27 December 2018
THE TRUTH ABOUT MELATONIN DOSING
You might be taking 10x more melatonin than you need. Here’s the proof. When it comes to taking a melatonin supplement – or any supplement, for that matter – one of the most important questions one needs to ask is “How much should I take?” With melatonin, the answer is simple: 300-1000 MCG, OR 0.3-1 MG Yes,…
You might be taking 10x more melatonin than you need. Here’s the proof.
When it comes to taking a melatonin supplement – or any supplement, for that matter – one of the most important questions one needs to ask is “How much should I take?”
With melatonin, the answer is simple:
300-1000 MCG, OR 0.3-1 MG
Yes, this means most commercial melatonin products, dosed in the 3-10mg range, are 3-30x more aggressively dosed than is necessary or ideal.
One key point to understand here is that melatonin does not follow a linear dose-response curve. In other words, it is not the case that taking more melatonin necessarily puts you to sleep faster and/or keeps you asleep longer than does taking less. Rather, low doses of melatonin (0.3-1mg) are more effective than both very low doses (e.g. 0.1mg) and higher doses (e.g. 3-5mg). If you look at the research which actually puts various melatonin doses head-to-head, this result is unequivocal.
For example, Zhdanova et al 1996 compared the effects of placebo, 0.3mg melatonin, and 1mg melatonin administered 2-4 hours prior to usual bedtime on sleep efficiency and sleep latency (time taken to get to sleep) in twelve young, healthy subjects (average age = ~29 years). It was found that while both 0.3mg melatonin and 1mg melatonin significantly improved sleep efficiency and sleep latency relative to placebo, 1mg melatonin was not superior to 0.3mg . Indeed, sleep latency was actually worse in the 1mg melatonin group, although not to a degree which was statistically or practically significant. Nonetheless, these results underline the apparent lack of the superiority of melatonin dosages outside of the physiological range; the 0.3mg melatonin dose increased plasma melatonin concentrations to an average of 112 pg/mL (still within the physiological range), whereas the 1mg dose increased plasma melatonin nearly five times more, to 521 pg/mL (well into the supraphysiological range). Again, as counterintuitive as this might be, this massively higher elevation in melatonin did absolutely nothing to improve sleep per the relevant measures – and keep in mind the higher dose in this study – 1mg – is only 1/3rd to 1/10th as high as most commercial melatonin products!
Similarly, in a 2001 study of the effects of melatonin on sleep in both elderly insomniacs and healthy control subjects, the same research group found that 0.1mg, 0.3mg, and 3mg melatonin taken 30 minutes before sleep reduced sleep latency in healthy subjects and improved sleep efficiency in insomniacs relative to placebo, with no statistically significant differences between dosages. Again, this means that a 10x higher dose (3mg) of melatonin worked no better than a lower dose (0.3mg). Indeed, 0.3mg melatonin actually outperformed 3mg melatonin in terms of sleep latency in healthy subjects and sleep efficiency in insomniacs, although these differences were not statistically significant; whether or not these differences are practically meaningful is not entirely clear, and likely depends on how high of a bar one sets for such differences being practically meaningful. That question aside, these data clearly indicate 1) melatonin works for both healthy persons and insomniacs, albeit in different ways and 2) again, melatonin’s effectiveness does not scale with dosage (at least not above a threshold likely between 0.3mg and 1mg), with 3mg melatonin being no more effective than .3mg.
Note that up to this point we have only discussed the effectiveness of melatonin. Although melatonin is naturally secreted by the pineal gland at night, and thus supplementation within physiological ranges can probably be reasonably assumed to be safe in the absence of contradictory evidence, the mere fact that melatonin is naturally occurring does not justify the conclusion that supraphysiological elevations in plasma melatonin – those induced by high doses of supplemental melatonin – are safe. Indeed, side effects have been noted in the melatonin literature, including hypothermia and next-day grogginess, likely caused by melatonin remaining in circulation into the following day.
^ The effects of melatonin supplementation on core body temperature; 0.1mg and 0.3mg caused no statistically or practically significant change relative to placebo, whereas 3mg caused a significant drop in core body temperature.
Now, why is it that higher doses of melatonin don’t work better than lower doses? From a research perspective, I think the best answer is “We don’t know.” Frankly, the melatonin research isn’t great (even though there is a lot of it); many studies simply used a single dosage (often 5mg) , rather than comparing the effects of multiple dosages. As such, really getting into the weeds and mechanistically discerning why high doses don’t work better simply hasn’t been done yet.
My personal hypothesis is that there is a ceiling for the effective range of plasma (blood) melatonin concentrations, and blowing way above this range by using more than ~1mg of melatonin (indeed, 1mg will likely already put you above the physiological range, but apparently not by so much as to cause reduced efficacy or adverse effects) just sets you up for potential adverse effects mediated by having too much melatonin floating around.
I think there is an imperfect-but-decent analogy to be made here between melatonin and stimulants. How so? Well, stimulants, as their name suggests, stimulate, and up to a certain dosage of any given stimulant, this results in improved mood, subjective alertness, objective cognitive and physical performance, and so on. However, when you surpass a certain threshold for stimulant dosages (one which is highly variable between persons, but which nonetheless exists in all cases), you begin to see decrements in at least some of these outcomes. In other words, just as it is not the case that continuously slamming more caffeine necessarily yields more of the desired results, it is not the case that taking 3mg of melatonin will put you to sleep 10x faster than 0.3mg. Indeed, the actual experimental evidence indicates the opposite is the case; for most, 3mg of melatonin is simply too much.
Thus, both from the perspective of wanting to maximize effectiveness and from the perspective of wanting to minimize adverse effects, the data lead us to the conclusion that 300mcg melatonin is likely the ideal absolute dosage guideline; while higher dosages still do work, they don’t work better, and they run a greater risk of producing undesirable effects.
References:
https://www.researchgate.net/publication/14360949_Effects_of_Low_Oral_Doses_of_Melatonin_Given_2-4_Hours_Before_Habitual_Bedtime_On_Sleep_in_Normal_Young_Humans
“ the 3-mg dose significantly lowed the group minimum core body temperature ” https://academic.oup.com/jcem/article/86/10/4727/2849013