The micro-clot finding in Long Covid — implications for the possible aetiology of ME/CFS

Wonko said:
Well.....my response was 'WTF is natto' - I'm 56 (I think) and I've never heard of it.

I did gather that at least one person considers it might be a type of food ;)

It turns out that the reason I've never heard of it, when I have heard of many, many, types of food, is because I'm from the NE of England, which suggests that I'm probably not Japanese, where natto seems to be from.

https://en.wikipedia.org/wiki/Nattō
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Indeed -
I'm in favour of researching anything that improves the health of people who are ill - may turn up something but I'd have thought a disrupted pathway (vitamin K2 or whatever) would have been flagged up in other studies.
 
A couple of recent articles on nattokinase —

Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants (2022)

Nattokinase (NK), known as a potent fibrinolytic and antithrombotic agent, has been shown to have antiatherosclerotic and lipid-lowering effects. However, data on human clinical studies are limited. In this clinical study involving 1,062 participants, our objective was to examine the efficacy of NK in atherosclerosis and hyperlipidemia and safety at the dose of 10,800 FU/day after 12 months of oral administration.

[...]

We found that NK at a dose of 10,800 FU/day effectively managed the progression of atherosclerosis and hyperlipidemia with a significant improvement in the lipid profile. A significant reduction in the thickness of the carotid artery intima-media and the size of the carotid plaque was observed. The improvement rates ranged from 66.5 to 95.4%. NK was found to be ineffective in lowering lipids and suppressing atherosclerosis progression at a dose of 3,600 FU/day.

[...]

The dose of 10,800 FU/day is safe and well tolerated. Some lifestyle factors and the coadministration of vitamin K2 and aspirin lead to improved outcomes in the use of NK. Our findings provide clinical evidence on the effective dose of NK in the management of cardiovascular disease and challenge the recommended dose of 2,000 FU per day.
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Degradative Effect of Nattokinase on Spike Protein of SARS-CoV-2 (2022)

When cell lysates transfected with S protein were incubated with nattokinase, the S protein was degraded in a dose- and time-dependent manner. Immunofluorescence analysis showed that S protein on the cell surface was degraded when nattokinase was added to the culture medium. Thus, our findings suggest that nattokinase exhibits potential for the inhibition of SARS-CoV-2 infection via S protein degradation.
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Andy said:
Prof Kell on Twitter, "To those doing well on nattokinase and/or serrapeptase and/or lumbricase pls can you tell #TeamClots which BRAND and frequencies you use. Just poss that some non-responders are using lousy brands. Can then at least then use those known to work."
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I read that as a request for info from the patient group. He's probably being asked by other patients about what brand is best - doesn't know - so puts it out to the patient group. I am not aware of any related drug trials involving this research team. They have obliquely referenced "nutraceuticals" in some of their publications.

And as Jo says, it is all pretty peculiar. I have observed a parallel, best effort attempt at data gathering by the patients. This is of course financially and technically unsupported and unrigorous (as often highlighted by those posting the data) but this is a new patient group in a dire situation, who are trying to help themselves — when help has not been forthcoming from authorities.

While we've talked about "microclots" in this thread and others, and it is highly unlikely to be the fundamental underpinning of LC (as proposed by this research group), hypercoagulability is very clearly an important feature of this disease (with evidence of involvement in ME too). Even in those without the ME phenotype, a large excess of cardiovascular events is occurring. Pathological amyloid clotting and platelet hyperactivation can explain a hypercoagulable state, despite standard clinical measures of coagulation remaining unhelpfully normal. This should be pursued, and yet funding for formal investigation was rejected.



So almost inevitably, you end up with —

 
SNT Gatchaman said:
He's probably being asked by other patients about what brand is best - doesn't know - so puts it out to the patient group.
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And in doing so endorses the use of this as a treatment. To me this is seriously problematic on an ethical level and something that we have seen before with various people promoting, or seeming to promote, various 'treatments' before there is good evidence that they are safe and actually work.
 
Yes, he could have not amplified, but it seems like a cat-out-of-the-bag situation — and there's no gatekeeping on these agents. People are encouraged by whatever level of evidence is available to them and reinforced whenever anecdotal posts like the following are made (which may of course be natural recovery for many) —


 
We've seen the 'everybody else is talking about it so where's the harm' type of argument before and for people who are in a position of potential influence it should be no defence at all, they should be exhibiting a reasonable amount of self restraint for the good of the patient population that they claim to be concerned for.
 
Swansea Bay Health News: Hospital team discovers why a routine treatment for severe Covid-19 can fail Also posted here.

Professor Evans said: “We have shown that Covid-19 can lead to the formation of an abnormally strong clot despite full anticoagulation treatment in many cases.
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Dr Watson said the research found that patients who died due to Covid-19 or required an admission to ICU had a compromised ability to break down clots compared to patients with a less severe infection.

“This effect can lead to microscopic blood clots forming in organs of the body leading to the multi-organ failure which is the cause of death in many Covid patients,” he said.
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See also this thread
 
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BrightCandle said:
Already published first set of results of this survey on Twitter on Nattokinase brand comparisons and dosage -
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Interesting result. Done and delivered quicker than it would take to sign the paperwork to get preliminary approval for a formal study. Even with dosage. Can't even think of a study that had such stark results.

In the early days, say the first year, of Long Covid, there was a flurry of experimentation with different drugs and Nattokinase is one of the few that stood the test of time, antihistamines being the other. Almost nothing else survived the experiment phase.

