In Part 1, we briefly looked at how our circadian systems time our daily patterns of behavior and biology, as well as how the this clockwork is synchronized with the 24 hour day. In doing so, we discussed how the foods we eat, and the types and amounts of nutrients available, are key to synchronizing the clocks in many of our bodies’ tissues. Today, we’ll delve deeper into this subject, exploring the many ways that when we eat influences our metabolic health. We’ll focus in particular on studies of breakfast-skipping.
Rodents suffer adverse health consequences when they eat at the “wrong” times
As we saw in Part 1, fasting/eating patterns produce changing levels of factors that circulate through the body, which can then modify the activity of the molecular clockwork that times the metabolic reactions in our cells. In this way, abrupt fasting/eating cycles facilitate robust rhythms in both our biology and our behavior. These strong rhythms are characteristic of a healthy circadian system, and we see this clearly in rodents.
When mice are fed high-fat high-sugar diets to their hearts’ content, these animals consume a greater proportion of their food during times when they would normally be inactive and fasting. This prolonged feeding period (more time each day in which food is being consumed) instigates rapid changes in daily gene expression and produces multiple adverse metabolic consequences, including fat gain, insulin resistance, and impaired lipid regulation, increasing fat deposition in the liver (1).
Promisingly, however, in all of these instances, “time-restricted feeding” (typically restricting food access to a period of 12 hours or less each day) confers all sorts of benefits to metabolism in mice. (In the soon-to-be-released course on fasting on humanOS, Dan and Jeff Rothschild refer to this as a shortened eating window. In these blogs I’ll refer to time-restricted feeding when discussing other animals and “time-restricted eating” in reference to studies of humans.) Restricting the feeding period in mice often leads to lower body fat and lower cholesterol levels, as well as higher insulin sensitivity (2).
But what about humans?
Time-Restricted Eating and Breakfast-Skipping: Studies of Humans
In contrast to rodents, it is less clear whether time-restricted eating benefits metabolic health in humans. Among healthy adults, confining daily food intake to a single evening meal has been shown to impair blood sugar regulation and increase blood pressure, cholesterol, and hunger in comparison to consumption of the same diet split into three meals each day (3, 4). This implies that drastically shortening the eating period to just one meal each day may not be the best thing, but might less severe time restriction still be useful?
Such controlled conditions may not be feasible for most of us, and people using time-restricted eating may eat less when left to their own devices: Some studies have shown that skipping breakfast (a form of time-restricted eating) reduces the number of calories people consume each day. However, this is offset by declines in physical activity, and careful studies have found that the primary effect of breakfast-skipping (in people that are not living in a lab setting) may be impaired blood sugar regulation, if anything (5 6). Perhaps the largest well-controlled trial exploring the effects of breakfast-skipping on weight loss in obese adults found that people did not lose additional weight when skipping breakfast (8).
Timing Nuances: Studies of Rodents
Perhaps you noticed that in the aforementioned studies people began eating later in the day. Well, could the timing of the eating period affect health? If, for example, the eating period is 10 hours, would it matter if it starts at 06:00 or 12:00?
In mice, when researchers restrict access to fructose to the period when mice are typically asleep, the rodents develop insulin resistance and gain fat in comparison to mice that have access to the fructose only during the period when they are active and normally eat (8). Similarly, restricting access to a high-fat, high-sugar diet to the time when mice usually sleep tends to lead to greater body fat. Doing so also flattens daily hormone rhythms and reduces energy expenditure and fat oxidation (9).
Diet timing within the active period may also matter, as mice fed a high-fat, high-sugar “meal” at the end of their day (active phase) gain more fat and are more insulin resistant than mice fed this same type of meal earlier in their day (10). This may be related to misalignment between energy intake and expenditure. Researchers can change the genetics of mice such that their clocks run more quickly, meaning that the mice they have internal days significantly shorter than 24 hours. When such mice feed at will, they consume many of their calories well before their physical activity peaks and promptly become obese. But if the mice are only given food near the time of peak physical activity, they do not become obese (11). The implication for us is that eating in close proximity to physical activity may have beneficial metabolic effects.
Timing Nuances: Studies of Humans
But is this another case of mice and men differing in responses?
Maybe… but maybe not.
In a controlled trial, overweight and obese women who consumed a larger proportion of their daily intake earlier in the day had greater improvements in blood sugar and lipids and lost more weight than those consuming more later in the day (12). Furthermore, eating lunch earlier has been associated with greater weight loss in cross-sectional studies (13). The finding that diet-induced thermogenesis (the increase in metabolic rate that follows eating and drinking) is higher earlier in the day (14) may help explain these findings. Other studies designed to unmask the roles of the circadian system in metabolic regulation have shown that many metabolic processes (such as glucose metabolism) are optimized relatively early in the day. And findings from the previously discussed Bath Breakfast Project studies also imply that eating earlier in the day may stimulate more daily physical activity, although this needs further testing.
