NLRP3 Inflammasome Cause Of Male Pattern Baldness

[Ras]

Inhibiting NLrp3 is one step. But the main reason hair cant grow back is calcifcation / fibrosis. SO you have to fix both problems at once.
You guys should try red clover or sheep sorrel. It might be all you need.

Do you need the sheep sorrel root, or can you use just the rest of the plant?

 

[Kenny]

Inhibiting NLrp3 is one step. But the main reason hair cant grow back is calcifcation / fibrosis. SO you have to fix both problems at once.
You guys should try red clover or sheep sorrel. It might be all you need.

Have any before after a backing this theory? I would love to some! It feels like the only people who ever have evidence are people on fin/min

 

[LeeLemonoil]

This is once again about Alopecia A. but the mechanism sounds like some aspects might be valid in mpb too

Double-stranded RNA induces inflammation via the NF-κB pathway and inflammasome activation in the outer root sheath cells of hair follicles - PubMed

Alopecia areata (AA), a chronic, relapsing, hair-loss disorder, is considered to be a T cell-mediated autoimmune disease. It affects approximately 1.7% of the population, but its precise pathogenesis remains to be elucidated. Despite the recent attention focused on the roles of inflammasomes in...

pubmed.ncbi.nlm.nih.gov

 

[LeeLemonoil]

Here is a review from 2029 listing substances thst both inhibit nlrp3 and alleviates fibrosis.
Quite some previously undisscused substances in mpb context but Quercetin once again is among it

Natural Products that Target the NLRP3 Inflammasome to Treat Fibrosis - PubMed

Fibrosis is a common pathway followed by different organs after injury, and it can lead to parenchymal scarring, cellular dysfunction, and even organ failure. The NLRP3 inflammasome is a multiprotein complex composed of the sensor molecule NLRP3, the adaptor apoptosis-associated speck-like...

pubmed.ncbi.nlm.nih.gov

 

[Inaut]

@LeeLemonoil Thanks. MSM would be a good supplement as well

 

[Ras]

Here is a review from 2029 listing substances thst both inhibit nlrp3 and alleviates fibrosis.
Quite some previously undisscused substances in mpb context but Quercetin once again is among it

Natural Products that Target the NLRP3 Inflammasome to Treat Fibrosis - PubMed

Fibrosis is a common pathway followed by different organs after injury, and it can lead to parenchymal scarring, cellular dysfunction, and even organ failure. The NLRP3 inflammasome is a multiprotein complex composed of the sensor molecule NLRP3, the adaptor apoptosis-associated speck-like...

pubmed.ncbi.nlm.nih.gov

2029, and they still haven't found the cure...

 

[keytothecity]

corticosteroid link to @ChemHead regrowth story on fin?


this drug reliably regrows existing hair to maximum density within days:

Curis, P&g, And The Lost Baldness Cure​

there are pics in this thread. regrowth in temples. 100% of users seem to have gotten some regrowth (in days to weeks)

problem is it reliably causes cancer.


one guy in the thread posted this study:
Identification of select glucocorticoids as Smoothened agonists: Potential utility for regenerative medicine

several glucocorticoids are smo agonists


maybe this is the fin mechanism (also regrowing hair in days in some)

Oral Steroid Made My Hair Grow Back Thicker!

Hey everybody, first time poster here. Felt the need to share this in the hope that somebody will give me an explanation. There's a lot more to this story but I'll make it brief and straight to the point. For the past 7 weeks I've been taking an oral steroid called Anavar (Oxandrolone) Over...

www.hairlosstalk.com

-->

One of the reasons why I strongly believe the steroid increased by finasteride may be a mineralocorticoid over a glucocorticoid is because mineralocorticoids regulate salt and fluid retention. When my hair gets thicker from finasteride, most of the thickening occurs in a pretty short time frame... I'm talking like inside of a week. It also transitions from thick to thin, dry, and falling out very rapidly... Like days. What could cause hair to increase and decrease in thickness that quickly? Surely, it can't be that the hair has created new proteins and then lost those proteins only days later. That wouldn't make sense. But what would make sense is that they swelled up due to fluid retention, from possibly a mineralocorticoid, and then rapidly deflated after that mineralocorticoid decreased back to it's normal deficient concentration. There's a lot of speculation on my part here, but everything I've discovered through experimentation currently leads me in this direction.

maybe this is what baldies hormonally lack, and what you don't get by fixing thyroid/inflammation.
the question is which corticoid does that through smo agonism and can we get it without getting cancer

is smoothened receptor agonism the missing link here?

 

[LeeLemonoil]

Yes @keytothecity, therein lies another clue to why mpb even exists. The interplay of corticoid and androgen signaling and conserved mechanisms to prevent specific oncogenic alterations.

That’s why it’s so tricky, messy and dangerous going down to the hedgehog.

I think it’s feasible that once the inflammatory and immunometabolic environment in mpb follicles are modulated to a more functional state, then it might be possible to recreate hairgrowth via that pathway without provoking cancer.

On the other hand, that might be a fallacy: to assume that what is going on in functional tissue is valid in a fundamentally altered „programming“ of sorts.

