In Part 1, we briefly looked at how the circadian system times our daily patterns of behaviour and physiology, as well as how the circadian system 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 will delve deeper into this subject, exploring the many ways that when we eat influences our metabolic health.
- Research has found that if other animals eat at times when they would typically be asleep (night-time for us), they tend to get fatter and experience other metabolic disorders. But when they can only eat in a shortened eating window of 12 or less hours each day they are leaner and healthier.
- In humans, it is unclear if eating within a shortened window benefits metabolic health, and very short eating windows might actually be bad for things like blood sugar control . Breakfast-skipping is one way to shorten the eating window, and skipping breakfast does not appear to substantially influence people’s weight loss efforts.
- The timing of the eating window may be important. It may be metabolically advantageous to eat around the same time that you are physically active, as well as consuming more of your daily food intake earlier in your waking day.
Rodents suffer from bad health effects 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 physiology and our behaviour (like when we do or don’t feel like eating). Strong rhythms are characteristic of a healthy circadian system.
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.
The prolonged feeding period (more time each day in which food is being consumed and therefore less time fasting) that results from high-fat, high sugar diets instigates rapid changes in daily gene expression and produces multiple unfavorable metabolic consequences, including fat gain, insulin resistance, and impaired lipid regulation that contributes to 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, we refer to this as a shortened eating window, and will do so for the rest of this series. Animals with a shortened eating window have lower body fat, lower cholesterol levels, and higher insulin sensitivity (2).
Animals that eat in a 12 hr (or less) window have ↓ body fat, ↓ cholesterol, ↑ insulin sensitivity
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But what about us humans?
In contrast to rodents, it is less clear whether a shortened eating window benefits metabolic health in humans. Among healthy adults, confining daily food intake to a single evening meal has been shown to impair glucose metabolism, and increase blood pressure, cholesterol, and hunger in comparison to consumption of the same diet split into three daily meals (3, 4).
Okay, so this implies that drastically shortening the eating window to just one meal each day may not be the best thing, but some restriction could still be useful. Let’s continue to explore this.
Some would then say that such controlled conditions might not represent how most people actually live, and that people practising a shortened eating window might eat less when left to their own devices. And they seem to be right, as some studies have shown that skipping breakfast (which shortens people’s eating windows) does indeed reduce the number of calories people consume each day.
But this is offset by reductions 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 glucose metabolism, if anything (5, 6). And perhaps the largest well controlled trial exploring the effects of breakfast-skipping on weight loss in obese adults found that, alas, people did not lose weight when skipping breakfast (8).
So, while no single study is definitive, the case for breakfast- skipping is contentious. More on this in a podcast from Jeff Rothschild, Dan Pardi, and me soon on humanOS Radio.
Perhaps you noticed that in the aforementioned shortened eating window and breakfast-skipping studies, that people began eating later in the day…
… But could the timing of the eating period affect our health? If, for example, the eating window was 10 hours regardless, would it matter if it started 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 had 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, reduces energy expenditure and fat oxidation, and alters daily gene expression profiles (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 (i.e. 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.
But is this another case of mice and men differing in responses?
Perhaps. But perhaps 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 glucose 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 observational studies (13). The finding that diet-induced thermogenesis (the increased 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 role 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.
Diet-induced thermogenesis, or ↑ metabolic rate after eating, drinking = higher earlier in day
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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, shortened eating window 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 information about that). This is particularly relevant for alarm clock users and night shift workers.
If you want to take a deeper look into what we’ve discussed here, I recommend reading a recent review to better understand the careful experiments that have documented the many detrimental metabolic health effects that result from disruption to the circadian system and sleep (see 18).
Related to this, 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 (soon to be Doctor) Dan Pardi.
Last, intermittent fasting (not a shortened eating window) has some particularly vocal proponents, and for good reason: Fasting is a promising metabolic therapy for many disease states and may be an effective prophylactic when used wisely (19).
In the next post in this series, we will consider the impact of eating at consistent times on a day-to-day basis, and how certain dietary components can alter circadian rhythms (for better and for worse).
More to come!
- 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.
- Garaulet M, Gomez-Abellan P, Alburquerque-Bejar JJ, Lee YC, Ordovas JM, Scheer FA. Timing of food intake predicts weight loss effectiveness. Int J Obes (Lond). 2013;37(4):604-11.
- Morris CJ, Garcia JI, Myers S, Yang JN, Trienekens N, Scheer FA. The Human Circadian System Has a Dominating Role in Causing the Morning/Evening Difference in Diet-Induced Thermogenesis. Obesity (Silver Spring). 2015;23(10):2053-8.
- Sadeghirad B, Motaghipisheh S, Kolahdooz F, Zahedi MJ, Haghdoost AA. Islamic fasting and weight loss: a systematic review and meta-analysis. Public Health Nutr. 2014;17(2):396-406.
- Garaulet M, Gomez-Abellan P, Rubio-Sastre P, Madrid JA, Saxena R, Scheer FA. Common type 2 diabetes risk variant in MTNR1B worsens the deleterious effect of melatonin on glucose tolerance in humans. Metabolism. 2015;64(12):1650-7.
- Eckel RH, Depner CM, Perreault L, Markwald RR, Smith MR, McHill AW, et al. Morning Circadian Misalignment during Short Sleep Duration Impacts Insulin Sensitivity. Curr Biol. 2015;25(22):3004-10.
- Potter GD, Skene DJ, Arendt J, Cade JE, Grant PJ, Hardie LJ. Circadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences, and Countermeasures. Endocr Rev. 2016;37(6):584-608.
- Longo VD, Mattson MP. Fasting: molecular mechanisms and clinical applications. Cell Metab. 2014;19(2):181-92.
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