Substances and behaviors that alter nighttime melatonin profiles. Considerations in the treatment of sleep disorders: Protocol for a systematic review

Background. Changing lifestyles and the widespread use of artificial lighting have contributed to the disruption of circadian rhythms in modern society. As various aspects of affect and cognition are also controlled by circadian rhythms, this is of concern. Thus, circadian phase assessment is increasingly applied in the diagnostic process in clinical practice, as knowledge of circadian timing and the etiology of symptoms associated with circadianVer misalignment inform treatment choices. However, clinicians should be aware that certain psychopharmaceuticals may influence endogenous melatonin profiles. Other pharmacological agents and behaviors have shown to mask, suppress, or promote DLMO and nighttime melatonin levels (e.g. caffeine, bright light, exercise). Moreover, health and nutritional organizations are increasingly emphasizing certain foods and dietary supplements (e.g. magnesium, tryptophan) that contain melatonin or boost the body’s natural melatonin production. Although it remains unclear whether the increase in melatonin through these foods and supplements can enhance sleep or cause a significant phase shifting effect for accurate diagnosis, it is important to consider possible masking effects when assessing DLMO and treating circadian misalignment. To date, a comprehensive overview of findings relevant for the application in routine clinical care is lacking.Aim. To review the melatonin altering effect of common behaviors, supplements and pharmaceuticals, which are relevant in clinical cases where circadian phase assessments are indicated. Findings will highlight the possible melatonin promoting and/or inhibiting pathways of certain behaviors or substances. We will end by providing suggestions for clinical practice and future research studies. Methods. First, a “mini systematic review” was conducted, in which a sample of papers was synthesized. This ensured that in the full review all important keywords are included in the search strings, and that the most useful and relevant information will be extracted. Next, the full systematic literature search will be conducted in the online databases of PubMed and EMBASE. To collect all relevant studies, we will search abstract, title and keyword fields, and if available, the corresponding Mesh term (for PubMed) and/or Emtree term (for EMBASE). Separate searches for the three main topics of this review will be conducted: 1) (Psycho)pharmaceuticals and substances; 2) food, beverages, and supplements; and 3) behaviors (light exposure, exercise, meal timing, and sleep scheduling).Results. Appendix A of the present systematic review protocol contains a comprehensive overview of the generated search strings.