How prolactin causes hair loss

[Mauritio]

I believe that gut health strongly influences hair loss, but I hesitate in believing it is the cause. If gut stimulated inflammation and prolactin release caused hair loss, it feels likely that this hair loss would be occurring everywhere on the body. But that doesn’t seem to be the case for most balding or hair loss. So, to me, there has to be a factor that is specific to the scalp, or head region which is causing or accelerating the damage caused by this gut hormone axis. The local prolactin receptor expression being stimulated by interferon gamma is a clue to the local process occurring, which to me indicates that the immune system is fighting something in the scalp. Now, I don’t think the solution to this is necessarily throwing every anti microbial at it, but I do think investigating why the scalp in balding men is supporting this growth might have promise.

Microbiome in the hair follicle of androgenetic alopecia patients

Androgenetic alopecia is the most common form of hair loss in males. It is a multifactorial condition involving genetic predisposition and hormonal changes. The role of microflora during hair loss remains to be understood. We therefore analyzed the microbiome ...

www.ncbi.nlm.nih.gov

The Potential Relevance of the Microbiome to Hair Physiology and Regeneration: The Emerging Role of Metagenomics

Human skin and hair follicles are recognized sites of microbial colonization. These microbiota help regulate host immune mechanisms via an interplay between microbes and immune cells, influencing homeostasis and inflammation. Bacteria affect immune responses ...

www.ncbi.nlm.nih.gov

Yeah good point. But then again the flora on the scalp is probably influenced by the gut flora, so it might start there too.

 

[golder]

I believe that gut health strongly influences hair loss, but I hesitate in believing it is the cause. If gut stimulated inflammation and prolactin release caused hair loss, it feels likely that this hair loss would be occurring everywhere on the body. But that doesn’t seem to be the case for most balding or hair loss. So, to me, there has to be a factor that is specific to the scalp, or head region which is causing or accelerating the damage caused by this gut hormone axis. The local prolactin receptor expression being stimulated by interferon gamma is a clue to the local process occurring, which to me indicates that the immune system is fighting something in the scalp. Now, I don’t think the solution to this is necessarily throwing every anti microbial at it, but I do think investigating why the scalp in balding men is supporting this growth might have promise.

Microbiome in the hair follicle of androgenetic alopecia patients

Androgenetic alopecia is the most common form of hair loss in males. It is a multifactorial condition involving genetic predisposition and hormonal changes. The role of microflora during hair loss remains to be understood. We therefore analyzed the microbiome ...

www.ncbi.nlm.nih.gov

The Potential Relevance of the Microbiome to Hair Physiology and Regeneration: The Emerging Role of Metagenomics

Human skin and hair follicles are recognized sites of microbial colonization. These microbiota help regulate host immune mechanisms via an interplay between microbes and immune cells, influencing homeostasis and inflammation. Bacteria affect immune responses ...

www.ncbi.nlm.nih.gov

Jamsey and others, what are your thoughts on applying ‘Hypochlorous Acid’ to the scalp?

 

[Mauritio]

Jamsey and others, what are your thoughts on applying ‘Hypochlorous Acid’ to the scalp?

Sounds very acidic and irritating to the scalp .

 

[Ismail]

I noticed that taking black cumin seeds is very effective for decreasing my hair loss. I use mostly the seeds but today I tried the oil directly on my hair and it makes it really soft too.
I also used the excess oil on my face and my skin is insanely smooth now. It increases tanning / melanin (Nigella sativa seed extract and its bioactive compound thymoquinone: the new melanogens causing hyperpigmentation in the wall lizard melanophores - PubMed)

Black cumin seems to lower prolactin quite effectively, almost as good as bromocriptine in this study!
View attachment 50668

- https://www.veterinarypaper.com/pdf/2018/vol3issue4/PartA/3-3-11-284.pdf

Hey buddy, long time no speak, hope all is well

How long have you been taking the seeds? Do you crush them first? Or chew?

How much do you take of the seeds?

 

[jondoeuk]

Yeah I had heard it was PGE2 that was good, which is why some people ingest castor oil for hair growth.

