RENIN-ANGIOTENSIN-ALDOSTERONE SYSYTEM And HAIR LOSS PROCESS

[mrchibbs]

thats true ! And we do know about it! Spirolactone lol. It works. Just with nasty side effects.

I think spiro’s side effects are more benign than finasteride ironically

 

[wavelength123]

Finasteride / Dutasteride side effects are massively overblown. If you’ve got enough T in the first place (which many hair loss sufferers may not have) you’ll be absolutely fine.

I’ll wager studies show very low sides because they’re picking up patients who aren’t hypogonadal to begin with. I’m quite convinced many who hop on 5ar inhibitors are in such a poor state of health, they can’t afford losing DHT. Me personally, I’m fine on those drugs. Most guys are totally fine.

same with spironolactone, same with accutane, same with most drugs. The nocebo effect is very strong on the internet because of vocal minorities. I’m not saying it never happens. But go ask any doctor in medicine or pharmacy (like Me).

in before typical internet anti fin/dut shitstorm...

 

[wavelength123]

That said. I agree that edema is very likely. When my scalp was very itchy I swear my hats were fitting tighter. There’s an issue with hypoxia and impaired blood flow that can’t be denied, it’s highly plausible that micro circulation gets hit first. This creates fibrosis and those ugly big skulls you can see everywhere among balding men/women. Cue the whole pro inflammatory cascade. Starch is the most surefire way to bloat me up whereas drinking milk all day makes me pee it all.

every time we trace back up to the root cause it’s hyper insulinemia / hyperglycemia.

.... in before “someone knows a diabetic who isn’t bald”. Yet.

 

[mrchibbs]

Finasteride / Dutasteride side effects are massively overblown

I completely disagree. I think finasteride’s side effects are worse than people even suspect. But you’re free to have your opinion, I just feel strongly about this one.

 

[tallglass13]

Everyone I've ever known that's taking finasteride said mainly the loss of morning wood, and feeling a disconnect between the body and the penis.
Even my transplant surgeon can't use finasteride he get side effects. Most people going into finasteride treatment are in hopes of regrowing hair, they want to stay positive. the fact is finasteride Is A Dangerous Drug that causes 90% side effects. I guess there's 10% of people that don't get them. But that is a lot different from the 1% side effects they tell the customer!

 

[mrchibbs]

Everyone I've ever known that's taking finasteride said mainly the loss of morning wood, and feeling a disconnect between the body and the penis.
Even my transplant surgeon can't use finasteride he get side effects. Most people going into finasteride treatment are in hopes of regrowing hair, they want to stay positive. the fact is finasteride Is A Dangerous Drug that causes 90% side effects. I guess there's 10% of people that don't get them. But that is a lot different from the 1% side effects they tell the customer!

I think it’s even more sinister than these sexual side effects, it leads to permanent neurological remodeling and dysbosis of the brain chemistry.

 

[GorillaHead]

That said. I agree that edema is very likely. When my scalp was very itchy I swear my hats were fitting tighter. There’s an issue with hypoxia and impaired blood flow that can’t be denied, it’s highly plausible that micro circulation gets hit first. This creates fibrosis and those ugly big skulls you can see everywhere among balding men/women. Cue the whole pro inflammatory cascade. Starch is the most surefire way to bloat me up whereas drinking milk all day makes me pee it all.

every time we trace back up to the root cause it’s hyper insulinemia / hyperglycemia.

.... in before “someone knows a diabetic who isn’t bald”. Yet.

Exceptions do not invalidate theories. I will say this again and again. Its the biggest lesson i learned.

Smoking causes long cancer. Yet there will be hella people who smoke for 30 years no lung cancer and they 75 or something.


Diabetic suffers if they eat hella sugar but if i eat hella i am side effect free.

its your vulnerability to the action that determines everything. We all have different levels of how we process things

 

[GorillaHead]

As someone who ignored everyone. Anti androgens are the worst thing ever. Who ever thought that was a great idea has scammed the world. I mean ***t for all the side effects at least give me progress. But no my experience made hair worse and side effects. I legit had a better chance drinking booze everyday than finasteride

 

[md_a]

Blood clotting & thrombosis

In healthy people the systems that are responsible for activating blood clotting and those that are responsible for inhibiting clotting and breaking down clots are in balance. In people with thrombosis the balance has been disturbed. The enzyme Plasminogen Activator Inhibitor-1 [PAI-1] may be too active, or the enzyme Plasminogen Activator [tPA] may not be active enough.

Strength training helps prevent thrombosisExplanation: tPA breaks down blood clots. PAI-1 inhibits tPA, and thus encourages the formation of blood clots.

Strength training helps prevent thrombosis

...

Hair Loss Study to Investigate PAI-1 Protein in Follicles

n observational study aiming to investigate whether people with any form of non-scarring hair loss condition have increased levels of a specific protein within their hair follicles compared to control subjects of the same age but without hair loss, is currently recruiting participants.


Volunteers aged 18 to 60 will be drafted from patients seen at Northwestern Memorial Hospital or Northwestern Medical Faculty Foundation physicians’ offices, which are affiliated to Chicago’s Northwestern University Feinberg School of Medicine where the study will take place.


Scalp Punch Device Used in FUE Hair TransplantsScalp biopsy required

Researchers will explore the protein PAI-1 and the extent to which it is expressed in test subjects both with and without non-scarring forms of hair loss, including male and female pattern hair loss (androgenetic alopecia), telogen effluvium and the autoimmune condition alopecia areata.


Eleven of the selected participants will have a scalp biopsy using a 4 mm punch, similar to those used in FUE hair transplants. This will allow PAI-1 levels in the scalp’s skin tissue to be determined through immunohistochemical staining.


Following each biopsy the sample skin will be formalin-fixed overnight at room temperature, processed and embedded with paraffin. Sections measuring six microns in depth will be prepared and stored at room temperature.


The amount of active PAI-1 in each total tissue area will be measured using imaging software. After this, the levels of PAI-1 found in scalp tissues both with and without hair loss will be recorded and the results compared.


What is PAI-1?What is PAI-1?

The protein known as PAI-1, or Plasminogen Activator Inhibitor-1, is a serine protease inhibitor (serpin) which is mostly produced in the cells lining the blood vessels. It is critical to the fibrinolytic system and plays an important role in preventing blood clots.


Elevated levels of PAI-1 are found in people who are obese or who have a number of diseases, including various forms of cancer. It has also been linked to patients with these conditions developing thrombosis.


Potential implications

The study’s resulting findings could help to not only further understanding of the behaviour of hair follicles, but also aid development of the next generation of hair loss treatments for various conditions.


For instance, should researchers discover higher levels of PAI-1 expression in the follicles of people with hair loss, this could open up a new avenue in the development of future treatments. It will also be interesting to discover if there are significant differences in PAI-1 levels between each of the hair loss conditions – so whether, for example, people with Alopecia Areata have a higher, lower or no meaningful difference in PAI-1 levels when compared to those with genetic hair loss.


