middle of summer and yet people are so concerned about getting a little sunlight for their own health. Sunlight and more outdoors is what we need, not less.

Ba.4/Ba.5 may be more infectious and virulent due to gaining more tropism for the lungs. Apparently there's an argument that the prior Ba.1 and Ba.2 variants may not have accessed cells through membrane fusion which would require use of the furin cleavage site and the TMSPR (can't remember the name, but the transmembranous serine protease that cleaves at the furin cleavage site). There's a few suggestions that the spike may have changed conformation for Ba.1 and Ba.2 and made the FCS inaccessible so instead it went through the endosomal route of entry. I have argued, although I'm not sure how substantiated the claim is, that the L452R mutation is likely to also be playing a big role. Delta had this mutation and it likely aided it in infecting cells.

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Jul 26, 2022·edited Jul 26, 2022Liked by Modern Discontent

"Learn, grow, and apply- do not become static"

That is one of the best phrases I have read over the past 2 1/2 years. It's certainly what the virus does, isn't it? You are part of my learning process, for which I am grateful.

BTW, I'm recommending the book Dissolving Illusions by Suzanne Humphries to everyone. It's the dismantling of the history of vaccines that we learned about as kids, pointing out that all these diseases were on the wane and headed towards zero due to sanitation, clean water, better nutrition and ventilation. A good look at germ theory vs terroir.

Aloha and thanks, as always.

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Jul 26, 2022Liked by Modern Discontent

I just started reading it last weekend. I feel like I have had many dissolving illusions the past year or so in the scientific field.

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Jul 26, 2022·edited Jul 26, 2022Liked by Modern Discontent

Yes, I knew already that hygiene, waste, clean water, nutrition were the prime drivers of the diseases disappearing. But I didn't know about the malfeasance, the toxins issue fur polio, the political pressure, etc. Seems like deja vu all over again

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Thanks Paul! That means a lot, and I know you've made comments about letting myself through more in my writing. I'm still trying to figure that out and just let my thoughts flow sometimes.

I've heard of that book and will likely give it a look in the future.

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Aug 2, 2022·edited Aug 2, 2022Liked by Modern Discontent

Good of Mike to comment further. I think he is crediting vaccine developers with the thought processes that “regular” drug designers go through. Because vaccines are subject to far lighter regulatory review than other drugs (no carcinogenicity testing, for example), I suspect the developers are more slap dash when it comes to product design. I’ve worked with both, and the vaccine people were just hell bent on getting antibody titres high, and everything else was secondary and seemed to be “cross your fingers and hope nobody dies”

Probably a legacy from the days when vaccines were based on attenuated live viruses. I’m just not sure they think too hard about other effects because they always think “the virus is worse”, which in their minds gives them free rein to do whatever the hell they please.

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Jul 27, 2022Liked by Modern Discontent

Sorry, but this is all crazy talk. If chart says thing, virus HAVE to do it! Immunology ONE OH ONE.

I agree about the Omi siblings being a restart. On the other hand I find the ^^^^^ "forever wave" pattern that emerged in the UK starting last summer and has appeared elsewhere to still be unnatural-seeming. So while I get just as annoyed when writers refer to seasonality as an axiom (or insist that viruses can't get more virulent over time), which I think is super misleading to the audience, even Delta era infection patterns did seem reflective of immune suppression - and now we have evidence that tolerance was already emerging by that time, pre-boosters. So my guess is that the Omi line has advantages on its own end and in the host.

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If only viruses would listen to the charts. Maybe if we point harder and start tapping they will listen!

For the actual extent of seasonality I really couldn't find any example of time. Seasonality is all hypothetical and derived from current evidence, so it's using current evidence to explain things that may have happened in the past. I really don't know how long it would take for a virus to become "seasonal". Is it months, years, decades? Unfortunately I couldn't find ye old journal archiving this information. So many post-post-post Delta may have headed towards seasonality, or maybe it would be post-post-post-post-post-post-post-post-post-post Delta. We probably wouldn't know so I kind of worked on "well, maybe if we can all fight off the virus to some degree adequately, maybe we can deal with humidity and winter months" 🤷‍♂️.