I don't know about the data, but do know a trial tested latanoprost https://www.jaad.org/article/S0190-9622(11)00601-3/fulltext

Also, cetirizine, which decreases PGD2 production https://www.tandfonline.com/doi/abs/10.1080/09546634.2017.1341610

 

[Mauritio]

Hey buddy, long time no speak, hope all is well

How long have you been taking the seeds? Do you crush them first? Or chew?

How much do you take of the seeds?

Hey,
glad youre still around , hope youre doing well :)
Ive been taking them for like 3-4 weeks but only like twice per week, because they do make me a little anhedonic/ too relaxed, but now I'm combining them with something dopaminergic like selegiline or phenylpiracetam and that works better.
I take between a fourth and half a teaspoon and chew them really throrougly for about 2 minutes until I get that chracteristic taste in my mouth (if you do that you will know what i mean, not exactly tasty), somtimes i take a bit of honey with it for the taste.
Whats cool is that this is really cheap and cant be banned or regualated since its a spice, I got a bag of it for 2 euros in the supermarket.

 

[supercoolguy]

Since the 1970s, aspirin has been thought of as an inhibitor of prostaglandin synthesis, but that is only part of its effect. Sometimes its effect is the opposite of the effects of other prostaglandin inhibitors.


It protects against the harmful effects of estrogen, prolactin, serotonin, cortisol, histamine, and radiation (u.v., x-rays, gamma rays).

Aspirin, brain, and cancer

 

[Mauritio]

Since the 1970s, aspirin has been thought of as an inhibitor of prostaglandin synthesis, but that is only part of its effect. Sometimes its effect is the opposite of the effects of other prostaglandin inhibitors.


It protects against the harmful effects of estrogen, prolactin, serotonin, cortisol, histamine, and radiation (u.v., x-rays, gamma rays).

Aspirin, brain, and cancer

In my experience aspirin doesn't help with hair loss...

 

[Ismail]

Hey,
glad youre still around , hope youre doing well :)
Ive been taking them for like 3-4 weeks but only like twice per week, because they do make me a little anhedonic/ too relaxed, but now I'm combining them with something dopaminergic like selegiline or phenylpiracetam and that works better.
I take between a fourth and half a teaspoon and chew them really throrougly for about 2 minutes until I get that chracteristic taste in my mouth (if you do that you will know what i mean, not exactly tasty), somtimes i take a bit of honey with it for the taste.
Whats cool is that this is really cheap and cant be banned or regualated since its a spice, I got a bag of it for 2 euros in the supermarket.

Thanks buddy, appreciate the kind words, genuinely nice to see you around still.

I was also doing this, ie chewing them etc., but it would give me an uncomfortable feeling in the back of my throat that would linger for the whole day - as if I’ve got an oncoming cold.

I ended up putting a large batch through a spice blender and making them into a powder and then encapsulating them.

Ran out of them, need to buy some more and continue - felt intangibly good, also felt as if my self diagnosed fatty liver was getting better (subjectively assessed through skin condition).

 

[supercoolguy]

In my experience aspirin doesn't help with hair loss...

Then prolactin may not be an issue.

Why hasn't MPB been resolved even by mainstream science?
I hear something promising, and then Never hear about it Again.

 

[ddjd]

Anyone know if NAC/, GLUTATHIONE increases or decreases prolactin??

 

[Mauritio]

Thanks buddy, appreciate the kind words, genuinely nice to see you around still.

I was also doing this, ie chewing them etc., but it would give me an uncomfortable feeling in the back of my throat that would linger for the whole day - as if I’ve got an oncoming cold.

I ended up putting a large batch through a spice blender and making them into a powder and then encapsulating them.

Ran out of them, need to buy some more and continue - felt intangibly good, also felt as if my self diagnosed fatty liver was getting better (subjectively assessed through skin condition).

I also felt a little sick today ,hopefully it's not related .
One thing is certain, it has strong anti-microbial effects, so there might be some die off.

There's tons of studies on black cumin and liver benefits, so it could certainly be !

 

[jondoeuk]

Then prolactin may not be an issue.

Why hasn't MPB been resolved even by mainstream science?
I hear something promising, and then Never hear about it Again.

