Melatonin: Everything You Need to Know


Everything produces melatonin, and it's benefits go way beyond just sleep!

In this article you will learn:

  • What melatonin is and why it's important for your health

  • The astounding research behind this compound and how to use it safely

  • Where to get my favorite, most effective kind for daily use

Lazy Reader's Section:

Melatonin is a compound that was initially discovered in humans but has recently been seen in plants as well. Every living thing seems to have melatonin, and it plays important roles in the body as a protective chemical, antioxidant, anti-cancer and recovery regulator. It's very useful for sleep, especially since many people have genetic issues with producing neurotransmitters in sufficient amounts, and is extremely non-toxic. The best melatonin is sublingual, and I use this one by OHS.


The Details:

Up until very recently I thought - like most everyone else - that melatonin is what you take for sleep. I had taken some here and there in the past to help with falling asleep, although rumors of supplementation affecting your own ability to produce melatonin steered me away from including it as a regular supplement - even when I was having trouble with my sleep.


If you research melatonin, you’ll find lots of mixed data and even alternative medicine sources lack thoroughness in compiling all there is to know about this magical chemical. That's why in this article I’m going to give you the No Bullshit tour so that you become a melatonin Superstar, should you decide to use it.


Did you know that melatonin actually does much more than help you sleep? Several ongoing studies have concluded that it helps detoxify the body and serves as a powerful antioxidant, helps with bone formation and reproductive and immune system regulation. It also has protective and therapeutic effects on the brain, heart, GI system and against cancer.(1,2,3)


Discovered in mammals in 1958 by physician Aaron Lerner, and then in plants in 1992 by other researchers,(4) melatonin seems to be in almost every living thing on the planet; as an important chemical for regulating growth, circadian rhythm and fighting oxidative stress.


Research findings have also implicated it in a number of therapeutic roles, and with a relatively low risk profile. For example, some research found it to be effective against bacterial diseases like tuberculosis,(5) and its anti-cancer(6) and chemo-protective effects(7) are well studied. It stimulates and modulates the immune system,(8) although the mechanism isn’t understood yet, and it also has anti-inflammatory and antioxidant properties.(9,10) It’s even been considered as a treatment for managing Ebola,(11) pain from surgery and the metabolic effects of bipolar medication.(12)


With all of these important roles and benefits, it is an interesting implication for aging if science has found that our melatonin levels steadily drop beginning in our 30’s to as much as 40% in our 60’s.(13,14) We’re also bathed in unnatural light 24/7 living in the city, and it’s been found that melatonin production decreases by as much as 50% even when exposed to light less than 30 lux, or the intensity of typical indoor lighting.(15) The same research found massive difference in light reactivity between individuals, and even blind people weren’t immune to these effects, suggesting an extremely sensitive sensory system in our body relating to light and light types.


Now, with all of this new information, are you ready to grab some melatonin?


Unfortunately, it’s not that simple. For how intriguing and beneficial most of this research is, melatonin is not without its considerations. Do a general search on Google about it and you’ll find all kinds of warnings, opinions on dosage, potential side effects and so on. Are these warranted? How can something that’s in every living being and shows so many protective effects also come with so many considerations? To get some answers you really have to dig, but lucky for you I’ve done some of the digging already.


Let’s consider some of the following:


1. A review of the literature on melatonin found several significant points regarding dosage and toxicology. First, no LD50 could be established in any animal studies even at an egregious 800mg/Kg of body weight. “LD50” means at what dosage a substance will kill off half of your testing population. For a 50Kg animal (110lbs) that means that even a dose of 40,000mg wouldn’t be toxic or deadly. Humans treated with up to 6600mg per day for 45 days showed no toxicity other than drowsiness, and another study reviewed 1400 women taking 75mg per night for 4 years with no side effects. Rats that already had high cholesterol had a harder time processing their LDL cholesterol when melatonin was introduced, which led to some arterial inflammation, but the exact cause was unknown and could be a cofactor issue rather than being due to melatonin.(16)


2. A study used 10mg for 28 days in 40 people with no difference in side effects between them and placebo.(17)


3. Dosing as little as 5mg can raise blood levels by as much as 25 times, but does not alter endogenous production.(18,19,20)


4. A review of over 2 dozen melatonin supplements, spanning 16 different brands, purchased at a grocery store in Ontario looked at the content of capsules, tablets and liquids. It found that most ranged from 80% to over 400% of the melatonin listed on the label and even had significant deviation within the product itself. Worryingly, 26% of the products also had serotonin in them which can lead to serious side effects like serotonin syndrome.(21) This is why it is important to utilize a quality brand with a quality product. It’s important to note that many of these inconsistencies alone, especially the added serotonin, explain a wide variety of the common short-term side effects people have reported like insomnia, anxiety or depression, rather than melatonin itself.


