Advanced Sleep Melatonin

Name: Advanced Sleep Melatonin

What other drugs will affect Advanced Sleep Melatonin (melatonin)?

Taking melatonin with any medicines that make you sleepy can worsen this effect. Ask your doctor before taking melatonin with a sleeping pill, antidepressant, sedative, narcotic pain medicine, muscle relaxer, seizure medicine, or herbal/health supplements may also cause drowsiness (tryptophan, California poppy, chamomile, gotu kola, kava, St. John's wort, skullcap, valerian, and others).

Do not take melatonin without medical advice if you are using any of the following medications:

  • an antibiotic;

  • aspirin or acetaminophen (Tylenol);

  • birth control pills;

  • insulin or oral diabetes medicine;

  • narcotic pain medicine;

  • stomach medicine--lansoprazole (Prevacid), omeprazole (Prilosec), ondansetron (Zofran);

  • ADHD medication--methylphenidate, Adderall, Ritalin, and others;

  • heart or blood pressure medicine--mexiletine, propranolol, verapamil;

  • medicine to treat or prevent blood clots--clopidogrel (Plavix), warfarin (Coumadin, Jantoven);

  • NSAIDs (nonsteroidal anti-inflammatory drugs)--ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib, diclofenac, indomethacin, meloxicam, and others; or

  • steroid medicine--prednisone, and others.

This list is not complete. Other drugs may interact with melatonin, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this product guide.

What is Melatonin?

Melatonin is the natural hormone your body secretes that helps to maintain your wake-sleep cycle (also called “biological clock”). The wake-sleep cycle is the process of sleep and wakefulness; in humans this averages 8 hours of nighttime sleep and 16 hours of daytime activity. Melatonin is also made synthetically and available without a prescription as an over-the-counter (OTC) dietary supplement in the U.S.

Endogenous melatonin release (melatonin made by our bodies) is increased each day in response to darkness, peaking between 11PM and 3AM at roughly 200 picograms (pg) per mL. Nighttime melatonin hormone levels are roughly 10 times higher than in the daytime. Levels fall sharply before daylight, and are barely detectable in the daylight hours. The rise and fall in endogenous melatonin levels signal wake and sleep times, known as our circadian rhythm.

Natural melatonin secretion starts from the amino acid tryptophan, with serotonin as an intermediary, and then is released to the melatonin receptors in the brain, eye and other areas to help control the sleep and wake cycles. The melatonin half-life is short, roughly 20 to 50 minutes. It is metabolized (broken down) by the CYP-450 enzyme system in the liver and then excreted in the urine or feces.

Shorter periods of melatonin production occur in the summer with longer days, and more prolonged periods of production occur in the winter. Light at night (such as from smartphones or the TV) blocks the production of melatonin and can lead to sleep disturbances. Age also suppresses the levels of nighttime melatonin that are released, which may contribute to the problem of insomnia and early awakening often seen in older adults.

Melatonin supplementation has been suggested to have many uses, from sleep disorders to cancer treatment , but robust studies are lacking for many uses. However, it has been widely studied for treatment of jet lag and other sleep disorders. Additional, early research to define melatonin suggests it has an anti-oxidative activity, a role in modulating immune responses, and possible anti-tumor activity.

What Should I Avoid While Taking Melatonin?

  • Avoid driving or operating machinery for at least 4 hours after taking melatonin.
  • Avoid using this medication with other prescription medications, over-the-counter drugs, or dietary supplements without asking your doctor, pharmacist or other healthcare provider.
  • Avoid alcohol while taking this medication.
  • Avoid coffee, tea, cola, energy drinks, or other products that contain caffeine, as it may counteract the effects of the melatonin or increase levels of melatonin in your blood.

What Happens if I Miss a Dose of Melatonin?

If you miss taking a dose of melatonin, there is no cause for concern. However, melatonin may impair your thinking and reaction time. If you will be driving or doing any hazardous activity, skip your dose as melatonin can cause drowsiness.

Otherwise, use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine or double your dose to make up the missed medication.

Melatonin and Pregnancy

Most dietary supplements like melatonin have not been studied in pregnant women, during breastfeeding, or in children. Seek advice from your healthcare provider before using any dietary supplement if you are pregnant, nursing, or considering the use of this product in a child under 18 years of age.

How Does Melatonin Come at the Store?

