Melatonin: Part 1
New Melatonin Research
I have written extensively on the subject of melatonin in Nutristart blogs and newsletters as well as devoting an entire chapter to the subject in Health Secrets for the 21st Century: Volume 2. Therein, I have discussed how melatonin is essential to supplement with, due to our constant exposure to electromagnetic frequencies, blue light, and nightime lighting. All of which are proven to reduce natural levels of melatonin.
In this previous material, I have examined how melatonin does much more than just help with our sleep cycles. It serves as a powerful antioxidant, a longevity agent, and supports heart and liver health, regulates body fat, and protects against cancer and neurological disorders (Alzheimer’s, ALS, Parkinson’s, etc). I also have one newsletter on Melatonin and Macular Degeneration.
Another newsletter, covering material not in the book or previous newsletters, is titled New Discoveries About Melatonin, and examines how melatonin is used to prevent hair loss, support skin health, and to fight sepsis infections (due to bacterial, fungal, or viral conditions) and pneumonia.
But, here I am addressing the subject yet again. And with good reason, as you will soon see. So join me on a voyage of discovery as we examine some new concepts about melatonin that, quite frankly, initially struck me as insane.
First, let’s look at the study that got me looking at melatonin again.
Melatonin and Children
Sales of melatonin have skyrocketed in the last few years and many of the products are chewable, sublingual, or in gummies, all of course being flavored. Which has attracted the interest of children who think they are candy. (Yet another reason for me to hate “gummies”, a subject addressed in Invasion of the Gummies.)
“We previously identified a 420% increase in ED (emergency dept.) visits for melatonin ingestions by children aged 5 or younger from 2009-2012 to 2017-2020,” said a spokesperson for the CDC. “In this study, we analyzed data from 2019-2022 and found that there were approximately 11,000 ED visits for unsupervised melatonin ingestions by young children.”
Perhaps it is time that melatonin manufacturers be obliged to put their product in child-proof containers, and parents be reminded to keep their melatonin products in the medicine cabinet, safely out of reach of children.
Now, on the surface of it, this may not appear too bad as “nearly 94% of the ED visits for melatonin ingestions by infants and young children in this study did not result in hospitalization.” “Similarly, a recent study of poison center calls found that the majority (98%) of pediatric melatonin exposures resulted in minimal or no effects.”
Side effects children might experience include agitation, excessive sleepiness, nausea, and nightmares. Some adults also experience excessive dreaming and/or nightmares from melatonin, and they simply have to find another approach. Like DreamStart, for example. This new product from NutriStart, has deliberately not included melatonin, both because some people can not take it, and also because the amount we should take varies from individual to individual.
“Though rare, kids who ingest large quantities of melatonin also may experience a drop in blood pressure, breathing difficulties, and repeated vomiting. One study found that a small number of kids who took melatonin unsupervised required ventilation at the hospital.” (Source)
This problematic situation has occurred because melatonin supplements are not approved by either the FDA or Health Canada for use by children, in part because there is limited research on the long-term usage and effects of melatonin in children.
However, I now see more and more medical practitioners prescribing melatonin for children with sleeping problems. The real problem is that it appears that none of these health professionals have actually done any research into melatonin.
I bring this up because there is one group that should not receive melatonin.
Who Should Not Take Melatonin? (From Health Secrets Volume 2)
Clearly Melatonin deficiency is a 21st century issue, and something all adults should consider supplementing with, unless they live a country life with minimal EMF exposure. I say adults because the one group that should not take Melatonin is adolescents.
As mentioned in the beginning of this chapter, one of the main functions of melatonin is to regulate and run the endocrine system. The endocrine system comprises all the glands that produce hormones from infancy, and throughout our life. During the development of the sex organs the body withholds melatonin, allowing other specific hormones to do their work moving the body into puberty. Doctors seem to be unaware of this, and often suggest that melatonin is suitable for children, and while small amounts may be safe for a while, by the time the child is approaching adolescence, it can be dangerous, and may impede sexual development.
A better approach for adolescents and children is to give them agents that increase serotonin levels, such as L-Theanine, 5HTP (5-hydroxytryptophan) or L-Tryptophan. Serotonin calms the nervous system allowing one to fall asleep and then some of it converts naturally into melatonin, raising it to a level that is no higher than their developing bodies would need. Also ensure that they get at least an hour of natural daylight outside (ideally more), in order to allow the body to regulate its own melatonin production. (These substances are in DreamStart and a low dose of one capsule can be suitable for children not on any mood altering medications.)
One other solution for children and adolescents is to use blue-ray blocking glasses. The glasses which block blue rays have been successfully used on children with no adverse effects.
Taking High Doses of Melatonin
Now let’s get to the juicy part. After I decided to do a bit on the information regarding melatonin and children, mostly to spread the word about not giving it to adolescents, a friend (thanks Dave) sent me this Youtube video: Anti-aging Channel: Why I Take 1000mg of Melatonin Every Day!
My first response was probably the same as yours: that sounds insane. After all, the daily recommended dose for someone who is 70 years old is only 3-5 mg, based on our biological requirements.
