Aspirin With Castor Oil For Hair Loss

[Travis]

"Moderate affinity" is not "zero affinity". Small effect does not equal zero effect. Anything that absorbs into your skin will, to some degree, enter the circulation,

A few molecules, certainly, but not enough to be detected.

...regardless of whether researchers decide it meets some level of statistical significance or not.

This wasn't statistics, this was high‐performance liquid chromatography.⁽¹⁾

Five percent spironolactone mixed with 'purified water 66.35%, propylene glycol 12%, vaseline oil 8%, cetostearyl alcohol 4.5%, cetomacrogol 1000 4%, adjuvants 0.65%.' had been applied over a body area comprising 55% of the total leading to undetectable levels. If applied to the head—or less than 55% of the total body area—you would expect even less to be absorbed (or negative undetectable, if there was such a thing.)

They also say this:

'Caminos-Torres et al. (6) revealed that no change occurred in the average concentration of pT [plasma testosterone] after a four week treatment with high doses of spironolactone (400 mg/ day) in normal men while the free fraction of testosterone increased significantly, probably due to the displacement of testosterone from plasma binding proteins as confirmed in vitro. In a five day study, Stripp et al. (7) did not find any change in pT concentration, but showed a significant rise in plasma 17a-OH-P which persisted throughout the study. Other authors, like Pentikainen et al. (8) observed a slight decrease of pT after moderate treatment over a short period of time.' ―Rey⁽¹⁾ ​

Certainly, eplerenone would be a better choice for most because it has essentially no androgenic effect. I cannot think of a reason to even take an antiandrogen—like finasteride—besides for those with prostate enlargement. But topically, I certainly can see no harm in using spironolactone—a cheaper, and more available drug than eplerenone (spironolactone is synthesized in relatively great amounts oversees).

And the reason why blocking the mineralcorticoid receptor works is that the scalp is characterized by a prostaglandin D synthase gradient⁽²⁾⁽³⁾ and the mineralocorticoid receptor is responsible for transcribing this enzyme—as determined by quantitative PCR.⁽⁴⁾ The prostaglandin D synthase gene also has been shown to have a mineralocorticoid response element.⁽⁵⁾

'PTGDS mRNA level was also increased in MAF from adipo-MROE mice when compared with MAF from control-MR littermates (relative PTGDS mRNA level: control-MR, 1.0±0.1 and adipo-MROE, 2.4±0.4) suggesting that MR [mineralcorticoid receptor] might directly control PTGDS transcription in adipocytes. Importantly, 10−8 mol/L aldo[sterone] increased PTGDS mRNA level in adipocytes derived from adipo-MROE SAT (Figure 5B). This increase was abolished by coincubation with 10−6 mol/L MR antagonist spironolactone (Figure 5B).' ―Urbanet
​

Why would you not address the underlying deficiencies and toxicities causing the adjusted homeostasis that's leading to the pathology? Wouldn't a much more logical resolution include managing lifestyle rather than an eternity of rubbing sorta-kinda-maybe-specific chemicals into your scalp? If serotonin, parathyroid, prolactin, prostaglandins, etc. are at the heart of hair loss, wouldn't it stand to reason there is more to rectified in the individual than just the "superficial" state of hair loss? Why would we not seek to heal the individual in totality, rather than patch symptoms? Even a cursory review of the literature demonstrates age-adjusted hair loss is associated with countless other pathologies.

I do routinely point out that linoleic acid is the only precursor to prostaglandin D₂. Prostaglandin D₃ can be made by eicosapentaenoic acid, but this hasn't been shown to cause hair loss. Besides avoiding linoleic acid for hair loss, this can also perhaps avoid cancer in some people. Prostaglandin E₂ upregualtes ornithine decarboxylase and increases proliferation. I have tried to find epidemiological evidence for linoleic acid consumption and hair loss, but I haven't seen any. Perhaps the best one can do is look at the observations of Ian Prior.

I haven't seen any evidence showing that serotonin, parathyroid, or prolactin were etioligical factors.

Aldosterone can be modified through sodium intake, and aldosterone has been shown a factor in hair loss.⁽⁶⁾ Just like cortisol, aldosterone binds the mineralocorticoid receptor. Cortisol can be modified by diet, but I would feel ashamed to recommend yoga: some people really need their adrenals, and not everybody has the luxury of having a stress‐free environment or occupation.

'Patients with AGA showed significantly higher systolic blood pressure values and aldosterone levels (197±35 vs. 133±71 pg mL) vs. controls.' ―Arias‐Santiago⁽⁶⁾​

Spironolactone can antagonize the mineralocorticoid receptor and would be expected to limit the induction of prostaglandin D synthase. Lowering aldosterone and/or cortisol by any mechanism (i.e. 11β-HSD₁ inhibitor, stress, or sodium), would be expected to do likewise.

