Francisco Romo-Nava, MD, PhD, a physician scientist, at the Lindner Center of HOPE and the University of Cincinnati talks about the role of the body’s sleep-wake cycles, known as the circadian clock, in binge eating.
Let’s start by asking you along those lines. We hear a lot about our circadian rhythms, especially when we’re coming up on time change on the East Coast. Can you tell me a little bit for our viewers who may not be really familiar what that is and how it works in the body?
ROMO-NAVA: Sure. Well, “circadian rhythms” refer to the cycles that happen on many of our bodily and brain functions throughout the day. Circadian rhythms are the result of the functioning of something that we call the circadian system. The circadian system, it’s a very interesting system with a profound physiological importance. The circadian system, we could say that it’s composed by a master pacemaker or main “biological clock” in the suprachiasmatic nucleus of the anterior part of the hypothalamus. This is a small brain region in the anterior part of our head. This master pacemaker, communicates or is able to send signals that inform our brain and bodily function about the different timings of the day. This master pacemaker is able to respond to several internal or environmental signals and is able to organize and maintain biological rhythms according to those signals. Perhaps the most important signals are light and darkness. It’s also able to respond to other internal input that comes from our body and shift its rhythm while coordinating with peripheral molecular clocks that are located in most cells of our body. This interaction can take place via neural signals in the central nervous system and the peripheral nervous system, like the autonomic nervous system. It’s also able to do this by non-neural communication. This is through hormones and neurotransmitters. This interaction between the master pacemaker and the peripheral clocks, we call the circadian system and is involved in most physiological processes. If you interrupt or disturb this communication, then you start getting into physiological stress that we’ve seen is associated with a lot of adverse health outcomes in not only animal models but also in human studies.
What are some of those adverse health effects from having an interruption in the system or having it out of whack?
ROMO-NAVA: Well, for example, the circadian system of each individual is different. Some tend to be more active during the morning and prefer to work in the morning, do everything in the morning and go to sleep early. There are others that don’t really have a preference. There are others that prefer to do everything at night. You may have heard about this. These are the chronotypes and the these are the three distinct chronotypes types, the morning, the intermediate or the evening types. It’s become more and more apparent that in particular, those with an evening type of chronotype may be susceptible to put their circadian system and their physiology under constant stress because they have to deal with not their organization or their internal functioning of the circadian system, but they have to contrast that functioning to the societal needs. They have to go to school early. They have to work early. They have to attend the office hours that correspond to the rest of the society. They are constantly challenged by that. We’ve seen that this evening chronotype is associated with a lot of adverse health outcomes, such as increased risk of diabetes, increased risk of obesity, increased risk of even depressive symptoms, increased risk of several other psychiatric disorders. Evening chronotype has also been associated with increased binge eating behavior.
So, tell me a little bit about what you and your colleagues are studying then in regard to the circadian rhythms and binge eating.
ROMO-NAVA: Well, we started looking into the function of the circadian system in a different context but focusing on the metabolic aspects of circadian system regulation. Then we started noticing that the literature regarding binge eating disorder was showing us that the circadian system may be involved. Binge eating disorder is the most prevalent eating disorders that you can find in the U.S. population. It’s even more prevalent than bulimia nervosa and anorexia nervosa. Binge eating disorder is characterized by episodes of consuming large amounts of food in a relatively brief period of time and with a sense of loss of control. This happens in a recurrent form at least once per week in the past three months. It’s associated with distress and suffering, and it’s associated with guilt. It’s associated with several adverse health outcomes, and we started getting interested in the function of the circadian system in this eating disorder because we noticed that there are certain time of day clinical characteristics of the binge eating behavior and food intake patterns. Binge eating behavior tends to occur on the second part of the day and more so into the evening and night. And we’ve seen that this is perhaps not only happening because of an increased window of opportunity, because it can also happen during the weekends. Of course, it’s not the only time at which it happens, but it’s more frequently throughout that time. Also, patients with binge eating disorder may tend to skip breakfast more often. They may tend to have more of their food intake later or night, and also binge eating, or the severity of binge eating is associated with eveningness or evening chronotype. For these reasons, we are now trying to study what is the role of the circadian system in binge eating disorder?
How are you going about doing that?
ROMO-NAVA: Well, what we will do is it’s a two-step study. It has two phases. The first phase is going to compare and what we call “characterize” the circadian system function in participants with obesity that don’t have binge eating disorder and also in participants with obesity that do have binge eating disorder. What we will do is we will try to know at what time is it that their circadian system shifts from day functioning modality into a night functioning modality? We do that by obtaining the most reliable marker of circadian system function that we have right now which is something called Dim Light Melatonin Onset. This is trying to identify at what time does this master pacemaker sends the initial signal to the rest of the brain and body that it is time to shift into a night mode by increasing the levels of endogenous melatonin. This is a very important physiological moment because it tells us when it shifts. So, we think that we will find differences between these two groups. Then we will also be able to know the internal timing as well as other eating behavior and metabolic parameters of patients with binge eating behavior and without binge eating disorder. For that first phase, we’re going to recruit 40 participants that are on the control group, on the group that doesn’t have binge eating disorder and 40 participants on the group that does have binge eating disorder. Then, only the participants that do have binge eating disorder will go into phase two, into the second part of the study, which is an interventional part. And at this moment, it’s important to mention that the second part is going to be an interventional part that is not designed to test the efficacy or the safety of an intervention. It is designed to try to know the mechanism by which binge eating behavior may occur or to which mechanism it may be associated. This we will try to interrogate or to investigate by assigning, this is a double blinded randomized study design on which some participants, half of the 40 individuals with binge eating disorder will be assigned to receive a combination of morning lights with a nightly capsule of either melatonin or placebo that is timed according to each individual’s internal timing or their circadian phase. By doing this, we aim to target the circadian system and evaluate if there’s any association with eating behavior. At the end of the study, we want to learn what is the role of the circadian system, if there are differences between the control group and the group with patients that have binge eating disorder, and if by targeting the circadian system in an individualized way, we can learn more about whether the circadian system could eventually become a therapeutic target. Again, this is not designed to try to test if melatonin or any form of light therapy works to treat the binge eating behavior. We would advise against using at this moment any form of light therapy or melatonin to treat binge eating disorder. We are trying to learn first what is the mechanism and whether this mechanism involves the function of the circadian system. That could lead into the development of chronobiological interventions, that means interventions that target the circadian system to try to help patients with binge eating disorder.