Far more is known about the cascade than before, with multiple drugs in development. However, most still fail when tested in humans. The best we can hope for over the next few years is that pyrilutamide is successful in the pivotal trial ongoing in China. Even more promising is GT20029


View: https://www.youtube.com/watch?v=mNNp_084wWQ&ab_channel=Haircafe

 

[ivy]

I hate to break the news to you guys, but the new drug might just be thyroid.

For those of you who missed it,

HairDAO and Ralf Paus' latest research project

I came across this website and was thrilled to see that Paus continues to research thyroid hormones and hair, and aims at producing topical t3 and t4 products, if toxicity is ruled out: https://www.hairdao.xyz/ Study details: View...

raypeatforum.com

 

[Jamsey]

Anyone know if NAC/, GLUTATHIONE increases or decreases prolactin??

Most likely decreases as dopamine is the main prolactin lowering neurotransmitter

N-acetylcysteine enhances production of dopaminergic neurons from mesencephalic-derived precursor cells - PubMed

Epidermal growth-factor-responsive rat mesencephalic precursor cells incubated in differentiation media produce only a small number of dopaminergic (DA) cells. Supplementation of the differentiation medium with N-acetylcysteine (NAC) induced a marked increase (approximately 400%) in the number...

pubmed.ncbi.nlm.nih.gov

 

[VitoScaletta]

Very interesting. I had a suspicion that prolactin was a significant co-factor in regards to hair loss based on what I read on this forum and other places online over the years.

 

[Jamsey]

Jamsey and others, what are your thoughts on applying ‘Hypochlorous Acid’ to the scalp?

Could be interesting to test. It seems like it should be fairly hair/skin safe and it’s active against cutibacterium acnes.

Topical Hypochlorite and Skin Acidification Improves Erythroderma of Omenn Syndrome - PubMed

We describe a case of Omenn syndrome displaying exudative erythroderma and other characteristic features, including alopecia, absent B and naïve T cells, hyper immunoglobulin E levels, and eosinophilia. A pathogenic recombination-activating <i>RAG1</i> homozygous genetic mutation confirmed the...

pubmed.ncbi.nlm.nih.gov

JCI - Topical hypochlorite ameliorates NF-κB–mediated skin diseases in mice

www.jci.org

https://californiahairsurgeon.com/wp-content/uploads/surgihealpro_forum_article_01_2021-1.pdf

An Integrated HOCl-Producing E-Scaffold Is Active against Monomicrobial and Polymicrobial Biofilms

Oxidizing agents like hypochlorous acid (HOCl) have antimicrobial activity. We developed an integrated electrochemical scaffold, or e-scaffold, that delivers a continuous low dose of HOCl aimed at targeting microbial biofilms without exceeding concentrations ...

www.ncbi.nlm.nih.gov

HOCl (Hypochlorous Acid) SPRAYS are the best thing I’ve tried lately *knock on wood* (Newsletter No. 23) — KRISTY LIN

Long marketed mainly for postoperative care, piercing care, blepharitis, burn treatment and as a safe cleaning solution for the home and hospitals (i.e. more health than beauty), hypochlorous acid HOCl has recently been rebranded as a hip cure that is in line with the current stage of the Into The

www.kristylin.com

 

[Jamsey]

More reading from mr Travis

Interferon-γ is released by T cells in response to foreign proteins, be they allergenic food proteins or those from an invading pathogen. This is likely the most powerful cytokine, on the same tier as interleukin-1 and TNF-α. Interferon-γ is responsible for the bald spots seen during certain parasitic infections, as it induces the transcription of phospholipase A₂ on target cells. Phospholipase goes on to cleave arachidonic acid from the cell membrane, where it is found, initiating the production of eicosanoids such as prostaglandin D₂. Gamma interferon also induces the enzyme inducible nitric oxide synthase.

