Melatonin

[Stavia]

What do you guys think about rather using the body's in-built mechanism for producing melatonin rather than a random supplemental dose that we don't know is an appropriate dose or not?

I have recently come off amitryptilene and the far too frequent zopiclone (zolidem to you USA people) after several years. I was terrified of not being able to sleep, because I have a pressurised high-level job and because I know sleep is imperative for preventing AD.
I read this book:
https://www.goodreads.com/book/show/135 ... earch=true

and armed with more knowledge did the following:
Bought a pink Tibetan salt (was the cheapest pink lamp actually) bedside lamp, a yellow plastic thingy for my ipad https://www.lowbluelights.com/products.asp?cid=57, got the "twilight app" for my phone (makes it reddish from sunset), stayed in my bedroom from 7pm with only the pink lamp on, eitherreading a book or on my ipad with the yellow filter - and VOILA!! sleeping brilliantly!!! from 9.30pm to waking 6am to 6.30am naturally. Oh my. Not what I expected. Its been sustained for a month now. If I have to go out of my bedroom I keep my eyes half closed and on the ground so as to get minimal blue light in them.

I am now about to buy the wraparound glasses from the lowbluelights website so I don't have to hide in my bedroom.

Only side effect is that going out with friends in the evening totally screws with my sleep for that night.
How interesting huh?

[circular]

Hi Stavia! Thanks for bringing this up. I've been taking 4.5 melatonin each night. I can't say it makes me sleep, in fact I read once it only "allows" sleep rather than causing it. But my sleep has been really screwy for years now and I figure melatonin is actually one of the more conservative options.

*Any*way, I use a program on my computer called f.lux. I tried finding "twilight" for my iPhone can can't find it in the App store. Is that the right name?

I will look into those other products. The glasses sound interesting too.

The deep sleep setting using the "brainwave" sound app for iPhone is really helping me get deeper sleep, though I seem to wake after 7 hours instead of the old 8 which was my normal good night's sleep.

[Stavia]

hi Circular, I have an android...dunno what the iPhone equivalent is.
I saw the brainwave phone thingy, not sure about the evidence behind it.
Maybe 7 hours is enough? If you wake refreshed, that is good

[circular]

I did finally get a reply from the brainwave developer. I need to cross-post this in the brainwave thread:

"My background is a mixture of physics, software development, and various forms of acoustic and signal processing research. The tones are really the result of work long pre-dating iOS and the iPhone, originally to help myself sleep and study as a Physics graduate student, but it's the advent of a programmable mobile platform that enabled the programs to evolve from static binaural mixes into dynamic programs."

I agree it's not vetted in peer review and I occasionally wonder if I could somehow be harming my brain using it, but it's very clear my sleep is deeper and it's hard to think that's worse than what was happening. We should continue to search for a "medical device" along these lines.

[Julie G]

I found this seemingly off-topic link really interesting. Apparently melatonin production is suppressed with even dim light in the room where you're sleeping ..such as that coming from under a door. Total darkness may be really important for us.

http://www.sciencedaily.com/releases/20 ... ce+News%29

[Gilgamesh]

Thanks, Julie. I'm now using extreme room-darkening methods, plus eye shades. It may not matter as much if we're taking supp'l melatonin, but who knows -- there could be plenty of effects of light other than melatonin suppression.

[circular]

Does lunar light have blue light? I would think so (?), but did it keep our ancestors awake? Just kind of curious how moonlight and it's variations (forest vs desert, cycles etc) affect melatonin and sleep.

[KatieS]

I keep trying to observe what my mother does to remain cognitively intact. Over a decade ago, she walled off her bedroom from any light. It's so pitch dark, that I argued that she might fall. Now I'm finding that wearing night shades seems to deepen my sleep. I've yet to try the orange len glasses a few hours before bedtime.

[MichaelR]

From Chris Kresser:

Melatonin is another commonly used sleep aid. But I don’t recommend it for anything more than emergency, short-term use. Why? Because melatonin is a hormone. Taking any supplemental hormone disrupts our natural regulatory mechanisms of that hormone and throws our internal production of it out of whack. This can create dependence over time and disrupt our circadian rhythm, which is crucial not only to sleep, but to overall health.

Chris Kesser is not a reliable source of health information. As in many other cases (usually where people are advocating for supplement use, often to sell it to you), this is mechanistically plausible but untrue in the real world:

Examine.com: Melatonin

Oral melatonin supplementation at 500mcg, over a period of a week in shift workers, did not influence basal secretion, as cessation for one day prior to measurements did not show differences when compared to secretion status prior to supplementation.[24] Twenty-four hour melatonin levels in this study, when graphed, essentially overlapped, suggesting next to no variance.[24] These results, indicating a lack of negative feedback, have been replicated with 2mg[25] and 5mg of melatonin.[26]

When a blind person supplemented a dose of 50mg in one case study (blind people being an example of a population with no sunlight-mediated melatonin production), this dose being 100-fold higher than the standard 500mcg, did not significantly influence basal secretion status.[24] In this population, lower doses of 500mcg are also effective and without apparent negative feedback.[27] ... [even when the] studies do control for persons with no conscious light perception.[27]

Regulation of melatonin secretion from the pineal gland does not appear to be negatively influenced by melatonin supplementation over the long term (multiple days) and no negative feedback from melatonin supplementation (less natural secretion after a period of supplementation) has been observed.