I haven't looked too deeply into immune suppression, but don't many viruses already have ways of escaping the innate immune system, and some may suppress the innate immune system. I guess with everything going on I'm hesitant to go down continuous black pills, especially as people appear to be growing more anxious and fearful.

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Do you mean the time for transition between "pan" and "epidemic"? I really don't think there are enough modern examples to ground any assertions here, so I regard most literature on this subject as story-telling. The problem is compounded by the fact that interest in "pandemics" skyrocketed in absence of the addition of raw data (from any actual modern pandemics; see for example the results timeline for "zoonotic" in a pubmed search). This squishiness is one reason why I dislike using either word.

Viruses must suppress *intracellular* innate immunity as a baseline requirement for replicating. One tactic is to be extremely inoffensive, like skin viruses / HPV. But ambitious viruses like coronavirus bring the full cellular break-in toolkit and the first proteins cleaved from the Orf1 polyprotein help silence the alarms - I added a review of the immune suppressing function of nsps1-3 at https://unglossed.substack.com/i/52208321/it-gets-better-not

These viruses can be thought of more like "hackers" in that they have genes that drive the genetic expression of the host cell in ways that are no less sophisticated than our own genes. Whereas non-co-evolved viruses are opportunistic, requiring a host that is metabolically on the fritz, or needing long term close exposure, etc.

In other respects it gets hard to distinguish between innate immune suppression and basic molecular function, like glycosylation of spike protein can fall into both. All the virus really cares about is whether having a nucleotide at a position leads to better or worse replication, not how.

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Jul 27, 2022Liked by Modern Discontent

I found

https://hillmd.substack.com/p/why-dont-covid-vaccines-target-membrane

interesting. I think I have seen that m protein antibody levels are associated with increased survival. My NCBI-fu is weak, so I am unable to find the specific publication.

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So I provided a response to sagemerat above in regards to the post. I think the information is very interesting, but personally there doesn't seem to be enough there yet to argue vaccination with the M protein. There's a lot that would need to be analyzed, and a cursory glance of the studies provided aren't enough to convince me at the moment. If we had additional evidence then maybe but as of now it really is hard to find any additional information on targeting the M protein.

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Jul 27, 2022Liked by Modern Discontent

Thanks for the input. I suppose that after BA.1, BA.2..... almost everyone has been exposed, and developed antibodies for S, N, M, and what ever other proteins Sars-CoV-2 expresses.

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Thanks for the link! That's really interesting. I would wonder if those with prior SARS-COV1 infections would have robust immunity, although time may reduce the adaptive immune response. I would like to dig a little deeper and see what would be going on mechanistically and what the studies cited state.

I'm not sure about the M protein and survival, but that may be based on observational evidence. I'll try looking around and see what I can find.

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Jul 26, 2022·edited Jul 26, 2022Liked by Modern Discontent

Modern Discontent - Any explanation why Mike Yeadon says that when he worked in a senior position at Pfizer, his team would have NEVER chosen the spike protein as the vaccine target?

He says this very confidently, and he says that this is what first alerted him to that the vaccines are being designed in malice. He says maybe one vaccine manufacturer might do something so harmful and stupid, but for all of them to do it, it must be on purpose.

What's your explanation, why would Mike Yeadon say this?

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So I don't know anything about Mike Yeadon to be honest. I've kind of been a bystander doing my own thing on Substack without any interaction with many of the otherwise high-profile people. I believe I have seen Mike Yeadon in the comment section remarking that he doesn't believe COVID is caused by a virus. I'm not sure where his position is on the matter and my memory is a bit hazy on what he said explicitly.

I think one think I've personally been curious about is how much of what we are seeing is some form of hindsight being presented as foresight. In a sense, most of us didn't know the spike protein would be cytotoxic until some research came out suggesting it. In hindsight, we may argue that we shouldn't make the vaccines using the spike. However, how many people would have actually known that the spike was cytotoxic to begin with? We really would have no clue, and so someone may make a comment suggesting that they always knew it was cytotoxic (foresight) rather than finding out the information at the same time many of us did and realizing it was a bad choice (hindsight).

