Conquering COVID Part 1.9 A & B (Another Double Issue):
“Sleep & 33% or one-third of your entire life?!”
(aka Sleep Health = Better Software Updates & Immune Health)
May 12, 2020

by Mark A. Moyad, MD, MPH

“I am concerned, of course, but I am also incredibly optimistic.”

Howdy Everyone! I am so happy you have joined me today!!! (Note: I love exclamation points!!!) I want to cover (no pun intended) a very interesting topic- SLEEP (or the lack of it)! Why? It is not only ASSOCIATED with many health issues, but it could also be the CAUSE of many health issues. It is incredible to think that we spend one-third of each and every day, and simply one third of our lives, sleeping or at least trying to sleep (emphasis on “trying”). Thus, if we were meant to spend such a vast amount of time sleeping then intuitively the importance of this activity to human health should receive large and constant amounts of awareness and attention as to the benefits of sleep, as well as how to improve the quality and/or quantity of sleep.

First, it is important to talk SLEEP CYCLES or STATES, or what is going on when we sleep in general. Human bodies, when sleeping, are usually in a state of NREM or REM sleep, and we bounce back and forth between these states throughout the night (or day if you work the nightshift) (Le Bon O. Sleep Med 2020;70:6-16). Let us review:

NREM stands for non-rapid eye movement sleep. NREM basically consists of three stages (there used to be four, but research now suggests there are three) of sleep, and each one involves DEEPER forms of sleep than the previous. So, NREM 3 is DEEP SLEEP, and NREM 1 and NREM 2 are more superficial or lighter stages of sleep.

REM is rapid eye movement sleep. In REM sleep, your eyes actually move back and forth and this is the time when the majority of dreams occur (note: R.E.M. is also the name of a popular rock band - just showing off my diverse knowledge). Notice how I said the “majority” of dreams occur. It is no longer true that all dreams only occur during REM (this is what I was taught in school), because recently researchers have determined that some dreaming can also occur during NREM sleep (Siclari F, et al. J Neurosci 2018;38:9175-9185).

Look, getting older is not easy for many reasons… well, let me take that back… getting older makes certain things easier, such as speaking your mind, and some things less easy, such as sleep (how about that for a weak segue?). Studies, in general, suggest people get less deep sleep (NREM 3) and less REM sleep, more light sleep (NREM 1 & 2), they are awake more, and experience more sleep interruptions with age. This is not fair, so achieving great wisdom with age does not always equate with great sleep while aging. “I just do not sleep like I use to sleep” has become a common phrase that makes sense as you get older. In other words, there is an impact on sleep quality and quantity. 

Problems sleeping become more noticeable during perimenopause and menopause for women. Part (but not all) of the reason may be the reduction in certain hormones with age, and this could also be the case for some men. For example, men on androgen deprivation therapy (ADT) for prostate cancer also appear to have more problems with sleep compared to men not on hormone therapy, and experiencing hot flashes at night (aka one cause of “night sweats”) are part of the reason for these sleep issues (Gonzalez BD, et al. Cancer 2018;124:499-506; & Koskderelioglu A, et al. Neurol Sci 2017;38:1445-1451). Still, cancer patients, including those dealing with prostate cancer, are at an increased risk of overall sleep issues. A recent study of over 3,300 prostate cancer survivors two to 18 years after their initial diagnosis found approximately 20% had sleep issues that could be partially explained by urinary symptoms (getting up at night), bowel issues, hormone therapy, or even anxiety/depression (Maguire R, et al. Support Care Cancer 2019;27:3365-3373). Trouble sleeping is also known to occur during chemotherapy and other treatments, and the more pills people require for other health conditions the greater the probability of potential sleep issues. One important behavior impacting sleep today is from ALCOHOL (sorry folks, because I also love my occasional beer or beers). Alcohol is one of the most utilized sleep aids (aka self-medications) in my opinion, but what is difficult to imagine is that alcohol actually REDUCES the QUALITY and even the QUANTITY of SLEEP despite generally helping some people fall asleep faster.  Booze causes people to generally spend less time in NREM 3 (deep sleep) and also reduces REM sleep. The end result is more light sleep and less deep sleep, so the next day it is hard to feel completely awake or refreshed. This negative impact on sleep can occur at any level of alcohol consumption (Ebrahim IO, et al. Alcohol Clin Exp Res 2013;37:539-549). 

