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Grey Hair And Melatonin

Discussion in 'Scientific Studies' started by Drareg, Jan 7, 2017.

  1. Drareg

    Drareg Member

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    I got the idea of grey hair being caused by melatonin from Peats article on Aging Eyes, Infant Eyes, and Excitable Tissues,he mentions animal hair colour changes with light.
    It seems at this point their are many ways to influence grey hair from research posted on here,this is another angle I wanted to highlight if anybody ever gets anymore info on it,it seems to be the one thing we haven't achieved on here or through Peats work is reversal of grey hair,surely this is a potent sign of improving health. In relation to the tryptophan-serotonin link to grey hair we could apply the same thinking to tryptophan and melatonin relationship.
    Another question is why do we loose head hair if it's a low energy adaption as speculated,it would make more sense for the body to keep the hair as warmth for the brain and loose all the other body hair like facial ,arm and pubic first?
    I understand nature doesn't evolve perfectly and we have some strange adaptions that take the Long way round.

    Quote from Peats article-
    "In snowy climates, it’s “ecologically” rational for animals to turn white in the winter, for camouflage. But tadpoles also turn white in the dark, or under the influence of melatonin, and the biological meaning of that isn’t so clear. It’s possible that being white would reduce their loss of heat through radiation, but I think it is more likely that it relates to an increased ability of weak radiation to penetrate their tissues, rather than being stopped near the surface by the melanin in the skin. The absence of melanin makes them more sensitive to light. Bright light suppresses their melatonin, and makes them turn dark brown or black, and this protects them from bright sunlight."


    Below study on melatonin and hair.

    "Abstract

    Melatonin, the pineal gland hormone and a strong antioxidant, has long been known, particularly in animal-experiment based research and the wool-producing industry, to be a potent regulatory neuroendocrine substance in relation to hair growth, hair color and hair cycle, depending on light periods, seasonal rhythms, environmental factors and reproductive rhythms. Nevertheless, the biological mechanisms of this extremely versatile hormone, especially with regard to human hair follicles, are not fully understood. In recent years, however, essential knowledge has been gained on the melatoninergic system of the skin, melatonin levels in keratinocytes and hair follicles, extrapineal intrafollicular melatonin synthesis and noradrenalin-induced increase in synthesis, as well as hair cycle-dependent expression of the membrane-bound melatonin receptor MT2 and the nuclear receptor RORalpha. Functional data on the growth of human hair both in vitro and in vivo show that melatonin might play an essential role in hair physiology."


    [The influence of melatonin on hair physiology]. - PubMed - NCBI

    Abstract
    The expression of retinoid-acid-related orphan receptor α (RORα) was evaluated at the mRNA level using real-time polymerase chain reaction (qRT-PCR), and its expression localization was determined by in situ hybridization of adult Inner Mongolian cashmere goats at different times of the year. In situ hybridization demonstrated that RORαwas expressed in secondary hair follicles of the hair shaft, inner root sheath, outer root sheath, medulla, and other parts that are target organs of the RORαreceptor gene. qRT-PCR results showed that there was no significant difference in the RORa mRNA abundance in February, April, August, and October (P > 0.05), and the only difference occurred in December relative to February, August, and October (P < 0.05). This difference revealed that melatonin possibly promotes cashmere growth through the nuclear receptor RORα. This study provides a good foundation for future studies on the relationship between the melatoninreceptor and cashmere growth; in addition, it provides new insights for increased cashmere production and quality.


