Does sleep protect us from illness?

We have all heard that getting more sleep decrease the likelihood of getting sick?  On the flip side, we know that illness commonly makes us tired but does sleep help us recover quicker?  By examining the medical literature, this blog post will attempt to answer these questions.

It is no secret that sleep rejuvenates our bodies and is essential for proper body functions.  For many years, the effect of sleep on the immune system was largely criticized and considered far-fetched. However, in recent years, many studies have investigated the relationship between a good night’s sleep and the effect it has on the immune system of the body. Although the literature does not define an exact mechanism for enhanced immunity associated with sleep, the evidence of a connection is quite clear.

The Immune System

Before discussing the studies, a primer on immunity is needed.  Our immune system protects our bodies from a disease and infection. It is triggered by a harmful stimulus or stress, which causes increased production and growth of the immune cells.  This system consists of a range of immune cells that protect the body from harmful antigens. The major cellular components are white blood cells (or leukocytes). Some of the white blood cells also produce protein based substances called cytokines which play an integral part in the immune response.

Cytokines are further classified in many subtypes. One of the types of classification divides cytokines into pro-inflammatory cytokines that include Interleukin-1 and Tissue Necrosis Factor (TNF), and anti-inflammatory cytokines that include Interleukin-4, Interleukin-13 and Interleukin-10.

All of the mentioned immune components can be affected by sleep and sleep loss.  In our discussion of the relationship between sleep and immunity, we will explore these cell types and mediators.

The Effect of Sleep on the Immune System

Now that we have discussed the different types of immune cells, we will consider how the individual component is affected by a good night’s sleep.

In a study conducted by Uthgennannt [2] and Schoolmann, 13 healthy men were asked to spend two nights in the sleep laboratory. Lights out was 11 pm and the subjects were allowed to sleep for 3.5 hours. They were then asked to stay awake till 7 am, when blood was sampled. In another condition, the subjects were asked to stay awake between 11 pm and 3 am and then permitted to sleep for 3.5 hours. Blood was sampled every 30 minutes.  In the first condition, when the subjects were allowed to sleep at night, there was a decreased amount of pro-inflammatory cytokines, TNF-alpha and Interleukin-1, while opposite results were observed for those who stayed awake.

In other studies, the serum level of Interleukin-7  which is involved in the maturation and migration of immature T-lymphocytes was observed to increase during the Slow Wave stage of sleep, with a subsequent rise in naïve T-lymphocytes themselves. [1]

Another study conducted by Matsumoto [5], on a 24-hour wake period, demonstrated a marked decrease in cytotoxic NK cells, important cells of inflammation.  In addition, there was a decrease in anti-inflammatory cytokines such as Interleukin-10.

Although the levels of cytokines fluctuate, and the exact pattern is pretty complex; in a nutshell, the main pro-inflammatory cytokines decrease during nocturnal sleep (usually in Slow Wave Sleep stage), whereas the levels of T-lymphocytes and cytokines that are involved in the growth and differentiation of T-lymphocyte as well as those that take part in adaptive immunity (more later) increased. This reflects that sleep, indeed, has a positive effect in boosting the immunity of our bodies since it allows for some cells and cytokines to peak levels while keeping other components at bay.

Another aspect of immunity that is theorized to enhance during sleep is the formation of immunologic memory. Normally when a person is infected by a particular pathogen, immune cells memorize the response.  By forming antigen specific antibodies, the body reacts more rapidly to any subsequent attacks by the same pathogen. Studies have revealed that subjects who stayed awake after a hepatitis A vaccine shot demonstrated lower levels of antigen-specific antibody titers compared to those who received the vaccine and slept regularly [1]. This proves that not only does sleep help in enhancing the cellular elements of the immune system, but it also helps in the formation of immunologic memory.

Adaptive Immunity vs. Innate Immunity

Numerous studies have established that sleep has a direct effect on adaptive immunity, and less so on innate immunity.