5. Bioavailability of oral tablets or capsules is only about 20-30%, compared to sublingual liquid formulations that are absorbed directly into the bloodstream.(22) Based on most of the research, it seems taking melatonin at night is the best option since morning may impair glucose metabolism(23) and cause more unpleasant side effects like drowsiness.


6. There was some concern for a while that melatonin may affect seizures in children, but a review of the literature found that it neither improves nor worsens these outcomes.(24)


7. There is limited research of melatonin causing diarrhea.(25,26) There are also several

anecdotal accounts of people discussing these experiences online and in various forums. The research is mixed, as some of these reports show positive effects on people with IBS, but in others with Crohn’s or ulcerative colitis, it seemed to exacerbate diarrhea. In some rat studies, melatonin reduced diarrhea in rats with colitis, but these mechanisms are not understood.


Interestingly, it’s been discovered that the gut has over 400 times more melatonin than the pineal gland, as well as several melatonin receptors scattered throughout it. It’s considered currently that melatonin plays a role in the motility (movement) of the gut muscles.(27)


One cause of diarrhea is that food moves too quickly through the gut before the water portion of stool can be absorbed. Since melatonin regulates circadian rhythm, perhaps there is an accelerating factor in gut movement when you take it as a supplement which in some people may lead to diarrhea.


8. Research is often conflicting because many factors aren’t accounted for. The form and quality of a supplement, the genes of a person, their inherent toxicities and deficiencies and so on, will all skew the results and give different answers. When it comes to your genes, there are two considerations that factor into melatonin supplementation. Certain genes like MAO A and B, COMT, PER 1 and 2, MTNR1 A and B, and CYP2D6 can all affect how you metabolize and handle melatonin.


If some of these genes have negative SNPs in them, you may need additional cofactors like P5P (vitamin B6) to help utilize the melatonin you’re taking and avoid most of the common side effects like anxiety, insomnia or drowsiness. Remember that tablet forms of supplements are usually poorer quality, and the bioavailability of sublingual is close to 100% compared to the 20-30% you’ll get from these other common sources. This factor can also affect your own dosage requirements and calculations, as 1mg of sublingual melatonin liquid would be equivalent to 3mg of a tablet form.


9. Continuing the discussion with genes, certain genes are responsible for detoxifying your body from prescription drugs. These are the cytochrome P450 genes, or the ones that start with “CYP”. These genes are also the ones that contribute to breaking down melatonin in your body. If you are taking certain drugs like blood thinners, anticonvulsants, diabetes medications or autoimmune medications, this may be something to speak with your functional medicine doctor about before trying melatonin. It can compete for detoxification with these drugs, and as a result, cause an unsafe concentration of them in your body if you take them together.


For a full list of drug interactions, you can visit:


https://www.drugs.com/drug-interactions/melatonin.html


In this listing you’ll find that there are 16 moderate interactions and 45 minor interactions.


Don’t let those numbers scare you, just do your homework. Echinacea is a plant that

stimulates the immune system and if you’re taking it with melatonin and have an autoimmune issue, this could be a problem. If you are on blood thinners or have serious

medical issues, it’s also something to consider and examine carefully. Melatonin is not as dangerous as the Internet makes it out to be, but it does need to be considered on a case-by-case basis.


10. There may be a relationship between melatonin and the thyroid gland if you supplement melatonin for an extended period of time. Although melatonin has a complicated dance with the thyroid and it comes with a few considerations, remember that it has an excellent safety profile in general. Firstly, recall that your thyroid is a powerful chemical factory synthesizing hormones and creating a ton of free radicals all the time. Imbalances in this process lead to autoimmune situations or dysfunction. Just like the thyroid has more selenium than any other organ as insurance, it also has specialized C-cells that can produce melatonin as a control on this process.(28,29)


Basically, melatonin acts as a “break” on the thyroid hormone conversion process by regulating the enzymes that do the job: iodothyronine-deiodinases. (Try saying that 10 times fast). Along with this safety control, melatonin also inhibits thyroid cell proliferation.(30,31,32,33) Interestingly, melatonin is also a powerful antioxidant, which the thyroid needs to buffer the conversion of hormones.


Altogether, these functions are very important for regulating and maintaining the health of your thyroid, and when you’re healthy, they are kept in Dynamic Balance by the complex dance between your pineal gland and thyroid.


Unfortunately, that sweet spot of Dynamic Balance isn’t always so easy to attain and in such a complex chain of parts something is bound to go wrong. This is where supplementation has many considerations. If you are hypothyroid, melatonin’s suppressive effects may slow down the thyroid even more because you are introducing an inhibiting factor into your system. Based on animal studies, using melatonin for hypothyroid would not be a good idea because it may slow down the process even more.


On the other hand, the limited human research that has been done has shown

that supplemental melatonin of 3mg actually improved perimenopausal and menopausal women’s hypothyroid symptoms,(34) and it has also been discussed as a therapeutic in autoimmune Hashimoto’s because of its antioxidant properties.(35)


There isn’t much research in this specific area, and the question is, do the antioxidant benefits of melatonin outperform the suppressive effects and help someone heal? Are there genetic and nutritional variants that predispose one group of people to profit from this therapy while others will get worse? If it does act as an antioxidant, but also suppresses the thyroid, how should you dose it and does taking iodine and other thyroid supporting nutrients cancel these effects out?


