#1604

I would like to see more research being done on Desmosterol and what else lowers/raises it.

#1605

I’m not sure what failed trial this was. If for Covid-19 or lowering HsCRP in Covid-19, not an issue, as I’ve never had it on my list of things to do for Covid-19.

The discussion in an AHA Journal has a reasonable take on it in the context of those with CAD or even theoretically for those with need for primary prevention of CAD - it looks like a reasonable thing to be on, so long as no side/adverse effects.

The article goes through a nice history of colchicine and concludes “Colchicine lowers hsCRP and may decrease coronary artery plaque volume.”

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#1606

I’ve been taking colchicine for a couple of years too based on that original study. I haven’t noticed any bad side effects and like you I think minimising inflammation is a good thing especially in respect of potential plaque build up.

Having said that it’s always good to keep an eye on possible interactions. For example I have temporarily stopped colchicine while on a course of Azithromycin as there appeared to be potential interactions.

1 Like
#1607

Well in fact LL-37 might not be a good choice for COVID even though it binds to the spike protein as it’s implicated in thrombotic complications:
Role of LL-37 in thrombotic complications in patients with COVID-19

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#1608

If I had an active COVID infection, I would think twice about using LL 37, if I was young. Typically as we age we produce less of the beneficial things. Although during any type of infection your body will produce more LL 37 than when you are not experiencing an infection response.

Due to how the body produces LL 37, it does increase during a Covid (any) infection. Because that is how it works. But as this paper indicates it MAY increase the potential for hypercoagulation DURING the infection.

Also Vit D increases or supports your natural production of LL 37 and yet Vit D is highly recommended as something that combats Covid. Maybe this is why Vit D is beneficial?

My simple thought process with this one is to use it prophylactically in an attempt to eliminate residual virus and bacterial and fungal infections that are known to “hide” and stay resident, while modifying our immune system so they go unmolested by the immune system.

Everyone (ok an exaggeration only 90%) on the planet have EBV present in their system. EBV is a know cause of 7 cancers. Staph infections are common and staph also modifies your immune system so it can stay resident, while making you less resistant to re-infection. Same for fungal infections. They all modify our immune system. My “hope” is that if LL 37 would eliminate these resident bugs my immune system, with the help of our modified TRIIM protocol and use of TA-1 will restore more functionality to my immune system.

I’m not “sick” with an infection, even though I have had a low level infection for about 2 years, it’s now gone after 2 weeks of LL 37 use.

These results suggest that cathelicidin antimicrobial peptide LL-37 is elevated during SARS-CoV-2 infection, which may induce hypercoagulation in COVID-19 patients by activating coagulation factors.

Our body responds to infections by producing more LL 37 and if not enough is produced an active infection can become worse.

At neutral pH, LL-37 is a cationic peptide with a net charge of + 6. In addition to its antibacterial properties, LL-37 has also antiviral properties, and lower LL-37 serum levels are associated with severity of illness and length of hospital stay.

https://www.nature.com/articles/s41598-022-13260-8

Upregulating Human Cathelicidin Antimicrobial Peptide LL-37 Expression May Prevent Severe COVID-19 Inflammatory Responses and Reduce Microthrombosis

Human antimicrobial peptide inactivation mechanism of enveloped viruses

https://www.sciencedirect.com/science/article/pii/S0021979723021744

Even in the very young LL 37 levels matter

Conclusions

In a large multicenter study of infants hospitalized with bronchiolitis, lower levels of serum LL-37 were associated with increased severity of illness. There was also an inverse relationship between LL-37 levels and the most common virus causing bronchiolitis, RSV. These findings highlight the role of LL-37 in the pathogenesis of bronchiolitis.

https://academic.oup.com/cid/article/65/6/967/3851790

2 Likes
#1609

I agree the use of LL-37 prophylactically seems useful.
That said it seems it’s not a clear case for acute COVID. There are also several paper on the role of LL-37 in atherosclerosis so it seems like a complicated case. Too little of it is bad but too much too for other reasons.
On the other hand thymosin alpha 1 seems to have mostly (only?) positive effects.

1 Like
#1610

Interesting. I heard of LL-37 in 2020 as a gut health peptide and went through a couple vials of it. Didn’t think for a second it might not have been safe. I can’t say I noticed anything from it subjectively.

#1611

Looks like there are plenty of papers on the role of LL-37 in atherosclerosis.
As I have severe CAD it’s probably not good for me.

Here are some AI searches:

LL-37, a human antimicrobial peptide, plays a complex role in atherosclerosis, primarily acting as an immune modulator that can promote inflammation and plaque development within the arteries by activating immune cells, enhancing adhesion molecule expression, and facilitating the recruitment of inflammatory cells to the atherosclerotic lesion site; however, research also suggests potential protective aspects depending on the context and level of LL-37 expression.

