麻豆传媒

IT IS sometimes referred to as the Dracula hormone because it emerges at night and lays low during the day. But most of us know it as melatonin, a hormone that has become intimately connected in our minds with nightfall and sleep. In the US, where melatonin supplements are available over the counter, millions of adults take them regularly to tackle insomnia, jet lag and night shifts. Thousands more dole out melatonin 鈥済ummies鈥� to their children to help them sleep through the night. In the UK, is available on prescription for the short-term treatment of insomnia in people aged 55 and over and for jet lag.

A huge group, then, believes melatonin is the answer to its sleep problems. So, you may be surprised to hear that nearly a quarter of a century ago, researchers writing in the journal Cell . 鈥淢elatonin鈥檚 [sleep-inducing] capability has鈥� been embellished,鈥� they wrote. 鈥淭he cure for melatonin madness is to ignore the hyperbole and histrionics and focus instead on hypothesis testing and sound science.鈥�

It seems that few people listened to the warnings. In the US, and recent news stories have reported increasing accidental ingestion of melatonin 鈥� the hormone and young adults under 19 years of age reported to the US National Poison Data System in 2021.

Where does the truth lie? Can melatonin really improve our sleep? Emerging research suggests we have misunderstood its effect on our body and brain. So who should really be taking it, and what are the risks?

The drive to sleep

The story of melatonin really begins with translucent tadpoles. In 1917, researchers at Johns Hopkins University in Baltimore were investigating how extracts from the pineal gland affect growth. This gland is a tiny structure towards the bottom of the brain. Tadpoles were fed bovine pineal glands and within 30 minutes, these dark-skinned creatures became so translucent that . Three hours later, the tadpoles returned to their usual colour.

The mystery of what substance had induced this colour change took more than 40 years to crack. In 1958, Aaron Lerner at Yale University and his team . Lerner, a dermatologist, initially thought it could treat conditions like vitiligo, in which patches of skin lose their colour. Later experiments showed that melatonin didn鈥檛 hold the key to treating disruptions in skin pigmentation. Instead, further work identified melatonin as having an important role in circadian rhythms 鈥� internally driven daily cycles that coordinate various body processes, including sleep.

To explore melatonin鈥檚 relationship with sleep, it helps to understand how sleep is regulated. First, there is what is known as sleep pressure. The longer you are awake, the more a chemical called adenosine is released by cells in the brain. Adenosine inhibits arousal and . Caffeine blocks adenosine receptors, which explains why it .

Sleep pressure is balanced by the force of a 24-hour circadian rhythm, known as 鈥渃ircadian alertness鈥�, which is synchronised to the external environment and can be modulated by things like sunlight. Melatonin plays a . Its synthesis is regulated by the brain鈥檚 so-called master clock 鈥� the suprachiasmatic nucleus 鈥� to produce release, with levels rising at dusk, and declining before dawn (see 鈥淭he daily drive to sleep鈥�, below). The suprachiasmatic nucleus has receptors that detect melatonin, providing another cue for synchronisation.

Sleep is an intricately choreographed process, easily disrupted by jet lag or working night shifts. Both of these are related to a mismatch between our innate circadian rhythms and the external environment. With jet lag, we cross time zones too rapidly for our circadian clock to adjust. The suprachiasmatic nucleus can adapt to a disrupted social schedule and the different timings of light and dark at our destination, but it takes a while 鈥� . With night shifts, sleep pressure may increase after an exhausting stint at work, but just as your head hits the pillow, your body clock may insist it is time to wake up. This isn鈥檛 helped by environmental cues, such as quiet streets, closed shops and dark skies during your shift, telling you everyone else is asleep.

No wonder melatonin was seen as a solution to sleep problems. Our urge to sleep closely correlates with the hormone鈥檚 rise and fall, so people assumed it was the cause of sleep, says at the University of Oxford. Initially, this idea seemed to be supported by case reports in the 1970s of people with spinal injuries who were paralysed from the neck down. They were unable to produce melatonin as a consequence of disrupted nerve signals and had extremely poor sleep. 鈥淧eople thought: 鈥楻ight, no melatonin equals awful sleep鈥�,鈥� says Foster. However, researchers later compared these results with people with spinal injuries affecting just their legs, whose melatonin nerve signals had been spared and so could produce the hormone. . So, poor sleep in these groups was independent of melatonin production.