In the U.S., melatonin pills can be purchased without a prescription in the pharmacy, grocery, or health food store. Melatonin strengths range from 1 milligram (mg) to 10 mg melatonin, but you should always start with the lowest dose to judge its effects. Some experts suggest to start with 0.3 to 0.5 mg thirty minutes before bedtime, instead of the higher doses. Cut a 1-mg immediate release melatonin tablet in half to get a 0.5 mg dose if lower doses are not available; don’t do this with time release melatonin. Also, don't drink alcohol with the time-release preparation, as it can disrupt the time-release mechanism. Melatonin comes as:

  • Melatonin tablet
  • Melatonin capsule
  • Melatonin lozenges
  • Time release melatonin or extended release melatonin
  • Liquid melatonin for kids
  • Sublingual melatonin (under the tongue)
  • Melatonin sprays
  • Melatonin drops
  • Chewable melatonin gummies

In addition to generic or store brands, examples of common melatonin brands in the U.S. include:

  • Natrol Melatonin
  • Nature Made Melatonin (all products USP verified)
  • Nature’s Bounty Melatonin
  • Nova Nutrition Melatonin
  • NOW Foods Melatonin
  • SleepMate Melatonin
  • Sundown Naturals Melatonin
  • Vitafusion Melatonin
  • Zarbees Natural Melatonin for Children

Ask your pharmacist about the best melatonin brands and products of high quality.

Interactions

Caffeine and fluvoxamine may increase the effects of melatonin, while melatonin may decrease the antihypertensive effect of nifedipine. Melatonin may possibly potentiate the effects of warfarin.

Adverse Reactions

Possible adverse reactions include depression, dizziness, enuresis, excessive daytime somnolence, headache, and nausea. Drowsiness may be experienced within 30 minutes after taking melatonin and may persist for approximately 1 hour and, thus, may affect driving ability. There may be an increased risk for seizures in children with severe neurological disorders.

Tips

  • Take melatonin as close to bedtime at your destination as possible (10 pm to midnight). For jet lag, one dose is usually taken each night for four nights.
  • Take short-acting rather than slow-release melatonin.
  • Buy melatonin from a reputable brand with good quality control measures.
  • Do not drive or operate machinery if you feel sleepy with melatonin or the sleepiness persists the next day.

Melatonin Levels and Effects while Breastfeeding

Summary of Use during Lactation

Melatonin is the hormone produced by the pineal gland that plays a role in regulating sleep and circadian rhythm. It is a normal component of breastmilk, with concentrations higher during nighttime than daytime.[1] Some authors suggest that mothers should nurse in the dark at night in order to avoid reductions in the melatonin content of breastmilk, which could disturb infant sleep patterns.[2] Differentiating milk pumped during the day from milk pumped during darkness has also been suggested for women pumping milk for their infants.[1][3] Some studies have attributed longer sleep time in breastfed infant than in formula-fed infants to melatonin in breastmilk.[4][5] Another study found higher colostrum melatonin levels at night which appeared to increase the phagocytic activity of colostral cells against bacteria.[6] Exogenous administration of melatonin has no specific use during breastfeeding and no data exist on the safety of maternal use of melatonin during breastfeeding. However, doses higher than those expected in breastmilk after maternal supplementation have been used safely in infants.[7] It is unlikely that short-term use of usual doses of melatonin in the evening by a nursing mother would adversely affect her breastfed infant, although some authors recommend against its use in breastfeeding because of the lack of data and a relatively long half-life in preterm neonates.[8]

Dietary supplements do not require extensive pre-marketing approval from the U.S. Food and Drug Administration. Manufacturers are responsible to ensure the safety, but do not need to prove the safety and effectiveness of dietary supplements before they are marketed. Dietary supplements may contain multiple ingredients, and differences are often found between labeled and actual ingredients or their amounts. A manufacturer may contract with an independent organization to verify the quality of a product or its ingredients, but that does not certify the safety or effectiveness of a product. Because of the above issues, clinical testing results on one product may not be applicable to other products. More detailed information about dietary supplements is available elsewhere on the LactMed Web site.

Drug Levels

Melatonin is a normal component of human milk which is synthesized from the amino acid tryptophan.

Maternal Levels. Ten nursing mothers who were 3 to 5 days postpartum had serum and breastmilk melatonin levels measured between 2 pm and 5 pm and again between 2 am and 4 am. The breastmilk melatonin level averaged 23 ng/L at night, an average of 35% of the maternal serum concentration. Melatonin was undetectable (<10 ng/L) in milk during the daytime. Six of the mothers collected milk after each feeding for 24 hours once within 3 months of delivery. All mothers exhibited a marked circadian rhythm of melatonin excretion into breastmilk with detectable levels first occurring in the evening and dropping to undetectable levels in the morning.[9]

Twenty-one mothers collected breastmilk samples 5 times in a 24-hour period between day 5 and 10 postpartum. The median melatonin concentration in daytime milk (10 an to 10 pm) was 1.5 mg/L and the median concentration in nighttime milk (10 pm to 10 am) was 7.3 ng/L. No statistically significant difference was found between the breastmilk of mothers with preterm and fullterm infants.[1]

Twenty-four healthy mothers and 24 mothers with allergic eczema were studied in a crossover fashion to watch either a humorous video, a nonhumorous video, or no video at 2-week intervals. Melatonin was measured in breastmilk 5 times between 10 pm and 6 am. Melatonin levels were higher at all times in the mothers who had watched the humorous video. The melatonin levels in mothers with eczema were generally lower than in normal mothers, but had a greater increase to similar levels in both groups after viewing the humorous video. The highest milk melatonin levels occurred at the 2 am sampling in all phases of the study, with a peak of 20.8 ng/L in healthy mothers and 19.9 ng/L in those with eczema.[10]

