Delayed Sleep Onset

The average time it takes a healthy adult to fall asleep is approximately 10 minutes [28]. When sleep onset exceeds 10 minutes, and particularly when it is consistently over 20 minutes, this is considered delayed sleep onset, a hallmark feature of disrupted melatonin secretion, either in terms of timing (phase delay) or inadequate production.

Normally, melatonin secretion begins 1 to 2 hours before habitual bedtime, preparing the body for sleep by lowering core body temperature, reducing alertness, and interacting with MT1 receptors in the hypothalamus to initiate the sleep cascade. When melatonin is secreted too late or in insufficient amounts, this signaling process is weakened or delayed, making it harder for the brain to switch into sleep mode.

Clinical trials have shown that melatonin support can reduce sleep onset latency by up to 40%, promoting faster and more natural sleep initiation.[27]

Evening Arousal

A deficiency in slow-wave sleep (SWS) caused by circadian disruption is thought to impair synaptic downscaling, the neurophysiological process by which cortical excitability is reduced and neural circuits are recalibrated. When this process is disrupted, the brain remains in a state of elevated excitability, leading to cognitive hyperarousal, particularly in the evening. 

This disruption is further compounded by elevated nocturnal cortisol levels, which have been associated with increased mental activation and difficulty initiating sleep. Chronic activation of the stress response system not only impairs sleep architecture but also disrupts hippocampal function and neuroimmune balance, perpetuating both sleep disturbance and depressive symptomatology [18].

Waking Unrefreshed 

Melatonin is vital for maintaining the structure and depth of sleep. It promotes the consolidation of deep, slow-wave sleep (N3), which is crucial for physical and cognitive restoration. Melatonin also helps organize the timing of various sleep stages, allowing for a more coherent and restorative sleep cycle.

Therefore, when melatonin is deficient, sleep becomes fragmented, less deep, and less rejuvenating, causing symptoms of waking up feeling unrefreshed despite spending adequate time asleep. 

Clinically Melatonin support has been found to improve next-day energy levels, in individuals with disrupted melatonin rhythms or reduced secretion.[27]

Light Sleep / Disturbed Sleep 

Melatonin deficiency or circadian rhythm disruption can compromise both the depth and stability of sleep by impairing melatonin’s normal signaling through MT1 and MT2 receptors. Under normal conditions, MT1 receptors help reduce neuronal excitability, while MT2 receptors coordinate the proper progression through sleep stages. 

When melatonin levels are insufficient or mistimed, this signaling becomes dysregulated, leading to poor transition into deeper phases of sleep. As a result, sleep becomes dominated by lighter stages, specifically N1 and N2, while stage N3 (deep sleep) and REM sleep are reduced. This imbalance contributes to a pattern of light, fragmented sleep, where individuals wake easily and struggle to maintain sleep continuity.

Pronounced Afternoon Slumps

The body runs on an internal 24 hour clock called the circadian rhythm, which regulates sleep, energy, hormones, and alertness. Within this cycle, there are natural energetic highs and lows. These low points are known as circadian troughs, and they typically occur between 1 - 3pm. Although energy decline here is a natural rhythm of the body, the pronounced effect of decline is more closely related to the quality and hours of sleep.

This occurs because the less hours of quality sleep regeneration the more ‘sleep pressure’ that builds up the longer you’re awake. If you are deprived of quality sleep, these troughs feel much sharper because your body already carries extra sleep pressure.

This is further demonstrated in many clinical studies. One example is a study on 38 participants who were kept awake for 29 hours. These participants experienced a 30 - 40% further decline in attention and focus during the circadian trough compared to those without sleep deprivation. Another study demonstrated that sleep restriction of 5 hours per night for 7 nights against well-rested controls demonstrated more magnified declines during the circadian troughs, appearing as impaired alertness and lower vigilance. [45][46]

Cognitive Impairments

Reduced sleep efficiency, prolonged sleep onset and frequent awakenings as a result of Circadian Disruption, have a profound negative impact on cognitive function. Research indicates that individuals with lower sleep efficiency or longer sleep onset face approximately 1.5 times greater odds of progressing to mild cognitive impairment (MCI), and the prevalence of sleep disturbances in individuals with cognitive impairment is especially high, with some studies reporting rates as high as 63%. [20] 

On a neurobiological level, the age-related decline in restorative deep sleep (N3 stage), which is essential for memory consolidation and brain detoxification, impairs cognitive recovery. Disrupted sleep has also been associated with increased accumulation of amyloid beta in the brain, a pathological hallmark of Alzheimer’s disease and other forms of cognitive decline. Furthermore, poor sleep is also linked to measurable impairments in attention and executive function such as planning and problem-solving, which can closely resemble the core symptoms of ADHD. [21]

Mood Disorders

Circadian Disruption impairs slow wave sleep, which is when the glymphatic system becomes most active, clearing neurotoxic waste products such as beta-amyloid and inflammatory metabolites. This reduction contributes to neuroimmune balance and reduces the burden of oxidative stress and inflammation, both of which are implicated in mood disorders. Therefore, reductions in SWS not only impair emotional resilience but also allow the accumulation of neurobiological stressors that perpetuate mood disorders.[18]

Poor Short-term Memory

Poor slow-wave sleep (SWS) significantly impairs short-term memory by disrupting the brain’s ability to consolidate new information. SWS is a critical phase of non-REM sleep during which the hippocampus actively communicates with the neocortex through coordinated neural patterns, namely, slow oscillations, sleep spindles, and hippocampal sharp wave ripples. 