    Expression of the RORα gene in Inner Mongolian cashmere goat hair follicles. - PubMed - NCBI

    Abstract
    Seasonal responses of many animal species are triggered by changes in daylength and its transduction into a neuroendocrine signal by the pineal gland through the nocturnal duration of melatonin (MEL) release. The precise central sites necessary to receive, transduce, and relay the short day (SD) fall-winter MEL signals into seasonal responses and changes in physiology and behavior are unclear. In Siberian hamsters, SDs trigger decreases in body and lipid mass, testicular regression and pelage color changes. Several candidate genes and their central sites of expression have been proposed as components of the MEL transduction system with considerable recent focus on the arcuate nucleus (ARC) and its component, the dorsomedial posterior arcuate nucleus (dmpARC). This site has been postulated as a critical relay of SD information through the modulation of a variety of neurochemicals/receptors important for the control of energy balance. Here the necessity of an intact dmpARC for SD responses was tested by making electrolytic lesions of the Siberian hamster dmpARC and then exposing them to either long days (LD) or SDs for 12wks. The SD typical decreases in body and fat mass, food intake, testicular volume, serum testosterone concentrations, pelage color change and increased UCP-1 protein expression (a proxy for brown adipose tissue thermogenesis) all occurred despite the lack of an intact dmpARC. Although the Siberian hamster dmpARC contains photoperiod-modulated constituents, these data demonstrate that an intact dmpARC is not necessary for SD responses and not integral to the seasonal energy- and reproductive-related responses measured here.

    An intact dorsomedial posterior arcuate nucleus is not necessary for photoperiodic responses in Siberian hamsters. - PubMed - NCBI

    Potentially Interesting in relation how the muzzle of animals and humans can go grey early?

    "Evaluating individual circadian rhythm traits is crucial for understanding the human biological clock system. The present study reports characterization of physiological and molecular parameters in 13 healthy male subjects under a constant routine condition, where interfering factors were kept to minimum. We measured hormonal secretion levels and examined temporal expression profiles of circadian clock genes in peripheral leukocytes and beard hair follicle cells. All 13 subjects had prominent daily rhythms in melatonin and cortisol secretion. Significant circadian rhythmicity was found for PER1 in 9 subjects, PER2 in 3 subjects, PER3 in all 13 subjects, and BMAL1 in 8 subjects in leukocytes. Additionally, significant circadian rhythmicity was found for PER1 in 5 of 8 subjects tested, PER2 in 2 subjects, PER3 in 6 subjects, and BMAL1 in 3 subjects in beard hair follicle cells. The phase of PER1 and PER3 rhythms in leukocytes correlated significantly with that of physiological rhythms. Our results demonstrate that leukocytes and beard hair follicle cells possess an endogenous circadian clock and suggest that PER1 and PER3 expression would be appropriate biomarkers and hair follicle cells could be a useful tissue source for the evaluation of biological clock traits in individuals."

    Rhythmic expression of circadian clock genes in human leukocytes and beard hair follicle cells. - PubMed - NCBI
    "
    Abstract
    The role of neurohormones and neuropeptides in human hair follicle (HF) pigmentation extends far beyond the control of melanin synthesis by α-MSH and ACTH and includes melanoblast differentiation, reactive oxygen species scavenging, maintenance of HF immune privilege, and remodeling of the HF pigmentary unit (HFPU). It is now clear that human HFs are not only a target of multiple neuromediators, but also are a major non-classical production site for neurohormones such as CRH, proopiomelanocortin, ACTH, α-MSH, ß-endorphin, TRH, and melatonin. Moreover, human HFs have established a functional peripheral equivalent of the hypothalamic-pituitary-adrenal axis. By charting the author's own meanderings through the jungle of hair pigmentation research, the current perspectives essay utilizes four clinical observations - hair repigmentation, canities, poliosis, and 'overnight greying'- as points of entry into the enigmas and challenges of .pigmentary HF neuroendocrinology. After synthesizing key principles and defining major open questions in the field, selected research avenues are delineated that appear clinically most promising. In this context, novel neuroendocrinological strategies to retard or reverse greying and to reduce damage to the HFPU are discussed.