Variously I did see the odd mention of psychoactive drugs like SSRIs, but I basically saw all of them mentioned, none stood out, and it seems probably related to immunological processes, which IMO is likely the only relevant mechanism of action for all those drugs. The very name antidepressant is very misleading, a historical blunder.
 
I did a quick search for "herxing" on this site and our colleague site. Just a few hits here, mostly in relation to (feisty) historic discussion about some near-fatalities with the Marshall protocol. Lots of hits on PR. I wonder whether the term "herxing" has been more broadly adopted by patients. Language evolves to suit needs I guess.

A relatively recent review article: The Jarisch–Herxheimer Reaction After Antibiotic Treatment of Spirochetal Infections: A Review of Recent Cases and Our Understanding of Pathogenesis (2017) indicates that the mechanism is not understood, so maybe this effect might have a broader aetiology? It seems like an interesting aspect that would be good to understand more fully in the above context.

The JHR has been variously attributed by authors for more than a century to release of toxins by dying spirochetes, hypersensitivity to spirochetes, removal of dead spirochetes by phagocytic cells, complement activation, DIC, and mediators of inflammation including cytokines and histamine. However, many of these mechanisms are unsupported and probably wrong.
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With the discovery that plasma cytokines rise in the JHR, it was inevitable that an analogy was drawn between the JHR and septic shock caused by other bacteria. The systemic inflammatory response syndrome of sepsis is similar in both conditions. However, the JHR is short lived over several hours, after which patients are improved, rarely die, and cytokines return to pre-JHR levels. Only two patients in this review, both with leptospirosis, required vasopressors for severe hypotension, whereas in septic shock the inflammatory response is more sustained with high case-fatality rates despite the use of vasopressors. Sustained shock in sepsis can be correlated with endothelial cell damage leading to failure of the microcirculation, which does not occur in JHR. Favorable prognosis in the JHR can be explained in part by spirochetes having a nonendotoxin pyrogen that is much less potent and less lethal than endotoxin.
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rvallee said:
Done and delivered quicker than it would take to sign the paperwork to get preliminary approval for a formal study. Even with dosage.
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Social media moves more quickly than established systems for formal trials? Of course it does, that should be no surprise to anybody. And what should not surprise anybody is that a quick Twitter poll, which will be open to all kinds of bias, on the efficacy of an alleged treatment should not be put forward as being as reliable or as worthwhile as a formal study.
 
SNT Gatchaman said:
I did a quick search for "herxing" on this site and our colleague site. Just a few hits here, mostly in relation to (feisty) historic discussion about some near-fatalities with the Marshall protocol. Lots of hits on PR. I wonder whether the term "herxing" has been more broadly adopted by patients. Language evolves to suit needs I guess.

A relatively recent review article: The Jarisch–Herxheimer Reaction After Antibiotic Treatment of Spirochetal Infections: A Review of Recent Cases and Our Understanding of Pathogenesis (2017) indicates that the mechanism is not understood, so maybe this effect might have a broader aetiology? It seems like an interesting aspect that would be good to understand more fully in the above context.
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The term herxing comes from Lyme-patients I think. It's used to describe symptoms flaring from excessive die-off of Lyme-spyrochetes during treatment. As for the scientific basis of all of it I don't know, but I know it's used in that context.
 
rvallee said:
Interesting result. Done and delivered quicker than it would take to sign the paperwork to get preliminary approval for a formal study. Even with dosage. Can't even think of a study that had such stark results.
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They look to me like well within the range of normal fluctuations, especially as it's a self selected sample with no information on length of treatment, what other treatments they are doing, length and severity of disease, and with much too small sample sizes to be statistically significant, no control group, no blinding, subjective outcomes etc. I suspect even CBT could show pretty graphs like this and would be equally misleading.
 
The term herxing has been used for decades by ME/CFS patients. It has been used for every type of response, from taking supplements to medications, social media encourages people to continue the treatments b/c 'something' apparently is 'dying off'.

An immune response if not the same as die-off, in fact it can make you worse.
 
Andy said:
Social media moves more quickly than established systems for formal trials? Of course it does, that should be no surprise to anybody. And what should not surprise anybody is that a quick Twitter poll, which will be open to all kinds of bias, on the efficacy of an alleged treatment should not be put forward as being as reliable or as worthwhile as a formal study.
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Regular academia is capable of moving this quickly, it's pretty much the norm in early stage research. Getting research grants to do RCTs is not supposed to be the first step in research, a problem with chronic illness research is that no one has discretionary budgets they can use for it to do this kind of quick iterative work.

This is hypothesis-generation. It's supposed to be quick. RCTs are supposed to follow much later, when there is a firm hypothesis that deserves to be tested rigorously. This here is supposed to be how it works, we just don't have it, there is not a single tenured professor of chronic illness that can use their own departmental resources to do this kind of work. The pragmatic trial paradigm is basically 99% waste when used to generate hypotheses.

That's the whole issue with NIH and not funding exploratory research. They usually come in long after this preliminary work has been done. We just never had anyone allowed to do it, so here someone is just going ahead and doing it.
 
rvallee said:
This is hypothesis-generation.
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No, it's not. It is encouraging desperate sick people to take something that they think is a treatment, and to report back in order to influence other people as to what the 'right' dose is. It's unethical and dangerous. We've seen it before with various 'cures', and no doubt will see it again, but let's not try to paint it as something it isn't.
 
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