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Join Date: Feb 2008
Location: Anaheim, California
Gender: Male
Age: 19
Posts: 1,430
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Melatonin Made Me Pale
A sort of extension to my previous thread: Melatonin - A Novel Antidepressant.
I started taking melatonin about 2-3 weeks ago every single day right before bed for sleep, antidepressant, and neuroprotective purposes. As of the last few days I've noticed that my skin has become freakishly pale. I asked one of my family members and they were quite aware of it as well. I literally look like ****ing paper. No joke. It's terrible. So I thought to myself, what the hell could be causing this?? The only thing I could think of was melatonin, as that's all I'm taking right now (besides multivitamin), and I know it's [sort of] associated with melanin, so I did a few PubMed searches and here's what came up:
The Effects of Oral Melatonin on Skin Color and on the Release of Pituitary Hormones:
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We studied the effects of prolonged ingestion of melatonin, 1 g per day, on skin color and the serum levels of pituitary hormones in 5 human subjects with hyperpigmented skin. Melatonin lightened hyperpigmented skin of one patient with untreated adrenogenital syndrome, but had no effect on three patients' skin with idiopathic hyperpigmentation and one patient with treated Addison's disease. Melatonin appeared to depress the level of luteinizing hormone (LH) in serum and may have inhibited in some patients the release of growth hormone from the pituitary gland after stimulation by stress or L-dopa. The subjects all noted increased drowsiness but through studies on the eyes, liver, kidneys, and bone marrow revealed no other evidence of toxicity.
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Melatonin Antagonizes α-Melanocyte-Stimulating Hormone (α-MSH) Enhancement of Melanogenesis in Mouse Melanoma Cells by Blocking the Hormone-Induced Accumulation of the C Locus Tyrosinase:
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Melatonin was found to have a small inhibitory effect on tyrosinase activity and a slight stimulatory action on dopachrome tautomerase activity in B16 mouse melanoma cells. These effects were time and dose dependent, with the maximal response being observed after 24-48 h treatment and at concentrations of melatonin higher than the physiologic levels of the circulating hormone. Although these effects on the melanogenic activities were modest, incubation of melanocytes with melatonin prior to the addition of the melanotropin mediated a dramatic inhibition of α-melanocyte-stimulating-hormone-(α-MSH)-induced melanogenesis. This inhibitory effect was evident at melatonin concentrations as low as 10 nM. Inhibition was nearly total at 0.1 mM melatonin, even at high concentrations of α-MSH (1 microM). The inhibitory effect of melatonin on α-MSH stimulation of melanogenesis was investigated. Melatonin appeared to act at least at two stages. Pharmacological concentrations of melatonin diminished the number of α-MSH receptors to about 75% of the control values without an apparent effect on receptor affinity, as determined by receptor-binding studies using 125I-[N-Leu4-D-Phe7]α-MSH as a probe. Physiological concentrations of melatonin also appeared to interfere with the intracellular events coupling increased cAMP levels and induction of the c locus tyrosinase, since it strongly inhibited the theophylline-mediated stimulation of melanogenesis. The inhibition of tyrosinase stimulation was higher in the microsomal than in the melanosomal fractions of cells which were treated with melatonin, then exposed to either α-MSH (1 microM) or theophylline (1 mM), suggesting that one of the main effects of melatonin might be inhibition of the induction of tyrosinase de novo synthesis.
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* Note that α-MSH is responsible for mediating the production of melanin in melanocytes, which results in skin pigmentation or darkening/browning. A lack of α-MSH will literally result in albinism.