This study is due to conclude in December 2016 after which time researchers will analyse the gathered data and release their findings. We will publish these results as soon as they become available so do check back for updates to this story.

https://www.belgraviacentre.com/blog/hair-loss-study-to-investigate-pai-1-protein-in-follicles/

PAI-1 Expression in Non-scarring Hair Loss - Full Text View - ClinicalTrials.gov

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A Potential Suppressor of TGF-β Delays Catagen Progression in Hair Follicles

TGF-β plays important roles in the induction of catagen during the hair cycle. We examined whether TGF-β2 could activate a caspase in human hair follicles. Using active caspase-9 and -3 specific antibodies, we found that TGF-β2 activated these caspases in two regions, the lower part of the hair bulb and the outer layer of the outer root sheath. In addition, we searched for a plant extract that can effectively suppress TGF-β action. We found that an extract of Hydrangea macrophylla reduced synthesis of a TGDβ-inducible protein. We confirmed that the extract has a potential to promote hair elongation in the organ culture system. Furthermore, it delayed in vivo progression of catagen in a mouse model. Our results suggest that the induction of catagen by TGF-β is mediated via activation of caspases and that a suppressor of TGF-β could be effective in preventing male pattern baldness.


Hair loss is the result of premature entry into catagen due to various causes, including androgens (Jahoda, 1998), anticancer drugs (Paus et al, 1994), and inflammatory reactions (Galbraith et al, 1984). Three distinct phases have been defined for the mammalian hair cycle: anagen (growing phase), catagen (regressing phase), and telogen (resting phase) (Kligman, 1959). It is important to understand the catagen induction mechanism in order to find ways to prevent hair loss.


We have previously reported two important findings in this process. First, catagen is characterized by the massive apoptotic cell death of follicular epithelial cells (Soma et al, 1998). Second, TGF-β2 appears in the lower part of the boundary area between the dermal papilla cells and the germinative matrix cells during anagen-catagen transition phase in vivo. Using hair follicle organ culture we have clearly demonstrated that exogenous TGF-β could induce morphological changes and apoptotic cell death indistinguishable from that which is seen in human catagen hair follicles. In progressing stages of catagen, TGF-β2-, TGF-βRII- and TUNEL-positive cells were colocalized at the regressing epithelial strand. Furthermore, we demonstrated that a neutralizing antibody to TGF-β prevented morphological changes and resulted in the elongation of hair shafts (Soma, submitted). These findings strongly suggest that TGF-β plays an essential role in catagen induction via activation of an apoptotic pathway.


Caspases are well-known expediters of apoptosis and 14 members are known in mammals (Kumar, 1999). Once the caspase cascade is activated, it inevitably leads to apoptotic cell death. It is now widely accepted that sequential activation of caspases is required in apoptosis processes.


In the present study, we investigated whether TGF-β2 could activate the expedition of apoptosis, the caspase cascade. In addition, we searched for a plant extract that could effectively suppress TGF-β action in catagen progression. We identified such an extract and confirmed that it can delay catagen progression in vivo.

Hydrangea macrophylla, a potential TGF-β2 antagonist, caused elongation of hair follicles

Suppression of TGF-β was hypothesized to prevent apoptosis and to delay catagen entry. Therefore, we sought a natural inhibitor of TGF-β action. We developed a screening method for TGF-β suppression by monitoring changes in PAI-1, a TGF-β responsive gene product. (Zhang et al, 1998). Over 400 plant extracts were screened. Among these, the extract from Hydrangea macrophylla (tea of Heaven) was most effective in suppressing PAI-1 synthesis (Figure 2a). Using the organ culture system, the effect of the H. macrophylla extract on hair follicle elongation was tested. Human hair follicles were cultured in the presence of the extract for 7 d. The resulting follicles showed significant elongation (Figure 2b). Treated follicles showed an average of 2.25 mm elongation, compared to an average of 2.0 mm for the controls. The difference is significant to a p-value of <0.05 as assessed by the one-way ANOVA and Dunnett's posthoc procedure.

...

Involvement of TGF-β in catagen induction is also suggested in mice. TGF-β1 levels increase in late anagen and remain at maximal throughout catagen (Foitzik et al, 2000). TGF-β type II receptor was restricted in hair follicles and was up-regulated in anagen-catagen transtion phase (Paus et al, 1997).


Our next goal was to test whether suppression of TGF-β2 could delay catagen entry. In this study, we identified an H. macrophylla extract as a potential suppressor of TGF-β2 action, because it could reduce PAI-1 production from dermal papilla cells. Although PAI-1 transcription requires both TGF-β activated Smad proteins and independently activated AP-1 (Zhang et al, 1998), we favor the model that this extract blocks TGF-β function because of its effect on hair follicles. The H. macrophylla extract was effective on hair elongation in organ culture system. Furthermore, using the in vivo mouse model, we showed that topical application of the extract leads to delay of catagen progression. Suppression of TGF-β is expected to provide a novel and efficient tool for hair cycle regulation.

A Potential Suppressor of TGF-β Delays Catagen Progression in Hair Follicles - ScienceDirect

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PAI-1 is a Marker and a Mediator of Senescence

Abstract

Plasminogen Activator Inhibitor-1 (PAI-1) is a member of the evolutionarily conserved serine protease inhibitor (SERPIN) family, and a potent and rapid-acting inhibitor of both of the mammalian plasminogen activators. Organismal homeostasis requires physiological levels of endogenous PAI-1 and increased PAI-1 production guides the onset and progression of numerous human diseases and contributes to the multimorbidity of aging. Both chronological and stress-induced accelerated aging are associated with cellular senescence and accompanied by marked increases in PAI-1 expression in tissues. Recent studies suggest that PAI-1 is not only a marker but also a key mediator of cellular senescence and organismal aging. Here, we review the significance of PAI-1 as a bonafide marker as well as a critical mediator of cellular senescence associated with aging and aging-related pathologies.

Conclusion and future directions

In this perspective, we summarized the science linking PAI-1 with cellular senescence. Furthermore, we discussed recent studies illustrating the role of PAI-1 as an important senescence mediator as genetic deficiency and/ or pharmacological inhibition of PAI-1 is sufficient to forestall cellular replicative senescence and prevent age-related pathology and morbidity in mammals. Therefore, the development of novel small molecule-based therapies targeting normalization/inhibition of elevated PAI-1 provides a novel and rational approach to control cellular senescence and age-associated pathologies including thrombosis, arteriosclerosis, obesity, diabetes, organ fibrogenesis, emphysema and major depressive disorders. There is broad acceptance among investigators that PAI-1 comprises an important component of the molecular signature of senescence. Beyond that, recent studies from our own and other laboratories indicate that PAI-1 is not a merely a marker of cellular senescence but also a key mediator of senescence at the cellular level and is also a major contributor to physiological aging. We are currently investigating the role of PAI-1 in aging and age-associated pathologies including insulin resistance, chronic kidney diseases and cardiac fibrosis, and testing the effects of novel pharmacological inhibitors of PAI-1 in reversal of PAI-1 associated pathologies in animals and humans. We anticipate that ongoing and future investigations will further establish PAI-1 as a central mediator of organismal aging and provide additional rationale for prospective trials designed to determine the role of specific PAI-1 inhibitors in delaying aging-related morbidity and mortality in humans.

PAI-1 is a Marker and a Mediator of Senescence

...

