#165 - Is Melatonin Safe? Yes - It's Life Saving
Melatonin does not have an LD50.
When 50% of rodents die after being injected with a drug, then this is considered the lethal dose (LD) - or LD50 for short.
In 1960, Lerner and Case injected 800mg per kg of melatonin into rodents. As quoted in Russell Reiter’s book Melatonin - “Even this massive dose “failed to produce death” in the animals” (page 20). For context, Circadin is a prescription medication available in Australia and Europe which has 2mg of melatonin.
Despite humans knowing melatonin has no LD50 for the past 65 years, there is this current belief that you can …
Overdose on Melatonin
In 2022, a study associated with the Center for Disease Control (CDC) reported that between 2012 to 2021 there was a 530% increase in pediatric ingestions of melatonin - as per it’s headline.
This led to distorted headlines in the traditional media …
BUT - if you search for the words ‘poison’ in the original study you will get 22 results - virtually all of them referring to ‘poison control centers’.
There’s not one mention of ‘overdose’.
But what is a little troubling to me is that when you search for ‘toxic’ - this statement gets picked up:
“… health care providers should warn parents about potential toxic consequences of melatonin exposure.”
This above statement was made despite the authors not finding evidence of toxicity in their data. Instead, a reference was made to the fact that some formulations of melatonin contain serotonin, which may cause toxicity in children.
When this 2022 study was released - I was highly sceptical of the toxicity of melatonin. I searched the original databases and found only 2 cases over the 12 years of data where the coroner attributed the primary reason of the child’s death was due to melatonin.
In contrast, this 12-year dataset shows vast numbers of children died due to ingesting batteries or cosmetics. But this didn’t appear in the media. One would think if we wanted to prevent fatal ingestions in children that we would inform parents via the media, right?
Now, I’m not a coroner, and I did not see the case files, nor the 2 children who are reported as dying from melatonin ingestion. But nonetheless …
I’m Still Sceptical
I first started using melatonin for my sleep clients in 2012, primarily to help teens with their circadian rhythm disorders.
I then learned that melatonin had soporific effects - that is, producing a sleepy effect - for school-aged children. So I began recommending liquid melatonin for certain cases.
Then I had a case where I recommended melatonin for a pre-schooler after the very first session. The parents were incredibly sleep-deprived due to being chronically woken by their 4-year old daughter. As a consequence, the dad had a fall at work. For context, he worked on the roofs of commercial houses. This family couldn’t wait for behavioural therapy to kick in. The following week, the child was sleeping straight away and through the night.
Finally, there was a …
Case of a 13-month old baby
… who I saw in 2017. The family had already tried extinction (cry it out) and it didn’t work. We tried bedtime fading and the infant was falling asleep well, but still waking through the night. We attempted graduated extinction but the infant’s awakenings didn’t abate.
So I turned to my clinical student who I was training at the time - Dr Gorica Micic - and gave her a homework task for the week …
“Dig into the scientific literature, and find out what the youngest age has been for a case where melatonin was used.”
The following week, Gorica’s answer was …
0 Days
In fact, zero days is conservative. Technically it should’ve been negative days.
Gorica found a study of premature infants with sepsis (ie, blood poisoning). There were two groups in this study - one who received the standard medical care - the other received the same care + melatonin.
Unfortunately, 3 out of 10 babies died from sepsis in the group who received only the standard medical treatment. In the group who received melatonin + standard medical care - zero babies died.
These premature babies were given 20mg of melatonin over the course of the first 24 hours of their life!
Thus, whenever someone mentions the possible harms of melatonin - my mind always returns to this study.
So ask yourself - if melatonin is so harmful, how come doses 10x higher than the amount prescribed for adults were given to the most vulnerable little humans and it didn’t kill any of them. Indeed, we should be flipping our thinking and realising that …
Melatonin Is Life-Saving
It wasn’t until 2022 that I started digging into why melatonin was given to premature infants with sepsis. This led to an understanding that melatonin isn’t just for helping kids sleep and changing circadian timing.
Melatonin:
also possessed anti-inflammatory properties
was the world’s best anti-oxidant
had both apoptopic (killing cancer cells) and anti-apoptotic (protecting healthy cells) properties.
I was diagnosed in 2021 with pre-cancerous cells in my upper lip - the sort of cells that can turn into a squamous cell carcinoma.
But before I turned to melatonin for my own potential cancer, our family received the news in early 2022 that our beloved 10-year pug - Rossi - had an oral melanoma.
After removal of the oral melanoma - and removal of a lymph node - and a course of immunotherapy - and removal of a master cell tumor that almost took his leg - and then a course of chemotherapy - our wonderful canine oncologist - Dr Anne Peaston - recommended a CT scan of Rossi’s chest.
Sure enough, Anne’s instincts were correct. Rossi had multiple lung cancers. Oral melanomas are likely to travel to lymph nodes - but after that - they can travel to the lungs.
We Were Devasted
Surgery was out of the question, so we believed this was the end. But my stubborness and belief in science saw me spend hours in front of a blue-enriched LED screen at night, scouring the scientific literature.
The following week we were going to throw the only intervention at these lung cancers, which was a final course of immunotherapy.
But what I learned from my reading of the literature was that melatonin had been provided to dogs with cancers alongside immunotherapy - and the survival rates were better when melatonin was added. I ran this idea past Dr Anne Peaston - who herself is an active researcher - and she said …
“Melatonin has a good safety profile. I don’t see why not.”
So in October 2022, Rossi began having 1 mg of melatonin, 3 times across the day. In February 2023 Rossi had a follow-up CT scan …
The News?
