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Sleep

 

Although melatonin has, in some ways, become synonymous with sleep, other clinical approaches would serve as first-line interventions before using melatonin. Dysfunctional sleep does not have one mechanism, such as reduced melatonin, but potentially several causes, some or all, may be impacting melatonin levels. With over eighty sleep disorders (1), full assessment and diagnosis are important for effective treatment. Underlying inflammation-related diseases may need to be addressed, such as metabolic syndrome, sleep apnea, and any type of joint or muscle pain (2,3). Even hormonal fluxes related to estrogen, cortisol, and insulin are essential to assess for imbalance and correct accordingly (4–6). Moreover, there may be an association between environmental toxins such as heavy metals (e.g., arsenic) and sleep disturbance (7,8). Sleep hygiene, such as room temperature, adequate darkness, noise, and comfort of bed and pillows, would be simple actions to ensure a healthy environment (9,10). Further to the sleeping room, engaging in healthy lifestyle practices such as refraining from stimulants, eating or being on devices too close to bedtime, and unwinding from the day’s stresses with relaxation practices such as a warm bath or physical activity, need consideration (11,12). From a nutritional standpoint, assessing dietary intake of macronutrients, especially tryptophan-containing sources of protein (12), along with micronutrients such as magnesium (13), vitamin D, and calcium, would be essential for ensuring a biochemical foundation that would foster healthy sleep (14). Thus, melatonin would be utilized preferentially when the other changes have been implemented if there was an indication.

 

Melatonin has a hypothermic action. A decrease in core body temperature is soporific (15). In this way, exogenous melatonin can have a direct effect on sleep. A meta-analysis of melatonin for the treatment of primary sleep disorders analyzed nineteen studies involving 1683 individuals. Melatonin had a statistically significant effect on reducing sleep latency and increasing total sleep time. Trials that used higher doses of melatonin and conducted over a longer duration demonstrated even greater effects on these two sleep issues, and overall sleep quality was also significantly improved in melatonin users (16,17).

 

A 2017 systematic review (18) identified 5030 studies on melatonin and sleep, but only twelve were included to meet their criteria for randomized, controlled, and single or double-blind studies. The summary concluded that melatonin is indicated for the following (18):

  • Insomnia: Immediate release 1–3 mg, <30 min before bed; slow-release can be used for sleep maintenance problems

  • Regulating sleep in blind individuals who often experience non-24 h sleep-wake rhythm disorder;

  • Replicating the normal endogenous pattern;

  • Delayed sleep phase.

 

In 2022, researchers at Harvard Medical School and Brigham and Women’s Hospital explored low (0.3 mg) and high (5 mg) dose melatonin in a relatively small sample of healthy older adults. Both doses improved sleep efficiency, but the higher dose impacted the biological day and night sleep patterns, the duration of non-REM sleep, and awakening time (19).

 

Melatonin supplementation has shown promise in a rare sleep disorder, idiopathic REM Behavior Disorder (iRBD). Patients with iRBD will retain muscle tone during REM sleep and can act out their dreams, posing a danger to themselves and others. Importantly, iRBD is a prodrome biomarker for Parkinson’s disease. In one study, six months of low-dose 2 mg melatonin supplementation taken at the same clock time (between 10–11 pm, personalized to the individual’s chronotype) resulted in a decrease in iRBD symptom severity over the first four weeks of treatment. This improvement was maintained over the follow-up period of 4.2 +/− 3.1 years (20).

 

Authors: Deanna Minich, Ph.D., Melanie Henning, ND, Catherine Darley, ND, Mona Fahoum, ND, Corey B. Schuler, DC, James Frame

Reviewer: Peer-review in Nutrients Journal

Last updated: September 22, 2022

 

References

1. National Center for Complementary and Integrative Health. Sleep Disorders: In Depth [Internet]. National Center for Complementary and Integrative Health. 2015 [cited 2022 Jul 30]. Available from: https://www.nccih.nih.gov/health/sleep-disorders-in-depth

2. Irwin MR, Opp MR. Sleep Health: Reciprocal Regulation of Sleep and Innate Immunity. Vol. 42, Neuropsychopharmacology. 2017.

