May 2019 Issue

Supplements: Melatonin
By Ginger Hultin, MS, RDN, CSO
Today’s Dietitian
Vol. 21, No. 5, P. 14

Research on this popular sleep aid demonstrates efficacy and safety, but clients should use it with caution.

Melatonin is a hormone the brain releases each night that’s critical for inducing sleep. It’s widely available and commonly taken in supplement form, especially by those with insomnia, circadian rhythm disorders, jet lag when traveling, shift work disorder, and some chronic conditions that disrupt sleep including chronic fatigue syndrome, fibromyalgia, Alzheimer’s and other forms of dementia, restless leg syndrome, ADHD, traumatic brain injury, and psychiatric disorders such as bipolar disorder, schizophrenia, depression, and seasonal affective disorder.1,2

As more research has been conducted, particularly on humans, a better understanding of melatonin’s role in sleep and other conditions has developed. It’s critical for RDs to stay abreast of quality testing of and dosing recommendations for melatonin, as patients may ask about supplementation. Questions about melatonin supplementation provide dietitians with the opportunity to discuss this supplement in the context of a conversation on how sleep affects health and nutrition.

Melatonin in the Brain
Melatonin is synthesized and released by the pineal gland in the brain upon exposure to darkness and is suppressed by light as part of the body’s circadian rhythm. It plays several roles in the body, namely regulating circadian rhythm, sleep patterns, and endocrine secretions. Melatonin production changes throughout life; it peaks between ages 2 and 3, declines in puberty, and then declines further in older adulthood.1

Supplement Form
Most melatonin available in supplement form is created synthetically, but some forms come from animal pineal glands or from plants.1,2 Melatonin does exist naturally in some foods but at very low levels.2 It’s available in immediate-release products to aid in falling asleep and delayed-release to support staying asleep. “Fast-acting” liquid melatonin is on the market, but no research has been conducted on this form regarding efficacy.  

ConsumerLab.com is a company that does third-party quality testing on supplements for quality assurance and public safety. Recently, it tested different brands of melatonin supplements regarding dosing, indications for use, and recommended dose. In its exploration, cost of melatonin varied greatly, ranging from one cent to nearly $3 per dose, with doses ranging from 0.3 mg to 10 mg in a variety of supplement forms including chewable, dissolvable, and immediate- and delayed-release tablets; softgels; liquids; and powders.2 (See table for ConsumerLab.com’s top picks.) A recent study of melatonin supplements from Canada found that 71% of 30 products tested weren’t within 10% of the dose of melatonin listed on the label.3

Safety
When used short term (up to six months), melatonin appears to be safe, and some patients can safely use it for as long as two years under medical supervision. Patients younger than 20, or their parents, should discuss melatonin use with their physicians, as they naturally produce higher levels of melatonin than adults 21 and older and melatonin levels are inversely related to gonadal development. Melatonin may suppress ovulation, negatively affecting fertility, so women wishing to become pregnant should avoid taking melatonin regularly, especially in high doses. Currently, studies are unclear on whether melatonin is safe during pregnancy or lactation, so women should consult their physicians.1

Melatonin generally is well tolerated, though adverse effects including headache, dizziness, nausea, and drowsiness can occur.1 There’s evidence that melatonin can affect testosterone and estrogen levels, and in some studies long-term use is associated with increased risk of bone fracture.2 Next-day drowsiness also can occur, so clients should use caution and start with a lower dose (<1 mg), increasing it as needed and tolerated.1,2

There are some moderate interactions between melatonin and blood thinners such as warfarin, anticonvulsants, diabetes medications, antihypertensive drugs, central nervous system depressants such as alcohol, contraceptives, immunosuppressants, methamphetamine, seizure medications, and cytochrome P450 substrates such as caffeine. It also can interact with herbs and supplements that decrease blood sugar or blood pressure, those with sedative properties, anticoagulants, and St John’s Wort.1

