Sleep

Nature’s Sleeping Pill

What if there were a safe and natural supplement that in addition to giving you a deep sleep would provide vivid dreams, eliminate jet lag, and also improve your mood? And what if it enhanced your immune system, could treat a variety of diseases, and… even could prolong your life span?
Melatonin, now available without a prescription, may be that very supplement.

A few years ago researchers in Switzerland gave mice melatonin in their drinking water (Maestroni, 1988). Another group of mice received plain water. At he start of the study all the mice were 19 months old (equivalent to about 60 years in humans) and healthy.

The researchers were surprised when the mice on melatonin showed such a striking improvement in their health, and most remarkably, lived so much longer! And after 5 months on melatonin, astonishing differences in the fur quality and vigor of the two groups became evident. The mean survival time of the untreated mice was 25 months (78 years in humans) versus 31 months (98 years) in the melatonin-treated group!

Melatonin is a natural hormone made by the pineal gland, which is located in the brain.

Melatonin helps to set and control the internal clock that governs the natural rhythms of the body. Each night the pineal gland produces melatonin which helps us fall asleep. Research about this hormone has been going on since it was discovered in 1958. But it is only in the last few years that much attention has been paid to melatonin. One reason for this growing interest is that we are realizing that deep sleep is not the only byproduct of melatonin. We are learning that it has a significant influence on our hormonal, immune, and nervous systems. Research is showing melatonin’s role as a powerful antioxidant, its anti-aging benefits, and its immune-enhancing properties. It is an effective tool to prevent or cure jet lag, an ideal supplement to reset the biological clock in shift workers, and a great medicine for those who have insomnia. Melatonin also may have a future role to play in the treatment of cancer and heart disease, in lowering cholesterol levels, in influencing reproduction, and more. A delightful bonus is that melatonin can promote vivid dreams.

With all these potential influences on our hormonal and immune systems, no wonder melatonin has been clouded by controversy.

A Controversy That’s Bound to Grow

Melatonin supplements became available in health food stores in 1993. Heavy media attention, including CBS, CNN, and major newspaper coverage, was focused on melatonin when a study by MIT researchers showed that it was an effective sleep inducer. Melatonin sales skyrocketed. However, the chief researcher who had directed the study, sent a letter to the press and appeared on CNN to caution consumers, “I hope that melatonin will become an approved drug quickly. Meanwhile no one should buy it and self-medicate.” He argued that there are no agreed-upon dosages, no controls over its purity, and no formal data demonstrating that melatonin is safe. Melatonin sales slumped. The media coverage slowed.

Shortly after this warning, the National Nutritional Foods Association (NNFA), issued an Action Alert to its members: “The leading suppliers and distributors of melatonin products in our industry will be discontinuing distribution of melatonin to health food stores. NNFA agrees with them that melatonin may be inappropriate as a product to be sold in health food stores and urges retailers to seriously consider the propriety of its continued sales.” Nervous health food store managers took melatonin off the shelves. It became more difficult for consumers to purchase melatonin. Many relied on mail order distributors for their supply.

Is Melatonin Effective?

We have found that 80% of all melatonin users like its sleep-promoting effects and would take it again if needed. About 10% did not feel a significant effect or felt it was too weak for them as a sleep aid, and the rest have not had a good experience with melatonin and did not wish to continue with it.

Is Melatonin Safe?

Whenever researchers want to test the dangers of a substance they give it to laboratory animals such as mice. they give progressively higher and higher doses of the substance until a lethal dose (LD) is reached where 50% of the test animals die. This level is called the LD 50. Back in 1967, at the National Heart Institute in Bethesda, Maryland, Barchas and his colleagues gave mice 800 milligrams (mg) per kilogram (kg) of body weight of melatonin. The mice exhibited no significant ill effects. The researchers needed to give more to find the LD 50, but they could not concentrate the melatonin any further in the amount of liquid that the mice had to drink. The 800 mg/kg is equivalent to giving an average-sized human over 50,000 mg. No other effective sleep inducer is this safe. As we’ll discuss later, most people do well with a nightly dose of 3 mg or less.

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 theatre, or even walk down a flight of stairs.

After reading this article, you, in consultation with your physician, will need to decide whether melatonin is appropriate for your needs and whether both of you feel comfortable with its safety.

Melatonin and Longevity

Wouldn’t it be great if science discovered supplements that could prolong our life span? Perhaps that time is not far away. Perhaps that time is now. Perhaps melatonin is one of these supplements.

Life Span Extension in Animals

In the introduction, we discussed the experiment by Maestroni and colleagues, published in 1988, that found an average 20% increase in longevity in middle-aged, male mice when they were given melatonin in their nightly drinking water. The researchers state, “To our surprise, chronic, nightly administration of melatonin resulted in a progressive, striking improvement of the general state of the mice and, most important, in a remarkable prolongation of their life. In fact, starting at 5 months from the initiation of melatonin administration, the body weight of the untreated mice still surviving started to decrease rapidly, and also astonishing differences in the fur and in the general conditions of the 2 groups (vigor, activity, posture) became increasingly evident. Melatonin treatment preserved completely optimal pelage (fur) conditions.”

