The Many Uses of Melatonin

Part I - A Sleeping Partner

We live in a society where 10% to 37% of the adult population suffers from insomnia, a problem which affects people’s psychomotor performance, causes sleepiness, accidents, and memory impairment.^{(1, 2)} These people usually fall into one of 3 categories: difficulty getting to sleep, maintaining sleep, and both.⁽¹⁾ Many people have heard about the use of melatonin for a better night’s sleep. However, there are also many uses of melatonin that people are generally unaware of. This article will focus on the role of melatonin for insomnia, cancer, jet lag and gastro-esophageal reflux (GERD, aka heartburn), as well as provide an overview of appropriate dosing and safety of melatonin.

Melatonin is a hormone that is found naturally in the body and is chemically related to serotonin, which makes us feel happy.⁽³⁾ It is produced by the pineal gland in the brain at night. Body levels follow a daily circadian rhythm, with secretion being stimulated by the evening onset of dim light, and suppressed by bright light.^{(4, 5)} This hormone has shown to be useful in insomnia and to adjust the circadian rhythm or internal clock. It is known that natural melatonin production decreases with age. Younger insomnia patients may also have low levels of melatonin.^{(6, 7)} A study published in 2010 in BMC Medicine investigated 791 adult patients aged 18–80 with insomnia, who were randomized to receive melatonin or placebo for 26 weeks. They found that melatonin reduced the amount of time required to fall asleep compared to the placebo, regardless of age.⁽⁷⁾ Another study of ten patients with persistent insomnia found that melatonin significantly increased rapid-eye-movement (REM) and improved the overall quality of sleep.⁽¹⁰⁾ A review of the scientific literature examined six studies on the use of melatonin for elderly patients. There were a total of 95 patients aged 65–79 that were treated with melatonin, between 0.5 mg to 5 mg and taken 30–120 minutes before bed. Sleep quality was objectively measured with a machine measuring brain wave patterns, and found that there were improvements in both of the following: difficulty getting to sleep, and sleep quality. No early-morning sleepiness or “hang-over” occurred.⁽¹¹⁾ Insomnia also affects children with symptoms of psychiatric disorders such as depression and attention-deficit hyperactivity disorder (ADHD). Persistent sleep disturbance in a young child can adversely affect the family. The mothers especially have been reported to be more irritable and less affectionate towards their children than mothers of such children without sleep problems.⁽⁸⁾ Melatonin has also been found to be effective for improving sleep in children with psychiatric disorders.⁽⁸⁾ Melatonin is a natural agent with a very good safety profile, and has been studies in children, adults, and the elderly as an agent to promote better sleep. Stay tuned for Part II of this series, where we switch the focus to a novel application of melatonin, the treatment of cancer.

The Many Uses of Melatonin - Not just for Sleep
Part II : Melatonin for Cancer Patients

In Part I we mentioned that melatonin has uses outside of just sleep. Did you know that melatonin is protective in cancer? Yes, melatonin has several actions that help protect against cancer. This was first discovered through studies of shift workers, who were found to be at increased risk of cancer, but may have more broad applications. This section discusses the anticancer activities of melatonin.

Shift workers have abnormal melatonin production patterns due to their irregular sleep schedules; they are often awake at night when melatonin secretion is usually at peak. Remember that melatonin secretion is stimulated by dark. So what else happens when you have continuous loss of sleep? It has recently become recognized that increased exposure to light at night carries an increased risk of breast cancer.⁽¹⁾ It has been hypothesized that this is due to insufficient or abnormal secretion of melatonin.^{(1, 2)} One study found that risk of breast cancer was increased 14% for each day of the week over the last ten years during which subjects frequently did not sleep during the period of the night when melatonin secretion is highest (roughly midnight to 2 am).⁽¹⁾ Melatonin exerts its anticancer effects through several mechanisms. Researchers found that melatonin anticancer activity is due to its immune-modulating, antiproliferative and antioxidant effects.^{(3, 4)} One study examined 20 cancer patients with metastatic disease (patients in whom cancer has spread throughout the body), with no other effective treatment available. Melatonin was given orally at 20 mg/day in the evening for at least 2 months. Researchers measured levels of a molecule called vascular endothelial growth factor (VEGF), which is the most active angiogenic factor. This means that VEGF promotes the growth of new blood vessels, a process that is known to promote the growth and spread of cancer. Researchers found that treatment with melatonin significantly decreased VEGF levels, suggesting that melatonin may reduced tumor growth by inhibiting the growth of new blood vessels.⁽⁴⁾ Another study found that melatonin may have anti-hormone effects in estrogen-dependent cancers, such as breast cancer. Estrogen is of course a very important hormone in cancer because it is known to promote tumor growth, particularly in breast cancer. Melatonin has anti-estrogenic, or estrogen-modulating effects.⁽⁵⁾ Melatonin is thought to change the way that estrogen acts on the estrogen receptor, resulting in a net decrease of its effects; in addition, melatonin is thought to influence the enzymes that produce estrogen, such as aromatase, resulting in less estrogen production locally by the tissues.^{(5, 6)} A meta-analysis of 21 human studies found that use of melatonin increased patients’ survival after one year, and may decrease side effects of chemotherapy.⁽⁷⁾ Please note that consultation with a licensed naturopathic doctor or medical oncologist is recommended for cancer patients prior to taking melatonin. To follow up this fascinating discussion, Part III of this series will focus on the role of melatonin as a remedy for jet lag and for gastro-esophageal reflux (GERD, a.k.a. heart burn).