The long-observed negative effect of cortisol on hair growth does not contradict the findings of Louis Garza, but only adds to the weight of evidence directly implicating prostaglandin D₂/J₂.

[1] Rey, F. O. "Lack of endocrine systemic side effects after topical application of spironolactone in man." Journal of endocrinological investigation (1988)
[2] Larson, Allison R. "A prostaglandin d‐synthase‐positive mast cell gradient characterizes scalp patterning." Journal of cutaneous pathology (2014)
[3] Garza, Luis A. "Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia." Science translational medicine (2012)
[4] Urbanet, Riccardo. "Adipocyte mineralocorticoid receptor activation leads to metabolic syndrome and induction of prostaglandin D2 synthase." Hypertension (2015)
[5] Wilhelm, Dagmar. "SOX9 regulates prostaglandin D synthase gene transcription in vivo to ensure testis development." Journal of Biological Chemistry (2007)
[6] Arias‐Santiago, S. "Elevated aldosterone levels in patients with androgenetic alopecia." British Journal of Dermatology (2009)​

 

[DuggaDugga]

A few molecules, certainly, but not enough to be detected.
This wasn't statistics, this was high‐performance liquid chromatography.⁽¹⁾

Five percent spironolactone mixed with 'purified water 66.35%, propylene glycol 12%, vaseline oil 8%, cetostearyl alcohol 4.5%, cetomacrogol 1000 4%, adjuvants 0.65%.' had been applied over a body area comprising 55% of the total leading to undetectable levels. If applied to the head—or less than 55% of the total body area—you would expect even less to be absorbed (or negative undetectable, if there was such a thing.)

They also say this:

'Caminos-Torres et al. (6) revealed that no change occurred in the average concentration of pT [plasma testosterone] after a four week treatment with high doses of spironolactone (400 mg/ day) in normal men while the free fraction of testosterone increased significantly, probably due to the displacement of testosterone from plasma binding proteins as confirmed in vitro. In a five day study, Stripp et al. (7) did not find any change in pT concentration, but showed a significant rise in plasma 17a-OH-P which persisted throughout the study. Other authors, like Pentikainen et al. (8) observed a slight decrease of pT after moderate treatment over a short period of time.' ―Rey⁽¹⁾ ​

Certainly, eplerenone would be a better choice for most because it has essentially no androgenic effect. I cannot think of a reason to even take an antiandrogen—like finasteride—besides for those with prostate enlargement. But topically, I certainly can see no harm in using spironolactone—a cheaper, and more available drug than eplerenone (spironolactone is synthesized in relatively great amounts oversees).

And the reason why blocking the mineralcorticoid receptor works is that the scalp is characterized by a prostaglandin D synthase gradient⁽²⁾⁽³⁾ and the mineralocorticoid receptor is responsible for transcribing this enzyme—as determined by quantitative PCR.⁽⁴⁾ The prostaglandin D synthase gene also has been shown to have a mineralocorticoid response element.⁽⁵⁾

'PTGDS mRNA level was also increased in MAF from adipo-MROE mice when compared with MAF from control-MR littermates (relative PTGDS mRNA level: control-MR, 1.0±0.1 and adipo-MROE, 2.4±0.4) suggesting that MR [mineralcorticoid receptor] might directly control PTGDS transcription in adipocytes. Importantly, 10−8 mol/L aldo[sterone] increased PTGDS mRNA level in adipocytes derived from adipo-MROE SAT (Figure 5B). This increase was abolished by coincubation with 10−6 mol/L MR antagonist spironolactone (Figure 5B).' ―Urbanet
​

I do routinely point out that linoleic acid is the only precursor to prostaglandin D₂. Prostaglandin D₃ can be made by eicosapentaenoic acid, but this hasn't been shown to cause hair loss. Besides avoiding linoleic acid for hair loss, this can also perhaps avoid cancer in some people. Prostaglandin E₂ upregualtes ornithine decarboxylase and increases proliferation. I have tried to find epidemiological evidence for linoleic acid consumption and hair loss, but I haven't seen any. Perhaps the best one can do is look at the observations of Ian Prior.

I haven't seen any evidence showing that serotonin, parathyroid, or prolactin were etioligical factors.

Aldosterone can be modified through sodium intake, and aldosterone has been shown a factor in hair loss.⁽⁶⁾ Just like cortisol, aldosterone binds the mineralocorticoid receptor. Cortisol can be modified by diet, but I would feel ashamed to recommend yoga. Some people really need their adrenals, and not everybody has the luxury of having a stress‐free environment or occupation.