    A neuroendocrinological perspective on human hair follicle pigmentation. - PubMed - NCBI

    Abstract
    Melatonin, the chief secretory product of the pineal gland, has long been known to modulate hair growth, pigmentation and/or molting in many species, presumably as a key neuroendocrine regulator that couples coat phenotype and function to photoperiod-dependent environmental and reproductive changes. However, the detailed effects and mechanisms of this surprisingly pleiotropic indole on the hair follicle (HF) regarding growth control and pigmentation have not yet been completely understood. While unspecific melatonin binding sites have long been identified (e.g., in goat and mouse HFs), specific melatonin membrane MT2 receptor transcripts and both protein and mRNA expression for a specific nuclear melatonin binding site [retinoid-related orphan receptor alpha (RORalpha)] have only recently been identified in murine HFs. MT1, known to be expressed in human skin cells, is not transcribed in mouse skin. After initial enzymologic data from hamster skin related to potential intracutaneous melatonin synthesis, it has recently been demonstrated that murine and human skin, namely human scalp HFs in anagen, are important sites of extrapineal melatonin synthesis. Moreover, HF melatonin production is enhanced by catecholamines (as it classically occurs in the pineal gland). Melatoninmay also functionally play a role in hair-cycle control, as it down-regulates both apoptosis and estrogen receptor-alpha expression, and modulates MT2 and RORalpha expression in murine skin in a hair-cycle-dependent manner. Because of melatonin's additional potency as a free radical scavenger and DNA repair inducer, the metabolically and proliferatively highly active anagen hair bulb may also exploit melatonin synthesis in loco as a self-cytoprotective strategy.

    Melatonin and the hair follicle. - PubMed - NCBI
    To assess the genetic variability in both the nocturnal increase pattern of melatonin concentration and photoresponsiveness in coat changes, an experiment on 422 Rex rabbits (from 23 males) raised under a constant light programme from birth was performed. The animals were sampled at 12 weeks of age, according to 4 periods over a year. Blood samples were taken 7 times during the dark phase and up to 1 h after the lighting began. Maturity of the fur was assessed at pelting. Heritability estimates of blood melatoninconcentration (0.42, 0.17 and 0.11 at mid-night, 13 and 15 h after lights-out respectively) and strong genetic correlations between fur maturity and melatonin levels at the end of the dark phase (-0.64) indicates that (i) the variability of the nocturnal pattern of melatonin levels is under genetic control and (ii) the duration of the nocturnal melatonin increase is a genetic component of photoresponsiveness in coat changes.



    Genetic variability of the pattern of night melatonin blood levels in relation to coat changes development in rabbits. - PubMed - NCBI

    Below slightly off topic but interesting.
    "Abstract
    Research into how the central nervous system (CNS) and the skin of mammals are physiologically connected and how this "brain-skin connection" may be therapeutically targeted in clinical medicine has witnessed a renaissance. A key element in this development has been the discovery that mammalian skin and its appendages, namely human scalp hair follicles (HFs), not only are important, long-underestimated target tissues for classical neurohormones, neurotrophins and neuropeptides, but also are eminent peripheral tissue sources for the production and/or release of these neuromediators. This essay summarizes the many different levels of biology at which human scalp HFs respond to and generate a striking variety of neurohormones, and portrays HFs as prototypic, cyclically remodelled miniorgans that utilize these neurohormones to autoregulate their growth, hair shaft production, rhythmic organ transformation, pigmentation, mitochondrial energy metabolism, and immune status. The essay also explores how preclinical research on human scalp HFs can be exploited to unveil and explore "novel" and clinically as yet untapped, but most likely ancestral functions of neurohormones within mammalian epithelial biology that still impact substantially on human skin physiology. Arguably, systematic investigation of the "brain-skin connection" is one of the most intriguing current research frontiers in investigative dermatology, not the least since it has reversed the traditional CNS focus in studying the interactions between two key organ systems by placing the skin epithelium on center stage."

