COMMENTARY

Treating Gastrointestinal Disorders Through Improved Sleep

David A. Johnson, MD

Disclosures

December 19, 2016

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Sleep Fragmentation's Considerable Costs

Hello. I am Dr David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia. Welcome back to another installment of GI Common Concerns—Computer Consult .

Today, I wanted to chat with you briefly about taking a good sleep history and understanding why sleep is important, not only for gastrointestinal (GI) disease but also for health in general.

When a patient comes into your office and says, "I am just not feeling well," we in turn might say, "Your inflammatory bowel disease is reasonably well controlled. Let's look at the biologic monitoring." We are treating a lot of these diseases with drugs and not looking outside the box to say, "What else can be affecting your health that we could augment your primary treatment with?"

Sleep is very critical here and essential for you to understand because it is one of those things that is not recognized. Certainly, if you do not recognize something, you do not know how to ask the right questions, address it, and properly direct the patient.

Sleep fragmentation is incredibly prevalent. It is estimated that in the United States, approximately 1 in 3 people sleep less than 7 hours a night.[1] That accounts for somewhere in the range of 50-70 million people in the United States, or about 37% of our adult population.

We know that it clearly is driven by a variety of things, including societal changes. We are all up late. We work hard. How many people get in their bed and start to check their email again? Their text messages go off in the middle of the night, waking them up. Over 20% of the US workforce now has shiftwork-type schedules, including doctors.[2]

This is a very difficult situation because as you start to fragment sleep, you adjust a tremendous, complex, intricately wound, organized cycle. The body works around a clock mechanism, and you rise and fall throughout the course of the day. You have a variety of circadian rhythms that are driven in this machinery by normal health and physiology. As you start to disrupt this, it becomes very apparent that you can have significant consequences.

Identifying Sleep Disorders

There are a tremendous number of diseases associated with sleep fragmentation—metabolic disease in particular, as well as cardiovascular diseases and diabetes. In GI disorders, a lot of patients are awakened at night from discordant disease. The classic case is in patients with heartburn who awaken at night, which we try to control for.

A lot of patients may not even remember that when they awaken the next day because sleep is amnestic. You ask them if they're sleeping well, and they may say, "I sleep fine." However, their bed partner will be saying, "You talked to me three times last night. You did not sleep well at all."

It is the sleep amnestic effect that leads us to understand that we may miss a lot of the nuances of sleep fragmentation if we just rely on the question, "How do you sleep at night?"

We do know that if you start to ask the question, you need to ask not only the individual but the bed partner and the family as well. "How do they sleep at night? Do they awaken frequently?" Then it is important that we ask the patient about next-day function. "How do you feel when you awaken in the morning? Are you refreshed? Do you feel vibrant? Do you have early fatigability, concentration deficits, things that start to make you more irritable, or are you more sensitive in the course of the day to pain or irritation?" These are very common parameters that would tell a sleep expert that a patient may not be sleeping very well.

There are physiologic ways to assess this. We can put patients in a sleep lab, although this is very cumbersome and not really realistic in real life. There are a variety of other measures you can use, such as iPhone sensors and wristwatch-like actigraphy monitors. I just like to ask the questions, "How do you sleep at night? How do you feel the next day? Function-wise, how do you do?"

We do know that there is profound interference the next day, and not only in daily quality of life.

We did a study[3] in reflux patients where we put them in a driving simulator and found that they operated as if they were functionally impaired, which is something that is pretty scary. Patients who are not sleeping well do not necessarily fall asleep at the wheel, but they have fatigability. Their attention to detail and lane variation over a period of time is attenuated, and their likelihood of having an accident is increased. We do know that sleep fragmentation and poor sleep account for an estimated 40% of the accidents in the United States.[2,4]

There is a great study[5] that looked at residents post call. They went home after 24 hours and were tested that morning for driving performance. The control group was residents who worked only a short shift and went home but then came back the next day. They had IV alcohol titrated to a blood alcohol content of 0.05. Who do you think drove worse? It was the drivers who had been up on call all night rather than the short-call and elevated blood alcohol content cohort. The point is that poor sleep does have a significant effect on next-day function.

Impact in GI Disease

The prevalence of sleep issues in GI disease is implicit across virtually everything with which we deal. We obviously already know about nocturnal awakening in reflux disease and that the average inflammatory bowel disease (IBD) patient has significant sleep disruption.