Key points about LL-37 and atherosclerosis:

  • Pro-inflammatory effects:

    • Immune cell activation: LL-37 can stimulate immune cells like neutrophils and macrophages, contributing to the inflammatory response within the arterial wall.
    • Endothelial cell activation: It can activate endothelial cells, leading to increased expression of adhesion molecules like ICAM-1, which further facilitates inflammatory cell recruitment to the plaque.
    • Neutrophil extracellular traps (NETs): LL-37 is a component of NETs, structures released by activated neutrophils that can contribute to thrombus formation and plaque instability.
    • Activation of Immune Pathways: LL-37 has been shown to interact with pattern recognition receptors (like toll-like receptors), potentially amplifying inflammatory signaling pathways. This could exacerbate local inflammation within plaques.

  • Plaque formation:

    • LDL uptake by macrophages: Studies suggest LL-37 may promote the uptake of LDL (low-density lipoprotein) by macrophages, contributing to the formation of foam cells, a key component of atherosclerotic plaque.
    • Mitochondrial DNA complex: Research has shown that LL-37 can form complexes with mitochondrial DNA, which can further enhance inflammatory responses and plaque development.

  • Impact on Plaque Stability:

    • Matrix Remodeling: Some evidence suggests that LL-37 may influence the behavior of vascular smooth muscle cells and the composition of the extracellular matrix. Changes in these parameters can affect plaque stability, with unstable plaques being more prone to rupture—a critical event leading to acute cardiovascular events.
    • Dual-Edged Regulation: In some contexts, the pro-inflammatory and remodeling actions of LL-37 might tip the balance toward plaque progression or destabilization, although this remains an area of active research.

  • Potential protective aspects:

    • Antimicrobial activity: While not the primary function in atherosclerosis, LL-37’s antimicrobial properties could potentially protect against infections within the plaque.
    • Wound healing: Some studies suggest LL-37 might play a role in vascular repair and re-epithelialization, potentially limiting plaque progression under certain conditions.
    • Anti-inflammatory Effects: In some settings, LL-37 can help modulate the inflammatory response. By influencing cytokine production and immune cell activation, it may promote a more controlled inflammatory environment, which is important for tissue repair and maintaining vascular health.
    • Promotion of Resolution: LL-37 has been reported in certain studies to help resolve inflammation by encouraging the clearance of pathogens and damaged cells, which might limit chronic inflammatory stimulation within the arterial wall.

Important considerations:

  • Disease stage:
    The role of LL-37 may vary depending on the stage of atherosclerosis, with higher levels potentially contributing to plaque progression in advanced stages.
1 Like
#1612

Sometimes looking at one thing in isolation doesn’t always provide the clearest path forward. Endogenous LL 37 is involved in a lot of processes. Just because it is present in a harmful process doesn’t mean it is doing the actual harm itself. If the other contributors are not present it may not have a negative effect.

Note the green arrow on the left under “Thrombosis”, that high dose appears to be beneficial. But under atherosclerosis Low dose is benefical.

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What we need to think about is that in specific studies targeting different pathological factors, we can well reveal the pharmacological effects of LL-37. However, cardiovascular disease is the result of multiple factors and multiple pathological processes, and a single pathological factor is not enough to truly simulate the disease.

https://www.sciencedirect.com/science/article/pii/S1043661824004742#sec0065

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#1613

Can’t disagree with that :slight_smile:

Keep in mind you are producing LL 37 as we speak. And anytime you have an infection, viral, bacterial, fungal, your immune system will produce more in response.

#1614

An example of 2 things coming together for harm. If you have low LDL would LL 37 still be an issue? it is a pretty complex group of interactions.

Good discussion, got me thinking about how I’m going to use this peptide going forward. Will use it for acute issues, may cut back a bit on timing for my prophylactic endeavour.

Since I’ve seen and experienced a significantly positive benefit in 2 instances, I can see the “good” side, now to decide on how to avoid the “bad” side :slight_smile:

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#1615

Good discussion indeed. Looks like LL-37 is a complex topic. It’s a little bit like rapamycin, the dose and frequency probably make whole the difference but it’s even less studied than rapamycin.

Sticking to Paxlovid and Thymosin Alpha 1 for my current acute COVID :slight_smile:

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#1616

“For total cholesterol and iron, higher levels increased the odds … of becoming a centenarian.”

Beautiful! :hugs::egg::drooling_face::cow:

#1617

Yes.

But it’s s only cohort study so you have to take it with a pinch of salt.
that may be just because anaemics, alcoholics, cancer patients and people liver disease can have extremely low total cholesterol for example.

3 Likes
#1618

or part of the good from Rapamycin is that it increases lipid levels. the mice lived so long because nobody gave them statins.

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#1619

Mice don’t die of heart attacks. Humans do.

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#1620

Is that because they die of cancer first?

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#1621

Yes. An almost exclusive majority of mice die of cancer. I’ve never heard of a mouse having a heart attack.

Except the ones that meet a boa constrictor in a dark alley. :wink:

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#1622

There is, however, here an issue of animal welfare. Mice will often be euthanised if they seem to have a really bad cancer. Hence if you are taking university animal studies the actual cause of death may in fact be euthanasia.

#1623

Yes. Euthanasia due to cancer is still considered death by cancer in studies (I believe).

1 Like