A similar experiment on middle-aged, male mice, done in 1991 by Pierpaoli and colleagues, also found a 20% increase in life span. What would melatonin do in the young? To find out, Pierpaoli and colleagues gave melatonin every night to young, female mice (strain C3H/He) starting at age 12 months until death. (There are various strains of laboratory mice and the effect of a particular substance may be different on each strain. That’s why it’s important to mention which one.) The average life span in this strain of mice is about 24 months. The age of 12 months (pre-menopause) would correspond roughly to age 35 in humans. To the surprise of everyone, melatonin shortened life span by 6%. A high rate of ovarian cancer occurred in these young mice. Apparently there are cells in the ovaries in this strain that overgrow when stimulated by melatonin, causing tumors. Another strain of young, female mice (NZB) was also given melatonin nightly starting at age 12 months, and they lived longer than the untreated group. A third group of NZB strain female mice was given melatonin at 5 months of age (Pierpaoli, 1994). They also lived longer than those not on melatonin. Obviously, different mouse strains respond to melatonin differently.

It is possible that if the mice who developed ovarian cancer had been given a lower dose of melatonin, they may have fared better. Based purely on a weight ratio, the amount of melatonin given the mice was many times the dose a human would normally use at night for sleep.

How did melatonin affect female mice who already had reached menopause? In one study, when 18 month old post-menopausal mice (strain C57BL/6) were given melatonin nightly, ovarian cancer was not detected. They lived 20% longer than those who were not given melatonin.

How can we interpret these animal studies in order to make practical recommendations for us humans? First, we have to realize that rodents and humans may respond differently to the same medicine. We have seen that even different strains of mice respond differently. We know by experience, however, in countless other studies and with various other medicines that there is often a similarity between the effects of a substance on rodents and that on humans. We should also consider the possibility that while one person may benefit from a medicine, another may be harmed. Just as there are differences in response between different strains of mice, there may be differences in response between different human beings.

In order for us to know what melatonin will do in humans when given for a lifetime, we would need to follow hundreds or thousands of people. Multiple groups would be needed to try different dosages. Such a comprehensive study is not under way at this time. Even if it were, the results would not be available until well into the 21st Century. What shall we do in the meantime?

Different scientists familiar with these studies may recommend different courses of action. One scientist may caution, “Let’s wait a few more years.” Another may advocate, “If we wait, we’ll have to wait decades. I’m 65 now and I’m having trouble sleeping at night. Melatonin provides me with great sleep. In addition it could extend my life span.” Who will eventually be proved right? No one can be sure at this time.

What is the ideal dosage?

Melatonin supplements are currently available in 0.2 mg, 0.3 mg, 0.5 mg, 0.75 mg, 1 mg, 1.5 mg, 2 mg, 3 mg, 5 mg, 10 mg, and 20 mg tablets or capsules. Some bottles list dosages in meg (micro-grams); 1 mg (milligram) equals 1000 mcg. Lozenges, which are dissolved in the mouth, are available in 0.5 mg, 1 mg, 2 mg, 2.5 mg, 3 mg, and 5 mg. In the summer of 1995, a slow release form of melatonin became available. Soon after, a liquid preparation came on the market.

Melatonin cannot be patented for exclusive sale, so a number of companies manufacture and distribute it. A wide range of doses works for people. Each person has a unique physiology, hence, no blanket statements can be made. A person may also require a higher dose during nights when he or she is extremely alert, upset, preoccupied, or had a caffeinated evening drink.

It may be best to swallow a melatonin pill on an empty stomach or with a small meal. Melatonin taken on a full stomach does not seem to be as consistently effective. This may be because the pill is not fully absorbed, or simply absorbed too slowly.

After swallowing a pill, peak levels in the blood are found in about 1 hour. An interesting finding in a previously discussed study (Waldhauser, 1990) was that the amount of melatonin present in the bloodstream of different volunteers sometimes varied by a factor of 300! This shows the uniqueness of each individual’s absorption and metabolism.

Melatonin in the range of 0.1 mg to 5 mg is effective in inducing a natural yawn and maintaining a deep sleep in most people.

An article published in the May, 1995, issue of Clinical Pharmacology and Therapeutics (57:552-8) and titled “Sleep-inducing effects of low doses of melatonin ingested in the evening” gives us a good idea on appropriate dosages. Drs. Zhdanova and Wurtman, from MIT, gave volunteers 0.3 mg of melatonin and found it to be effective. This low dose was able to raise blood melatonin levels above 120 picograms per milliliter, a level present at night in children while in deep sleep (a picogram is one millionth of a milligram).

If you are planning to take melatonin for the first time, start with a dose in the range of 0.1 to 0.5 mg. Most tablets come in doses much higher than this so you may need to break them in small pieces. Capsules can be opened and a portion used. If these low doses are not effective, then you can take more the following nights.

If there is no response to pills, sublingual lozenges can be tried. Lozenges seem to be more consistently effective in inducing sleep than pills since they are not absorbed from the stomach and metabolized by the liver— which can greatly reduce the amount reaching the bloodstream. Instead, the melatonin dissolves in the mouth and directly enters the bloodstream. Some individuals find that a small dose from a lozenge may be as effective as a large dose from a pill.