    Exploring the "brain-skin connection": Leads and lessons from the hair follicle. - PubMed - NCBI
     
  2. Bahaa El wazzan

    Bahaa El wazzan Member

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  3. David PS

    David PS Member

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    Drareg - very nice review. I had some similar thoughts last winter and I started a thread, Topical Melatonin For Hair Growth And Repigmentation Because of that thread I have reconsidered the use of melatonin. Now, I even avoid foods, such as cherries, which contain melatonin.

    I used a benefit-versus-burden analysis to change my thinking. From Aging Eyes, Infant Eyes, and Excitable Tissues, I learned the burden of melatonin:
    • Retinal injury is caused by ordinary light, when the eyes are sensitized by melatonin, prolactin, and polyunsaturated fats.
    • melatonin, tryptophan, fish oils, St. John's wort, and the various omega -3 oils, all increase the risk of retinal light damage and macular degeneration.
    • melatonin inhibits progesterone production but stimulates estrogen production, and it’s widely recognized that melatonin generally inhibits the thyroid hormones,
    • In some animals, melatonin has been shown to be responsible for whitening of the hair during the winter
    • Melatonin increases the concentration of free fatty acids during the night
    • Melatonin lowers body temperature, causes vasoconstriction in the brain, heart, and other organs, and slows reactions.
    • For me the possible benefit of melatonin on hair was not justifiable. But, reasonable men do differ.
     
  4. OP
    Drareg

    Drareg Member

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    I seen some studies where they implied hair regrowth was from down regulating androgens,they were of the belief that DHT Causes hair loss.

    Nevertheless if it's increasing for animals when their coat colour changes it's interesting,perhaps humans from colder climates can have an epigentic expression of sort for lack of sunlight,hibernation from lack of resources,aging could be providing a similar cue to the genome that the lack of sunlight cues the animals,aging is a sort of progressive hibernation in a way.
    They all come under the guise of cellular energy,this allows for a vast array of contexts,artificial lighting has been shown to stop animals hibernating in cities,this could be similar for humans with artificial lights also,however as they age and stress metabolism takes over we get progressive hibernation,the body construe this as winter,its readying itself for cold weather so it changes its fur.
    The question is why the top of the head changes first? Perhaps it's camouflage to protect the brain form attack,in snow and ice obviously.

    The ROS theory of grey hair along with melatonins claim to reduce ROS is another spanner in the works,I haven't seen anything on coat colour changes for animals regarding ROS,the stress of low sunlight is likely to increase it.

    Nothing but wild speculation for now......
     
  5. Elephanto

    Elephanto Member

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    All studies I've read on the subject actually indicate the opposite.

    Melatonin directly stimulates the secretion of progesterone by human and bovine granulosa cells in vitro. - PubMed - NCBI

    Protective role of melatonin in progesterone production by human luteal cells. - PubMed - NCBI

    Effect of melatonin on estrogen and progesterone receptors in relation to uterine contraction in rats. - PubMed - NCBI

    The results reveal a significant reduction (59%) in the number of uterine estrogen receptors with concomitant increase in the progesterone receptors (53%) in melatonin-pretreated rats as compared to the control ones.

    Melatonin blocks the activation of estrogen receptor for DNA binding. - PubMed - NCBI

    -

    So taking this into account, it only makes sense that they find low melatonin in men with prostate cancer, a cancer driven by concomitant estrogen excess and progesterone deficiency.

    Urinary melatonin levels, sleep disruption, and risk of prostate cancer in elderly men. - PubMed - NCBI

    And there are many studies showing its antiproliferative actions on prostate cancer, I don't think any estrogenic substance could have such effect, but if you have any study backing what you claimed I'll be glad to read them.
     
  6. David PS

    David PS Member

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    To put things into context, all of the bullet points that I posted above are direct quotes from Ray Peat's Aging Eyes, Infant Eyes, and Excitable Tissues. The full quote for the offensive bullet point identified above reads:
    In 1994 A.V. Sirotkin found that melatonin inhibits progesterone production but stimulates estrogen production, and it’s widely recognized that melatonin generally inhibits the thyroid hormones, creating an environment in which fertilization, implantation, and development of the embryo are not possible. This combination of high estrogen with low progesterone and low thyroid decreases the resistance of the organism, predisposing it to seizures and excitotoxic damage, and causing the thymus gland to atrophy.​

    Ray provides 2, 1994 references to Sirotkin articles that may be of assistance.