But most important to the psychology of the immune response is the ability of interferon-γ to powerfully effect tryptophan metabolism. This is the only precursor for indole neurotransmitters such as serotonin and melatonin, so a reduction in this amino acid would be expected to produce psychological effects. Fernstrom has shown that brain serotonin synthesis is a direct function of the ratio of serum tryptophan over it's five competing amino acids (tyrosine, phenylalanine, leucine, isoleucine, and valine). Teleologically, it's effect on tryptophan metabolism serves to restrict this amino acid from the invading pathogen—but is entirely pathological in the case of food allergy, and serves no real beneficial function. The body does not seem capable of differentiating a seed storage protein fragment, such as wheat gluten or oat avenin, from a protein derived from an invading pathogen; the body releases interferon-γ as a response to many proteins, whether injected, inhaled, or ingested (or transdermal invasion in the case of some such parasites such as hookworm). Gamma interferon lowers tryptophan levels by inducing the enzyme indolamine diooxygenase:

'The IFN-γ-mediated IDO induction observed in vitro is consistent with the results from in vivo treatment. Plasma levels of tryptophan and urine levels of kynurenine were measured in individuals who had received iv. bolus injections of either IFN-α or IFN-γ. Plasma tryptophan levels were not altered in patients receiving IFN-α, but at 6 and 24 h after administration of IFN-γ, plasma levels were reduced and urinary kynurenine levels were elevated. In these studies it was not possible to correlate plasma tryptophan levels or urinary kynurenine levels with doses of IFN or neoplasia. Complete amino acid analysis of plasma from three patients showed that the catabolic effect was confined to tryptophan. Of the 22 amino acids examined, only tryptophan levels were significantly reduced (to 36.7% of pretreatment levels).' ―Taylor​

This is a significant reduction in tryptophan (63.3%), and would be expected to reduce brain serotonin synthesis. This would also serve to reduce new protein synthesis, perhaps explaining the thinness and weakness observed in those with with ongoing parasitic infections—an observation perhaps wrongly attributed to the insignificant 'nutrient theft' by the parasites themselves (parasites sometimes acquire the mythological ability to sequester all dietary minerals in places such as curezone.com). A reduction in any one amino acid of this magnitude would be expected to reduce new protein synthesis, and especially in the case of the relatively scarce tryptophan; serotonin is also responsible for releasing growth hormone from the pituitary. Eating enough protein—say about 100 grams per day—could be enough to overcome the reduced protein synthesis and slightly normalize the tryptophan ratio, but the induction of interferon-γ would still be a detriment. Eating more food does nothing about the prostaglandins produced; on the contrary, it would likely serve to increase them by introducing more linoleic acid.

Through interferon-γ you would expect people with severe food allergies to model those with parasitic infections. There are many parallels; parasitic infection, injection of peanut protein, and ingestion of gluten can cause hair loss. Below is a study demonstrating this, with peanut protein-sensitized mice exhibiting a type of hair loss reminiscent of mice genetically-manipulated to express interferon-γ on the skin and also canine leishmaniasis:

Li, Xui-Min. "Murine model of atopic dermatitis associated with food hypersensitivity." Journal of allergy and clinical immunology (2001)​

Ciaramella, P. "A retrospective clinical study of canine leishmaniasis in 150 dogs naturally infected by Leishmania infantum." Veterinary record (1997)​

Carroll, Joseph M. "Transgenic mice expressing IFN-γ in the epidermis have eczema, hair hypopigmentation, and hair loss." Journal of investigative dermatology (1997):​

And predictably: vaccination has been reported to cause hair loss.

'Within 1 day after her first dose of HBV, a 30-year-old female nurse developed mild hair loss, arthralgias, fatigue, and weakness, which lasted 1 week. One month later, her second dose was followed 1 day later by recurrent onset of hair loss and, about 2 weeks later, by recurrent arthralgias, fatigue, and weakness. Alopecia progressed for a few months until she estimated that half of her hair remained in a diffuse distribution with a thinned appearance. Her hair later regrew without treatment or workup.' ―Wise​

Nothing is associated more with hair loss than is prostaglandin D₂, an eicosanoid in which interferon-γ increases by inducing the transcription of phospolipase A₂. Of interest is the fact that the powerful hair growth drug cyclosporine A completely blocks interferon-γ production.

