A Circadian Rhythm of Metabolism

To be healthy, we need to be flexible at the right times. In other words, the cells and tissues in our body need to know when to transition from burning primarily sugars to burning fats. This is known as metabolic flexibility.

Each of our human cells can change their metabolic states cyclically throughout the day, based on a variety of internal and external cues. This happens because of what is known as the circadian rhythm. Our brain, organs, and tissues such as fat and muscles undergo cyclical changes in gene expression and other cellular and metabolic pathway activities. These changes can be driven by a variety of stimuli such as light fluctuations and nutrient availability. For example, the circadian clock dictates when our mitochondria, the energy producers in our cells, are most active and efficient. The levels of energy molecules including ATP present in various parts of our body, including in regions of our brain, normally cycle every 24 hours, based on daylight and feeding cues.

“The circadian clock controls protein phosphorylation to regulate the timing of metabolic pathways. The activity of kinases downstream of the insulin/insulin-like growth factor 1 (IGF1) receptor, measured as the phosphorylation of their substrates, is high during the active phase.” — Paschos & FitzGerald, 2017

The circadian clock helps our bodies know when to enter the most efficient metabolic state based on nutrient availability, such as moving from burning sugars to burning fats overnight. But if we eat in discordance with our biological clock, such as when we are more insulin resistant in the evenings, we can force our bodies into a less efficient metabolic state, or even prompt metabolic dysfunction such as seen in people with type 2 diabetes.

This imbalance happens as a result of a battle between the body and the brain. We all have a master clock contained within a small region of the brain known as the superchiasmatic nucleus. It tells us when we should be awake and when we should be at rest. However, it is not perfect and can be influenced by outside stimuli such as food, temperature and social cues, collectively known as zeitbergers. If our liver, muscles and adipose tissue are being told to be active (think late night snacking or the graveyard shift) while the brain is saying the opposite, we become biologically confused about which metabolic state we should be in, according to the time of day, sunlight and our sleep pattern.

The Master Clock. Credit: LifeOmic.

“Desynchronization of the suprachiasmatic nucleus master clock in the brain and peripheral circadian clocks in liver, fat, and skeletal muscle cells may increase the risk of chronic diseases. Feeding signals appear to be the dominant timing cue for the rhythms of peripheral clocks, including those that control metabolic pathways.” — Patterson & Sears, 2017

The interplay between circadian clocks and metabolic health is often visible in people with insomnia, jetlag, or who work night shifts. Shift work and jetlag can “throw circadian clocks out of synchrony to accelerate metabolic dysfunction and move towards the development of the metabolic syndrome,” (Paschos & FitzGerald, 2017).

Circadian rhythm disruption is associated with metabolic issues including insulin resistance, elevated blood glucose levels and prediabetes. When we eat can impact our health both directly and through setting of our circadian clocks. When we eat at night, our blood glucose, HbA1c and insulin levels increase more and say elevated longer than when we eat earlier in the day, which can result in an elevated risk of type 2 diabetes over time. People who eat and sleep a full 12 hours out of phase from their habitual patterns can experience raised blood pressure, glucose intolerance, hunger due to lowered activity of the satiety hormone leptin, and cortisol level changes.

The LIFE Fasting Tracker app helps you plan and practice time-restricted feeding through different time zones. Download on the Apple App Store or at lifefastingtracker.com.

One way to avoid this circadian clock confusion is through the use of time-restricted feeding regimens that limit our hours of eating to 9–12 hours earlier in the day. Research has revealed this practice can help us better regulate our body weight and energy metabolism. In fact, time-restricted eating or eliminating night eating altogether may help establish better circadian rhythms in people who travel through different time zones or who experience insomnia, with associated improvements in melatonin levels, sleep patterns and metabolic health.

Time-restricted feeding can be protective against diet-induced obesity and diabetes. In a 2012 Cell Metabolism study in mice, animals provided a high-fat diet chow throughout the night and day wound up obese and metabolically dysfunctional, with a high risk of developing type 2 diabetes. But mice on the same diet albeit where the availability of the chow was restricted to 8 hours during their active phase were protected from obesity, metabolic dysfunction and inflammation.

In human observational studies, prolonged overnight fasting (at least 13 hours per night) has been associated with reduced risk of breast cancer recurrence in women, reduced risk of elevated HbA1c (HbA1c or glycated haemoglobin is associated with glucose in the blood, high levels of which are associated with diabetes), and reduced inflammation.

“Using data from the National Health and Nutrition Examination Surveys […], we have shown that each 3-hour increase in nighttime fasting duration was associated with significantly reduced odds of elevated HbA1c and significantly lower CRP [C-reactive protein] concentrations in women who ate less than 30% of their daily calories after 5:00 p.m.” — Patterson & Sears, 2017

Disrupted metabolism, which circadian misalignment (those late night snacks again!) and disruption (graveyard shifts) can trigger, is also known to accelerate aging and diseases of aging. Researchers today are investigating whether we may be able to delay aging by improving the amplitude of our circadian rhythms, for example through time-restricted feeding. This is still an outstanding question in human aging science, but it is the subject of concentrated research efforts.