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Melatonin Side Effects & Interactions You Should Know About

Melatonin is a hormone produced naturally by the body and is most commonly known for its important role in regulating our body’s cycle of falling asleep and waking up.

Beyond regulating our sleep cycles, melatonin has been found to play important roles including acting as an antioxidant, in females reproductive cycles, in cardiovascular health, as well as immunity. [1] With melatonin supplementation becoming increasingly more popular, it is important that we are well clued up on the side effects and interactions that can occur.


melatonin for sleep

Common Melatonin Side Effects

The most common side effects that have been reported include daytime drowsiness, dizziness, headache and nausea.

With more studies being done on melatonin, further side effects include blood thinning, daytime drowsiness and reduced body temperature have been reported. Below, we take a closer look at the evidence that supports the common and more recent side effects as well as interactions that exist with melatonin supplements.


1. Dizziness/Headache/Nausea

Up to now, research has shown that melatonin supplementation is generally considered safe in the short-term (3 months or less), even when taken in very high doses.[2] In a large review looking at the safety of melatonin supplementation in humans, several studies did, however, report general side effects, including dizziness, headache and nausea[3]. It was concluded, however, that these side effects were equally common in the treatment and placebo groups and could therefore not be linked directly to the melatonin supplement.

 

2. Daytime Drowsiness

In a recent study, it was found that the daytime ingestion of 5 mg melatonin subjectively increased sleepiness. Further findings in the study showed that the melatonin induced drowsiness was not improved even when subjects were exposed to bright light which highlights the importance of taking melatonin at night and not during the day.[4]

These findings are supported by another study which included twenty healthy men and women aged 21-57 years. The study looked at the effects of melatonin (5mg) supplementation and daytime driving performance. The study found that selective attention and selective sleepiness were significantly affected by melatonin but the values still remained with the normal range. [5]


3. Blood-thinning Effects

A single dose of melatonin (3mg) has been shown to significantly lower the levels of blood-clotting markers. [6] This finding was discovered in a 2008 study that included forty-six healthy men (mean age 25 +/- 4 yr.)

The subjects were randomly given either 3 mg of oral melatonin or placebo medication. The study found that within 60 minutes after receiving the melatonin supplement, the subjects presented with lower plasma levels of blood clotting factors. It was concluded that there might be a dose-response relationship between the concentration of melatonin and blood clotting ability.

4. Lowers Body Temperature

One of the most significant Melatonin side effects is its effect on reducing body temperature. In a randomized study done on healthy males, a dosage of  0.5 mg, 3 mg, or 9 mg of melatonin was administered. The study found that, in comparison with placebo, melatonin significantly suppressed core body temperature at the 3-mg and 9-mg doses. Body temperature was only slightly suppressed at the 0.5mg dose. The authors concluded that melatonin supplementation significantly reduces core body temperature in a dose-dependent manner. [7]

common melatonin side effects

 

Important Melatonin Interactions

 

1. Melatonin and blood-thinning medicine

 

Melatonin has been shown to interact with the body’s ability to clot blood and it is therefore not recommended to take melatonin supplements with blood-thinning medication such as warfarin, aspirin and NSAIDs.

There is very limited research confirming the relationship of melatonin with blood thinning. However, in a 2008 study, using a dose of 3mg of melatonin or placebo medication, it was concluded that the administration of a single dose of melatonin is significantly associated with a decrease in blood clotting factors. [8]

Further research on the effects of taking melatonin and blood-thinning is very limited but given the possible effect of blood-thinning, it is advisable to not take melatonin supplements when taking blood-thinning medication such as warfarin, aspirin and NSAIDs.


2. Melatonin and sleeping pills

Research does not support the use of melatonin in conjunction with sleeping aids.