Innate immunity involves the protection against a foreign antigen by the body’s defense mechanisms that do not include the antigen-specific immune cells. These defense barriers include the skin, chemicals in the body and cytotoxic immune cells. Adaptive immunity is more complex and encompasses the reaction of antigen-specific immune cells which includes recognizing the antigen, releasing a cascade of immune cellular components and mediators, and finally removing the pathogen.

Research on the decreased levels of Interleukin-6 during sleep which acts as both a pro-inflammatory and anti-inflammatory agent and takes part in innate immunity suggests that innate immune response is less affected during sleep. Similarly, the serum level of interferon-alpha that plays a core role in the innate immune response against viral infection also declined during sleep. On the other hand, Interleukin-7, an important mediator of adaptive immunity, showed a marked increase during sleep. [6]

The Effect of Prolonged Wakefulness on the Immune System

While inflammation is an early response to infection, an inflammatory response unchecked can be detrimental. Several studies have looked at the relationship between sleep deprivation and immunity. The results of these studies were fairly consistent that the levels of the immune cells were impacted by sleep quantity.

Blood samples from individuals subjected to prolonged wakefulness showed a marked increase in inflammatory mediators such as interleukin-6 levels, pro-inflammatory cytokines, TNF-alpha, interleukin-1 and C-reactive protein [7] An increase in these pro-inflammatory cells made the subjects more vulnerable to stress. In addition, the elevated levels of these inflammatory markers is associated with cardiovascular disease and type 2 diabetes. [1]

Does Sleep Decrease the Likelihood of Getting Sick?

Although the relationship between sleep and immunity is still being researched, many studies indicate a strong relationship between a proper sleep/wake cycle and improved immunity of the body.  There is little doubt that a good night’s sleep can decrease the likelihood of getting sick.

 

References

  1. Besedovsky, Luciana, Tanja Lange, and Jan Born. “Sleep and immune function.” Pflugers Archiv. Springer-Verlag, Jan. 2012.
  2. Uthgenannt, D., D. Schoolmann, R. Pietrowsky, H. L. Fehm, and J. Born. “Effects of sleep on the production of cytokines in humans.” Psychosomatic medicine. U.S. National Library of Medicine, n.d.
  3. Sarosh J. Motivala, Michael R. Irwin. “Current Directions in Psychological Science”Vol 16, Issue 1, pp. 21 – 25, June 24. 2016
  4. Dinarello, C. A. “Proinflammatory cytokines.” Chest. U.S. National Library of Medicine, Aug. 2000.
  5. Matsumoto Y, Mishima K, Satoh K, Tozawa T, Mishima Y, Shimizu T, Hishikawa Y. Total sleep deprivation induces an acute and transient increase in NK cell activity in healthy young volunteers.Sleep.2001;24:804–809.
  6. Dimitrov S, Lange T, Nohroudi K, Born J. Number and function of circulating human antigen presenting cells regulated by sleep.Sleep.2007;30:401–411
  7. Meier-Ewert HK, Ridker PM, Rifai N, Regan MM, Price NJ, Dinges DF, Mullington JM. Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk.J Am Coll Cardiol.2004;43:678–683.

Sleep and Memory

For many years, scientists have been trying to understand the connection between sleep and memory. A multitude of research, experiments and studies have been conducted for this purpose, however the underlying mechanism of this connection is still a question mark. Although there is no clear mechanism by which sleep affects our memory, there is no denying that the two are interrelated.

Before we jump into the theories that have been proposed by researchers on this topic, we first need to be familiar with the different types or stages of sleep, as well as the types of memories first.

SLEEP: REM vs. Slow Wave Sleep

Relative to sleep, we need to better understand 2 of the 4 stages of sleep: Rapid-eye-movement (REM) and Slow-Wave Sleep, also known as deep sleep. The two stages occur alternatively with marked changes in the brain waves. The characteristics of deep sleep as seen on an EEG are high amplitude and low frequency brain waves and deep sleep tends to occur more towards the beginning of the night. Dreaming in this stage is rare, and if dreaming does occur, it is usually forgotten once you wake up.

