Want the Most Benefit from Exercise? Timing is Everything.

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Exercise is typically “prescribed” as a specific frequency (how many times per week), intensity, type, and time (duration). In exercise science, this is known as the FITT principle.

By combining different variations of frequency, intensity, type, and time, we can customize an exercise program to meet the specific needs of an individual and achieve the desired benefits — whether they be related to performance or health.

Recently, with the discovery that nearly every cell and tissue in our body has its own circadian rhythm, another component of exercise prescription is being added to the list. That component being the time of day at which the exercise is completed.

A comprehensive overview of circadian rhythms is beyond the scope of this post, but I’ve covered circadian rhythms as well as their relation to exercise in previous posts.

Briefly, circadian rhythms can be thought of as our internal and ever-oscillating “clocks.” These rhythms determine when we sleep, when we get hungry, and a myriad of other metabolic and physiological functions. They’re largely driven by the light-dark cycle, but also respond to feeding-fasting and rest-activity cycles. Food, sleep, and activity are known as zeitgebers (time-givers) — they are external cues that regulate our internal clocks to maintain health and function.

How do circadian rhythms relate to exercise?

For one, circadian rhythms in our muscles regulate energy production, body temperature, and other aspects of function which can affect exercise performance.

You have likely experienced this first hand. It is quite easy to notice how differently you perform in the evening vs. the morning, or vice-versa. While this is largely a matter of personal preference, it undoubtedly has something to do with circadian rhythms.

Most studies in humans find that exercise performance is higher in the afternoon/early evening compared to the morning.

Why does this matter? If we have a certain goal in mind, say, improving blood glucose levels, then determining the best time of day to exercise to improve blood glucose levels could help maximize our effort — allowing us to get the most bang for our buck.

Accordingly, if it’s performance that you’re after, then determining when your peak exercise capacity occurs would give you some insight into when it’s best to go for a run or pump some iron.

Fortunately, studies are investigating these very topics, with the hope of stripping the biology of exercise down to an exact science —a science of time.

While unofficial, this new paradigm in exercise science has been termed “chrono-exercise”.

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If you want peak athletic performance, is it best to exercise in the morning or at night?

A majority of studies find that exercising later in the afternoon leads to better performance compared to that done in the early morning.

Mice were monitored during three different exercise intensities (low, moderate, and high) at two different times of day (early active and late active phase, corresponding to morning and afternoon in humans, respectively).

+1 for afternoon exercise. Mice who ran at low and moderate intensities later in the day ran substantially longer than those running in the early morning. Interestingly, there weren’t any differences in exercise capacity at the high exercise intensity.

Study graphical summary from Ezagouri et al.

The effects of exercise were totally dependent on an in tact circadian clock system. When the researchers repeated this study using mice lacking core components of their circadian clocks (the genes PER 1&2), there were zero differences in performance in late vs. early exercise.

So, performance is better in the afternoon. But why?

This might have something to do with energy metabolism. For one, after exercise in the early phase, mice had high levels of biomarkers in their blood which the researchers concluded might indicate incomplete utilization of fatty acids during early morning exercise and as a result, a compromised exercise capacity. This make sense, since only low and moderate intensity exercise were impaired, but not high. Fatty acids are the primary fuel utilized during low to moderate exercise intensities.

Mice who exercised later had more activation of a protein known as AMPK; which stimulates glycolysis (the breakdown of glucose) and beta-oxidation (the breakdown of fatty acids) to produce ATP. A better ability to produce ATP theoretically (and in this case, experimentally) means a greater exercise capacity.

This study also took a group of young, healthy men and put them through moderate-intensity exercise in the morning (8 a.m.) and afternoon (6 p.m.) to see how the metabolic response to exercise differed according to time of day.

Interestingly, the men used less oxygen, had a lower heart rate, and a lower perceived exertion during exercise in the afternoon compared to the morning.

Metabolic parameters during morning and afternoon exercise. Ezagouri et al.

In essence, they became more “efficient” when they exercised in the afternoon. This increased efficiency was accompanied by a greater utilization of carbohydrates during exercise in the afternoon, consistent with the fact that carbohydrates require less oxygen per gram to produce the same amount of ATP as fat.

What about the effects of exercise on metabolic regulation and control? How does this (or does this) depend on the time of day at which exercise is performed? Might working out at a certain time of day boost exercise’s benefits even more?

This question was probed by another study (in mice) that compared the effects of exercise at different times of day on factors in skeletal muscle related to metabolism.

Mice exercised for 1 hour during their early active phase or their early rest phase. The early rest phase, in this study, might be comparable to the “late active” phase utilized in the previous study — representing the “afternoon/evening” time period for humans.