PAI-1 Antagonists: The Promise and the Peril

Abstract

The plasminogen activator (i.e., fibrinolytic) system is one of the key endogenous defense mechanisms against intravascular thrombosis. Thrombolytic agents represent the only direct way of augmenting fibrinolytic activity in humans, and have proven to be of value in the treatment of acute myocardial infarction and stroke. Although these agents are efficacious in the acute setting, they are not a viable option for long-term use. Net fibrinolytic activity is plasma is largely determined by the balance between tissue-type plasminogen activator (t-PA) and its natural, fast-acting inhibitor, plasminogen activator inhibitor-1 (PAI-1). The recent development of specific PAI-1 antagonists promises to expand the limits of understanding of the role of the fibrinolytic system in human disease, and to break through the current confines of therapeutic options that can effectively restore and augment the activity of the fibrinolytic system.


The fibrinolytic system is one of the key endogenous defense mechanisms against intravascular thrombosis (1). At present, thrombolytic agents represent the only direct way of augmenting fibrinolytic activity in humans. Although these agents are proven to be efficacious in the treatment of acute thrombotic events, they are not a viable option for long-term use. Net fibrinolytic activity in plasma is largely determined by the balance between tissue-type plasminogen activator (t-PA) and its natural, fast-acting inhibitor, plasminogen activator inhibitor-1 (PAI-1). There are numerous drugs available that indirectly increase fibrinolytic activity by reducing plasma levels of PAI-1, including angiotensin converting enzyme (ACE) inhibitors, insulin-sensitizing agents, and the hormones used in hormone-replacement therapy in women. Plasma PAI-1 is derived from several sources, including the vascular endothelium, adipose tissue, and the liver. Plasma PAI-1 levels reflect a complex calculus of genetic factors; hormonal, metabolic, and inflammatory stimuli; and body mass. There is also a well-recognized circadian variation in the plasma activity of PAI-1, and this fluctuation in PAI-1 activity is responsible for the diurnal variation in net fibrinolytic activity (2).


Probably the most common clinical condition associated with increased PAI-1 production is obesity. Although plasma PAI-1 activity is consistently elevated in patients with obesity and insulin resistance, the precise source of PAI-1 is debated, and may include the vascular endothelium, liver and/or adipose tissue, including both adipocytes and stromal cells (3) located within visceral fat. In encoding a protein involved in fibrinolysis, the PAI-1 gene is remarkable for its responsiveness to a variety of metabolic and hormonal factors that are associated with obesity. Analytical studies of the upstream regulatory region of the PAI-1 gene has allowed the identification of relevant transcriptional response sites, including a glucocorticoid response element (GRE) that also localizes aldosterone responsiveness (4), a very-low-density lipoprotein (VLDL) response site (5), and two Sp1 sites that appear to mediate glucose/glucosamine responsiveness (6). In the aggregate, probably the most important determinants of plasma PAI-1 in a given individual include the molecular clock, body mass index (BMI), genetic determinants, and hormonal, inflammatory, and metabolic factors. At the molecular level, the hierarchy of factors that regulate transactivation of the PAI-1 promoter are the molecular clock, inflammatory cytokines, and hormonal and metabolic factors, while the suppressors of PAI-1 expression are less well defined, but include nitric oxide and cyclic nucleotides (7).

PAI-1 Antagonists: The Promise and the Peril

...

Clearly the plasminogen activator system plays a role in hair-follicle cycling and growth. I don't know if PAI-1 plays a direct role in hair loss associated with the administration of chemotherapy. As I showed a few moments ago, PAI-1 antagonists can promote the growth of hair in PAI-1-overexpressing mice. We will soon test this in other models of alopecia.




Plasminogen activator inhibitor-1 expression is regulated by the angiotensin type 1 receptor in vivo

DISCUSSION

In the current study, we demonstrate that Ang II acutely induces PAI-1 expression in the rat. This effect of Ang II is largely mediated via the AT1 receptor and appears to be independent of blood pressure effects, although a minor component contributed to by local pressure effects cannot be definitively excluded based on our measurements of systemic blood pressure. Thus, normalization of Ang II-induced hypertension with hydralazine had no effect on PAI-1 induction. This induction by Ang II of PAI-1 may be a key contributor to the effects of Ang II in promoting tissue injury and/or blunting reparative responses. Although activation of the RAS is generally associated with increased fibrosis, there is substantial evidence that inhibition of the RAS ameliorates progressive renal injury beyond that which can be attributed to blood pressure effects alone1, 3, 16. In the 5/6 nephrectomy hypertensive rat model of progressive renal disease, simple blood pressure reduction with hydralazine failed to attenuate glomerulosclerosis, while ACEI or AT1RA (with similar systemic blood pressure effect) were effective in this regard17. In the nonhypertensive radiation nephropathy rat model, both ACEI and AT1RA completely prevented tissue injury14. These results show that inhibition of the RAS can attenuate tissue injury via the AT1 receptor independently of antihypertensive actions and suggest that merely controlling blood pressure with nonspecific antihypertensives may not have the same antifibrotic potential. The implication follows that the local RAS, rather than only systemic blood pressure, may play a predominant role in the development of sclerosis.


Activation of the RAS has previously been shown to induce multiple growth factors that have been implicated in fibrosis, such as transforming growth factor-β; (TGF-β and platelet-derived growth factor-B (PDGF-B)3, 18, 19, 20. Induction of these growth factors appears to be mediated by Ang II acting at the AT1 receptor21. TGF-β; itself is known to regulate PAI-1 expression through a Smad-dependent signaling pathway22. However, the early induction of PAI-1 by Ang II in vitro in mesangial cells is TGF-β; independent23. The link between the RAS and the PAI-1 proteolytic pathway has only been recognized more recently, but may be a key mechanism of Ang II-induced injury24. We have previously shown that the hexapeptide metabolite of Ang II, Ang IV, stimulates PAI-1 expression in vitro6,7. This relationship between Ang and PAI-1 was also demonstrated in animal studies with aortic injury25 or renal microvascular injury induced by radiation14. The colocalization of injury with increased PAI-1 expression supports a pathogenic role for PAI-1 in tissue injury14. Furthermore, the prevention of injury in the radiation model by either an AT1 antagonist or ACEI was tightly linked to decreased, albeit not normalized, PAI-1 expression14. Studies in PAI-1 knockout mice also support a role for PAI-1 in tissue injury. Pulmonary fibrosis in response to bleomycin was significantly reduced in PAI-1 knockout mice when compared with wild-type controls12. Studies in humans also show an effect of Ang II on PAI-1. Infusion of Ang II in patients specifically induced PAI-1 plasma levels and activity without affecting t-PA levels26. Activation of the endogenous RAS is also associated with increased plasma PAI-1 levels in humans27. Conversely, ACEI in patients after acute myocardial infarction resulted in decreased PAI-1 levels and activities28. Epidemiological studies point to adverse consequences of increased PAI-1 levels, with an association with increased cardiovascular disease29, 30, 31.


The association of PAI-1 with either thrombotic or fibrotic injuries in both animal models and humans thus points to this molecule as a key target in progressive renal and/or cardiovascular injuries. However, a more precise understanding of the mechanisms of induction of PAI-1 by the RAS in vivo may yield more optimal targets for intervention. Our studies indicate that in vivo induction in the rat of PAI-1 by Ang II is mediated by the AT1 receptor, contrasting our previous observations of the role of the AT4 receptor in this induction in vitro. Obviously, species and cell and/or tissue differences may exist to account for these results. It is appropriate to caution that the specific receptor(s) that regulates the interaction of the RAS and PAI-1 in humans has not been definitively determined. The current studies have not directly tested a possible contribution of the AT4 receptor to the PAI-1 induction. A cell-specific contribution of the Ang IV metabolite via the AT4 receptor cannot be excluded by the current study. Further delineation of the potential role of the AT4 receptor thus awaits its cloning and the availability of specific tools with which to regulate this receptor in vivo.


