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Melatonin Supplementation: Too much of a good thing?
Known as the ‘hormone of darkness’, melatonin is the major sleep hormone. It is secreted at night, as part of a complex circadian clock, and governs wake and sleep cycles in response to light and dark.1 In addition to promoting healthy sleep, melatonin has attracted significant therapeutic interest for its longevity, anti-inflammatory and antioxidant properties. Research also suggests melatonin supplementation may support psychological health and wellbeing, reduce the risk of cancer and provide endothelial protection.2-7
Within cells in the pineal gland, the amino acid L-tryptophan is converted to serotonin and ultimately acetylated to produce melatonin.1
What alters melatonin secretion?
Many factors result in insufficient production and secretion of melatonin, including:2,3,4
A meta-analysis of 19 randomised placebo-controlled trials on 1,683 patients found that melatonin supplementation improves sleep quality, increases total sleep time, and decreases sleep latency.5
How much is too much melatonin?
The body naturally produces approximately 0.3mg – 1.0mg of endogenous melatonin per day. In contrast, far higher pharmacological doses (ranging from 3mg – 20mg) are routinely prescribed. This has led to concern over whether supplementation with high doses of exogenous melatonin may cause a blunting of melatonin receptors, resulting in a reduced capacity for the pineal gland to produce sufficient endogenous physiological amounts.1,8
According to some researchers, high pharmacological doses of melatonin over long periods, may disrupt the delicate mechanism of the circadian system.1,8
Prescribe physiological, not pharmacological, doses
Evidence suggests that after administration of a 0.3mg physiological dose of exogenous melatonin, blood melatonin levels typically reach 100pg/mL, which is similar to those observed in normal healthy subjects in the middle of the night.1 For example, in a double-blind placebo-controlled study on sleep efficiency, 30 women over 50 years of age were given melatonin for 1 week. The results showed that the higher dose of 3.0mg was less efficacious than a 0.3mg dose. In addition, the higher dose was shown to elevate melatonin levels well into the following day and produce unwanted hypothermic effects.8
Lower physiological doses of supplemental melatonin may provide a safer and therapeutically effective solution to supporting healthy sleep patterns.
Practice Safe Stress
The terms “distress” and “eustress” were coined in the early 1970s to distinguish whether a stress response was initiated by negative or positive factors.1 Unlike detrimental or overwhelming stressors, mild stressors (termed eustress) are able to condition the body and mind, act as a stress buffer, build resilience and strengthen defenses.2,3
Eustress, or positive stress:
Distress, or negative stress:
How a person experiences stress however, depends on a plethora of interactions within the body, mind and the environment, which appears more complex than the eustress/distress model would suggest.1
The response to stress, can switch quickly from resilience to vulnerability with a shift in intensity or duration.1,4
The dose (and duration) makes the poison
Centuries ago, Paracelsus first stated “the dose makes the poison”.1 This still fits within modern concepts of stress, such as allostasis. Allostasis looks at the resilience of an individual, weighed against the total physical and psychological stress burden including the type of stressor, duration, intensity and the person’s psychological and physical history.3
Stress phenotypes are produced due to the same stressors, but which are of varying intensity, type, and duration. Stressors therefore cannot be clearly defined as intrinsically good or bad.1
Practicing safe stress
It may be difficult to untangle the significant changes needed to alleviate persistent negative stress, however resilience building strategies which target reducing the duration and intensity of the stressor may create a much-needed buffer to reduce the negative impact of an ongoing distressful environment.4 A healthy diet, lifestyle changes, supplementation and a positive outlook, can also help. In addition, understanding key allostatic biomarkers can help assess a patient’s eustress/distress status and exactly how much support is required.5,6
1.Bienertova‐Vasku, J., Lenart, P., & Scheringer, M. (2020). Eustress and Distress: Neither Good Nor Bad, but Rather the Same? BioEssays, 1900238. doi:10.1002/bies.201900238
2. Li, C.-T., Cao, J., & Li, T. M. H. (2016). Eustress or distress. Proceedings of the 2016 ACM International Joint Conference on Pervasive and Ubiquitous Computing Adjunct - UbiComp ’16. doi:10.1145/2968219.2968309
3. Guidi, J., Lucente, M., Sonino, N., & Fava, G. A. (2020). Allostatic Load and Its Impact on Health: A Systematic Review. Psychotherapy and Psychosomatics, 1–17. doi:10.1159/000510696
4. Kupriyanov, R., & Zhdanov, R. (2014). The eustress concept: problems and outlooks. World Journal of Medical Sciences, 11(2), 179-185.
5. Tabibnia, G., & Radecki, D. (2018). Resilience training that can change the brain. Consulting Psychology Journal: Practice and Research, 70(1), 59.Doi.org/10.1037/cpb0000110
6. Rosemberg, M.-A. S., Granner, J., Li, Y., & Seng, J. S. (2020). A scoping review of interventions targeting allostatic load. Stress, 1–10. doi:10.1080/10253890.2020.1784136