All of the lung cancers had shrunk - by at least 50%. Some had disappeared.
Whilst this was great news, there was also some more devasting news. When Rossi was under for his CT scan, the surgeons noticed a lump in his mouth. They took a biopsy - meaning they removed about one-third of the lump for analysis. Sure enough, it was another oral melanoma.
Upon hearing this news, I upped Rossi’s melatonin. We had both 1 mg and 3 mg capsules of melatonin, so I switched to 3mg capsules 3 times a day. A total of 9mg for a 9kg pug (ie, 1mg/kg). In contrast, I’m around 75 kg and thus by taking 2 mg of melatonin, this would equate to 0.03mg/kg.
So Rossi was on a lot of melatonin.
The following week he went into surgery and the lump was removed. Indeed, the surgeon found it hard to find the lump.
But the following week, we got a ‘good news’ phone call. Looking back, I’d now call it …
The Miracle Phone Call
Here’s how that phone call went …
Dr Olaf: “Do you want to hear some good news"?
My wife and I said “We don’t get good news.”
Dr Olaf: “When it comes to the margins, we got all the cancer. There was no cancer in it.”
My wife and I breathed a sigh of relief. Imagine cancer has tentacles that reach out of it’s lump. These tentacles go into a region around the lump called ‘The Margins’. If there’s no cancer in the margins - you managed to get all the cancer removed …
Dr Olaf: “Do you want to hear some more good news?”
My wife and I frowned at each other: “Yeaaahhh”
Dr Olaf: “Do you know how there was cancer from the biopsy two weeks ago? Well, there was no cancer at all in the lump we removed.”
Mrs and Mr MG: … stunned silence. Both turn to look at Rossi. Rossi looks at his mum, tilts his head, wondering if it’s dinner time …
Dr Olaf: “We’ve never seen anything like this before.”
Rossi’s wonderful vets attributed this disappearance of cancer to - somehow - the course of immunotherapy he finished recently for his lung cancers.
Immunotherapy was the ‘standard of care’ (SOC) for all dogs at this clinic.
But I bet there wasn’t dog owners who were also giving their beloved pet 1mg per kg of melatonin each day.
Was This A Miracle, Or Was This Science?
I don’t know. But what I do know is that science takes years to produce a single study.
Cancer is faster.
So I decided to speak publicly about what I believed people should know - just in case it may prove useful, even life-saving.
This was unusually non-scientific of me - and I certainly received my criticisms …
I had to ask myself whether I was experimenting on Rossi?
Well - yes. But before I begun, I spoke to our vet who assured me of melatonin’s safety.
Although Rossi was diagnosed with lung cancer in October 2022, he lived a further 2 fulfilling years. I’d say that was an experiment worth embarking on.
“Uncle Vic …”
… has a mass in his brain.” said my dad on the phone on Friday September 27 2024 - a couple of hours before I was to give 2 talks at the European Sleep Research Society conference in Spain.
“@$#%” I sighed …
The following week I was on the phone with my cousin. I’d done some reading of the literature - and to my surprise - I found a table in a meta-analysis that surprised me.
Regardless of the type of cancer, study after study had shown that 20mg of melatonin in the evening - alongside chemotherapy and/or radiotherapy - reduced the side effects from these nasty treatments, and also improved the survival rates of people 1-year later.
It was discovered that Uncle Vic had a glioblastoma, which 99% of it was removed. He’s been given the standard medical treatment of combined radiotherapy and chemotherapy. To our relief, his oncologists did not disagree with him taking melatonin - and so he did - and continues to.
To our surprise, he sailed through his combined radiotherapy and chemo. And he continues to take melatonin every night, albeit the dose is now around 300mg.
As for me, I got up to … 1500-2000mg
I titrated myself up to this amount over time. I certainly noticed some vivid dreams at the start, and the need to nap - but these drifted away after getting above the 150mg mark.
But why take this much?
On Doris Loh’s website, she provides recommended doses for different conditions - based on one’s body weight. There you will see that recommendations exceed 1,000 mg.
Whilst Russell Reiter is the world expert when it comes to melatonin for non-sleep and circadian issues - Doris Loh is the next generation who will increase our understanding of this - safe - and amazing molecule.
Is 478% More Melatonin Too Much?
To round up this mindset-flip about melatonin, you may have heard of a study that compared the amount of melatonin on the label vs its content.
A key soundbyte from this study was that there was 478% more melatonin in one batch that was tested.
But won’t you don’t hear is this …
The label on that batch said 1.5mg of melatonin - but there was 8.67 grams in the batch - 7.17 grams more.
50 different melatonin formulations were tested. The average deviation from what was on the label was 9.2% more.
The average deviation of the amount of melatonin was 0.28 mg more.
An excellent sleep and circadian scientist - Dr Helen Burgess - informed me that she used to do some consulting for Naturol who said they need to put more contents of a supplement in a formulation when it ships, as it’s concentration declines over time.
I’ll detail in a future blog where I get my melatonin from - as I do not wish for that crucial information to get lost. It deserves its own blog.
Conclusions?
Melatonin is indeed safe.
And yet, you will hear people caution against it. In response, remind yourself of the studies done with premature infants. Remember melatonin’s toxicity couldn’t be achieved.
But then let your mind turn to melatonin’s life-saving properties.
And if one day you become curious like I did - start reading research reviews about what melatonin can do for you.
- Prof MG
Disclaimer: The headline image was created by Midjourney and is supposed to represent a melatonin molecule sitting on a cloud - however, this is not what a melatonin molecule looks like - this is …