Melatonin : Safety

by MedlinePlus

(Page 5 of 6)

Allergies

There are rare reports of allergic skin reactions after taking melatonin by mouth. Melatonin has been linked to a case of autoimmune hepatitis.

Side Effects and Warnings

General: Based on available studies and clinical use, melatonin is generally regarded as safe in recommended doses for short-term use. Available trials report that overall adverse effects are not significantly more common with melatonin than placebo. However, case reports raise concerns about risks of blood clotting abnormalities (particularly in patients taking warfarin), increased risk of seizure, and disorientation with overdose.

Neurologic (general): Commonly reported adverse effects include fatigue, dizziness, headache, irritability, and sleepiness, although these effects may occur due to jet-lag and not to melatonin itself. Fatigue may particularly occur with morning use or high doses (greater than 50mg), and irregular sleep-wake cycles may occur. Disorientation, confusion, sleepwalking, vivid dreams and nightmares have also been noted, with effects often resolving after cessation of melatonin. Due to risk of daytime sleepiness, caution should be taken by those driving or operating heavy machinery. Headache has been reported. Ataxia (difficulties with walking and balance) may occur following overdose.

Neurologic (seizure risk): It has been suggested that melatonin may lower seizure threshold and increase the risk of seizure, particularly in children with severe neurologic disorders, as reported in 4 out of 6 children in one study and in an adult in whom symptoms recurred when melatonin was given a second time. However, multiple other studies actually report reduced incidence of seizure with regular melatonin use. This remains an area of controversy. Patients with seizure disorder taking melatonin should be monitored closely by a healthcare professional.

Psychiatric: Mood changes have been reported, including giddiness and dysphoria (sadness). Psychotic symptoms have been reported in at least two cases, including hallucinations and paranoia, possibly due to overdose. Patients with underlying major depression or psychotic disorders taking melatonin should be monitored closely by a healthcare professional.

Hematologic (blood clotting abnormalities): There are at least six reported cases of alterations in prothrombin time (a measurement of blood clotting ability) in patients taking both melatonin and the blood-thinning medication warfarin (Coumadin®). These cases have noted decreases in prothrombin time (PT), which would tend to decrease the effects of warfarin and increase the risk of blood clots. However, blood clots have not been noted in these patients. Rather, minor bleeding was noted in two of these cases (nosebleed and internal eye bleed), which may have been due to the blood-thinning effects of warfarin alone without a relationship to use of melatonin, or possibly to an interaction between melatonin and warfarin. It is not known if melatonin has effects on blood clotting in people who are not taking warfarin. Based on these reports, melatonin should be avoided in patients using warfarin, and possibly in patients taking other blood-thinning medications or with clotting disorders.

Cardiovascular: Melatonin may cause drops in blood pressure, as observed in animals and in preliminary human research. Whether these reductions in blood pressure are clinically relevant is not clear. Caution is advised in patients taking medications that may also lower blood pressure. Based on preliminary evidence, increases in cholesterol levels may occur. Preliminary research suggests that regular use of melatonin may increase atherosclerotic plaque buildup in humans and animals. Caution is therefore advised in patients with high cholesterol levels, atherosclerosis, or at risk for cardiovascular disease. There are several poorly described reports of abnormal heart rhythms, fast heart rate, or chest pain, although in most cases patients were taking other drugs that could account for these symptoms.

Endocrine (blood sugar elevations): Elevated blood sugar levels (hyperglycemia) have been reported in patients with type 1 diabetes (insulin-dependent diabetes) and low doses of melatonin have reduced glucose tolerance and insulin sensitivity. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Serum glucose levels may need to be monitored by a healthcare provider, and medication adjustments may be necessary.

Endocrine (hormonal effects): Hormonal effects are reported, including decreases or increases in levels of luteinizing hormone, progesterone, estradiol, thyroid hormone (T4 and T3), growth hormone, prolactin, cortisol, oxytocin and vasopressin, although there are other reports of no significant hormonal effects. Variations may occur based on underlying patient characteristics. Gynecomastia (increased breast size) has been reported in men, as well as decreased sperm count (both which resolved with cessation of melatonin). Decreased sperm motility has been reported in rats and humans.

Gastrointestinal: Mild gastrointestinal distress commonly occurs, including nausea, vomiting, or cramping. Melatonin has been linked to a case of autoimmune hepatitis and with triggering of Crohn's disease symptoms.

Ocular (glaucoma): It has been theorized that due to effects on photoreceptor renewal in the eye, high doses of melatonin may increase intraocular pressure and the risk of glaucoma, age-related maculopathy and myopia, or retinal damage. However, there is preliminary evidence that melatonin may actually decrease intraocular pressure in the eye, and it has been suggested as a possible therapy for glaucoma. Patients with glaucoma taking melatonin should be monitored by a healthcare professional.

Pregnancy and Breastfeeding

Melatonin supplementation should be avoided in women who are pregnant or attempting to become pregnant, based on possible hormonal effects, including alterations of pituitary-ovarian function and potential inhibition of ovulation or uterine contractions. High levels of melatonin during pregnancy may increase the risk of developmental disorders. In animal studies, melatonin is detected in breast milk and therefore should be avoided during breastfeeding. In men, decreased sperm motility and decreased sperm count are reported with use of melatonin.

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