This synchronized activity enables the transfer and integration of newly acquired short-term memories into stable storage. Therefore the resulting decrease in slow-wave activity (SWA) compromises synaptic plasticity, leading to poor memory retention.[19]

Easily Overwhelmed / Low Stress Tolerance

Sleep deprivation and poor slow wave sleep (SWS) sleep significantly increases emotional sensitivity to even mild stress. This is because SWS facilitates neurophysiological processes essential for brain recovery and emotional stability. During SWS, neuronal firing slows and becomes highly synchronized, creating an optimal environment for synaptic downscaling, a process that reduces synaptic strength accumulated during wakefulness. This downscaling is critical for recalibrating emotional circuits and maintaining efficient connectivity between the prefrontal cortex, amygdala, and hippocampus, which are key regions involved in emotion regulation. 

When SWS is deficient, this recalibration is impaired, leading to heightened amygdala reactivity, reduced prefrontal inhibition, and dysregulated hippocampal processing of emotional memories. Together, these disruptions contribute to increased emotional reactivity and poor stress tolerance.

In one study researchers found that just one night of total sleep deprivation led healthy adults to report greater levels of subjective stress, anger, and anxiety when faced with low-level cognitive stressors, such as simple tasks like counting backwards by twos, suggesting that sleep loss makes mild challenges feel more overwhelming. [17]

Prone to Sickness / Recurring Sickness [ Innate Immune Impairment ]

When the body doesn’t produce enough melatonin, it weakens important parts of the innate immune system, the part that provides our first defense against infections. This includes a drop in the number and activity of natural killer (NK) cells and macrophages, which are frontline cells that attack harmful invaders. Melatonin deficiency also interferes with the ability of immune cells to move toward infection sites, and how they clear out pathogens. Altogether, these changes weaken the body’s initial ability to fight off infections.

Melatonin deficiency also disrupts the adaptive immune system, which provides targeted and long-lasting defense. It hinders the growth and activation of T lymphocytes by reducing IL-2 signaling, which is an important pathway for turning on these immune cells. At the same time, B cell function and antibody production also declines. As a result, both antibody-based and cell-mediated responses become less effective in defending the body.[24]

Chronic Pain + Autoimmunity 

Melatonin plays a significant role in controlling inflammation and pain perception. It inhibits cyclooxygenase-2 (COX-2), an enzyme central to the inflammatory response, which produces prostaglandins, molecules that cause swelling, redness, and pain. By blocking COX-2, melatonin helps suppress the inflammatory cascade and reduces the overall inflammatory reaction in the body.

In a clinical trial rats with paw swelling were given melatonin at doses of 1 mg per kg and demonstrated a 29% reduction in swelling, respectively, compared to untreated rats. It also raised the pain threshold by 40%, showing that the rats were less sensitive to pain after melatonin [2].

Another human trial on 27 patients with fibromyalgia syndrome (FMS) received 5 mg of melatonin nightly for a duration of eight weeks. Results demonstrated a statistically significant reduction in pain intensity, fatigue, morning stiffness, sleep quality, physical function, and emotional well-being.[26]

Furthermore Melatonin is also a critical inhibitor of nuclear factor-kappa B (NF-κB) activation. In the absence of melatonin, this regulatory mechanism is lost, resulting in unchecked cytokine production. This dysregulation heightens not only pain but the development and exacerbation of autoimmune disease.[24]

Prone to Migraines

Melatonin acts as an analgesic, reducing pain, and also has anti-nociceptive properties, blocking pain signals. It attaches to specific receptors in parts of the brain involved in migraines, namely the trigeminal ganglia and brainstem and calms the activity of the trigeminal vascular system, a major nerve pathway involved in migraine attacks. 

In a study with 146 migraine patients, researchers found migraine sufferers compared to healthy people had much lower levels of 6-sulphatoxymelatonin, a marker of nighttime melatonin production.

In another study, 34 migraine patients took 3 mg of melatonin at bedtime and saw a decrease in how often and how intensely they had migraines, as well as how long the attacks lasted. Another treatment using a drug that works like melatonin also reduced migraine frequency and duration when taken at 25 mg daily for three months. [25]