Correcting Sleep Dysfunction in ME/CFS and Long-COVID

(This article was originally published on the ProHealth website on September 18, 2019.)

Sleep problems are one of the most common symptoms of ME/CFS (myalgic encephalomyelitis / chronic fatigue syndrome). Sleep dysfunction is a critical piece of the complex puzzle that is chronic fatigue syndrome, and ME/CFS and long-COVID patients are eager for treatments that will help to improve and normalize their sleep. When I was diagnosed with ME/CFS by my primary care physician, she said, “The first thing to do is to correct your sleep problems. That will make all of your other chronic fatigue syndrome symptoms improve.” She was right! Here are ways to help you fall asleep faster, sleep better, and wake up feeling refreshed.

 

Normal, Healthy Sleep

In order to treat ME/CFS sleep dysfunction, it helps to understand what healthy sleep looks like. A night of refreshing sleep consists of sleep cycles, moving through various stages in a predictable pattern: 

• Stage 1 and 2 sleep (light stages of sleep)
• Stage 3 and 4 sleep (deeper stages of sleep)
• REM (Rapid Eye Movement) when we dream. 

 

Those deep Stages 3 and 4 are especially important for immune health, endocrine (hormone) function, and energy; it’s when our bodies recover and rebuild.

 

A healthy endocrine system, which produces hormones at the right times and in the right amounts, helps regulate sleep (and everything else), as follows:

• A hormone called tryptophan is converted into 5-hydroxytryptophan (5-HTP), with the help of vitamins and minerals including iron, magnesium, calcium, B6, and folic acid.
• 5-HTP is then converted into serotonin, with the help of magnesium, zinc, vitamin B6, and vitamin C.
• Serotonin has many important functions in the body, including regulating mood and ensuring good quality sleep by converting into melatonin.
• Melatonin directly regulates wakefulness and sleep. A healthy body naturally makes more melatonin at night, when it gets dark, and less during the day when it is light.

Note that melatonin and cortisol work together to regulate the sleep-wake cycle. In a healthy body, daylight triggers the body to stop producing melatonin and increase cortisol. Throughout the day, cortisol gradually declines, and darkness triggers the body to start producing melatonin and stop producing cortisol. Many studies have shown that most ME/CFS and long-COVID patients have low cortisol levels all the time. Luckily, the reverse is also true: that correcting sleep dysfunction can also help to normalize cortisol levels.

 

Sleep Dysfunction in ME/CFS

Why do ME/CFS patients feel like we are half-awake all night and still exhausted in the morning? Traditional sleep studies comparing ME/CFS patients to healthy controls often find no measureable differences in our sleep cycles, though some show reduced total sleep time and sleep efficiency. Newer studies, using entirely different ways of measuring sleep, though, are finding that ME/CFS patients have more disruptions in REM sleep and deep stage (3 & 4) sleep. Our brains will sometimes jump right from REM or even deep stage sleep into being awake or in light Stage 1 sleep, instead of cycling through each stage, as is normal. These REM disruptions in the studies correlated with worse symptoms the next day.

 

The hormone side is also not entirely clear. The few studies of serotonin levels in ME/CFS patients have shown contradictory results, though some do show abnormal serotonin function, indicating our bodies aren’t controlling serotonin the way a healthy body should. This matters because sleep deprivation causes a multitude of serious health problems, worsening every aspect of ME/CFS.

 

Sleep Studies

When an ME/CFS patient mentions sleep problems, doctors usually send him/her for a sleep study. The problem is, as noted above, that even carefully controlled scientific studies often fail to show abnormalities in our sleep using standard measures. Sleep studies do have an important function, though. They are designed to diagnose primary sleep disorders, like sleep apnea, restless legs syndrome, and narcolepsy. Plenty of ME/CFS patients also have a sleep disorder (some studies indicate we have a greater risk of primary sleep disorders), and it’s important to diagnose and treat those. Consider a sleep study to diagnose or rule out a primary sleep disorder but don’t expect it to find much with respect to your ME/CFS sleep dysfunction.

