I would like a new non-dogmatic look at melatonin. Please consider that rat models might be backwards given their opposite (nocturnal wakefulness), it seems to me that circadian amplitude is most likely the key factor and needs to be incorporated in to the Peat friendly body of work. From a practical/ therapeutic standpoint, I am open to alternatives that are more in line with Peat and reduced stress, so for sleep induction I would have: Progesterone, small bits of Thyroid, niacinamide, cyproheptadine and perhaps glycine and magnesium (along with milk and sufficient calories/sugar). I generally do this plus add small bits (<1mg) of melatonin, I generally prefer sleep on the melatonin, but I might have blown our my endogenous receptors. I am trying to make sense of the research pointing in both directions with a clarified model/understanding. Here is something I recently wrote to an forum member in a n individual email:
As per melatonin, have you personally looked into it? I understand Ray has seen that it is a potential vasoconstrictor and inducer of serotonin or estrogen as well as an exacerbator of depression. I would love to either change my mind about melatonin (and stop using something harmful) or see if my logic makes sense. My first and biggest argument is that melatonin is known to reduce dramatically over the lifesapan and many older people have trouble sleeping while kids do not. My second argument is that I think the basic test model might be backwards as rats circadian rhythms are inverse to humans, meaning that melatonin might signal opposite pathways for thermo-regulation and sleep/repair - i.e. melatonin signals dark, but only initiates sleep via vasodialation when the organism would typically sleep. In rats it signals wakefulness and vasoconstriction (and perhaps a stress cascade seemingly related to the need for heightened vigilance) It seems I can find evidence of a different response in humans (Melatonin differentially affects vascular blood flow in humans) and a number of other benefits related to reduced cancer etc. I came to melatonin from basic evolutionary logic i.e artificial light damps or erases normal evening signaling and circadian regularity. I personally like it enough to prefer sleep on it to not ( I only take small sublingual doses), but there is a case for mild dependence. In my understanding the amplitude of temperature and wakefulness is very important for health. Higher daytime heat is associated with an inverse reduction of temperature. That said, I also think melatonin also poses risks for depression, fertility, and pigmentation. These, I think ,are related to it also being a signal of seasons. It seems that high absolute melatonin (or low daytime melatonin supression) suppresses sex hormones. The studies that use melatonin counter-circadian cycles seem to induce these problems. Similarly increasing melatonin seems to reduce/eliminate fertility which would be counter productive in the winter for many mammals but maybe not humans (this needs more work as humans seem to have a fertility season with July-Sept peaks in norther hemisphere suggesting a late fall gestation - meaning this is probably different than rats (
Pre-Baby Boom Era, the birth peak occurred as early as June in the northern states of Oregon and Maine, whereas the peak occurred as late as November in Florida. The variation in birth peak timing was largest during the Pre-Baby Boom Era, when the most out-of-phase states differed by more than five months. Source: Human birth seasonality: latitudinal gradient and interplay with childhood disease dynamics. - PubMed - NCBI). I would assume incrementally reducing melatonin would also signal something perhaps increasing thryoid.
http://rspb.royalsocietypublishing..../F2.large.jpg?width=800&height=600&carousel=1
These are taken from just the first page of pubmed when I type "melatonin"
For:
Melatonin brain death reduction:
Melatonin attenuated brain death tissue extract-induced cardiac damage by suppressing DAMP signaling. - PubMed - NCBI
Breast cancer reduction:
Melatonin: A Molecule for Reducing Breast Cancer Risk. - PubMed - NCBI
Wrinkle Reduction:
Antiaging efficacy of melatonin-based day and night creams: a randomized, split-face, assessor-blinded proof-of-concept trial. - PubMed - NCBI
Promoter of autophagy:
Melatonin as an endogenous regulator of diseases: The role of autophagy. - PubMed - NCBI
Contra:Thyroid, insomnia, and the insanities: Commonalities in disease
Lower thyroid and causes seasonal depression:
Secondary to excessive melatonin synthesis, the consumption of tryptophan from outside the blood-brain barrier and melatonin over-signaling in the ... - PubMed - NCBI
Thyroid, insomnia, and the insanities: Commonalities in disease
Golilocks:
Small perfectly timed amounts seem helpful:
The phase shift hypothesis for the circadian component of winter depression
All thoughts and insights are appreciated.
