Time-restricted feeding – the secret for healthy aging?

This summer I discovered Dave Asprey’s Bulletproof podcast, a massive podcast with more than 500 records so far and self-proclaimed #1 health podcast. Asprey is the creator of the Bulletproof Coffee, this “high-performance drink” which first appeared in the media a couple of years ago. The Bulletproof Coffee consists of adding caprylic acid triglycerides and butter to your coffee during your morning routine – and drink this instead of your usual breakfast. Caprylic acid triglycerides are mostly found in coconut oil and sold on Asprey’s Bulletproof blog under the name Brain Octane Oil (because hey, it sounds much better – and this is also a good way to make some money). The aim? Suppress hunger, provide steady lasting energy, and give a much better mental clarity [1].

You might now wonder whether we should all replace our breakfast with this exotic mixture. Caprylic acid is a saturated fatty acid – a class of lipids we have discussed in a previous post – that is getting more and more attention. Why? Caprylic acid triglycerides belong to the medium-chain saturated triglycerides, lipids that might have a positive effect on satiety, food intake, adiposity and thermogenesis (heat production promoting weight loss).

Oh, you used again the term “might have” – probably because there is not enough scientific evidence yet to support this hypothesis and we need more larger, well-designed studies?

Yes, and the mechanisms underlying the possible positive effects of medium-chain triglycerides are also not totally clear. The Bulletproof Coffee has also not been tested in clinical studies yet, therefore it remains difficult to evaluate its potential benefits compared to a normal black coffee – and this despite the 300k posts on Instagram tagged with #bulletproofcoffee. One thing is certain – I am allergic to information such as “caprylic acid is a smart fat” that accompanies this Brain Octane Oil product.

A “smart” fat. Seriously.

Anyway, despite the sometimes doubtful information and recommendations given by Dave Asprey and his guests, this podcast had the advantage of giving me a lot of new ideas of lifestyle-related topics I would like to discuss in this blog.

Since the title of this post is “time-restricted feeding”, it looks like you haven’t planned to focus on this Bulletproof Coffee.

Satchin Panda, Professor in the Regulatory Biology Lab at the Salk Institute for Biological Studies in California, was one day invited by Dave Asprey to speak about the effect of circadian rhythm and time-restricted feeding on our health. The influence of circadian rhythm on our body is something I find simply fascinating. But time-restricted feeding? Is that another trendy name for intermittent fasting? I slowed down my pace – I was running and since I am legendary slow this means I just stopped running – to focus my attention on Panda’s words.

Fasting – the voluntary abstinence or reduction from some or all kinds of food, drink or both, for a specific period of time – is not something new. The fact that nutrition and the moment when food is consumed can prevent diseases and promote health is also not a new concept. Hippocrates, the father of Modern Medicine, already wrote more than 2000 years ago: “When more food than is proper has been taken, it occasions disease. We must consider, also, in which cases food is to be given once or twice a day, and in greater or smaller quantities, and at intervals.” Another example comes from Maimonides, a medieval philosopher and doctor, also known for his famous quote “Eat like a king in the morning, a prince at noon, and a peasant at dinner” [2].

That sounds very poetic, but why would people decide voluntarily to stop eating during a certain period of time, even if they feel hungry?

Multiple and diverse reasons can explain why more and more people are getting interested in fasting or caloric restriction approaches. If you ask Google or the scientific literature, you will for instance find the following examples [3]:

  • To lose weight, since fasting approaches can lead to lower amount of calories consumed and/or impact hormones involved in satiety and metabolism;
  • To live longer and prevent diseases, since caloric restriction/fasting can increase our healthspan (e., the period of time we stay healthy despite getting older);
  • To support a therapeutic treatment in case of severe diseases (typically cancer); and
  • To increase the efficacy of therapeutic treatments, since a lot of proteins that are drug targets or involved in absorption or elimination of drugs have a circadian rhythm and are impacted by food intake.

Researchers and clinicians are now slowly but surely realizing that modulation of nutrition and alternative feeding interventions may be much more efficient in preventing – or even curing – chronic metabolic diseases than giving medicine.

You have mentioned caloric restriction, fasting, and time-restricted feeding. Isn’t it basically the same?

Not exactly. Caloric restriction is defined as an overall reduction in energy intake well below the amount of calories that would be usually consumed in a “normal” situation, but without leading to malnutrition [4]. Intermittent fasting refers to any diet that alternates between periods of restricting calories and eating normally. A very popular example is the so-called 5:2 diet, where a normal caloric consumption is observed five days a week while less than 500-600 kcal are consumed on the remaining two days. Time-restricted feeding (also sometimes called time-restricted eating) belongs to the intermittent fasting approaches, where a fasting period occurs every day and lasts between 12h-16h followed by a 8-12h eating window. Periodic fasting is the last one commonly found in the literature, where periods of fasting last between 2 and 21 (or more) days and with at least one week between fasting cycles [5].