In fact, if you start asking the IBD patients in your practice about sleep fragmentation, it may be a predictor for who in remission is going to go to a flare in the next 6 months, with odds ratios increasing anywhere from two to three times. Physiologically for IBD patients, when they have fragmented sleep, they are upregulating things like tumor necrosis factor-alpha, C-reactive protein, interleukin (IL)-6, and IL-10. These are things that we try to suppress when we treat an IBD patient. Here, we are upregulating things in the patient that may otherwise just be treated with their biologic or immunosuppressive drug. We are missing that opportunity if we ignore the sleep fragmentation aspect.

We also increase toll-like receptor (TLR) pathways, in particular TLR4, which is the IBD pathway primarily linked with colonic cancer and neoplastic degeneration. A variety of other cancers are also driven by this TLR4 pathway. We do know that cancer is increased in patients with sleep fragmentation, notably in those shift workers.

Talk to your patients with IBD about quality sleep being an endpoint that you want to maximize for those in remission, or conversely about recognizing and minimizing sleep fragmentation when it is present.

I put my patients on 5 mg of melatonin, which I tell them to take 30-60 minutes before bed. Physiologically, that also has some anti-inflammatory components. In fact, you block the induction of drug-induced colitis in mice if you premedicate them with melatonin.[6] I think that it is a very easy thing to do in our patient population.

When you talk about other diseases, like what we used to call functional irritable bowel syndrome and also dyspepsia, there is a clear inference that sleep fragmentation increases the likelihood that these patients are going to have symptoms or worse symptoms. It lowers sensory thresholds.

We have done a study[7] in mice that indicated that sleep fragmentation has a profound effect on the microbiome. The microbiome then plays into a variety of things that change sensory perception and also brain-gut interaction. We can see these effects on gene arrays that we can do both on brain biopsies and at the local gut level.

Sensory thresholds are really important, and patients need to understand that they need to get a good night of sleep.

One of the key markers for our patients with cirrhosis is looking at those with day-night disruption. Looking at nonalcoholic fatty liver disease, even alcoholic hepatitis, these disease states have a clear microbiologic footprint of dysbiosis. Given the interrelated effect of sleep and the microbiome, we are missing the boat here if we're not accentuating to patients how important sleep is and suggesting that they begin prioritizing it.

In our obese patients or our fatty liver patients, we may tell them that they need to lose weight and encourage that they eat less. That is not adequate. You need to talk to them as best as you can about a structured diet, and possibly refer them to a dietician, but do not miss the opportunity to talk to them about sleep. With fragmentation of sleep, you start to change ghrelin and leptin receptors. In particular, what happens is that you change the biologic premise of upregulating appetite and downregulating satiety.

These things are all driven by sleep fragmentation.

Taking the Wider View

When I talk to my obese patients, I take a very strong sleep history. Patients with metabolic syndrome and sleep apnea obviously could have some risk there. So I talk to them about the importance of sleep and put this in perspective.

When it comes to GI disorders, nearly everything I can think of has some footprint of dysbiosis or, as we now know, sleep fragmentation. Therefore, talk to your patients about next-day function and consider adding something like melatonin.

I talk to my patients about trying to get ready for sleep, about setting a timeframe when they know they are going to go to bed, just like we told our kids when they were growing up. About half an hour before that timeframe is their downregulation time when they put away all of their electronic distractions; their computer, emails, and iPhone should not be in the room with them. Instead, they should start to get ready for bed. If they're going to take melatonin, they will want to do so 30-60 minutes before. There is also some evidence that a little bit of lavender spray on the pillow can be somewhat helpful.

As sleep prioritization has become increasingly important, it is equally important for us to start asking our patients questions about it. I now treat patients as a whole, rather than with a nail-and-a-hammer mentality where, for example, if you present with IBD, you just get a biologic drug and that's it. I want to talk to patients about their diet, sleep habits, exercise, whether they take probiotics or prebiotics, and whether they are using artificial sweeteners.

All of these things are very much integrated into a better care plan, and sleep is a vital component of that. We need to start taking a better history. Start asking about it, thinking about it. It is time for us all to open our eyes to the value of closing them. It is really important for our patients.

I am Dr David Johnson. Thanks again for listening.

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