Doctor, right now when you have a patient with binge eating disorder, what options do you offer them, can you offer them? And my Part B to that question is why is it important to have additional avenues down the road and additional therapies or treatments for people that are struggling?
ROMO-NAVA: Well, that is a very important question because there’s several options in terms of psychotherapeutic interventions that can help patients with binge eating disorder. But of course, not every patient with binge eating disorder may respond to psychotherapeutic interventions. Sometimes these may not be available, or these may be a resource that is not available to a specific patient. There’s one FDA approved medication for the treatment of patients with binge eating disorder. Of course, also not all patients with binge eating disorder may respond to this pharmaceutical intervention. There are others that are being developed. There are other medications that may be prescribed with an off-label indication. Each patient should consult with their care provider to evaluate which could be the best option. There is a need, as I mentioned earlier, binge eating disorder is the most prevalent eating disorder. Unfortunately, there are still very limited options or targeted options for treating binge eating disorder. It is an understudied area, and it is very important to know more about this important eating disorder and find a way to develop new treatment alternatives.
I have a couple of questions just as I’m writing and for clarification. Is there any indication how many people in the United States might have binge eating disorder?
ROMO-NAVA: It is estimated that approximately 1.6 percent of females in the US may have binge eating disorder and approximately .8 of males. So, there’s a gender difference. And that’s perhaps the most used number.
In terms of testing to find when individuals systems do that switch, you had mentioned a saliva test. Is there a sleep study involved where technicians are doing the saliva test? Or can you just describe for me how this would work to gain that information during the trial?
ROMO-NAVA: Of course, of course. And thank you very much for that question because it’s actually one of the most important parts of the study because traditionally this measure of circadian phase that is called Dim Light Melatonin Onset is done on sleep laboratories or in hospital settings because as its name implies it needs to be conducted under dim light conditions. It’s been difficult and costly to do it that way, but now we’ve been collaborating with colleagues to try to use an at-home DLMO method. So, what we do is every participant during the study on the first phase, they come in here. We evaluate whether this study is for them or not. If we see that this study is for them, then on the next visit, they start wearing a watch, which is an actimeter that we’ll be able to track activity cycles. Also, they take home a sleep diary and an eating behavior diary. When they come back after two weeks of recording this information, then we are able to estimate their average sleep onset time for the past seven days. We use that to try to identify when is the best moment to conduct the saliva sample collection? And we do it six hours before each individual’s sleep onset time. We show participants how to collect the saliva samples every 30 minutes until their sleep onset time. They take home a kit that has all of the materials and is fairly straightforward with very detailed instructions about how to do this and how to prevent exposure to light. We have several ways of monitoring this exposure to light to show that these saliva sample collections were conducted under these dim light conditions. By doing this, then we are able to capture that moment.
Starting six hours before?
ROMO-NAVA: Six hours before.
That’s a lot of saliva, right?
ROMO-NAVA: That’s 13 samples. They put them in their freezer. Then we’ll receive the samples on the next day. That way it’s easier for participants. We aim to navigate outside the sleep laboratories and outside the hospital setting because we think it’s very important to start doing these kinds of assessments for many clinical research purposes.
The only other question I had, you had mentioned people either are the early morning, I think you use the word is…
ROMO-NAVA: Chronotype.
…Or late evening or some kind of intermediate?
ROMO-NAVA: Yes.
Are those the people that are, you know, popularly called the early birds versus… The night owls? Is it OK to say, you know, if you think of yourself as a night owl, someone who does that functioning better at night or an early bird?
ROMO-NAVA: That’s correct. That’s correct. Among the population, it’s estimated that between 10 and 15 percent of the population will be morning type, clearly morning types. Then most of the population will be intermediate types between 70, 75 percent. Only about five percent of the population is a true evening type. But there’s also variations, it depends how it’s measured.
Is there anything I didn’t ask you, doctor, that you would want to make sure our viewers know?
ROMO-NAVA: No. Just perhaps just emphasize that this is an initial step, and this is proof of mechanism study. Know – and we need to be very clear about that. That we’re trying to learn about the function of the circadian system. This is not a therapeutics study. This is a proof of mechanism study.
The hypothesis is there that if you bring this system back into balance, it will have an impact on the binge eating.
ROMO-NAVA: Yes, of course. Eventually we would like to evaluate whether this intervention is able to shift or resynchronize the time of this physiological phenomenon. By doing this, whether this is associated with a change in eating behavior and binge eating episodes.
If you would like to learn more about this study, you can visit www.lcoh.info
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
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