Melatonin Inhibits Proliferation and Melanogenesis in Rodent Melanoma Cells:
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The effects of melatonin on proliferation and on the induction of melanogenesis in rodent melanoma cells were investigated. It was found that melatonin at low concentrations (0.1-10 nM) inhibited cell growth but had no effect on melanogenesis, while at high concentrations (> or = 0.1 microM) it inhibited the induction of melanogenesis but not cell growth. These effects were specific since corresponding concentrations of the direct precursor and product of melatonin degradation N-acetylserotonin (N-Ac-5HT) and 5-methoxytryptamine (5MT), respectively, did not have any effect on cell proliferation or melanogenesis. At very high concentration (100 microM) both N-Ac-5HT and melatonin could stimulate melanoma proliferation while 5MT inhibited it. The demonstration of differential and unparalleled effects of melatonin on cell proliferation and melanogenesis suggests that melatonin can regulate or modify both processes via different mechanisms.
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Comparative Biological Activities of α-MSH Antagonists in Vertebrate Pigment Cells:
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We have previously reported that melatonin [is] an effective lightening agonist in the teleost Synbranchus marmoratus, the amphibians Rana pipiens and Bufo ictericus, and in the lizard Anolis carolinensis. The hormone, previously applied to the preparations, effectively inhibited α-MSH darkening activity in a dose-independent manner, and was also able to reverse MSH-induced darkening. We presently describe the inhibitory effect of the indoleamine on the murine melanoma cell proliferation. Interestingly, the hormone also stimulated tyrosinase activity, with a correlated increase in melanin content. We also demonstrate that in a diverse lizard species, Urosaurus ornatus, the indoleamine was totally ineffective. The competitive MSH antagonistic activity of H-His-D-Arg-Ala-Trp-D-Phe-Lys-NH2 has been demonstrated previously in R. pipiens and U. ornatus. Herein, its inhibitory activity is also reported in another lizard species, A. carolinensis. However, this MSH analogue was inactive in S. marmoratus, and in murine melanoma cells. On the other hand, the 7 thru 10 α-MSH fragment, Ac-Phe-Arg-Trp-Gly-NH2, although ineffective in S. marmoratus and R. pipiens, was an α-MSH antagonist in A. carolinensis. Surprisingly, in the melanoma cell line, the MSH fragment exhibited no agonist or antagonist activity, but dramatically potentiated the MSH-induced increase in tyrosinase activity. These data might suggest that the fragment is participating either in the process of facilitation or in positive cooperativity. The present results, taken together with our previously reported data, demonstrate a major interspecies diversity of the MC1 subtype of melanocortin receptor, and point out the relevance of the membrane microenvironment for the final receptor configuration.
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Melatonin Desensitizing Effects on the In Vitro Responses to MCH, α-MSH, Isoproterenol and Melatonin in Pigment Cells of a Fish (S. Marmoratus), a Toad (B. Ictericus), a Frog (R. Pipiens), and a Lizard (A. Carolinensis), Exposed to Varying Photoperiodic Regimens:
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Melatonin is a weak dose-independent lightening agonist in fish skin, a moderate dose-dependent lightening agonist in toad skin and a potent lightening agent in frog and lizard skins (reversing in a dose-dependent manner the darkening caused by α-melanocyte-stimulating hormone). In frog skins, previous exposure to melatonin reduced further lightening actions of the indoleamine, and in toad skins, increasing concentrations of melatonin elicited decreasing lightening responses, suggesting an autodesensitizing action of the hormone. Various concentrations of melatonin diminished the responses to the lightening agonist melanin-concentrating hormone (MCH) in fish skins and to the darkening agonists α-MSH in toad, frog and lizard skins and isoproterenol in frog skins. In vitro inhibitory actions of melatonin are mimicked in the absence of the hormone in skin preparations from toads kept in continuous darkness for 48 hr. The lipophylic nature of the indoleamine associated with the results herein described suggests intracellular actions of melatonin on vertebrate pigment cells.
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I just ran out of melatonin yesterday and I was going to buy more, but now I'm not going to do that anymore after what it's done to my skin color. I wonder how long it will take for my pigmentation to recover? I'm curious, has anyone else experienced this effect from melatonin or any other melatonergic agent (e.g., ramelteon, agomelatine, etc) for that matter?
I find this to be ridiculous and kind of funny, but at the same time (when I look in the mirror) not..
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12-02-2009, 12:00 PM
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