As per melatonin, have you personally looked into it? I understand Ray has seen that it is a potential vasoconstrictor and inducer of serotonin or estrogen as well as an exacerbator of depression. I would love to either change my mind about melatonin (and stop using something harmful) or see if my logic makes sense. My first and biggest argument is that melatonin is known to reduce dramatically over the lifesapan and many older people have trouble sleeping while kids do not. My second argument is that I think the basic test model might be backwards as rats circadian rhythms are inverse to humans, meaning that melatonin might signal opposite pathways for thermo-regulation and sleep/repair - i.e. melatonin signals dark, but only initiates sleep via vasodialation when the organism would typically sleep. In rats it signals wakefulness and vasoconstriction (and perhaps a stress cascade seemingly related to the need for heightened vigilance) It seems I can find evidence of a different response in humans (Melatonin differentially affects vascular blood flow in humans) and a number of other benefits related to reduced cancer etc. I came to melatonin from basic evolutionary logic i.e artificial light damps or erases normal evening signaling and circadian regularity. I personally like it enough to prefer sleep on it to not ( I only take small sublingual doses), but there is a case for mild dependence. In my understanding the amplitude of temperature and wakefulness is very important for health. Higher daytime heat is associated with an inverse reduction of temperature. That said, I also think melatonin also poses risks for depression, fertility, and pigmentation. These, I think ,are related to it also being a signal of seasons. It seems that high absolute melatonin (or low daytime melatonin supression) suppresses sex hormones. The studies that use melatonin counter-circadian cycles seem to induce these problems. Similarly increasing melatonin seems to reduce/eliminate fertility which would be counter productive in the winter for many mammals but maybe not humans (this needs more work as humans seem to have a fertility season with July-Sept peaks in norther hemisphere suggesting a late fall gestation - meaning this is probably different than rats (
Pre-Baby Boom Era, the birth peak occurred as early as June in the northern states of Oregon and Maine, whereas the peak occurred as late as November in Florida. The variation in birth peak timing was largest during the Pre-Baby Boom Era, when the most out-of-phase states differed by more than five months. Source: Human birth seasonality: latitudinal gradient and interplay with childhood disease dynamics. - PubMed - NCBI). I would assume incrementally reducing melatonin would also signal something perhaps increasing thryoid.
http://rspb.royalsocietypublishing..../F2.large.jpg?width=800&height=600&carousel=1
These are taken from just the first page of pubmed when I type "melatonin"
For:
Melatonin brain death reduction:
Melatonin attenuated brain death tissue extract-induced cardiac damage by suppressing DAMP signaling. - PubMed - NCBI
Breast cancer reduction:
Melatonin: A Molecule for Reducing Breast Cancer Risk. - PubMed - NCBI
Wrinkle Reduction:
Antiaging efficacy of melatonin-based day and night creams: a randomized, split-face, assessor-blinded proof-of-concept trial. - PubMed - NCBI
Promoter of autophagy:
Melatonin as an endogenous regulator of diseases: The role of autophagy. - PubMed - NCBI
Contra:Thyroid, insomnia, and the insanities: Commonalities in disease
Lower thyroid and causes seasonal depression:
Secondary to excessive melatonin synthesis, the consumption of tryptophan from outside the blood-brain barrier and melatonin over-signaling in the ... - PubMed - NCBI
Thyroid, insomnia, and the insanities: Commonalities in disease
Golilocks:
Small perfectly timed amounts seem helpful:
The phase shift hypothesis for the circadian component of winter depression
All thoughts and insights are appreciated.