More on Melatonin

Welcome to the Nutrition Facts podcast.  I’m your host, Dr. Michael Greger.  I am thrilled that you have decided to join me today.  Because the more I learn about the latest in nutrition research–the more convinced I am that this information can make a real difference in all our lives.  And I like nothing better–than sharing it with you.

On today’s show – I could induce sleepiness – by speaking in a monotone.  OR, I could tell you about the fascinating sleep inducing properties of melatonin.  The body normally produces melatonin every evening to let us know when to sleep and wake.  But sometimes – we need a little help regulating those important functions. 

In our first story, over-the-counter melatonin supplements may not contain what they say they do, and the contaminants could be dangerous.

If you’re crossing three or more time zones, and you plan on staying at your destination long enough to make it worthwhile, you can adjust your body clock to the new time with behavioral methods or pharmacological methods. The behavioral method is light exposure and light avoidance at specific times of the day, based on which direction you’re going and how many time zones you cross. The pharmacological intervention is melatonin, the so-called ‘‘darkness hormone.” It’s secreted by a little gland in the center of your head as soon as it gets dark, and shuts off when the sun comes up in the morning, thereby helping to set your circadian rhythm. There’s been a lot of research done on treating jet lag, but most of it has come from lab rats instead of people. But, most of the handful of human trials that have been done have found taking melatonin “close to the target bedtime at the destination” to try to sync your body to the new time can effectively decrease jet lag symptoms after long flights. Now, unlike “most or [really] all other drugs, the timing of the dose is critical and determines the effect: given at the wrong time,” it can make your jet lag even worse—for example, if you were to take “melatonin at bedtime when traveling west.”

Dose-wise, taking between 0.5 and 5 mg seems to be “similarly effective” in terms of helping with jet lag symptoms. But the higher dose does seem to have more of a kind of a sleeping-pill-type effect, which appears to plateau at about 5 mg, but those are massive doses. Even just taking a 3 mg dose produces levels in the bloodstream 50 times higher than normal nightly levels.

Yeah, it works, but we don’t know how safe that is. After all, melatonin in the early days used to be known as the “antigonadal hormone,” with human equivalent doses of just a milligram or two reducing the size of sex organs and impairing fertility in laboratory animals. Now obviously, rats aren’t people, but “[c]onsidering the pronounced effects of…melatonin on reproductive physiology in [other] mammals, to assume that [it] would not have some sexual effects in humans would almost seem naive.” In fact, they speculate maybe melatonin could one day play a role as some sort of “a contraceptive agent.”

Wouldn’t we know about these effects, though? Well, how? Melatonin is available over the counter as a dietary supplement. So, there’s no post-marketing surveillance like there is with prescription drugs. And, then, there’s the purity problem. Supplements are so poorly regulated that you never really know what’s actually in them. “For these reasons, melatonin [supplements] cannot be recommended…”

Is the purity issue just theoretical, though? You don’t know, until you put it to the test. And, indeed, due to the “poor quality control of over-the-counter melatonin, what they say is often not what you get.” Melatonin is not only one of the most popular supplements among adults, but children too, which makes it even more “egregious” that actual melatonin content varied up to nearly 500% compared to what it actually said on the label, based on an analysis of 31 different brands, and most had just a fraction of what they said. And, “the most variable sample was a chewable tablet,” which is what kids might take. It said it had 1.5 mg, but actually had 9, which could result in like a hundred times higher than natural levels. “In short, there was no guarantee of the strength or purity of [over-the-counter] melatonin,” leading these researchers to suggest it should be regulated as a drug so that, by law, at least it would have what it says on the bottle. Okay, but that’s strength.

What about purity? Four of six melatonin products from health food stores—two-thirds—”contained [unidentified] impurities.” With no exclusive patent, “[n]o pharmaceutical company wants to pay for the [necessary] toxicological studies”—the stuff is just sold so dirt cheap. They recommend buying it from some “large reputable pharmacy chain” and [just] hope for the best.”

But, this study suggests it’s not worth the risk. “Contaminants present in” tryptophan supplements were reported to be responsible for a 1980s outbreak of a disease that affected more than a thousand people, and resulted in dozens of deaths. “Given the structural similarities of [tryptophan] and melatonin,” maybe when you’re trying to synthesize melatonin, those same toxic contaminants could be created, suggesting melatonin supplements may just be “another accident [another] [epidemic] waiting to happen.”

As it turns out, there may be a way to get the benefits of over-the-counter melatonin supplements without the risk.  Here’s the story.

