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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 estrogen excess, accelerate the formation of lipofuscin.”
...
From: Eric Justin Levinson
Folic acid is known to prevent birth defects.
How does one become deficient?
Methanol and formaldehyde require the same dehydrogenase enzymes to be oxidized into formic acid.
Retinol > retinaldehyde > retinoic acid (vitamin A)
Alcohol > acetaldehyde > acetic acid
Same pathway.
The acid forms require a oxidizing agent to eliminate them safely.
Acetic acid requires a mineral base.
Retinoic acid requires taurine.
Formic acid requires folinic acid.
Folinic acid is the fully reduced folic acid, ready for the body to use.
Formaldehyde/methanol exposure is going to deplete folic acid. And aldehydes, including formaldehyde, acetaldehyde, and retinaldehyde cause birth defects.
Here we have a study that proved folic acid also prevented birth defects caused by retinoic acid.
“Administration of retinoic acid at all doses resulted in statistically significant decreases in mean fetal weight and mean fetal height and the increase in mortality rate, and caused se- vere ultrastructural damages in Meckel’s cartilage. Folic acid administration prevented the decrease in mean fetal weight and height of the embryos treated with retinoic acid of 40 mg/kg.”
http://www.journal.med.tohoku.ac.jp/2051/TJ2051_04.pdf
Now you know why, women supplementing with vitamin A in a prenatal multi, in addition to their dietary and fortified vitamin A, need very high doses of folic acid to compensate for the dangers of the high vitamin A intake.
...
Retinol is actually "vitamin A alcohol," and causes similar problems as alcohol, including birth defects known as fetal retinoid syndrome.
It's metabolized by the same dehydrogenase enzymes as alocohol and methanol, which creates aldehydes.
Much better would be to support the dehydrogenase system and eliminate the build up of toxic aldehydes.
Targeting Aldehyde Dehydrogenase 2: New Therapeutic Opportunities
............
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
...
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.
It requires about 10 days after initial sun exposure for melanin synthesis to peak, which is why pale-skinned individuals tend to suffer sunburns of the epidermis initially. Dark-skinned individuals can also get sunburns, but are more protected than are pale-skinned individuals. Melanosomes are temporary structures that are eventually destroyed by fusion with lysosomes; this fact, along with melanin-filled keratinocytes in the stratum corneum sloughing off, makes tanning impermanent.
Too much sun exposure can eventually lead to wrinkling due to the destruction of the cellular structure of the skin, and in severe cases, can cause sufficient DNA damage to result in skin cancer. When there is an irregular accumulation of melanocytes in the skin, freckles appear. Moles are larger masses of melanocytes, and although most are benign, they should be monitored for changes that might indicate the presence of cancer (Figure 2).
Pigmentation | Biology for Majors II
...
Parents often cite having teenagers as the cause of gray hair. This is a good hypothesis, but scientists continue to investigate why hair turns gray. In time, everyone’s hair turns gray. Your chance of going gray increases 10-20% every decade after 30 years.
Initially, hair is white. It gets its natural color from a type of pigment called melanin. The formation of melanin begins before birth. The natural color of our hair depends upon the distribution, type and amount of melanin in the middle layer of the hair shaft or cortex.
Hair has only two types of pigments: dark (eumelanin) and light (phaeomelanin). They blend together to make up the wide range of hair colors.
Melanin is made up of specialized pigment cells called melanocytes. They position themselves at the openings on the skin’s surface through which hair grows (follicles). Each hair grows from a single follicle.
The process of hair growth has three phases:
With age comes a reduction of melanin. The hair turns gray and eventually white.
Moreover, Dr. Tobin suggests that hair turns gray because of age and genetics, in that genes regulate the exhaustion of the pigmentary potential of each individual hair follicle. This occurs at different rates in different hair follicles. For some people it occurs rapidly, while in others it occurs slowly over several decades.