 

Treatments for ME/CFS Sleep Dysfunction

The key to correcting our sleep dysfunction at its source is to target those hormones that are responsible for good quality sleep. This is different than taking sedatives to knock you out; it means actually correcting the problem so that your sleep feels normal and natural and you wake up feeling refreshed. There are different approaches to try, and it often takes some trial and error, sometimes combining treatments, to find what works best for you. Work with a doctor to find the right combination and to prevent increasing serotonin too much.

• Melatonin. You can directly supplement with melatonin, which is readily available in any drugstore, at bedtime. Most use 3-5 mg of melatonin, but you can start low, with just 1 mg, and go up, as needed, as high as 8-10 mg. Most patients find melatonin slightly helpful, but it rarely completely corrects sleep dysfunction. Note that regular melatonin helps you fall asleep but quickly wears off, so it won't help you stay asleep. Extended release melatonin can help with both falling asleep and staying asleep.
  
• Tricyclic Antidepressants (TCAs). Most antidepressants work by affecting levels of serotonin, and this class of TCAs, which increase serotonin, are particularly sedating for most people, especially nortriptyline and amitriptyline. TCAs also increase epinephrine (a hormone which affects pain threshold), so they can also be helpful for pain. Use a lower dose for sleep dysfunction than would normally be used for depression, and take it 30 min–2 hours before bed. Nortriptyline comes in a liquid, so it can be started at tiny doses and very gradually increased. A study of ME/CFS patients taking 60 mg of nortriptyline at bedtime showed improved symptoms (but start lower).
• Trazodone. A favorite choice of most ME/CFS experts for treating sleep dysfunction, trazodone is also an antidepressant that increases serotonin but in a different class than TCAs. One study of 66 fibromyalgia patients concluded that “trazodone markedly improved sleep quality.” It is known to increase stage 3 and 4 deep sleep, and it is the least likely sleep treatment to lose its effectiveness over time. However, about 20% of the fibro patients tested experienced tachycardia (racing heart rate). If that happens to you, try reducing the dose or try something else. TCAs and trazodone also block acetylcholine, another hormone, which can cause dry mouth or eyes, digestive problems, and other issues with long-term use. Of the three, amitriptyline has the most anticholinergic effect, nortriptyline less, and trazodone the least of the three. Most start with 25 mg trazodone for sleep and go up, as needed, to 50-200 mg. All doctors should be familiar with using TCAs and trazodone to help with sleep, as these are older, very common medications.
• Tryptophan. Alternatively, you can move further up the hormone chain to increase tryptophan (which converts to 5-HTP and then to serotonin). Although tryptophan is found in some foods, most of those are protein-rich, and both tryptophan and serotonin drop after eating protein.  So, experts suggest taking tryptophan supplements instead, along with a carb-heavy snack or get your tryptophan from more carb-rich foods, like asparagus, leafy greens, soybeans, sea vegetables, cauliflower, and sunflower or sesame seeds. For supplements, start with 200-500 mg and work up – as needed – to 1000-1500 mg, taken before bedtime. However, experts do not recommend supplementing with 5-HTP because it blocks other important neurotransmitters and thus will only be effective short-term and then will stop helping sleep and cause side effects. Don’t combine tryptophan with TCAs or trazodone; that would increase serotonin too much.
• Adequate Nutrients. Whichever treatments you try, make sure you are getting the vitamins and minerals necessary for each of these hormones to convert effectively into the next (see Normal, Healthy Sleep above). This includes plenty of magnesium, which some people also find mildly sedating, so you can take it before sleep. Be sure to get a form of magnesium that is well-absorbed, like glycinate, malate, or l-threonate (which also helps with cognitive function). Common types of magnesium found in most drugstores, like oxide and citrate, are so poorly absorbed that they are used as laxatives!
• Prescription Sedatives. Traditionally known as sleeping pills, sedatives are not the best choice for correcting sleep dysfunction. They help you fall asleep and stay asleep, but they will not improve the quality of your sleep. Older ones, like Valium, actually worsen your sleep quality, further disrupting the deep sleep stages. Newer choices, like Ambien, Lunesta, and Sonata, will not disturb sleep, but they also won’t improve it. They do have a place, though, as an occasional extra treatment, when more help is needed.
• Over-the-Counter Sleep Aids. Antihistamines like Bendaryl (diphenhydramine), anything with a “PM” in the name, and other over-the-counter sleep aids are best used short-term only. Most use diphenhydramine as a sedative, but your body quickly gets used to it and then it won’t work as well. Additionally, it will not improve your sleep quality and has anticholinergic effects over time. These are best used for just for a few days at a time, when you need some extra help, especially if you need them for other reasons, like an allergy flare or temporary pain.