These studies implicate PAI-1 as an important factor activated by Ang II and demonstrate yet another facet of the broad spectrum of Ang actions. These results also indicate that inhibition of Ang-induced PAI-1 can be accomplished by antagonism of the type 1 receptor in the rat. The link between the RAS and PAI-1 provides an additional mechanism whereby the RAS might promote sclerotic mechanisms, namely by increasing PAI-1 activity and the consequent activation of both thrombotic and sclerotic injuries. Thus, strategies that effectively inhibit the pathological increases in PAI-1 consequent to increased RAS activity are likely to be particularly efficacious in preventing end organ damage. These in vivo studies point to the feasibility of manipulating the PAI-1 induction with specific Ang antagonists. Future approaches may include PAI-1 specific antagonists, instead of or in addition to RAS inhibitors in patients with pathological activation of these systems. The current findings thus have important implications for strategies to optimize the prevention and treatment of Ang and PAI-1–mediated adverse events in human disease.

Plasminogen activator inhibitor-1 expression is regulated by the angiotensin type 1 receptor in vivo - ScienceDirect

 

[wavelength123]

Everyone I've ever known that's taking finasteride said mainly the loss of morning wood, and feeling a disconnect between the body and the penis.
Even my transplant surgeon can't use finasteride he get side effects. Most people going into finasteride treatment are in hopes of regrowing hair, they want to stay positive. the fact is finasteride Is A Dangerous Drug that causes 90% side effects. I guess there's 10% of people that don't get them. But that is a lot different from the 1% side effects they tell the customer!

Don't see why select few anecdotes and made up statistics prove a point, but let's all agree to disagree and leave anti androgens on the side for now.

I think it's more interesting to say that if cell metabolism/thyroid is healthy, none of that matters.

Probably the most common clinical condition associated with increased PAI-1 production is obesity. Although plasma PAI-1 activity is consistently elevated in patients with obesity and insulin resistance, the precise source of PAI-1 is debated, and may include the vascular endothelium, liver and/or adipose tissue, including both adipocytes and stromal cells (3) located within visceral fat. In encoding a protein involved in fibrinolysis, the PAI-1 gene is remarkable for its responsiveness to a variety of metabolic and hormonal factors that are associated with obesity. Analytical studies of the upstream regulatory region of the PAI-1 gene has allowed the identification of relevant transcriptional response sites, including a glucocorticoid response element (GRE) that also localizes aldosterone responsiveness (4), a very-low-density lipoprotein (VLDL) response site (5), and two Sp1 sites that appear to mediate glucose/glucosamine responsiveness (6).

In the aggregate, probably the most important determinants of plasma PAI-1 in a given individual include the molecular clock, body mass index (BMI), genetic determinants, and hormonal, inflammatory, and metabolic factors. At the molecular level, the hierarchy of factors that regulate transactivation of the PAI-1 promoter are the molecular clock, inflammatory cytokines, and hormonal and metabolic factors, while the suppressors of PAI-1 expression are less well defined, but include nitric oxide and cyclic nucleotides (7).

AKA our usual suspects!

 

[md_a]

Folates take part producing red blood cells and hemoglobin, which transport oxygen to tissue building hair. Folate is responsible for "Stimulating of rebuilding of hair follicle cells, prevent hair graying and falling out, and regulating sebum glands functioning"

...

Support Proteoglycan Production

In the skin, there are molecules called proteoglycans. They have various functions.

One proteoglycan, decorin, has been shown to block the effects of TGF-β, the growth factor that contributes to scalp calcification (16).

The synthesis of decorin requires amino acids from proteins in the diet and a galactosaminoglycan called dermatan sulfate.

The synthesis of dermatan sulfate requires sulfation by an enzyme called sulfotransferases (17). Sulfation is a process by which sulfur is added to a molecule.

This process requires a sulfur donor. This can be achieved by dietary sulfur, however, many factors can limit sulfur absorption including extremely common imbalances in gut bacteria (18).

A majority of the sulfur supply is derived from homocysteine metabolism (19). This is a series of enzymatic conversions that detoxifies homocysteine to produce cysteine and methionine, two important sulfur donors.

Four B-vitamins are absolutely essential to this process:

Riboflavin (B2)

Pyridoxine (B6)

Folate — not folic acid (B9)

Cobalamin (B12)

B6 is essential for the transsulfuration of homocysteine to cysteine.

B6 and B2 are involved in the enzymatic conversion of folate to 5-methyltetrahydrofolate (5-MTHF) that allows 5-MTHF and B12 to convert homocysteine to methionine.

Because they exist in a cycle, all reactions are dependent on each other. So, while each nutrient is important for individual reactions, they all work synergistically for the functionality of the whole cycle.

Another way to boost sulfur levels is through the skin. Magnesium sulfate, in the form of Epsom salts or magnesium oil, is another possible route of absorption.

Bolstering sulfur levels in these ways may be beneficial for sulfotransferase reactions which play a role in decorin synthesis. However, this hasn’t been directly studied.


Key Takeaways:

Decorin is a proteoglycan that requires dermatan sulfate. Dermatan sulfate is produced through sulfotransferase reactions.

Sulfotransferase reactions require sulfur donors from the diet or sulfur produced by reactions in the body. However, sulfur absorption from the diet can be limited by a myriad of factors including the common gut dysbiosis.

B2, B6, B9, and B12 play key roles in the production of cysteine and methionine, two sulfur donors that are used for sulfotransferase reactions.

Magnesium sulfate from epsom salts and magnesium oil may also provide sulfur to the body through the skin, which bypasses the problematic digestive absorption.

Because sulfur is essential for sulfotransferase activity, dermatan sulfate is produced through sulfation, and decorin synthesis is dependent on dermatan sulfate, bolstering sulfur levels in this way may boost decorin synthesis. However this hasn’t been directly studied.

Scalp Calcification & Hair Loss: Is There a Connection? - Hair Science

A newly discovered linkage between proteoglycans and hair biology: decorin acts as an anagen inducer

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Intracranial calcification mimicking the Sturge-Weber syndrome A consequence of cerebral folic acid deficiency?

Abstract

Cerebral cortical calcification identical to that of the Sturge-Weber syndrome was observed in two children. In one child the calcification appeared after intrathecal administration of methotrexate and skull irradiation because of leukemia involving the central nervous system. In the other child, who had coeliac disease and epilepsy, the calcification appeared after treatment with anticonvulsants. This treatment was also contributing to the development of profound megaloblastic anemia. The unspecificity of the Sturge-Weber calcification is stressed and the hypothesis is put forward that the calcification may be secondary to folic acid deficiency interfering with the metabolism in the central nervous system.

Intracranial calcification mimicking the Sturge-Weber syndrome A consequence of cerebral folic acid deficiency?