24: Matsumoto M, et al The amplitude of endogenous melatonin production is not affected by melatonin treatment in humans . J Pineal Res. (1997)
25: Wright J, et al The effects of exogenous melatonin on endocrine function in man . Clin Endocrinol (Oxf). (1986)
26: Arendt J, et al Some effects of melatonin and the control of its secretion in humans . Ciba Found Symp. (1985)
27: Hack LM, et al The effects of low-dose 0.5-mg melatonin on the free-running circadian rhythms of blind subjects . J Biol Rhythms. (2003)

The overnight 6SMT [melatonin metabolite] excretion (between 22:00 and 10:00) in 15 patients who completed 6 months of daily [prolonged-release melatonin, 2 mg] administration and the following 2 weeks withdrawal of treatment was mean ± SD of 15.3 ± 7.7 μg, median 15 μg, range 4–30 μg. These levels were significantly higher than those of a large reference population of patients with insomnia of the same age group (mean ± SD of 9.5 ± 7.9 μg, range 0–47 μg/12-hour night; t-test, P < 0.01) and similar to those without insomnia of the same age group (mean ± SD of 18.1 ± 12.7 μg per 12-hour night) (Figure 3).17,19 Fourteen out of the 15 patients were considered to be within the normal range ... A clear diurnal rhythm in melatonin production was evident in these patients, with levels of 6SMT over daytime hours (10:00–22:00) of mean ± SD 9.80 ± 5.06, range 3–19 μg/12-hour day, which is significantly lower than the night-time levels (mean ± SD of 15.3 ± 7.7 μg, median 15 μg, range 4–30 μg; t-test, P < 0.01).

Lemoine P, Garfinkel D, Laudon M, Nir T, Zisapel N. Prolonged-release melatonin for insomnia - an open-label long-term study of efficacy, safety, and withdrawal. Ther Clin Risk Manag. 2011;7:301-11. doi: 10.2147/TCRM.S23036. Epub 2011 Jul 26. PubMed PMID: 21845053; PubMed Central PMCID: PMC3150476.

(It would have been better for this last study to have done same-patient pre- and post-testing; fortunately this is covered in the Examine.com citations).

I do still agree that it's sensible to at least give your pineal a "wake up" (pun intended) by alternating on and off of it (unless you find it's the only thing that lets you sleep); and also to do things to enhance your own circadian rhythm, including endogenous M production, including going to bed and getting up at the same time daily; ditto, to the extent possible, for meal eating; bright light in the early morning, and dimness or blue-block sunglasses at night; and taking 500 mg tryptophan on an empty stomach not long before bed (provided this doesn't worsen your sleep by leading to additional nighttime trips to the bathroom).

On tryptophan: it's highly advisable IMO to get a brand of tryptophan that uses "TryptoPure" for its raw material (Doctor's Best, Life Extension, and Swanson all do, and there are others), because this is a very high-quality company made by Ajinomoto, a Japanese food, chemical, and pharmaceutical company with a long track record of safe production of this and other amino acids (including MSG ). Some of you may be aware that tryptophan was yanked off of the US market in the late 1980s, due to an outbreak of eosinophilia-myalgia syndrome which caused the death of 37 people and permanently disabled 1500 more. The epidemic is generally accepted, based on extensive epidemiological evidence and some limited chemical and toxicological data, to have been the result of contaminated tryptophan supplements produced using raw material from Showa Denko, a chemical manufacturer that had previously been implicated in a massive mercury toxicity scandal in Japan. SD had just introduced a novel recombinant DNA-based way to synthesize the molecule, and had "simplified" their purification process, which left residues of several low-level contaminants; one or more of these is thought to be responsible for EMS, though no one knows for sure. (The alternative hypothesis of histamine overproduction in the Wikipedia Showa Denko article is in my view not very plausible, granted the large number of people who have taken Trp supplements before and since, as it's inconsistent with the epidemiology at the time and the lack of any EMS epidemic prior to the disaster or of any re-emergence after the reentry of Trp onto the US market from 2001-2005).

Also, supplemental Trp should probably be avoided by people taking SSRIs, SNRIs, MAOIs, and other drugs with strong effects on serotonin metabolism, for risk of Serotonin syndrome; this doesn't happen with Trp alone because its conversion into serotonin (and thence to melatonin) and later degradation in the synapse is under physiological regulation, with which SSRIs interfere.

[Silverlining]

Thank you! Really appreciate the summary and references. I've wondered about the endogenous feedback loop with exogenous supplementation.