Could alopecia be as simple as a zinc deficiency?

[Baz493]

https://pubmed.ncbi.nlm.nih.gov/20523772/ When I went bald, during my late teens, I had no idea that the primary cause of my condition was coeliac disease. That took me decades to learn. I also had no idea that dandruff is a sign of skin conditions resulting from either bacterial (staphylococcus) or fungal (malassezia) infections. Funny thing about all of these is that they induce, among other things, zinc deficiency in the skin. Zinc is required not only for preventing sebum from blocking pores of the skin (comedogenic) but also for a wide range of factors affecting both skin health and hair growth. Stem cells, throughout our bodies, change into cells which are required at the time and may revert to being stem cells if the body signals that it requires different cells. Not only does that signaling become disrupted when zinc deficiency occurs but the normal process, stabilising the workhorse cells they have become and preventing them from reverting, lacks the essential zinc needed to maintain it. https://pubmed.ncbi.nlm.nih.gov/35172118/ Conditions such as atopic dermatitis occur in the skin and even the bone of the skull can lose integrity, due to the same stem cell differentiation which occurs in the skin. The normal pattern of alopecia develops because of the galea apotoneurotica, a fibrous mat of collagen which connects the muscles on either side of the scalp. This mat contains numerous fibroblasts, which all require lots of zinc to both maintain their own stem cell stability and to produce all of the required collagen to maintain the apotoneurosis. The scalp on top of the head is like a zinc sponge, requiring constant feeding. So if you add conditions like coeliac disease, inducing nutrient deficiencies, and/or disruption of the top layer of the skin (stratum corneum) allowing infections to enter the skin then that zinc sponge suddenly becomes an open drain. The hair bulges, containing stem cells which produce the hair, rise to the surface of the skin and differentiate into skin keratinocytes and the skin thins. Hair canals need to be at least 4mm deep inside the skin in order to be able to produce mature hair. Ironically, dietary zinc levels don't necessarily equate to tissue zinc levels. Some people have SLC30 or SLC39 gene mutations which reduce the levels of proteins which transport zinc, and other minerals, around the body. Once a zinc deficiency occurs you become even more vulnerable to allergic reactions as zinc helps to prevent Th2 allergic response from switching into Th17 response. https://www.researchgate.net/public...the_Dermis_Particularly_around_Hair_Follicles https://pubmed.ncbi.nlm.nih.gov/20215335/ You always hear people blaming dihydrotestosterone for hair loss but it is the Th2 and Th17 responses which are actually responsible. Interleukin signaling, involved in Th2 and Th17 responses, tells stem cells in the hair bulges to enter resting stage of hair growth. https://pubmed.ncbi.nlm.nih.gov/34281739/ Dihydrotestosterone actually tries to reduce that signaling. https://pubmed.ncbi.nlm.nih.gov/1830499/ As I have read about cases of excessive dietary zinc inducing alopecia I am cautious regarding supplementing the diet. Find a way to reduce the underlying factors inducing zinc deficiency in the scalp and the problem will hopefully be eliminated.

 

[Baz493]

I was able to find this additional 2013 study which examines zinc deficiency in alopecia, with additional study of copper and magnesium. https://anndermatol.org/DOIx.php?id=10.5021/ad.2013.25.4.405 It is obvious, from the study, that copper deficiency is not necessary for alopecia to develop. However, I suspect that when it is present it is likely to lead to a greater likelihood of fungal infection, as copper tends to inhibit fungals. Magnesium deficiency, on the other hand, was suggested to be more a consequence of the skin conditions involved in alopecia in this next article from 2013. https://pubmed.ncbi.nlm.nih.gov/939335/ From what I was able to see of nutrient deficiencies involved in alopecia they tend to involve either the zinc or its cofactors, as covered in this 2019 article. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380979/

 

[jaminhealth]

I would not discount this zinc need, easy enough to supplement.