Further work shows that people who have had their pineal gland removed due to illness with little change in sleep. 鈥淲hen you take away melatonin in humans by these rather drastic means, it doesn鈥檛 affect sleep very much,鈥� says Foster. In other words, melatonin is important for optimal circadian function, but not essential to it. It is one of many factors that together help to promote sleep. 鈥淥ur propensity to sleep closely correlates with melatonin鈥檚 profile, but we shouldn鈥檛 mix this up with causation,鈥� says Foster. 鈥淢elatonin is a mild modulator of sleep, but this is not how sleep is governed.鈥�

Melatonin also turns out to have many other roles. It has antioxidant and anti-inflammatory functions, it regulates energy metabolism 鈥� including body weight, insulin sensitivity and glucose tolerance 鈥� and it helps control blood pressure.

So does melatonin help you sleep at all? Well, that depends on who you are and how much extra sleep you are hoping for. The truth is that, for most adults, melatonin supplements will buy extra minutes of sleep, not hours. Hardly the stuff of dreams.

Jet lag cure

A 2013 meta-analysis of nearly 1700 participants found that, compared with a placebo, , or the time taken to fall asleep, by 7 minutes on average. Total sleep time increased by around 8 minutes. This year, an international meta-analysis of 154 trials that included 44,000 people also reached a disappointing conclusion: .

What about helping to 鈥渞eset鈥� the body clock to cure jet lag? Discerning melatonin鈥檚 effect in this context has proved difficult, in part because the symptoms of jet lag disappear fairly quickly by themselves. England鈥檚 decision to allow melatonin to be prescribed for the short-term treatment of jet lag was , many of which were small and didn鈥檛 provide thorough outcome measures, used to assess the effect of the intervention. Half failed to detail the dose of melatonin or whether it was taken as a tablet or a liquid. And although some trials showed that melatonin lessened the severity of symptoms, none eradicated them completely.

There is more promise in another area, though: it may have benefits in children, especially those with neurodevelopmental differences, such as autism. In the UK, the licensed version of melatonin is used 鈥渙ff label鈥� as a treatment to help sleep problems in children once non-pharmacological measures have been exhausted. In 19 randomised controlled trials, melatonin had a sizeable effect, cutting sleep latency in children by 11 to 51 minutes and boosting sleep duration by 14 to 68 minutes. . Child and caregiver quality of life was often enhanced, too.

These positive results have been explained by in some people with neurodevelopmental differences. But Foster remains cautious, pointing to a lack of randomised controlled trials that have been validated through repetition.

Still, it is easy to see melatonin鈥檚 attraction. experiencing poor sleep include setting consistent bedtime routines, avoiding electronics before bed and encouraging them to fall asleep and stay asleep without parental help. Many families would argue that relying on these tactics alone is unrealistic 鈥� in which case, the mere possibility of increasing sleep duration by up to 68 minutes seems like a reward worth aiming for.

But what about the risks? The says that , there are few reported severe effects in adults. However, common side effects in adults include headaches, dizziness, irritability, dry mouth, strange dreams and night sweats. Melatonin can also interfere with prescription medications. The AASM reports an association with a rise in depressive symptoms and caution is required for those with epilepsy or those taking the blood-thinning drug warfarin.

Standard prescribed doses of melatonin differ depending on where you live. In the UK, can be prescribed 2 milligrams per night for up to 13 weeks. For jet lag, the dose is up to 6 milligrams per day for up to five days. Taken in the short term, for adults at least, it seems a safer bet than drugs like benzodiazepines and benzodiazepine receptor agonists (so-called Z-drugs) that are sometimes prescribed for insomnia, which can result in considerable adverse effects, including falls, lowered mood, confusion, cognitive impairment, dependence and withdrawal. .

Puberty problem?

Short-term use of melatonin in children also appears fairly safe: in 2014, researchers met in Rome to discuss the matter and concluded there was no evidence of serious adverse effects in children, although acknowledged this was based on limited trials. There have been , possibly by disrupting the decline in night-time melatonin levels that occur at the onset of puberty. Indeed, some early studies suggested that .

