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Should You Worry About Serious Melatonin Side Effects?

Melatonin is a very popular dietary supplement. How good is it for promoting sleep. Are there melatonin side effects you should know about?
Should You Worry About Serious Melatonin Side Effects?
MOSCOW – SEPTEMBER 24, 2017: Melatonin tablets by Natrol company. Illustrative editorial photo

More than three million Americans take melatonin to get to sleep. That’s twice the number that used this supplement in 2007 (National Center for Complementary and Integrative Health). This makes melatonin one of the most popular natural products on pharmacy and health food store shelves. How effective is it for promoting sleep? Are there melatonin side effects people should be aware of. This reader wants to know:

Melatonin Is Helpful but Not Perfect:

Q. I have taken zolpidem (Ambien) for years. You have written about the dangers of such sleep aids, so I decided to cut back. I spent several weeks hardly sleeping at all.

Melatonin has been helpful, though not perfect. Are there melatonin side effects I should know about?

Where Does Melatonin Come From?

A. Your body makes melatonin. When it gets dark, specialized cells in the eye send messages to the brain. Eventually the pineal gland responds by secreting melatonin. Some experts have called melatonin a hormone of darkness rather than a sleep hormone.

Our ancestors did not have computers, tablets or smart phones stimulating their retinas. Go back further and humans did not have electric lights. They went to sleep earlier because candlelight was not that powerful.

These days we are surrounded by bright lights. And we stare at our screens, often right up till bedtime. Researchers have discovered that light exposure has a profound impact on melatonin production (Journal of Clinical Endocrinology & Metabolism, March, 2011):

Results:

“Compared with dim light, exposure to room light before bedtime suppressed melatonin, resulting in a later melatonin onset in 99.0% of individuals and shortening melatonin duration by about 90 min. Also, exposure to room light during the usual hours of sleep suppressed melatonin by greater than 50% in most (85%) trials.

Conclusions:

“These findings indicate that room light exerts a profound suppressive effect on melatonin levels and shortens the body’s internal representation of night duration. Hence, chronically exposing oneself to electrical lighting in the late evening disrupts melatonin signaling and could therefore potentially impact sleep, thermoregulation, blood pressure, and glucose homeostasis.”

When Do Melatonin Levels Peak in the Body?

The later it gets at night, the more melatonin the body makes. Peak levels of melatonin normally occur between 2 and 4 am (Scoliosis, April 4, 2007). Any student who has pulled an all-nighter to work on a paper or prepare for an exam knows that fighting off sleepiness gets hardest between 2 and 4 in the morning.

Does Melatonin Work to Help People Sleep?

Melatonin has been used to help people like you reduce their reliance on benzodiazepine or z-type sleeping pills such as zolpidem (European Journal of Pharmacology, Sep. 5, 2015).  A randomized double-blind placebo-controlled trial showed that melatonin could improve sleep quality in people who have suffered traumatic brain injury (BMC Medicine, Jan. 19, 2018).

A meta-analysis of randomized, double-blind, placebo-controlled trials concluded that “Melatonin appears to be effective and safe in improving sleep quality in patients with AD” (International Journal of Geriatric Psychiatry, Jan. 2017).

It has also been used to help cancer patients sleep (Aging Clinical and Experimental Research, Oct. 2013).  A Cochrane Collaboration review suggests that night shift workers may sleep longer after taking melatonin (Cochrane Database of Systematic Reviews, Aug. 12, 2014). Another independent Cochrane analysis of melatonin for coping with jet lag concluded (Cochrane Database of Systematic Reviews, 2002):

“Melatonin is remarkably effective in preventing or reducing jet-lag, and occasional short-term use appears to be safe. It should be recommended to adult travelers flying across five or more time zones, particularly in an easterly direction, and especially if they have experienced jet-lag on previous journeys. Travellers crossing 2-4 time zones can also use it if need be. The pharmacology and toxicology of melatonin needs systematic study, and routine pharmaceutical quality control of melatonin products must be established. The effects of melatonin in people with epilepsy, and a possible interaction with warfarin, need investigation.”

Drugs That Deplete the Body of Melatonin:

Many health professionals are unaware that medications can reduce melatonin levels in the body. The University of Maryland Medical Center has gathered a list of “Drugs that Deplete: Melatonin.”

Here are just a few examples:

Corticosteroids (oral, inhaled and topical):

Budesonide (found in Rhinocort Aqua, Symbicort)

Fluticasone (found in Advair, Flonase and Flovent)

Hydrocortisone

Prednisone

Triamcinolone (in Azmacort)

NSAIDs (nonsteroidal anti-inflammatory drugs):

Diclofenac (found in Cataflam, Voltaren)

Ibuprofen (Advil, Motrin IB, etc)

Naproxen (Aleve, Naprosyn)

Meloxicam (Mobic)

Beta Blocker Heart Meds:

Atenolol

Metoprolol

Propranolol

Should people taking drugs that deplete melatonin from the body take extra melatonin? As far as we can tell, that question has not been answered with good research. Many people would like to have an answer!

Are Melatonin Side Effects Serious?

As far as we can tell, melatonin side effects are rarely, if ever, serious. Some people report nausea, dizziness or headaches. We were intrigued to learn that in Europe, melatonin is generally not sold over the counter in most pharmacies or health food stores. It is usually found as a prescription drug (Circadin).