 

[Baz493]

Even the melanocytes, which give our skin and hair colouration and protection from the sun, appear to need zinc in order to facilitate their development. https://www.sciencedirect.com/science/article/pii/S0171933522000759 Melanin, produced by the melanocytes, is a really powerful antioxidant which helps to protect both skin and hair from oxidative insults. This article explains how a particular gene, involving a specific melanin receptor, affects the skin. I have included it because it demonstrates the amount of detail which is now known about melanin. https://onlinelibrary.wiley.com/doi/full/10.1111/php.12335 Variation between the presence of that receptor, eumalenin, and pheomalenin, affects the colour of our skin and hair. The balance of these are, somehow, directly involved in the development of alopecia. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948107/ It is very possible that this may relate to the ability of fungi, such as malassezia, to absorb melanin, so enhancing fungal pathogenesis. https://pubmed.ncbi.nlm.nih.gov/12734441/

On the one hand zinc will help the body to resist microbial infections and yet, via the melanin, it may also help to promote the infections ability to resist our body. I will try to find if anyone has looked at possible solutions to this yet.

 

[Baz493]

I have been able to dive even deeper into hair loss and discovered something very interesting. Skin cancers, otherwise known as melanoma's, involve glycoproteins known as laminins. These glycoproteins bind together tissues. Laminin 511, 322, and 10, all appear to be integral to hair growth. In chemotherapy they will target these glycoproteins to eliminate specific types of cancer; the reason that hair loss is so common during treatment. With melanoma the laminins anchor either melanocytes or keratinocytes in place so loss of the glycoproteins results in loss of adhesion of the hair follicles to the scalp. Of course, that kind of hair loss is over the entire scalp, rather than just above the galea apotoneurotica. However it does indicate something about the same processes being involved in alopecia areata. Although collagen 17 is anchored in tissues by laminin 322 I am still assuming that the loss of collagen 17 alpha 1, found in alopecia areata, is still due to ADAM17 cleavage, rather than a deficiency in laminin 322.

 

[Not dead yet!]

I can't tell if you are saying too much zinc or too little zinc is causing alopecia? Most dandruff shampoos have plenty of zinc and they do increase the local zinc availability of the scalp. So is that good or bad?

In my experience biotin has a very good effect on both hair retention and retaining the color of hair later in life. I tend to react badly to biotin though. Not sure why that is.

 

[Baz493]

In essence I am saying that it's possible for both deficiency and excess to cause alopecia although zinc deficiency is the most likely to result in long term alopecia. Zinc, iron, and copper compete for absorption and transport in the body, as the same factors are involved, so any excess in the levels of any of them will affect the levels of the others. This won't necessarily be reflected in blood levels of them but will affect the tissues. Hair production requires all three, to varying degree's, so deficiency in any of them will affect hair. However it appears that so much zinc is required, not only all around the body but particularly in the scalp, that deficiency of it is most likely to appear in the region where we tend to lose our hair. Involvement of laminins, which require sulphur bonding (they have disulphide bonds between sugar and protein molecules), also has me looking at whether the taking sufficient sulphur can also help. It seems to be the zinc which is the integral element though since it is required to help in preventing microbes, which live on our skin, from penetrating the skins surface. Once they do you get the conditions which are related to hair loss; dandruff, dermatitis, etc.

 

[Baz493]

I love it when research turns around and surprises me. Assuming that I am correctly interpreting the research then hair loss often revolves around skin/hair pigmentation (melanins) and the hormone dopamine. However it takes a bit of explaining. https://link.springer.com/article/10.1007/s11046-019-00345-8 One of the melanins produced by fungal infections is called dihydroxyphenylalanine. Our own bodies produce this type of melanin though, and I could be incorrect, I don't believe that they are a precise chemical match. The use of this melanin in the body, like those of other fungal melanins, can produce pathogenic effects. The form of the melanin produced by our bodies is a precursor to dopamine and excess iron can actually convert dopamine back into dihydroxyphenylalanine. They use this melanin in the medication used for people with Parkinson's disease, where its pharmaceutical name is Levodopa. So sensitization of the body to this melanin appears to predispose dark haired people to hair loss. The lighter your hair colour the lower your chances of losing your hair. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948107/ There are many other genetic or toxic factors which can be involved, such as coeliac disease and other intestinal conditions, but that seems to be the basic direction of current evidence. There appears to be an autoimmune response to the melanin in our hair follicles and melanocytes and it seems to be due to the reaction to the fungal melanin, failing to discern between the different types of melanin. https://pubmed.ncbi.nlm.nih.gov/19700020/ Some people will regrow their hair by simply resolving their intestinal issues, restoring normal levels of nutrient intake and eliminating the damage induced by the fungal skin infection. It's surprising but some people even find that losing all pigment from their hair can result in hair regrowth. https://pubmed.ncbi.nlm.nih.gov/25244170/ Antifungal shampoo's, marketed as preventative of hair loss, generally contain both selenium and zinc but also tend to contain fairly toxic chemicals which can also, ultimately, lead to hair loss.