'Patients with AGA showed significantly higher systolic blood pressure values and aldosterone levels (197±35 vs. 133±71 pg mL) vs. controls.' ―Arias‐Santiago⁽⁶⁾​

Spironolactone can antagonize the mineralocorticoid receptor and would be expected to limit the induction of prostaglandin D synthase. Lowering aldosterone and/or cortisol by any mechanism (i.e. 11β-HSD₁ inhibitor, stress, or sodium), would be expected to do likewise.

The long-observed negative effect of cortisol on hair growth does not contradict the findings of Louis Garza, but adds to the weight of evidence directly implicating prostaglandin D₂/J₂.

[1] Rey, F. O. "Lack of endocrine systemic side effects after topical application of spironolactone in man." Journal of endocrinological investigation (1988)
[2] Larson, Allison R. "A prostaglandin d‐synthase‐positive mast cell gradient characterizes scalp patterning." Journal of cutaneous pathology (2014)
[3] Garza, Luis A. "Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia." Science translational medicine (2012)
[4] Urbanet, Riccardo. "Adipocyte mineralocorticoid receptor activation leads to metabolic syndrome and induction of prostaglandin D2 synthase." Hypertension (2015)
[5] Wilhelm, Dagmar. "SOX9 regulates prostaglandin D synthase gene transcription in vivo to ensure testis development." Journal of Biological Chemistry (2007)
[6] Arias‐Santiago, S. "Elevated aldosterone levels in patients with androgenetic alopecia." British Journal of Dermatology (2009)​

Thank you for the thoughtful, referenced response.

I don't think there's any contention that modifiable environmental factors, amplified by some genetic predisposition, are at the core of hair loss and virtually every pathology outside of a few, rare congenital diseases. It seems we bifurcate when it comes to intervention. Maybe I'm biased because I was able to halt and slowly reverse hair loss through management of stress, inflammation and the subsequent metabolic dysregulation and soft tissue calcification.
That said, I'm not ashamed to recommend yoga and mindfulness practice as a means to lower ACTH and the inflammatory response. Might not be for everyone, but it's done wonders for me. The effect of mindfulness meditation training on biological acute stress responses in generalized anxiety disorder. - PubMed - NCBI
Contrary to the commonly accepted androgen-based theory of hair loss, increasing testosterone and lowering glucocorticoids and mineralcorticoids seems a more logical and integrated approach. Plus you get the benefits of good skin, increased musculature, libido, elevated mood, etc. I think we agree there.

I also agree with you that natural intervention is more difficult for some than others. But I would counter that the logistical and cost barriers of spirolactone treatment have their own barriers (not that I would recommend that anyways).

So I guess we'll have to sort of agree to sort of disagree. I hope you won't mind me playing devil's advocate during our co-existence on this forum, and vice versa

 

[Wagner83]

I never really wore hats and I always lost hair... but I daresay my friends with the best hair have the worst diet...

I had the most incredible, luxurious, thick, dark and shiny hair while feeling like crap, with stress and eating whole grains and salmon. Ray has said he thought hair had their use in keeping the brain warm, perhaps having higher body temperatures can be detrimental to hair health in some people, hair becoming an unnecessary feature of the body if the brain is warm (or even slightly too warm).

 

[DuggaDugga]

I had the most incredible, luxurious, thick, dark and shiny hair while feeling like crap, with stress and eating whole grains and salmon. Ray has said he thought hair had their use in keeping the brain warm, perhaps having higher body temperatures can be detrimental to hair health in some people, hair becoming an unnecessary feature of the body if the brain is warm (or even slightly too warm).

Why would you just lose it directly on the galea then?

 

[Travis]

Why would you just lose it directly on the galea then?

Microcirculatory regions have been shown to concentrate steroids when their respective binding globulins, and serum albumin, are squeezed by increasing pressure. Either that, or it's simply a function of the increased surface area. For example, take one artery of x radius and reduce this value by two. To maintain constant volume—and constant pressure—you need four such branches (κ).

π(x)²=κπ(¹⁄₂x)²

π(x)²=κπ(¹⁄₄)(x)²

1=κ(¹⁄₄)

4=κ​

The surface area cross section (σ) would then be increased by:

σ·2π(x)=4×2π(¹⁄₂x)

σ·2π(x)=8π(¹⁄₂x)

σ·2π(x)=4π(x)

σ·2=4

σ=⁴⁄₂

σ=2​

The sum cross sections would be increased two‐fold with one branch point (maintaining constant volume and pressure), leading to more contact with the arterial wall. The surface area is simply the cross sections times the length. The most studied microcirculatory regions are those of the liver and the blood–brain barrier, where first‐pass tryptophan⁽¹⁾ and sex steroid⁽²⁾ uptake has been experimentally proven to be greatly increased over expected using radio‐labeled molecules followed by quick decapitation.