Among those, time-restricted feeding is considered the most promising when it comes to health and diseases, due to its close link with the circadian clock.

The circadian clock? What is that?

Those who had the chance to study Latin in their youth may remember that circa means “approximately” or “around” and dies means “day”. A lot of organisms – and almost every cell in our body – have an internal clock following a 24h period (approximatively). In order to be sure that this clock remains “calibrated” every day, we are equipped with a master clock called suprachiasmatic nucleus  located in the hypothalamus. The latter is  a small but very smart portion of the brain also involved in body temperature, sleep, hunger, thirst, and attachment behavior.

The suprachiasmatic nucleus? Why are all these words always so complicated? It sounds like and asthmatic nucleus.

Just to give you a nice opportunity to show off during your next dinner with friends (but please skip the asthmatic part). The suprachiasmatic nucleus is a network of neurons which also treats the external outputs such as light and darkness that influence our circadian rhythm [6]. Why is this circadian rhythm then so important for our health? Because a lot of biochemical processes in our organism follow a circadian rhythm, which can lead to pathological conditions if they are altered. In the important compounds that are subject to a fine-tuned diurnal regulation, we find for instance fats, glucose, cholesterol, and many hormones such as insulin, glucagon, melatonin and cortisol. This explains why shift workers, who typically suffer from significant circadian disruption, show increased risks for cardiovascular disease, metabolic disorders, immune disorders and cancer. Now you may start to understand why jet-lag is also not totally harmless to our body [6].

But what is then the link between circadian rhythms and time-restricted feeding?

A very simple one: our daily eating pattern can significantly affect the amplitude and phases of our circadian rhythm. Since the circadian rhythm is strongly involved in our health, this means that we could “hack” our health by adjusting our eating pattern, as if we would reprogram our circadian clock. Experiments carried out in laboratory rats and mice have already shown that indeed, time-restricted feeding seems very promising in age-related disorders such as diabetes, cardiovascular diseases, cancer, Alzheimer’s disease and Parkinson’s disease, where it could even counteract the disease progression.

Counteract the progression of so many diseases? How is this biologically possible?

Because all the fasting approaches result in several metabolic changes, leading for instance to better blood glucose levels, mobilization of fatty acids (with generation of ketones, a trendy topic that will be also covered in this blog), and modification of hormones involved in appetite and satiety. All these changes have a positive impact on a lot of diseases, especially the ones linked to “sugar and fat” (diabetes, atherosclerosis, stroke, etc.). It is actually quite impressive: multiple studies have shown that intermittent fasting and time-restricted feeding can prevent or even cure type 2 diabetes in animal models [7]. You might think that this anti-diabetic effect happens because mice and rats eat less when they have to fast, but this is not the case with time-restricted feeding since these animals typically consume the same amount of food if they get it for 8h/days versus during the whole day. The positive effects observed with fasting approaches are therefore truly linked to hormonal and other biochemical changes.

That sounds very interesting, but we don’t really feel concerned as we aren’t laboratory mice or rats.

Even though we still miss more research comparing all fasting approaches and measuring multiple outcomes, some nice studies investigating the effect of fasting in humans have been published over the last couple of years. A common issue in human dietary studies, compared to animal studies, is that it is very difficult to accurately trace what (and when!) people have eaten, since we tend to forget the piece of chocolate we have eaten just before going to bed, or lie on the bag of chips we had before dinner. Mice and rats don’t drink wine while they cook dinner, and don’t eat chips and chocolate.

That is why I really like an article published by Panda and his co-workers in Cell Metabolism, a very good journal, where they first developed a smartphone app to monitor food intake in healthy adults and then carried out a small pilot study to investigate the effect of time-restricted feeding on overweight people [8]. Why a smartphone app? Because volunteers could simply take a picture of what they were eating and drinking while still enjoying their life, which gave an objective information on what and when calories had been consumed. They also received regular push notifications to be sure they would not forget any item consumed throughout the day.

Interesting method indeed. Obviously, the authors found that we tend to eat three meals with one or two snacks within around 12 hours, don’t we?

Not at all. Among the 156 individuals included in the study (aged 21-56 years, male and female, healthy and with a body mass index between 19 and 36 – a diverse population, even though rather young), nearly 50% ate during more than 15h/day and only 20% ate three meals/day. Only 20%, despite the fact that most of the participants reported that they had eaten 3 meals/day. Also, 50% of this population consumed something (food or beverage) less than 2h before going to bed. Half of the population – that is quite a high proportion.

