Rhonda: Is there a difference between the melatonin produced in the pineal gland versus melatonin being made in your gut, which is something that is even produced from eating food that contains the amino acid tryptophan, which gets converted into serotonin in the gut and ultimately into melatonin, what are your thoughts on supplementing with melatonin maybe regularly, or, even is there an age-dependent factor in there?

Satchin: So that's a very tricky question because, melatonin is not regulated in the U.S., but in other countries it is regulated. And the reason why it's not regulated in the us is you can feed a lot of melatonin to a mouse and the mouse will never die. In that sense when you give various drugs or chemicals to an animal, then there is LD 50, or lethal dose, 50 at which, some animals would die.

So based on that, we think that melatonin is safe. And of course there is not much adverse effect of melatonin shown in any major experiments. But having said that, we don't know what are the long-term adaptation of our body to melatonin, whether you start with a milligram of melatonin and your body will slowly become resistant to that milligram and we'll need more and more, but at the same time, People think that melatonin is a good alternative to sleeping pill, which can have more adverse side effect.

And maybe that's one reason why we have seen almost 40% to 60% rise in melatonin use in the last couple of years alone. So coming back to your question about melatonin, the natural melatonin versus, supplementing melatonin with a pill, it's really hard to make those connections because as you know, melatonin rises in the middle of our sleep and there's a kinetic to it it's not easy to detect melatonin.

It's not like a continuous glucose monitor that you can stick to your arm and it will collect melatonin data because melatonin is present in such a low concentration that it needs more fancy method to detect it. So that means we have to sample blood in every 30 minutes or an hour when we're sleeping, And then use that inexpensive method to measure melatonin.

And that might be one reason why not much studies have been done to differentiate between, exogenous application or taking a melatonin pill versus pineal melatonin. The second thing is when we take a melatonin pill, nearly 70 to 90% of it is broken down in the liver and kidney within an hour. So whatever we take only a small fraction of it stays in our bloodstream during our sleep.

So as a result, melatonin in experimental and clinical studies has been shown to improve sleep latency. So that means it can help people to fall asleep, but it might not be that good in sustaining sleep throughout the night. At least that's what the clinical studies have. shown. But in some people they feel that melatonin helps them to stay asleep throughout the night and, unlike this, pill, our endogenous melatonin actually rises roughly a couple of hours before our habitual sleep time.

it slowly rises and then it reaches almost its peak up to one hour into our sleep and maintains that peak throughout the night. And after we wake up around that time, it begins to decline and it goes down to its lowest level, maybe two hours after we wake up. Whereas if you take a pill, it will just spike for 15 minutes to half an hour just after you took the pill and then it will come down and slowly continue to go down throughout the night.

And by the morning when you get up there might be very little, depending on how much melatonin you took these days. A lot of people are...and actually, there is a shift in the dosing of melatonin, for example, almost 20 years ago when I was a student, I could find 1-milligram melatonin pill, and it was very difficult to find a 3-milligram pill.

And now it's almost impossible to find a 1-milligram pill. in any drugstore, and the common is around 3 to 5-milligram pill. So that means when people are taking this 5-mg, it's possible that they have a very huge spike. And then when it comes down, it actually stays at a pretty high level throughout the night.

And maybe even two to three hours after they wake up, they still have significant amount of melatonin in their system. So unfortunately these are some of the studies that need to be done and have not been systematically done.