'The above model emphasizes the view that the transportability of albumin-bound testosterone and other ligands [i.e. cortisol] into tissues in vivo arises from specific interactions of the binding protein with the endothelial lining microcirculation.' ―Pardridge⁽³⁾​

Since the scalp is characterized by a prostaglandin D₂ synthase gradient, has a microcirculatory region, and that prostaglandin D synthase is expressed by cortisol, aldosterone, and nothing else: Logic dictates that the prostaglandin D synthase gradient is synonymous with the cortisol + aldosterone gradient.

If this sounds speculative, that is probably because you haven't read these:⁽³⁾⁽⁴⁾

'The transport of hormone from the plasma protein-bound pool is believed to occur via a mechanism of enhanced dissociation. That is, owing to rapid interactions between the surface of the binding protein and the surface of the microcirculation, there are conformational changes about the hormone-binding site that ensue and allow for enhanced rates of release of hormone from the binding protein relative to what occurs in vitro in the absence of protein-microcirculation interactions.' ―Pardridge⁽³⁾

'Previous studies have provided direct in vivo measurements of elevated dissociation constants within the brain microcirculation. Moreover, these studies show that permeability to the hormone in the albumin-bound form is no greater than permeability to the free hormone. The change in conformation about the hormone-binding site on albumin that is necessary to cause the enhanced rates of dissociation in vivo may be very slight indeed, and may have marked effects on the free energy of albumin-binding of a particular steroid hormone or any other ligand. This principle is true in general for protein binding of ligands. For example, recent X-ray diffraction studies show that the loss of a single hydrogen bond between the ligand and a protein-binding site results in two to three log order differences in the binding dissociation constant.' ―Pardridge⁽³⁾

'A conformational change about the albumin-binding site (caused by interactions with the surface of the organ microcirculation, see below) would result in a partial uncoiling about the binding site and markedly increase rates of hormone dissociation.' ―Pardridge⁽³⁾

'Conformational changes about ligand-binding sites on the albumin molecule may be mediated by interactions between the surface of the plasma protein and the surface of the organ microcirculation. Although albumin receptors have been proposed to exist in the organ microcirculation, the original reports purporting to demonstrate the presence of such receptors in liver have not been confirmed. Moreover, no specific saturable albumin receptor is identifiable in isolated bovine brain capillaries [...] Although specific albumin receptors do not appear to mediate the transient interactions between the surface of the organ microcirculation and the albumin molecule,' ―Pardridge⁽³⁾

'The expansion of the testosterone dissociation constant in the brain microcirculation in vivo is nearly ten-fold greater as compared to the increased dissociation constant observed in lymph node capillaries. Conversely, the increased estradiol dissociation constant in lymph node capillaries is more than double the value observed in the brain microcirculation (TABLE 1).' ―Pardridge⁽³⁾

'In addition to organ specificities, there are also binding site specificities for albumin‐mediated delivery of ligands to tissues in vivo. The dissociation constant of bovine albumin binding in the rat brain microcirculation in vivo has been measured for eight different ligands and the in vivo dissociation constant has been compared to that found in vitro (TABLE 2). Testosterone dissociation is increased fifty-fold in the brain microcirculation, whereas corticosterone dissociation from bovine albumin is increased only five-fold.' ―Pardridge⁽³⁾

'Owing to the rapid bolus injection of human serum labeled with [²H]testosterone or [²H]estradiol into the common carotid artery of the anesthetized rat, there is little mixing of the injection solution with the circulating rat plasma during this first passage through the brain microcirculation. The bolus is 96% through the head within the first two seconds after injection, and the first pass extraction is measured by determination of brain radioactivity following decapitation.' ―Pardridge⁽³⁾

'charge-selectivity mechanism appears to involve interactions between the surface of the plasma protein and the surface of the organ microcirculation that results in a conformational change about the hormone-binding site, and concomitantly, enhanced dissociation of the hormone' ―Pardridge⁽³⁾

'These results indicate that there are specific interactions between SHBG and CBG such that conformational changes about the oestradiol and corticosteroid binding sites, respectively, occur in rat liver at the microcirculation level.' ―Pardridge⁽⁴⁾

'The transport of hormone from the circulating plasma protein-bound pool involves tissue-mediated enhanced dissociation of the hormone from the protein without significant exodus of the plasma protein from the microcirculation compartment. The tissue-mediated enhanced dissociation mechanism varies in activity between different organs and is a much more important factor than organ differences in capillary transit times in regulating the amplification of hormone delivery to different tissues.' ―Pardridge⁽⁴⁾​

Besides its eponymous binding globulin, the corticosteroids—like tryptophan—are carried by serum albumin; this is a spongy protein characterized by seven deformable α-helices, which will more than likely enhance dissociation upon any physical disturbance. So whether you hold surface area constant (an increase in pressure) or volume constant (an increase in surface area), any arboration of the capillary network would be expected to increase steroid uptake in those regions.