However, these studies were mainly carried out in cats, rats, mice and hamsters, rather than humans. Reassuringly, a 2021 study of 80 children and adolescents, most of whom were autistic, and who were given a nightly dose of up to 10 milligrams of melatonin for two years, showed there were and sexual development.

As with any supplement, you need to be careful where it is stored. Melatonin is the , with the annual number increasing by 530 per cent between 2012 and 2021. During this time, five children required mechanical ventilation and two died.

Finally, there is one factor you may want to consider before popping a nightly pill: it can be hard to know what is actually in the bottle. Melatonin for human use tends to be sourced from pigs or produced synthetically. It is basically indistinguishable from your body鈥檚 version, says at the University of the Fraser Valley in British Columbia, Canada. However, there are no requirements in Canada or the US for companies to test pills to confirm the melatonin content they are advertising.

In 2017, Erland and at the University of Guelph in Ontario, Canada, analysed 31 melatonin supplements from local grocery stories and pharmacies in Guelph. Melatonin content than what was claimed on the bottle or packet. For 71 per cent of supplements, the amount didn鈥檛 fall within a 10 per cent margin of what was promised. One chewable tablet for children contained 9 milligrams of melatonin, says Erland, rather than 1.5 milligrams.

These unexpectedly high levels aren鈥檛 harmful to most people, she adds, but the risks rise in people taking medications that interact with melatonin and in people with health conditions that increase their susceptibility to the drug鈥檚 side effects.

A quarter of the tested supplements also contained serotonin 鈥� a precursor of melatonin that is a much more strictly controlled substance. The amount was tiny and the researchers say it was unlikely to have significant health outcomes. They report that it may have come from plant extracts in some of the supplements, but its presence in supplements lacking these extracts is more difficult to explain.

So where does this leave us? The recent evidence for melatonin鈥檚 poor results as a sleep aid for adults has led to a change of heart by some professional bodies, although recommendations by one often contradict those by another. The AASM says , which is where insomnia occurs at least three times a week for three months, in adults. But it does acknowledge its utility in treating jet lag if taken at an 鈥渁ppropriate time鈥�. Unfortunately, it doesn鈥檛 specify what an appropriate time actually is, although in associated information for patients, it states that doctors recommend taking melatonin before the time you want to go to bed, beginning before your trip and continuing for a few days after your arrival. This contradicts , which says melatonin should be taken for up to five days, with the first dose taken at bedtime after you have arrived at your destination.

The European Sleep Research Society says 鈥� because of low efficacy鈥�. The , meanwhile, says melatonin may be useful in delayed sleep-wake phase disorder, which includes jet lag, as well as a difficulty falling asleep at the desired time and struggles with waking at the required time, but acknowledges that behavioural regimes can also be used.

Melatonin-rich food

If you are keen to avoid drugs altogether, you might have considered consuming melatonin-rich food and drinks to help promote better sleep. Walnuts, oranges, grapes, eggs, dairy and wine have all been touted as helping us sleep. Sadly, at the University of Adelaide, Australia, says this is wishful thinking. His review of several studies analysing the effect of melatonin-rich food on sleep shows that most of them were poorly conducted and uncritical in their evaluation.

Kennaway concludes that it is unlikely that the amount of melatonin in so-called melatonin-rich foods will have any physiological impact. Instead of changing your diet, most organisations recommend cognitive behavioural therapy as a first-line treatment for insomnia, and there are many new studies that show promising results in this area.

Nevertheless, when it comes to poor sleep, desperate times call for desperate measures, and even Foster has turned to the hormone of darkness when he was flying between the UK and Australia a lot. It didn鈥檛 work for him, yet he continued to take it 鈥� just in case. Only when it began to lower his mood 鈥� a rare side effect with an unknown mechanism 鈥� did he stop. Indeed, the prospect of a good night鈥檚 sleep is just too tantalising for many, and the popularity of melatonin supplements shows no signs of waning, despite a lack of evidence supporting their worth for most. Across the world, the supplements continue to emerge from bottles each evening, and so, for now, the Dracula hormone lives on.