Melatonin: A Critical Protector in Modern Health

Melatonin is marketed in the US as a sleep aid, but its role in human health extends far beyond regulating sleep cycles. It serves as one of the body’s most potent neuroprotective agents and antioxidants, safeguarding against oxidative stress, inflammation, and systemic damage. Melatonin influences cellular repair, immune regulation, and the prevention of chronic diseases that include cancer and neurodegenerative disorders. Its unique ability to cross the blood-brain barrier makes it essential to protect the brain and spinal cord from the oxidative damage that accelerates aging and cognitive decline. Despite its importance, modern lifestyles actively suppress melatonin production and leave the body vulnerable to long-term health consequences.

The widespread suppression of melatonin is not idiopathic; it results from profound changes in our culture driven by the advent of technology and man-made electromagnetic fields (MEMF). The rapid pace of technological advancement has dramatically altered human physiology and behavior. Prolonged screen use, chronic stress, poor diet, irregular schedules, and artificial light disrupt the natural rhythms of melatonin secretion. Populations such as night shift workers, first responders, and military personnel face heightened risks, as circadian misalignment increases their susceptibility to cancer, cognitive decline, and immune dysfunction. Trauma survivors face unique challenges, with significant derangement of normal cortisol rhythms (which also suppress nighttime melatonin secretion).  In children and adolescents, early exposure to screens and irregular sleep patterns distort the developing cycles mediated by the ANS.  This can lead to lifelong disruptions to circadian function and systemic health.

The Cancer Connection

Melatonin is not just a sleep-regulating hormone; it plays a critical role in protecting against cancer. Clinical research shows that melatonin inhibits tumor growth, reduces inflammation, and enhances immune response, demonstrating its oncostatic properties. Cancer patients have plasma melatonin levels reduced by as much as 68% compared to healthy individuals, which suggests that its depletion contributes to tumor progression. What remains puzzling is why melatonin isn’t used more preventively. Despite its proven ability to support cancer treatment, reduce inflammation, and protect against cognitive decline, public health strategies rarely address its role beyond sleep.

Night shift workers face a 40–50% higher risk of hormone-related cancers, such as breast and prostate, associated with chronic melatonin suppression and circadian disruption. While Western medicine has not fully admitted a causal relationship, the International Agency for Research on Cancer (IARC) has classified night shift work involving circadian disruption as a probable human carcinogen. Research also shows significant alterations in circadian timing among night workers, including delays or shifts in melatonin rhythms, which further compromise systemic health. Despite robust evidence supporting melatonin’s safety and efficacy, public health strategies rarely address its role beyond sleep.

NTP Review of Shift Work at Night, Light at Night, and Circadian Disruption

 Melatonin and Metabolic Regulation

Melatonin plays a critical role in regulating nighttime metabolic processes, particularly in the liver and pancreas. Through the M1 and M2 receptors, melatonin inhibits nighttime insulin production, slows glycolysis, and preserves blood glucose levels for the brain, which depends heavily on this energy source. Without sufficient melatonin, liver glycolysis accelerates, depleting blood sugar levels prematurely. As a result, the liver must release adrenaline to mobilize stored glucose, causing individuals to wake throughout the night. Over time, these disruptions compromise lipid metabolism, which serves as the most significant precursor to insulin resistance and type 2 diabetes. The link between melatonin deficiency, circadian disruption, and metabolic imbalance is another example of its role in systemic health.

Blue Light and Screens

The widespread use of screens and artificial light suppresses melatonin production and disrupts circadian rhythms across all age groups. Blue light from phones, computers, and other devices inhibits the pineal gland’s melatonin secretion, particularly in the evening or at night, and effects can last more than up to two hours after exposure.  . In children, the effects are especially pronounced. Light exposure one hour before bedtime has been shown to reduce melatonin levels by 69% to 99% in children aged 3 to 4.9 years, and evening light exposure suppresses melatonin twice as much in children compared to adults. In adults, the effects of screen exposure are cumulative, with consistent nighttime light exposure delaying melatonin secretion, reducing sleep quality, and amplifying sympathetic nervous system activity. Over 90% of studies on screen time show a strong link to delayed bedtimes and shorter total sleep durations, effects that compound over time and contribute to systemic health risks. These disruptions impair immune resilience, metabolic regulation, and cognitive function across the lifespan. Limiting evening screen exposure is essential to preserving melatonin secretion, protecting circadian rhythms, and reducing long-term health risks.