Ercan, A. R. "Interferon‐gamma in alopecia areata." European Journal of Dermatology (2004)​

Larson, Allison R. "A prostaglandin d‐synthase‐positive mast cell gradient characterizes scalp patterning." Journal of cutaneous pathology (2014)​

Garza, Luis A. "Prostaglandin D₂ inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia." Science translational medicine (2012)​

The clinical presentation of celiac disease, also characterized by very high interferon-γ levels, involves weight loss:

'This form is characterized by gastrointestinal manifestations starting between 6 and 24 months of age, after the introduction of gluten in the diet. Infants and young children typically present with impaired growth, chronic diarrhea, abdominal distention, muscle wasting and hypotonia, poor appetite, and unhappy behavior. Within weeks to months of starting to ingest gluten, weight gain velocity decreases and, finally, weight loss can be observed.' ―Fasano​

But since this involves a prominent reduction of the intestinal villi, and likely reduced absorption of certain things, this is not conclusive. However, alopecia is also observed in celiac disease—a condition dominated by interferon-γ.

Corazza, Gino R. "Celiac disease and alopecia areata: report of a new association." Gastroenterology (1995)​

Fasano, Alessio. "Clinical presentation of celiac disease in the pediatric population." Gastroenterology (2005)​

Nilsen, Ellen M. "Gluten induces an intestinal cytokine response strongly dominated by interferon gamma in patients with celiac disease." Gastroenterology (1998)​

Celiac disease isn't the best model since gluten also has exorphins—small peptides about five amino acids in length—which act through the δ-opioid receptor; this raises prolactin and perhaps causes psycho-opiate effects.

This may seem speculative to those who haven't read many of these studies, but it's not really. I found one person who thinks along these lines, will confirm many things I had written, and has conducted an interesting study on this topic:

Maes, Michael. "Increased neopterin and interferon-gamma secretion and lower availability of L-tryptophan in major depression: further evidence for an immune response." Psychiatry research (1994)​

(Neopterin is a product of GTP, usually found increased in proportion with interferon-γ.)

'However, immune responses may be accompanied by signs of immune activation (e.g., hypersecretion of cytokines and prostaglandins, T-cell activation) as well as immunosuppression.' ―Maes​

​

'Recently, it was suggested that lower plasma L-tryptophan (L-TRP) levels, which frequently occur in major depression, may be related to the immune response. Indeed, our laboratory found significant inverse relationships between various immune or inflammatory markers and plasma L-TRP concentrations or the L-TRP/competing amino acid (CAA) ratio [The Fernstrom Ratio]. Activation of cell-mediated immunity is known to accelerate L-TRP catabolism through induction of indoleamine 2,3-dioxygenase, with subsequent depletion of plasma L-TRP. This phenomenon could compromise central serotonergic turnover, since L-TRP plasma concentration or the L-TRP/CAA ratio provides an index of the availability of L-TRP to the brain (Fernstrom et al., 1973; Fernstrom, 1984; Moller et al., 1986), which, in part, determines central serotonin synthesis (Moir and Eccleston, 1968; Fernstrom and Faller, 1977). '―Maes​

​

'Procedures. In study group I, fasting blood samples were collected at 8 a.m. for determination of plasma neopterin, L-TRP, valine, leucine, isoleucine, tyrosine, and phenylalanine.' ―Maes​

​

'Table 2 shows that the L-TRP/CAA ratio was significantly lower in depressed subjects than in normal control subjects. The lowest L-TRP/CAA values were observed in subjects with simple major depression and melancholia. The number of subjects with lower L-TRP/ CAA values differed significantly among the four study groups. Up to 77.4% of the major depressed subjects showed lower L-TRP/CAA values with a specificity of 96.7% and a PV of 95.9%; the area under the ROC plot was 92.6%. Table 3 shows that up to 43.0% of the variance in the L-TRP/ CAA ratio was explained by diagnostic classification.' ―Maes​

​

'IFNy and Major Depression. IFNy secretion was significantly higher in major depressed subjects (mean = 710 IU/ml, SD = 775) than in normal control subjects (mean = 206 IU/ml, SD = 244). These differences remained significant after covariation for age.' ―Maes​