[1] Oldendorf, William H. "Brain uptake of radiolabeled amino acids, amines, and hexoses after arterial injection." American Journal of Physiology--Legacy Content (1971)
[2] Pardridge, William M. "Effects of human serum on transport of testosterone and estradiol into rat brain." American Journal of Physiology-Endocrinology And Metabolism (1980)
[3] Pardridge, William M. "Selective Delivery of Sex Steroid Hormones to Tissues In Vivo by Albumin and by Sex Hormone‐Binding Globulin." Annals of the New York Academy of Sciences (1988)
[4] Pardridge, William M. "Serum bioavailability of sex steroid hormones." Clinics in endocrinology and metabolism (1986)​

 

[DuggaDugga]

Microcirculatory regions have been shown to concentrate steroids when their respective binding globulins, and serum albumin, are squeezed by increasing pressure. Either that, or it's simply a function of the increased surface area. For example, take one artery of x radius and reduce this value by two. To maintain constant volume—and constant pressure—you need four such branches (κ).

π(x₀)²=κπ(¹⁄₂x₀)²

π(x₀)²=κπ(¹⁄₄)(x₀)²

1=κ(¹⁄₄)

4=κ​

The surface area cross section (σ) would then be increased by:

σ·2π(x₀)=4×2π(¹⁄₂x₀)

σ·2π(x₀)=8π(¹⁄₂x₀)

σ·2π(x₀)=4π(x₀)

σ·2=4

σ=⁴⁄₂

σ=2​

The sum cross sections would be increased two‐fold with one branch point (maintaining constant volume and pressure), leading to more contact with the arterial wall. The surface area is simply the cross sections times the length. The most studied microcirculatory regions are those of the liver and the blood–brain barrier, where first‐pass tryptophan⁽¹⁾ and sex steroid⁽²⁾ uptake has been experimentally proven to be greatly increased over expected using radio‐labeled molecules followed by quick decapitation.

'The above model emphasizes the view that the transportability of albumin-bound testosterone and other ligands [i.e. cortisol] into tissues in vivo arises from specific interactions of the binding protein with the endothelial lining microcirculation.' ―Pardridge⁽³⁾​

Since the scalp is characterized by a prostaglandin D₂ synthase gradient, has a microcirculatory region, and that prostaglandin D synthase is expressed by cortisol, aldosterone, and nothing else: Logic dictates that the prostaglandin D synthase gradient is synonymous with the cortisol + aldosterone gradient.

If this sounds speculative, that is probably because you haven't read these:⁽³⁾⁽⁴⁾

'The transport of hormone from the plasma protein-bound pool is believed to occur via a mechanism of enhanced dissociation. That is, owing to rapid interactions between the surface of the binding protein and the surface of the microcirculation, there are conformational changes about the hormone-binding site that ensue and allow for enhanced rates of release of hormone from the binding protein relative to what occurs in vitro in the absence of protein-microcirculation interactions.' ―Pardridge⁽³⁾

'Previous studies have provided direct in vivo measurements of elevated dissociation constants within the brain microcirculation.' Moreover, these studies show that permeability to the hormone in the albumin-bound form is no greater than permeability to the free hormone. The change in conformation about the hormone-binding site on albumin that is necessary to cause the enhanced rates of dissociation in vivo may be very slight indeed, and may have marked effects on the free energy of albumin-binding of a particular steroid hormone or any other ligand. This principle is true in general for protein binding of ligands. For example, recent X-ray diffraction studies show that the loss of a single hydrogen bond between the ligand and a protein-binding site results in two to three log order differences in the binding dissociation constant.' ―Pardridge⁽³⁾

'A conformational change about the albumin-binding site (caused by interactions with the surface of the organ microcirculation, see below) would result in a partial uncoiling about the binding site and markedly increase rates of hormone dissociation.' ―Pardridge⁽³⁾

'Conformational changes about ligand-binding sites on the albumin molecule may be mediated by interactions between the surface of the plasma protein and the surface of the organ microcirculation. Although albumin receptors have been proposed to exist in the organ microcirculation, the original reports purporting to demonstrate the presence of such receptors in liver have not been confirmed. Moreover, no specific saturable albumin receptor is identifiable in isolated bovine brain capillaries [...] Although specific albumin receptors do not appear to mediate the transient interactions between the surface of the organ microcirculation and the albumin molecule,' ―Pardridge⁽³⁾

'The expansion of the testosterone dissociation constant in the brain microcirculation in vivo is nearly ten-fold greater as compared to the increased dissociation constant observed in lymph node capillaries. Conversely, the increased estradiol dissociation constant in lymph node capillaries is more than double the value observed in the brain microcirculation (TABLE 1).' ―Pardridge⁽³⁾

