Melatonin for Sleep: What to Know Before You Try it

Imagine you haven’t had a good night’s sleep for a while and as a result, you’ve been irritable and fatigued all day. You’ve tried just about everything to help you with sleep, but unfortunately nothing seems to work. So, you take a quick stroll down the vitamin section of the supermarket to see what sleep aids are available. Sound familiar?

You aren’t alone. Insomnia is one of the most prevalent health concerns in the United States. About 20% of Americans suffer from insomnia and of that 20%, about half are suffering from chronic insomnia.[1] 

So back to the imaginary vitamin aisle, you see that there are a lot of sleep aids to choose from and the one you see the most is melatonin. In your head, you might be thinking, “there sure is a lot of this melatonin here, it must be safe and effective.” Before we possibly conclude that, here are some things about melatonin you should know that we will be unpacking in this article:

  • When melatonin works.
  • What are the side effects of melatonin?
  • When melatonin doesn’t work so well.
  • How melatonin is dosed.
  • Is melatonin safe for kids?
  • What are melatonin’s interactions?

What is melatonin and why is it used for sleep? 

Melatonin is the most popular sleep supplement on the market. It is a sleep hormone made in the pineal gland deep in the center of your brain. It plays a fundamental role in regulating the sleep-wake cycle that determines your internal internal clock known as your circadian rhythm

In the United States, melatonin is sold as a dietary supplement rather than a drug and is therefore unregulated by the Food and Drug Administration in the way drugs are. As a supplement, it is marketed to promote total sleep time, help with fatigue from jet lag, and balance dysfunctional circadian rhythms. 

Individuals with initial insomnia (trouble falling asleep) have lower melatonin levels compared to those who fall asleep without trouble. There is some evidence that taking melatonin supplements may be beneficial for alleviating some insomnia symptoms, for example, reducing the amount of time it takes to fall asleep by between four and 11.7 minutes.[3] 

Melatonin production in the brain occurs only under dark conditions in the late evening and night.4  It’s important to contextualize that melatonin’s primary role is the regulation of the body’s circadian rhythm, namely, our sleep cycle. It does this by triggering the secretion of other sleep hormones.

It’s basically nature’s way of saying, “Ok, the sun has gone down, it’s bedtime!” Melatonin’s job is to induce sleepiness — not fall asleep, but feel tired. That said, by feeling tired, you tend to fall asleep faster. It is kind of a chicken and egg relationship.

Here’s how your body makes melatonin. Before becoming the sleepy feeling hormone, it starts off as tryptophan, an essential amino acid. Tryptophan is then converted to 5-hydroxytryptophan (5-HTP), then serotonin, and lastly melatonin. 

When melatonin gets to the brain, it increases the binding of gamma-aminobenzoic acid (GABA) to its receptors. Now GABA, like serotonin, is one of the main neurotransmitters with an important role for sleep. It also helps people fall asleep by making the central nervous system less excited. 

At this point you are probably thinking, “melatonin seems to be doing a lot to help us sleep!” And you’re not wrong. What we’re talking about here is the melatonin that your brain naturally produces. 

As you well know, melatonin is also sold as a supplement. You might be wondering what these melatonin supplements are from.

Even though you can find melatonin in the vitamin section, they’re not herbal. You can’t get melatonin from food. The only way to supplement melatonin in your system is by synthetic melatonin or from animals: extracted from the pineal gland of cows.

Melatonin side effects[6]

In general, melatonin is well tolerated when taken orally for a short duration. But, you may wonder if it is it bad to take it every night.

Side effects usually occur when taking melatonin daily in higher doses than recommended. Though side effects are uncommon, they can manifest, particularly in cases associated with long-term use. Also, because melatonin is a hormone that has many functions, it's important to keep an eye out for potential side effects. These could include:

  • Cardiovascular: May increase levels of very low-density lipoprotein cholesterol (V-LDL) and triglycerides, abnormal heart rhythms, palpitations, fast heart rate or chest pain
  • Dermatologic: Papular skin rash, itching, cutaneous flushing
  • Endocrine: gynecomastia (long-term use), reduced sperm concentration and sperm motility
  • Gastrointestinal: Nausea, abdominal cramps, abdominal pain, diarrhea, constipation, decreased appetite, abnormal feces, odd taste in mouth, reflux esophagitis, exacerbation of Crohn’s disease, bladder rupture
  • Genitourinary: Enuresis, spotting or menstrual flow in perimenopausal women, decreased libido
  • Hematologic: Nose-bleeding 
  • Musculoskeletal: Increased fall risk due to increased postural swaying while standing on one or both feet in healthy adults, ataxia
  • Neurologic/CNS: Migraine-like headache, excessive drowsiness, irregular sleep-wake cycles, confusion, disorientation, nighttime awakening, mood swings, agitation, excitement before bedtime, nightmares, more intense dreams, reduced alertness, epilepsy, hyponatremia
  • Psychiatric: Mood changes, dysphoria, dips in mood, nervousness, transient depression, delusions/ hallucinations, aggressiveness, or psychotic episodes
  • Hepatic: Autoimmune hepatitis 

Melatonin dosing and safety[6]

If you’re wondering if and when melatonin is safe to consume, here are a few general guidelines:

Adults

For adults, it is usually considered safe when taken orally, for short-term or as a single one-time dose (0.1-3mg). Melatonin can be safe when used for up to six months. Higher doses, such as 5mg for shorter durations (one week) can also be used. Be mindful of the possible side effects that could occur from higher doses of melatonin. 

Children

Melatonin should only be taken by children for medical purposes. It should not be used to promote sleep in healthy children. It is usually considered safe when taken orally and appropriately in low doses for short-term periods to treat sleep problems associated with autism spectrum disorder and ADHD.

One 2017 study assessed the use of melatonin in children (age 2-17.5) who had autism spectrum disorder (ASD) with or without ADHD. The study found that during the 13 week trial, children who took melatonin slept an average of nearly one hour longer that those who took a placebo.

These findings indicate that there is some benefit to be had from melatonin use among this specific population. With this in mind, parents considering giving melatonin to their children should always seek medical advice before doing so.[10]

It’s important to note that there is insufficient research available about the safety of using melatonin for children in the long term. It is often advised that a daily dose of melatonin be limited to 3 mg daily for children and infants of six months and older and, 5mg daily for adolescents. Melatonin may adversely affect gonadal development in children and may delay puberty.[6] 

Pregnancy and Lactation

Pregnant and breast-feeding women are advised to avoid using melatonin. It is unknown if melatonin is safe for use throughout pregnancy and lactation. It is possibly unsafe when used orally in high, frequent doses (75-300mg).

Melatonin taken at these high doses seem to inhibit ovulation which causes a contraceptive effect. There is insufficient reliable information available regarding the use of lower doses in pregnancy. 

How long and how fast does melatonin work?[6] 

Depending on the person, about 3%-76% of the melatonin that you take is actually active and the rest is excreted from the body. In doses of 1-5mg, melatonin supplementation can increase serum concentrations by 10-100 times of the usual night-time peak for a patient. This is significant depending on the person. Melatonin is metabolized mainly through the liver. 

It takes about one hour for melatonin to start-working with the immediate-release formulas and then about 30-60 minutes for the melatonin half-life. Lastly, it takes about 4-8 hours for these levels return to baseline. 

Melatonin and age

As you get older, your body becomes less responsive to melatonin treatment and aging is correlated with reduced potency of melatonin receptors.[5]  Additionally, if you take it on a routine basis, for example every night, your body will become used to the sleep-promoting effects.

In other words, you can become tolerant to melatonin’s effects. In such a case, you wouldn’t find your usual dose of melatonin would initiate that sleepy feeling and so you might feel inclined to increase your dose.

But, if you’re worried about melatonin dependency or if you’re wondering whether melatonin is habit forming, the answer is yes. If you decide to increase your dose, this is where you really do need to tread with caution.

Melatonin can have multiple side effects. and if your body gets used to a higher doses of melatonin and then supplementation is stopped, your body may have a difficult time adjusting. In this case you might experience melatonin withdrawal. 

Melatonin and jet lag[8]

There is evidence that melatonin supplements are effective for jet lag. Jet lag occurs when the external time is not in sync with your circadian rhythm — a lot of this comes down to natural light exposure.

Jet lag becomes more severe as we get older because we become more prone to physical stress.[7] The desynchronization of the body’s circadian rhythm with the rise and fall of the sun is the reason why you might experience some fatigue and sleep disturbances. 

Since melatonin concentration starts rising at night-time, taking melatonin right before bed tells the body it is time to go to bed and helps you re-sync your body with the current time zone. 

