By Mario Kratz, PhD
Published May 2, 2022
On April 21, the results of a major new clinical trial looking at the effects of time-restricted eating on weight loss were published in the prominent New England Journal of Medicine. This publication triggered a lot of discussion on social media as well as in traditional media. The New York Times, for example, published an article with the following headline:
In this blog post, we will take a thorough look at this clinical study, and others that have looked into the same question, to find out whether time-restricted eating really has no benefits for weight loss.
What Is Time-Restricted Eating?
Time-restricted eating, or TRE, has been a very popular form of intermittent fasting for the last 8 to 10 years. In TRE, all food intake is concentrated inside of a window of usually 6-10 hours each day. Outside of that window, calorie intake is discouraged.
A popular version is 8/16-TRE where all meals are eaten within an 8-hour window and then the remaining 16 hours of the day are a fasting period. In 8/16 TRE, one could eat between, say, 8 AM and 4 PM every day, and then fast from 4 PM until 8 AM the next day. Or, as another example, one could eat only between 12 Noon and 8 PM every day, and then fast between 8 PM and 12 Noon the next day.
Many other forms of TRE have been proposed, ranging from an extreme 1/23 (sometimes also called OMAD or one-meal-a-day) to 12/12-TRE. In countries such as the United States where food intake tends to be spread out over a period of 14-16 hours each day for most people, any eating period of 12 hours or less could be considered time-restricted.
The eating period can be chosen freely during the daytime, with a general recommendation that eating should not start in the first hour after waking and no-calorie intake should occur in the last two to three hours before bedtime. In general, we speak of early-TRE whenever usual first calorie intake occurs before Noon, or late-TRE if calorie intake is restricted to the afternoon hours.
You may have tried TRE, maybe because you heard that it can help you lose some weight. What is that idea even based on?
I think it’s fair to say that, particularly on the internet, but also in many published diet and nutrition books, there is a lot of content that makes it seem that TRE is the end all be all of achieving and maintaining a healthy body weight. And that may be based partly on some of the first studies done on TRE. So let’s go back to the birth of the concept of TRE as it relates to the regulation of body weight.
First Mouse Studies Showing that Time-Restricted Eating Prevents Weight Gain
The first major study that linked TRE to body weight regulation was conducted in mice, about 10 years ago. Investigators noticed that if they gave mice a high-fat diet instead of their usual boring chow diet, they would gain a lot of weight and become obese.
Well, that wasn’t the interesting part; that mice become obese on specific high-fat diets was already well known. What was interesting is that the investigators noticed that mice love this high-fat diet so much that they would even wake up frequently during their normal sleeping time to feed. Basically eating 24 hours a day if they had access to it.
So they tried a very simple experiment: they gave the mice the same high-fat diet, but limited access to it to 8 hours per day. What they observed was pretty stunning. The mice quickly learned that the yummy stuff would be taken away from them after a while, and so they started eating a lot more during the 8 hours during which they had access to the food, eventually eating almost as many calories as when they had access to it for 24 hours. But: they didn’t gain nearly as much weight.
What this study suggested is that limiting food intake to 8 hours and then fasting for the remaining 16 hours every day had some kind of almost magical protective effect against weight gain, even when the mice were overeating fatty food.
Of note, the paper suggested not that TRE prevents weight gain because mice eat less, but because they burn more calories.
The idea that TRE protects against weight gain caught fire quickly, probably because it’s so appealing to be able to eat as much as you want, maybe even regularly overheat, and still not gain any weight.
Chinese Time-Restricted Eating Trial Published in the New England Journal of Medicine
So the natural question is: has this idea been tested in people? Yes, several randomized controlled trials have investigated this question, and the largest of these studies was just published last week.
This new paper that was published on April 21, 2022, by a Chinese group of researchers in the New England Journal of Medicine actually asked the question of whether adding TRE to a calorically restricted diet has additional weight loss benefits.
The researchers recruited 139 patients with obesity and randomized them either to restrict their calorie intake, or the same calorie restriction in addition to 8/16 TRE where all calories had to be consumed over just 8 hours. Both groups were told to reduce their daily calorie intake to about 75% of their usual intake. The TRE group was also asked to eat only between 8 AM and 4 PM, and to fast between 4 PM and 8 AM the next day.
Participants were asked to follow their assigned intervention for 12 months. The pre-defined primary endpoint was the difference between the two intervention groups in how much body weight they lost.
So, what happened?
As one would expect, participants in both groups lost weight. Those who were asked to restrict their calorie intake only in the control group lost an average of 6.3 kg or 13.9 pounds over these 12 months. That average weight loss is shown as a green square in this graph below.