Unfortunately, there is “no guarantee of the strength or purity” of over-the-counter melatonin supplements, which have been found to contain impurities that “raise serious [safety] questions.”

“For these reasons, melatonin [supplements] cannot be recommended.” Too bad there’s no way you can get the benefits without the risks—unless melatonin was somehow found naturally in certain foods you could eat. “Melatonin was first discovered in plants…in 1995,” and has since been found throughout the plant kingdom. But, enough that eating them actually affects your levels? Yes. You randomize people to eat more or less vegetables, and you can see the effect.

Hard to get people to eat vegetables though. How about beer? The “[m]elatonin present in beer contributes to [an] increase [in] the levels of melatonin [in the human bloodstream].” Though, alcohol consumption may actually mess with your own “endogenous melatonin secretion,” so beer probably isn’t the best choice.

Eat two bananas, or drink the juice of about two pounds of oranges or pineapple, and you can get significant bumps in melatonin concentrations in your blood. And, the melatonin levels found in those fruits are pretty “modest compared to” some other foods.

We make melatonin, so it should come as no surprise that other animals do, too. The most melatonin-rich meat tested was salmon, but because there’s only billionths of a gram per serving, you’d have to sit down and eat about 200 pounds to get the effect.

Okay. So, forget meat. What about whole grains? The highest recorded was a strain of corn so rich in melatonin you’d only have to eat 16 ears of corn. All right, scratch that. What about other vegetables? Plain white button mushrooms top the list. Only two pounds. A hundred times more melatonin than meat. But still, they’re so light; two pounds is like eating 10 cups of mushrooms. That’s a lot in one sitting. Thankfully, cranberries to the rescue; the most melatonin-rich fruit. Just a single ounce, and it’s like you just took a melatonin supplement, with only good side effects—other than, of course, the extreme sourness.  That’s about a third of a cup of cranberries. They’re pretty sturdy. So, you could travel without them getting smooshed. But what do you do with them once you get there? Easy to blend into a smoothie, but what if you’re stuck in a hotel? Can you eat dried cranberries, like, what are they called—Craisins?

A study of various tart cherry products suggests that the drying process wipes out the melatonin. So, no melatonin in dried cherries, and presumably dried cranberries either—nor in juice. The level of melatonin in cherry juice concentrate was almost nondetectable. So, drinking cranberry juice would also presumably be a wash, which brings us to nuts.

Pistachios are not just the most melatonin-rich nut, they are simply off-the-charts as the most melatonin-rich food ever recorded. To get a physiological dose of melatonin, all you have to eat is two. Two what? No.  Just two pistachios. More than 200 micrograms of melatonin per gram, 0.2 milligrams per gram. And, you can get the normal daily spike your brain gives you taking just 0.3 micrograms: so, just two nuts. So, taking a whole handful of pistachio nuts is like taking one of those high-dose melatonin supplements. So, the best food for jet lag appears to be appropriately timed pistachios.

In our final story, we’ll use a cheat sheet to figure out exactly when and how to treat jet lag using light exposure and light avoidance at specific times of the day, based on which direction you’re flying and how many time zones you cross.

“Jet lag is a blessing to circadian biologists, because the disruption of mental and physical well-being immediately highlights the importance of” their work, the study of “our internal ‘body clock.’” Much of the general malaise we may experience on long journeys may just be so-called ‘‘travel fatigue,’’ which can occur regardless of the time zone, leaving people feeling disorientated, generally weary, headachy. Dehydration has been blamed. The air circulated in the cabins of commercial airlines is pretty dry. Yeah, it can make your throat, skin, and eyes feel dry. But, if you do the math, the “maximum loss of fluid” through like breath and sweat wouldn’t be more than like an extra half cup; so, it’s not like you’re in Death Valley or something. And, that “calculation assumes that the passenger would be nude,” and I’m sure they’d charge extra for that.

Of course, giving people salty pretzels doesn’t help. The vegetarian option tends to be healthier, if they’re serving meals, but you have to specify that when you book. “BYOF — Bring Your Own Fruit — is a good rule to fly by.” Or, unsalted nuts as a snack.

The cabin air isn’t just dry, but low in oxygen pressure—about what you’d get 10,000 feet above sea level, like twice as high as Denver. And that alone can make you feel not-so-great. Then, when you land, if you’ve crossed enough time zones, you can suffer from jet lag, which is the temporary disconnect between the new time at your destination, and that of your own internal body clock, which is still on home time. This is abnormal, since our internal clock is normally synced to the outside world. But, the symptoms of jet lag go away as our body becomes hip to the new time.

