These three biochemicals are the cornerstones of the sleep architecture, and only by optimizing them can we address sleep deprivation and insomnia sustainably.
This story does not include health advice. It is for information, inspiration, and awareness purposes.
Like millions of other people, I also struggled with sleep deprivation and insomnia, which caused me metabolic and mental health issues like prediabetes, abdominal obesity, and brain fog. Sleep is critical for our health and well-being. It is a fundamental requirement for our physical and mental health.
The body and mind cannot survive without adequate sleep and thrive without restorative sleep. We might sleep long hours, but if our sleep is not quality with optimal hormonal levels, the body cannot recover, and the neurons cannot create memories efficiently.
Sleep is critical for cellular, metabolic, immune, endocrine, and neurological health. Therefore, understanding its architecture and the role of circadian rhythm in health and disease formation can be invaluable.
Circadian rhythm is one of the biological rhythms for surviving and thriving. Disturbance of the circadian rhythm “has been associated with disease states, like metabolic disorders, depression, and cancers.” Another paper also informs that “disturbances in circadian rhythm have been linked to chronic diseases like insomnia, hypertension, diabetes, and depression.”
Circadian rhythm is part of the body’s internal clock in 24 hours. This rhythm manages our sleep-wake cycles. Cortisol, melatonin, and adenosine are closely related. These three biochemicals play a critical role in sleep quality and wakefulness state. They are vital to determining the behavior of the circadian rhythm.
As I studied hormones, neurotransmitters, enzymes, and other biochemicals for metabolic and mental health methodically, I want to give you a high-level perspective without going into scientific or technical details using my personal experiences.
1 — Cortisol: The Main Stress Hormone
I will start with cortisol, as it is a master hormone that can affect the behavior of all other hormones. Cortisol is the primary hormone that manages stress. There are other stress hormones like adrenalin and nor-adrenalin, which I introduced in previous stories.
A few years ago, I wrote a story titled Fat Loss Remains a Dream Unless We Manage Cortisol. New readers who missed my related stories ask me why cortisol, as a stress hormone, is important for metabolic health, especially since they wanted to know how it affects insulin resistance and sleep.
Elevated cortisol in my bloodstream raised serious alarm bells in my younger years. My primary healthcare professional raised her concerns and referred me to an endocrinologist who diligently focused on my hormonal profile.
Elevated cortisol was the root cause of my hormonal imbalance. For example, the higher the cortisol, the lower my testosterone, according to my endocrinologist. With heightened cortisol and lowered testosterone, many disease and discomfort symptoms started bothering me, affecting my performance and killing the joy of life.
The root cause of my elevated cortisol was chronic (emotional, mental, and physical) stress. This hormone was trying to save my life, which was terrific. However, I had no clue why my stress and anxiety were so high.
As the body’s emergency alarm system, cortisol responds to stress for survival. When we encounter stress, the brain triggers the HPA axis (hypothalamic-pituitary-adrenal), a complex stress response system.
This prompts adrenal glands to release cortisol into the bloodstream, priming the body for fight or flight by increasing blood sugar, suppressing the immune system, and boosting heart rate and blood pressure.
However, cortisol levels can fluctuate, either becoming excessively high, low, or remaining elevated for prolonged periods due to chronic stress, trauma, illness, injury, or certain medications.
Elevated and prolonged cortisol levels can detrimentally impact metabolism, leading to insulin resistance, blood sugar fluctuations, inflammation, immune system irregularities, fatigue, sleep issues, anxiety, depression, cognitive impairment, visceral fat buildup, and muscle loss.
Moreover, elevated cortisol levels can inhibit fat burning, promoting fat storage, particularly around organs, and induce muscle breakdown. Balancing cortisol is vital for losing visceral fat and retaining muscle mass.
I want to give a few tips on optimizing cortisol based on my experience. You can read the details in my previous story titled Optimize Cortisol to Melt Belly Fat and Keep Lean Muscles with Three Tips, which introduces strategies for optimizing cortisol levels to support a healthier body composition and overall well-being.
Firstly, prioritize stress management through relaxation techniques like meditation, diaphragmatic breathing exercises, or yoga to regulate cortisol release. Ensure quality sleep, as inadequate rest can elevate cortisol levels.
Regular physical activity and workouts can aid in balancing cortisol and promoting overall well-being. A balanced diet with adequate nutrients supports adrenal health, impacting cortisol regulation. Building a routine with structured meal times and breaks helps manage stress and cortisol responses.
Additionally, mindfulness practices, including meditation and social connections, assist in reducing chronic stress, ultimately supporting balanced cortisol levels.