'In addition to organ specificities, there are also binding site specificities for albuminmediated delivery of ligands to tissues in vivo. The dissociation constant of bovine albumin binding in the rat brain microcirculation in vivo has been measured for eight different ligands and the in vivo dissociation constant has been compared to that found in vitro (TABLE 2). Testosterone dissociation is increased fifty-fold in the brain microcirculation, whereas corticosterone dissociation from bovine albumin is increased only five-fold.' ―Pardridge⁽³⁾

'Owing to the rapid bolus injection of human serum labeled with [²H]testosterone or [²H]estradiol into the common carotid artery of the anesthetized rat, there is little mixing of the injection solution with the circulating rat plasma during this first passage through the brain microcirculation. The bolus is 96% through the head within the first two seconds after injection, and the first pass extraction is measured by determination of brain radioactivity following decapitation.' ―Pardridge⁽³⁾

'charge-selectivity mechanism appears to involve interactions between the surface of the plasma protein and the surface of the organ microcirculation that results in a conformational change about the hormone-binding site, and concomitantly, enhanced dissociation of the hormone' ―Pardridge⁽³⁾

'These results indicate that there are specific interactions between SHBG and CBG such that conformational changes about the oestradiol and corticosteroid binding sites, respectively, occur in rat liver at the microcirculation level.' ―Pardridge⁽⁴⁾

'The transport of hormone from the circulating plasma protein-bound pool involves tissue-mediated enhanced dissociation of the hormone from the protein without significant exodus of the plasma protein from the microcirculation compartment. The tissue-mediated enhanced dissociation mechanism varies in activity between different organs and is a much more important factor than organ differences in capillary transit times in regulating the amplification of hormone delivery to different tissues.' ―Pardridge⁽⁴⁾​

Besides its eponymous binding globulin, the corticosteroids—like tryptophan—are carried by serum albumin; this is a spongy protein characterized by seven deformable α-helices, which will more than likely enhance dissociation upon any physical disturbance. So whether you hold surface area constant (an increase in pressure) or volume constant (an increase in surface area), any arboration of the capillary network would be expected to increase steroid uptake in those regions.

[1] Oldendorf, William H. "Brain uptake of radiolabeled amino acids, amines, and hexoses after arterial injection." American Journal of Physiology--Legacy Content (1971)
[2] Pardridge, William M. "Effects of human serum on transport of testosterone and estradiol into rat brain." American Journal of Physiology-Endocrinology And Metabolism (1980)
[3] Pardridge, William M. "Selective Delivery of Sex Steroid Hormones to Tissues In Vivo by Albumin and by Sex Hormone‐Binding Globulin." Annals of the New York Academy of Sciences (1988)
[4] Pardridge, William M. "Serum bioavailability of sex steroid hormones." Clinics in endocrinology and metabolism (1986)​

Good stuff.

I was being a tad rhetorical in my response. I think the decreased vascularization at the galea diminishes ability to dissociate and recover from inflammatory mediators, promoting extended bouts of disrupted detoxification and inability to maintain oxidative metabolism at a site responsible for sustaining "mini-organs" with high energy-demands, hair follicles. In other words, I doubt there's any sort of evolutionary advantage to losing hair. Rather, it's a condition of metabolic origin

 

[Travis]

I had the most incredible, luxurious, thick, dark and shiny hair while feeling like crap, with stress and eating whole grains and salmon. Ray has said he thought hair had their use in keeping the brain warm, perhaps having higher body temperatures can be detrimental to hair health in some people, hair becoming an unnecessary feature of the body if the brain is warm (or even slightly too warm).

Those fish oils do tend to inhibit prostaglandin synthesis, either by displacing and enriching the membrane or by competing with arachidonic acid for cyclooxygenase—but probably both. I find the articles by David Rose⁽¹⁾ some of the best for in vitro prostaglandin studies, where he shows these effects. Ray Peat cites David Rose, and he's also a good writer:

'Eicosapentaenoic acid is incorporated into phospholipids at the expense of AA and competes for the same enzymes in the eicosanoid biosynthetic pathway, thus suppressing prostanoid synthesis (38). Corey et al. (39) found DHA to be an inhibitor of PG synthesis and to a lesser extent of the lipoxygenase responsible for leukotriene biosynthesis from AA, and, in a dietary study of mammary carcinogenesis induced by DMBA, feeding ω−3 FA‐rich menhaden oil not only lowered tumor incidence but caused a reduction in both leukotriene B₄ and PGE levels in the tumors which did develop (40).' ―Rose​

[1] Rose, David P. "Effects of fatty acids and inhibitors of eicosanoid synthesis on the growth of a human breast cancer cell line in culture." Cancer research (1990)​

 

[Sheik]

I tried some topical spironolactone cream and it made me feel very ill (twice), though I'm not sure what all the ingredients were. Maybe there was something to enhance absorption. Who knows.

