Around this time of year, many societies advance their clocks by one hour to make efficient use of seasonal daylight. Americans switched to Daylight Saving Time last week, and this week Europeans will revert to Summer Time. When this happens, we all “lose” an hour of sleep, because we have to get up and get things done an hour earlier than we have been. This is in relation not just to the light and dark cycles of the day, but also to our body clocks. One hour sounds like a small change, but it can make a big difference in how we function, at least in the short term. For example, data from the past two decades shows that there is a statistically significant spike in the number of car wrecks on the Monday immediately following the shift to Daylight Saving Time in the US. As we all adjust to the time change, it’s worthwhile to consider how other aspects of our lives can sway our circadian rhythms. Circadian clocks govern the rhythms of sleep and activity in virtually all animals and are responsive to a variety of stimuli like light and stress. Research is starting to suggest that our eating patterns – specifically when we eat – affects our circadian rhythms. This has implications for what the best time to eat is.

 

The best time to eat depends on cellular energy needs, which change throughout the day

Mitochondria are often referred to as “power plants” because they are the main source of cellular energy, via the breakdown (oxidation) of carbohydrates and fats. But the need for energy production changes considerably across the 24-hour period based on energy demands. Consider that energy supplies, in the form of food, do not flow into the body continuously – they enter the body in bursts when we consume meals. Therefore, theoretically, a body may handle a burst of calories from a meal more or less effectively depending on what time of day it is, and what types of enzymes are being churned out at that time. The time-of-day production of enzymes is somewhat predetermined by what has been the regular exposures for the animal, including patterns of activity, light exposure, and food intake time and type.

A recent study by Dr. Neufeld-Cohen and colleagues of the Weizmann Institute has shed some light on why this may be the case. The investigators were interested in looking at how mitochondria are able to deal efficiently with fluctuations in time-of-day energy supplies.

The researchers used 3-month-old mice of two different types: one group “wild type” (not genetically atypical or bred for particular traits), and the other group had a genetic mutation that interferes with their biological clocks. These mice are called PER1/2 named after the PERIOD gene, which helps influence the timing of cellular functions. The PER1 and PER2 proteins that are usually produced by the gene are inactivated in these mutant strains.

The mice were kept in controlled conditions and fed either a) whenever they wanted or b) exclusively when the animals were awake and active. After two weeks, the mice were sacrificed at 4-hour intervals over the course of two days. This way, each time point across the day-night cycle was represented by four animals. Their livers were harvested and analyzed, and the researchers took on the arduous task of quantifying hundreds of mitochondrial proteins, building perhaps the first ever comprehensive mitochondrial proteome – a complete database of all of the mitochondrial proteins.

 

The best time to eat depends on metabolism, which changes throughout the day

The team identified and analyzed many essential proteins in this mitochondrial proteome.They found that about 40% of the animals showed oscillations in protein production across one full day (24-hours). One protein that they looked close at was pyruvate dehydrogenase. This is an enzyme that determines the rate of glucose utilization for generating energy. In the normal mice, the highest production of this enzyme occurred during the part of the 24-hour cycle where these animals sleep. This suggests that mitochondrial ability to burn sugar is probably greatest at this time as well. When the team tested this hypothesis by supplying the mitochondria with glucose, the metabolism of sugar was found to be at its highest level, too.

Similarly, the researchers looked at an enzyme responsible for shuttling fatty acids into the mitochondria (carnitine palmitoyltransferase I). They found that this protein is produced at the highest rate during the period of day when mice are awake and physically active. Again, this indicates that the mitochondria are best able to use lipids during the wake period, and again, subsequent tests confirmed that fats were indeed utilized most efficiently at this time.

The daily changes in these key enzymes, however, were not evident in mice that had the specific circadian genes deleted (Per1/2). The amounts of these cellular proteins remained steady throughout the day, as did the utilization of sugars and fats, suggesting that the timing of fuel preference by cells depends on the activity of these clock proteins.

These findings are also bolstered by a previous study from the very same lab showing that if mice only eat during their active period, levels of triglycerides in the liver will be dramatically lower than if they eat during the time they usually sleep. It’s clear that cellular metabolism is at least partially coordinated by the circadian system. 

 

Why does this matter to us?

This study helps us better understand the mechanisms behind something that has already been recognized in previous research: erratic eating patterns – including eating very late in your day – appear to disturb the circadian system, which then disturbs our metabolism.  For example, research by Frank Sheer at Harvard and colleagues had healthy human subjects eat and sleep during the opposite 12 hours to which their bodies were conditioned, which is equivalent to what happens during some shift work schedules (e.g., eating when you typically sleep, and vice versa). Blood measurements taken after only a few days on this opposite schedule showed that these otherwise-healthy people were regulating blood glucose like a prediabetic. More recently, another experiment found that the day after eating lunch late, compared to eating it earlier, resting energy expenditure was lower, the ability to handle blood glucose effectively after a meal was impaired, body temperature elevation in response to food intake was diminished, and morning and afternoon cortisol levels were blunted.

 

What is the best time to eat? Eating late at night increases risk of obesity and results in metabolic disorder. Click To Tweet

 

Clearly, circadian clocks are crucial to the orchestration of our physiology. Long term, the regular disruption of our daily timing rhythms – whether it be via the wrong exposure to light, or eating late in your day and / or eating later than you typically eat – can wreak havoc on our metabolism, and consequently, if the unhealthy patterns are sustained, our health. We learned from the Dr. Neufeld-Cohen study mentioned above that metabolism appears to differentially support functions occurring at specific times of day. Below, the work by both Sheer and colleagues, and separately the work by Bandin and colleagues, implicate meal timing to be important for humans. While many of us may feel fine eating big meals late at night, there is a real possibility that doing this affects the body negatively, even if it’s hard to perceive any immediate impact. Therefore, eating dinner on the early side appears to be a sensible part of one’s health practice – which is something I currently try to implement – and I look forward to more work on this subject in the coming years. 

 

References

1. Varughese J and Allen RP. Fatal accidents following changes in daylight savings time: the American experience. 2001. Sleep Medicine 2(1):31-36.
2. Neufeld-Cohen A, Robles MS, Aviram R, Manella G, et al. Circadian control of oscillations in mitochondrial rate-limiting enzymes and nutrient utilization by PERIOD proteins. 2016. Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1519650113
   
3. Adamovich Y, Rousso-Noori L, Zwighaft Z, Neufeld-Cohen A, et al. Circadian clocks and feeding time regulate the oscillations and levels of hepatic triglycerides. 2014. Cell Metabolism 19(2):319-330.
4. Scheer FA, Hilton MF, Mantzoros CS, Shea SA. Adverse metabolic and cardiovascular consequences of circadian misalignment. 2009. Proceedings of the National Academy of Sciences 106(11):4453–4458.
5. Bandín C, Scheer FA, Luque AJ, Ávila-Gandía V, et al. Meal timing affects glucose tolerance, substrate oxidation and circadian-related variables: A randomized, crossover trial. 2015.Int J Obes 39(5):828-33.