2 — Melatonin: Sleep-Inducing Hormone
As pointed out in this study, “In adults, the melatonin onset typically occurs during low cortisol secretion. With aging, the production of melatonin declines and is shifted to later hours while the production of cortisol increases, and its peak occurs earlier in the night.”
The body produces melatonin naturally when it senses darkness. However, I frequently used exogenous melatonin as a shift worker who traveled overseas on long trips. It helped regulate my circadian rhythm and temporarily solved my jet lag issues.
The problem was, after a while, using exogenous melatonin did not work at certain times. I had difficulty sleeping and had insomnia. I used to take one-milligram tablets as prescribed by my doctor.
Melatonin was sold over the counter in several countries I visited. More surprisingly, the dose they recommended was five and even ten milligrams. One day in a foreign country, I asked the pharmacist about the dose, considering people consumed five and even ten times more than what I used to take. She said melatonin was the safest supplement.
She also mentioned that taking 10mg would not have any side effects. Besides, she said it was a potent antioxidant and immune booster. The pharmacist said melatonin was used in much higher doses, like 20 and 50 milligrams, for chronic diseases requiring higher immunity.
I believed the pharmacist but was not fully convinced. So, I started taking 10mg tablets. Unfortunately, I saw no benefits after trying it for a week. It even made me feel worse. My mood was extremely low in the morning, and I felt drowsier, which affected my work.
I thought something must be wrong with the dose. So, when I came back to Australia, I shared my experience with my specialist physician friend. He gave me a brief education session on the side effects of exogenous melatonin, especially in higher doses. His points made sense.
Exogenous melatonin was great for solving jet lag issues but not effective for solving chronic stress issues. Learning about the roles of opposing hormones empowered me to make lifestyle changes.
I focused on addressing my accumulating stress rather than using exogenous melatonin. Looking at the sun first thing in the morning and refraining from electronic devices at night optimized my melatonin levels. Then, optimizing adenosine solved my sleep issues.
3 — Adenosine: A Purine Nucleoside
Adenosine is a significant sleep and wakefulness regulator. Unless we understand its role and align our lifestyles based on its architecture, I cannot think of any other way to solve sleep issues.
Adenosine is a naturally occurring molecule in the body that regulates sleep/wake cycles and has several other roles. As a nucleoside, it comprises a nitrogen-containing base called adenine and ribose sugar. A purine nucleoside is a genetic enzyme serving as a building block of nucleic acids.
As documented in this paper, adenosine is so critical that it exists in all cells in various forms. Besides regulating sleep and wakefulness, it is also involved in energy metabolism, blood flow regulation, inflammation, and neuroprotection.
The most critical information is the delicate balance of this compound in the body, as imbalances can cause severe physical and mental health disorders. However, measuring adenosine levels in the bloodstream is challenging as they rapidly form or disappear, as explained in this paper.
For healthy sleep and wakefulness, we need more adenosine during the night and less of it during the day. However, those who suffer from sleep deprivation or insomnia have the opposite: they have too much adenosine during the day and too little at night.
Adenosine makes us drowsy so that we fall asleep quickly. But, drowsiness during the day can affect our focus, attention, memory, and mood. When we are drowsy, we cannot be creative or productive. We also have low mood and energy, as the molecule controls the energy system.
Those who easily fall asleep and wake up feeling refreshed have high adenosine levels at night and very low levels in the morning, gradually building up during the day.
Adenosine plays a critical role in regulating blood flow and blood pressure. It is a regulator of coronary blood flow. It acts as a vasodilator. It means that it causes the blood vessels to widen or dilate. This process increases blood flow and decreases resistance to blood flow, which helps lower blood pressure.
Adenosine’s ability to dilate blood vessels can reduce inflammation and promote tissue repair. This makes it an essential molecule in maintaining cardiovascular and immune health. The less known and spoken aspect of adenosine is its anti-inflammatory and pain-relieving properties. Ironically, it also has pro-inflammatory effects. It is complex and context-driven. It has multiple functions for preventing or causing inflammation.
The critical point is that balancing adenosine can lower its pro-inflammatory effects and increase its anti-inflammatory effects. This delicate balance can also balance energy levels in cells.
Adenosine can recruit immune cells, like Tregs, which can suppress inflammation by releasing anti-inflammatory cytokines. And by triggering ATP, it can produce two major pro-inflammatory cytokines (IL-1beta and IL-18). This paper in Nature informs that “targeting adenosine receptors directly for the treatment of rheumatic diseases is currently under study.” Its anti-inflammatory features look promising for treating arthritis.
Studies investigating adenosine in central nervous system diseases indicate that adenosine can inhibit the release of glutamate and aspartate after ischemia and reduce the cytotoxic effects of these excitatory amino acids synthesized by the exact mechanism of gamma-aminobutyric acid.