    J Pineal Res 1994 Oct;17(3):112-7. Direct influence of melatonin on steroid, nonapeptide hormones, and cyclic nucleotide secretion by granulosa cells isolated from porcine ovaries. Sirotkin AV. “It was found that melatonin is able to inhibit progesterone and stimulate estradiol secretion.” “The present observations suggest a direct effect of melatonin on the steroid, nonapeptide hormone, and cyclic nucleotide release from porcine ovarian cells.”

    J Pineal Res 1994 Oct;17(3):112-7. Direct influence of melatonin on steroid, nonapeptide hormones, and cyclic nucleotide secretion by granulosa cells isolated from porcine ovaries. Sirotkin AV.

    I have not read either of these references. My earlier post was merely to point out that supplementing with melatonin is risky business and that after reading Ray's article, I decided not to take the risk. I decided that restoring the color and fullness of my hair to more youthful times was not worth the risk of the types of things that Ray wrote about and that I posted in the bullets. For me, after reading Ray's article the use of melatonin to win the battle-of-the-bald, would be a Pyrrhic victory. I had not intended to claim anything and I apologize for my ambiguity and for my cherry-picking from Ray's article. As always, read his works for yourself and draw your own conclusions.

     
  7. schultz

    schultz Member

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    Interesting thread!
     
  8. OP
    Drareg

    Drareg Member

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    Indoleamines and the UV-light-sensitive photoperiodic responses of the melanocyte network: a biological calendar?


    "The pineal, serotoninergic and pigmented neurons are associated with light-dependent sleep/arousal, serving as a biological clock with a circadian rhythm. This rhythm is maintained by melatonin which serves to recognise the ‘dark’ phase. The neural network that responds to seasonal variations in day/night length has not been identified. The present study demonstrates that melanocytes in human skin respond to changes in the duration of UV exposure, and can serve as a biological calendar. These responses are mediated by two indoleamines, serotonin and melatonin. Higher melatonin levels correspond to long nights and long days (short UV pulse), while high serotonin levels in the presence of melatonin reflect short nights and long days (long UV exposure). This response recapitulates the sleep/arousal patterns in animals exposed to large variations in day/night cycle that cause changes in coat colour from pure white in winter to complete repigmentation in summer."

    Interesting the colour goes from white in winter to complete repigmentation in summer.

    I just posted this in another thread-https://raypeatforum.com/community/threads/role-of-serotonin-in-melanogenesis-in-the-skin.14807/
    If we antagonize melanin,won't this increase greying potentially?
     
  9. OP
    Drareg

    Drareg Member

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    Djungarian Hamster- from wiki

    "As winter approaches and the days shorten, the Djungarian hamster's dark fur is almost entirely replaced with white fur. In captivity, this does not always happen"

    "In the winter, the fur is more dense.[11] They sometimes have a grey tint on their head.[12] More than ten percent of the hamsters kept in the first winter develop the summer coat. In the second winter, only a few change into the winter coat and winter colour is less pronounced. The moulting in the winter fur starts in October or November and is completed in December, while the summer coat begins in January or February and is completed in March or early April.[7] The ears are grey with a pinkish tint.[2] Moulting both run jobs on the head and the back of the spine to the sides, the legs and the underside.[13] The hairs grow longer in the summer, to about ten millimetres long.[6]

    The pigmentation of hair is controlled by the hormone prolactin and colour genetics.[14] Day length must be less than fourteen hours to initiate the change to winter coat. The change to the winter coat can be triggered in the summer by the short day lengths. The change occurs back to the summer coat in the autumn, when the length of the days change again. At internal temperatures hamsters in captivity start later with the changes. The winter colour is less pronounced in them.[7] The eyes of the Djungarian hamster are black, unless it is albino in which case they are red.[6]

    Fascinating that those in captivity don't change coat colour,less stress from the environment or they just get summer light all day year round?

