Risks of Melatonin Use in Children

Evidence indicates that the use of melatonin among children increased from 0.1% to 0.7% between 2007 and 2012 (Black et al. 2015). It is tempting to speculate that social changes, such as the growth in the number of families with two working parents, an increase in stressors, and an apparent elevation of profound fatigue may have contributed to increased reliance on sleep aids such as melatonin, which do not have proven long-term safety.

Melatonin is an indoleamine neurohormone synthesized from tryptophan and secreted by the pineal gland. Like most hormones, melatonin interacts with many families of receptors and has a range of target organ effects. Among the most prominent effects are those involving chronobiology/circadian rhythms, antioxidation, anti-inflammation, and free radical scavenging (Kor et al. 2014). 

The off-label use of melatonin among children appears to be increasing in the general pediatric population (Hartz et al. 2015). Despite the fact that melatonin continues to be used to promote sleep onset in children, safety evaluation and large clinical trials with healthy children who suffer with delayed sleep and insomnia are limited. Nonetheless, support for the use of melatonin derives from clinical studies of both immediate and extended release forms in children who suffer developmental disorders, autism, ADHD, seizure disorders, and type II diabetes (Bruni et al. 2015; Schwichtenberg and Malow 2015; Ayyash et al. 2015; Bendz and Scates 2010).

Despite a consensus that melatonin is safe and effective in these patients, we agree with others that a prudent caveat is that treatment with this hormone must be restricted to short-term use. Apart from the scarcity of rigorous safety studies, there are a number of overarching reasons for caution.

Melatonin is often sold as an herbal supplement. There are no regulated manufacturing standards in place for many herbal compounds, and some marketed supplements have been found to be contaminated with toxic metals or pharmaceutical agents. Most importantly, the public literature indicates melatonin has not undergone the formal safety testing expected for a new drug, especially regarding long-term safety in children (Kennaway 2015). 

The risk of bacterial contamination is also present in any pharmacologically active substance prepared outside the hygiene, standards, and practices of the regulatory environment. Moreover, the use of melatonin derived from animal pineal tissue may carry the risk of viral contamination or the means of transmitting viral material. Mundane risks of melatonin at the conventional pediatric dose have been reported to include morning drowsiness, increased enuresis, depressed mood and/or irritability, abdominal pain, headache, and dizziness (Rossignol & Frye 2011).

The use of melatonin in special populations of patients has demonstrated that occasional use in general populations is likely appropriate and safe, but the apparent consensus from pediatricians seems to be not for more than seven to 10 days at a time and never with a greater frequency than two or three times a year.

The principal risk of chronic melatonin use in prepubertal and pubertal children may involve Gonadotropin Inhibitory Hormone (GnIH). This neurohormone was found to have a direct opposing effect on Gonadotropin Releasing Hormone (GnRH), a critical peptide in all mammals for the development of normal puberty and successful fertility (Ubuka et al. 2005; Chowdhury et al. 2010).

In animal studies, chronically administered melatonin increases the production of GnIH. In a recent study, birds were given melatonin via injection and had triple the levels of GnIH in their body as a result. Genetic models involving melatonin’s effects confirm that melatonin increases the messenger RNA needed to produce GnIH. Studies in rodent models confirmed that melatonin binds directly to neurons in the hypothalamus brain tissue, which is associated with increased production of GnIH. The end effect was associated with a significant decrease in size and function of the testes and ovaries (Gingerich et al. 2009).

In summary, melatonin is likely safe and effective in promoting sleep in healthy children with benign sleep problems otherwise unresponsive to sleep hygiene management. However, only products known to be synthetically manufactured under stringent control should be administered and only in physician-prescribed pediatric dose ranges over short time periods. The theoretical possibility that reproductive organs may be adversely affected during the critical periods of growth and development should give us pause until more rigorous safety and toxicology data are available.

References cited in this article are available from the authors.

Roger Clemens, DrPH, CFS, Contributing Editor
Adjunct Professor, Univ. of Southern
California School of Pharmacy, Los Angeles, Calif.
[email protected]

Heather Rodriguez, RD, a member of IFT, is a
clinical dietitian with the Peterson Regional
Medical Center, Kerrville, Texas
([email protected])