“Okay, Dr. Moyad so I get less sleep, but a tiny drink here and there helps me relax and heaven knows we need a little comfort during these unpredictable or turbulent COVID-19 times, right?” I hear you and, in fact, the sales of most types of alcohol has moon rocketed, which is more than a sky rocket, during this pandemic ( I am not saying you need to eliminate all alcohol (I am not giving up on my occasional beer), but rather to analyze or become more aware of the profound impact alcohol has on what we are supposed to spend 33% of our lives doing, which is SLEEPING. Ergo, whether it is alcohol or any other disturbance to your sleep, there must be other health impacts from head-to-toe when sleep, over a long period of time, is compromised. Right? 

For example, why doesn’t exercise or physical activity of any kind get more attention as a beautiful way to increase the amount of time you spend in deep sleep! Yes, that is right!  Research has shown for some time that one of the countless benefits of physical activity is that it INCREASES YOUR ABILITY TO ENTER DEEP OR MORE REFRESHING SLEEP, EVEN AS YOU GET OLDER. One of the largest analyses in the medical literature of the over 60 studies completed since the 1960s to almost present day, from my new BFF researchers from Boston, arrived at the following conclusion that I wish would have been headlined in one news story, and that was the following (abridged by Moyad to cut to the chase): “In summary, our meta-analysis presents compelling evidence supporting exercise as an evidence-based intervention to improve perceived and objective metrics of sleep… our results indicate that the benefits of exercise for sleep are realized immediately… our results suggest that regular exercise leads to even greater subjective and objective benefits over time, with subjective benefits being comparable to those produced by behavior therapy or pharmacotherapy for insomnia… in light of this evidence there is support for the use of exercise as a prescriptive to improve sleep quality…" (Kredlow MA, et al. J Behav Med 2015;38:427-449) SAY WHAT? YES! YES! YES! I told you earlier I like exclamation points!!! (Where is that TV commercial when you need it?).

Basically, there are countless potential health benefits when at least trying to improve your sleep QUALITY and/or quantity and knowing the impact of alcohol or exercise or anything that is also in your control is critical ( FYI…doctor heal thyself - I already exercise too much but I did stop alcohol for approximately several weeks before writing this column and I have slept more like a tired happy baby than a crying cranky baby). I also believe spending the actual time investigating the highest quality cost-sensitive mattresses, pillow or sheet options (for example, OR are as important as spending the same amount of time finding the perfect laptop, smartphone, or big screen television (again see You are supposed to be sleeping 33% of your day, and who spends that amount of time on the computer, smartphone, or big screen television? (apart from my kids, nephews, the kids in my neighborhood and my dad… oh and me during binge watching of “The Last Dance”- Michael Jordan Series on ESPN and Netflix).

Okay, now here comes the piece de resistance of this column. Another reason to improve your sleep or seek help to improve your sleep that needs more attention is the potential improvement in IMMUNE HEALTH. More work needs to be done in this area but some of the preliminary research is fascinating and important. For example, in a study of 153 healthy adults infected with a rhinovirus (aka a common cold virus…btw I have always disliked the word “rhino” as a medical term for the word “nose”…many of us born with generous size noses, including myself, would prefer something more regal or majestic sounding such as “the nasally chosen ones,” but I digress), those with less efficient sleep were approximately three to five times more likely to actually develop a cold (Cohen S, et al. Arch Intern Med 2009;169:62-67)! Yikes! Studies have suggested getting at least seven hours of sleep a night were associated with better immune protection against cold virus exposures (Prather AA, et al. Sleep 2015;38:1353-1359). In this latest and more rigorous study, 164 women and men had their sleep patterns measured with a device for seven consecutive days and then received nasal drops with a cold causing rhinovirus (there is that word "rhino" again), and then were isolated/quarantined in a hotel and followed for five days. Participants sleeping six or less hours compared to more than seven hours per night had four-fold greater risk of getting a cold. I would not become obsessed with the specific amount of sleep here, but rather regular sleep deprivation or inefficiency could be immune unhealthy, and some of these latest studies did not just rely on the sleep patterns self-reported by the participants, but had their sleep objectively measured with a device (aka “actigraphy”). 