This usually takes, in days, “two-thirds the number of time zones crossed eastwards, compared with half the number of zones crossed westwards.” So, London is like six time zones east away from Chicago; so, flying there, it may take four days before you’re back to normal, whereas Londoners flying to Chicago should get over their jet lag in only three days. The reason it’s easier to go west, where the day is longer, than east is because our internal clock is naturally set for longer than 24 hours and has to be reset every day. That’s why they call the daily rhythm “circadian,” meaning “about a day.”

In fact, you can see this in Major League Baseball performance. Researchers churned through 40,000 games, mining 20 seasons, and found “surprisingly specific results of circadian misalignment”—jet lag, and, indeed, the problems arose most after eastward travel, with very limited effects after westward travel, consistent with the greater-than-24-hour cycle length of the human circadian clock. Okay, but how do you treat it?

First, you need to figure out if it needs treating at all. If you’re just traveling one or two time zones, you don’t have to worry about it. If you’re crossing three or more time zones, like traveling coast to coast, it then depends on how long you plan on staying. If it’s just a few days, it’s probably not worth treating it, since then you’ll have to switch back as soon as you get home. If you have control over your schedule, it’s better to “time appointments in the new time zone to coincide with daytime” back home. So, it’s pretty much common sense. If you travel east, your body will still think it should be sleeping in the morning. So, you should push stuff later, and vice versa.

But, if you are going to be gone for a while, you can adjust your body clock using behavioral methods and/or drugs, supplements, or foods. “There is only one sure fire way of avoiding jet lag altogether and that is to adapt to the new time zone before [your trip].” However, changing your home sleep schedule more than a few hours can be counterproductive by interfering with your pre-trip sleep, and you don’t want to be going into a long trip already sleep-deprived.

Before your trip, you want to maximize your sleep. In flight, the recommendation is to immediately “adjust…to [the] destination meal schedule”—easier said than done, and then, once you land, you want to try to “maintain [the] destination sleep schedule.” Try not to nap more than a few minutes, and you don’t want to be driving around when your body thinks it’s the middle of the night.

But, the key to treating jet lag is light therapy. Going east, you expose yourself to the bright light in the morning, and avoid bright light in the evening, and vice versa going west. But, it’s more complicated than that. The advice switches if you’ve traveling “through more than six time zones,” because “[y]our biological clock may then adjust in the wrong direction.” And, it’s even more complicated than that! “The effects of light acting upon the body clock” are actually only during a specific window around the time your body temperature bottoms out: this is usually around 4 am. You drop from 98.6 down to like 97.6, even when you’re not sleeping—it’s just part of our circadian rhythm.

The bottom line, if you fly from LA to London, eight time zones east, you’d avoid light between 6 am and noon local time, and expose yourself to light between noon and 6 pm local, and the rest of the day, it doesn’t matter and won’t affect you either way. Okay, now but that’s just on day one. “On subsequent days, the local times of light avoidance and exposure need to be advanced [earlier] by [one to two hours] each day, until light avoidance coincides with [when you’re sleeping].”

But, on those first few days after traveling east, you’ll note you’re going to want to be avoiding morning light, which can be difficult, if that’s when your flight gets in. One thing you can do is wear really dark glasses until you get indoors. But, if they’re too dark, you can’t really drive. So, that’s where these kinds of ugly orange lenses that block blue wavelengths can come in handy, preventing the dip in melatonin you get just wearing regular sunglasses. Regardless, the next day, I know there’s the urge to get out and about, but that could actually make your jet lag worse, by taking you in the opposite direction.

What about if you’re flying more than eight time zones east? Then, you subtract the number from 24, and treat it as travel west. So, a ten-time-zone trip to the east, like New York to Delhi, should be treated as a westward flight, requiring a delay of the body clock, across 14 time zones. In that case, it would be easy to get outside and get some sun. But if you just went four time zones west, and need to get light in the middle of the night, what do you do?

A gadget company came up with like light-emitting headphones, the theory being you could bathe your brain in light directly through the ear canals. They stuck them on the heads of cadavers and did seem to get some light penetration, but you don’t know, until you…put it to the test. “This randomized, double-blind, placebo-controlled trial demonstrates that…transcranial bright light exposure via the ear canals [could] alleviate…jet lag symptoms.” Or, you could just turn on a lamp.

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