 

[Baz493]

The 'glue' which holds our bodies together is really a set of glycoproteins called laminins. Each of them is designed to serve a specific purpose within our bodies. When our bodies lose a specific type of laminin, for any reason, the body attempts to compensate by replacing them with less efficient laminins. Laminin 511 is essential for anchoring of melanocytes and mature hair follicles and, when it is destroyed, it is replaced by laminin 322, a much weaker type of 'glue'. The result is the loss of the hair follicles.

In the intestines of people suffering from coeliac disease the villi structures are lost and the intestinal walls become smooth, losing their efficiency in nutrient absorption and ability to produce lactase, the enzyme which digests milk sugars (lactose). The loss of these structures is due to the destruction of laminin 511. In both coeliac disease and irritable bowel syndrome there is an overgrowth of the fungal yeast called candida. Candida has the ability to destroy laminin 511 so it makes sense that this fungal overgrowth is connected with the loss of the villi. https://pubmed.ncbi.nlm.nih.gov/19486268/ DIetary zinc plays an integral role in combating candida in our gastrointestinal tract and body.

Medical research appears to indicate that the same conditions occurring in the intestines are also affecting the scalp, inducing atopic dermatitis and alopecia. Inefficient zinc absorption, due to the gastrointestinal issues, on top of the galea aponeurotica's great need for zinc to produce collagen leads to the perfect situation for fungal malassezia overgrowth on the scalp. I am presuming that this type of fungal infection likely has the same capacity to destroy laminin 511 that fungal candida has. This would force the body to replace the laminin 511 with the less efficient laminin 322 which occurs in alopecia areata, so weakening the bond between the skin and the hair follicles so leading to the hair falling out. The fungal melanin involvement, leading to autoimmune assault upon melanocytes, is likely to be involved in this destruction of laminin 511 as this type of laminin specifically anchors the collagen 17 alpha 1 which anchors melanocytes found in the roots of hair follicles.

Since the same requirement for zinc is involved in production of keratin, melanin, filaggrin, collagen, and hair, the scalp is simply the one of the perfect points of weakness for evidence of zinc deficiency to demonstrate.

 

[Baz493]

I was finally able to dig deep enough into the medical research to find the base cause of alopecia. It is a set of enzymes called serine proteases. They are actually a normal part of the process of hair cycles, responsible for the release of hair follicles from the scalp during the exogen phase of hair growth. https://pubmed.ncbi.nlm.nih.gov/23992282/ They break down proteins so that their constituent materials can be recycled or discarded. In coeliac disease it is the generation of excess levels of these enzymes which destroys the laminin 511 which maintains the structural integrity of the intestinal lining and its villi. Excessive levels of candida seem to be involved in this process and fungal serine proteases are likely to be contributing to our own in inducing the excess levels. A similar situation appears to occur in the scalp with malassezia infections contributing fungal serine proteases to our own bodies.

The serine protease is able to cleave laminin 511, so cutting the tie between the skin and collagen 17 with its connection to the melanocytes and hair follicles, so resulting in the loss of the hair. Loss of the arrector pili muscles, which stimulate movement of the hair, is similarly related. Laminin 511 and laminin 211 are both skeletal muscle 'glues' in similar types of striated muscles. Specific serine protease are able to cleave these glues which hold those muscle in place, so resulting in the disappearance of the muscles.