Now, the question was, did the addition of TRE to the calorie restriction cause participants in the intervention group to lose more weight?
Participants in the calorie restriction + 8h-TRE group lost an average of 8.0 kg, or 17.6 pounds over these 12 months, shown in the orange square. That may seem like yes, TRE plus calorie restriction did cause greater weight loss than calorie restriction alone.
However, according to the paper, the average difference between these two groups of 1.8 kg, or 4 pounds, was not statistically significant.
And so the paper concluded that “Among patients with obesity, a regimen of time-restricted eating was not more beneficial with regard to reduction in body weight […] than daily calorie restriction”. And that is exactly why the New York Times titled that TRE has no benefits.
How can that be? 8 kg is quite a bit more than 6.3 kg, right?
One important thing to understand is that responses to any weight loss intervention are highly variable. Probably obviously, not all participants in the TRE group lost exactly 8 kg, and not all in the control group lost 6.3 kg. If that had been the case, this difference for sure would have been highly statistically significant.
Instead, the degree to which individual participants lost weight varied a lot, in both groups. In the TRE group, for example, several participants lost more than 20% of their baseline body weight, while eight or nine participants gained a modest amount of weight. Quite an amazing spread considering they all were exposed to the same dietary intervention.
That is simply because some people are super motivated when they volunteer, and they lose a ton of weight no matter what the intervention is. Others may lose interest in the study mid-way through, or maybe they go through some life crisis, or for whatever reason, they don’t lose much weight or even gain weight.
So, in other words, it is clear that how much weight people will lose in a 12-month intervention like this is only partly affected by the actual intervention, and partly by things that have nothing to do with the study.
It is certainly also possible that the degree to which people lose weight in response to a weight-loss intervention such as TRE differs from person to person. These could be biological reasons, such as a person’s chronotype, or it could be their baseline diet and eating window, snacking habits, or any of a large number of other factors.
That is exactly why we usually enroll many participants into this type of trial, and randomize them to the intervention groups. We hope that because of this randomization, those types of other random factors that may affect weight loss will average out between the two groups. And if the study is large enough, it usually does.
Still, the large variation in weight loss within each group reduces our confidence that the observed average weight loss is a reflection of the ‘real’ effect of each intervention. That’s why we need to somehow consider these differences in weight loss within an intervention group when we interpret the results. And scientists do this by considering something called the 95% confidence interval. That may sound complicated, but it’s actually a pretty simple concept.
You see, because the individual participants in the TRE group lost so dramatically different amounts of weight, we cannot be 100% confident that if we ran the study one more time, we would again get an average weight loss of exactly 8 kg in that group. But the data tell us that we could be 95% confident that the average weight loss would be on the 95% confidence interval line, or, in numbers, between a weight loss of 6.4 kg and 9.6 kg in the TRE group.
This range was calculated from the differences in weight loss within that TRE group, and the assumption underlying that range is that if we ran the study again, the relative numbers of people who lose a lot vs. little weight may shift slightly, leading to a different average weight loss number.
And similarly, there was a lot of variation in weight loss in the control group. The 95% confidence interval in that group covers the range from -7.8 to -4.7 kg.
So, really, the problem is that there is some uncertainty about the ‘real’ weight loss in both groups, and therefore also about the ‘real’ difference between them, because there is quite a bit of overlap in the 95% confidence intervals. We therefore just don’t have enough confidence that this difference of 1.8 kg seen here in this study reflects an actual difference between these interventions and isn’t just the result of random variation.
Another way to look at this is by considering the differences in weight loss between the two groups. The average difference between the TRE intervention and the control group came out to 1.8 kg here. Just like we couldn’t have 100% confidence in the weight loss numbers in each of the intervention groups, we also cannot be 100% confident that the difference between these groups would always be 1.8 kg if we re-ran the study. But we can have 95% confidence that the difference would be in the range from -4.0 to +0.4 kg. That is a wide range, because of the large differences in weight loss within each group. And as you can see, that range includes zero and even the possibility of slightly greater weight loss in the control group.
If the 95% confidence interval did not include zero, that would mean that we could have 95% confidence that TRE adds at least a little bit of extra weight loss to a calorie-restricted diet, and the difference would be statistically significant.
Was the Sample Size of the Study Insufficient?
I have seen many people argue on social media that the investigators should have simply enrolled a few more people into this study. That very same difference of 1.8 kg between the two groups could have been statistically significant if more people had been enrolled. That point is true, because the 95% confidence intervals tend to get more narrow as we enroll more participants into the study. And if the 95% confidence intervals are more narrow, there will be less overlap between the TRE group and the control group, increasing our confidence that what we are seeing is a real difference and not the result of random variation. So, yes, enrolling more participants would have increased our statistical power, but that’s not something one can decide after a randomized controlled trial has been completed, with good reason.