Now, I was aware that during Covid a study was done showing that 20 mg of melatonin three times daily was helpful in treating that condition. And I knew that higher doses were also sometimes used to accompany chemotherapy, for those with cancer. But I had never heard of value in taking such massive amounts of melatonin. So, I watched the video and was intrigued enough to look into the idea in more detail. Fortunately the author of this video (who is not a health professional) included a number of links to studies that supported his thesis.
Following is my analysis of those links that he included, during which I will try to determine if this is a valid theory or just plain nuts.
Neurological Disorders
The first study I examined confirms the powerful effects of Melatonin as an Anti-Aging Therapy for Age-Related Cardiovascular and Neurodegenerative Diseases. However, it does not suggest super high doses are required to attain these benefits, except when we look at animal studies and extrapolate them to human doses. And even then, the highest dose recommended is 100 mg.
“Notably, sleep behavior disorder in patients with Parkinson’s Disease may precede the development of motor symptoms and is a marker of a worse prognosis for this pathology. In this regard, it has been demonstrated that daily bedtime administration of 3–12 mg of melatonin is effective in the treatment of sleep behavior disorders and may stop or slow neurodegeneration associated with these diseases. However, if doses of melatonin that have been effective in animal models to reduce not only sleep disorders but also the symptomatology of PD are projected to humans, these would be in the range of 40–100 mg/day, a dose that is consistent with studies in which melatonin was used to inhibit COVID-19 infections.”
Further to the subject of neurodegeneration, one of the studies included confirms how electromagnetic fields reduce our melatonin levels and how it can be used to prevent and treat dementia. In this study, Light, Water, and Melatonin: The Synergistic Regulation of Phase Separation in Dementia, we are looking at rodent experiments, which do not always translate well to humans (thus the use of Thalidomide with pregnant women, which had no ill effect on rats). Therefore, we should not rely too heavily on the massive doses concluded to be the Human Equivalent Dose (HED).
Before we get into the doses a few words about this study (which is long and technically complicated). The mice in this study were tested for the prevention of amyloid plaque development in the brain, a symptom of both dementia and Alzheimer’s disease.
Massive Doses of Melatonin
Mice receiving a low dose of melatonin (2.13 mg/kg) at age 14 months (equal to 35 human years) showed no benefit in reduction of plaque formation or oxidative stress levels.
Mice receiving 66.66 mg/kg daily starting at age 4 months (equal to 21 human yrs) showed a significant reduction in amyloid plaque levels in brain tissues, but the greatest benefit was found in those mice given 266.66 mg/kg daily starting at age 4 months (21 human yrs), when they were “sacrificed” at 15 months (79, in human yrs).
“When Tg2576 mice from two separate experiments were administered ~266.66 mg/kg melatonin in drinking water daily starting at age 4 months until termination at 15.5 months, survival was significantly increased in treated compared to untreated mice.”
“The HED (Human Equivalent Dose) obtained before the bioavailability adjustment is 2499 mg. Without solubility enhancement, the adjusted bioavailability HED dose is 4831 mg. After correcting for a 50% enhancement in bioavailability, the final HED is a staggering dose of 10,621 mg.”
A 1,000 mg dose daily doesn’t sound so insane now, does it?
Let’s unpack this a bit. The HED dose keeps going up because the mice were fed melatonin in a highly bioavailable solution, whereas in the manner in which we take melatonin supplements they break down quickly in the body. Thus all high dose recommendations are for divided doses throughout the day.
To wit: “Accordingly, total HED should also be administered in divided doses of 885 mg × 12. This hypothetical HED now resembles the HED used by Martin et al. to elevate ATP production via complex I and COX activities in the brain and liver mitochondria of rats.”
In conclusion, our researchers confidently state that “the estimated daily total HED of 10,621 mg obtained from Tg2576 mice taking 266.6 mg/kg in drinking water becomes quite reasonable and theoretically justifiable”.
Toxicity of Melatonin
LD50 is the scientific term used to determine how toxic a substance is. It refers to the point at which 50% of the mice die (Lethal Dose to 50%) after receiving a given amount of the compound being tested.
“Even though the toxicity of melatonin as defined by LD50 has not been determined in human or rodents, where early studies failed to produce death in mice at 800 mg/kg, and acute oral toxicity that result in LD50 in rats is reported at concentrations higher than 3200 mg/kg (in one single dose).”
So, considering our mice in the study we are referring to were given 266.6 mg/kg (equavalent to 10,621 mg for a human), we at least know that we have no worries about overdosing on melatonin.
In Part 2, I will continue to follow up on the links embedded in the video that launched this investigation, and we will examine some other high-dose melatonin studies done with humans, to back up the rodent studies.
(Author: All newsletters and blogs are written by Ken Peters who has worked as a nutritional consultant for the last 30 years, and as product designer for NutriStart for the last 25 years. He has also authored two books – Health Secrets Vol. 1&2. He may be reached at: kenpetersconsulting@gmail.com)