I am definitely not saying Mike Yeadon is doing this, but I should also be frank and say that sometimes this thought crosses my mind when it appears that someone just happened to know all along what is going to happen.

Again, I don't know why Mike Yeadon is saying that. I don't know him, and I actually don't know most people who are in this circle, so I really can't argue if it is through him actually knowing beforehand or if it is something else. Apologies for not being able to give you an actual answer.

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Jul 27, 2022Liked by Modern Discontent

I agree. I don’t think people knew. Many attempts to make a SARS virus were made after 2003, and although the S, N, M and E proteins were studied, mostly it was S antigens and sometimes S,N combos that were taken forward as they elicited greater antibody numbers (which is the first thing you look for, when developing a vaccine). I’m guessing S,N was examined as they knew the spike was mutable and wanted double action? Anyway, all abandoned as led to ADE.

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Well I'll always remember that in June (or maybe late Spring) of 2020 when there was a press briefing on vaccines Fauci made a comment that it would likely take years due to prior animal studies showing ADE. So there was always that concern that kind of was swept under the rug. I'm not sure of the effects of ADE now, but it's rather surprising it's not being looked into extensively.

And from what I've seen it's been the case that it's either the spike or a cocktail of antigens up to the whole virion. It's never just N or just M, likely because they may not provide full neutralization and inhibit the virus.

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Jul 27, 2022Liked by Modern Discontent

It was always my primary concern: that 2-3 years in, when neutralising antibody levels waned, we would be at risk of ADE. They’d never avoided it before, why would they now? And then came the poor durability, slew of other side effects, and me having caught & recovered rapidly from covid.

So it’s a bit fat NO from me.

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I think there's a bit more going on before I can argue that it would lead to ADE since that would require some association with OAS which I'm not convinced on. Animal studies showing ADE for other coronavirus vaccines is concerning, but I'm not aware of this having extensively from natural infection, which suggests that something about the antibodies produced from vaccination are targeting specific regions. But then there's a matter of whether ADE could be overcome by novel immune responses, which then again brings into question OAS. I haven't looked extensively into animal studies and ADE there so I can't make any viable judgements outside of superficial assumptions at the moment.

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My fears were also based on what I know of dengue and RSV vaccines as well.

To be clear, I’ve no evidence this is happening or can still happen - but given I was never concerned that the virus would get me (even less so now I’ve had it), I felt it prudent to wait and see how things panned out as ADE was listed as a potential concern by both regulators and manufacturers. There are multiple mechanisms of ADE and it’s poorly understood, so my view was to wait for long term real world evidence of it not being a concern rather than take a risk for no good reason and have a mild infection become a deadly one.

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Aug 2, 2022Liked by Modern Discontent

I ran into Mike on Joel Smalley's Substack. I raised this question with him and he replied:

https://metatron.substack.com/p/scientific-proof-that-the-mrna-causes/comment/8097429

I reproduce his comment (fixes in square brackets are my own):

"I didn’t read every word as I’m knackered and awake at 4am, but the argument made that antigen can only be spike protein “because it’s the point of attachment” is bogus.

1. It’s not the case that vaccines have to prevent the first step in infection in order to work. In fact, that can’t be right. Your immune response only begins once you’ve been infected, albeit at sub clinical levels (that is, before you’ve been made sick). Infected cells register that fact by displaying on their surfaces pieces of that with which they’ve become infected & this triggers memory (if you’ve immunity).

2. Unless the vaccines induce mucosal immunity, you still couldn’t prevent infection, even with spike as antigen. Mucosal immunity includes secretory IgA. I don’t believe that’s even been looked for in the clinical trials. If correct, why didn’t they look? It’s probably because injected vaccines aren’t a good way to induce mucosal immunity.

3. Once cells are infected by viruses, so goes the narrative adjacent cells can become infected by lateral spreading, and antibodies are far too large to be present in this anatomical location. Alternatively, if infection proceeds by [lytic] destruction of infected cells in the airway, again, circulating IgG antibodies aren’t in airway surface liquid to mop up released pathogen.

4. Apparent immune memory against infection does yield apparent immune responses against spike protein but these are the minority. In aggregate, spike antigens are overwhelmed by numbers of responses to non-spike antigens.