In a February 2005 Science article (Nishimura, et al.) Harvard scientists proposed that a failure of melanocyte stem cells (MSC) to maintain the production of melanocytes could cause the graying of hair. This failure of MSC maintenance may result in the breakdown of signals that produce hair color.
In 2009, scientists in Europe described how hair follicles produce small amounts of hydrogen peroxide. This chemical builds on the hair shafts, which can lead to a gradual loss of hair color. (Wood, J.M et al. Senile hair graying: H2O2 mediated oxidative stress affect human hair color by blunting methionine sulfoxide repair. FASEB Journal, v. 23, July 2009: 2065-2075).
www.loc.gov
...
Oxidative stress caused by hydrogen peroxide (H2O2) leads to cell death and has been implicated in the pathogenesis of vitiligo. The nuclear factor E2-related factor 2 (Nrf2)-antioxidant response element (ARE), a major antioxidant pathway, regulates oxidative stress-related cytoprotective genes. We hypothesized that the Nrf2-ARE pathway protects human melanocytes from H2O2-induced oxidative damage through the induction of downstream antioxidative genes. Thus, we used Nrf2 short interfering RNA (siRNA) and pCMV6-XL5-Nrf2 to downregulate or upregulate Nrf2 expression in immortalized human melanocyte cell line PIG1. The melanocytes were then analyzed under different oxidative stress conditions for cell viability and apoptosis. Our study demonstrated that heme oxygenase-1 (HO-1) was the most induced antioxidant gene in PIG1 cells after treatment with H2O2. Knockdown of Nrf2 or zinc protoporphyrin IX (ZnPP) treatment increased cell death caused by H2O2 in melanocytes, but upregulation of Nrf2 or hemin treatment reduced cell death caused by H2O2 in melanocytes. In addition, the H2O2-induced Nrf2-ARE/HO-1 pathway was confirmed in primary cultured human melanocytes by examining the expression and translocation of Nrf2 and HO-1. These data suggested that regulation of the Nrf2/HO-1 pathway can reduce H2O2-induced oxidative damage in human melanocytes. Our data demonstrate that HO-1 protects human melanocytes from oxidative damage via the Nrf2-ARE pathway.
Heme Oxygenase-1 Protects Human Melanocytes from H2O2-Induced Oxidative Stress via the Nrf2-ARE Pathway
......
Oxidative stress management in the hair follicle: Could targeting NRF2 counter age-related hair disorders and beyond? - PubMed
….
….
In the present study, we found that taurine significantly increased the expression of β-catenin and that the protective effects induced by taurine are partially eliminated by a Wnt/β-catenin signaling inhibitor (i.e., DKK1). Interestingly, the inhibition of β-catenin by DKK1 not only led to elevated oxidative stress and reduced ALP but also caused the decreased expression of ERK, compared to taurine-treated cells. These results suggest that taurine inhibits oxidative stress-induced apoptosis and promotes osteoblast mineralization by activating the Wnt/β-catenin signaling pathway. More importantly, we found that Wnt/β-catenin signaling can regulate ERK phosphorylation, thereby increasing antioxidant response to oxidative stress.
Our findings indicate that taurine activates Nrf2, induces the expression of antioxidant enzymes (i.e., NQO1, HO1, and GCLC), and reduces H2O2-induced cell death by activating ERK and the Wnt/β-catenin pathway in osteoblast cells. Considering the partial reduction of ERK, antioxidants, and ALP activities by DKK1, a Wnt/β-catenin inhibitor, it is possible that other signaling molecules and pathways could be involved (Fig. 5). Thus, to explore other pathways that likely participate in taurine-mediated antioxidant effects, such as the PI3K/AKT signaling pathway (Jang et al., 2016), further research is necessary.
Cytoprotective Effect of Taurine against Hydrogen Peroxide-Induced Oxidative Stress in UMR-106 Cells through the Wnt/β-Catenin Signaling Pathway
......
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).
vitaminDskincolor
...
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.
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 estrogen excess, accelerate the formation of lipofuscin.”