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Progressive Intracranial Calcification in Dihydropteridine Reductase Deficiency Prior to Folinic Acid Therapy

Abstract

Hyperphenylalaninemia in infants and children may be caused by a deficiency of dihydropteridine reductase (DHPR). Recommended therapy includes folinic acid as a source of tetrahydrofolate, a phenylalanine-restricted diet, and both dopamine and serotonin precursors. We report a child with progressive basal ganglia and other subcortical calcifications prior to the use of folinic acid. Six other reported cases of DHPR deficiency demonstrated similar calcifications prior to folinic acid therapy. Since this pattern of calcification also resembles that seen in CNS folate deficiency caused by both congenital folate deficiency and that which is methotrexate-induced, we propose that intracranial calcification in DHPR deficiency is caused by inadequate CNS tetrahydrofolate and may be prevented by the use of folinic acid. Our patient achieved excellent seizure control following the use of folinic acid, suggesting either a direct or indirect anticonvulsant effect of this compound in patients with DHPR deficiency.

Progressive Intracranial Calcification in Dihydropteridine Reductase Deficiency Prior to Folinic Acid Therapy - PubMed

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Hyperhomocysteinemia, Angiotensin, and Hypertension

Angiotensin II is the main peptide of rennin–angiotensin system and activation of angiotensin type 1 (AT1) receptor leads to the production of ROS. Although studies have demonstrated AT1 receptor-mediated production of ECM components, very little is known about AT1 receptor regulation and its consequences in hyperhomocysteinemia. We have demonstrated that homocysteine induced the AT1-receptor induced MMP-9 and collagen synthesis in vascular endothelial cells [85]. Laggner et al. [86] showed that H2S inhibited angiotensin-converting enzyme (ACE) activity of endothelial cells. Therefore, it is possible that during hyperhomocysteinemia reduced-H2S will promote ACE activity that may lead to upregulation of angiotensin II and subsequently hypertension. However, this mechanism needs to be investigated thoroughly before a conclusion can be drawn. A possible pathway of angiotensin II modulation by H2S during hyperhomocysteinemia resulting in vascular fibrosis and hypertension has been shown in Fig. 6.

Homocysteine to Hydrogen Sulfide or Hypertension

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Hyperhomocysteinemia and Psoriasis

Psoriasis is a chronic inflammatory disease of the skin that affects the 3% of the population. It is characterized by erythema-squamous plaques distributed symmetrically in typical sites (elbows and knees, sacral region and scalp). Several studies demonstrated that psoriasis was related to increased mortality for coronary heart disease (124), cerebrovascular disease and pulmonary embolism (125). Other studies have shown that psoriasis was connected to subclinical vascular alterations like intima-media thickness, arterial wall stiffness and coronary calcifications, confirming the tight association between atherosclerosis and psoriasis (126).

Interestingly, psoriatic patients showed an increased risk of developing atherothrombotic diseases, and in parallel, psoriasis duration and severity seem also to be correlated with an increased cardiovascular risk, although biomarkers are still missing. In line with such an interaction between psoriasis and cardiovascular disease, classical systemic anti-psoriatic therapy (cyclosporine, retinoids, and methotrexate) can increase the risk factor for cardiovascular attack together with an increased homocysteine expression level (127) (Figure 2).

Furthermore, HHCys seemed to be associated with psoriatic disorder and with platelet hyperactivity that promotes prothrombotic events, which determine increased risk of death caused by arterial and venous thrombosis. Dietary modifications appear relevant in helping the global management of patients with moderate to severe psoriasis (128). However, in a study on psoriatic patients, the decrease in folic acid level was more attributed to an increased consumption from proliferating keratinocytes rather than to the correlation between the serum folate level and the duration or extent of clinical psoriasis (129). Plasma HCys directly correlated with psoriasis severity according to skin psoriasis area and severity index (PASI) score (the clinical gold standard measure of psoriasis severity), whereas it was inversely correlated with plasma folic acid levels, which were lower in psoriasis patients than in the controls and lower than the normal range in 13 of 40 (32.5%) psoriasis patients studied (127).

Hyperhomocysteinemia as a Risk Factor and Potential Nutraceutical Target for Certain Pathologies

...

Hydrangea Macrophylla for Hair Loss Captures the Attention of Scientists

The hydrangea plant extract may offer a natural form of treatment to help control hair loss

Hydrangeas which belong to the Saxifragaceae family, are known for their beautiful pink and lavender colored flower clusters. Although they are cherished in gardens and given as gifts, the lower part of the plant (the roots and rhizomes, or the underground stem segments) also offer therapeutic benefits. Extracts have been used for medicinal purposes to dissolve kidney stones and promote urinary tract health. But in recent years, Hydrangea macrophylla for hair loss has been captivating the interest of modern scientists.


This particular plant species is native to Japan. Other than being a colorful, eye-catching bloom, it is now the subject of research, offering a potentially new approach for treating male pattern baldness.


Suppressing TGF-B2 to Treat Hair Loss Using Hydrangea Leaf Extract

The hydrangea plant extract may offer a natural form of treatment to help control hair loss


Hair loss is characterized by the early entrance into the catagen stage of the hair follicle cycle. At this point the epithelial cells die, causing the hair follicle to enter the telogen resting stage.


The three main causes leading to the catagen stage include inflammatory reactions, anti-cancer drugs and androgens.


Alopecia and Transforming Growth Factor Overview

Androgen-induced alopecia, also known as androgenic alopecia or male pattern baldness involves the breakdown of testosterone to DHT. Hair follicles enter the catagen stage and miniaturize when DHT binds to genetically sensitive receptors on these structures. However, there are other pathways which also instigate the catagen stage which induces hair loss. One includes the role of TGF-B2 (transforming growth factor).


TGF-B2 activates caspases which are protease enzymes that promote various forms of programmed cellular death (e.g. apoptosis, pyroptosis, and necroptosis) as well as inflammation. In-vivo studies show that this compound is secreted in the lower part of the hair follicle during the transition between the anagen and catagen phase.


Role of TGF in Hair Health & Natural Hair Treatments

Researchers also applied external sources of TGF-B2 to cultured human hair follicles which induced cellular death. These findings confirmed it’s damaging effects on follicular health and it’s potentially prominent role in hair loss.


As TGF-B2 plays a role in cellular death, it not only instigates the catagen phase, but also transitions the follicle to the telogen resting phase. Through this paradigm, suppressing this compound could potentially be an effective approach to preventing male pattern baldness.


Although it is possible to design synthetic drugs, such chemicals may exert toxic side effects on various other regions of the body. Drug chemicals tend to operate through a single active component. While this may be beneficial for the target treatment area, it could be detrimental in other regions of the body.


Natural plant extracts, on the other hand, include a number of neutralizing compounds which balances out the excessive activity of the main compound. This helps to avoid dangerous toxic effects.


Many researchers are now interested in finding natural alternatives to synthetic hair loss drugs. A group of scientists wanted to investigate the potential of plant extract, including hydrangea leaf extract to suppress PAI -1, a TGF-B1 gene product.


How Scientists Discovered that Hydrangea Macrophylla Leaf Extract Could Grow Hair

The benefits of using hydrangea macrophylla for hair loss may include its ability to target a different chemical pathway other than DHT.

The benefits of using hydrangea macrophylla for hair loss may include its ability to target a different chemical pathway other than DHT.


A team of researchers obtained human hair follicles from plastic surgery skin samples and cultured them outside the body in a petri-dish. They isolated the anagen stage follicles and exposing them to TGF-B2 for two days. After this period, they looked for evidence of caspase-9 and caspase 3 activation.