Collectively, these findings support a possible benefit to assigning more of your daily energy intake to the first half of your waking day, although there may be caveats. First, although confounded by myriad factors, not the least of which is an emphasis on abstinence from overeating, Ramadan studies often show that people lose weight when they can only eat during darkness (15). Second, time-restricted eating studies have often lacked objective measures of body composition. Third, as melatonin is synthesized during darkness and may acutely impair insulin signalling (16), it may be wise to avoid eating so late or so early that it is your body’s biological night (17) ( see this blog for more on this). This is particularly relevant for alarm-clock users and night shift workers.
We tend to make poorer decisions when our circadian systems are misaligned and our sleep has been disrupted. Many people are improving our understanding of how this influences our dietary decisions, including Dan.
Finally, intermittent fasting (not necessarily synonymous with time-restricted eating) is a promising metabolic therapy for many disease states and may be an effective prophylactic when used wisely (18).
In the next post in this series, we will consider the impact of eating at consistent times on a day-to-day basis, as well as how certain dietary components can alter circadian rhythms (for better and for worse).
More to come!
- If other animals feed at times when they would typically be asleep, they are predisposed to obesity and other metabolic disorders. Time-restricted feeding helps offset these effects.
- In humans, it is unclear if time-restricted eating benefits metabolic health, and very short eating periods might actually be bad for things like blood sugar control . Skipping breakfast does not appear to substantially influence people’s weight loss efforts.
- The timing of the eating period may be important. It may be advantageous to eat around the same time that you are physically active, and you may benefit from consuming more of your daily food intake earlier in your waking day.
- Eckel-Mahan KL, Patel VR, de Mateo S, Orozco-Solis R, Ceglia NJ, Sahar S, et al. Reprogramming of the circadian clock by nutritional challenge. Cell. 2013;155(7):1464-78.
- Chaix A, Zarrinpar A, Miu P, Panda S. Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges. Cell Metab. 2014;20(6):991-1005.
- Carlson O, Martin B, Stote KS, Golden E, Maudsley S, Najjar SS, et al. Impact of reduced meal frequency without caloric restriction on glucose regulation in healthy, normal-weight middle-aged men and women. Metabolism. 2007;56(12):1729-34.
- Stote KS, Baer DJ, Spears K, Paul DR, Harris GK, Rumpler WV, et al. A controlled trial of reduced meal frequency without caloric restriction in healthy, normal-weight, middle-aged adults. Am J Clin Nutr. 2007;85(4):981-8.
- Betts JA, Richardson JD, Chowdhury EA, Holman GD, Tsintzas K, Thompson D. The causal role of breakfast in energy balance and health: a randomized controlled trial in lean adults. Am J Clin Nutr. 2014;100(2):539-47.
- Chowdhury EA, Richardson JD, Holman GD, Tsintzas K, Thompson D, Betts JA. The causal role of breakfast in energy balance and health: a randomized controlled trial in obese adults. Am J Clin Nutr. 2016;103(3):747-56.
- Dhurandhar EJ, Dawson J, Alcorn A, Larsen LH, Thomas EA, Cardel M, et al. The effectiveness of breakfast recommendations on weight loss: a randomized controlled trial. Am J Clin Nutr. 2014;100(2):507-13.
- Morris M, Araujo IC, Pohlman RL, Marques MC, Rodwan NS, Farah VM. Timing of fructose intake: an important regulator of adiposity. Clin Exp Pharmacol Physiol. 2012;39(1):57-62.
- Bray MS, Ratcliffe WF, Grenett MH, Brewer RA, Gamble KL, Young ME. Quantitative analysis of light-phase restricted feeding reveals metabolic dyssynchrony in mice. Int J Obes (Lond). 2013;37(6):843-52.
- Bray MS, Tsai JY, Villegas-Montoya C, Boland BB, Blasier Z, Egbejimi O, et al. Time-of-day-dependent dietary fat consumption influences multiple cardiometabolic syndrome parameters in mice. Int J Obes (Lond). 2010;34(11):1589-98.
- Liu Z, Huang M, Wu X, Shi G, Xing L, Dong Z, et al. PER1 phosphorylation specifies feeding rhythm in mice. Cell Rep. 2014;7(5):1509-20.
- Jakubowicz D, Barnea M, Wainstein J, Froy O. High caloric intake at breakfast vs. dinner differentially influences weight loss of overweight and obese women. Obesity (Silver Spring). 2013;21(12):2504-12.