Melatonin Benefits and Preferred Delivery Form

Most people who use dietary supplements are probably familiar with Melatonin as a sleep aid —for which it is indeed effective. But not everyone is aware that sublingual Melatonin (a small lozenge type tablet placed under the tongue and allowed to dissolve and enter the blood stream through diffusion) is likely more effective than a standard Melatonin capsule or tablet. This article will discuss the research on sublingual melatonin: but first let’s review the general science behind Melatonin as a sleep aid.

Melatonin Overview
Melatonin is a hormone secreted by the pineal gland.¹ It is produced from tryptophan, which after being metabolized, is converted to serotonin, and ultimately to Melatonin.² Melatonin’s primary role is regulation of the body’s circadian rhythm, endocrine secretions, and sleep patterns.^3,4 The way it works is that light inhibits Melatonin secretion and darkness stimulates secretion. Therefore, at night Melatonin is secreted which initiates sleep. However, people who suffer from an insufficient amount of environmental light, such as office workers in windowless buildings⁵ and the elderly who do not get outside very much, often have decreased endogenous Melatonin secretion.⁶ Furthermore, research suggests that some individuals may have inadequate levels of Melatonin to promote sleep. This includes elderly people^7,8 (who may make less melatonin), people with chronic fatigue syndrome⁹ and others.^10,11,12,13

In addition, Melatonin is a potent antioxidant; with 6–10 times the antioxidant activity of vitamin E.¹⁴ It acts as an oxygen free radical scavenger and prevents several enzymatic reactions that generate reactive oxygen species (ROS).¹⁵

Difficulty Sleeping in Adults
In adults with difficulty sleeping, short-term use of Melatonin modestly reduce the time it takes to fall asleep (sleep latency).16 In addition, some patients report minor improvement in subjective feelings of sleep quality.^17,18,19 Furthermore, research has shown that Melatonin supplementation is effective in adults with difficulty sleeping, secondary to other causes.²⁰ For example, Melatonin may improve difficulty sleeping secondary to mood and mental health issues^21,22,23 age-related decline in memory function²⁴, hospitalization²⁵, and difficulty sleeping relating to “ICU syndrome”—referring to sleep disturbances while in the intensive care unit.²⁶ A pooled analysis of studies using Melatonin for difficulty sleeping, secondary to other causes, suggests that it modestly increase sleep efficiency.²⁷

In individuals with a circadian rhythm sleep disorder; supplementation with Melatonin improves difficulty falling asleep and other quality of life factors such as mental health, vitality, and bodily pain.^28,29,30 In addition, taking Melatonin also helps improve circadian rhythm sleep disorders in blind children and adults. Melatonin has FDA orphan drug status for this indication.^{31,32,33,34,35}

Difficulty Sleeping In Children
In children with delayed onset of sleep, Melatonin seems to shorten the time that it takes to fall asleep and increase the duration of sleep.³⁶ Clinical research also demonstrates Melatonin may improve insomnia in children with attention deficithyperactive disorder (ADHD) who are taking stimulants.^37,38

Furthermore taking Melatonin is helpful for sleep-wake cycle disturbances in children and adolescents with mental retardation, autism, and other central nervous system disorders.^{39,40,41,42,43}

Melatonin also improves the time to fall asleep in children with developmental disabilities, including cerebral palsy, autism, and mental retardation.⁴⁴ Melatonin supplementation seems to subjectively improve difficulty sleeping, secondary to other causes, associated with various sleep-wake cycle disturbances.^45,46,47,48

Drug Withdrawal and Related Sleep Issues
Supplementation with Melatonin has been shown to be beneficial for facilitating benzodiazepine withdrawal in elderly people with sleep difficulties.^49,50 Likewise, Melatonin supplementation 3.5 hours after nicotine withdrawal in smokers reduced subjective symptoms of anxiety, restlessness, irritability, depression, and cigarette craving over the next 10 hours.⁵¹ Although not related to withdrawal issues, beta-blockers such as atenolol and propranolol decrease Melatonin levels. Naturally, this may result in sleep difficulties. Supplementation with Melatonin supplement can decrease sleep difficulties caused by betablockers.^52,53

Jet Lag
Flying from one time zone to another can result in jet lag. Research shows that supplementation with Melatonin modestly improves some symptoms of jet lag such as alertness and psychomotor performance. In addition, Melatonin mildly improves daytime sleepiness and fatigue.⁵⁴ A range of doses from 0.5 to 5 mg appear to be equally effective, and 2 to 3 mg of Melatonin is particularly useful when taken at local bedtime on the day of arrival and for two to five nights thereafter in those traveling eastward through five or more time zones. The usefulness of Melatonin for westward travel or over fewer time zones is less clear.^{55,56,57,58,59,60,61,62}

Sublingual Melatonin
With all of the aforementioned research, it is clear that Melatonin is effective as a sleep aid when used in the form of standard dietary supplement dosing (capsules and tablets). However, additional research shows that a sublingual form of Melatonin appears to be the preferred way to use this supplement.

First-pass metabolism is a phenomenon whereby the concentration of a drug, or in some cases a nutraceutical, is greatly reduced by clearance in the liver before it reaches the systemic circulation. This is also true of Melatonin. Research shows that 44–90 percent of a standard Melatonin supplement absorbed into the blood is cleared by the liver in a single passage.⁶³ Conversely, other research⁶⁴ shows that the amount of Melatonin absorbed in the mouth (i.e. sublingual) and reaching systemic circulation was 80 percent greater than the standard oral tablet, and the peak concentration of Melatonin was 50 percent higher as well.

In addition to bioavailability, there are other advantages associated with the use of sublingual Melatonin over the standard delivery form.

Research has shown that, surprisingly, Melatonin has both receptor-mediated and receptor-independent actions in cells of the oral cavity. Functions of Melatonin in the oral cavity are likely to relate primarily to its anti-inflammatory and antioxidant activities. According to one study published in the Journal of Periodontal Research, “These actions may suppress inflammation of the gingiva and periodontium, reduce alveolar bone loss, abrogate herpes lesions, enhance osteointegration of dental implants, limit oral cancer, and suppress disorders that have a free radical component. Sublingual Melatonin tablets or oral Melatonin sprays and topical Melatonin-containing gel, if used on a regular basis, may improve overall oral health and reduce mucosal lesions.”⁶⁵

Furthermore, research has demonstrated that sublingual Melatonin has anti-anxiety effects. Two studies^66,67 examined the effects of sublingual Melatonin in patients prior to surgery. The results were that sublingual Melatonin exerted a significant anti-anxiety effect.

Another study⁶⁸ used sublingual Melatonin on emergency physicians who worked night shifts and slept during the day. Results showed that sublingual Melatonin improved day sleep and night alertness. The improvement in night alertness was probably a function of getting adequate sleep during the day. These effects suggest that sublingual Melatonin is likely able to help night workers adapt better to the shift in normal sleeping patterns.

Conclusion
As a dietary supplement, Melatonin has been shown to offer benefit in a number of situations and populations who need an effective sleep aid. This is true whether or not Melatonin is used as a capsule, tablet or as a sublingual lozenge (sometimes referred to as a mini-tablet, mini-lozenge or dot). Still, research shows that the sublingual form of Melatonin may have greater bioavailability and offer additional benefits beyond those of standard supplementation forms. In any case, a good dosage range is 3–6 mg for most people.

Endnotes

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3. Ibid.
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11. Weiss MD, Wasdell MB, Bomben MM, et al. Sleep hygiene and Melatonin treatment for children and adolescents with ADHD and initial insomnia. J Am Acad Child Adolesc Psychiatry 2006;45:512–9.
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