One of the theories of inadequate or impaired sleep quality is that it can lead to a type of mild inflammation, which is possible based on past research (Mullington JM, et al. Best Pract Res Clin Endocrinol Metab 2010;24:775-784). Laboratory evidence suggests that multiple inflammatory markers could be increased when getting less sleep, including REM sleep (Pandey AK, et al. Biochem Biophys Res Commun 2011;410:242-246). Thus, the body is always fighting for the perfect balance between a pro- and anti-inflammatory state, and part of the theory is that a lack of regular or quality sleep is just one factor that can move the body heavily towards more inflammation versus anti-inflammation. The more the chronic or long-term inflammation the more potential to negatively impact immune function - be it from high blood pressure, sugar, cholesterol, weight gain, poor diet, tobacco or alcohol exposure, stress or even a lack of efficient sleep (a type of stress). More recent studies of insomnia have even demonstrated an increasing risk of some respiratory tract infections, which supports the potential role of sleep on adequate immune function (Nieters A, et al. Sleep 2019; doi: 10.1093/sleep/zsz098). In one of the largest surveys to address this issue in the U.S., there was an association with sleep problems and a higher reported number of head or chest colds, and other types of infections (Prather AA, et al. JAMA Intern Med 2016;176:850-852).

What is also fascinating about a lack of efficient sleep is the potential to impact other aspects of health or the efficacy of other immune interventions.  For example, one study suggested sleep deprivation negatively impacts the ability of the body to better respond to the influenza vaccine (Spiegel K, et al. JAMA 2002;288:1471-1472). In addition, adequate sleep on the night after receiving a hepatitis A vaccination produced a significantly stronger immune response four weeks later (Lange T, et al. Psychosom Med 2003;65:831-835). A follow-up small study in healthy adults also receiving hepatitis A vaccinations and followed for one year found that adequate sleep appeared to further improve immunological memory, which is needed for long-term efficacy for any vaccine (Lange T, et al. J Immunol 2011;187:283-290). Hepatitis B vaccination responses appear to be less robust in people getting less sleep the week they receive the injection (Prather AA, et al. Sleep 2012;35:1063-1069).  In fact, there are now recent studies even suggesting, with supportive data, the need for adequate sleep the night before receiving common vaccinations, including the flu shot, in order to improve the odds of an adequate antibody response (Prather AA, et al. Int J Behav Med 2020; doi: 10.1007/s12529-020-09879-4).

Now, in no way am I suggesting that if cancer treatment is impacting your sleep then it is impacting the efficacy of your treatment, but rather the way to better handle treatment side effects, or optimize the effects of treatment, is to address any issues with your sleep that you are having with your healthcare team. And, in no way am I implying that if you improve sleep quality or quantity then you will be better prepared to prevent or fight this particular coronavirus, because we have no idea. However, improving sleep could further improve our mental and physical abilities to handle these tough times and to be nicer to each other. There is a reason the often utilized saying such as “Did you sleep on the wrong side of the bed last night?” has been around since ANCIENT ROMAN TIMES (no kidding). Originally, it was meant to imply getting out of bed in the morning on the left side (vs. the right) was sinister, but interestingly this saying evolved over time to actually suggest a person was being irritable or grumpy that day because of a lack of adequate sleep! Adequate sleep increases the odds of an adequate daily mood - one better equipped to handle daily life ( Ben Simon E, et al. Trends Cogn Sci 2020;24:435-450 ).