REM sleep, on the other hand, predominates in the second half of the night as the body becomes more and more rested. True to its name, REM sleep is characterized by muscles twitches and eye movements as well as vivid dreaming. Brain waves on the EEG during REM sleep show low amplitude, high frequency waves.

MEMORY: Declarative vs. Non-Declarative

Long-term memory is broadly categorized in two forms: Declarative and non-Declarative. One basic difference between the two forms is whether or not the hippocampus is involveda part of the brain’s limbic system) is involved or not. [1] Declarative memories encompass those that can be easily recalled and consist of the knowledge of facts and events, involving visual and verbal input. Declarative memory itself is divided into semantic memories, the knowledge of facts and world events, and episodic memories that store more personal, autobiographical information. Neuronal circuits in the hippocampus are an integral part in the formation of declarative memories.

Non-declarative memories, also sometimes referred to as procedural memories, are those that store a person’s memory of a skill. [3] This includes all types of ‘how to do’ memories such as cooking a particular dish or playing the piano. Unlike the former type, non-declarative memory does not involve the active participation of brain cells in the hippocampus; instead, motor areas in the frontal cortex are involved.

Memory Processing During Sleep

The process of memory formation isn’t as simple as it might seem. While a lot is still unknown about how memories are truly processed in our brains, we do know the process takes place in three core stages: Acquisition, Consolidation and Recall. [1]

The introduction of a particular memory in the brain is known as acquisition. The consolidation stage occurs after the memory has been introduced when it gets further sorted and stored (or consolidated). Finally, the recall process is simply recalling or remembering a stored memory.

Clinical experiments on rats and humans have demonstrated a possible relation between sleep and the consolidation of memories. Acquisition and recall, on the other hand, take place when the person is wide awake. It is hypothesized that one you fall asleep, the acquired memories become consolidated and stored in their final destination. Not all memories are stored in the same area of the brain. According to Dr. Robert Stickgold of the Sleep Department at Harvard, the memory of what you ate for breakfast yesterday is not stored in the same area of the brain where the memory of what your favorite breakfast is stored. It is when you fall asleep that these memories are sorted into their respective places. [3]

A primary question relative to sleep and memory is during which stage of sleep are memories actively processed.  Although a definitive pathway has not been elucidated, studies have suggested a relationship between consolidation of memories (especially the non-declarative type of memory) and REM sleep.

In a recent research study, subjects who were asked to learn a foreign language demonstrated increased periods of REM sleep during the night. [3]  As far as declarative memories were concerned, none of the studies could prove the connection between verbal/visual memories and REM sleep.

This led to the hypothesis that perhaps Slow Wave Sleep had some role in the consolidation of memory, particularly the declarative type. Research is still scarce concerning this theory and the studies that have been conducted show inconsistent findings.

Effects of Sleep Deprivation on Memory

The effect of sleep deprivation on an individual’s memory is a topic that has been explored extensively. Many studies have been conducted where subjects were kept awake for over 35 hours to test the effect sleep deprivation had on their long-term memory. Results showed that a 24-hour sleep deprivation period did not have a significant effect on memory recall.  However, a 35-hour sleep deprivation period results in impaired facial recognition (a type of episodic memory), recall and verbal memory. [3]

Although a relationship was established between sleep deprivation and memory through these studies, we still do not know if it was sleep deprivation that directly affected the neuronal circuitry involved in memory consolidation, or if the effects were more metabolic.