3. Haack M, Simpson N, Sethna N, Kaur S, Mullington J. Sleep deficiency and chronic pain: potential underlying mechanisms and clinical implications. Vol. 45, Neuropsychopharmacology. 2020.

4. de Nys L, Anderson K, Ofosu EF, Ryde GC, Connelly J, Whittaker AC. The effects of physical activity on cortisol and sleep: A systematic review and meta-analysis. Vol. 143, Psychoneuroendocrinology. Elsevier Ltd; 2022.

5. Kline CE, Hall MH, Buysse DJ, Earnest CP, Church TS. Poor Sleep Quality is Associated with Insulin Resistance in Postmenopausal Women with and Without Metabolic Syndrome. Metab Syndr Relat Disord. 2018;16(4).

6. Sondrup N, Termannsen AD, Eriksen JN, Hjorth MF, Færch K, Klingenberg L, et al. Effects of sleep manipulation on markers of insulin sensitivity: A systematic review and meta-analysis of randomized controlled trials. Vol. 62, Sleep Medicine Reviews. 2022.

7. Rahman HH, Niemann D, Yusuf KK. Association of urinary arsenic and sleep disorder in the US population: NHANES 2015–2016. Environmental Science and Pollution Research. 2022;29(4).

8. Shiue I. Urinary arsenic, pesticides, heavy metals, phthalates, polyaromatic hydrocarbons, and polyfluoroalkyl compounds are associated with sleep troubles in adults: USA NHANES, 2005–2006. Environmental Science and Pollution Research. 2017;24(3).

9.  Morgenthaler T, Kramer M, Alessi C, Friedman L, Boehlecke B, Brown T, et al. Practice parameters for the psychological and behavioral treatment of insomnia: An update. An American Academy of Sleep Medicine Report. Vol. 29, Sleep. 2006.

10. Brown TM, Brainard GC, Cajochen C, Czeisler CA, Hanifin JP, Lockley SW, et al. Recommendations for daytime, evening, and nighttime indoor light exposure to best support physiology, sleep, and wakefulness in healthy adults. PLoS Biol. 2022;20(3).

11. Birch JN, Vanderheyden WM. The Molecular Relationship between Stress and Insomnia. Adv Biol. 2022 Jul 13;2101203.

12. Sejbuk M, Mirończuk-Chodakowska I, Witkowska AM. Sleep Quality: A Narrative Review on Nutrition, Stimulants, and Physical Activity as Important Factors. Nutrients. 2022 May 2;14(9):1912.

13. Zhang Y, Chen C, Lu L, Knutson KL, Carnethon MR, Fly AD, et al. Association of magnesium intake with sleep duration and sleep quality: findings from the CARDIA study. Sleep. 2022;45(4).

14. Ikonte CJ, Mun JG, Reider CA, Grant RW, Mitmesser SH. Micronutrient inadequacy in short sleep: Analysis of the NHANES 2005–2016. Nutrients. 2019;11(10).

15. Reid K, van den Heuvel C, Dawson D. Day-time melatonin administration: Effects on core temperature and sleep onset latency. J Sleep Res. 1996;5(3).

16. Wunsch N.-G. Sales of Melatonin 2020 [Internet]. 2021 [cited 2022 Jul 30]. Available from: https://www.statista.com/statistics/1267421/sales-of-melatonin-in-the-united-states/

17. Ferracioli-Oda E, Qawasmi A, Bloch MH. Meta-Analysis: Melatonin for the Treatment of Primary Sleep Disorders. PLoS One. 2013;8(5).

18. Auld F, Maschauer EL, Morrison I, Skene DJ, Riha RL. Evidence for the efficacy of melatonin in the treatment of primary adult sleep disorders. Vol. 34, Sleep Medicine Reviews. 2017.

19. Duffy JF, Wang W, Ronda JM, Czeisler CA. High dose melatonin increases sleep duration during nighttime and daytime sleep episodes in older adults. J Pineal Res. 2022 Aug 13;73(1).

20. Kunz D, Stotz S, Bes F. Treatment of isolated REM sleep behavior disorder using melatonin as a chronobiotic. J Pineal Res. 2021;71(2).

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