Again, many factors impact immune health, and sleep is just one aspect of your overall health report card, but it is a critical one. Numerous other factors mentioned earlier, including smoking, lack of exercise, poor diet, excess weight, alcohol above moderation, etc. are also associated with a higher risk of respiratory tract infections (Maccioni L, et al. BMC Public Health 2018;18:271), less than optimal immune function, and some of these factors could also negatively impact the successful conventional treatment of certain types of infections (Chaves Torres NM, et al. PLoS One 2019; 14: e0226507). Even a positive mood, yes, let me repeat that because it is so interesting… even a positive mood on the day of an influenza/flu shot was associated with an improved response to this vaccination (Ayling K, et al. Brain Behav Immun 2018;67:314-323). This was a study of 138 adults aged 65-85 years old and the researchers looked at antibody responses approximately four months after receiving the vaccination. Again, getting up on the right side of the bed is tantamount to a positive mood.  Anyone, at any time, can attempt to will themselves to be more positive, just like anyone can wake up any day and say that today is going to be different, but the success rate with this method is low (aka the New Year’s resolution approach to life). However, truly being or becoming more positive, on a more consistent basis, involves actually trying (putting in the work) to improve the different aspects of your health that are in your control, and better sleep efficiency is one of the many beautiful avenues that can help you reach that wonderful destination. (Sorry, but I had a sudden and uncontrollable motivational speaker moment that I had to put on paper). 

Finally, one of the best ways to conventionally treat insomnia that still does not get enough attention is CBT (not CBD - although I am sure some folks reading this now would love to hear more about CBD - that is for another time) or cognitive behavioral therapy. CBT teaches you methods to change your behaviors so you can increase the probability of more (quantity) and better (quality) sleep. It works with our lifelong requirement to get sleep for better health, and our circadian patterns. CBT involves many things including changing the bedroom environment, not forcing yourself to sleep, anxiety reduction or sleep relaxation such as the Benson Relaxation Response and countless other methods ( Please check out this reference - it is fabulous. 

CBT training usually takes one-to-two months and benefits are observed usually within weeks.  Online or even telemedicine programs have NEW preliminary evidence that they can work almost or as well as in-person CBT (Arnedt JT, et al. & Conroy DA, et al. Sleep 2019; 42-Suppl 1: A147-149) . It is easier than ever to access a CBT expert by just going online. There are many options, for example, go to (from the American Academy of Sleep Medicine), select your state, and it should give you multiple options, or EVEN BETTER - just talk your health care team, for example your primary care provider, for more information including a potential reference to a local expert. 

Finally, I want you to think of getting higher quality and potentially quantity sleep in this kind of wacky up-to-date Moyad way: Your body receives some of its best software updates and cybersecurity protection measures or instructions when you are sleeping, and especially when sleeping with excellent quality and enough quantity. This is part of the reason researchers continue to believe that evolution, or God, or both, or whatever you believe in, were unified in deciding to dedicate approximately 33% or ONE-THIRD of your entire life to the act of not being awake (SLEEP)!  Again, your body needs this sleep efficiency time, not only for REST and RECOVERY, BUT REPAIR AND SOFTWARE UPDATES TO YOUR ALWAYS AGING SYSTEM (aka body and mind). System checks from the brain-to-toe, and even to the immune system are conducted each and every night of our lives during this special time which, again, is part of the reason so much time was dedicated to sleep.  
And yet, all of this is simultaneously and wonderfully interdependent and bi-directional, because better sleep better prepares us to improve the different aspects of our health (better mood, less stress, more focus, stamina, less fatigue, more optimal immune function…) and this is part of the reason sleep is a reflection of health. But, as we improve seemingly different aspects of our health (exercise, diet, quit tobacco, quit self-medicating, increase our support network, more spiritual or charitable health…) it also improves our sleep!

Thank you for reading my latest installment and I wish you and your family the best of health. I am concerned, of course, but I am also incredibly optimistic! I look forward to modern day science and you of course, kicking COVID-19 and cancer in the gluteus maximus! 

All of my best always,

Mark A. Moyad MD, MPH 

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