In sum, there are many factors to take into account before supplementing with melatonin, and guidelines suggest it’s best taken as needed rather than on a long-term or regular basis.2

Dosing and Efficacy
Melatonin has been studied most for treating primary insomnia and sleep disorders rather than sleep difficulties caused by other conditions.4,5 A recent meta-analysis involving 19 studies of 1,683 subjects explored melatonin’s efficacy in helping participants fall asleep and stay asleep. Using melatonin longer and at higher doses had better outcomes for both measures; subjects who used melatonin fell asleep about seven minutes more quickly (p<0.001) and slept for eight minutes longer (p=0.013). Overall, sleep quality significantly improved in those who used melatonin compared with placebo (p<0.001).6 Supplemental melatonin may be especially beneficial for older adults with insomnia—especially if they’re melatonin deficient due to the natural aging process—but studies are mixed. In one study, sustained-release melatonin dosed at 2 mg nightly appeared to help with sleep quality in older adults.1

Melatonin dosing for jet lag is more specific than for general sleep. Doses ranging from 0.5 to 5 mg appear to help travelers adjust their circadian rhythms more quickly. When traveling eastward through five or more time zones, 2 to 3 mg of melatonin, either immediate- or delayed-release, can be useful when taken at local bedtime on the day of arrival and for two to five nights after that while the body adjusts to the new time zone. Research is less clear on the usefulness of melatonin for westward travel or through fewer than five time zones.1

Future Research and Exploration
Though melatonin appears effective for sleep and some other conditions, more research is needed. Endogenous melatonin production changes throughout the lifespan, so dosing and usage also should change over time. There’s some preliminary research on the use of melatonin for many conditions, including irritable bowel syndrome and other gastrointestinal diseases; nicotine, drug, and alcohol withdrawal; menopause; polycystic ovary syndrome; and headaches. However, more high-quality human studies are necessary to assess its potential efficacy.1

Recommendations for Clients
There are many reasons for sleep disturbances, and melatonin may be one way to help people get more rest. Before discussing supplementation, dietitians should be sure to explore other aspects of sleep hygiene, including timing of meals, physical activity, and caffeine use in addition to screen time and blue light (emitted from smartphone and computer screens and energy-efficient lights, for example) exposure before bed. If melatonin supplements seem appropriate and drug/nutrient interactions aren’t a concern, there’s evidence that using melatonin about 45 minutes before bed may help clients fall asleep. Guidelines suggest it should be used as needed on a short-term basis. Clients should start with 1 mg or less and work up to 3 mg or more, consulting with their physician regarding safety related to health conditions, medications, or other supplements.2

— Ginger Hultin, MS, RDN, CSO, is a nutrition and health writer and certified specialist in oncology nutrition based in Seattle. She’s past chair of the Vegetarian Nutrition Dietetic Practice Group, past president of the Chicago Academy of Nutrition and Dietetics, and owner of concierge nutrition practice Champagne Nutrition LLC.

References
1. Melatonin. Natural Medicines Database website. https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=940. Updated March 13, 2019. Accessed March 18, 2019.

2. Melatonin supplements review. ConsumerLab.com website. https://www.consumerlab.com/reviews/melatonin-supplements/melatonin/. Updated March 19, 2019.

3. Erland LA, Saxena PK. Melatonin natural health products and supplements: presence of serotonin and significant variability of melatonin content. J Clin Sleep Med. 2017;13(2):275-281.

4. Sletten TL, Magee M, Murray JM, et al. Efficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: a double-blind, randomised clinical trial. PLoS Med. 2018;15(6):e1002587.

5. Chojnacki C, Kaczka A, Gasiorowska A, Fichna J, Chojnacki J, Brzozowski T. The effect of long-term melatonin supplementation on psychosomatic disorders in postmenopausal women. J Physiol Pharmacol. 2018;69(2).

6. Ferracioli-Oda E, Qawasmi A, Bloch MH. Meta-analysis: melatonin for the treatment of primary sleep disorders. PLoS One. 2013;8(5):e63773.