Chrononutrition and mathematical models level-up study of the human body’s master clock

25 Aug 2023 --- Researchers from the University of Waterloo and the University of Oxford have developed a mathematical model to understand the resilience of the circadian master clock or suprachiasmatic nucleus (SCN) in the brain. Meanwhile, chrononutrition, a new field of study that analyzes the effects of nutrition on circadian rhythm, is branching out into the influences of behavior and exercise on the mechanism.

“Mathematical models allow you to manipulate body systems with specificity that cannot be easily or ethically achieved in the body or a petri dish,” Stéphanie Abo, a Ph.D. student in applied mathematics and the study’s lead author, tells Nutrition Insight. “This allows us to do research and develop good hypotheses at a lower cost.” 

“In recent years, evidence has emerged that the circadian clock can interact with the nutrients we consume to influence how our bodies work. The term ‘chrononutrition’ refers to this relatively new field.”

The new models are being used to understand how the body regulates the rhythms and can hopefully help scientists find ways to improve its resilience in people with weak or impaired circadian rhythms.

Chrononutrition and circadian rhythm
The team of applied mathematics researchers modeled the SCN as a macroscopic system comprising an infinite number of neurons, using mathematical modeling techniques and differential equations. The study was published in the SIAM Journal on Applied Dynamical Systems.

“Throughout the day, our blood glucose follows a circadian rhythm. The body can better manage blood glucose earlier in the day, when food is typically consumed, but less so at night, when fasting is typically observed. Hormones involved in glucose metabolism, such as insulin and cortisol, also exhibit circadian rhythms,” Abo explains.

Eating when the body expects insulin to rise improves insulin response and glucose removal from the bloodstream, allowing people to maintain normal blood sugar levels. “This ultimately results in lower insulin levels during fasting hours, which is a good thing,” she says.

“Food can throw your brain clock out of sync with your body clocks, and when these clocks don’t communicate well, you don’t get optimal results.” 

Managing eating habits during daylight hours allows the body to anticipate and know when it can expect a food load, especially glucose/sugars, allowing it to be prepared and provide the most appropriate responses.

Analyzing neuron connectionsCreating set patterns for eating and exercise helps regulate the body’s circadian rhythm.
The researchers focused on understanding the system’s couplings – the connections between neurons in the SCN that allow it to achieve a shared rhythm. Sustained disturbances to the body’s circadian rhythms eliminated the shared rhythm, implying a weakening of the signals transmitted between SCN neurons. 

The scientists were surprised that a minor disruption strengthened the connections between neurons. 

“Notably, disrupting circadian rhythms, such as chronic jet lag, shift work, irregular sleeping and feeding habits and the lack of physical activity has been linked to an increased risk of cancer, obesity, heart disease, diabetes and memory issues,” explains Abo.

Daylight savings time or even late-night phone scrolling also significantly affects these rhythms. 

“Current society is experiencing a rapid increase in demand for work outside of traditional daylight hours. This greatly disrupts how we are exposed to light and other habits such as eating and sleeping patterns,” says Abo.

Timing critical in biological routine
Human circadian rhythms are roughly 24-hour cycles followed by the body’s systems, alternating between wakefulness and rest and coordinated by the SCN, a cluster of neurons. Sustained disruptions to circadian rhythm have been linked to diabetes and memory loss.

Environmental and behavioral signals, known as “zeitgebers,” such as the timing of meals, exercise and sleep-wake cycles, can fine-tune the circadian rhythm in addition to the light-dark process. 

Exercise is a strong zeitgeber of the muscle clock, which can effectively reset circadian rhythms. Because physical ability fluctuates throughout the day, knowing the body’s rhythms can significantly improve health, such as knowing that physical strength and skeletal muscle function peak in the late afternoon.

“Our bodies have a peripheral clock system that is primarily composed of muscle, adipose tissue, the liver and gut, which also participates in regulating the circadian rhythm,” Abo continues.

“Exercise and food, in particular, have the ability to reset the clocks of all of our peripheral tissues. This has no effect on the brain clock as the SCN continues to synchronize with the sun, but peripheral clocks are actually more controlled by the timing of food and exercise.”

Flowing with the light-dark cycleChrononutrition is an emerging field of study linked to circadian rhythm, which is beginning to branch out.
In another study published in Nutrients on the connection between circadian rhythms and nutrition, Dr. Marian Lewandowski, from the department of neurophysiology and chronobiology at the Institute of Zoology and Biomedical Research, Jagiellonian University, highlights the importance of synchronizing external influences. 

One of the main synchronizers of the circadian clock is the changing day and night (light/dark) cycle, a consequence of the Earth’s rotational movement around its axis, determining our most important rhythm of sleep and wakefulness. 

Food is another crucial “non-photic” synchronizer of the biological clock. Several studies have shown that food, always taken at the same time of day, develops the anticipation of its administration time in our behavior, otherwise known as intake, i.e., food anticipatory activity. 

Biological clock and chronotypes
In one of the studies analyzed for Lewandowski’s research, the authors demonstrated that an evening chronotype, the endogenous properties of our biological clock, mainly characterized overweight and obese subjects.

In addition to late (unhealthy) food intake, they consumed food much more quickly than people with the morning chronotype. 

Lewandowski explains that chrononutrition, a term from chronobiology, highlights the importance of eating at the right time. This is also very important in the proper functioning of the musculoskeletal system, the main system affecting our daily activities, including motor activity. Restriction of motor activity affects quality of life.

The study concludes that greater cooperation is needed between dieticians and physiologists in the field of chrononutrition, which can lead to a better understanding of the physiological mechanisms behind mutual interactions. 

Such an exchange of knowledge and expertise can lead to more effective prevention of musculoskeletal disorders. Developing appropriate nutritional strategies protects the body’s energy homeostasis by providing calcium and vitamin D for healthy bones and preventing osteoporosis, a pathogenesis linked to fluctuations in the circadian rhythm. 

By Inga de Jong