 

[mayweatherking]

But why do normal people get away with normal levels of cortisol and PUFA with a full head of hair?

its when the magnesium starts getting leaked, then the digestion issues get in there, i think that causes the muscles in the skull to get tense.. although i don't know why it doesn't happen to women also, although i know it does, not nearly at the same level.

i wonder what the prolactin levels are of those people? prolactin would show that magnesium (and calcium) aren't going where they should

 

[Wagner83]

Those fish oils do tend to inhibit prostaglandin synthesis, either by displacing and enriching the membrane or by competing with arachidonic acid for cyclooxygenase—but probably both. I find the articles by David Rose⁽¹⁾ some of the best for in vitro prostaglandin studies, where he shows these effects. Ray Peat cites David Rose, and he's also a good writer:

'Eicosapentaenoic acid is incorporated into phospholipids at the expense of AA and competes for the same enzymes in the eicosanoid biosynthetic pathway, thus suppressing prostanoid synthesis (38). Corey et al. (39) found DHA to be an inhibitor of PG synthesis and to a lesser extent of the lipoxygenase responsible for leukotriene biosynthesis from AA, and, in a dietary study of mammary carcinogenesis induced by DMBA, feeding ω−3 FA‐rich menhaden oil not only lowered tumor incidence but caused a reduction in both leukotriene B₄ and PGE levels in the tumors which did develop (40).' ―Rose​

[1] Rose, David P. "Effects of fatty acids and inhibitors of eicosanoid synthesis on the growth of a human breast cancer cell line in culture." Cancer research (1990)​

Does that mean you think fish fat can actually help? There are quite a few studies on fish oil anti inflammatory effects, while their methods, fundigs and conclusions can be discussed from what you say it could be a decent tool in the box if it doesn’t act as bad as the prostaglandins or zrachidonic acid they reduce or compete with.

 

[Kibs]

If it was that effective at regrowing hair, there’d be much more surrounding it.

try It?

 

[Frankdee20]

try It?

Internally ?

 

[Travis]

Does that mean you think fish fat can actually help? There are quite a few studies on fish oil anti inflammatory effects, while their methods, fundigs and conclusions can be discussed from what you say it could be a decent tool in the box if it doesn’t act as bad as the prostaglandins or zrachidonic acid they reduce or compete with.

Yeah. Check out the David Rose study. These are remarkably straightforward and he only uses things such as arachidonic acid, indomethacin, and various competing fatty acids to measure cancer cell proliferation. He also measures the prostaglandins afterwards, showing how other fatty acids (i.e. oleic and eicosapentaenoic acids) inhibit cyclooxygenase and prostaglandin production.

But the highly unsaturated fatty acids found in fish still could contribute to lipofuscin—although probably not as much as free iron, homocysteine, and aluminum.

 

[Travis]

I tried some topical spironolactone cream and it made me feel very ill (twice), though I'm not sure what all the ingredients were. Maybe there was something to enhance absorption. Who knows.

Well, spironolactone has been determined unabsorbable. Moreover, it would theoretically not even be expected to be (see here).

 

[eddiem991]

its when the magnesium starts getting leaked, then the digestion issues get in there, i think that causes the muscles in the skull to get tense.. although i don't know why it doesn't happen to women also, although i know it does, not nearly at the same level.

i wonder what the prolactin levels are of those people? prolactin would show that magnesium (and calcium) aren't going where they should

Which muscles in the skull?

 

[Sheik]

Well, spironolactone has been determined unabsorbable. Moreover, it would theoretically not even be expected to be (see here).

Very interesting. I don't know what it was but not even topical estrogen cream made me feel that bad. I found the ingredients list... S5 spiro contains: 5% Spironolactone, 1% Caffeine, 0.025% Retinol, Menthol, Rosemary Oil.

 

[mayweatherking]

Which muscles in the skull?

i don't know, there are tons of theory sites that show the muscles in the skull getting tight, something with the galea. there was some study where they put botox into some guys head to relax the muscles and the guy managed to regrow his hair. someone else did it, but it didn't work, but not really sure how it went or if they even did it right.

all those guys that look into it though they think if they do scalp massage or something, it will fix the problem. i don't think it is accurate, i don't think that fixes the problem. its the cortisol is high, or lack of magnesium, or a backed up digestive system, or lack of pregnenlone, i'm not sure what it is exactly, but it causes the muscles in the head to get strained, like on the side of the head. you notice people who are bald, their skull is shiny, like it was stretched out somehow. i don't know the process though.

but it seems like the right course of events, like fungus buildup, lack of vitamin A, digestion problems, it leads to this chain of events where the muscles get strained. it doesn't make sense why it doesn't happen to women though, i don't know why, maybe it's the DHT that causes the muscles to strain, i really don't know as i keep saying lol, but i have felt the muscle strain and felt it relax as well.

