insomnia

Why Are There So Few High-Quality Melatonin Studies? 

Author: Dr. Stephen Chaney

Insomnia is a major problem in our world. The reasons are not hard to see:

• We live in troubled times. Conflicts abound and the days of reasoned discussions and compromise have become distant memories.

• We live in difficult times. Many of us have lost jobs or loved ones. We have all lost our freedoms. We live in forced isolation. The consoling hug of a friend or neighbor has become a distant memory.

• We live in fast-paced times. We are constantly “on” from the moment our feet hit the floor in the morning to the moment our head hits the pillow at night. We are also on our devices until the time we go to bed, and most of the news on those devices is bad.

The reasons are also physiological:

• When we turn off the lights our pineal gland produces a hormone called melatonin that calms our brain and prepares us for sleep.

• However, as we age our body produces less melatonin because:

• • Our pineal gland produces less melatonin.

• • Many medications commonly prescribed to older Americans suppress melatonin synthesis.

Whatever the reason, insomnia has become a major problem for millions of Americans.

• One third of all Americans and 69% of older Americans suffer from insomnia. That is a concern because severe insomnia:

• Affects their quality of work.

• Affects their quality of life.

• Increases the risk of accidents.

Medications abound, but they have a long list of side effects. Plus, long term drug use can result in tolerance (the drug loses its effectiveness) and/or dependence (sleep without the drug becomes impossible).

It is no wonder melatonin supplements have become popular among people who have trouble getting a good night’s sleep.

People have been asking me about melatonin supplements. “Do they work? Are they safe?”

It turns out that these aren’t easy questions to answer. Most published studies on melatonin are poor quality and/or have been performed by the company that wants to sell you their melatonin supplement. This raises the question, “What is the truth about melatonin?”

Fortunately, I came across a recent study (F Auld et al, Sleep Medicine Reviews, 34: 10-22, 2017) which is a review and meta-analysis that included only high-quality studies in its analysis. This is the one I will discuss today.

How Was This Study Done?

The scientists in charge of this review and meta-analysis started by identifying 5030 studies of the effect of melatonin on various aspects of sleep that had been performed between 1990 and May 2015. Next, they excluded all poor-quality studies from their analysis.

I will list the exclusion criteria below with comments on why these exclusion criteria are important.

#1: Commercially sponsored research: You will often see clinical studies of melatonin supplements reported on their company’s website. The graphs look impressive. The website will say something like. “Our scientists found…” My question is, “If the scientists had not found that their company’s product worked, would they have a job tomorrow?”

Sometimes the research has been done by outside scientists who were supported by funding from the company. These studies are sometimes biased in favor of the company’s product.

#2: Unpublished research: Many companies will cite unpublished “white papers” showing their products work. Often these studies have been done by scientists not directly affiliated with the company. While that sounds impressive, my questions are, “What weaknesses in the study are they trying to hide? Why are they afraid to submit their study to the rigors of peer review so it can be published?”

#3: Research that did not use well established criteria and measurements of sleep disorders: There is an international classification system and rigorous protocols for evaluating sleep disorders. Studies using subjective measurements of sleep quality instead of internationally- recognized protocols are considered low-quality. [For example, a subjective measurement of sleep quality would be to ask subjects, “Did you sleep better?” Whereas, the gold standard objective protocol for sleep quality measures brain waves, heart and breathing rates, and eye and leg movements.]

#4: Research design that was not placebo-controlled. Many of the published clinical studies just gave melatonin to their subjects and asked if sleep quality improved. The placebo effect for something as subjective as sleep quality can be huge. Without a placebo control those studies are worthless.

#5: Research design that was not blinded: The investigators only included double- and single-blinded studies in their analysis. In the single-blinded studies the subjects did not know whether they got melatonin or the placebo. This is the most important aspect of blinding because it avoids the placebo effect.

In double-blinded studies, neither the subjects nor the investigators know who got melatonin and who got the placebo. This is considered the “gold standard” of clinical studies, but investigator blinding is only important when investigators are using subjective criteria to measure outcomes.

#6: Research design that was not randomized. Randomization simply means that the subjects were randomly assigned to the melatonin and placebo groups. This assures that the two groups are alike in every characteristic except whether they received melatonin or placebo.

Once they had excluded all low-quality studies, the investigators were left with 12 high-quality studies. [You didn’t misread that. They started by identifying 5030 studies on melatonin and, after carefully analyzing those studies, ended up with only 12 high-quality studies.] I can’t resist making two comments here.

• Now you understand why many scientists are skeptical about the value of melatonin. There are too many low-quality studies.

• Now you understand why I chose this particular paper to report on in today’s “Health Tips From the Professor”.

Most of the high-quality studies were small (had relatively few subjects), so the investigators combined studies of similar design in their meta-analysis.

They were able to assess the effect of melatonin supplements on something called sleep latency (the time it takes to fall asleep). This can be a problem at any age but is most common in the elderly.

What Is The Truth About Melatonin?

The investigators identified five high-quality randomized, blinded, placebo-controlled clinical studies with a total of 1,113 subjects that addressed sleep latency (the time it takes to fall asleep). Subjects were given 2-3 mg of melatonin and the studies lasted 4-5 weeks.

When they combined the data from all 5 studies, there was a highly significant reduction in the time to fall asleep for melatonin-treated subjects compared to placebo. The p value was 0.004 (For comparison, p values <0.05 are considered significant, and p values <0.01 are considered highly significant.)