Melatonin for Anxiety[6]

Unfortunately there is a lack of substantial evidence to support the use of melatonin for anxiety, and the evidence that does exist is limited and conflicting. It is recommended that you speak to your doctor or healthcare provider first before using melatonin for treatment of any kind. 

Can you overdose on melatonin?[5]

You’ve read the side effects and you know that mainly these side effects occur when people take them for long periods of time and at high doses, but you may be wondering if there is such a thing as a “melatonin overdose”.

The short answer is no. High doses of melatonin may produce any of the above side effects in a way that manifests very differently from person to person. Some people may feel extremely sleepy and others may feel more awake. The individual’s response to melatonin (as a function of their unique biochemistry) is what determines the side effects that they will experience at high doses. 

With that said, one of the most common side effects of taking too much melatonin is next-day grogginess, resulting in a hangover-like effect.  

What amount of melatonin is safe? 

While doses as high as 10mg are available, normal physiologic levels of melatonin can be achieved with doses as low as 0.1-0.3mg. This dosage is the recommended range to reduce unpleasant side effects while still being effective for sleep induction. 

Interactions with drugs[6]

Melatonin has various drug interactions, even as a supplement. If you or someone you know is taking multiple medications and considering melatonin, it may be worth considering this section. 

There is a moderate interaction with combining melatonin and anticoagulant/antiplatelet drugs and herbs/supplements such as warfarin. Melatonin may decrease coagulation activity; this means that is an increased risk for bleeding within one hour after taking it. 

Also, there is a moderate interaction when combining melatonin with anticonvulsants because it may inhibit the effects of anticonvulsants. Similarly, melatonin has an interaction with seizure threshold lowering drugs.  

Other drugs that melatonin may interact with include antidiabetic drugs. Melatonin impairs the use of glucose in the body and increases the risk of insulin resistance, which is the opposite of what antidiabetic drugs should do.

With melatonin, blood pressure decreases in healthy adults but elevates blood pressure in hypertensive patients. That is how it decreases the effectiveness of certain hypertensive medications. 

There are some drugs that may increase the sedative properties of melatonin and increase other side effects as well, including caffeine, central nervous system depressants, contraceptive/birth control drugs, and fluvoxamine. This also means that you probably shouldn’t be taking alcohol and melatonin together because they both have sedative effects. 

Conversely, melatonin can exacerbate the adverse effects of amphetamine and can stimulate the immune function to interfere with immunosuppressive therapies for transplant patients. So, it is important to avoid the use of melatonin in transplant patients on immunosuppressive therapies. 

Interactions with natural products

Let’s move away from drugs and into the melatonin interactions with natural products. 

Somewhat similarly, there are also interactions with natural products that have anticoagulant/antiplatelet, hypotensive, and sedative properties just like their prescription counterparts. Vitamin B12 has a unique effect on melatonin as it decreases melatonin’s concentration in the body. 

Despite all the interactions it may have with prescription drugs and natural products, it does not have any food interactions. 

How is melatonin being misused?

The use of melatonin in the United States has been rapidly increasing. Between 2007 and 2012 alone, melatonin use in the US rose from 0.1% to 0.7% among children and from 0.6% to 1.3% among adults. This means that over 3 million Americans report taking this product and the numbers are continuing to grow. Unfortunately, as the use of melatonin increases, so has its misuse.[9]

The trend of misuse is particularly problematic in the case of melatonin use for children. Misuse of melatonin is often a result of parents seeking a quick, over-the-counter fix to help their children fall asleep rather that addressing the core issues of their sleep problems. 

Factors such as high sugar intake, bright light exposure at night, irregular sleep patterns, and poor bedtime routines are often major contributors to difficulty sleeping and poor sleep quality, and so should always be addressed before seeking the help of medications or supplements for sleep. [9] 

Additionally, it is not uncommon for people to falsely assume that melatonin is safe simply because it can be purchased over-the-counter as a supplement. While melatonin is generally well tolerated, it can have some negative effects if taken incorrectly or by certain patient populations. Particularly those on other medications, as melatonin has the potential to interact with common drugs such as those used for anticoagulation, diabetes, and high blood pressure. 

