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Circadian Rhythm and Metabolism by Christina Badaracco, MPH, RD, LDN

Sleeping and eating are likely the two human behaviors we most associate with following a regular daily schedule. But our bodies exhibit this pattern in many different ways on both a molecular and a behavioral level. Aspects of our diet, environment and lifestyle affect our metabolism, microbiome and other internal processes in these patterns called circadian rhythms. 


What are circadian rhythms?

The body operates circadian systems that result in a rhythm over each 24-hour period. “Circadian” in fact comes from the Latin words “circa,” meaning about, and “dies,” meaning day. These systems synchronize our internal, oscillating processes with signals from the surrounding environment. Rhythms vary among people but always serve to regulate these internal physiological processes.


How are circadian rhythms regulated?

Externally:

The external signals that entrain the body’s circadian rhythms are called zeitgeibers, the most dominant of which is light. We (as well as most other living organisms) have evolved to function optimally under the ambient conditions imposed by our daily cycle of light and dark; we are most alert and coordinated during the day and in the presence of light, for example. Other examples of zeitgeibers include atmospheric conditions, social interactions and eating. Food is one of the dominant zeitgeibers for our peripheral clocks.


Internally:

The hypothalamus of our brain contains a small region called the suprachiasmatic nucleus (SCN), which serves as the primary internal pacemaker for rhythms in our sleep and wake cycles, hormone secretion, metabolism and other systems. It regulates these peripheral functions directly, by affecting the way we eat, sleep and exercise, as well as indirectly, by affecting metabolic processes such as insulin secretion, lipogenesis (or fat formation) and nutrient absorption. Many peripheral tissues (such as liver, fat and muscle) also function with their own circadian rhythms, independent of the central nervous system. Those peripheral rhythms also lead to cyclical changes in the production of hormones that regulate metabolism. See the image below for a display of the output of these cues and their corresponding regulated patterns.  


External cues and output from circadian rhythms; SCN: suprachiasmatic nucleus (derived from Green et al. 2008)

Feedback loops establish circadian rhythms in both the SCN and peripheral tissues. These loops are systems of biochemical control that regulate the production of proteins, thereby controlling their function. In the context of circadian rhythms, increasing the production of a certain protein during the day can block the production of downstream proteins and reduce their concentrations. But when the production of that protein decreases at night, production of downstream proteins is no longer inhibited and their concentrations can increase. Many proteins involved in metabolism follow such feedback loops, including hormones (such as insulin and ghrelin) and enzymes.


How does our microbiome affect circadian rhythms?

Just as scientists continue to shed light on the connections between various physiological systems and our microbiome (i.e., the many microorganisms living within the body), they are learning that the microbiome interacts bidirectionally with our internal clock. Our gut microbiota have their own circadian rhythms, exhibiting fluctuation in composition and function throughout the day. They also produce metabolites that affect the regulation of our circadian rhythm, which in turn affects our metabolism. This relationship shows how disruption of the gut microbiota can impair circadian rhythms throughout the body. The timing and composition of food intake control the oscillations of bacteria, with a recent study even showing that this relationship is impaired by an unhealthy diet. Circadian rhythms altered by jet lag and shift work have also been shown to disrupt our microbiota, potentially leading to other negative health effects.


What happens when circadian rhythms are disrupted?

Disruptions to circadian rhythms are caused by sleep deprivation (and even delayed sleep patterns), shift work, and travel between time zones and the corresponding jet lag. Further, concerns about the proliferation of electronics with screens that emit blue light have led to research that showed that blue light inhibits melatonin production even more strongly than other types of light. Exposure to blue light should therefore be minimized, especially close to bedtime. 

All of these disruptions can lead to metabolic imbalances, including weight gain by altering lipid metabolism on a molecular level and on a macroscopic level by contributing to the consumption of unhealthy foods. It is possible that restricting the time of eating can combat these negative effects. Animal studies have suggested that following a high-fat diet that would normally lead to weight gain, when restricted in time, can help to maintain circadian rhythmicity in metabolism and a steady weight. The potential benefits of such time-restricted feeding has led to the popularity of intermittent fasting for its ability to reduce insulin resistance and increase glucose tolerance in the short term and lead to weight loss and possibly even increased longevity in the long term.