Overall, skeletal muscle energy metabolism was profoundly different during and after exercise, and this was highly dependent on the time of day.

There were two primary signal pathways affected by early active phase exercise. One of these — PDGF — is involved in the growth of new blood vessels(angiogenesis). The other pathway involves glycolysis — the process that we use to breakdown glucose and produce energy in the form of ATP. Early active phase exercise resulted in a significant upregulation of these pathways.

Active phase exercise also exerted a profound effect on blood glucose. In fact, muscle and blood glucose levels were reduced ONLY after exercise in the early active phase. This was probably due to another important signaling molecule known as hypoxia-inducible factor-alpha (HIF); which was significantly higher after active phase vs. rest phase exercise.

Study graphical summary. Sato et al.

One final interesting observation was the impact of time-of-day on systemic energy utilization. After active phase exercise, the mice were utilizing more fat. This was proposed to occur as a result of the mice depleting their glucose stores during exercise, and thus relying more on energy from other pathways (fat and protein breakdown as well as the use of ketones).

Thus, exercising at the “right time” might be more beneficial in terms of enhancing metabolic energy utilization and training the body to “switch” between fuel sources in the post-exercise window.

What do these two studies tell us, if anything, about WHEN we should exercise.

Well, here are my interpretations.

If you want to optimize performance output — maximize power, strength, speed, endurance, etc. — then performing your training in the afternoon is likely the way to get there. More studies than these two show that power output and other performance measures are highest in the afternoon.

In addition to what the molecular data say, most people might find performance to peak in the afternoon due to other extrinsic factors like nutrition, feeling more “awake”, and having more time to loosen up during the day. Maybe we’re just more “motivated” in the afternoon.

On the other hand, we must also consider the logistics of training and performance, recognizing that we can’t always optimize our training how we want to.

Some people only have the morning hours to get in their training, and find that morning workouts just work better (I’m including myself here). The body can adapt to performing at any time of day. I’m by no means comfortable saying that afternoon exercise is a must if you want to maximize your performance.

But, looking at the data — a lower perceived exertion, more efficiency, and greater training output in the p.m. might allow you to do more and adapt faster.

Conversely, for metabolic benefits, exercise early in the morning might take the cake. Given the data above, a.m. exercise might be one way to stress metabolism in such a way as to benefit overall health. Depleting glucose, utilizing fatty acids, and upregulating genes related to metabolism were all observed during exercise in the early active phase of mice (corresponding to morning exercise in humans).

I think the application of these findings can tie in to the discussion on fasted vs. fed exercise. When we exercise early in the morning, we’re more likely to be fasted (like the mice in this study) or at least have lower substrate availability than we might in the afternoon after having a few meals throughout the day. For this reason, we’ll have less glucose/glycogen available, and tend to make use of other fuel sources as a result.

While performance might take a small hit in the morning, the metabolic benefits might be enhanced.

For people with metabolic diseases like diabetes, obesity, or insulin resistance, optimizing exercise timing could drastically improve metabolic health.

Strategies to get the most out of exercise for sick (and healthy) individuals, in addition to the usual frequency, intensity, and duration prescription, might now have to include the component of timing.

And why not? While it might seem trivial (exercise is exercise, right?), the emerging data are pretty convincing — the time we perform exercise matters!

How much does it matter? The answer to this question isn’t quite as clear. The benefits one achieves by switching their training from morning to afternoon, or vice-versa, might be statistically insignificant, but still “clinically meaningful”, at least at an individual level.

When it comes down to it though, structuring exercise at the correct time is much less important than actually starting to exercise in the first place. The initial barrier for most people is just exercising at any time, much less crafting the ideal time to break a sweat. But once a solid routine is established (or if it already is), small tweaks in the routine might be able to generate minor but meaningful improvements in health and performance.

After all, if something can get closer to perfect, then why not try?

References

Ezagouri S, Zwighaft Z, Sobel J, et al. Physiological and Molecular Dissection of Daily Variance in Exercise Capacity. Cell Metab. 2019;30(1):78–91.e4.

Sato S, Basse AL, Schönke M, et al. Time of Exercise Specifies the Impact on Muscle Metabolic Pathways and Systemic Energy Homeostasis. Cell Metab. 2019;30(1):92–110.e4.

Chaix A, Panda S. Timing tweaks exercise. Nat Rev Endocrinol. 2019;15(8):440–441.

PhD candidate at the University of Florida — Science writing with a particular focus on exercise and nutrition interventions, aging, health, and disease.

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