We were surprised to discover that there have not been a lot of large, long-term, well-controlled melatonin trials to assess safety. That said, a review of most of the small, published trials to date concluded that (Clinical Drug Investigation, March, 2016):

“melatonin is safe for short-term use, even when given in extreme doses. Mild adverse effects, such as dizziness, headache, nausea and sleepiness have been reported in levels corresponding to placebo treatments. Final conclusions concerning long-term safety of melatonin are limited by a general lack of randomized, double blind, placebo-controlled studies, and methodical weaknesses in the reporting of possible adverse effects. However, the sparse data available suggest no serious adverse effects, even with long-term use.”

Some experts have raised concerns about drug interactions. For example: would people taking blood thinners be at greater risk of hemorrhage if they also take melatonin? Sleeping pills like zolpidem (Ambien) may be more dangerous when combined with melatonin. People should always ask the pharmacist and physician to check for such interactions.

What About Dependence as a Melatonin Side Effect?

Unlike many prescription sleeping pills or anti-anxiety agents, melatonin does not appear to cause withdrawal symptoms when stopped. The authors of the review of melatonin state:

“melatonin is neither physiologically nor psychologically addictive.”

A study of melatonin PR (prolonged release 2 mg) was published in the journal Drugs & Aging (Nov. 2012). It concluded:

“In 3-week and 6-month, randomized, double-blind clinical trials in patients with primary insomnia aged ≥55 years, melatonin PR 2 mg 1-2 h before bedtime was associated with significant improvements relative to placebo in many sleep and daytime parameters, including sleep quality and latency, morning alertness and health-related quality of life. Melatonin PR 2 mg was very well tolerated in clinical trials in older patients, with a tolerability profile that was similar to that of placebo. Short- or longer-term treatment with melatonin PR 2 mg was not associated with dependence, tolerance, rebound insomnia or withdrawal symptoms.”

An Unresolved Melatonin Side Effect Issue:

All this is quite comforting. One issue that remains unresolved, however, does concern us. When people take hormone pills, the body may cut back on its own production of that hormone. Will taking so-called exogenous melatonin interfere with the body’s own production of melatonin? One short-term study (seven days) suggested that was not a problem (Journal of Pineal Research, Jan. 1997). We would like to see much longer-term investigations to verify that this is not a problem.

Other Benefits of Melatonin:

There is some suggestion that melatonin may reduce “the severity of essential hypertension” and “should be more widely considered.” This was reported in the Annals of Medicine (May 6, 2010). The authors also suggest it may be helpful for patients suffering from heart failure.

There has been some research to suggest that women with low melatonin levels may be at increased risk for breast cancer. Ditto for men and prostate cancer. Whether supplementing with external (exogenous) melatonin will lower the risk for these tumors is yet to be proven.

Also up for consideration are claims that melatonin might help moderate tinnitus symptoms (ringing in the ears). There have also been claims that this hormone could help ease symptoms of overactive bladder. We would like to see better research before recommending melatonin for such purposes.

Increase Melatonin Levels Naturally:

Did you know that Montmorency cherries are rich in melatonin? Studies have shown that drinking tart cherry juice in the afternoon or evening can improve sleep quality and duration (European Journal of Nutrition, Dec., 2012; Journal of Nutrition, Health & Aging, vol. 17 No. 6, 2013).

Learn more at this link:

Overcoming Insomnia with Tart Cherry Juice

Stories from Readers:

Lou Ann is a runner in Raleigh. She says beware unexpected melatonin side effects:

“I would not recommend taking Melatonin on a daily basis if you are an athlete. I have trained for and have run 9 marathons. I started taking Melatonin to help me sleep in the fall 2017.

“During an 18 mile run, my body essentially shut down and my pulse dropped to 32. I had to call 911 and be taken to the emergency room where I was told I had a vagal response and was about to faint. I stopped the Melatonin and was able to complete a 20 mile training run and successfully run my marathon. I am convinced it was the Melatonin. I had been taking it every night for a couple weeks.”

Sarah in Charleston, SC, loves melatonin and raisins:

“3 mg Melatonin work beautifully for me! I got a big-box store brand of tablets and chew one about an hour before bedtime. It doesn’t help to take it immediately before bedtime.

“Also tried your suggestion of some raisins before bed to keep from getting up in the nite. Why they work I don’t know, and don’t care, but it’s miraculous! I get up only once, if at all!”

Joy in Florida reports good results with sublingual melatonin:

“I went almost three weeks of barely sleeping trying to quit Ambien cold turkey. Melatonin (1mg) dissolved under my tongue worked well or a product called Midnight which contains 1.5 mg Melatonin with lemon balm, chamomile, and lavender. Midnight also can be purchased as a CVS store brand for a few dollars less and is the exact same formulation as Midnight. You can also take it again in the middle of the night if you wake up, as long as you have 3 hours left to sleep.”

Ruby in NC got no benefit from a whopping dose of melatonin:

“Don’t waste your money! I tried the 10mg Melatonin tab and could have gotten better results with an aspirin. Didn’t even make me yawn. Total ripoff.”

Dagny in Philadelphia, PA, had good results with sublingual melatonin and cherry juice:

“I use Source Naturals spray melatonin and find it quite effective. The ‘sublingual’ part of the dosing seems to be key. I tried taking the pill form that’s supposed to be taken a few hours before bedtime some years back and it was unpredictable. It failed more often than it worked.

“I also recommend tart cherry juice, an ounce (a standard jigger or two tablespoons) sipped about half an hour before bedtime. I think I read about that remedy here, as a matter of fact.”

You can learn more about melatonin and other approaches to overcoming insomnia in our online resource, Getting a Good Night’s Sleep. It is available at www.PeoplesPharmacy.com.

Share your own melatonin story in the comment section below.

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.” .
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