 

[Travis]

Well prostaglandin D₂ does cause artery constriction; prostaglandin E₂ causes dilation. An analogous thing can be said about the lungs.

When acting on Gpr44—the prostaglandin D₂ receptor suggested by Garza to be the mediator (a.k.a. CRTH2 and DP‐2)—prostaglandin D₂ causes calcium influx and the production of cAMP. I think these are one event, because the transformation from ATP to cAMP represents a loss of ATP‐bound Mg²⁺. Calcium influx and cAMP always seem to happen concurrently, and I think perhaps the formation of cAMP itself drives the Ca²⁺ influx by releasing its counterion Mg²⁺. There is also phospholipase C which releases inositol phosphates from phospholipids, which chelate Ca²⁺ in vitro. But despite the undeniable and well known affinities between ATP and Mg²⁺, and between inositol phosphates and Ca²⁺, a membrane pump is invoked to describe this. Since Gilbert Ling has shown one of them cannot possible do as supposed (Na⁺/K⁺‐ATPase, which actually appears to a membrane aldosterone receptor), I don't think we should feel compelled to accept the idea of the similar 'Ca²⁺ pump'—especially since the Ca²⁺ influx is always proceeded by the release of the strongest endogenous calcium chelator (IP₃) or the loss of the body's most ubiquitous Mg⁺ chelator (ATP ⟶ cAMP).

The mitochondrial membrane has an electrical potential of roughly −150·mV on average. The cell's four main ions—Mg²⁺, Ca²⁺, Na⁺, and K⁺—are all positively charged. Trypan blue, an anion, is excluded from the cell until it dies (i.e. mitochondria stops functioning). At that point, trypan blue diffuses into to the cell and this can be visualized. Despite these obvious facts, the partitioning of all four main ions—Mg²⁺, Ca²⁺, Na⁺, and K⁺—are explained through the use of 'pumps' with impossible modes of action.

And the death of a cell results in an equilibration of all ions with the surrounding fluid, despite the residual ATP in the cell and environs remaining to power all hypothetical pumps. Adenosine triphosphate was invoked to link mitochondrial respiration with ion partitioning, but you don't even need that; oxidative respiration produces a strong negative charge at the mitochondria which attracts ions of opposite charge—no unicorns required.

So if prostaglandin D₂ ultimately exerts its effects through constriction—either of the blood supply or the root sheath—by shifting calcium (long known to be involved in muscle contraction), then Mg²⁺ would seem logical.

But I don't think there are any muscles along the very top of the head, the place most prone to hair loss. Is prostaglandin D₂ causing local ischemia or thinning the hair or by constricting the root sheath? Garza's research had suggested that Gpr44 was responsible, but I haven't seen anyone else try to explain anything downstream from that. It's common for people to stop the explanation at the point of the ligand–receptor event, but some of these interactions can be understood on a deeper level. Perhaps it all really does come down to local ischemia after all?

cortisol ⟶ ptgds ⟶ PGD₂ ⟶ ishemia? ⟶ hair loss
​

Although there are no large muscles on the top of the head, you would think that there would be very small ones—perhaps actin filaments—lining the capillary walls. After all, constriction does happen somehow.

Perhaps the Ca²⁺/Mg²⁺ ratio is nearly as important as linoleic acid? These are two things that separate humans from the other primates: Besides eating much less linoleic acid, other primates would consume far more magnesium for their body weight. I don't think any other animals get alopecia besides the spotty type seen during parasitic infection (i.e. canine leishmaniasis, a.k.a. interferon-γ creating PGD₂ in spots by upregulating phospholipase A₂).

 

[Travis]

it doesn't make sense why it doesn't happen to women though, i don't know why, maybe it's the DHT that causes the muscles to strain, i really don't know as i keep saying lol, but i have felt the muscle strain and felt it relax as well.

Well, human males are known to produce more cortisol than females. They are also known to have more prostaglandin D₂. This is expected, since cortisol activates the transcription of ptgds, an enzyme which catalyzes it's formation.

A slightly more esoteric fact, but also true, is that males have more interferon-γ in the thymus. There is a sex differential of immunity, with males having a more TH1-dominated profile and females having a more TH2-dominated profile. Only the TH1 cells produce γ-interferon, and this increases all prostaglandins by greatly upregulating an enzyme which helps to make them: phospholipase A₂. Believe it or not, finasteride has been shown to lower interferon-γ (and the thymus has high-affinity androgen receptors.)

 

[Sheik]

Well prostaglandin D₂ does cause artery constriction; prostaglandin E₂ causes dilation. An analogous thing can be said about the lungs.

About artery constriction/dilation, do you think co2 could help with hair loss if you were to have, say, an airtight bag over your scalp and fill it with co2? I've wondered this and I've got a co2 tank but haven't tried it.