Abstract Circadian rhythms (CRs) are entrainable endogenous rhythms that respond to external stimuli and regulate physiological functions. The suprachiasmatic nucleus (SCN) in the hypothalamus is the mammalian master clock that synchronizes all other tissue-specific peripheral clocks, primarily through gamma-aminobutyric acid (GABA) and vasoactive intestinal polypeptide (VIP). The SCN follows Earth's 24-hour cycle by light entrainment through the retinohypothalamic tract. At the cellular level, the core clock genes CLOCK , BMAL1 , PER1–PER3 , CRY1 , and CRY2 regulate CRs in a negative feedback loop. The circadian disruption of the sleep–wake cycle manifests in at least six distinct clinical conditions. These are the circadian rhythm sleep–wake disorders (CRSWDs). Their diagnosis is made by history, sleep diaries, and actigraphy. Treatment involves a combination of timed light exposure, melatonin/melatonin agonists, and behavioral interventions. In addition, CR disturbances and subsequent misalignment can increase the risk of a variety of illnesses. These include infertility and menstrual irregularities as well as diabetes, obesity, fatty liver disease, and other metabolic syndromes. In addition, a disruption in the gut microbiome creates a proinflammatory environment. CR disturbances increase the risk for mood disorders, hence the utility of light-based therapies in depression. People with neurodegenerative disorders demonstrate significant disturbances in their CRs, and in their sleep–wake cycles. Circadian realignment therapies can also help decrease the symptomatic burden of these disorders. Certain epilepsy syndromes, such as juvenile myoclonic epilepsy (JME), have a circadian pattern of seizures. Circadian disturbances in epilepsy can be both the consequence and cause for breakthrough seizures. The immune system has its own CR. Disturbances in these due to shift work, for instance, can increase the risk of infections. CR disturbances can also increase the risk of cancer by impacting DNA repair, apoptosis, immune surveillance, and cell cycle regulation. Moreover, the timing of chemotherapeutic agents has been shown to increase their therapeutic impact in certain cancers.

Humans spend approximately one third of their life asleep but, as counterintuitive as it may sound, sleep is far from being a quiet state of inactivity. Sleep provides the opportunity to perform numerous biological and physiological functions that are essential to health and wellbeing, including memory consolidation, physical recovery, immunoregulation, and emotional processing. Yet, sleep deprivation, chronic sleep restriction, and various types of sleep disorders are all too common in modern society. Failure to meet the recommended 7-9 hours of restful sleep per night is known to increase the risk of several health conditions, reason why regular and adequate sleep should be seen as a priority instead of an unnecessary commodity easily traded as required by the commitments of our busy lives. While both the quantity and the quality of sleep can be largely improved with relatively straightforward practices dictated by good sleep hygiene, emerging research suggests that dietary and supplementation protocols focused on certain foods, nutrients, and biochemical compounds with sleep-promoting properties can act as subsidiary sleep aids in complementing these behavioral changes. The scope of this narrative review is to summarize the available evidence on the potential benefits of selected nutraceuticals in the context of circadian rhythm and sleep disturbances, namely melatonin, magnesium, omega-3 fatty acids, tart cherry juice, kiwifruit, apigenin, valerian root, L-theanine, glycine, ashwagandha, myoinositol, Rhodiola rosea, and phosphatidylserine. A comprehensive recapitulation of the relevant literature is provided, alongside corresponding evidence-based nutritional protocols to promote and improve restful sleep.

Time-Restricted Eating is an eating pattern based on the circadian rhythm which limits daily food intake (usually to ≤12 h/day), unique in that no overt restriction is imposed on the quality, nor quantity, of food intake. This paper aimed to examine the effects of two patterns of TRE, traditional TRE, and Ramadan fasting, on two markers of circadian rhythm, cortisol and melatonin. PubMed and Web of Science were searched up to December 2020 for studies examining the effects of time restricted eating on cortisol and melatonin. Fourteen studies met our inclusion criteria. All Ramadan papers found statistically significant decrease in melatonin (p < 0.05) during Ramadan. Two out of the three Ramadan papers noted an abolishing of the circadian rhythm of cortisol (p < 0.05). The non-Ramadan TRE papers did not examine melatonin, and cortisol changes were mixed. In studies comparing TRE to control diets, Stratton et al. found increased cortisol levels in the non-TRE fasting group (p = 0.0018) and McAllister et al. noted no difference. Dinner-skipping resulted in significantly reduced evening cortisol and non-significantly raised morning cortisol. Conversely, breakfast skipping resulted in significantly reduced morning cortisol. This blunting indicates a dysfunctional HPA axis, and may be associated with poor cardio-metabolic outcomes. There is a paucity of research examining the effects of TRE on cortisol and melatonin. The contrasting effect of dinner and breakfast-skipping should be further examined to ascertain whether timing the feeding window indeed has an impact on circadian rhythmicity.

tonin levels begin increasing in the late evening, reaching the maximum in the early hours between 2:00 and 4:00 a.m., followed by a slow decline to lower daytime levels. Daytime levels of melatonin are barely detectable. In addition to sunlight, artificial indoor lighting can be bright enough to prevent the nocturnal release of melatonin. Normal production of melatonin can vary considerably between individuals. In general, melatonin production decrease with aging. Among the other factors that have been most consistently linked to modified melatonin levels are disrupted light–dark cycles, night work and being overweight. In addition, it has been demonstrated that some nutritional factors could also modify melatonin production, however less intensely. Weather dietary factors contribute only to the pineal production of melatonin or also to the extra-pineal sites such as the gastrointestinal production is not known. Once synthesized, melatonin is not stored in producing cells, but is quickly released into the blood and begins circulation. Thus, the concentration in plasma faithfully reflects pineal secretion. In addition melatonin concentration can be measured in other body fluids as saliva and urine. Saliva levels are about 40% of those in plasma. Endogenous nocturnal melatonin production has been estimated to be about 10–80 µg per night, the daytime production being significantly less. The metabolism of melatonin is rapid, and its half-life in humans varies between 10 and 60 min following exogenous administration. It is deactivated mostly by the liver and excreted in urine. Urinary metabolite, 6-sulphatoxymelatonin (6-SMT) reflects the plasma melatonin profile and can be used for evaluation of melatonin status. In urine, 50–80% of 6-SMT appears in the overnight sample. Dietary compounds There are several studies indicating dietary influence on the synthesis or the concentration of melatonin. Energy restriction Strong influence of food on melatonin synthesis is detect