​

'IFNy and Depression. The second major finding of this study is the significantly increased IFNγ secretion in culture supernatant of mitogen-stimulated PBMC of major depressed subjects compared with normal control subjects. It has been suggested that disturbances in cytokine synthesis or secretion (e.g., IFNγ) can best be studied under dynamic conditions by stimulating immunocompetent cells with polyclonal activators and that the pattern of cytokine production offers an index of in vivo cytokine secretion. Since it is known that IFNγ is released from activated immune T cells, the present results corroborate our previous findings that major depression is characterized by T-cell activation.' ―Maes​

​

'L-TRP Availability and Depression. This study replicates previous findings on lower total L-TRP availability in major depressed patients compared with normal control subjects. In the present study group, lower L-TRP/CAA values were highly sensitive and specific for major depression: up to 77% (sensitivity) of major depressed patients exhibited lower L-TRP/CAA values with a specificity and predictive value of 97% and 96%, respectively.' ―Maes​

​

'This may be explained by the fact that the major depression-related hypersecretion of IFNγ is the common denominator of both phenomena. However, the putative relationship between activation of cell-mediated immunity and lower L-TRP availability in depression may not only be explained by increased IFNγ secretion, but also by IL-l and IL-6-related mechanisms. These cytokines may induce muscle proteolysis and increased uptake of amino acids into hepatocytes for the synthesis of APPs and secretory proteins.' ―Maes​

Perhaps, but I looked a bit more into histamine. This is another, small molecule neurotransmitter involved in the immune response. Under an allergenic challenge, you'd expect high histamine along with low serotonin. Here are some quotes from a review article (it would be interesting to read the individual studies):

'Aggressive behaviour: Strong evidence from studies with animals suggests that drugs which modify brain histamine activity also alter aggressive behaviour. Furthermore, there is some evidence for distinct H₁ and H₂ receptor mechanisms. Several types of aggressive behaviour have been studied. One is fighting behaviour in mice. This can be induced by putting two previously isolated male mice into the same cage. Alternatively, pairs of mice or rats are given electric shocks to their feet, eliciting aggressive interactions between them. A third method is to lesion the septum of rats. The other main type of aggressive behaviour studied involves inter-species interactions. Rats which spontaneously kill mice introduced into their cages are selected and used for study. Three main studies have examined the effects of compounds altering histaminergic function on shock-induced fighting. The results are not entirely consistent. Ray showed that intracerebroventricularly‐administered histamine decreased aggressive behaviour, while Nath showed that this behaviour increased as a result of histamine administration. The difference may be in the species: rats were used in the former study and mice in the latter. However, Costentin showed that a dose of the precursor histidine which was sufficient to increase brain histamine levels by 80–120% depressed shock-induced fighting in mice—a result consistent with the findings of Ray. It should also be noted that Nath used a relatively high dose: 25–100 μg compared with 5 μg used by Ray. (1981). Ray further showed that the H₁ agonist 2‐pyridylethylamine decreased aggressive behaviour and the H₂ agonist 4‐methylhistamine increased it. These effects were blocked by the respective antagonists, mepyramine and cimetidine. While these authors found no effect when the antagonists were administered by themselves, Nath reported an increase in aggressive behaviour following mepyramine administration and a decrease following metiamide. Both groups report an enhancement after combinations of histamine and mepyramine; combinations of histamine and an H₂ antagonist resulted in a decrease or no change. While there are some contradictions (which may be a result of differences in species, dose or the conditions used to elicit the behaviour), the results are fairly convincing demonstrations of the role of histaminergic systems in footshock aggression. The data suggest that activation of H₁ receptors is inhibitory and activation of the H₂ receptors facilitatory for this type of aggressive behaviour. It is interesting to observe the opposite role for H₁ and H₂ receptors, just as in so many peripheral functions. The results are somewhat different when other types of aggression are considered. H₁ antagonists have been found to suppress isolation-induced fighting in mice. The effect occurs at doses which are not producing a general suppression of motor activity. However, anticholinergics are also effective inhibitors of isolation-induced fighting and the order of potency of antihistamines in the test suggests that their anticholinergic activity may be more important than their antihistaminic activity. The only other study to examine within-species aggressive behaviour used septal‐lesioned rats and found no effect on their hyperirritabilty and aggressiveness. The results of two studies examining muricide in rats show that H₂ antagonists can decrease this behaviour. One author noted the effect only with chlorpheniramine and not with other antihistamines studied; the other group observed the same change with diphenhydramine and promethazine, but not with astemizole. Histamine itself and histamine synthesis inhibitors both suppressed muricide. To date there has been some effort to characterize the role of histaminergic mechanisms with foot-shock induced aggression only. Further research is needed to determine the roles of H₁ and H₂ receptors in other types of aggressive behaviour. Case reports from humans taking H₂ antagonists suggest that aggressive behaviour may be one adverse symptom associated with cimetidine use. Finally, several studies should be mentioned in which behaviour resembling aggression was induced by administration of histidine. Pairs of animals were observed to rear and face each other and rhythmically beat each other with their forepaws. Other characteristic patterns of rat aggressive behaviour were not present. The relationship between this" bizarre" behaviour and norreal aggression is not clear.' ―White​