A nice way to represent all these numbers is by using a polar plot, which shows all the ingestion events (more than 5 kcal) of each individual depending on the time of the day, and this during the three weeks of the study:

Polar plot of the 156 individuals included in this study, showing all the ingestion events depending on the time of the day. Easy to see that our gastro-intestinal tract is used much more than what we would expect. Reprinted from [8] with permissions.
Our ancestors would probably have had a heart attack if they would have seen this graph. Our dear friend Maimonides as well, since the largest portion of our daily caloric intake appears to be consumed in the late afternoon and evening hours. We are very far from the “Eat as a peasant at dinner”.

So what about the effect of time-restricted feeding on overweight individuals?

Based on these results, the authors wanted to see if altering the daily eating duration would impact health benefits in overweight people. They selected 8 subjects with a BMI higher than 25 (considered “overweight”) who had a >14h eating duration during their study. During 16 weeks, these subjects ate their entire daily caloric intake within a self-selected 10-11h window. What happened? Participants lost up to 4% body weight in 16 weeks, and they kept this weight loss for up to one year. Not a huge loss indeed, but still significant. They also reported improved sleep quality at night. According to the authors, the benefits observed might be explained by a reduction in the daily caloric intake (less late-night snacks and alcohol) and the restoration of the diurnal rhythm of feeding/fasting.

Eight subjects only, younger than 56 years and not really diseased except overweight? This is far from a well-designed large-scale study.

Indeed, that is why the authors stressed out that it was a preliminary study. Preliminary, but still a nice illustration showing that we could indeed “hack” our circadian clock to positively impact our health, especially on the long-term perspective. Based on the amount of animal-based studies published in the last 2-3 years showing the multiple health benefits we have discussed here, I wouldn’t be surprised to read more about this topic in the mass media in the coming years, once confirmed with human studies.

What should we then do in the meantime, if we want to live longer and in the best shape ever?

If I would know the answer to this question, I would be rich and famous. I am neither rich nor famous, but my blood cholesterol and glucose levels are doing well, thank you. Maybe because I have been raised in a family where the three-meals-per-day was a rule rather than an exception. A routine that I am trying to keep – even if the mass consumerism we are currently facing makes it quite challenging.

What would therefore Dr. Iza advise? Well, maybe the most important: realize what you are eating during the day. Yes, also the piece of chocolate or the slice of cheese before dinner, and the Scotch before going to bed – this also enters in the category “eating and drinking”. The sugar in the tea as well. The fake creamer in the coffee as well (which mostly contains glucose syrup anyway). This orange juice in the morning as well. And if you are concerned by your health, your blood glucose level, your weight or the quality of your sleep, maybe think twice before eating this apple or those two cookies before going to bed.

Maybe consider simply skipping those – you aren’t hungry anyway, are you?

Dr. Iza

tl; dr

  • A new trend has been observed in the last couple of years linked to fasting approaches, which include intermittent and periodic fasting.
  • Time-restricted feeding is a subcategory of intermittent fasting and consists of a fasting period that occurs every day and lasts between 12h-16h followed by a 8-12h eating window.
  • Many studies, mostly conducted in animal models, have shown that time-restricted feeding could increase the healthy lifespan by positively impacting blood glucose and cholesterol levels, body weight and body fat, inflammation, composition of the microbiome, endurance, sleep and cardiac function.
  • Preliminary studies carried out in humans, mostly in overweight populations, also showed that dietary manipulations based on fasting approaches may lead to similar results – even though more large-scale and long-term studies are needed. It is also not totally clear now if the effect is dependent on the age, where the population younger than 65-70 years old would benefit the most.
  • Adopt time-restricted feeding as a lifestyle to see significant effects on our health? Too early to recommend this, but having in mind when we are eating seems to be as important than what we are eating.


  1. Bulletproof Coffee. https://www.bulletproof.com/pages/bulletproof-coffee (Accessed 27th December 2018)
  2. G. Asher, P. Sassone-Corsi, Time for food: the intimate interplay between nutrition, metabolism and the circadian clock. Cell 161 (2015) 84.
  3. J. Simpson, D.G. Le Couteur, D. Raubenheimer, S.M. Solon-Biet, G.J. Cooney, V.C. Cogger, L. Fontana, Dietary protein, aging and nutritional geometry. Ageing Res Rev 39 (2017) 78.
  4. W. Bales, W.E. Kraus, Caloric restriction: implications for human cardiometabolic health. J Cardiopulm Rehabil Prev 33 (2014) 201.
  5. D. Longo, S. Panda, Fasting, circadian rhythms, and time-restricted feeding in healthy lifespan. Cell Metab 23 (2016) 1048.
  6. N.C. Manoogian, S. Panda, Circadian rhythm, time-restricted feeding, and healthy aging. Aging Res Rev 39 (2017) 59.
  7. P. Mattson, V.D. Longo, M. Harvie, Impact of intermittent fasting on health and disease processes. Ageing Res Rev 39 (2017) 46.
  8. S. Gill, S. Panda, A smartphone app reveals erratic diurnal eating patterns in humans that can be modulated for health benefits. Cell Metab 22 (2015) 789.

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