As discussed earlier, Melatonin plays an important role in regulating our ability to fall asleep, with a common side effect being drowsiness. It is therefore not recommended to take melatonin supplements if you are already on any sleeping aids such as. Research has shown that taking melatonin with zolpidem (a commonly used sleeping aid) significantly exacerbates cognitive function deficits when compared to taking zolpidem alone. [9]

 

3. Fertility and Pregnancy

Melatonin may help to support fertility but there is limited research to recommended routine use for fertility and for pregnancy outcomes.

There have been a number of studies that have looked at the impact of Melatonin supplementation in improving fertility and pregnancy outcomes.

One study investigated the role of Melatonin supplementation in 115 patients who failed to become pregnant in a previous cycle of IVF. The study used a dose of 3 mg/day throughout the IVF cycle and found that the fertilization rate was significantly higher in the Melatonin group when compared with their first cycle were no melatonin was administered.

There was a slight improvement in the pregnancy rate in the melatonin group, however, it was not statistically significant.[10] Melatonin use in infertility treatment still lacks sufficient evidence to recommend routine use and there is not enough statistical evidence to support Melatonin supplementation in improving pregnancy outcomes[11]

 

3. Melatonin and Diabetes

There is mixed research on the interaction of melatonin in diabetes. It is not recommended to take melatonin supplements if you suffer from diabetes without consulting your doctor first.

Research suggests that there is a link between Melatonin levels and type 2 diabetes. Patients who suffer from diabetes produce little to no insulin (the hormone responsible for lowering blood sugar levels).

A study looked at the link between melatonin levels and insulin production in healthy individuals. In the study, subjects took 4mg of melatonin before they went to bed at night for a period of 3 months. The researchers compared blood sugar and insulin levels taken the start and end of the treatment period.

After the 3 months of melatonin treatment, all participants had higher levels of blood sugar and the authors concluded that increased Melatonin levels are associated with a decreased ability to produce insulin.[12]
 

Contrast to these findings, however, a more recently published study found that the administration of Melatonin in combination with metformin (a commonly used oral drug in diabetes) significantly improved insulin sensitivity, in a rat model. The authors concluded that the combination of melatonin and metformin could be beneficial in the treatment of type 2 diabetes. [13]

melatonin interactions with medication

 

Melatonin Supplementation for Children

It is known that melatonin supplementation is increasing amongst adults and that it is generally regarded as safe,  but what about children? Melatonin supplementation is being increasingly prescribed for children with sleep disorders. [14]

The potential safety issues in the use of the hormone melatonin in paediatrics were reviewed. It was found that most of the studies that have looked at supplementation in children have had major shortcomings.

Therefore, it is recommended that the administration of melatonin to any child should only be considered once a medical diagnosis of an underlying sleep abnormality has been determined. The authors further concluded that because melatonin is considered a dietary supplement and not a drug in the USA, it has not been appropriately evaluated for safety by the FDA in any population group, including children.

In a larger, more recent review, researchers concluded that Melatonin supplementation can be safe and effective in treating sleep disorders in children but there is still uncertainty on the correct dosage.

The researchers highlighted that the dose of Melatonin given to children needs to be individualized depending on the severity and type of sleep problem.[15] Given the large variety of Melatonin supplements currently available in today’s market and the current inconclusive evidence on Melatonin dosage in children,  your doctor should definably be your first step before considering supplementing your children.

Conclusion

Research shows that general supplementation of Melatonin is generally regarded as safe in adults but it is not recommended in children given the lack of research on appropriate dosing. Common Melatonin side-effects that can occur include headaches, nausea and dizziness.

It is not recommended to take Melatonin supplements during the day due to the risk of day time drowsiness occurring or if you are currently taking any sleeping aids as melatonin has been shown to enhance the effects leading to increased drowsiness.

Furthermore, this supplement has been shown to have interactions with blood-thinning medication and diabetes. Further research is required to determine the safety of using melatonin in these conditions. melatonin for a good night's sleep

Medical Disclaimer


Not intended to treat, diagnose, or cure any disease or ailment. Please read and fully understand the potential adverse effects before using this product. These statements have not been reviewed by the FDA and are not written by a medical professional. Please consult your doctor before using any supplements, especially if you have any medical conditions.