I think it is too complex to judge with the current knowledge.


From a current review:

„Hedgehog signaling pathway originally identified in the fruit fly Drosophila is an evolutionarily conserved signaling mechanism with crucial roles in embryogenesis, growth and patterning. It exerts its biological effect through a signaling mechanism that terminates at glioma-associated oncogene (GLI) transcription factors which alternate between activator and repressor forms and mediate various responses. The important components of the pathway include the hedgehog ligands (SHH), the Patched (PTCH) receptor, Smoothened (SMO), Suppressor of Fused (SuFu) and GLI transcription factors. Activating or inactivating mutations in key genes cause uncontrolled activation of the pathway in a ligand independent manner. The ligand-dependent aberrant activation of the hedgehog pathway causing overexpression of hedgehog pathway components and its target genes occurs in autocrine as well as paracrine fashion. In adults, aberrant activation of hedgehog signaling has been linked to birth defects and multiple solid cancers. In this review, we assimilate data from recent studies to understand the mechanism of functioning of the hedgehog signaling pathway, role in cancer, its association in various solid malignancies and the current strategies being used to target this pathway for cancer treatment“


So. even if the pathway isn’t deranged by mutations messing around with ligands is unpredictable and potentially dangerous.
Some single corticoid could possibly do a lot of things on it, as the trials you mentioned showed, including causing both cancer and hairgrowth at the same time.
Maybe even Chemheads transient hairgrowth caused oncogenic proceedings. Unknown, but possible.

Best thing to search the web for info on physiological ligands of the pathway and look if a connection to mpb can be found

 

[keytothecity]

so basically eat a veggie diet with lots of garlic, onion + add dairy + green tea + isoflavones for estrogen

I am doing this (minus the isoflavones for now) following @hunchoz and @ChemHead (sort of, he is completely vegan) for 3 days now. TONS of raw veggies all day. Some fruit. 1 L Milk with several cups of green/black tea/day, 1 cup of coffee, one raw egg a day. Will be adding bone broth starting tomorrow.

My energy is skyrocketing, my skin got better, pores smaller. I look younger already. My guess is that inflammation is getting eradicated and excess DHT removed, acidity getting balanced too. I'll definitely keep going for a lot longer, just for the energy benefits already. Possibly, I'll try the isoflavones later. I'm loving it. But I am also an active person normally, so IDK if it will be sustainable when I do more sports again. Thinking of adding potatoes if this is going to be the case.

I'll add some iodine starting tomorrow to counter the anti thyroid fluoride in the green tea.

I am taking D, K, E but not sure if this is good or bad.

It also took fin a decade ago, so like in chemheads case my energy improvement might come down to dodging autoimmune triggers associated with PFS

 

[keytothecity]

Oral Steroid Made My Hair Grow Back Thicker!

Water going up into the hair shaft and making it thicker is an absolutely bonkers proposition. You're making too many generalizations, which is exactly why no one gets anywhere in the hair loss industry. Water making the hair shaft thicker is absolutely not bonkers unless you're also willing to...

www.hairlosstalk.com

new chemhead replies, dare I say they are interesting

he also started replying here

Dealing with accutane hairloss (help) (suicidal)

I would agree with this but the problem is that I’ve run into a few people with accutane hair loss. And it’s the same thing, diffuse loss with curlier hair. Dry and different textured hair. And an inflamed scalp sometimes. Plus there’s not much family history of early balding. If it was really...

www.hairlosstalk.com

@LeeLemonoil
@GorillaHead

 

[GenericName86]

Have you still going to try applying topical estrogen @keytothecity?

 

[keytothecity]

Have you still going to try applying topical estrogen @keytothecity?

No. Chemhead seems to think its useless. You need feminization from it. Chemhead explained the mechanism read it

 

[LeeLemonoil]

Thanks @keytothecity

 

[keytothecity]

Thanks @keytothecity

Thoughts on the newer chemhead passages? I’m still on his diet and feeling good. Better skin, better energy, deeper voice. Worse temps.

 

[LeeLemonoil]

Thoughts on the newer chemhead passages? I’m still on his diet and feeling good. Better skin, better energy, deeper voice. Worse temps.

Not read them yet. I will.

 

[LeeLemonoil]

Topical Melatonin for Treatment of Androgenetic Alopecia

In the search for alternative agents to oral finasteride and topical minoxidil for the treatment of androgenetic alopecia (AGA), melatonin, a potent antioxidant and growth modulator, was identified as a promising candidate based on in vitro and in vivo ...

www.ncbi.nlm.nih.gov

 

[334c]

Topical Melatonin for Treatment of Androgenetic Alopecia

In the search for alternative agents to oral finasteride and topical minoxidil for the treatment of androgenetic alopecia (AGA), melatonin, a potent antioxidant and growth modulator, was identified as a promising candidate based on in vitro and in vivo ...

www.ncbi.nlm.nih.gov

probs worth a shot

 

[keytothecity]

a dermatologist once told me of a patient who swore by topical melatonin as an alternative to mainstream pharmaceuticals. probs worth a shot

also read that circardian rhytm influences t:epitesterone. whether that would be further connected to melatonin idk

 

[ChemHead]

Thoughts on the newer chemhead passages? I’m still on his diet and feeling good. Better skin, better energy, deeper voice. Worse temps.