5. If the only potentially viable design of a vaccine was spike, that ends the project. It’s way too dangerous. Those who argue “vaccination with spike protein antigen is the same as infection” are mistaken. Natural infection doesn’t result in persistent circulation of spike protein whereas injecting someone with an uncontrolled gene sequence encoding spike definitely does & was always going to do that. Not faintly similar. An honest research scientist at the point would have argued against proceeding with this project as its fatally flawed. That wouldn’t be a particularly surprising or unusual opinion. We were our own best critics & a large proportion of early ideas were stopped for exactly this kind of reason: we didn’t think we could safely “reduce to practise”.

To the point of dismissing my decades of relevant experience by pretending that vaccine developers understand this & I don’t, is fatuous.

No, this isn’t how ANY previous vaccine works. Therefore, it’s the vaccine designers who are way out on thin ice.

What we’re looking at is drug design, something [I've] spent decades involved in.

Drug design considers multiple factors simultaneously. How to hit the intended target in a way that yields effective treatment. How to assess the risks of unwanted effects. Best options for formulation, for stability, safety & delivering the payload to the intended anatomical target & not everywhere else. Lessons from past toxicity, such as use of lipid nanoparticles homing to ovaries.

Up to you. I can’t make people believe anything. I can only try to explain why what’s being claimed as a Star Trek style breakthrough is actually an act of unequivocal & deliberate harm."

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Thanks for the post. It's true other antigens can be targeted, but if the intent was to stop any infection then why would you target antigens during the infection period? That's the general argument with the spike and why you wouldn't choose other antigens. The other antigens may reduce severe infection, but again I believe the intent was to prevent the infection in the first place. However, this was something that we should have been made aware of would not be possible via the flu vaccines which still allow for infection and transmission. He's right about the mucosal immunity because targeting that would stop the virus at the point of entry, but again the flu vaccines should have pointed us to mucosal immunity not being stimulated unless administered intranasally. I'm not sure if he's factored in the flu vaccine targeting the hemagglutinin antigen alone which has been around for quite some time and if that would be considered myopic.

I do appreciate how dismissive many of these comments end up being (not yours, but many doctors in this field). I've never claimed to be an expert- I'm just trying to piece things together. It'd be more appreciated if people didn't have to resort to appeals by authority when that's what most people have been arguing against when it comes to Fauci, Walensky and the rest of their ilk. Let the work stand on its won without having to talk down to people- if you have the expertise, speak of your expertise and not what expertise you may hold.

When it comes down to it denis don't take everything as the solemn truth- I always ask people to never do that with my work. Look at the information that is presented and piece it together yourself. See where the information makes sense and where it doesn't, and when there's conflicting data try to understand why that may be. In general it's always important to be skeptical and curious. I think there's far too many people take people at their word right now.

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Aug 2, 2022·edited Aug 2, 2022

As you said - how can you prevent the infection in the first place if the virus is respiratory, and the vaccine does not create mucosal / secretory antibodies?

And then: can stopping the virus from entering cells even work? Based on what Yeadon described, this is not even something that happens. What happens is that the virus DOES get into cells - maybe less so if there's spike antibodies, but it does infect cells. The cells then display the various components of the virus, which includes ALL proteins, and the immune system gets to work.

So the vaccines would work better, and less lethally, if they chose several other proteins instead of the spike. It seems to me, if the vaccine designers don't understand this, they must be real rookies at their job. It seems much more likely they are not, and the intent was always what we are seeing: democide with plausible deniability. "Oh, we just made mistakes! It's so complex!"

Any lingering doubts are swept away by how there's no backtracking after visible harm. There's no attempt to do the right thing. There's a continued push for endless injections; including injections for other viruses; at the same time as the CDC ignores VAERS and is tampering with death records.

This, and the global coordination and consistency with which it happens, makes it an open-and-shut case. No honest person does this. It's democide, and it was democide from the start.

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Here's the thing denis, for me I personally did not know any of this until recently. It was only until I looked into vaccination and mucosal immunity that I started to realize how difficult it is to produce mucosal immunity. So my point comes from a hindsight perspective- I didn't know it at the time, and so my position prior to a few months ago was that the vaccine would have provided protection. That's not my perspective now, mostly because I know about the mucosal immunity stuff now.

