Dr. Rhonda Patrick: Okay. Well, let's talk about a couple of supplements. I definitely want to get into jet lag a little bit later, but the top-of-mind supplement people think about when they think about sleep is melatonin.

Dr. Michael Grandner: Melatonin is a hormone. It's a very old molecule. It's in plants. It's in other things. It's not a sleep hormone except by association. Melatonin is the hormone of darkness. Melatonin is a nighttime signal. You produce it at night.

A great example of how it's not a sleep signal is that it has no sedating properties whatsoever. You give melatonin to a nocturnal animal, and it wakes them up because it's a nighttime signal. To the degree to which your body gets a nighttime signal and that makes you sleepy, yes, it can promote sleep. Melatonin can promote sleep in humans for that reason. It can help you fall asleep faster, stay asleep, and sleep more restfully because it's strengthening that nighttime signal. That's what it does.

It's also why it is almost universally useless for insomnia. If you have conditioned arousal, your body already knows it's nighttime and still can't sleep. Taking melatonin is almost never going to work to treat an insomnia condition. But if you don't have conditioned arousal and just need a little bit of a boost, melatonin probably works just fine.

You also produce it naturally. During the day, your levels are almost nonexistent. They start rising in the early evening, peak during the night, and then drop off right about the time you expect the sun to come up. Light suppresses it. Even if you're at peak levels during the night, turning on a bright bathroom light makes it plummet. Then you turn off the light. As long as the clock still thinks it's nighttime, it will regenerate again. It might take a delay, especially as you get older and the system becomes less flexible, but that happens naturally. Some people who take melatonin might be taking the wrong dose at the wrong time.

Dr. Rhonda Patrick: And then there's the other problem. A few studies have been published where almost all these melatonin supplements on the market have huge variations. Some of them have 100 times more melatonin than what's actually on the label.

Dr. Michael Grandner: That's the thing. A lot of them can be unreliable, especially from manufacturers that don't have good quality control. It is regulated by the FDA. There's just not enough money for enforcement, so there's not a lot of enforcement. But the larger companies are actually going to have pretty good quality control. If you look at the bigger companies with products on the shelf, they are almost always right on target for what they should be.

I say that because what's on the bottle is actually not what's supposed to be in the bottle. A lot of people don't know this, but the bigger companies with higher quality control are following the law. The law says that the amount on the bottle has to be within a certain percentage of the amount that's in the pill at the expiration date. That is the definition.

If you have a supplement sitting on a shelf with a three-year expiration date and you're working with a company that's trying to do everything well and correctly, your chemists and food scientists have to calculate exactly how much they have to put in that pill so that, as it degrades naturally over time, it hits the target two to three years out. That's actually the calculation they're making. With melatonin, that answer is usually 30 to 50 percent. When you buy melatonin off the shelf and it says five, it's probably closer to seven or eight. Then, two to three years later, it's five because they did their job. They followed the law and had high standards in their manufacturing.

You're probably taking a higher dose, and they can't tell you because of the way the law is written. If you tell people what's in there is different from what's on the bottle, you've changed the label and now you have to meet that. It's complicated. The law was written in a way that I think didn't foresee this problem. People need to know that if it's a good brand, it's actually going to be higher than what's on the bottle because they calculate the overage needed to degrade to the point that it hits the target. Isn't that crazy? People don't know this.

Dr. Rhonda Patrick: So less is more, for sure.

Dr. Michael Grandner: That's also why I say that if you're still having effects, your dose might be too high. Just cut it in half.

Dr. Rhonda Patrick: A question I get from people is whether taking a melatonin supplement will make you stop producing endogenous melatonin.

Dr. Michael Grandner: To my knowledge, there is no evidence that actually happens. It's a worry, but melatonin is so old that you're going to produce it. The way to stop producing natural melatonin would be aging. That reduces it. But to my knowledge, there are no data showing that continual use of supplementary melatonin changes or reduces your ability to produce it naturally at night.

Dr. Rhonda Patrick: With that said, are there any others? I've heard of a variety of supplements like magnesium, lavender, glycine, and L-theanine.

Dr. Michael Grandner: There is moderate evidence that some of these work. A lot of them have evidence that they are definitely not nothing. None of them have beaten placebo to treat insomnia. The closest was valerian, but when you pool the data, it still doesn't beat placebo for insomnia. It can be sedating and calming.

Magnesium also seems to promote sleep in a number of different ways. It doesn't usually treat insomnia, but it can help promote sleep. There are also great data on glycine showing that it can help people fall asleep and stay asleep a little bit better. A lot of these supplements can help you fall asleep and stay asleep a little bit better.

Some of them don't do anything to sleep itself, but they work in terms of calming. Calming isn't sleep-inducing for people who have insomnia. If you have conditioned arousal, you can be calm and still not sleep. But for people for whom a little bit of calming and relaxation is helpful, that's where things like L-theanine, chamomile, and some of those other calming things can be helpful, even if they don't technically do anything on the sleep side.

Other things that can help promote sleep include things that have anti-inflammatory and antioxidant properties. Your body is doing a lot of healing at night, and you can help give it those raw materials. There are certain supplements that seem to have some of those anti-inflammatory properties, and when you take them, you might sleep better. When people take ibuprofen, they can also sleep a little bit better because awakenings and arousals due to discomfort might be reduced and that might help them sleep through the night a little more.

Just because something is not nothing doesn't mean it is a cure-all. It's not black and white. A lot of these supplements can be helpful. I recommend them for all the things they do, but I also recommend them for none of the things they don't do. There's a gray area that people have a hard time wrapping their heads around.

Dr. Rhonda Patrick: Yeah. I'm definitely not talking about insomnia. Some people just like to have a little bit of help. Glycine is interesting. That's one I've been interested in. Have you seen any of the thermal-regulation work on that, like core body temperature?

Dr. Michael Grandner: I haven't seen the thermal-regulation work, but it seems unclear to me whether that's a cause or an effect.

Dr. Rhonda Patrick: Right.

Dr. Michael Grandner: But either way, does it matter if that's what you're taking it for?

Dr. Rhonda Patrick: It's more of a GABA inhibitory effect.

Dr. Michael Grandner: Yeah, it does seem to promote those inhibitory effects. A lot of people take workout supplements at night for recovery. If you're taking amino acids at night, branched-chain amino acids in general could be good for recovery, especially after training. If it has some extra glycine in it, all the better. But if it has a lot of glutamine in it, you don't want to use that because glutamine is activating. I've had athletes complain about insomnia, and it turned out they were taking nighttime supplements with a lot of glutamine. That's what was getting in their way.

It's not just about supplements at night that can be helpful. It's also about avoiding things that can get in the way, like B12. B vitamins are good to take because they can help with recovery. B12 helps boost the ability of light to suppress melatonin. You don't want to take that at night. You want to take it in the morning. B12 is great in the morning. It can help wake you up a little more for a number of reasons, including its ability to help light suppress melatonin. But you don't want it at night, when even a little bit of light can start getting in the way.

Dr. Rhonda Patrick: Fascinating. So take your multivitamin in the morning, not in the evening.

Dr. Michael Grandner: Yeah. I have this dream of having an AM vitamin and a PM vitamin. Some things might be better at night. If sleep is all about recovery and repair, put those raw materials in play at the time you want to use them, if they're going to degrade. Or you could just take them in the morning if they're going to hang out all day anyway.