As pointed out in a post in Harvard Health Publications, the effects of too little sleep on memory impairment could be due to other known harmful effects of sleep deprivation on the heart and circulation. Sleep deprived patients usually have a consistent high blood pressure that could directly affect brain cells that consolidate memory. [4]

Improving Memory with Sleep

Several researchers have hypothesized that obtaining the recommended hours of sleep can benefit the individual’s memory. To test this hypothesis, a study was conducted on a group of twenty female and twenty male adolescents, between 10 and 14 years. The group was divided into two – a sleep group, and a non-sleep group. All subjects were given the paired-associate test, a standard for testing declarative memory. The paired-associate test consists of remembering two related (tree/leaf) and two unrelated (tree/shoe) words. In addition, the two groups were given the letter-number test which consists of sequencing a list of mixed numbers and letter in an ascending order.  The sleep group was given the task at 9 pm and was tested at 9 am after a night of sleep. The non-sleep group was given the task at 9 am and tested at 9 pm at night with continuation of normal day activities and without naps. The paired-associate test did not result in any significant differences.   However, utilizing the letter-number test, there was a 20.6% increase in long term memory in the sleep group showed versus the non-sleep group. [5]

Even though the direct effect or mechanism of sleep on memory is still being studied, it is clear that improves cognition and refreshes the body. Therefore, a good night’s sleep is essential for optimal functioning through the day.  Obtaining 7-8 hours of sleep nightly at a consistent time along with proper diet and exercise can greatly contribute to a great night’s sleep.

References

  1. Rasch, Björn, and Jan Born. “About Sleep’s Role in Memory.” Physiological Reviews. American Physiological Society, Apr. 2013.
  2. Alhola, Paula, and Päivi Polo-Kantola. “Sleep deprivation: Impact on cognitive performance.” Neuropsychiatric Disease and Treatment. Dove Medical Press, Oct. 2007.
  3. “Sleep, Learning, and Memory.” Sleep, Learning, and Memory | Healthy Sleep. N.p., n.d.
  4. LeWine, M.D. Howard. “Too little sleep, and too much, affect memory.” Harvard Health Blog. N.p., 29 Oct. 2015.
  5. Potkin, Katya Trudeau, and William E. Bunney. “Sleep Improves Memory: The Effect of Sleep on Long Term Memory in Early Adolescence.” PLoS ONE. Public Library of Science, 2012.

It’s good to breathe

Obstructive sleep apnea can be quite dangerous when not treated.  Restricted airflow which occurs repetitively in individuals with sleep apnea stresses the body in several ways.  We know that people who suffer from obstructive sleep apnea have a higher risk of high blood pressure, stroke, irregular heart rhythms, elevated blood glucose levels, car accidents and even sudden cardiac death.  In addition, people with sleep apnea often feel tired, complain of non-restorative sleep and have a poor quality of life.  Having untreated sleep apnea does not necessarily mean that an individual will ever suffer these ailments, but it does raise the risk.   The more severe the sleep apnea, the higher the likelihood of ever suffering from one of these entities.

Untreated sleep apnea results in these ill effects for two main reasons.  First of all, the oxygen levels dip which stresses the body. The second reason is that sleep apnea results in fragmented and poor quality sleep.

When people don’t breath well at night,  oxygen levels repetitively dip resulting in bodily stress.  As most people are aware, our body tissues need adequate oxygen for optimal function.  It can thought of as a stress test every night.  When a person’s upper airways narrow, airflow is limited and oxygen levels drop.    Most people’s oxygen levels remain at 97-100%.  Associated with apnea events, oxygen levels drop by at least 3%.  It is not uncommon for oxygen levels to drop even further.  Individuals with severe sleep apnea commonly have drops of their oxygen levels into the 70-80% range.  I have seen patient’s with oxygen levels dipping into the 50s%!     When the tissues are starved of adequate oxygen, the risk of heart attack and stroke increases.  The sympathetic nervous system is activated which results in elevated blood pressures with frequent surges in blood pressure and heart rate.   In addition, inflammatory mediators are released which can further damage tissues.