The Many Uses of Melatonin - Not just for Sleep
Part III : Get Back on Time
In Part II we discussed a new application of melatonin: cancer treatment and prevention. A better- known application of melatonin is the treatment of jet lag. Jet lag is fatigue caused from flights that cross several time zones. It is thought to be due to a disruption of the circadian rhythm, which affects sleep-wake cycles. Melatonin supplementation can help rebalance the body’s natural rhythm.

Not surprisingly, the trials of melatonin on jet lag involved studying flight crew! Researchers investigated the efficacy of oral melatonin in alleviating jet lag in flight crews after a series of international flights. This was done for 52 international cabin crews using 2 different dosing strategies compared to placebo; early melatonin (5 mg started three days prior to arrival and continued until five days after return home); late melatonin (placebo for three days prior to arrival, then 5 mg melatonin until five days after return home); or placebo.⁽¹⁾ The results of the study revealed that six days after arrival,the late-dosing melatonin group reported significantly less jet lag and sleep disturbance following the flight compared to placebo. The late melatonin group also showed a significantly faster recovery of energy and alertness compared to the early melatonin group, which reported a worse overall recovery than placebo. These findings show melatonin during and after travel may have potential benefits for long-haul travelers, while taking early melatonin prior to travel may not help.⁽¹⁾ Another study compared the different dosages amounts needed for relief of jet lag. The volunteers in the study received either: a) melatonin 0.5 mg, b) melatonin 5 mg, c) melatonin 2 mg slow release, or d) placebo. The study medication was taken once daily at bedtime in the four days following an eastward flight. The 5 mg melatonin group had significantly improved sleep quality, shortened the difficulty getting to sleep, and reduced fatigue and daytime sleepiness after the intercontinental flight. Surprisingly, the lower dose of 0.5 mg was almost as effective as the higher, more typical dose of 5 mg.^{(2, 3)} The benefit is likely to be greater the more time zones are crossed flying eastward, and less for westward flights.⁽²⁾ Melatonin dosing may have inter-individual variability, with some people responding very well to smaller dosages, while others may require higher amounts of melatonin. Melatonin supplementation during and after travel can decrease symptoms of jet lag. Part IV of this article will address the use of melatonin in digestive health, as well as appropriate dosing of melatonin and safety considerations.

The Many Uses of Melatonin - Not just for Sleep
Part IV : Melatonin for GERD
In earlier sections we reviewed the uses of melatonin in insomnia, cancer, and jet lag. In this installment, we review the (surprising!) use of melatonin in digestive health, as well as the relative dosages for various applications of this fascinating substance, based on our discussion so far.

It is not really surprising that melatonin is useful for brain- or sleep-related conditions, since melatonin is a hormone produced by the brain. However, it does come as a surprise that melatonin should also be useful for digestive problems! The reason for this is that large amounts of melatonin are actually produced locally in the gut!⁽¹⁾ Yes, melatonin is not only a hormone of the brain, but is a local signal for digestive activity.⁽²⁾ Upon further consideration, this makes sense, in fact, since digestion is also very much a circadian activity, with clear daily patterns.⁽²⁾ Specifically, melatonin has been found to be helpful in gastro-esophageal reflux (GERD), also known as “heartburn.” GERD results from excess exposure of the esophageal lining to the stomach acid, which is refluxed into the esophagus or “food pipe,” causing “heart burn.” Melatonin appears to protect against acid induced damage, and has anti-inflammatory effects.^{(3, 2)} A study examined 36 people with GERD who were divided into 4 groups: melatonin alone, an acid inhibiting drug, a combination of melatonin and drug, or no treatment (control) for eight weeks. Researchers found that melatonin resulted in marked improvement of GERD symptoms regarding heartburn and “stomach” pain, improved esophageal sphincter function, and decreased basal acid production (acid production in the absence of food).⁽¹⁾ Another study found that patients taking melatonin in addition to other nutrients such as B vitamins resulted in regression of GERD in all treated patients.⁽⁴⁾ Although in general melatonin appears to be quite safe, it is recommended that individuals consult a licensed naturopathic doctor before taking melatonin, as there is risk for interactions with some medications such as a type of blood pressure medication called calcium channel blockers.⁽⁵⁾ In addition, melatonin may not be advisable in some medical condition, particularly certain types of cancers. The following table summarizes dosing for the application of melatonin covered in this series. Overall, melatonin appears to be a safe and effective natural agent with lot of potential in a wide array of conditions, however consultation with a licensed healthcare provider is recommended prior to use if you are on medications or if you have been diagnosed with cancer.

Table 1. Applications of Melatonin Supplementation th{ background-color:#AEAE9E;}