Medications using zinc are being researched for inhibiting serine proteases due to the minerals ability to bind to the enzymes, so inhibiting their activity. Although there are already medications which also inhibit the activity of these enzymes there have been studies performed on a range of natural ingredients for their inhibition. https://pubmed.ncbi.nlm.nih.gov/11737259/

Due to the nature of these enzymes they are implicated in the pathogenesis of a wide range of different diseases. As they trigger immune responses via allergic mast cell activation this can involve fairly unlikely conditions. https://pubmed.ncbi.nlm.nih.gov/2467915/

 

[Baz493]

Integrins play an essential role in laminin binding to tissues. https://pubmed.ncbi.nlm.nih.gov/27852744/ Integrin beta 1 has been found to be essential to healthy hair growth so its involvement in antifungal response by the skin stands out, given everything I have already detailed. Not only do fungals produce serine proteases which destroy the laminin 511, which binds the hair in place, but lack of a healthy level, and form, of integrin beta 1 results in out of control fungal growth. Here is an article which connects laminin 511 and integrin beta 1 with healthy hair. https://link.springer.com/article/10.1186/1471-213X-10-112 Bacteria, and acne, appears to share similar characteristics. https://pubmed.ncbi.nlm.nih.gov/17684752/

 

[Baz493]

From what I can now see the picture of hair loss and associated skin conditions involves an out of control serine protease cascade. Researchers appear to have been focusing upon the role a protease called trypsin in hair loss. It is not only capable of cleaving the connection between laminin 511 and its associated integrins, so being involved in inducing a breakdown of gastrointestinal lining structure as well as the breakdown of healthy skin barriers. It not only cleaves the connection between hair roots and the skin but is also known to break down the structure of hair itself, leaving it thin and fragile. https://www.researchgate.net/figure...-from-hair-follicle-just-after_fig3_236039713 In coeliac disease the body appears to overproduce proteases like trypsin to try to break down gluten which a healthy intestinal microbiome would normally break down without such support. Dietary protease inhibitors can actually impact upon health in a bad way, so do not appear to be the solution. I am currently looking at things like copper to ameliorate the issue. Copper binds to trypsin, so converting into a powerful antioxidant which scavenges superoxide from the body. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5800238/ I am also testing colloidal silver in a topical manner for trypsin inhibition. https://pubmed.ncbi.nlm.nih.gov/4842294/ I am very cautious regarding dietary colloidal silver due to the risks of argyria.

 

[Baz493]

I was finally able to find this piece of medical research, connecting serine protease enzyme activity and hair loss, along with speculations on medication inhibition of enzyme activity. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4265249/ It turned out that it's actually the 5 alpha reductase enzyme, which converts testosterone into dihydrotestosterone, which triggers the sebaceous glands to produce trypsin-like enzymes which break down both the laminin/integrin in the skin and the hair follicles. This is the cause of both the dermatitis/dandruff associated with hair loss and the thinning and loss of hair. Coeliac induces this via not only reduction of zinc and copper intake but also through overproduction of trypsin (for gluten breakdown) and by inducing deficiency of antitrypsin (normally produced by our bodies to limit the presence of protease enzymes in our bodies). Usually it is our skins acidity which helps to maintain low levels of trypsin on the surface of our skin, as the acidity denatures the protease enzymes, however many kinds of assault can reduce that acidity. This provides the opportunity for trypsin levels, fungal assaults, etc, to compromise the integrity of our skin. The collagen fibres in the galea aponeurotica, which forms the pattern of male pattern baldness, are particularly susceptible to reduction by trypsin. This is the cause of skin thinning in this region, so reducing the blood flow through it, which is associated with hair loss.

While many sources discuss anecdotal evidence of topical application of things, like apple cider vinegar or lemon juice, in hair restoration they fail to connect the dots to the resulting denaturing of protease enzymes responsible for breakdown of skin and hair. They also fail to account for the internal issues which are causing the high trypsin levels. Topical applications do have their place in hair restoration but are not the complete picture.

 

[Baz493]

There hasn't been much interest in this subject but I have a little more to add to explain the picture of hair loss.