The two histamine receptors antagonize each other, and biphasic effects are often noted: first an increase or a decrease in a response, followed by its opposite. These two histamine receptors are found on T cells, where the H₁ receptor acts to release interferon‐γ. Mice genetically‐manipulated to lack the H₁ receptor have essentially negligible interferon‐γ levels. Histamine directly controls interferon‐γ, and not the other way around. This sets the mast cells and the basophils on a higher regulatory level than the helper T cells which produce most relevant cytokines, so the protein–immune response likely starts here.

In a mouse model of autism, a histamine three receptor (H₃) antagonist was able to completely reverse all symptoms tested including exploratory behavior and social interaction. The Fernstrom Ratio is found lower in autism, implicating interferon‐γ and immune response. This vindicates the observational associations between autism, vaccines, and cow's milk allergy, and biopterins in the urine have been found threefold increased (another biomarker of interferon‐γ). A lower Fernstrom Ratio coupled with increased biopterins would indicate the activity of interferon‐γ, and hence the increase in histamine. The immunogenic neurotransmitter profile would then most likely be characterized by both a relative decrease in serotonin and an increase in histamine. The biopterins themselves could also be a factor.

This could explain the consistent beneficial findings of niacin in autism. Molecularly similar to histamine, this small molecule vitamin creates a flush and releases prostaglandin D₂—histamine does the exact same thing. Large doses of niacin of this type are not exerting their effects by becoming NADH, and nobody is claiming a metabolic theory of schizophrenia or autism. What niacin does, ostensibly, is serve either as a ligand of one of the histamin receptors (H₁, H₂, or H₃). Niacin also removes methyl groups from the body, an unambiguous experimental finding which could have relevance.

I think Hoffer's mechanism for niacin's effects was exceedingly drawn‐out, prolix, and indirect. It would be a great simplification if niacin were proven to bind a histamine receptor directly (or the so‐called 'niacin receptor' was also a histamine receptor).

'HISTAMINE: Current research indicates that the neurotransmitter histamine also plays an important role in the formation of schizophrenia. Although only recently acknowledged, there actually appears to be much more evidence for the etiological role of histamine rather than dopamine.' ―Heleniak​

​

'Research in this area was done as early as 1938. Researchers at this time found that subcutaneous injections of histamine produced favorable therapeutic responses in schizophrenic patients.' ―Heleniak​

​

'Histaminase metabolized histamine and it has been frequently noted that schizophrenics show a significantly lower incidence of colds and allergic reactions such as eczema, asthma and hayfever, when compared to the general population. They also show a reduced sensitivity to both cold and pain. In addition, schizophrenics have small wheal and flare reactions to intradermal injections of histamine. This indicates that low levels of histamine are involved. It has also been shown that a schizophrenic-like psychosis may be induced in a normal population by administering a high amount of anti-histamines, particularly the H₂ blockers.' ―Heleniak​