...
From: Eric Justin Levinson
Folic acid is known to prevent birth defects.
How does one become deficient?
Methanol and formaldehyde require the same dehydrogenase enzymes to be oxidized into formic acid.
Retinol > retinaldehyde > retinoic acid (vitamin A)
Alcohol > acetaldehyde > acetic acid
Same pathway.
The acid forms require a oxidizing agent to eliminate them safely.
Acetic acid requires a mineral base.
Retinoic acid requires taurine.
Formic acid requires folinic acid.
Folinic acid is the fully reduced folic acid, ready for the body to use.
Formaldehyde/methanol exposure is going to deplete folic acid. And aldehydes, including formaldehyde, acetaldehyde, and retinaldehyde cause birth defects.
Here we have a study that proved folic acid also prevented birth defects caused by retinoic acid.
“Administration of retinoic acid at all doses resulted in statistically significant decreases in mean fetal weight and mean fetal height and the increase in mortality rate, and caused se- vere ultrastructural damages in Meckel’s cartilage. Folic acid administration prevented the decrease in mean fetal weight and height of the embryos treated with retinoic acid of 40 mg/kg.”
http://www.journal.med.tohoku.ac.jp/2051/TJ2051_04.pdf
Now you know why, women supplementing with vitamin A in a prenatal multi, in addition to their dietary and fortified vitamin A, need very high doses of folic acid to compensate for the dangers of the high vitamin A intake.
...
Retinol is actually "vitamin A alcohol," and causes similar problems as alcohol, including birth defects known as fetal retinoid syndrome.
It's metabolized by the same dehydrogenase enzymes as alocohol and methanol, which creates aldehydes.
Much better would be to support the dehydrogenase system and eliminate the build up of toxic aldehydes.
Targeting Aldehyde Dehydrogenase 2: New Therapeutic Opportunities
............
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
...
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.
It requires about 10 days after initial sun exposure for melanin synthesis to peak, which is why pale-skinned individuals tend to suffer sunburns of the epidermis initially. Dark-skinned individuals can also get sunburns, but are more protected than are pale-skinned individuals. Melanosomes are temporary structures that are eventually destroyed by fusion with lysosomes; this fact, along with melanin-filled keratinocytes in the stratum corneum sloughing off, makes tanning impermanent.
Too much sun exposure can eventually lead to wrinkling due to the destruction of the cellular structure of the skin, and in severe cases, can cause sufficient DNA damage to result in skin cancer. When there is an irregular accumulation of melanocytes in the skin, freckles appear. Moles are larger masses of melanocytes, and although most are benign, they should be monitored for changes that might indicate the presence of cancer (Figure 2).
Pigmentation | Biology for Majors II
...
Parents often cite having teenagers as the cause of gray hair. This is a good hypothesis, but scientists continue to investigate why hair turns gray. In time, everyone’s hair turns gray. Your chance of going gray increases 10-20% every decade after 30 years.
Initially, hair is white. It gets its natural color from a type of pigment called melanin. The formation of melanin begins before birth. The natural color of our hair depends upon the distribution, type and amount of melanin in the middle layer of the hair shaft or cortex.
Hair has only two types of pigments: dark (eumelanin) and light (phaeomelanin). They blend together to make up the wide range of hair colors.
Melanin is made up of specialized pigment cells called melanocytes. They position themselves at the openings on the skin’s surface through which hair grows (follicles). Each hair grows from a single follicle.
The process of hair growth has three phases:
- Anagen: This is the active growth stage of the hair fiber and can last from 2- 7 years. At any given moment 80-85% of our hair is in the anagen phase.
- Catagen: Sometimes referred to as the transitional phase, which is when hair growth begins to “shut down” and stop activity. It generally lasts 10- 20 days.
- Telogen: This occurs when hair growth is completely at rest and the hair fiber falls out. At any given time, 10-15 % of our hair is in the telogen phase, which generally lasts 100 days for scalp hair. After the telogen phase, the hair growth process starts over again to the anagen phase.