There were a few high-quality studies addressing the effect of melatonin on other sleep disorders. There appeared to be a beneficial effect of melatonin on some of those disorders, but there were not enough subjects in these studies for the effect of melatonin supplementation to be statistically significant.

The investigators concluded, “These findings highlight the potential importance of melatonin in treating certain sleep disorders. Meta-analysis of the data emphasized in particular the improvement in sleep latency [time it takes to fall asleep] with melatonin in these patients.”

Why Are There So Few High-Quality Melatonin Studies?

The investigators went on to say, “The development of large-scale, randomized, placebo-controlled trials is recommended to provide further evidence for therapeutic use of melatonin in a variety of sleep difficulties.” However, they acknowledged that future large-scale studies of melatonin supplements are unlikely.

In the words of the authors, “Future research may be hindered by the…lack of financial incentives that may decrease motivation to undertake such trials. Funding agencies are more likely to support research on novel medications, which leads to new treatments and increased revenue for pharmaceutical companies, than to supply funding for a supplement (melatonin) that has been easily purchased over the counter since the 1990’s.”

Finally, someone has pointed out the elephant in the room. There is a good reason that it is so hard to find large, high-quality studies on supplements – and it is called money. It takes lots of money to fund large high-quality clinical studies. Companies don’t make enough money from supplement sales to justify those kinds of studies.

Let me give you an example. There is a sleep disorder called “Non 24-hour sleep wake syndrome” in blind patients. Simply put, the pineal gland relies on the transition from light to darkness to regulate when melatonin is released. If a blind person cannot distinguish between light and darkness, they have no signal for melatonin release. They have no physiological signal that it is time to sleep.

Sometimes they can overcome this with a set bedtime every day. However, some blind people really struggle falling asleep and waking up on a regular schedule.

In the review I described above, two very small high-quality studies were identified that suggested melatonin supplementation may help blind people normalize their sleep and wake times. However, the studies were too small to be statistically significant.

On the other hand, a drug company spent hundreds of thousands of dollars developing and testing a drug which mimics the effect of melatonin. Because the drug does not occur in nature, they could patent it. And because they could afford to pay for large-scale, randomized, placebo-controlled clinical trials of the drug, the FDA approved it. They will probably make millions from this drug. You may have even seen it advertised on TV.

How Can You Get A Good Night’s Sleep?

The study described above confirms that melatonin is effective at reducing sleep latency (the time it takes to fall asleep). It may be useful for other sleep disorders, but the evidence to support those uses is inconclusive at present.

However, holistic approaches are always best. If you toss and turn at night, you might want to start by trying these “sleep hygiene” tips from the CDC:

• Be consistent. Go to bed at the same time each night and get up at the same time each morning, including on the weekends.

• Make sure your bedroom is quiet, dark, relaxing, and at a comfortable temperature.

• Remove electronic devices, such as TVs, computers, and smart phones, from the bedroom.

• Avoid large meals, caffeine, and alcohol before bedtime.

• Get some exercise. Being physically active during the day can help you fall asleep more easily at night.

You may also want to try relaxation techniques like yoga before bedtime.

When sleep hygiene fails, try melatonin to help you fall asleep. Here are a few things to know:

• Melatonin is cleared from the body very rapidly (usually within 1-2 hours).

• • That means melatonin is much less likely to cause drowsiness the next morning than many of the insomnia drugs.

• • It also means that melatonin helps you fall asleep, as the review and meta-analysis described above confirmed. However, it doesn’t stick around long enough to help you stay asleep. Other herbs like valerian are more effective for that purpose.

• Our ability to clear melatonin from our system declines as we age.

• • Therefore, doses of 2 or 3 mg are usually recommended for people over 50, while 5 or 10 mg are sometimes used for teenagers and young adults.

• • However, we are all different, so you may need to experiment to find the best dose for you.

• Melatonin has remarkably few side effects compared to the widely prescribed insomnia drugs. It also appears less likely to create dependence.

• Melatonin is often considered an occasional use supplement.

• • That is fine if you only have trouble falling asleep occasionally.

• • If you suffer from insomnia on a regular basis, you will be comforted to know that clinical studies have reported no side effects or dependency with daily use of low-dose melatonin for up to 6 months.

• • However, if you do have chronic insomnia, it is always a good idea to discuss your situation with your health professional to make sure it is not caused by an underlying medical condition.

The Bottom Line

Insomnia is a major problem in our world. Medications abound, but they have a long list of side effects. Plus, long term drug use can result in tolerance (the drug loses its effectiveness) and/or dependence (sleep without the drug becomes impossible).

It is no wonder melatonin supplements have become popular among people who have trouble getting a good night’s sleep. People have been asking me about melatonin supplements. “Do they work? Are they safe?”

It turns out these are not easy questions to answer. Most published studies on melatonin are poor quality and/or have been performed by the company that wants to sell you their melatonin supplement. This raises the question, “What is the truth about melatonin?”

Fortunately, I came across a recent review and meta-analysis that included only high-quality studies in its analysis. This study concluded that melatonin is effective at reducing sleep latency (the time it takes to fall asleep). It may be useful for other sleep disorders, but the evidence to support those uses is inconclusive at present.

For more details about this study, how to use melatonin, and a holistic approach to improve your quality of sleep read the article above.

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure, or prevent any disease.