    Prolactin stimulating colour?
    Physiological doses of prolactin stimulate pelage pigmentation in Djungarian hamster.
    Duncan MJ, Goldman BD.
    Abstract
    The Djungarian hamster exhibits a dark agouti pelage during the summer. Under the influence of decreased daylength, this species molts and develops a predominantly white winter coat. After a patch of white fur was plucked from hamsters housed in short photoperiod, chronic infusion of 10 or 20 micrograms ovine prolactin (o-PRL)/day led to the growth of a patch of pigmented fur, thus reversing the effect of the decreased daylength. Circulating o-PRL levels produced by the 10-micrograms/day infusions ranged from 17.9 +/- 4.0 to 35.1 +/- 13.8 (SE) ng/ml and thus approximated the endogenous circulating prolactin levels found in hamsters with the dark summer pelage (6, 9). Infusion of o-PRL stimulated pigmentation of the pelage of castrated as well as intact hamsters, suggesting that the testes do not mediate this effect. Infusion of ovine growth hormone (20 micrograms/day) did not stimulate pigmentation, and infusion of alpha-melanocyte-stimulating hormone (10 micrograms/day) gave inconclusive results.

    Physiological doses of prolactin stimulate pelage pigmentation in Djungarian hamster. - PubMed - NCBI

    Molting in the Djungarian hamster (Phodopus sungorus Pallas): seasonal or continuous process?
    Kuhlmann MT1, Clemen G, Schlatt S.
    Author information

    Abstract
    After transfer into a short daylight regimen, the brownish summer pelage of the Djungarian hamster (Phodopus sungorus) changes into the whitish winter phenotype. Although changes in serum prolactin levels are identified as the initiating hormonal signal, morphological data about molting in that species are sparse. The aim of this study was to characterize in detail the summer and winter pelage of the Djungarian hamster and to analyze the alterations in the skin and pelage induced by photoperiodic changes. The main difference between summer and winter hair types is the pattern of pigmentation. In contrast to other mammalian species showing seasonal changes, the winter coat of the Djungarian hamster is not characterized by an increase in hair density. Molting patches were observed at all times, even in the winter coat, showing that the light regimen does not control the process of molting itself but the pattern of pigmentation and eventually the loss of hair during the single molting wave.

    Molting in the Djungarian hamster (Phodopus sungorus Pallas): seasonal or continuous process? - PubMed - NCBI
     
  10. OP
    Drareg

    Drareg Member

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    This study is a good description of melatonin influence on mammal coat colour,table 2 gives a quick overview.

    Melatonin and the hair follicle

    In relation to djungarian hamster-
    "Pattern of melatonin release induced by experimentally induced photoperiods modifies molt into summer pelage"

    Below from the study is interesting.
    "While melanocortins like alpha-melanocyte-stimulating hormone (a-MSH) and adrenocorticotrophic hormone (ACTH) have been the main focus of endocrinologists interested in hair pigmentation, many additional (neuro-)hormones, neurotrophins, neuropeptides and neurotransmitters are involved in the control of hair pigmentation in various mammalian species (e.g., beta-endorphine, histamine, estrogen, POMC, and NGF, to name but a few prominent examples) [4, 174–177]. Melatonin has been described to increase number of melanocytes in culture [120]."