Sleep apnea also results in fragmented  and poor quality sleep.  After a good night’s sleep, a person should feel refreshed and ready for a full day’s activities.  Optimal sleep should last 7-8 hours in adults during which a person cycles through stages of sleep.   There should be 3-4 sleep cycles during which a person transitions from light sleep, to deep sleep and then into REM sleep.  We call this sleep architecture.  Each stage of sleep is associated with important bodily functions like memory consolidation, hormone secretion and clearing of accumulated waste products.   If an individual’s sleep is disrupted by sleep apnea, sleep architecture becomes fragmented and the full benefits of sleep are not achieved.  The breathing events associated with sleep apnea frequently cause arousals.  Essentially, arousals are ‘brain awakenings’ which disrupt sleep architecture.    For example, a person with moderate or severe sleep apnea will commonly have more than 15 arousals per hours which prevents them from entering the restorative stages of sleep such as deep sleep.  This is why a patient with sleep apnea will commonly state that they never feel like they slept.

Indeed, it is good to breathe.  This article explains why obstructive sleep apnea leads to an increased risk of cardiovascular problems, as well as excessive daytime sleepiness.

What is Sleep Medicine?

Sleep Medicine is a new field of medicine dedicated to evaluating and managing individuals with sleep disorders.  It is made up of practitioners from a wide range of backgrounds including internal medicine/pulmonary, otolaryngology/ear nose and throat, neurology, psychiatry, family medicine, pediatrics, family medicine and anesthesiology.   Board certification in Sleep Medicine is reached through fellowship training and/or through extensive clinical experience.  Sleep Medicine physicians must pass an Board certification examination every 10 years and maintain regular continuing medical education credits.

The most common conditions evaluated by sleep medicine physicians are insomnia, sleep apnea and restless legs syndrome. As I mentioned, the field is quite diverse.  As a result, physicians with different backgrounds are more likely to have expertise in managing certain sleep disorders.  For example, an ear nose and throat physician, is most adept at evaluating and managing patients with sleep apnea and snoring since they are very familiar with the upper airway anatomy.  Similarly, a neurologist will be considered more of an expert in evaluating someone with restless legs syndrome or narcolepsy since it involves problems with the nervous system.   It is possible that even if someone is seeing a sleep medicine physician, they may not be the ideal person to evaluate a particular sleep condition.  For example, a pulmonologist is probably not ask adept as a pulmonologist at evaluating and treating insomnia.

Most hospitals and heathcare organizations will have sleep medicine physicians on their staff.  Most healthcare websites will have a ‘find by specialty’ option which would allow people to identify the sleep medicine physicians.

Sleep medicine physicians are actively involved in oversight of sleep laboratories where patients with certain sleep conditions are tested.  The sleep physician oversees the testing protocols and oversight of the sleep laboratory staff.  He/she will be responsible for reviewing the data collected from overnight sleep studies and generating an interpretation.  The most common diagnosis rendered from a sleep study would be obstructive sleep apnea, a condition characterized by restricted airflow caused by upper airway narrowing.  The most common symptoms are snoring, non-restorative sleep and daytime sleepiness.

 

 

Why I Started This Blog

My name is Noah Siegel and I am a Sleep Medicine physician practicing in Boston.  I created this blog as an outlet for sleep related content for the general population because almost everyone has sleep ‘issues’ or lives with someone who does.    Common sleep issues include inadequate sleep, difficulty falling asleep, night time pain or problems with snoring.   We used to believe that sleep was simply a time when the body shuts down and not much really happened.  This could not be further from the truth.  Our understanding of sleep is rapidly advancing and we are beginning to understand the tremendous power of sleep!  Essentially, sleep is recovery.  Sleep is our body’s way of restoring itself, consolidating memory, clearing the waste from our brains and so much more.  Optimal sleep promotes cognition/memory, performance, learning  and even can reduce our risk of cancers, heart disease and stroke.    My goal is to regularly provide my readers with information on advances in our understanding of sleep and suggest ways to optimize their sleep.