Melatonin

links: Hormones reference: 4-11-2021

Melatonin #

• Made from N-Acetylserotonin via HOMT; acetylserotonin being made from serotonin via Serotonin N-Acetlytransferase
  • Converted back to NAS via CYP1A2, CYP2C19
    • CYP1A1 metabolism as well, which it also inhibits.
• Peaks at 3AM, and hits 0 at about 6-7AM. Apparently it exists for sleep initiation, not so much for staying asleep.
  • That’s brutal if you have to get up at 5AM when it’s still high. I guess person by person you can offset this by an hour or 2. But sleeping 10-7 looks like a good idea.
  • Plumments when puberty is initiated.
• Positively correlated with TSH in hypothyroidism and negatively with T3 in hyperthyroidism R
• Antioxidant, and special in that it doesn’t convert to a pro-oxidant. Alex Chen says it’s the best antioxidant.
• Hypothermic
• Upregulated in ADHD R
• Melatonin mediated antidepressant-like effect in the hippocampus of chronic stress-induced depression rats: Regulating vesicular monoamine transporter 2 and monoamine oxidase A levels
  • Melatonin treatment in the CUMS rats prevented the stress-induced decrease in VMAT2 mRNA and protein levels, whereas it reduced the increase of the mRNA of COMT and protein levels of MAO-A.
  • Chronic treatment with melatonin failed to alter the gene expression of DBH or NET in the hippocampus of the CUMS rats.
  • Enhances VMAT2 expression and norepinephrine storage, whilst it reduces norepinephrine degrading enzymes (… MAO?)
• Melatonin Acts as an Antidepressant by Inhibition of the Acid Sphingomyelinase/Ceramide System
• Central depressant and nootropic effects of daytime melatonin in mice
• Melatonin improves memory acquisition under stress independent of stress hormone release
  • Increase in Prolactin secretion, via its action on hypothalamic dopaminergic neurons
• Melatonin’s actions are not limited to sleep
• Melatonin modulates the GABAergic response in cultured rat hippocampal neurons
• TRPV4 Stimulation Induced Melatonin Secretion by Increasing Arylalkymine N-acetyltransferase (AANAT) Protein Level
• https://www.rapamycin.news/t/melatonin-megadoses/2613/49
  • After puberty, daytime levels begin to diminish. After age 35-55, nighttime levels decrease.
  • Melatonin helps set the biological clock of a developing fetus. Nursing children for 3-4 months and maybe as long as 5-6 months do not produce melatonin – they get it from nursing. Babies who do not nurse do not receive this melatonin. Some have speculated that SIDS could have a correlation with melatonin, but this has not been studied.
  • No negative feedback since the pineal gland is not part of the endocrine system.
  • The amplitude of endogenous melatonin production is not affected by melatonin treatment in humans
  • Cells produce them, even in the daytime. Bit it’s not released into the bloodstream
• [Melatonin receptors in pancreatic islets: good morning to a novel type 2 diabetes gene]
  • 
    • The superior cervical ganglion projects Norepinephrine to the Pineal Gland to raise cAMP, inhibiting the ubiquitin proteasomal system, which normally degrades Serotonin N-Acetlytransferase.
• https://bengreenfieldlife.com/article/supraphysiological-dosing-melatonin/
• The neuroprotective role of melatonin in neurological disorders

Neurogenesis #

• Melatonin facilitates short-term memory
• Melatonin increases NMDA receptor subunits 2A and 2B concentrations in rat hippocampus
• Neural stem cells express melatonin receptors and neurotrophic factors: colocalization of the MT1 receptor with neuronal and glial markers
• Melatonin regulates the viability and differentiation of rat midbrain neural stem cells

Dose #

• Doses below 1 or above 20mg are fine. Anything in between is bad for some reason. 300mcg is kind of the standard physiologic dose. Megadose for longevity = 1g+?, or some take 180 mg. I think you can OD on a few hundred miligrams?
• Quicksilver’s liposomal melatonin (which I believe is a nasal spray)
• Parasympathetic Nervous System

Megadose #

• Bluetorch does 300mg 3x per day, and 300mg up to 2x per night (like after waking and stuff). Or just do 1g before sleep.
  • He also reported his head/neck got way whiter, so let’s fucking go
  • This guy also says Xanthohumol for Skin whitening works because of how strong of an antiinflammatory it is, especially for covid