Unlocking the Mysteries of Melatonin: Exploring Safety and Efficacy

More and more people are turning to melatonin supplements, which are widely used to support sleep and circadian rhythm regulation. 

Many people consider melatonin to help manage sleep disturbances such as:

• Insomnia
• Delayed sleep phase syndrome
• Jet lag
• Shift work sleep disorder
• Sleep disturbances associated with conditions like autism spectrum disorder (ASD) or Attention-Deficit Hyperactivity Disorder (ADHD) in children
• Age-related declines in melatonin production in elderly people  
• Sleep issues in people dealing with anxiety and stress

This article describes the hormone melatonin, its potential uses, general dosage guidelines, safety, and possible side effects. It also describes normal natural melatonin levels and functional medicine labs that measure melatonin levels. 

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What is Melatonin?

Melatonin (N-acetyl-5-methoxytryptamine) is a hormone produced by the pineal gland, which is located in the brain and is part of the endocrine system.  

• Melatonin is produced in response to darkness and helps regulate the sleep-wake cycle and circadian rhythms. This process is initiated by photic (light)  input to the suprachiasmatic nucleus (SCN) in the brain, which serves as the primary circadian pacemaker. 
• The pineal gland receives information about the sleep-wake cycle (day-night cycle) from the eyes' retinas. When it senses that it is dark outside, then melatonin production increases. It continues to be secreted throughout the night to help people achieve continued sleep. 
• Melatonin is inversely related to the hormone cortisol. When a person is exposed to light, the SCN triggers the activation of the Hypothalamic Pituitary Adrenal (HPA) axis. This leads to the synthesis and release of cortisol, a glucocorticoid hormone that peaks in the morning upon waking. This is known as the Cortisol Awakening Response (CAR). As cortisol levels decrease as the day goes on, then melatonin increases. 

Melatonin is produced every night in humans. Light exposure in the evening can hinder melatonin production for the first part of the night and delay melatonin production the following night. Melatonin secretion is also determined by the day length, meaning that in short days of the winter, melatonin secretion is longer and shorter during the longer days of summer.  

Supplemental Melatonin Dosing 

Melatonin has been sold as a dietary supplement in the United States since 1994. Supplements are not regulated by the Food and Drug Administration (FDA), so the dose of the supplements cannot be verified. This means that the actual dose of melatonin could be more or less than what is advertised. 

Melatonin supplements come in doses of 1 mg to 10 mg. It is often suggested to start with 1 mg and increase the dose by 1 mg weekly until a dose helps the person fall asleep faster. It is important to take melatonin supplements at the correct time to ensure they are most effective. 

The best time to take melatonin is when the person is feeling tired, prior to bedtime.  It is very easy to overcome the effects of melatonin. If a person starts watching television, playing video games, or using their phone and is exposed to light, the supplement may not work. That is why the timing of administration is important. 

Dosing of melatonin is dependent on age. Dosing suggestions for children are:

• Ages 3 to 5: 1 to 3 mg
• Ages 5 to 10: 2 to 5 mg
• Adolescents: 5 to 10 mg

The maximum dose that should be given to children is 12 mg. The dose should start low and gradually increase. It is often suggested that children only use melatonin for 2 to 3 weeks, but there are some exceptions. Children who have attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) may need long-term supplementation with melatonin. 

Some children should not be given melatonin. This includes children under 2 years of age because the brain is still maturing, children who have migraines with auras, and children with immune disorders because of melatonin’s immunomodulating properties. 

What Are Normal Melatonin Levels? 

Melatonin levels vary based on a person’s gender and age.

• Newborn babies do not produce a substantial amount of melatonin. They receive it from the placenta in utero and through breast milk after birth. Regular melatonin production starts occurring at 2 to 3 months of age. 
• Melatonin levels increase in childhood and peak at puberty. 
• In all ages after puberty, melatonin levels are higher in women than men.
• Melatonin levels gradually decline after the age of 40. 

Side Effects 

If a person takes too much melatonin or takes it late in the day, then it can cause drowsiness, sluggishness, or decreased reaction time the next day. Some common side effects of melatonin include:

• Abdominal cramps
• Bad or vivid dreams
• Dizziness
• Drowsiness
• Headaches
• Nausea
• Irritability
• Hypotension (low blood pressure)
• Mild anxiety
• Temporary depression

Mild side effects in children include headache, dizziness, nausea, and sleepiness. 

Functional Medicine Labs That Test Melatonin Levels 

To determine if a patient might benefit from melatonin supplementation, practitioners may choose to assess melatonin levels using various methods. 

Testing via saliva and urine is the most common way to determine melatonin levels. Serum blood levels are not commonly used because they vary greatly over a 24-hour period. 

One common saliva test used is called the Melatonin Profile. This test involves collecting saliva at different times throughout the day. The report gives a reading of levels in the morning, evening, and night to determine if melatonin is produced at the appropriate levels and at the appropriate times. 

The DUTCH (Dried Urine Test for Comprehensive Hormones) Plus test uses urine samples collected over a 24-hour period to assess hormone levels and their metabolites. This includes estrogen, progesterone, and androgens and their metabolites, as well as extra markers like melatonin, which is measured as 6-OH-Melatonin-Sulfate.  

Alternatives to Melatonin 

There are other supplements that have been shown to support sleep, but most of them, like melatonin, are only meant to be used short-term. Some of these include:

• Valerian Root
• Magnesium
• Lavender Oil
• L-theanine
• Glycine

Lifestyle modifications should also be considered in conjunction with any sleep supplementation. These include getting to the root cause of the sleep issue and adjusting as needed. This can include changes to sleep hygiene habits and changes in diet. 

Is Melatonin Safe?

Melatonin appears safe for short-term use, but there is insufficient information to determine long-term safety and effects. Some of the concerns regarding melatonin include:

Interactions with Medications

• People with epilepsy and who are taking blood thinners should be under medical supervision when taking melatonin supplements. 
• Some medicines may increase the effects of melatonin. Examples include enasidenib, used for managing leukemia, mexiletine, for the management of heart arrhythmias, and fluvoxamine, used for managing depression, increase the level of the hepatic enzyme CYP1A2.

Regulated as a Dietary Supplement 

• The FDA less strictly regulates dietary supplements than prescription medications. In some countries, melatonin is available only with a prescription. 

Safety Concerns for Older People

• The 2015 guidelines by the American Academy of Sleep Medicine recommend that melatonin use be avoided in people with dementia. 
• The supplement may stay active in older people longer due to decreased metabolism. This may result in daytime drowsiness. 

Safety Concerns for Children

• Melatonin supplements could affect hormone development, including puberty, menstrual cycles, and overproduction of the hormone prolactin. 

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Key Takeaways

• Melatonin supplementation, when used short-term in children and adults, is generally considered safe. 
• More long-term studies are needed to show the safety of melatonin use beyond 2-3 weeks. 
• If melatonin is needed for longer than 3 weeks, a thorough workup should be done that includes a dietary and lifestyle assessment and lab testing to determine any underlying cause of insomnia.