There are no concrete answers to these questions. But it may be worth a shot if your approach to healing your hypothyroid isn’t working with a complete nutrition program, a good diet, some glandulars, iodine, boron and managing your stress.


My personal opinion: it’s unlikely that you wouldn’t be improving with all of these efforts, but as a last-ditch effort it may be worth investigating, as long as you monitor your thyroid closely and start with a conservative amount like 1mg sublingually.


If you are hyperthyroid, taking melatonin may definitely not be a good idea. One more feature of melatonin we didn’t discuss is that it stimulates the production of TSH,(36,37) and in this case, it may aggravate your symptoms as per some animal studies using hyperthyroid rats.(38) If you are deficient in melatonin, it may be a useful therapy to help you combat the insomnia of hyperthyroidism, but in these cases it’s probably best to avoid it and treat the underlying issue of your thyroid and melatonin deficiency with the principles just discussed. In either situation, always monitor your thyroid frequently if you decide to take melatonin.





So, now that you’ve got most of the data on this interesting molecule, what do you do with it?


I’ve included it in here because the benefits are extremely promising for so many things, and the risk is relatively low for most people. How you integrate it personally will be a dance between all of the factors we’ve just discussed and your own life circumstances, but it is worth knowing about in full detail, nonetheless. For me, the sublingual melatonin listed above helped me regulate my circadian rhythm, but it also gave me diarrhea. After testing a few times through elimination protocols, it was clear that melatonin for me had an accelerating effect on the bowels even at extremely low doses,

like 10 or 20 drops (half a dropper).


Interestingly, I took some chelated zinc later in the evening along with melatonin and this effect was considerably diminished. Zinc is needed in the processing of melatonin, so this may be a valuable hack to help you use this powerful supplement. For me personally, I need about 30mg of zinc at night with half a dropper to avoid loose stools.


While I believe melatonin is relatively safe and offers massive amounts of benefits, it is one that you will have to consider with your own research and consulting your functional medicine doctor.


Unfortunately, even most alternative professionals aren’t aware of this research on melatonin, nor of its safety profile as referenced in these studies. Dr. Marc Harris, who formulated the above product, recommends taking a few droppers per night and even more so if you’re going in for some sort of radiation or similar procedure as a protective measure. If you aren’t on any serious medications and your stomach can handle it, this may be a great addition to your complete nutrition program as an overall support formula for the anti-aging and protective benefits.



References

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5405617/

2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334454/

3. https://life-enhancement.com/pages/wake-up-call-formelatonin

4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2635004/

5. https://pubmed.ncbi.nlm.nih.gov/10103215/

6. https://pubmed.ncbi.nlm.nih.gov/23348932/

7. https://www.hindawi.com/journals/omcl/2020/6841581/

8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3645767/

9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632922/

10. https://pubmed.ncbi.nlm.nih.gov/20152967/

11. https://pubmed.ncbi.nlm.nih.gov/25262626/

12. https://www.drugs.com/npp/melatonin.html

13. https://pubmed.ncbi.nlm.nih.gov/15582288/

14. https://pubmed.ncbi.nlm.nih.gov/3783419/

15. https://www.pnas.org/content/116/24/12019

16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1395802/

17. https://pubmed.ncbi.nlm.nih.gov/11068941/

18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1463812/

19. https://pubmed.ncbi.nlm.nih.gov/22311380/

20. https://pubmed.ncbi.nlm.nih.gov/21104186/

21. https://aasm.org/study-finds-that-melatonin-content-ofsupplements-

varies-widely/

22. https://pubmed.ncbi.nlm.nih.gov/9091795/

23. https://pubmed.ncbi.nlm.nih.gov/25197811/

24. https://pubmed.ncbi.nlm.nih.gov/23532506/

25. http://www.grupoaran.com/mrmUpdate/lecturaPDFfromXML.a

sp?IdArt=4621096&TO=RVN&Eng=1

26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3198018/

27. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3949259/

28. https://pubmed.ncbi.nlm.nih.gov/14647000/

29. https://pubmed.ncbi.nlm.nih.gov/26579570/

30. https://pubmed.ncbi.nlm.nih.gov/23295738/

31. https://pubmed.ncbi.nlm.nih.gov/10766971/

32. https://pubmed.ncbi.nlm.nih.gov/23723263/

33. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515663/

34. https://pubmed.ncbi.nlm.nih.gov/16399909/

35. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5096296/

36. https://pubmed.ncbi.nlm.nih.gov/11083464/

37. https://pubmed.ncbi.nlm.nih.gov/11083464/

38. https://www.nature.com/articles/s41598-019-42442-0

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