Ischemia is a health condition. Those with this condition suffer from blood flow problems to vital organs like the brain and heart. For example, ischemia can reduce the heart muscle’s ability to pump blood. A sudden and severe heart artery blockage can lead to a heart attack.
Reducing the cytotoxic effect can protect neurons. Cytotoxic agents are harmful to healthy cells and neurons. However, cytotoxic agents can be used as a medication to kill cancer cells.
Various lifestyle factors can disrupt the balance of adenosine. The most common cause of adenosine imbalances is lack of sleep. It is scientifically proven and well-documented in the literature that caffeine is an adenosine antagonist.
Adenosine builds up in the brain during the day, making us feel tired and promoting sleep. However, caffeine blocks the adenosine receptors by binding to the same receptors that adenosine would bind to. So caffeine can keep us awake and alert by preventing adenosine from making us tired.
Exercise can increase the release of potent neurotransmitters such as dopamine and norepinephrine. It is a good thing. However, these neurotransmitters can counter adenosine’s sedative effects, which are essential for falling asleep and having restorative sleep.
When we exercise at earlier times of the day, exercise can increase the production of ATP. It can then be broken down to adenosine to bind to the receptors. Thus, the brain accumulates more adenosine throughout the day, and when it reaches its peak at night, we fall asleep quickly and “sleep like a baby.”
However, there are more biochemical factors like melatonin and cortisol hormones and the balance of neurotransmitters for sleep. But without adenosine, sleep does not happen; therefore, I highlight this fundamental.
I want to highlight three critical points to explain the value of sunlight during the day. The key point concerns the neurotransmitter serotonin, which regulates mood, sleep, and appetite.
In this context, serotonin can inhibit adenosine formation by inhibiting the enzyme's activity that converts adenosine monophosphate (AMP) to adenosine.
As a second point, sunlight exposure can also inhibit adenosine kinase activity. This enzyme can break down adenosine. Therefore, it can gradually increase adenosine levels in the brain, peaking at night.
The third point is that sunlight exposure can modulate the expression of adenosine receptors in the brain. This modulation can increase the number of receptors available to bind adenosine. So, it has the same effect as the previous item.
Finally, alcohol can increase the release of adenosine from nerve cells, inhibiting the enzyme that breaks down adenosine. This process can cause the levels of adenosine in the brain to rise more and can lead to feelings of drowsiness and sedation. You might think this is a good thing. But when we closely look at it, we notice it is a bad habit. Those who use alcohol as a sleeping aid learn this hard lesson.
Conclusions and Takeaways
Ironically, deprived sleep was increasing my stress and causing the secretion of more cortisol. It was a sign of a catch-22 situation. I approached the issue using a two-pronged method. The first approach was to learn about effective stress management techniques. The second approach was to learn about increasing sleep quality from credible sources.
In addition, I obtained advice from a sleep therapist and guidance from several stress management experts in various fields. I adjusted my diet and exercise for stress management.
I used seven simple yet effective techniques to solve sleep problems. You may read the details in a previous story titled Here’s How I Corrected My Sleep Issues in 7 Steps and Reaped Many Health Benefits.
Here is a summary of the approach.
1 — Fully darkroom during the sleep
2 — Noise cancellation using earplugs
3 — Cool room around 18 Celsius degrees
4 — Three minutes mixed and cold showers
5 — Preventing my eyes from blue lights at night
6 — Increasing magnesium intake
7 — Using an air cleaner in the bedroom
In addition to these seven points, I later discovered that not eating three hours before bedtime was an excellent sleep regime to improve my condition. I learned this technique from a centenarian friend, 105-year-old Algor, who never eats anything within six hours before bed.
Besides, mindfulness and meditation were excellent contributors to solving my stress and sleep issues. Through a mindful approach to my thoughts, emotions, and behavior, I addressed health issues and improved my life satisfaction. Let’s keep in mind that the brain needs three types of rest, one of which is restorative sleep.
For temporary relief, doctors may prescribe sleep medication as a last resort, which may be necessary for some patients with sleep deprivation and insomnia. However, these medications can lead to addiction problems and exacerbate sleep issues in the long run.
Balancing and optimizing cortisol, melatonin, and adenosine levels can improve our sleep, stay awake during the day in a good mood, balance neurotransmitters and hormones, have better cardiovascular health, lower inflammation, and protect our neurons and nerve cells.
Thank you for reading my perspectives. I wish you a healthy and happy life.
If you found this story helpful, you may also check out my other articles on NewsBreak. As a postdoctoral researcher and executive consultant, I write about important life lessons based on my decades of research and experience in cognitive, metabolic, and mental health.