 

Michaela

Michaela

BSc(Med)(Hons) Nutrition & Dietetics Researched & written by Michaela and verified by the Liftmode.com Research Team

 

 

Citations and Supporting Literature

[1] Tordjman, S., Chokron, S., Delorme, R., Charrier, A., Bellissant, E., Jaafari, N., & Fougerou, C. (2017). Melatonin: Pharmacology, Functions and Therapeutic Benefits. Current Neuropharmacology15(3), 434–443.

[2] Buscemi, N., Vandermeer, B., Hooton, N., Pandya, R., Tjosvold, L., Hartling, L., Vohra, S. (2005). The efficacy and safety of exogenous melatonin for primary sleep disorders. A meta-analysis. Journal of general internal medicine20(12), 1151–1158.

[3] Andersen LP, Gögenur I, Rosenberg J, Reiter RJ. ( 2016). The Safety of Melatonin in Humans. Clin Drug Investig, 36(3):169-75.

[4] Lok, R., van Koningsveld, M. J., Gordijn, M. C. M., Beersma, D. G. M., & Hut, R. A. (2019). Daytime melatonin and light independently affect human alertness and body temperature. Journal of Pineal Research.

[6] Wirtz, P. H., Spillmann, M., Bärtschi, C., Ehlert, U., & von Känel, R. (2008). Oral melatonin reduces blood coagulation activity: a placebo-controlled study in healthy young men. Journal of Pineal Research, 44(2), 127–133.

[7] Satoh, K., & Mishima, K. (2001). Hypothermic action of exogenously administered melatonin is dose-dependent in humans. Clinical Neuropharmacology. 24(6), 34-340.

[8] Wirtz, P. H., Spillmann, M., Bärtschi, C., Ehlert, U., & von Känel, R. (2008). Oral melatonin reduces blood coagulation activity: a placebo-controlled study in healthy young men. Journal of Pineal Research, 44(2), 127–133.

[9] Otmani, S., Demazières, A., Staner, C., Jacob, N., Nir, T., Zisapel, N., & Staner, L. (2008). Effects of prolonged-release melatonin, zolpidem, and their combination of psychomotor functions, memory recall, and driving skills in healthy middle-aged and elderly volunteers. Human Psychopharmacology: Clinical and Experimental, 23(8), 693–705.

[10] Tamura H, Takasaki A, Miwa I, Taniguchi K, Maekawa R, Asada H, Taketani T, Matsuoka A, Yamagata Y, Shimamura K, Morioka H, Ishikawa H, Reiter RJ, Sugino N. (2008) Oxidative stress impairs oocyte quality and melatonin protects oocytes from free radical damage and improves fertilisation rate. J Pineal Res, 44(3):280–87.

[11] Fernando, S., & Rombauts, L. (2014). Melatonin: shedding light on infertility?--A review of the recent literature. Journal of ovarian research7, 98.

[12] Paddock C. (2016). Type 2 diabetes: Study explains the link to sleep hormone melatonin. Retrieved July 17 2019, from https://www.medicalnewstoday.com/articles/310321.php

[13] Dantas-Ferreira, R. F., Raingard, H., Dumont, S., Schuster-Klein, C., Guardiola-Lemaitre, B., Pevet, P., & Challet, E. (2018). Melatonin potentiates the effects of metformin on glucose metabolism and food intake in high-fat-fed rats. Endocrinology, Diabetes & Metabolism.

[14] Kennaway, D. J. (2015). Potential safety issues in the use of the hormone melatonin in paediatrics. Journal of Paediatrics and Child Health, 51(6), 584–589.

[15] Esposito, S., Laino, D., D'Alonzo, R., Mencarelli, A., Di Genova, L., Fattorusso, A., Mencaroni, E. (2019). Pediatric sleep disturbances and treatment with melatonin. Journal of translational medicine17(1), 77.