Using this research design, the scientists tested over 400 plant essences. They isolated dermal papilla cells and incubated them with TGF-B2 and various plant extracts. Out of the 400 botanical types, they found that hydrangea macrophylla for hair loss performed the best in causing the follicles to elongate (i.e. grow hair).


Based on this phenomenon, it seemed that it acted as an antagonist to the TGF-B2. The researchers were able to find quantitative support for this concept by monitoring the levels of PAI-1, a precursor gene product of TGF-B1.


A Closer Look at the Hydrangea Plant Extract and Hair Growth

The researchers investigated another sample of cultured human hair follicles. This time they exposed them for seven days to the Hydrangea macrophylla leaf extract.


After the week long incubation period, the researchers observed significant hair growth. The follicles treated with hydrangea macrophylla for hair loss exhibited elongation by 2.25mm. The untreated control group of follicles only showed an average measurement of 2.0mm.


Hydrangea leaf extract has helped cultured human hair follicles grow longer hair in-vivo.


In-Vivo Studies on Hydrangea Macrophylla for Hair Loss in Mice

The experiments described earlier were conducted using cultured follicles from humans. Researchers were interested in knowing whether or not comparable findings could be seen in living organisms. They decided to perform studies on C57BL mice, a common strain of dark-haired laboratory mice.


They used wax removal to remove hair from the backs of the animals in order to start a new hair cycle where all the follicles are synchronized. Next they applied a 2% concentration of Hydrangea macrophylla for hair loss to certain zones on the treated area. Other zones were left as control samples. The researchers performed this treatment protocol for ten days to observe the stage of the catagen phase, compared to the follicles in the control zone. The researchers found that half the follicles in the regions treated with the Hydrangea leaf extract remained in much earlier catagen stages compared to the non-treated control zones.


These observations suggested that the Hydrangea extract delayed the progression of the catagen stage. Furthermore, the researchers found that this treatment reduced the production of PAI-1 from the derma papilla cells of the hair follicles.


The Future of Research on Hydrangea Macrophylla Leaf Extract for Hair Growth

This overall study sheds new light on using hydrangea extract as a way to manage androgenic alopecia by exerting greater control over the hair life cycle. As previously stated, much attention has been given to inhibiting the formation of DHT and yet there are still numerous other pathways that also contribute to pattern baldness. As shown by this study, TGF-B2 plays a significant role in the hair loss process by causing follicular cells to die and inducing the catagen stage. The authors of this research study have illustrated the ability of Hydrangea macrophylla for hair loss to suppress TGF-B2. Yet further levels of investigation are still needed to form a more complete picture for the use hydrangea macrophylla in the fight against hair loss.


Research shows that the Hydrangea leaf extract may prove to be an effective topical agent that helps improve hair loss conditions


The portion of the research study which dealt with human hair was performed in-vitro, by culturing follicles outside the body. Mice models were used to confirm these findings within living systems. Yet additional research on the effects of the hydrangea leaf extract within the human body is still necessary. Scientists would need to determine how the living environment which surrounds the follicles may affect the performance of the hydrangea extract. Although plant essences are typically much safer than synthetic drugs, researchers should also investigate potential side effects which may arise in other parts of the body.


Frequently Asked Questions – Hydrangea Macrophylla for Hair Loss

Will drinking Hydrangea Macrophylla tea help me control my hair loss or even grow new hair?

Hydrangea macrophylla tea may be made from either the flowers or the plant’s roots. However, the effects of a tea may not be likely to produce noticeable improvements in your hair loss condition. First, there are no documented studies or anecdotal evidence which supports the effects of drinking hydrangea tea to treat hair loss. Low concentration levels of the active therapeutic agents present in tea may be one reason. Also, how natural ingredients are processed can affect their therapeutic qualities. For example, dried plant extracts may not perform as well as pressed or distilled versions of an herb.


Is it better to ingest Hydrangea macrophylla orally or to apply it topically to the skin as a hair loss treatment?

This study only examined the topical use of the Hydrangea macrophylla for hair loss. Further studies on the oral consumption (e.g. powdered form in capsules) would be needed to determine how effective this delivery method would be. With topical approaches, it is possible to create a more direct path between the active agents of the Hydrangea macrophylla extract and the hair follicles. This can surely lower the potential for side effects and offer a more targeted form of treatment. The challenge of making topical forms of treatment work has been the issue of penetrating the skin at sufficient depths to affect the hair follicles. However, the use of safe and natural skin penetrating agents helps to make this a viable possibility.


What are the components of the Hydrangea macrophylla leaf extract that allow it to benefit the hair follicles and other areas of health?

Researchers have yet to isolate and study specific constituents found in the Hydrangea macrophylla plant extract to determine which components responsible for controlling hair loss. However, the general compounds that are believed to have health benefits include flavonoids, alkaloids, hydrangin ( a phytochemical solvent, as well as minerals such as calcium, magnesium, phosphorous and sulfur.


References

(1) Tsuji Y, Denda S, Soma T, et al. A potential suppressor of TGF-beta delays catagen progression in hair follicles. J Investig Dermatol Symp Proc 2003;8(1):65-8.

Does Hydrangea Macrophylla For Hair Loss Really Work? | Dr.UGro.

 

[md_a]

Regarding gray hair, I want to mention that besides a good thyroid, red light, copper ... folic acid is also important, which is easily lost when estrogen is high, retinoids, UV, alcohol, maybe even coffee ...

Oxidative stress by decreasing melanin production contributes to depigmentation.

As a tyrosine derivative, melanin is responsible for pigmentation.

Vitamins B2, B3, B6, B12 and folic acid inhibit the production of excess homocysteine. Homocysteine regulates the activity of tyrosinase, an enzyme responsible for the production of melanin, and in excess homocysteine generates free radicals (hydrogen peroxide), which leads to the destruction of melanocytes and hair bleaching.

“Age pigment, lipofuscin, is produced in oxygen deprivation, apparently from reduced iron which attacks unsaturated fats. It has its own “respiratory” activity, acting as an NADH-oxidase. Melanin is produced by polymerization of amino acids, with copper as the catalyst. With ageing, iron tends to replace copper. Melanin is an antioxidant. Thus, there is a sort of reciprocal relationship between the two types of pigment. A vitamin E deficiency relative to consumption of polyunsaturated fats, and an oestrogen excess, accelerate the formation of lipofuscin.” Ray Peat

...

As the scientific knowledge deepens, we continue to discover more about the role of melanin and the triggering factors for grey hair. Scientist may one day at will, manipulate Melanin – the pigment that colors our hair and skin – to reduce and even eliminate grey hair.


To recap, melanin is a form of an amino acid known as tyrosine, which helps support healthy brain function. As a derivative of tyrosine, melanin is responsible for the pigmentation – essentially the color of our hair and skin. In addition to providing us with our unique skin and hair colors, melanin’s primary function is to absorb harmful UVA rays and transform them into energy, thus reducing our chance of developing deadly skin diseases and cancers. Melanin deficiency can result in a range of diseases, including albinism an even Parkinson’s Diseases – and of course, this deficiency also directly contributes to grey hair.


