In France, melatonin is used in medicinal products, extemporaneous preparations and food supplements. Melatonin is a hormone secreted naturally during the night. One of its physiological functions is to promote sleep. In addition to its effects on the biological clock, melatonin has other properties: modulation of mood and the immune system, regulation of body temperature and intestinal motricity. It also has vasodilatory, vasoconstrictor and proinflammatory activity. Under certain circumstances, or when interacting with other substances, these physiological effects can lead to the occurrence of adverse effects.
Ninety cases of adverse effects occurring following the intake of food supplements containing melatonin have been reported to the National nutrivigilance scheme run by ANSES. A variety of different effects have been reported: general symptoms (headaches, dizziness, drowsiness, nightmares, irritability) as well as neurological (tremors, migraine) and digestive (nausea, vomiting, abdominal pain) disorders. Each case was analysed individually and the conclusions were shared with the parties reporting the cases and the manufacturers.
The retrospective analysis of all these cases led ANSES to initiate an assessment of the risks associated with the consumption of these food supplements. The risks were characterised by an in-depth analysis of the literature, leading ANSES to issue recommendations aimed at manufacturers/producers, consumers and health professionals.
The Agency's recommendations for consumers
The analysis of the reported cases and the scientific literature led the Agency to recommend that people suffering from inflammatory or autoimmune diseases, as well as pregnant and breastfeeding women, children and adolescents, and anyone carrying out any activity requiring sustained vigilance where drowsiness could pose a safety problem should not consume melatonin in the form of a food supplement.
People with epilepsy, asthma, or suffering from mood, behaviour or personality disorders, or anyone being treated with medication should seek medical advice regarding the consumption of melatonin in the form of food supplements.
In the absence of sufficient data on the long-term effects of melatonin consumption, the Agency recommends limiting the consumption of these food supplements to occasional use.
More generally, the Agency recommends that consumers seek medical advice before consuming food supplements and inform their doctor that they are taking food supplements.
In France, the regulations authorise the marketing of food supplements providing less than 2 mg of melatonin per day. Given the variability in the status of melatonin and the regulatory limits governing its use within the European Union, and in the absence of sufficient data on the safety of daily consumption of 2 mg of melatonin, the Agency has questions about the place of melatonin on the market in food supplement form at doses comparable to those of the medicinal product. It believes it necessary for a harmonised regulatory framework to be defined at European level on the basis of safety studies conducted for doses below 2 mg.
ANSES also reminds healthcare professionals of the need to report to the national nutrivigilance scheme any adverse effects likely to be associated with the consumption of food supplements about which they become aware.
Lastly, ANSES emphasises the value of setting up a joint international project on the monitoring of adverse effects associated with the consumption of food supplements.