 

Our Experiences

My son and I both have ME/CFS, plus tick infections, but I listened to my doctor all those years ago and treated sleep dysfunction first. Once my son got sick, we did the same for him, and we have both been sleeping a solid 9-11 hours of good quality, normal-feeling sleep every night for over sixteen years … and waking up feeling refreshed most mornings.

 

I first tried amitriptyline at its lowest dose, but it left me groggy in the morning. Next, I tried nortriptyline liquid in tiny doses (and we started with that for my son) and gradually increased the dose as needed, until we each leveled out at an effective dose; then we switched to more convenient capsules. After a year or two, the nortriptyline wasn’t working quite as well, so we added trazodone, again starting low, at just 25 mg. We both ended up (he’s an adult now) at a combination of 50 mg nortriptyline and 100 mg trazodone (low doses compared to what is used for depression). 

 

We both also take timed-release melatonin supplements (3 mg for me and 5-10 mg for him), and I have a prescription for low-dose Ambien that I only use rarely, when I travel. We both also take plenty of magnesium (both malate and l-threonate) and the other nutrients listed above. Lab tests can help to show which nutrients you need more of and which you have plenty of; for instance, we are both very high in B6, so we don't supplement with it.

 

My doctor was right: correcting sleep dysfunction has helped to improve all of our symptoms. When combined with other treatment approaches, like treating orthostatic intolerance and immune dysfunction, my cortisol levels normalized, too.

 

You can read more about our own experiences using trial and error to find the right combination treatment in my earlier post on Correcting Sleep Dysfunction.

 

Sleep Hygiene

Although the sleep dysfunction of ME/CFS can’t be corrected just with standard guidelines for “sleep hygiene,” you do need to promote better sleep, in addition to whatever treatments you try. As one sleep expert explains, getting a good night’s sleep requires an intricate coordination of many different elements, including some of the basics:

• Keep your room dark and cool. Studies show people sleep most soundly when their room is 60-67 degrees Fahrenheit (blankets are fine). Use room-darkening blinds, shades, or curtains.
• Get plenty of daylight during the day. As soon as you wake up in the morning, open the curtains and get lots of natural light throughout the day--it tells your body to stop making melatonin and make more cortisol, making you more alert. That also helps when it gets dark, to tell your body it’s time to sleep.
• No screens two hours before bedtime. Besides electronic devices being stimulating, blue light emitted from them tells your body to stop making melatonin. Try reading a print book, listening to an audio book, or just listening to relaxing music before bed. If you must use an electronic device in the evening, use bluelight-blocking glasses (cheaper or try these, top picks in testing) or screen protectors. I sometimes read with an e-reader before bed, but you can adjust the display for less blue light. On my iPad Mini, I go to Settings, then click on Display and Brightness. Click on Night Shift, and you can set a time period each day when the display will switch to less blue light. Mine is set for Night Shift from 9 pm to 7 am, and I have the "color temperature" all the way to More Warm (which is less blue light). These settings should work on any Apple device.
  
• Wear warm socks. Research shows that warm feet helps you to fall asleep more easily and sleep more soundly. I tried wearing soft, warm socks for my naps and found that it works.
  
