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Circadian Rhythm Disorders


Circadian rhythm sleep-wake disorders are either intrinsic or extrinsic. Intrinsic circadian rhythm disorders appear when the individual’s body clock is either off-set from the norm, as in delayed or advanced sleep-wake phase disorder, or irregular, as in non-24 sleep-wake rhythm disorder. Lifestyle factors can result in extrinsic circadian rhythm disorders such as shift work disorder or jet lag disorder (1). Melatonin supplements can be used therapeutically for both conditions (2).


Studies using melatonin have explored how shift work, particularly night work with its exposure to light at night, may increase the risk of cancer, aggravate both gastrointestinal and cardiovascular disease, complicate pregnancy, and interfere with drug therapy (3). Multiple studies, opinions, and guidelines have suggested melatonin as primary therapy for improved health and sleep of shift workers (4–6). Thus, at a larger, more macroscopic level, as mentioned previously, imbalances in melatonin may be associated with what might be referred to as a “darkness deficiency,” or a lack of adequate evening darkness to initiate the secretion of melatonin by the pineal gland.


Delayed sleep-wake phase disorder is a persistent shift in sleep-wake times later than social norms, causing insomnia-like symptoms, difficulty waking in the morning, and excessive daytime sleepiness. This condition is best treated with precisely-timed melatonin, considering the desired bedtime and wake time. A randomized study of people with delayed sleep-wake phase disorder found that a low dose of melatonin (0.5 mg) an hour before the desired bedtime, along with behavioral strategies for four weeks, resulted in earlier sleep onset, improved sleep efficiency during the first third of the night, and reduced subjective complaints (7).


With increasing travel and global connectivity, more individuals need to recover from jet lag sooner and faster. Many studies support melatonin’s use in reducing the ill effects of jet lag and speeding up the normalization of circadian rhythms (8). In a Cochrane review, nine out of ten trials found that melatonin effectively reduced jet lag symptoms in travelers, especially if traveling eastward or over five time zones (9). Specific phase-shifting protocols support the sleep phase during travel across time zones. Therapeutics include precisely-timed melatonin, light, and dark. These protocols are best known by sleep specialists (10).


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



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3. Iguchi H, Kato KI, Ibayashi H. Age-dependent reduction in serum melatonin concentrations in healthy human subjects. Journal of Clinical Endocrinology and Metabolism. 1982;55(1).

4. Knutsson A. Health disorders of shift workers. Vol. 53, Occupational Medicine. 2003.

5. Zee PC, Goldstein CA. Treatment of shift work disorder and jet lag. Vol. 12, Current Treatment Options in Neurology. 2010.

6.Morgenthaler TI, Lee-Chiong T, Alessi C, Friedman L, Aurora RN, Boehlecke B, et al. Practice Parameters for the Clinical Evaluation and Treatment of Circadian Rhythm Sleep Disorders. Sleep. 2007;30(11).

7. Sletten TL, Magee M, Murray JM, Gordon CJ, Lovato N, Kennaway DJ, et al. Efficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: A double-blind, randomised clinical trial. PLoS Med. 2018;15(6).

8. Srinivasan V, Spence DW, Pandi-Perumal SR, Trakht I, Cardinali DP. Jet lag: Therapeutic use of melatonin and possible application of melatonin analogs. Travel Med Infect Dis. 2008;6(1–2).

9. Herxheimer A, Petrie KJ. Melatonin for the prevention and treatment of jet lag. Vol. 2010, Cochrane Database of Systematic Reviews. 2002.

10. Janse van Rensburg DC, Jansen van Rensburg A, Fowler PM, Bender AM, Stevens D, Sullivan KO, et al. Managing Travel Fatigue and Jet Lag in Athletes: A Review and Consensus Statement. Vol. 51, Sports Medicine. 2021.

Shift Work, Delayed Sleep-Wake Phase Disorder, Jet Lag

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