In studies in which exogenous oral melatonin was given to women, the resulting serum melatonin was variable, but peak serum concentrations ranged from 1.1 to 2.6 mcg/L for each 1 mg administered.[11][12][13] This would result in an average increase in breastmilk melatonin concentration from 0.4 to 1 mcg/L for each 1 mg administered to the mother, based on an average milk concentration of 35% of the maternal serum concentration. While the resulting concentrations would be higher than the typical physiologic peak milk concentrations of 0.02 mcg/L,[9][10] it would present a considerably lower dose to the infant than the 10 mg/kg dosages of melatonin that have been safely administered to neonates in clinical studies.[2][7]

One study found that breastmilk melatonin concentration was inversely correlated with breastmilk prolactin concentration and was higher in women experiencing fatigue in the morning.[14]

Five nursing mothers provided breastmilk samples every 2 hours over a 24-hour period. Melatonin was undetectable during the day, but began to rise at about 8 pm, reaching a peak at about 3 am, and then declining.[4]

Thirty women who were 48 to 72 hours postpartum provided 2 colostrum samples, one at noon and one at midnight. Melatonin levels in colostrum averaged about 16 ng/L at noon and 36 ng/L at midnight.[6]

Infant Levels. A study of 8 breastfed and 6 formula-fed infants found different patterns of the melatonin metabolite, 6-sulfatoxymelatonin, in their urine. Breastfed infants had a sinusoidal excretion pattern with a peak at 6 am and a trough at 6 pm. Formula-fed infants had a simple increase in the metabolite that was at baseline between about 8 pm and 4 am with a peak at about noon.[15]

Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

References

1. Katzer D, Pauli L, Mueller A et al. Melatonin concentrations and antioxidative capacity of human breast milk according to gestational age and the time of day. J Hum Lact. 2016;32:NP105-NP110. PMID: 27121237

2. Sanchez-Barcelo EJ, Mediavilla MD, Reiter RJ. Clinical uses of melatonin in pediatrics. Int J Pediatr. 2011;2011:892624. PMID: 21760817

3. Arslanoglu S, Bertino E, Nicocia M, Moro GE. Potential chronobiotic role of human milk in sleep regulation. J Perinat Med. 2012;40:1-8.

4. Cohen Engler A, Hadash A, Shehadeh N, Pillar G. Breastfeeding may improve nocturnal sleep and reduce infantile colic: Potential role of breast milk melatonin. Eur J Pediatr. 2012;171:729-32. PMID: 22205210

5. Rudzik AE, Robinson L, Ball HL. Infant sleep duration and melatonin levels in exclusively breastfed and exclusively formula fed infants. Am J Hum Biol. 2016;28:294. Abstract P43. DOI: doi:10.1002/ajhb.22831

6. Honorio-Franca AC, Hara CC, Ormonde JV et al. Human colostrum melatonin exhibits a day-night variation and modulates the activity of colostral phagocytes. J Appl Biomed. 2013;11:153-62. DOI: doi:10.2478/v10136-012-0039-2

7. Gitto E, Aversa S, Reiter RJ et al. Update on the use of melatonin in pediatrics. J Pineal Res. 2011;50:21-8. PMID: 21029156

8. Andersen LP, Gogenur I, Rosenberg J et al. The safety of melatonin in humans. Clin Drug Investig. 2016;36:169-75. PMID: 26692007

9. Illnerova H, Buresova M, Presl J. Melatonin rhythm in human milk. J Clin Endocrinol Metab. 1993;77:838-41. PMID: 8370707

10. Kimata H. Laughter elevates the levels of breast-milk melatonin. J Psychosom Res. 2007;62:699-702. PMID: 17540228

11. Fourtillan JB, Brisson AM, Gobin P et al. Bioavailability of melatonin in humans after day-time administration of D(7) melatonin. Biopharm Drug Dispos. 2000;21:15-22. PMID: 11038434

12. DeMuro RL, Nafziger AN, Blask DE et al. The absolute bioavailability of oral melatonin. J Clin Pharmacol. 2000;40:781-4. PMID: 10883420

13. Markantonis SL, Tsakalozou E, Paraskeva A et al. Melatonin pharmacokinetics in premenopausal and postmenopausal healthy female volunteers. J Clin Pharmacol. 2008;48:240-5. PMID: 18071190

14. Groer M, Davis M, Casey K et al. Neuroendocrine and immune relationships in postpartum fatigue. MCN Am J Matern Child Nurs. 2005;30:133-8. PMID: 15775810

15. Cubero J, Valero V, Sanchez J et al. The circadian rhythm of tryptophan in breast milk affects the rhythms of 6-sulfatoxymelatonin and sleep in newborn. Neuro Endocrinol Lett. 2005;26:657-61. PMID: 16380706

Administrative Information

LactMed Record Number

946

Last Revision Date

20170411

Disclaimer

Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.

(web3)