• Naps are probably OK! One common sleep hygiene rule you should NOT follow is the advice to avoid daytime naps. That’s for healthy people, not us. Our bodies often don’t make enough energy to get through the whole day. It is far better to take a nap mid-day than to push yourself to stay awake until you are “wired and tired,” making it even harder to sleep at night. My after-lunch nap is an essential part of my day and allows me to function into early evening. My How to Nap video has lots of practical tips for getting effective, proactive rest before you crash.
  

 

Myalgic encephalomyelitis/chronic fatigue syndrome and long-COVID are a complex web of intricate causes and effects, involving every system in the body. When sleep is disrupted, problems in the endocrine, immune, and nervous systems occur, worsening all ME/CFS symptoms in a vicious cycle. Similarly, when you treat sleep problems in ME/CFS, there will be improvements in all of these systems, leading to improved symptoms. Best of all, improving those systems will lead to even better quality sleep, in a positive domino effect. The best treatment approaches not only help you fall asleep and stay asleep but improve the quality of your sleep so that you wake up feeling refreshed and ready for a new day.

 

Suzan Jackson is a freelance writer who has had ME/CFS since 2002 and also has Lyme disease. Both of her sons also got ME/CFS, in 2004 at ages 6 and 10, but one is now fully recovered after 10 years of mild illness and the other is living on his own and working, with ME/CFS plus three tick-borne infections. She writes two blogs, Living with ME/CFS at http://livewithcfs.blogspot.com and Book By Book at http://bookbybook.blogspot.com, and wrote the book, Finding a New Normal: Living with Chronic Illness, available everywhere. You can follow her on Twitter at @livewithmecfs.

 

References

 

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Alban, D, Alban P. “Use Tryptophan to Boost Serotonin for Better Mental Health.” Be Brain Fit website (April 3, 2019).

 

Bell, D. “Sleep in CFS.” Lyndonville News (January 2005) 2(1).

 

Castro-Marrero, J, Sáez‐Francàs, N, et al. “Treatment and Management of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: All Roads Lead to Rome.” British Journal of Pharmacology (March 2017) 174(5), pp. 345-369.

 

Cleare, A. “The Neuroendocrinology of Chronic Fatigue Syndrome.” Endocrine Reviews (April 1, 2003) 24(2), pp. 236-252.

 

Field, T, Hernandez-Reif, M. et al. “Cortisol Decreases and Serotonin and Dopamine Increase Following Massage Therapy.” International Journal of Neuroscience (July 7, 2009), pp. 1397-1413.

 

Jackson, ML, Bruck, D. “Sleep Abnormalities in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Review.” Journal of Clinical Sleep Medicine (December 15, 2012) 8(6), pp. 719-28.

 

Kishi, A. Presentation: “Sleep Disturbances in ME/CFS.” The National Academies of Science, Engineering & Medicine – Health and Medicine Division. May 5, 2014.

 

Kishi, A., Natelson, BH., et al. “Sleep-stage Dynamics in Patients with Chronic Fatigue Syndrome with or without Fibromyalgia.” Sleep (November 1, 2011) 34(11), pp. 1551-60.

 

Lapp, C. “Using Antidepressants to Treat Chronic Fatigue Syndrome.” CFIDS Chronicle (Summer 2001).

 

Morillas-Arques, P, Rodriguez-Lopez, CM, et al. “Trazodone for the treatment of fibromyalgia: an open-label, 12-week study.” BMC Musculoskeletal Disorders (Sep 10, 2010) 11, p. 204.

 

Rowe, PC, Underhill, RA, et al. “Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: a Primer.” Frontiers in Pediatrics (June 19, 2017).

 

Yamamoto, S, Ouchi, Y, et al. “Reduction of Serotonin Transporters of Patients with Chronic Fatigue Syndrome.” NeuroReport (December 3, 2004) 15(17), pp. 2571-4.

 

Yavropoulou, Maria P, et al. "Protracted Stress-induced Hypocortisolemia May Account for the Clinical and Immune Manifestations of Long-COVID." Clinical Immunology (December 2022), p. 245.

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