Previously, we looked at the effect of caffeine on supporting wakefulness during the day.
After Waking Up, Do We Really Need Caffeine?
After we’ve completed that workout and let our maintenance crew do their jobs, eventually morning arrives.
But really, it’s not going to be a “cure all” situation, and in fact, it actually does mask the detrimental effects that a lack of sleep has on the immune system.
We can drink coffee. We can block those adenosine receptors. We can convince ourselves that we’re ready to power through another day.
But our bodies don’t necessarily agree.
And when we repeatedly use caffeine to push through insufficient sleep, there is another system that may eventually start complaining.
That system is, unfortunately, our immune system. Sleep isn’t merely something that makes us feel rested. It is also closely connected to how our bodies regulate inflammation and coordinate our immune responses.
The problem of insufficient quality sleep has been declared by the United States Centers For Disease Control And Prevention (CDC) to be a public health epidemic for a very long while, where a 2024 survey showed that 30.5% of the adults averaged less than 7 hours of sleep in a 24 hour period.
And there doesn’t seem to be any abatement to that issue, unfortunately.
According to the American Sleep Apnea Association,
Additionally, people are chronically sleep deprived as a result of demanding lifestyles and a lack of education about the impact of sleep loss. Sleepiness affects vigilance, reaction times, learning abilities, alertness, mood, hand-eye coordination, and the accuracy of short-term memory. Sleepiness has been identified as the cause of a growing number of on-the-job accidents, automobile crashes and multi-model transportation tragedies.
As we can see, there are many issues associated with a lack of sleep, especially with demanding lifestyles.
Stressors such as social isolation, a worry about finances and a worry about one’s health can cloud our minds and make it even more difficult to sleep.
But what else do we have to look out for?
The problem with sleep deprivation is that it doesn’t just affect our “vigilance, reaction times, learning abilities, alertness, mood, hand-eye coordination, and the accuracy of short-term memory.” There are real, long-term health consequences due to lack of adequate sleep.
We know what it feels like to wake up in the morning after having not slept properly the night before. The grumpiness, irritation and the need for coffee is there.
And so is the inflammation.
In this article, it is said that:
Approximately one-third of adolescents and adults in developed countries regularly experience insufficient sleep across the school and/or work week interspersed with weekend catch up sleep.
As this sleep disruption becomes a chronic, habitual pattern, there will be an increased expression of pro-inflammatory cytokines in the human body. These include cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α).
These cytokines do not bode well for our immune system.
The relationship between sleep and our immune system appears to work in both directions.
It is said in this article that:
In modern times, chronic social threats can drive the development of sleep disturbances in humans, which can contribute to the dysregulation of inflammatory and antiviral responses.
When we’re stressed, it becomes harder to relax or sleep properly.
And unfortunately, the problem does not necessarily stop there.
Sleep deprivation can itself act as a physiological stressor, further activating pathways involved in the body’s stress and inflammatory responses. The result can become a vicious cycle: stress disrupts sleep, insufficient sleep amplifies physiological stress, and repeated sleep disruption can promote greater pro-inflammatory activity.
Over time, this can contribute to a state of immune and inflammatory dysregulation, where the body’s inflammatory and antiviral responses are no longer regulated as effectively as they should be.
And that means our immune system may not perform at its best when we actually need it.
It may even take us longer to recover when faced with something as seemingly “mild” as the common cold.
In fact, experimental studies have found that people who habitually sleep less are more susceptible to developing a cold after exposure to a rhinovirus.
What happens as we sleep?
This article summarises some of the biochemistry involved in melatonin production.
In the dark, norepinephrine is released by the superior cervical ganglion to stimulate the pineal gland in the brain to release melatonin into the blood. The pineal gland synthesises melatonin sequentially from the amino acid tryptophan, which is converted into serotonin as an intermediate. All of this activity (and our circadian rhythm) is regulated by the suprachiasmatic nucleus in the brain.
The important point here is that melatonin production is closely tied to our circadian rhythm. The suprachiasmatic nucleus acts as the body’s central clock, helping to coordinate the timing of melatonin production with the day-night cycle.
When this circadian system becomes disrupted, melatonin production and signalling can also become disrupted. And because melatonin is one of the signals that helps tell our bodies that it is biological night, disturbances to this system can make it harder to maintain a normal sleep-wake cycle.
How else does melatonin production get affected?
There is another rather interesting interaction between melatonin and our immune system.
During an acute inflammatory response, inflammatory signalling can temporarily suppress melatonin production by the pineal gland. At the same time, activated immune cells at the site of inflammation can produce melatonin themselves.
This is part of what has been described as the immune-pineal axis.
In simple terms, the body appears to be able to shift some of its melatonin production from the pineal gland to immune cells during an acute inflammatory response. The melatonin produced locally by these immune cells can act in an autocrine and paracrine manner, while also contributing to the regulation of oxidative and inflammatory processes. Once the acute inflammatory response begins to resolve, pineal melatonin production can recover.
This is a fascinating example of how closely interconnected sleep, circadian biology and the immune system actually are.
But there is a problem when sleep deprivation becomes chronic.
Repeated insufficient sleep has been associated with increased pro-inflammatory activity and changes in immune regulation. At the same time, sleep loss can disrupt normal circadian and melatonin signalling. The result is not simply a matter of “less melatonin means less sleep”. However, sleep, melatonin, inflammation and immune function form a complicated feedback system in which the disruption of one component can have a cascading effect on the other factors.
And this brings us back to our earlier discussion.
When we repeatedly use caffeine to mask sleepiness and power through another day, we may be able to temporarily interfere with the brain’s perception of sleep pressure.
But caffeine cannot make up for the biological processes that should have taken place while we were sleeping.
Our immune system still has to deal with the consequences of insufficient sleep.
So perhaps the real problem with repeatedly powering through fatigue with caffeine is not the cup of coffee itself.
Caffeine can certainly help us feel more awake.
But it cannot replace the sleep that our bodies actually need.
We can block the adenosine receptors. We can convince our brains that we are ready to power through another day. But underneath that temporary feeling of alertness, the biological consequences of insufficient sleep can continue to accumulate.
Our immune system still has work to do.
Our inflammatory responses still need to be regulated.
And the maintenance crew still needs its time to do the job properly.
So the next time we find ourselves reaching for another cup of coffee after a terrible night’s sleep, we do need to bear in mind that we are not actually fixing the problem.
We are simply buying ourselves a little more time before the bill arrives.
And speaking of inflammation, there is another rather interesting question:
If inflammation is part of the body’s defence and repair system, how exactly do non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen interfere with it?
That’s another story to be continued next week.
In the meantime, if you’re interested in more sleep-related content, do feel free to check out how our brains balance glutamate and gamma-aminobutyric acid (GABA) to help us enter a more restful state:
After That Workout, I'm Going To Need More Than Just A Protein Shake
After all that talk about intense workouts, lactate and the punishment we subject our knees to, there is one rather obvious question left.
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