With age comes a reduction of melanin. The hair turns gray and eventually white.
So why does our hair turn gray or white?
Dr. Desmond Tobin, professor of cell biology from the University of Bradford in England, suggests that the hair follicle has a “melanogentic clock” which slows down or stops melanocyte activity, thus decreasing the pigment our hair receives. This occurs just before the hair is preparing to fall out or shed, so the roots always look pale.Moreover, Dr. Tobin suggests that hair turns gray because of age and genetics, in that genes regulate the exhaustion of the pigmentary potential of each individual hair follicle. This occurs at different rates in different hair follicles. For some people it occurs rapidly, while in others it occurs slowly over several decades.
In a February 2005 Science article (Nishimura, et al.) Harvard scientists proposed that a failure of melanocyte stem cells (MSC) to maintain the production of melanocytes could cause the graying of hair. This failure of MSC maintenance may result in the breakdown of signals that produce hair color.
In 2009, scientists in Europe described how hair follicles produce small amounts of hydrogen peroxide. This chemical builds on the hair shafts, which can lead to a gradual loss of hair color. (Wood, J.M et al. Senile hair graying: H2O2 mediated oxidative stress affect human hair color by blunting methionine sulfoxide repair. FASEB Journal, v. 23, July 2009: 2065-2075).
Why does hair turn gray?
It is well known that gray hair results from a reduction of pigment, while white hair has no pigment, but why this happens remains somewhat of a mystery. Ayer’s hair vigor for the toilet: restores gray hair to its natural vitality and color, 1886. Prints & Photographs Division, Library of...www.loc.gov
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Oxidative stress caused by hydrogen peroxide (H2O2) leads to cell death and has been implicated in the pathogenesis of vitiligo. The nuclear factor E2-related factor 2 (Nrf2)-antioxidant response element (ARE), a major antioxidant pathway, regulates oxidative stress-related cytoprotective genes. We hypothesized that the Nrf2-ARE pathway protects human melanocytes from H2O2-induced oxidative damage through the induction of downstream antioxidative genes. Thus, we used Nrf2 short interfering RNA (siRNA) and pCMV6-XL5-Nrf2 to downregulate or upregulate Nrf2 expression in immortalized human melanocyte cell line PIG1. The melanocytes were then analyzed under different oxidative stress conditions for cell viability and apoptosis. Our study demonstrated that heme oxygenase-1 (HO-1) was the most induced antioxidant gene in PIG1 cells after treatment with H2O2. Knockdown of Nrf2 or zinc protoporphyrin IX (ZnPP) treatment increased cell death caused by H2O2 in melanocytes, but upregulation of Nrf2 or hemin treatment reduced cell death caused by H2O2 in melanocytes. In addition, the H2O2-induced Nrf2-ARE/HO-1 pathway was confirmed in primary cultured human melanocytes by examining the expression and translocation of Nrf2 and HO-1. These data suggested that regulation of the Nrf2/HO-1 pathway can reduce H2O2-induced oxidative damage in human melanocytes. Our data demonstrate that HO-1 protects human melanocytes from oxidative damage via the Nrf2-ARE pathway.
Heme Oxygenase-1 Protects Human Melanocytes from H2O2-Induced Oxidative Stress via the Nrf2-ARE Pathway
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Oxidative stress management in the hair follicle: Could targeting NRF2 counter age-related hair disorders and beyond?