Conclusion

Under specific circumstances, melatonin can be an effective sleep aid for addressing short-term sleep issues. It is the most sought out sleep supplement because it has been shown to reduce sleep onset delay by 4-11.2 minutes. Additionally, it’s a helpful general solution for some sleep disorders associated with circadian rhythm disruption, such as shift work or jet lag, particularly graveyard shift workers or when flying east for greater than three time zones, respectively. 

With that said, it isn’t for everyone. It is safest taken seldomly rather than over longer periods as the long-term effects of melatonin remain unclear. Plus, it also has a lot of interactions not only with other drugs but also diseases/conditions. 

Taking melatonin in higher than standardly recommended doses can increase the risk of side effects and probably is not the best way to treat long-term sleep problems. Remember, just because it’s popular doesn’t mean it’s the right solution for you. 

Glossary

  • Autoimmune: is a condition arising from an abnormal response to a normal body part. 
  • Dysphoria: state of unease or generalized dissatisfaction with life. 
  • Enuresis: involuntary urination 
  • Gynecomastia: enlargement or swelling of breast tissue in males. 
  • Half-life: The time it takes the concentration of a drug in the body to decrease by half.
  • Human Growth Hormone: It is a hormone produced in the pituitary gland that helps regulate body composition, body fluids, muscle and bone growth, sugar and fat metabolism, and possibly heart function. 
  • Hyponatremia: low sodium concentration in the blood 
  • Luteinizing Hormone: It is a hormone produced in the anterior pituitary gland. In females, an acute rise of LH triggers ovulation and development of the corpus luteum. In males, it stimulates Leydig cell production of testosterone. 
  • Oxytocin: It is a hormone secreted by the posterior lobe the pituitary gland. It plays a role in social bonding, sexual reproduction, childbirth, and the period after childbirth. 
  • Prolactin: Also known as a luteotropic hormone or luteotropin. It is made in the pituitary gland and is known for its role in enabling females to produce milk. 
  • Pruritus: an itch (localized or generalized)
  • Vasopressin: It is called the “anti-diuretic hormone” secreted by the pituitary gland. It acts on the kidneys and blood vessels to prevent the loss of water from the body by reducing urine output and helping kidneys reabsorb water into the body. 

References

  1. Buysse, D. (2013). Insomnia. JAMA, 309(7), 706-716.

  2. Carter, M. D., & Juurlink, D. N. (2012). Melatonin. CMAJ : Canadian Medical Association journal  journal de l'Association medicale canadienne, 184(17), 1923. 
  3. Pandi-Perumal S, Srinivasan V, Spence D, Cardinali D. Role of the melatonin system in the control of sleep: therapeutic implications. CNS Drugs. 2007;21:995–1018. 
  4. Claustrat B, Leston J. Melatonin: Physiological effects in humans. Neurochirurgie. 2015 Apr-Jun;61(2-3):77-84. doi: 10.1016/j.neuchi.2015.03.002. Epub 2015 Apr 20. Review. 
  5. Zhdanova IV. Melatonin as a hypnotic: pro. Sleep Med Rev. 2005 Feb;9(1):51-65. Review. 
  6. Melatonin. (19, April 16). Retrieved from https://naturalmedicines-therapeuticresearch-com.proxy.hsl.ucdenver.edu/databases/food,-herbs-supplements/professional.aspx?productid=940#scientificName. Accessed August 22, 2019.
  7. A.J. Davidson, M.T. Sellix, J. Daniel, S. Yamazaki, M. Menaker, G.D.Block. Chronic jet-lag increases mortality in aged mice. Curr Biol, 16 (2006), pp. R914-R916
  8. Srinivasan V, Spence DW, Pandi-Perumal SR, Trakht I, Cardinali DP. Jet lag: therapeutic use of melatonin and possible application of melatonin analogs. Travel Med Infect Dis. 2008 Jan-Mar;6(1-2):17-28. doi: 10.1016/j.tmaid.2007.12.002. Epub 2008 Jan 28. Review. PubMed PMID: 18342269.
  9. (2017, September 24). Melatonin. Retrieved from https://nccih.nih.gov/research/statistics/NHIS/2012/natural-products/melatonin
  10. Gringras P, Nir T, Breddy J, Frydman-Marom A, Findling RL. Efficacy and safety of pediatric prolonged-release melatonin for insomnia in children with autism spectrum disorder. Journal of the American Academy of Child & Adolescent Psychiatry. 2017; 56(11): 948-957. PMID #29096777