Melatonin sensitizes the system

Bear with me here… this could be very important (or just all in my imagination haha)

Fact: melatonin secretion happens at night (or at least that’s when it’s supposed to happen):


circadian melatonin


And it’s important to adopt healthy circadian behaviors early on to prevent or minimize the age-related decline in melatonin secretion:


melatonin in aging



Part 2: Melatonergic signaling is intrinsically inhibitory in many cell types:


inhibitory melatonin signaling


It turns down certain processes, and this is why many cell types proliferate at night.  See: Sunlight and the Circadian Rhythms in your Skin.  Skin cells shouldn’t be proliferating while they’re simultaneously trying to protect themselves from UV rays during the day.  Something similar happens in skeletal muscle cells, beta cells, and many others (N.B. in these studies, pretreatment with melatonin in cell culture can be interpreted as analogous to overnight exposure to melatonin in humans, so the beneficial impact is most highly manifest in the morning).


As these programs aren’t being used (or being actively inhibited by melatonin), it’s said they are becoming sensitized.


By the time you wake-up in the morning, some of these programs like endogenous antioxidant enzymes and those involved with proper protein processing,  attenuating ER stress, etc., are primed and and ready to process a big influx of nutrients (eg, breakfast).

We know skipping breakfast and eating late dinners is no bueno, long term… maybe this is why



A properly functioning circadian clock is necessary for this – without it, oxidative stress goes out of control and you age faster (rodent studies, but still).


As the day progresses, the protective mechanisms become progressively de-sensitized and less able to effectively manage [cellular] metabolic stressors like a big meal.



There just might be a reason things happen this way.  Bright light in the morning makes you less sensitive light-induced melatonin suppression in the evening (eg, Kozaki et al., 2015).  Avoiding artificial light at night or simply wearing hot blue blockers bolsters melatonin secretion which enhances sensitization, making you more able to optimally partition nutrients when the system is fully sensitized -> in the morning.




Mythology?  maybe… but seems legit to me

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  • Wab Mester

    “it’s important to adopt healthy circadian behaviors early on to prevent or minimize the age-related decline in melatonin secretion”

    Any evidence that behavior modifies the age-related decline? What happens in other species, for example?

    • studies on light exposure in the morning and minimizing artificial light at night show positive effects in both young and elderly populations… no big longitudinal [intervention] studies have been done to my knowledge, but still strongly suspect it works

      as to other species, with the exception of those exposed to chronic light pollution, they live perfect circadian environmental conditions… so likely no great age-related circadian arrhythmia

  • Deborah Gordon, M.D.

    Very interesting info… And melatonin has a complicated relationship to insulin signaling. Perhaps improves age-related greater insulin resistance, , perhaps it raises blood sugar (which seems contradictory), but I like these points you raise. And for those of us over 60 and evidently in melatonin decline, we should probably supplement with melatonin, IMO!

  • Eve

    Melatonin supplements are the only thing that allows me to sleep several hours uninterrupted. Otherwise, I wake up with a jolt, ravenous, 1.5h after falling asleep, and need to eat in order to fall back asleep. It’s a frustrating and vicious cycle because if I eat at night, I don’t want to eat again in the morning.

    • Interesting.
      Just curious, do you get bright light in the morning and block artificial light at night?

      • Eve

        Not sufficiently. I blacked out the bedroom windows because of the street lights, but one of the windows is unfortunately the only direct (and brief) source of sunlight in my apartment. The other windows face our neighbours. I use f.lux, and keep my phone as dim as it’ll allow, but I can’t really avoid the lights at work, gym, or metro, when coming home late in the evening. When I take Vit D, I do so in the 10-20k range in the morning.

        • TechnoTriticale

          re: …can’t really avoid the lights at work, gym, or metro, when coming home late in the evening.

          Blue blockers: the Honeywell UVEX brand can be had inexpensively from Amazon and similar resellers. If you don’t wear glasses, consider the S9133X. If you do wear glasses, get the admittedly clunky looking S0360X. Helps keep the ipRGCs unstimulated.

          • agree, of course, but the gym at night can be a circadian nightmare — bright lights blazing from all angles, music blaring, mental & physical stimulation, etc.

            If it doesn’t impact your rhythms & sleep quality, go for it, but if all those other ducks aren’t in a row….

  • David Andrews

    Do you recommend melatonin supplementation? (I am 71 year old male). Is the age-related decline associated with testosterone decline?
    I have no trouble falling asleep, but tend to wake up after 4-5 hours and then doze for another 2-3 hours.

  • Melatonin in regulation of inflammatory pathways in rheumatoid & osteoarthritis: involvement of circadian clock genes