Abstract
Widespread expression of the transcription factor, nuclear factor (erythroid-derived 2)-like 2 (NRF2), which maintains redox homeostasis, has recently been identified in the hair follicle (HF). Small molecule activators of NRF2 may therefore be useful in the management of HF pathologies associated with redox imbalance, ranging from HF greying and HF ageing via androgenetic alopecia and alopecia areata to chemotherapy-induced hair loss. Indeed, NRF2 activation has been shown to prevent peroxide-induced hair growth inhibition. Multiple parameters can increase the levels of reactive oxygen species in the HF, for example melanogenesis, depilation-induced trauma, neurogenic and autoimmune inflammation, toxic drugs, environmental stressors such as UV irradiation, genetic defects and aging-associated mitochondrial dysfunction. In this review, the potential mechanisms whereby NRF2 activation could prove beneficial in treatment of redox-associated HF disorders are therefore discussed.Oxidative stress management in the hair follicle: Could targeting NRF2 counter age-related hair disorders and beyond? - PubMed
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In the present study, we found that taurine significantly increased the expression of β-catenin and that the protective effects induced by taurine are partially eliminated by a Wnt/β-catenin signaling inhibitor (i.e., DKK1). Interestingly, the inhibition of β-catenin by DKK1 not only led to elevated oxidative stress and reduced ALP but also caused the decreased expression of ERK, compared to taurine-treated cells. These results suggest that taurine inhibits oxidative stress-induced apoptosis and promotes osteoblast mineralization by activating the Wnt/β-catenin signaling pathway. More importantly, we found that Wnt/β-catenin signaling can regulate ERK phosphorylation, thereby increasing antioxidant response to oxidative stress.
Our findings indicate that taurine activates Nrf2, induces the expression of antioxidant enzymes (i.e., NQO1, HO1, and GCLC), and reduces H2O2-induced cell death by activating ERK and the Wnt/β-catenin pathway in osteoblast cells. Considering the partial reduction of ERK, antioxidants, and ALP activities by DKK1, a Wnt/β-catenin inhibitor, it is possible that other signaling molecules and pathways could be involved (Fig. 5). Thus, to explore other pathways that likely participate in taurine-mediated antioxidant effects, such as the PI3K/AKT signaling pathway (Jang et al., 2016), further research is necessary.
Cytoprotective Effect of Taurine against Hydrogen Peroxide-Induced Oxidative Stress in UMR-106 Cells through the Wnt/β-Catenin Signaling Pathway
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Tyrosinase may protect human melanocytes from the cytotoxic effects of the superoxide anion
Reactive oxygen species (ROS) are potentially cytotoxic and several mechanisms have evolved to protect against their damaging effects. In melanocytes, tyrosinase may have such a rôle by utilising the superoxide anion (O2-) in the production of melanin. In the present study, we have examined the cytotoxic effects of O2- and hydrogen peroxide (H2O2) in human melanocytes both before and following the activation of tyrosinase. Xanthine oxidase (XO, 5-150 mU.ml-1) and glucose oxidase (GO, 0.1-20 mU.ml-1) were used to generate the O2- and H2O2 respectively, and the cytotoxic effects assessed by measuring cell survival using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium (MTT) assay. 3 h later, dose-related decreases in melanocyte survival were seen. Similar experiments with keratinocytes and fibroblasts showed that these cells were more resistant to the cytotoxic effects of O2- than were the melanocytes. The effect of increasing tyrosinase activity was examined by growing the melanocytes in the presence of an analogue of melanocyte-stimulating hormone (MSH) Nle4DPhe7 alpha-MSH (10(-8) M), for 48 h. This increased tyrosinase activity, melanin content, the ability to trap O2- and the resistance of the melanocytes to the cytotoxic effects of this ROS, but failed to alter their susceptibility to the damaging effects of H2O2. Nle4DPhe7 alpha-MSH had no effect on the resistance of keratinocytes and fibroblasts to either O2- or H2O2. After 3 h, XO, as opposed to GO, also increased the melanin content of human melanocytes; this effect was not accompanied by an increase in tyrosinase activity. The present results suggest that tyrosinase may utilise O2- to produce melanin and that this process may protect melanocytes from the potentially damaging effects of this ROS.Tyrosinase may protect human melanocytes from the cytotoxic effects of the superoxide anion - PubMed
..........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
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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).
vitaminDskincolor
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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
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“(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.