There are some people who respond weakly even to high doses. Ted, a 23 year old student, informs me, “I took what I believe was an overdose, two 3 mg pills and two 5 mg lozenges, a total of 16 mg. It did seem to induce in me that sleepy state right before one falls asleep, but the feeling wasn’t overwhelming. In fact, I only felt sleepy when I laid on my bed; otherwise I think I could have stayed up longer.”

Wayne, a 24 year old computer programmer from Seattle, asserts, “I have severe chronic insomnia and I’ve used melatonin twice. Neither time did it seem to improve my sleep. (My body is amazingly good at resisting sleep.) Both were 3 mg doses taken just a few minutes before bed.”

Keep in mind that melatonin is subtle compared to the effects of prescription sleeping pills. It doesn’t have their knockout punch. Matthew, a 26 year old teacher, tells me, “I am impressed at the similarity between melatonin and natural sleep. As someone who has suffered periodic bouts of insomnia, melatonin provided natural sleepiness without the drowsiness of some prescription medicines that I’ve taken in the past.” Heather, a 24 year old massage therapist, nods, “Sleep comes on naturally and peacefully.”

Some individuals do very well with small doses. A survey respondent wrote, “I’m 57 years old and have been taking melatonin regularly for insomnia for a year. Previously, I would sleep 4 or 5 hours, then wake up and not be able to go back to sleep. With 1 mg of melatonin I sleep through the night. If I do happen to wake up, I am able to easily fall back asleep. I’ve had no side effects at all and wake up refreshed.”

For most people melatonin is effective the very first night. Some of my patients report feeling an effect after the first week. However, some may take up to a month before noticing a difference. MacFarlane and colleagues also noted this: “Improved sleep is in evidence from the first treatment night, but an increased efficacy is observed with repeated treatments.”

When is the Best Time to Take Melatonin?

People vary widely in their response times. Pills are effective for most people when swallowed about half an hour to 90 minutes before bed. Lozenges dissolved in the mouth seem to work more quickly. You may take them between 10 minutes and an hour before going to bed. Most people notice a natural yawn within half an hour of dosing.

I, personally, do well with 0.25 mg taken 45 minutes before bedtime. When I put my head on the pillow, I’m out! I have found that a low dose is more effective when taken at least an hour or two before bed while a high dose can be taken closer to bedtime. One of the most common mistakes people make with melatonin is taking it too close to bedtime. This is not a prescription sleeping pill and doesn’t work as quickly. For the most part, a good hour is required for best results. Let’s also keep in mind that tablets and lozenges from different manufacturers may be absorbed at different rates.

Terri, a 45 year old social worker, tells me, “I took a 1 mg lozenge right before bed. I didn’t feel any effects from it and had trouble falling asleep. I tried it again a few nights later right before bed. Still no effect. I was almost going to give up on melatonin until you suggested I try it at least 1 hour before bed. This seemed to make all the difference; I went to sleep within a couple of minutes of putting my head on the pillow.”

One survey respondent wrote that he has chronic insomnia and takes 10 mg of melatonin an hour before bed. He wakes up at 3 or 4 am and takes another 10 mg. This works for him; he feels fine the next day. Another user noted that he once woke up at 3 am and couldn’t fall asleep. He hadn’t taken any melatonin the night before. After an hour of tossing in bed, he took two 3 mg pills at 4 am and had trouble getting out of bed the next day. He felt groggy most of the morning. It’s best to take melatonin to accentuate our natural sleep rhythm avoiding the use at a late hour where it could shift our cycle to an undesired time.

One friend has found that breaking a pill in small portions and taking about 0.2 mg 90 minutes before bed and taking another 0.2 mg 30 minutes before bed gives her a better sleep than taking it all at one time. This is a good option for some since melatonin is gradually produced by the pineal gland at night. One could therefore take small doses maybe 2 hours, 1 hour, and 30 minutes before bed. I tried this approach recently, using tiny doses, and it worked well. I must have taken a total of less than 0.3 mg.

These anecdotes indicate the importance of trial and error in finding out the best dose and the best time for your unique self. If melatonin doesn’t work for you initially, don’t give up. Experiment with varying doses and times. You may also try another brand if the first is not effective. As a rule, if you have trouble falling asleep, consider sublinguals. If you have no trouble falling asleep but wake up in the middle of the night or early morning, consider taking a pill just before bed with food, or the slow release form, which stays in your system longer. If you have difficulty in both falling asleep and staying asleep, you could combine low doses of sublinguals and the slow release.

Slow-release (also known as sustained, time, or controlled-release) melatonin will likely become more popular in the future. A 1995 study published in The Lancet found a 2 mg slow release pill to be very helpful in older insomniacs, especially after regular use for 3 weeks (Garfinkel). It is possible that smaller doses, such as 0.5 mg, may also be just as effective.

Those who are used to taking prescription sleeping pills may require a few days or weeks before noticing the subtler effects of melatonin.