Instead, it is best practice to spend some time before you even start your trial thinking long and hard about what kind of difference in your outcome you would consider clinically important. In this particular study, the investigators decided they wanted to be able to detect a difference in weight loss of 2.5 kg between the groups over 12 months. That’s 5.5 pounds. The way investigators do this is by using statistics to determine how many people would be needed in each group to be able to detect a difference between the groups of 2.5 kg, while considering the expected differences in weight loss within each group.
This was appropriately done here. But I think this is important to understand: the study was designed to detect a difference of 2.5 kg or more between the two intervention groups. That’s why the 1.8 kg greater average weight loss in the TRE group was not statistically significant.
That leaves us in a bit of a pickle, because how do we interpret this: does this mean that there is no benefit for sure?
No, in my interpretation, it only means that the difference in weight change between these two interventions was not substantial enough to be detectable in this study because the study was designed to detect differences greater than 2.5 kg. It is still possible that TRE added to calorie restriction could still have a meaningful impact on weight loss, but quite likely less than 2.5 kg over 12 months.
Now, to clarify this, because it could be confusing to some: it is not really clear that the ‘real’ effect of 8h-TRE when added to calorie restriction could not be larger than 2.5 kg. See the 95% confidence interval for the difference, which ranges from +0.4 kg (i.e. 0.4 kg greater weight loss in the control group) to -4.0 kg (i.e., 4.0 kg greater weight loss in the TRE group). Thus, the study leaves the possibility open that the real difference could be as large as 4.0 kg, or 8.8 lbs. It’s just that the average difference in this study was only 1.8, and so this difference was statistically not significant. And this is then interpreted as ‘no effect’.
I would suggest that there are two reasons why we should be interpreting this ‘null’ result with more caution.
One is that, yes, the investigators picked a somewhat arbitrary threshold of 2.5 kg that they wanted to be able to detect in this study. Had they picked, say, 1.5 kg (which would have necessitated probably around two- to three-times as many participants in each group), the difference may have been statistically significant and people would be talking about this study – and TRE – very differently.
The second point is that even with this non-significant finding, the 95% confidence interval gives us 95% confidence that if we ran the study again, we may find a difference between TRE and control of as much as 4.0 kg, which I would consider quite substantial.
I think this is one of those examples where people place too much emphasis on the p-value. It makes a lot more sense to look at the actual data here, and interpret the findings in an unexcited and nuanced way. What the data really suggest is that it is indeed possible that 8h-TRE added to calorie restriction does absolutely nothing to weight loss. But it is more likely that TRE does contribute a small amount of additional weight loss. It is uncertain whether this is the case, and how much additional weight loss one may see on average, but that is the most accurate interpretation of these findings.
Impact of the Interventions on Energy Intake
Another reason why I am thinking that it is somewhat likely that TRE may have some small additional benefit when added to calorie restriction is that participants in the TRE group consistently were able to reduce their calorie intake quite a bit more, by around 100 kcal/day. That result to me suggests that the observed difference in weight loss of an additional 1.8 kg in the TRE group was probably not just the result of random variation, but the result of participants managing to maintain a lower calorie intake in the TRE arm of the study.
Change in Eating Window Too Small?
So, I’d say that looking thoroughly at the data, the New York Times headline “Scientists Find No Benefit to Time-Restricted Eating” is at least a bit premature. To me, the data on weight loss and calorie intake suggest that adding 8/16 TRE to an intervention of calorie reduction may slightly increase the amount of weight loss.
To me, even that is slightly surprising, for two reasons that I’d like to discuss next.
First, the change in the eating window in this study was quite small. Participants on average had an eating window of ten and a half hours at baseline. That appeared to increase slightly to just under 11 hours in the control group, and declined to around 8 hours in the TRE group. So, the difference here between the groups was about three hours. Certainly notable, but quite different from what I would expect in, say, the United States, where most published data suggest an eating window between 14 and 15 hours per day for most people. It stands to reason that in the US, a reduction from 14 to 8 hours would have a greater impact on weight loss than in these Chinese participants where the eating window was reduced from around 11 to 8 hours.
Adding Time-Restricted Eating to Calorie Restriction
The second point is that this study investigated specifically whether adding TRE to a weight loss intervention focused on calorie counting and calorie reduction would have additional benefits. I think the study adequately answered that question, but I would argue that this is not the most relevant question.
