There are a lot of mysteries involving melatonin, eg, relative importance of gut vs. pineal-derived melatonin.  Does brain melatonin talk to peripheral MT receptors?  Does gut melatonin talk to brain MT receptors?


What we do know: oral melatonin works in people with circadian-related sleep disorders.  This may suggest that oral/gut melatonin talks to brain MT receptors OR that oral/gut melatonin corrects circadian sleep problems by acting in the periphery.  OR a major target of brain melatonin is peripheral MT receptors.  I don’t know.


And as a further testament that melatonin supps aren’t sleeping pills is that they’re non-addictive and can at least temporarily “fix” circadian sleep problems: after prolonged treatment, people report no withdrawal symptoms and still sleep better even up to two weeks after discontinuation (Lemoine et al., 2011)!



In general, melatonin supps are thought to improve sleep quality, not necessarily sleep duration (although they may do that as well in some people).  And poor sleep quality ruins everything.  Health, cognition, well-being, quality of life -> increased risk of practically every disease, fat gain, increased risk of crashing your car… everything goes to shit.


Melatonin is the chemical expression of darkness


As for supplements, extended release is favored because it more closely mimics physiological melatonin plasma levels (regardless of whether plasma melatonin comes from brain or gut).  The Lemoine study used 2 mg extended release melatonin, but other studies have shown efficacy with a range of doses.  Ymmv.



In this study, urinary 6-sulfoxymelatonin was 15ug/night in treated insomniacs, compared to 10ug in non-treated insomniacs, compared to 18ug in non-insomniacs.



“The long-term administration of PRM did not cause suppression of endogenous melatonin production as evident by the rhythm in 6SMT in the urine. The presence of such rhythm also confirms that the 6SMT was endogenous rather than a metabolite of the residual PRM discontinued 2 weeks before. The reported observations are confirmatory and compatible with earlier reports in the literature on the lack of the suppressing effect of exogenous melatonin on its endogenous production.”  [seems like good news]




Sunlight and food intake in the morning strengthens the circadian rhythm of melatonin and makes it more resilient against night time light exposure (eg, Wada et al., 2013).  AND VICE VERSA:  Less exposure to daily ambient light in winter increases sensitivity of melatonin to light suppression (Higuchi et al., 2007).

LED light hitting your eyes from above at night is literally the worst.  If you want to read at night, try a candle at or below eye level.  Or an amber bulb.  And blue blockers.

This is especially important for kids: Increased sensitivity of the circadian system to light in early/mid-puberty (Crowley et al., 2015).  And old people (eg, Haimov et al., 1994), who may stand to benefit more from a supp (Garfinkel et al., 1995 & Peck et al., 2004).


Sleep well.

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  • Daz

    Thx for another post Bill.

    Do you have a ref/link re the ‘…light hitting your eyes from above at night is literally the worst’ ,
    So I can read some more. Icr seeing anything on above/below eye light, led or otherwise, before.

  • Jack Kruse

    Oral melatonin appears to reach the eye through the circulation. When it is administered at a time of day when it is not usually present, melatonin appears to reduce input to retinal cones. The same is not true to the non visual opsin receptors that control the central retinohypothalamic pathways. Taking melatonin orally chronically without blocking blue light can lead to eye damage.taking oral melatonin might be a real bad idea. Why? Oral melatonin is an inhibitor of retinal dopamine production. If you use it for sleep you might be lowering ocular dopamine to cause elongation of the globe and worsen mypia and set you up for retinal detachment. When this change occurs in the globe it then changes the pathways from the retina that project to the frontal lobes ability to make dopamine. This changes the reward circuits dopamine levels which leads to circadian disorders may affect cone functioning. What else can it do? Dopamine controls hormone release from the pituitary via the central retinal pathways so you can also lose control of the proper release of your hormones via solar light. How do we know this is true? Bio hack the impact of oral melatonin usage on your cone response and the regeneration of your retina using electroretinography (ERG). You might be shocked at the results you get.