Circadian rhythms in multiple systems within the body regulate blood glucose balance. These rhythms are exhibited through glucose transporters in our skeletal muscle cells, oxidation rates and other related parameters. Disrupted circadian rhythms in muscle glucose uptake and oxidation in people with type 2 diabetes (T2D)—a disease characterized by impaired regulation of blood glucose—have been associated with the insulin resistance that leads to diabetes. The liver, fat tissue and pancreatic islet cells (which produce insulin) also follow circadian rhythms. Disruption in any or all of these tissues can lead to impaired glucose metabolism, insulin resistance and, ultimately, T2D.


Photo by Rayia Soderberg on Unsplash

Melatonin, the hormone produced by the pineal gland in the brain that regulates sleep and wake cycles, also follows a circadian rhythm. Its production is affected by a variety of factors, such as light, cortisol and body temperature. Impaired melatonin production or function will also increase the risk of developing T2D, in addition to tumor growth and other health concerns.


Caffeine is a particularly important external factor that regulates circadian rhythms. It can delay the production of melatonin in a dose-dependent manner. Over time, it can lengthen the period of circadian rhythms regulated by the SCN beyond 24 hours, potentially impacting various downstream metabolic processes discussed above. While people’s sensitivity to caffeine can vary, avoiding caffeine later in the day, and particularly when poor sleep and/or insulin resistance are a concern, can help to reduce these negative effects.


During the COVID-19 pandemic, many people are reporting getting too little and/or low-quality sleep. In addition to increased stress and anxiety, typical sleep-wake cycles surrounding work and school have been disrupted and people are likely exposed to less sunlight, interfering with natural circadian rhythms. As quality sleep is important for both physical and mental health, it is more important than ever to prioritize healthy sleep behaviors.


What are the best ways to promote a healthy circadian rhythm?

  • Try to follow a consistent sleep schedule. This means not staying up or sleeping in by too much on the weekends and then struggling to adapt to a weekday schedule. See our previous post about sleep for more information.

  • Block as much light as possible while trying to sleep and let plenty of light into your home during the day. Aim to spend 15 minutes outside in natural light each day during the summer and even more in the winter (remembering to apply sunscreen to protect exposed skin) to maintain your circadian rhythm as well as allow your skin to produce some vitamin D. 

  • Do your best to get adequate sleep each night, ideally about eight hours. The amount varies by individual—so while you may know someone who can function well on five or six hours of sleep, that is not true for most people. And children likely need several hours more. Besides supporting your body’s physiology, a good night’s sleep will also help to impose healthy behaviors, such as eating balanced meals and avoiding mindless snacking.

  • Eat meals on a fairly regular schedule and try to avoid eating late at night and within a few hours of bedtime.

  • Eat foods that fuel healthy microbiota, such as fiber and fermented foods, so they can support a healthy circadian rhythm.

Resources

  • Burke TM, et al. Effects of caffeine on the human circadian clock in vivo and in vitro. Sci Transl Med. 2015;7(305):305ra146.

  • Green C, Takahashi JS, Bass J. The Meter of Metabolism. Cell. 2008;134(5):728-742.

  • Farhud D, Tahavorgar A. Melatonin hormone, metabolism and its clinical effects. Iranian Journal of Endocrinology and metabolism. 2012;2:211–223. (In Persian).

  • Javeed N, Matveyenko AV. Circadian Etiology of Type 2 Diabetes Mellitus. Physiology (Bethesda). 2018;33(2):138–150.

  • Macauley M, et al. Diurnal variation in skeletal muscle and liver glycogen in humans with normal health and Type 2 diabetes. Clin Sci (Lond). 2015;128(10):707-13. ncbi.nlm.nih.gov/pubmed/25583442

  • Thaiss CA, et al. Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations. Cell. 2016;167(6):P1495-1510.e12.

  • Thaiss CA, et al. Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. Cell. 2014;159(3):514-29.


Christina Badaracco, MPH, RD, LDN

Christina is a registered dietitian and author who aims to improve access to healthy and sustainable food and educate Americans about the connections between food and health. She loves to experiment with healthy recipes in the kitchen and share her creations to inspire others to cook.


Christina completed her dietetic internship at Massachusetts General Hospital and earned her Master of Public Health degree from the University of California, Berkeley. Previously, she graduated with a degree in Ecology and Evolutionary Biology from Princeton University, after conducting her thesis on sustainable agriculture and energy in Kenya. She has done clinical nutrition research at the National Institutes of Health, menu planning and nutrition education at the Oakland Unified School District and communications at the Environmental Protection Agency’s Office of Water. She has also enjoyed contributing to children’s gardens, farmers’ markets and a number of organic farms.


cbadarac@gmail.com

www.linkedin.com/in/christina-badaracco/



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