Studies have shown that hair with large amounts of melanin are more saturated in color than their deficient counterparts; therefore, when melanin death occurs (which can arise due to the natural aging process, stress and genetics), the hair follicles become less saturated with color and are effectively bleached into grey hair. So it stands to reason that if a decrease in melanin production contributes to greying, then an increase in melanin production can re-saturate the hair with pigmentation, thereby effectively reversing the process.


And that’s exactly what scientists set out to test.


In a two-year study conducted by the Department of Dermatology at University Hospital in Uppsala, Sweden, researchers discovered that folic acid, vitamin B12 (also called cobalamin) and sun exposure could help encourage re-pigmentation of the skin and hair. One hundred patients with vitiligo – a condition where the skin loses its pigmentation – were treated with folic acid and B12, and told to increase their exposure to the sun. After three to six months, researchers noted that re-pigmentation was evident in 64% of patients, with six patients experiencing total re-pigmentation.


These findings were further supported by a study conducted by researchers at the Department of Dermatology at the University of Alabama, where scientists discovered that patients who suffered from vitiligo often displayed diminished blood levels of folic acid. By increasing folic acid consumption through oral administration, researchers noted that patients experienced re-pigmentation without side effects.

How the Lack of These 2 Vitamins May Be Causing Your Gray Hair!

...

Improvement of Vitiligo After Oral Treatment With Vitamin B12 and Folic Acid and the Importance of Sun Exposure

The aim of this 2-year study was to test the hypothesis that folic acid, vitamin B12 and sun exposure could be helpful in treating vitiligo. One hundred patients with vitiligo were treated with oral folic acid and vitamin B12 after being informed that sun exposure might enhance repigmentation. They were requested to keep a record of sun exposure in summer and UVB irradiation in winter. The minimal treatment time suggested was 3-6 months but should be longer if improvement was achieved. Clear repigmentation occurred in 52 patients, including 37 who exposed their skin to summer sun and 6 who used UVB lamps in winter. Repigmentation was most evident on sun-exposed areas, where 38% of the patients had previously noted repigmentation during summer months. Total repigmentation was seen in 6 patients. The spread of vitiligo stopped in 64% of the patients after treatment. Folic acid and vitamin B12 supplementation combined with sun exposure can induce repigmentation better than either the vitamins or sun exposure alone. Treatment should continue as long as the white areas continue to repigment. Further studies are needed to determine ideal minimal dosages of vitamins and UV exposure, as well as treatment time.

Improvement of Vitiligo After Oral Treatment With Vitamin B12 and Folic Acid and the Importance of Sun Exposure - PubMed

...

Senile Hair Graying: H2O2-mediated Oxidative Stress Affects Human Hair Color by Blunting Methionine Sulfoxide Repair

Abstract

Senile graying of human hair has been the subject of intense research since ancient times. Reactive oxygen species have been implicated in hair follicle melanocyte apoptosis and DNA damage. Here we show for the first time by FT-Raman spectroscopy in vivo that human gray/white scalp hair shafts accumulate hydrogen peroxide (H(2)O(2)) in millimolar concentrations. Moreover, we demonstrate almost absent catalase and methionine sulfoxide reductase A and B protein expression via immunofluorescence and Western blot in association with a functional loss of methionine sulfoxide (Met-S=O) repair in the entire gray hair follicle. Accordingly, Met-S=O formation of Met residues, including Met 374 in the active site of tyrosinase, the key enzyme in melanogenesis, limits enzyme functionality, as evidenced by FT-Raman spectroscopy, computer simulation, and enzyme kinetics, which leads to gradual loss of hair color. Notably, under in vitro conditions, Met oxidation can be prevented by L-methionine. In summary, our data feed the long-voiced, but insufficiently proven, concept of H(2)O(2)-induced oxidative damage in the entire human hair follicle, inclusive of the hair shaft, as a key element in senile hair graying, which does not exclusively affect follicle melanocytes. This new insight could open new strategies for intervention and reversal of the hair graying process.

Senile Hair Graying: H2O2-mediated Oxidative Stress Affects Human Hair Color by Blunting Methionine Sulfoxide Repair - PubMed

...

The Vitamin D–Folate Hypothesis as an Evolutionary Model for Skin Pigmentation: An Update and Integration of Current Ideas

Abstract

Vitamin D is unique in being generated in our skin following ultraviolet radiation (UVR) exposure. Ongoing research into vitamin D must therefore always consider the influence of UVR on vitamin D processes. The close relationship between vitamin D and UVR forms the basis of the “vitamin D–folate hypothesis”, a popular theory for why human skin colour has evolved as an apparent adaption to UVR environments. Vitamin D and folate have disparate sensitivities to UVR; whilst vitamin D may be synthesised following UVR exposure, folate may be degraded. The vitamin D–folate hypothesis proposes that skin pigmentation has evolved as a balancing mechanism, maintaining levels of these vitamins. There are several alternative theories that counter the vitamin D–folate hypothesis. However, there is significant overlap between these theories and the now known actions of vitamin D and folate in the skin. The focus of this review is to present an update on the vitamin D–folate hypothesis by integrating these current theories and discussing new evidence that supports associations between vitamin D and folate genetics, UVR, and skin pigmentation. In light of recent human migrations and seasonality in disease, the need for ongoing research into potential UVR-responsive processes within the body is also discussed.

The Vitamin D–Folate Hypothesis as an Evolutionary Model for Skin Pigmentation: An Update and Integration of Current Ideas

...

The Vitamin D–Folate Hypothesis as an Evolutionary Model for Skin Pigmentation: An Update and Integration of Current Ideas

Abstract

Vitamin D is unique in being generated in our skin following ultraviolet radiation (UVR) exposure. Ongoing research into vitamin D must therefore always consider the influence of UVR on vitamin D processes. The close relationship between vitamin D and UVR forms the basis of the “vitamin D–folate hypothesis”, a popular theory for why human skin colour has evolved as an apparent adaption to UVR environments. Vitamin D and folate have disparate sensitivities to UVR; whilst vitamin D may be synthesised following UVR exposure, folate may be degraded. The vitamin D–folate hypothesis proposes that skin pigmentation has evolved as a balancing mechanism, maintaining levels of these vitamins. There are several alternative theories that counter the vitamin D–folate hypothesis. However, there is significant overlap between these theories and the now known actions of vitamin D and folate in the skin. The focus of this review is to present an update on the vitamin D–folate hypothesis by integrating these current theories and discussing new evidence that supports associations between vitamin D and folate genetics, UVR, and skin pigmentation. In light of recent human migrations and seasonality in disease, the need for ongoing research into potential UVR-responsive processes within the body is also discussed.

The Vitamin D–Folate Hypothesis as an Evolutionary Model for Skin Pigmentation: An Update and Integration of Current Ideas

...

Albinism is a genetic disorder that affects (completely or partially) the coloring of skin, hair, and eyes. The defect is primarily due to the inability of melanocytes to produce melanin.

Pigmentation | Biology for Majors II

...