My current information on alopecia is relatively involved. Levels of mast cells in tissues around the body can vary, depending upon allergic responses, infections, disease, and even sun exposure. In the scalp it has been found that various levels of mast cells relate to specific skin conditions known to cause dandruff and hair loss. The more mast cells, histamine, and tryptase release, the more severe the skin condition which results.

With allergies, affected mast cells release prostaglandin D2, so triggering an increase in histamine and tryptase release. Tryptase can cleave integrins holding the melanocytes at the base of hair follicles, so inducing hair loss in a very similar way to that which occurs during chemotherapy (which also cleaves these integrins).

This next bit is just my own speculation, based upon what I know from research. Testosterone is required for production of healthy skin and hair so, when mast cell activity and prostaglandin D2 causes a reduction in testosterone levels, it is likely that this triggers the body to commence producing dihydrotestosterone (DHT). This hormone is a far more potent version of testosterone, theoretically helping to stabilise decreasing health of skin. However the 5-alpha reductase enzyme, which converts testosterone into DHT, triggers sebaceous gland release of the enzyme trypsin. Trypsin not only cleaves laminin 511, freeing keratinocytes at the base of hair follicles from the skin and causing hair loss, but also contributes to degradation of the hair follicles themselves. The pores, from which hair follicles emerge in our scalps, gradually shorten as our skin thins, the muscles which induce the phenomenon of hair standing on end actually disappear, and our scalps develop that familiar shiny appearance. Many, if not all, of us will be familiar with excessive oily sweating from our scalps, in the form of sebum released from the sebaceous glands also releasing the trypsin. We all think that the sweat somehow relates to our hair loss but we are never sure why. Now we do know. It's very likely that this form of sebum is also highly comedogenic, blocking the already smaller pores of the skin in our scalps. Different forms of alopecia relate to varying levels of mast cell numbers in the scalp, just like they relate to different types of skin condition.

 

[Baz493]

I wasn't able to explain the reason for increased quantities of mast cells in the scalp until now. The answer is homocysteine. Many of us have poor methylation of homocysteine, leading to increased risk of developing cancer or other health issues. It turns out that the body increases numbers of mast cells in order to try to protect tissues from homocysteine induced damage. https://pubmed.ncbi.nlm.nih.gov/15591099/ As the methylation enzymes, for reducing homocysteine, are zinc dependent it explains why zinc is essential for hair growth. https://pubmed.ncbi.nlm.nih.gov/25467853/ Homocysteinylation, the addition of a thiol group, induces a wide range of damaging effects to tissues. In the opening statement of this article it explains that homocysteinylation inactivates trypsin, explaining why the body would choose to overproduce the enzyme by whichever mechanisms remain available to it. https://www.researchgate.net/public...l_consequences_of_elevated_homcysteine_levels That's why gene mutations affecting methylation, such as the MTHFR mutations, result in hair loss. Homocysteinylation of hair results in keratin damage and the release of trypsin, which further degrades the hair. https://pubmed.ncbi.nlm.nih.gov/30345292/ Mast cell release of tryptase only further adds to the damage resulting from all of this.

 

[Baz493]

It's still early to tell but a new piece of the puzzle of hair loss may have been added thanks to some Chinese research published in 2019. For a long time lysine supplementation has been suggested as a possible way of reducing hair loss and the new research might explain the reason. High lactic acid/lactate levels have been connected to a process called lactylation. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222712/ The lactate binds to certain proteins when this occurs and lysine is one of them. It alters the way in which those proteins function and affects the function of whichever processes they are involved in. Lysine plays a number of essential roles in production of hair and it's highly likely that compromised lysine function is going to be devastating to hair growth.