Now, should the researchers have known this? Yes, but for some reason they didn't measure these. But once again my argument was based on the information we had at the time and my lack of examining mucosal immunity extensively. So when I make my argument I am not suggesting at this moment that intramuscular vaccinations should create mucosal immunity. Many researchers are now looking at intranasal vaccination for that same reason now, but I'm still weary about the possible side effects.

And honestly, I'm not sure what Yeadon is getting at about an infection needing to take place, or maybe it's a misinterpretation. The whole point of circulating anti-spike antibodies is that the antibodies can bind to the spike before it enters into cells. They're essentially surveying the landscape and targeting the virus before most of them can enter into cells. It doesn't mean it's perfect but that's part of the job of these antibodies. That's why we produce tons of antibodies after an infection so that our immune system surveys around in case the virus comes back. It's only after a certain amount of time our body stops producing antibodies because it just becomes wasteful if we are not constantly exposed to the antigen.

I don't think the body actually exposes all of the proteins. Possibly epitopes of the proteins, but again if HLA class 1 antigens present N-protein epitopes, how are T-cells supposed to target these proteins? If they're inside the virus T-cells can't just sneak inside the virion and target the N-proteins. They need to be presented with the antigen in order to target it, in which case the N protein must be expressed within the extracellular space.

However, infected cells that express the N-protein epitopes could be told to commit cell death, but if they're presenting spikes anyways then they would already be told to undergo apoptosis or be engulfed by cells anyways.

There's a lot more nuance to the situation than just saying that we can target other antigens and it will be safer. I would like to know what other antigens Yeadon would target and how he would go about doing so, because for me right now I don't see how targeting any other antigen solely will stop the infection. I suppose we could look at Sinovac and gain insights from them due to using whole virus in their vaccines and see what type of antibodies are produced there.

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The videos of people collapsing in China don't seem to inspire confidence either.

I think the only reasonable conclusion at this time is no injections or "prophylactic" interventions with new drugs - not for Covid, and not for anything whatsoever.

There is ample evidence that vitamin D alone works to prevent severe disease. For doctors who were able to use them, cheap, safe medicines with which we have decades of experience have worked in tens of thousands of patients.

It is fairly obvious that anyone who's trying to push a new intervention for this is a schemer, should be assumed to be guilty, and should just be hanged. My honest opinion.

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Mike Yeadon didn’t work in vaccines. He worked in respiratory medicine. I feel like this is not his area of expertise, although I think very highly of his input in general and believe him to be a honest and courageous person.

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deletedJul 27, 2022Liked by Modern Discontent
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So I can't provide any information in a way of medical advice, but from a mechanistic standpoint I believe it was argued that at least HCQ and Quercetin may be Zinc ionophores. I wrote a series on Quercetin in my Anthology Series.

https://moderndiscontent.substack.com/p/the-quercetin-anthology-series-archives

However I think Quercetin was at least assumed to be an ionophore through in vitro models using constructed membranes, so to the extent in may happen in actual cells may be a bit more tricky to elucidate. I think the best thing to do is just consider your overall health including diet, exercise, and sleep. It's really taking into account all of the factors that matters.

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deletedJul 27, 2022Liked by Modern Discontent
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That's good to hear, aside from reading too much being bad. Considering that most people are not reading enough as is, I think being someone who reads a lot is something that is needed even more these days!

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deletedJul 28, 2022Liked by Modern Discontent
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That's the general impression I get from people and it's perfectly understandable. It's hard to gauge how much science I should include in my posts, but I generally do so with the hope that people may eventually gain the skills and knowledge to piece together that information for themselves.

Micro nutrients are definitely things that should be given more attention because most supplements aren't going to capture putting fruit and vegetables in a bottle, so we could be missing out on plenty of things we should be getting on a daily basis.

Turmeric is considered to be an anti-inflammatory I believe, and so that may be a reason for that, although I haven't looked into it extensively.

Anyways, apologies for the late reply and thank you!

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