Melanin occurs in two primary forms. Eumelanin, the most common form of melanin, exists as black and brown, whereas pheomelanin provides a red color. Dark-skinned individuals produce more melanin than those with pale skin. Exposure to the UV rays of the sun or a tanning salon causes melanin to be manufactured and built up in keratinocytes, as sun exposure stimulates keratinocytes to secrete chemicals that stimulate melanocytes. The accumulation of melanin in keratinocytes results in the darkening of the skin, or a tan. This increased melanin accumulation protects the DNA of epidermal cells from UV ray damage and the breakdown of folic acid, a nutrient necessary for our health and well-being. In contrast, too much melanin can interfere with the production of vitamin D, an important nutrient involved in calcium absorption. Thus, the amount of melanin present in our skin is dependent on a balance between available sunlight and folic acid destruction, and protection from UV radiation and vitamin D production.

Pigmentation | Biology for Majors II

...

The pathogenesis of premature canities is not yet clear but various hypotheses have been suggested including alteration in pH and cysteine levels in melanosomes, the role of trace metal ions, vitamin B12 and folic acid, vitamin D3, and oxidative stress.

...

In the present study, an almost similar percentage of cases and controls were found to have folic acid deficiency (n = 20, 38.5% vs. n = 19, 36.5%). Nevertheless, the mean folic acid levels were found to be significantly lower in cases. It was also noted that 65% of cases with folic acid deficiency had concomitant Vitamin B12 deficiency as compared to 21% of controls. In addition, the serum folic acid levels correlated positively (Spearman ρ = 0.173) with serum Vitamin B12 levels though this was not significant (P = 0.221). It is a well-known fact that Vitamin B12 deficiency impairs the metabolism of folic acid, leading to a functional folate deficiency (the folate trap). In the present study, we got a deficiency of both the micronutrients suggesting possible role of both Vitamin B12 and folic acid in premature canities.

Prospective Analytical Controlled Study Evaluating Serum Biotin, Vitamin B12, and Folic Acid in Patients with Premature Canities

...

It has been stated that the default human skin color is most closely related to that of Ethiopians (a light brown shade). However, as stated above, there is a large variation in colors. Obviously, there is a factor that alters the default situation to other tones. Essentially, there is an adaptation that causes a lighter skin color and an adaptation that creates a darker skin color than the default (17, 18).

The darker adaptation seems to come from a need for folate. If there is not enough melanin in the skin at lower latitudes (near the equator), too much UV radiation is able to penetrate the skin. The intense UV causes a halt to the folic acid synthesis - the result of the lack of folate can cause neural tube defects in unborn fetuses. A higher level of melanin allows normal folate synthesis by absorbing the UV radiation, and can allow for normal gestation and fetal development. Essentially, evolution allowed for a feature (darker skin) that would allow healthy and successful reproduction.


The lighter adaptation allows for a greater quantity of vitamin D synthesis. A greater amount of epidermal melanin blocks UV penetration which is needed for the transformation of 7-dehydrocholesterol to calciferol (vitamin D3).

https://www.sas.upenn.edu/~zhall/chem507/vitDskin.html

...

Too much ultraviolet radiation penetrating the skin may cause the breakdown of folate in the body, which can cause anemia. Folate is derived from folic acid (one of the B vitamins) in our food. Pregnant women who are deficient in folate are at a higher risk of having miscarriages and babies with neural tube defects. Because folate is needed for DNA replication in dividing cells, its absence can have an effect on many body processes, including the production of sperm cells. It may be that the ability to produce melanin was selected for in our early human ancestors because it helped preserve the body's supply of folate in addition to reducing the chances of developing skin cancer.

Human Biological Adaptability: Skin Color as an Adaptation

...

“(Vitiligo) has been corrected by giving pantothenic acid or PABA.” (PABA is a constituent of folic acid.) Let’s Get Well, by Adelle Davis, A Signet Book from New American Library.

“Copper-containing polyphenoloxidases such as tyrosinase are involved in the production of melanin from tyrosine. This process is extremely responsive to changes in copper status; loss of pigment from wool, hair, and feathers is a sensitive index to changes in copper deficiency.” Copper in Animals and Man, Volume II, by John Howell, McC., D.V.Sc., F.R.C.Path., Jeffrey M. Gawthorne, Ph.D., CRC Press, Inc., Boca Raton, FL.


“Copper, folic acid, and pantothenic acid have been successful in recoloring gray hair.” Know Your Nutrition, by Linda Clark, Keats Publishing, Inc., New Canaan, CT.

Studies Show Which Vitamins to Take for Vitiligo | Recouleur® Vitamins for Vitiligo

 

[not_James_Bond]

@mrchibbs @GorillaHead @Ableton
What do you think about Hydrangea Macrophylla

@md_a Do you suffer with hairloss?

 

[Estradiol]

All these studies are great but none of these explains why women are immune to hair loss.

 

[wavelength123]

All these studies are great but none of these explains why women are immune to hair loss.

newsflash they aren’t, like, at all.

 

[Estradiol]

newsflash they aren’t, like, at all.

They clearly are. You don't see a 20 years old girl with a NW3? WTF is your problem.

 

[wavelength123]

They clearly are. You don't see a 20 years old girl with a NW3? WTF is your problem.

I'd say YOUR problem is you may need to look at people in real life, instead of being another aggressive internet moron who resorts to arbitrary N=1 to try to prove a laughable point. They lose their hair a lot, just a different pattern. You may not know too many women tho, which isn't my problem LOL.

By the way I wanted to thank @md_a for sharing quality data, in the midst of low level thinkers who only debate in terms of "XYZ food is good/evil" and "your whole theory is flawed because of my inane observation of someone somewhere on this planet"

 

[mrchibbs]

@wavelength123
@Estradiol

Lets not go down this road again. be respectful to one another, you both have made great contributions to the discussion.

@md_a ’s research is great, always useful and well thought out.

With respect to women, I think its clear they are relatively protected by the hormonal benefits of their ovarian cycle- i.e. the high estrogen and progesterone. Women with menstrual difficulties start exhibiting MPB characteristics and if they have straight up PCOS they can bald aggressively, same with postmenopausal women.

 

[wavelength123]

idk how much of it is hormonal considering how prevalent hypothyroidism is in females. They're diffuse thinning like crazy for the most part. Talking about Norwood scale in 20yo girls is downright dumb since it's the Savin/Ludwig scale that's to be used anyway.

I'd say they do have more SHBG, less free androgens, tend to eat and drink less trash (more alkaline foods), less adrenaline seeking, less absurd overtraining. Yet, there's TONS of diffuse thinning all over the place. Many rely on hair extensions and expensive cosmetics to save the day.

 

[mrchibbs]

idk how much of it is hormonal considering how prevalent hypothyroidism is in females. They're diffuse thinning like crazy for the most part. Talking about Norwood scale in 20yo girls is downright dumb since it's the Savin/Ludwig scale that's to be used anyway.

I'd say they do have more SHBG, less free androgens, tend to eat and drink less trash (more alkaline foods), less adrenaline seeking, less absurd overtraining. Yet, there's TONS of diffuse thinning all over the place. Many rely on hair extensions and expensive cosmetics to save the day.

Definitely. Hair quality and density has declined in girls as well, and many wear extensions like you say. I saw many young otherwise healthy early 20s girls with severe thinning.

Ray has said that the high progesterone of the menstrual cycle interrupts the stress of relative hypothyroidism and can protect women from the continous degeneration, at least for a time.

I dont care much for the standardized scales personally. I am a man and when I lost hair it was in a diffuse pattern. I dont think MPB is a male shape, its just how hair loss progresses because of the scalp vascularisation. Its seen in both sexes at different points of life.