Low temperature is something I kind of deal with on a regular basis. Part of it is genetic and the other part is the nature of my diet. I'm specifically eating a pretty low calorie diet for the time being and I've often "fasted" for 14-18 hours daily. The longer I go without eating, the lower my body temperature drops and although I feel this is a good thing for overall longevity, it gets uncomfortable. This is also why I tend to save longer term fasts for the summer.. because it's easier to tolerate the lowered body temperature.

Regarding the genetic aspect of my low temperature: based on experimentation and observation over my lifetime, I believe that I have a naturally low expression of aromatase and/or low estrogen receptor expression. It doesn't matter whether it's one or the other or both. What's important is that within various tissues (including hair follicles) my overall estrogenic activity is lower relative to what would probably be considered normal (if we had an effective way of measuring it). This doesn't necessarily mean that serum estrogen concentrations would show up low. It just means that in most tissues that synthesize their own estrogens, the estrogenic activity is low relative to most people.

Now, why this is important is because when I've gone through periods of short-term elevated serum estrogens, my body temperature is elevated and at a much more comfortable (and, I would suspect, "normal" for most people) level. I don't know exactly what the mechanism is behind this, however. I'm not sure if it's increased vascular estrogenic activity or if the increased estrogenic activity is having some effect on the sympathetic nervous system that is affecting vasodilation at the core and, more importantly (in my case), at the extremities. Higher estrogenic activity, though, improves my thermogenesis.

I should probably also clarify that when I talk about body temperature, I'm not referring to measured temperature, but more qualitative feeling throughout the body. However, when I fast, my body temperature quite noticeably drops when measured. I would actually say that if your body temperature measured by thermometer is normal, but your extremities are cold, then you could maybe consider your body temperature low... because obviously if your extremities are cold, your body has decided that it needs to restrict blood flow to those extremities because it is unable to cope with the energy loss through heat if it were to allow blood to flow at a rate which would keep the extremities warm. I have a feeling that Raynaud's syndrome could be related to insufficient estrogenic activity.

Regarding the better skin, energy, and deeper voice: you're body is likely increasing steroid synthesis as these can all be directly attributed to this. The reason why you're able to increase steroid synthesis, however, is likely due to a decrease in serum estrogens and also just, generally, your body's ability to operate properly due to having better nutrition and less inflammation that it has to waste its energy handling. The higher your energetic burden, the less energy your body will have to use in biochemical processes. And inflammation is something your body must deal with... it can't just ignore it. So, if you decrease inflammatory burden, you free up some energy that can be used in bodily repair and maintenance. This is especially significant for any chronic source of inflammation. Your body not only doesn't need to handle the inflammation, but it no longer needs the biochemical "tools" or proteins that it is accustomed to producing in order to neutralize the chronic inflammation. So, after some time, it just stops making them.

Now, lower serum estrogens means that the hypothalamus can signal a command to increase steroid synthesis. Estrogenic activity within the hypothalamus is somewhat of a gatekeeper for steroid synthesis, which is why it is targeted by SERMs like Tamoxifen or Clomifene citrate as a way to trick the hypothalamus into signaling a call for higher LH and FSH from the pituitary.

So, by having lowered serum estrogens (or at least lowered estrogenic activity at the hypothalamus), we get a call for higher steroid synthesis and, in my opinion, I believe we also possibly get an upregulation of aromatase and/or estrogen receptor expression (because higher androgenic activity with upregulate estrogenic activity). So, being healthier allows your body to command higher estrogen synthesis from tissues.

People like to generalize and say high estrogen = bad and high testosterone = good, but it's not quite that simple. Yes, a "high" serum concentration of estrogens is bad, but only because it actually reduces your overall estrogen synthesis within tissues. I think the ideal model is that you want your tissues (hair follicles, skin, vascular tissue, muscle tissue, joint tissue, etc.) to synthesize as much estrogen as they're capable of (as well as other autocrine steroids... DHT is another example) and then the serum concentration of those steroids that is measured ends up being the result of whatever small leakage of those steroids occurs from tissues into serum. Steroids like estrogens and metabolites of testosterone are specialized steroids that belong in the tissues they're synthesized in... which is why they're generally very low in concentration relative to steroids like testosterone, DHEA, etc.

The optimal state, in my opinion, is where the body is producing high amounts of these specialized steroids only in the tissues where they belong and when the tissues are finished with them, they are (ideally) metabolized further and prepared to be safely eliminated. How steroids like estrogens end up in high concentrations in serum is something I've not really looked into, but it's something I'd be interested in exploring further. Obviously, conditions like having an excess of fat tissue will cause an excess of serum estrogens (and apparently vice versa, which can produce a vicious circular feedback loop), but I'm not sure of the actual mechanism of the estrogens ending up in serum since I've not really researched this.

 

[LeeLemonoil]

@ChemHead

Very interesting read, thanks!