​

'Direct evidence for histamine being a primary causative factor in schizophrenia, as opposed to dopmine, comes from recent work by Nakai. They found that there was a down-regulation of the H₁ receptor in the frontal cortex and suggested that this may be etiologically significant in schizophrenia. Frontal lobe H₁ receptors are involved in sleep/wakefulness, feeding/drinking, locomotor/catalepsy, and neuroendocrine regulation. Schizophrenic patients may exhibit dysfunction in any or all of these areas. Related evidence for the primacy of histamine in schizophrenia comes from the fact that schizophrenics show a scarcity of mast cells in the skin, and Stellato demonstrated how anaesthetics induce histamine release selectively from human mast cells. Taking this one step further, a lack of mast cells would lead to a histamine deficiency in these individuals.' ―Heleniak​

Heleniak, E. "Histamine and prostaglandins in schizophrenia: revisited." Medical hypotheses (1999)
Naushad, Shaik Mohammad. "Autistic children exhibit distinct plasma amino acid profile." (2013).
Messahel, S. "Urinary levels of neopterin and biopterin in autism." Neuroscience letters (1998)
White, Jason M. "Behavioural effects of histamine and its antagonists: a review." Psychopharmacology
Jutel, Marek. "Histamine regulates T-cell and antibody responses by differential expression of H₁ and H₂ receptors." Nature (2001)
Baronio, Diego. "Effects of an H₃R antagonist on the animal model of autism induced by prenatal exposure to valproic acid." PLoS One (2015)
D'Eufemia, P. "Low serum tryptophan to large neutral amino acids ratio in idiopathic infantile autism." Biomedicine & pharmacotherapy (1995)

I’d like to draw attention to this sentence.

Mice genetically‐manipulated to lack the H₁ receptor have essentially negligible interferon‐γ levels.

It struck my interest.

 

[golder]

Could be interesting to test. It seems like it should be fairly hair/skin safe and it’s active against cutibacterium acnes.

Topical Hypochlorite and Skin Acidification Improves Erythroderma of Omenn Syndrome - PubMed

We describe a case of Omenn syndrome displaying exudative erythroderma and other characteristic features, including alopecia, absent B and naïve T cells, hyper immunoglobulin E levels, and eosinophilia. A pathogenic recombination-activating <i>RAG1</i> homozygous genetic mutation confirmed the...

pubmed.ncbi.nlm.nih.gov

JCI - Topical hypochlorite ameliorates NF-κB–mediated skin diseases in mice

www.jci.org

https://californiahairsurgeon.com/wp-content/uploads/surgihealpro_forum_article_01_2021-1.pdf

An Integrated HOCl-Producing E-Scaffold Is Active against Monomicrobial and Polymicrobial Biofilms

Oxidizing agents like hypochlorous acid (HOCl) have antimicrobial activity. We developed an integrated electrochemical scaffold, or e-scaffold, that delivers a continuous low dose of HOCl aimed at targeting microbial biofilms without exceeding concentrations ...

www.ncbi.nlm.nih.gov

HOCl (Hypochlorous Acid) SPRAYS are the best thing I’ve tried lately *knock on wood* (Newsletter No. 23) — KRISTY LIN

Long marketed mainly for postoperative care, piercing care, blepharitis, burn treatment and as a safe cleaning solution for the home and hospitals (i.e. more health than beauty), hypochlorous acid HOCl has recently been rebranded as a hip cure that is in line with the current stage of the Into The

www.kristylin.com

Thanks for sharing your knowledge man. Out of curiosity do you use anything topically for your hair at all? I know everyone has strengths/weaknesses in different vectors regarding hair loss so there’s degrees of personalisation, but would be interested to hear about your protocol.

 

[Mauritio]

More reading from mr Travis




I’d like to draw attention to this sentence.

It struck my interest.

Thanks for sharing .
Wild how much work Travis put into his posts. It would take ages to go through everything and fact check , so I'll just believe him for now.

About 2-3 years ago I took doxylamine succinate twice per week to help me sleep.
The next day I would often be irritable and agressive, there were a few instances where I acted almost out of character and it took me many months to make the connection to the anti-histamine . Until now I didn't know the molecular mechanism behind it ,so thanks