Frank A. J. L. Scheer
BOSTON — Variations in circadian rhythms can increase the risk for obesity and CVD, according to a presentation at the Cardiometabolic Health Congress.
“The circadian system causes changes in cardiovascular risk factors that may contribute to, for example, the promotion of thrombosis in the morning,” Frank A. J. L. Scheer, PhD, associate professor of medicine at Harvard Medical School and director of the Medical Chronobiology Program at Brigham and Women’s Hospital, said in the presentation.
Scheer presented new research showing that the circadian system has cardiometabolic relevance regarding the daily distribution of MIs, shift work, genetics and food timing. CV events are more likely to occur in the morning with a broad peak at about 9:00 AM, as shown in a study published in The New England Journal of Medicine in 1985, and there are similar profiles for stroke, ventricular arrhythmia and sudden cardiac death. However, from these epidemiologic studies, it cannot be determined whether this daily increase is caused by behavioral triggers such as waking up, abruptly changing to an upright body posture or becoming physically active in the morning, or whether there are changes in CV risk factors that would change regardless of what we do, or in other words, whether they are caused by our internal body clock, also known as the circadian system.
The circadian system influences a number of CV risk factors, which may play a role in the morning peak in CV events. Some factors under control by the circadian system that may contribute to the increased morning risk include cortisol, platelet activation, pro-thrombotic factor PAI-1 and the sympathetic nervous system activation following exercise, according to studies published in Proceedings of the National Academy of Sciences in 2010 and in Blood in 2014.
Working at night or rotating shifts are associated with obesity, diabetes and CVD. Scheer presented evidence from a study published in the Proceedings of the National Academy of Sciences in 2009, that circadian misalignment, the mistiming of sleeping and eating relative to the circadian system that is typical in shift work, leads to impaired glucose tolerance.
A study published in Proceedings of the National Academy of Sciences in 2016 found that other effects caused by circadian misalignment include increases of numerous inflammatory markers and 24-hour systolic BP. In a separate study published in the Journal of Biological Rhythms in 2017, it was shown that even chronic shift workers are not immune to these adverse events.
The circadian system is relevant not just to shift workers, but to all of us. A clear example is the daily rhythm of glucose intolerance.
“The clock time at which a meal is consumed is the main driver of the decrease in glucose tolerance from morning to evening,” Scheer said. “An effect stronger than the combined effect of the sleep/wake, fasting/feeding and dark/cycle.”
In collaboration with Marta Garulet, PhD, professor of physiology and physiological basis of nutrition at the University of Murcia in Spain, Scheer studied whether meal timing may also be important for humans. Indeed, they showed that the timing of the main meal was predictive of weight-loss success, as people who ate lunch later lost about 25% less body weight across a 20-week weight-loss intervention, Scheer said.
Not only does the circadian system influences the response of the body to meals at different times, but it also contributes to when people crave food,” he said.
Not everybody responds the same to meals at different times. Diabetes risk can be predicted by genetic polymorphisms of the human melatonin 1b receptor gene.
Daytime melatonin administration caused impaired glucose tolerance, a risk factor for type 2 diabetes, both in the morning and evening. This effect was only observed in carriers of the melatonin 1b receptor risk variant, according to a study published in Metabolism in 2015.
In a study published in Clinical Nutrition earlier this year, when individuals were randomly assigned to eat late, they had a significant impairment of glucose tolerance compared with when they were assigned to eat early. Also, this adverse effect of eating late was only observed in those individuals who were carriers of the melatonin 1b receptor risk variant.
“The presented data demonstrate the intricate connection between the circadian system and metabolism, with clear relevance for cardiometabolic health,” Scheer said.
The Nobel Prize in medicine and physiology was recently awarded to researchers of the circadian system, Scheer said. – by Darlene Dobkowski
Scheer FAJL. Sleep Science: Effect of the Circadian Rhythm on Obesity and CVD. Presented at: Cardiometabolic Health Conference; Oct. 4-7, 2017; Boston.
Disclosure: Scheer reports he received speaker fees from Bayer Healthcare, Philips and Sentara Healthcare.