When human subjects were given as much as 6000 mg nightly for 1 month, some of them complained of abdominal discomfort (Waldhauser, 1990). These high doses did lead to sleepiness the next day, but only for a few hours. No serious side effects were reported. In a longer-term study using high doses, ovarian function was inhibited (similar to the effect of birth control pills) when women took 300 mg nightly for 4 months (Voordouw, 1992). No other side effects were noted. The researchers speculate that high doses of melatonin could be used as an effective oral contraceptive. In some rodent studies, long-term supplementation with melatonin at high doses has led to reduction of sex hormones such as testosterone and shrinking of the size of gonads.
When 6 healthy men were given 2 mg of melatonin each evening for 2 months, no changes in testosterone or other hormone levels were found (Terzolo, 1990).
Twenty young, healthy volunteers were kept in a sleep laboratory for several consecutive nights and were monitored and subjected to a battery of tests (Waldhauser, 1990). After a few nights of this routine, half of the subjects were given a placebo and the other half were given 80 mg of melatonin. Those who received melatonin spent less time in bed falling asleep and had fewer awakenings during the night. There was little or no hangover effect the next morning. In fact, the volunteers seemed to perform better in different mental tests and felt more balanced and active. They had a sensation of well-being and emotional stability. This pleasant feeling lasted several hours.
Since melatonin is produced naturally, the body has evolved mechanisms to remove excessive amounts. It is metabolized by the liver and possibly other organs. No reports of any serious side effects have yet been reported in the medical literature. Only rare individuals I have treated have reported any significant complaints. Almost all the side effects reported have been minor and have quickly disappeared upon discontinuation. I do want to emphasize that melatonin is a new product on the market. It will take many more years before we fully understand all potential positive and/or negative effects.
No substance on this planet can be guaranteed to be 100% safe. Our drinking water can be contaminated. Pure water can even be fatal if a person consumes enormous amounts at one sitting. No activity we engage in is fully safe either. We take a risk every time we go skiing, get in the car to go to the movie theater, or even walk down a flight of stairs.
The National Nutritional Foods Association, by reviewing my book in its August, 1995, newsletter mailed to thousands of health food stores, appeared to soften, or reconsider, its position against the sale of melatonin: "Many NNFA members continue to distribute or sell melatonin, or have begun to do so since the April 11, 1994, alert was sent. That being the case, it would seem advantageous to them and to the consumer to learn as much as possible about this substance. A good way to accomplish this is by reading Dr. Ray Sahelian's book."
On the other hand, in the September, 1995, issue of Modern Medicine, a publication mailed to over 120,000 physicians nationwide, Dr. Wurtman reaffirmed his position, "I am actively discouraging people from taking melatonin until an adequate preparation is available, which could be very soon." On September 12, 1995, Interneuron Pharmaceuticals announced that it had been issued a use patent from the US Patent and Trademark office to sell a low dose (0.3 mg), non-prescription melatonin formulation.