The Cortisol-Melatonin Connection

Cortisol and melatonin are the two key hormones that regulate the body’s circadian rhythms. Their relationship is inverse: cortisol peaks in the morning to promote wakefulness, while melatonin rises at night to prepare the body for sleep and repair processes. However, chronic stress, sympathetic dominance, or circadian disruption elevates cortisol levels at inappropriate times, disrupting this delicate balance.

1. Suppression of Melatonin Production:
   Elevated nighttime cortisol directly suppresses melatonin secretion from the pineal gland. This is particularly problematic for populations experiencing chronic stress or circadian misalignment, such as night shift workers and individuals with trauma-related hypervigilance. Without sufficient melatonin, the body cannot fully engage in nighttime repair processes, amplifying oxidative stress and systemic inflammation.
2. Delayed Circadian Timing:
   Dysregulated cortisol disrupts the body’s internal clock, delaying the onset of melatonin secretion. This delay pushes the sleep-wake cycle out of sync, leading to poor sleep quality and extended periods of wakefulness. NASA’s research on astronauts demonstrated how disrupted light-dark cycles elevate cortisol, delaying melatonin secretion and impairing cognitive performance.
3. Feedback Loop of Sympathetic Overdrive:
   Chronically elevated cortisol not only suppresses melatonin but also perpetuates sympathetic dominance, creating a feedback loop. Sympathetic overdrive prevents the parasympathetic nervous system from taking over at night, leaving the body in a heightened state of alertness. This contributes to insomnia, increased adrenaline release, and metabolic dysfunction.
4. Systemic Consequences:
   Cortisol’s suppression of melatonin has cascading effects on systemic health. Reduced melatonin impairs glucose metabolism, lipid regulation, and immune resilience, increasing the risk of metabolic syndrome, type 2 diabetes, and cardiovascular disease. Elevated cortisol levels also accelerate neurodegenerative processes, heightening the risk of cognitive decline over time.

Key Takeaways:

• Elevated nighttime cortisol suppresses melatonin secretion and delays its onset, disrupting circadian rhythms.
• Chronic stress and sympathetic dominance create a feedback loop that perpetuates melatonin suppression and systemic stress.
• Reduced melatonin impacts glucose metabolism, lipid regulation, and immune function, increasing risks of metabolic syndrome, diabetes, and cardiovascular disease.
• The combination of cortisol dysregulation and melatonin suppression underscores the need for interventions targeting both stress and circadian alignment.

General Risks of Melatonin Suppression and Circadian Disruption

Certain populations face heightened risks from melatonin suppression. Night shift workers, trauma survivors, and children are particularly vulnerable, as circadian disruptions cause sleep disturbances, metabolic dysfunction due to elevated cortisol, higher cancer rates, and cognitive impairment. For the general population, these risks usually remain subclinical but accumulate over time, leading to long-term issues like metabolic syndrome, cardiovascular disease, and neurodegeneration.

Altered Cortisol Patterns in Nurses:

Nurses working rotating shifts show abnormal cortisol patterns. Elevated cortisol levels appear in the evening (before shifts) and late at night, contributing to higher stress and disrupted sleep. This disruption links to chronic fatigue, decreased immune function, and an increased risk of stress-related diseases (Kondratova et al., 2012). As a 20+ year clinician serving first responders and medical staff for Work Comp, not one of them had heard of melatonin supplementation, even though many of my nurses were aware of the elevated cancer risks.

Cortisol and Metabolic Risks in Night Shift Workers:

A systematic review in PLOS ONE finds that night shift workers experience both short-term and long-term disruption to cortisol secretion, directly linking this disruption to an increased risk of metabolic disorders, such as obesity, insulin resistance, and cardiovascular diseases (Wright et al., 2013).

Research in Chronobiology International shows that night shift workers exhibit significantly higher cortisol levels than day workers. This disruption impairs metabolic function and increases stress, with cortisol peaks at inappropriate times during night shifts, failing to drop in the early morning as they would in a regular diurnal pattern (Chtourou et al., 2011).

 

A New Frontier: Liposomal Melatonin

Melatonin suppression is more than an individual problem; it is a public health crisis. To confront these challenges, we must reframe how melatonin is viewed and used. Waiting until a catastrophic diagnosis or relying solely on symptom-based interventions is not sufficient. We can proactively address melatonin deficiency through supplementation, education, and systemic change, which offers a path to reduce the long-term burden of chronic disruption caused by modern technology on the nervous system. This is an opportunity to take a simple, cost-effective step toward improving health outcomes for at-risk groups and the population as a whole.