    It turns out the reason your retina has more DHA than the brain dose per gram is because of how ocular melatonin regenerates rods and cones via the Bazan effect’s short loop in the retina. Melatonin is the hormone that controls the process because it also controls the mtDNA of the RPE which the photoreceptors sit within.

    Oxidative stress is involved in activating photoreceptor death in several retinal degeneration experimental set up leading to retinal tears.

    Growth is necessary in the eye for wellness, but it is always stimulated by damage (ROS) and limited by regeneration. So how does the eye accomplish this?

    Docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in the retina. It protects cultured retina photoreceptors from apoptosis induced by oxidative stress and promotes photoreceptor differentiation. It works with dopamine to accomplish this task. So why does the retina have more DHA? It is the one part of the human that has ability to make DHA from EPA. Investigations have shown that eicosapentaenoic acid (EPA) is the booster to making more DHA in a complex photochemical dance using the side chains of tyrosine and UV light. EPA is a metabolic precursor to DHA and it has been shown to have an effect on retinal neurons so that they could activate ?6 desaturase (FADS2), which introduces the last double bond in DHA biosynthetic pathway to metabolize EPA to DHA. In the retina, because of melatonin and dopamine EPA is able to promote photoreceptor differentiation and rescued photoreceptors from oxidative stress-induced apoptosis from light through its elongation and desaturation to DHA. Experiments have now shown in humans for the first time, that isolated retinal neurons can synthesize DHA in culture.

    This increase of DHA is important in running the SCN faster than all other circadian clocks.

    • Jack Kruse

      Red light therapy (670 nm, 4 J/cm2) has been shown to restore glutathione redox balance upon toxicological insult and enhance both cytochrome c oxidase and energy production, all of which may be affected by melatonin cycles in the eye. Blue light destroys melatonin in the eye and red light is the antidote to it. 42% of sunlight is infrared A light which can repair the eye. This is a better option than oral melatonin.

      • Matthew Klein

        Hi Jack,

        Awesome post, very informative! I’m wondering, do you know anything about the safety of vitamin d lamps? Negative side effects?


        • Max

          There are multiple studies showing the safety and efficacy of the Sperti Vitamin D lamp when used properly. I use mine almost every day, and for the first winter ever I’m not groggy and bummed out all day.

      • Carolina Villalobos Sandoval

        I have adrenal insufficiency and one of the supp that my doc has me on (he is one of the adrenal authorities in the country but not an hypothalamus expert like Dr Kruse) is oral melatonin (only 6mg though). I am going to stop it and get my body to produce it the way Dr K is suggesting. I use the blue light blocking glasses too already.I just recently started the CT protocol, hoping to see improvements once I cold adapt. I have always suspected and even told my doc that my problem is a signaling issue and not my adrenals precisely (before ending up in bed with extreme fatigue I used for a couple months meth sublingually and was also put on Prozac for six months which I think disturbed my HPA axis). My doctor is very wise but he’s more focused on giving my adrenals support thru nutrition, supplements, and stress management techniques but I think it would make a huge difference if we could really tap into the hypothalamus and pituitary gland as the CT protocol seems to. I avoid foods I am sensitive to and already am on a keto paleoish diet, need to add more sea food though to make it more epi paleo compatible. The bioidentical hormones my doc has me on now are very gentle so I should be able to stop them easily if my hypothalamus in fact wakes up 🙂 1200 mg of pregnenolone daily and 10mg progesterone cream during the luteal phase. Doing also ACE drops and porcine adrenal cortex pills to strengthen the adrenals among other vitamins and minerals.
        I was using more bioidentical hormones before but as I have been improving my doc has been taking me off them :))

  • alan2102

    Nice post, thanks.

    “…lack of the suppressing effect of exogenous melatonin on its endogenous production. [seems like good news]”

    Yes, good news. Another specious argument against melatonin dies a well-deserved death. There are so many of them.