Melatonin – the natural sleep hormone!

It is a neurotransmitter-like compound that is a derivative of serotonin and is mainly produced in the pineal gland, near the center of the brain. The role of melatonin is to normalize biological rhythm and adjust the timing across various critical biological processes.

Melatonin release follows the circadian rhythm - in response to the day and night cycle. In fact, the enzymes that synthesize melatonin are activated and depressed by darkness and light, respectively. This clock-setting property means that melatonin is described as a chronobiotic compound.

The many Health Benefits of Melatonin

Melatonin supplements are primarily used to normalize irregular sleep patterns such as insomnia. Insomnia is a common sleep disorder that involves difficulty in going to sleep or the inability to remain asleep.

The end result is not enough quality sleep. People with insomnia have a multitude of downstream negative effects on their physical and mental state during waking hours.

Physical symptoms of irregular sleep patterns can result in fatigue, increased muscular tension and daytime sleepiness or daytime napping. The mental symptoms of sleep disorders can include mental fatigue and behavioral changes such as irritability, negative moods and listlessness.

In addition to these symptoms, people who are tired and suffering from poor sleep quality are more prone to accidents. A significant number of car accidents that result in injury or death are the result of fatigue and tiredness associated with sleep disorders.

Melatonin supplementation has a number of possible clinical and wellness enhancing uses, including:

• Effective regulation of circadian rhythm in sleep disorders
• Correcting jetlag after travelling across time zones
• Improved sleep quality in some cases of insomnia
• Improved sleep quality in cases of depression
• Correct sleep/wake rhythm in individuals with narcolepsy
• Therapeutic agent against seasonal affective disorder
• Effective healing of gastric and stomach ulcers
• Potent anti-oxidant properties
• Anti-aging hormone
• Anticonvulsant activity in some cases of epilepsy

Overall, irregular sleeping patterns and poor sleep quality are associated with multiple health problems. Supplementation with melatonin can not only improve sleep directly, but indirectly it can improve health problems, associated with poor sleep.

Melatonin and Sleep Disturbances

Melatonin supplementation has the therapeutic potential to correct circadian rhythm disturbances and other sleep disorders.

Studies have shown that there is an association between melatonin levels and sleep. In fact, as we age the level of melatonin significantly drops, which means there is a negative effect on the quality and duration of sleep.

The sleep-promoting effects of melatonin are attributed to its action on receptors present in the hypothalamus within the brain. The hypothalamus is the control center for the regulation of sleep and arousal where it has been shown to turn down arousal systems to begin the onset of sleep.

These systems primarily use the neurotransmitter GABA, to exert inhibitory control over these arousal systems during sleep. After sleep, arousal neurotransmitters such as noradrenaline and acetycholine are released to counteract sleep and force wakefulness.

Clinical trials have shown that melatonin’s action as a chronobiotic—a substance that alters biological rhythms—can assist in improving sleep quality. In addition, melatonin supplementation can significantly decrease the latency time between awake and sleep phases as well improving the quality of sleep.

Melatonin supplementation can be beneficial in a variety of sleep disorders including:

• Melatonin can help with primary insomnia or insomnia caused by beta-blockers or other prescription medications.
• Supplementation may help in cases of narcolepsy, a chronic neurological disorder of excessive daytime sleepiness.

Melatonin and Jet Lag

Jet lag is a common affliction for those of us who cross multiple time zones (crossing five or more) in a short space of time. Jet lag usually happens happen after a long flight and whether it is for work or holiday purposes, the imbalance in circadian rhythm can have a great impact on your wellbeing and ability to function properly.

The result is that the body’s internal body clock becomes desynchronized with the day-night cycle at the destination. Jet lag is characterized by extreme fatigue, disorientation, general malaise and even loss of appetite.

Studies have shown that melatonin is remarkably effective at not only decreasing the severity of jet lag at the point of destination but, if taken prior to flying, can even prevent jet lag.

To optimally use melatonin supplements to beat jet lag, the following guidelines can help:

• Melatonin works better the more time zones that you cross
• Melatonin appears to be more effective when travelling in an eastward direction rather than a westward direction
• Melatonin is only effective if taken in the evening at the destination

Melatonin Heals Stomach Ulcers

Melatonin has notable healing and gastroprotective effects against aspirin-induced or helicobacter pylori infected gastric and stomach ulcers. The mechanism of melatonin’s gastroprotective action can be attributed to the enhancement of gastric blood flow as well as through exertion of its anti-inflammatory properties.

Studies have shown that daily supplementation with melatonin can positively assist in the healing of gastric and stomach ulcers that were aspirin-induced or are positive for the bacterium, helicobacter pylori.

In one study, there was a significant increase in healing rate of helicobacter pylori infected ulcers when compared against standard treatment (omeprazole) on its own. It was also shown that melatonin was gastroprotective when co-ingested with aspirin and therefore can even prevent the formation of aspirin-induced ulcers.

Melatonin and Cancer

Some scientists have suggested that the extended periods of artificial light (light pollution) is a possible reason for the dramatic increases in cancer rates in the Western world.

It is hypothesized that artificial light disrupts the day/night cycle and the biological processes that rely on the accuracy of the biological clock. In support of this, studies have shown that there is an increased prevalence of cancer diagnoses in night shift workers.

Night shift workers are exposed to long periods of artificial light during the night and then natural sunlight during the day. The increased exposure to light is associated with a melatonin-secretion profile that never quite adjusts properly. This effect results in an overall reduced secretion of melatonin, which is hypothesized to be the reason for the increased cancer prevalence.