Liposomal melatonin is one such innovation. This recent advancement boosts the bioavailability of melatonin compared to traditional oral supplements, which fail due to poor absorption and rapid metabolism, which leads to suboptimal plasma concentrations. Liposomal encapsulation protects melatonin from digestive degradation, allowing direct absorption through the membranes and bypassing first-pass metabolism, ensuring a sustained release into the bloodstream.

A recent study on melatonin-loaded solid lipid nanoparticles demonstrated that oral administration of 3 mg melatonin via solid lipid nanoparticles (SLNs) maintained plasma levels above 50 pg/mL for approximately 24 hours, which indicates a prolonged and stable release profile. These findings suggest that liposomal melatonin formulations can achieve higher and more sustained plasma concentrations that have the potential to improve therapeutic outcomes for circadian rhythm disturbances. 

 Public Health's Oversight of Circadian Disruption

Recent history offers us numerous examples where profit motives and public health policy resulted in widespread harm. The Sackler family and Purdue Pharma aggressively marketed OxyContin despite knowing its addictive potential, fueling an opioid crisis that continues to devastate communities. The tobacco industry similarly withheld information about the dangers of smoking for decades, prioritizing profits over public health. In other cases, such as the delayed recognition of birth defects linked to drugs like flutamide, harm emerged unintentionally, illustrating the risks of insufficient oversight and transparency. These examples highlight the danger of tying public health messaging to financial incentives, as individuals cannot make an informed choice without clear, accurate data.

The downplaying of circadian disruption—whether from blue light, irregular shifts, or trauma—represents a public health failure of staggering proportions. Disruptions from melatonin suppression contribute to metabolic disorders, insulin resistance, cardiovascular disease, cancer, and cognitive decline. This is particularly harmful to children, whose developing circadian systems are regulated by the autonomic nervous system (ANS). Early exposure to screens and irregular sleep patterns distorts circadian rhythm development and contributes to lifelong issues with immune function, metabolism, and cognitive health.

Traditionally, oral melatonin supplementation provides limited benefit due to poor absorption, but newer formulations like liposomal and intranasal increase bioavailability and offer a safe alternative to protect circadian balance. Disruptions to melatonin-cortisol rhythms also contribute significantly to sympathetic dominance and autonomic dysregulation. As we introduce treatment strategies for harmonizing autonomic function, it is essential to understand how to support proper circadian cycling.

We could prioritize the preventive benefits of melatonin to reduce health risks faced by night shift workers, first responders, military personnel, and trauma survivors rather than waiting to use it as an adjunct for chemotherapy.

As consumers become more aware of the deep implications of melatonin suppression on the nervous system, they can make informed choices and take steps to protect their health and the health of their families.

 

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  Chtourou, H., Souissi, N., & Kallel, C. (2011). Shift work and sleep patterns: A review of the current literature. Chronobiology International, 28(8), 643-657.

  Hansen, M. V., Danielsen, A. K., Hageman, I., Rosenberg, J., & Gögenur, I. (2014). The therapeutic or prophylactic effect of melatonin in cancer patients: A systematic review and meta-analysis. Cancer Treatment Reviews, 40(4), 539–546. https://doi.org/10.1016/j.ctrv.2013.11.005

  International Agency for Research on Cancer. (2019). Night shift work and cancer risk. Retrieved from https://blogs.cdc.gov/niosh-science-blog/2021/04/27/nightshift-cancer/

  Kondratova, A. A., Kondratov, R. V., & Barreira, C. A. (2012). Circadian rhythms in health and disease: Insights from human shift workers. Journal of Physiology, 590(6), 1635–1655.

  Reiter, R. J., Tan, D. X., & Galano, A. (2014). Melatonin: Exceeding expectations. Physiology, 29(5), 325–333. https://doi.org/10.1152/physiol.00018.2014

  Rao, D., Yu, H., Bai, Y., & Zheng, X. (2015). Night shift work and the risk of prostate cancer: A meta-analysis. OncoTargets and Therapy, 8, 2651–2658. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC4599640/

 Seely, D., Wu, P., Fritz, H., Kennedy, D. A., Tsui, T., Seely, A. J., & Mills, E. (2012). Melatonin as adjuvant cancer care with and without chemotherapy: A systematic review and meta-analysis of randomized trials. Integrative Cancer Therapies, 11(4), 293–303. https://doi.org/10.1177/1534735412455408

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   Zisapel, N. (2018). New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation. British Journal of Pharmacology, 175(16), 3190–3199. https://doi.org/10.1111/bph.14116