 

[Englishlady]

I don’t know all the technical details but I have had episodes of a sudden increase in overall hair loss. This happened after giving birth and has also happened a few times since. It was driving me mad - hair all over my clothes, hairbrush filling up, hair on my hands, too much hair in the sink, a hair seemed to appear in the middle of whatever I was doing! I was diagnosed with zinc deficiency on one occasion and supplements worked. My hair stopped falling out and became thicker. On other occasions, my zinc status has been described by doctor as ‘low’ but not technically deficient. However, on those occasions, and based on past experience, I took high-strength zinc supplements and the hair loss slowed and stopped. I know it is the first thing I would try if my hair started to fall out again. I realise this is not the same alopecia but if I suffered from that I would try zinc for a while at least

 

[Baz493]

I have been trying to understand how recent research into macrophage polarization is involved in all of this. The science is getting extremely deep and they now know that a variety of influences will convert the same macrophages into specific forms to perform different tasks, dependent upon need. So inflammatory signaling will emanate from some types of macrophage while anti-inflammatory signaling will emanate from others. This, in turn, will directly influence cells throughout the body, including the mast cells identified in alopecia. Medical researchers have been publishing articles on how natural products and supplements can influence this macrophage polarization. I still can't explain why zinc can benefit the situation through macrophages but the answers must still be out there. M2 macrophages are required for hair growth. https://www.nature.com/articles/s41467-019-09402-8 Yet zinc supplementation seems to inhibit M2 polarization. https://pubmed.ncbi.nlm.nih.gov/28687933/ That article also details how zinc deficiency increases M1 polarization, which increases inflammation. So zinc seems to reduce the inflammatory signaling emanating from M1 macrophages so reducing the need for the M2 macrophages. My guess, regarding the contradictory information from the nature article, is that an increase in the number of M2 macrophages will help to reverse alopecia even when zinc deficiency is continuing to induce the polarization of M1 macrophages and inflammation.

 

[Baz493]

A while ago I began working on the assumption that clogged pores, in alopecia, might be a consequence of hydrogenation of sebum. I found that amino acids could play a role in this and assumed that serine protease breakdown of proteins were involved in hardening the sebum. I'm now fairly certain that the specific amino acids which have to be accounted for, in hydrogenation of sebum, are cysteine and histidine. Both of these have been found to be deficient in people suffering from alopecia. https://www.nicehair.org/cysteine-hair-loss-prevention-hair-growth-promotion/ https://www.diviofficial.com/blogs/ingredients/histidine-benefits-for-treating-hair-loss-studies In order to produce histamine the body requires histidine in the diet so a deficiency of that is easily explained. Similar seems to be the case with cysteine as it is required to produce N-acetyl cysteine, involved in reducing the bodies response to histamine. The reason that both of these are fascinating is that they both possess an affinity for the mineral, nickel. https://onlinelibrary.wiley.com/doi/10.1002/9780470028131.ch3 In studying hydrogenation I was able to learn that companies use nickel to hydrogenate oils. I have been reading up on the connection between nickel deficiency and dermatitis. It seems to be almost impossible to tell the difference between that caused by nickel allergy and that caused by fungal infection. Nickel actually inhibits serine protease inhibitor function, leading to increased trypsin, tryptase, and such, activity such as I have previously described.

Anyway, all of that led to a range of information which could be of use. One example is this article which, near the bottom of the page, proposes a connection between methylation, high homocyteine levels, and mast cell activation syndrome. https://geneticgenie.org/article/ma...-chronic-illness-and-its-role-in-methylation/ This is interesting because high blood nickel levels can inhibit hyperhomocysteinemia. https://pubmed.ncbi.nlm.nih.gov/18465090/ That doesn't mean that the nickel fixes the problem but seems to be preventive of the more severe effects. The solution is likely to be exactly that recommended by all of the MTHFR mutation websites; supplements specific to fixing the methylation issues. Essentially I believe that our bodies are designed to raise nickel levels to combat hyperhomocysteinemia as a safety mechanism when nothing else has worked. Nickel, of course, is a heavy metal and toxic to the body so it's a compromise.

 

[Baz493]

It turns out that nickel has a high affinity for binding to the filaggrin protein in the top layer of the skin. Once there it disrupts the integrity of the skins surface, opening the skin to an increased risk of infection. Why this can form the pattern of male pattern baldness I can't yet fully explain but it can. https://www.naturalhealthgroup.com.au/heavy-metal-toxicity/do-you-have-nickel-toxicity/ It turns out that sweat increases the rate of nickel binding to filaggrin.