Current research into melatonin’s action against tumors shows that it may restrain tumor initiation and progression. Melatonin has also been shown to have activity against the metastasis of various cancers, melanomas and leukemia. In particular, one meta-analysis showed that daily supplementation with melatonin significantly improved mortality rates in patients with solid tumor cancers after one year.

Although further research is required into the efficacy and safety of melatonin as a therapeutic oncostatic agent, the effects appear to be promising.

Current cancer research into melatonin therapy, include:

• Clinical studies into melatonin efficacy for the prevention and treatment of breast cancer.
• Melatonin plays a role in prostate and colorectal cancers by preventing proliferation and differentiation of carcinomas.
• Efficacy and timing of melatonin injections in the treament of tumors is being investigated.
• Melatonin administration appears to help cancer patients better tolerate chemotherapy.

Melatonin and Mental Disorders

The function of melatonin is primarily to maintain the biological rhythm through promotion of synchronization and stabilization of multiple processes.

There is increasing evidence that disturbances in these biological rhythms play an important role in the development of mental disorders such as major depressive disorder, bipolar disorder and seasonal affective disorder.

At present, there are studies ongoing that are looking into bright light therapy as a treatment to restore the circadian rhythm in patients with severe mental disorders such as major depressive disorder. Bright light therapy aims to increase melatonin production and may provide improvements in circadian rhythmicity and overall cognitive functioning in individuals with mental disorders.

Taken together, melatonin theoretically offers a novel approach to treat these disorders through adjustment of circadian rhythm abnormalities. As such, synthetic derivatives of melatonin are being trialed for their possible antidepressant activity.

Melatonin and Anti-Aging

Melatonin can help prevent the signs of aging through its potent antioxidant properties.

Melatonin is a direct scavenger of reactive oxygen species (ROS), which are implicated with the free radical theory of aging. The free radical theory of aging involves toxic ROS, which are highly reactive compounds that can directly damage a number of important biological structures.

The process of aging is associated with cancer, arthritis, neurodegeneration, and diabetes all of which are linked with oxidative stress and oxidative damage.

Through its ROS-scavenging properties, melatonin is able to directly counteract the damage these free radicals would potentially cause. Melatonin also has indirect anti-oxidative properties through its ability to enhance the activity of various anti-oxidative enzymes such as super oxide dismutase.

Super oxide dismutase plays a critical role in the defense of cells against the toxic effects of oxygen radicals and its activation helps to suppress cell damage.

In addition, the skin produces its own melatonin and therefore supplementation with melatonin capsules would appear to offer a novel approach to premature skin aging. Melatonin can also protect the skin against environmental damage such as that caused by UV radiation.

Who Should Use Melatonin?

Melatonin supplementation may be beneficial if you are someone with the following:

• Sleep disturbances
• Jet lag
• Insomnia
• Narcolepsy
• Mood disorders
• Seasonal affective disorder
• Concerned with unhealthy skin aging

Has Melatonin side effects?

Melatonin has low toxicity and is generally well tolerated. Nevertheless, sensible people may experience side effects, including:

• Headache
• Insomnia
• Upset stomach
• Nightmares
• If given in the AM, it can stimulate tumor growth in some cancers

Melatonin Interactions

Melatonin is an active neurohormone and therefore is likely to have some drug interactions. Although there is not much research at present on melatonin’s drug interactions, individuals taking the following should consult their GP before supplementing with melatonin.

• Antidepressants
• Antipsychotic medications
• ADHD medication
• Anti-diabetes medication
• Immune-suppressants
• Anti-coagulants or anti-platelet medication
• Sedative medications
• Blood Pressure medication
• Sedative medications
• Birth control pills

Melatonin Combinations

• Combine melatonin with vitamin C for enhanced anti-oxidative benefits.
• For enhanced gastroprotective effects, take melatonin when prescribed omeprazole.

Melatonin Dosage

Melatonin comes in a tablets, capsules, sublingual tablets or liquid. Depending on its intended use, melatonin can be dosed at 0,5 to 10 milligram per day.

Why Take Melatonin?

People take melatonin supplements for a variety of reasons, including:

• Inability to fall asleep
• Insomnia caused by prescription medication
• To correct jetlag
• May help treat some types of solid tumors
• To assist in healthy skin aging
• To protect against stomach ulceration

Other Names of Melatonin

N-acetyl-5-methoxytryptamine, 5-methoxy-N-acetyltrptamine, pineal hormone, MEL, melatonine

Melatonin Studies and References

1. Malhotra S, Sawhney G, Pandhi P. ​The therapeutic potential of melatonin: A review of the science. ​ Med Gen Med. 2004; 6(2): 46

2. Mills E, Wu P, Seely D, Guyatt G.. ​Melatonin in the treatment of cancer: a systematic review of randomized controlled trials and meta-analysis. ​J Pineal Res. 2005 Nov;39(4):360-6.

3. Lemoine P, Nir T, Laudon M, et al. ​Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects. ​J Sleep Res. 2007; 16(4): 372-380

4. Luthringer R, Muzet M, Zisapel N, et al. ​The effect of prolonged-release melatonin on sleep measures and psychomotor performance in elderly patients with insomnia. ​2009; 24(5): 239-249

5. Celinski K, Konturek O, Konturek S, et al. ​Effects of melatonin and tryptophan on healing of gastric and duodenal ulcers with Helicobacter pylori infection in humans. ​J Physiol Pharmacol. 2011; 62(5): 521-526

6. Cutando A, Lopez-Valverde A, Arias-Santiago S, et al. ​Role of melatonin in cancer treatment. ​Anticancer Res. 2012; 32(7): 2747-2753

7. Hill S, Belancio V, Dauchy R, et al. ​Melatonin: an inhibitor of breast cancer. ​Endocr Relat Cancer. 2015; 22(3): 183-204