Melatonin

95% of your melatonin is produced in mitochondria during the day — not the pineal gland at night

Most people think of melatonin as a nighttime sleep hormone from the pineal gland, but 95% of the body's melatonin is actually produced as subcellular melatonin inside mitochondria during the day. This daytime melatonin acts as an on-site antioxidant, protecting against reactive oxygen species.

"what's called subcellular melatonin, subcellular sub below cell the cell, below the cell. So in the mitochondria, and this melatonin is produced in much more in quantity than pineal melatonin for nighttime, right?"

Dim lights an hour before bed to boost melatonin

Walker explains that modern humans are a dark-deprived society. Dimming half the lights in your house an hour before bed can dramatically increase sleepiness by stopping the suppression of the sleep hormone melatonin.

"We are a dark, deprived society in our modern era, and we need darkness at night to trigger the release of a sleep hormone called melatonin."

High-dose melatonin at 200mg for immune and mitochondria

Matt Blackburn takes 200mg melatonin nightly for mitochondrial enhancement and immune health, not just sleep architecture.

"I take 200 milligrams before I go to bed every night. That's not just to improve my sleep. I do it for mitochondrial enhancement and immune health."

87-year-old melatonin researcher took it for 29 years

Russell Ryder, world expert on melatonin, has taken it for 29 years and says it does not disrupt testosterone or other hormones.

"This is episode 273 of MitoLife Radio. I'm Matt Blackburn, your host, and today we have Russell Ryder on the show. I was really excited about this one. I consider him the world expert on melatonin. He's been taking it himself for 29 years. He's 87 years old."

Melatonin production drops to near zero by age 55

Melatonin production declines throughout life, reaching near zero by middle age. Supplementation becomes necessary for cellular protection.

"And like I say, I didn't start taking it for that reason, but that's when we discovered it was such a good antioxidant. So, you know, say you shouldn't supplement, you can't have adequate amounts. That's not true. You just don't produce as much as you age. And everything tells us that this is consequential in terms of deterioration of the cell. I mentioned the mitochondria being very important in the cell."

Melatonin at wrong circadian time disrupts your rhythm

Taking melatonin at the wrong time of day can disrupt your circadian rhythm. For jet lag, flying westerly reduces severity.

"If you take melatonin at the wrong circadian time, you may actually totally disrupt your circadian rhythm. It's not a soporific. It does not force you to sleep."

Melatonin dose should scale with body weight and age

Ryder has taken up to 300mg melatonin. Dose should scale with body weight since more cells means more mitochondria and more free radicals.

"Body weight. If you take a milligram per kilogram body weight, if you weigh 100 pounds versus 500 pounds, that's a very different dose. And more cells, more mitochondria, more free radicals. Obesity is an example. It's a very high free radical-related disease. And melatonin should..."

Start melatonin at 5mg and experiment upward

Five milligrams is a good minimum starting dose. Matt Blackburn personally takes 200mg nightly and recommends experimenting with higher doses.

"I think five milligrams is a good minimum, no matter what age. Obviously not medical advice, but I think that's a great place to start. And then you could increase from there if you want to experiment. I'm personally taking a lot of it. I'm taking the 50 milligram dose and I take four of those every night. So I'm actually taking 200 milligrams every night and I feel great with that amount."

That increases the serotonin and it helps coordinate the distribution of oxygen to the brain

That increases the serotonin and it helps coordinate the distribution of oxygen to the brain. But serotonin does other things, both in the brain and throughout the entire rest of the body, that help...

"That increases the serotonin and it helps coordinate the distribution of oxygen to the brain. But serotonin does other things, both in the brain and throughout the entire rest of the body, that help meet energy demands during relative hypoxia. And this is that it goes into the cell through the serotonin transporter. It then acts on the outside of the mitochondria and goes into the mitochondria, gets turned into melatonin,"

and just titrate up very slowly, just in the way you would want to taper off SSRIs very slowly

and just titrate up very slowly, just in the way you would want to taper off SSRIs very slowly. And you can experiment with what is the right dose for you anywhere between that microdose and 20 grams...

"Very clear evidence whether there is a risk of dependence long-term if you pound those high doses. We have no idea if there's a risk of dependence when you go a year or two out on 50 milligrams of melatonin a day. We can also use some strategies to increase mitochondrial turnover. And my fasting feeding reset, I think, is a great way to do that. Exercise is a great way to stimulate mitochondrial activity."

Melatonin starts the sleep race but doesn't run it: why it won't improve sleep quality

Walker explains melatonin is like a starting official -- it signals sleep timing but doesn't generate sleep itself. Short-term use shows no feedback loop damage, but nobody has studied chronic use over years. Supplemental doses of 3-10mg are supraphysiological, and in juvenile male rats, high melatonin caused testicular atrophy.

"And so you could think of melatonin like the starting official at 100 meter Olympic race, that melatonin brings all of the races to the line and begins the race, but it doesn't participate in the race itself. That's a whole different set of chemicals. So melatonin is potentially useful when you're traveling between different time zones. But once you're stable in a time zone, that evidence is very clear when we look across all of the studies and we gather them together in the same statistical bucket, and it's called a meta-analysis approach, what you find is that melatonin will only increase the speed with which you fall asleep by 3.9 minutes, which is really not that different to placebo. And it only increases your sleep efficiency by just 2.2%, which is really not fantastic as a sleep aid."

Melatonin inhibits androgenic development in rats: a caution for adolescent supplementation

High-dose melatonin in juvenile rats inhibited normal testicular development by blocking androgenic hormone promotion. The direct administration route makes human dose translation tricky, but Walker notes most supplements come in 5-10mg -- far above physiological levels.

"It was inhibiting that androgenic development. Most supplements, you're lucky if you can find three milligrams. Most will be five or ten milligrams."