    While the classical ‘skin lightening’ effects of melatonin, which reflect primarily the induction of melanosome aggregation e.g., in frog melanophores, are well-known from work in amphibian skin [2, 179], much less is known on the effect of melatonin on mammalian melanocytes [3, 120, 165, 180, 181]. Given the numerous biological differences between epidermal and HF melanocytes [3, 172], however, it is quite unclear whether these findings are at all relevant to hair pigmentation. Evidently, this is even more the case for the reported inhibitory effects of melatonin on melanoma cell melanogenesis and/or growth, which may be antagonized in part by α-MSH [119, 182]. Therefore, the best currently available evidence for pigmentary effects comes from organ culture studies using hamster, mouse and human HFs – all of which are hampered by the shortcomings and limitations that are inherent to such complex assays [6,

    "Melatonin (0.1 nm–1 μm) reportedly inhibits the post-tyrosinase steps of melanogenesis in hamster HFs [118], and we have found that high dose-melatonin (0.01–100 μm) can inhibit follicular tyrosinase activity in organ-cultured mouse skin with all HFs in anagen growth phase [66] (Table 2). Thody and co-workers reported that melatonin administration slightly reduced coat darkening in young mice in vivo, when hair re-growth after shaft plucking was examined [176]. However, when we checked the effect of 0.001–1000 nm melatonin on organ-cultured human scalp HFs in anagen, no consistent and significant effects on the histochemcially detectable melanin content of human anagen VI hair bulbs in situ could be identified (as assessed by quantitative Masson-Fontana histochemistry) [11] (Table 2). While this study certainly does not rule-out effects of melatonin on human HF pigmentation under physiological conditions, it makes it likely that this indole is not a major modulator of human hair pigmentation. This conclusion is further supported by the lack of case reports of pigmentary effects induced by melatonin dietary supplementation, despite the copious, almost ‘epidemic’ consumption of sometimes massive oral doses of melatonin worldwide."

    My opinion on the last quote would be confirmation bias by people supplementing it,they want to seem like it's helping and will ignore contradictory evidence until it gets really bad,a few extra greys never get reported and probably get dyed.
    I would also like to ask the researchers who uses melatonin for hair regrowth if it increased greying,they did not look for this so it's likely they would put the greying down to normal aging,again potential confirmation bias.
     
  11. OP
    Drareg

    Drareg Member

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    Methylene blue increasing melatonin? If I recall some on here mentioned increased greying from methylene blue when they took it,it could be from the serotonin dump MB is known to cause? Pigmentation should reverse after stopping use no?


    Effect of methylene blue and related redox dyes on monoamine oxidase activity; rat pineal content of N-acetylserotonin, melatonin, and related indo... - PubMed - NCBI
    Effect of methylene blue and related redox dyes on monoamine oxidase activity; rat pineal content of N-acetylserotonin, melatonin, and related indoles; and righting reflex in melatonin-primed frogs.

    Oxenkrug GF1, Sablin SO, Requintina PJ.
    Author information

    Abstract
    The ability of methylene blue (MB) to inhibit the nitric oxide-induced stimulation of N-methyl-D-aspartate receptors has been suggested as a possible mechanism of MB's clinical antidepressant action. This study evaluated the alternative/additional mechanisms of the antidepressant effect of MB on biochemical and behavior levels. Selective inhibition of monoamine oxidase type A (MAO-A) is widely accepted as a major mechanism of the clinical antidepressant effect. MB and the related redox dyes toluidine blue O (TBO), thionine (TN), brilliant cresyl blue (BCB), and toluylene blue (TB) were reversible competitive inhibitors of both MAO-A and MAO-B and were highly selective toward MAO-A. TBO was the most potent inhibitor, followed by TN, BCB, MB, and TB. The dyes studied increased rat pineal N-acetylserotonin (NAS) and melatonin content, in accordance with our previous observations of the stimulating effect of selective inhibition of MAO-A on pineal melatonin biosynthesis. The redox dyes exerted antidepressant-like activity in frogs; that is, they suppressed the righting reflex in melatonin-primed frogs. This study's results indicate that selective inhibition of MAO-A might mediate the clinical antidepressant effect of MB through NAS stimulation and melatonin biosynthesis.
     
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