I have always felt that the premise of TRE was that simply reducing the window of time during which food intake was “allowed” would reduce snacking outside of this window, for example in front of the TV in the evening, and thereby automatically reduce calorie intake. And by prescribing a specific number of calories that were allowed per day, I would have thought that this potential benefit of TRE would not be able to materialize.
To summarize, what we learned here in this randomized controlled trial is that if someone is already restricting their calorie intake, then reducing the eating window from around 11 hours per day to around 8 hours per day either doesn’t lead to further weight loss, or – at best – to a small amount of additional weight loss.
Review of Other Notable Clinical Trials on Time-Restricted Eating and Weight Loss
How does this study compare with other studies that have looked at the effect of TRE on weight loss? I looked for randomized controlled trials with a follow-up duration of at least 8 weeks, because if we are looking at weight loss as an endpoint, shorter studies won’t tell us much.
One additional study has been published with a somewhat similar design, in which participants were asked to restrict their calorie intake either with or without TRE. In this case, it was 12h TRE, so not a particularly restricted eating window, but it was conducted in the United States, where the average eating window is between 14 and 15 hours per day for most people. So the reduction in the daily eating window may have been similar to the Chinese study. A big difference here was that weight loss was assessed only over 8 weeks.
Even though this study was a lot shorter, the results look quite similar, shown on the right side of the figure above, with the results from the Chinese RCT published last week shown on the left side. In this study, the difference between TRE and control was of similar magnitude, but almost statistically significant. The average difference in weight loss was 1.6 kg, and the 95% confidence interval only just grazed zero. If this 95% confidence interval did not include zero, then this would be considered “statistically significant” because then we could be 95% confident that TRE adds additional weight loss to an otherwise calorie-restricted diet.
Another four studies have directly compared the effect of TRE on weight loss against a control group that did not follow TRE. In all of these studies, participants did not follow a calorie-restricted diet, so TRE was the only intervention tested.
Two of these studies did not show an effect of TRE. The one on the far left in the figure below was a 6-month trial comparing 12h-TRE vs. a non-TRE control that ate in a window of at least 14 hours. Again, I suppose one could argue that eating in a 12-hour window isn’t really TRE. In the Chinese study we discussed earlier, for example, the control group had an eating window of 11 hours. That is an illustration of one challenge in this field, namely that it isn’t all that well defined what TRE is, and what an adequate eating window in a control group would be.
The other study that did not show an effect of TRE on weight loss was a 12-week trial comparing 8-hour TRE vs. a control group that was asked to eat over at least 11 hours. This study here showed basically no real weight loss in either group, and no difference between the two groups whatsoever.
The other two studies did show an effect of TRE on bodyweight though.
These diets were not by design calorie-restricted, but participants spontaneously reduced their calorie intake on the TRE diet and lost weight. One of these studies was a 12-week randomized controlled trial comparing 10h TRE to a control group eating over a 15h window. In that study, participants on TRE lost 2.1 kg more over 12 weeks than controls. That is equivalent to 4.6 pounds.
The other study was an 8-week randomized controlled trial in which investigators compared two TRE groups against a control group eating in a 13 and a half-hour window. The TRE groups were asked to limit their food intake to either 4h per day or 6h per day. In both of these TRE groups, participants lost 3.3% more than controls over 8 weeks. (My apologies that I am showing these data here partly as kg and partly as percent; that’s the way the data are shown in the papers.)
Of note, it does seem that studies that restricted the eating window more saw greater weight change. At the same time, the two studies that demonstrated an effect of TRE on weight loss were relatively short-term studies, at 8 weeks and 12 weeks. That is why the 12-month RCT published by the Chinese investigators received so much attention, and with good reason.
Overall Conclusion
So, which conclusions are we drawing from all of these studies on the impact of TRE on body weight:
First, one thing is now absolutely clear: the early finding from mouse experiments that TRE somehow makes calories irrelevant and mice magically resistant to obesity does not apply to people. In humans, TRE is no miracle intervention on its own when it comes to normalizing body weight.
Second, there are really two ways to interpret the modest weight loss, or trend towards slightly greater weight loss, seen with TRE in some studies. One, we could look at the averages and conclude that TRE has no or – at best – a very modest effect on weight loss. That’s the interpretation I see the most, and it isn’t wrong. On average, people should expect a few pounds of weight loss at best in time frames of up to one year.
However, I think another interpretation fits the data better. We discussed earlier that the degree of weight loss differed tremendously in the Chinese trial, particularly in the TRE group. And this is something that was seen in all of the published TRE-weight loss studies. Now, it is possible that this variation in weight loss is largely related to other factors, such as how motivated people are to lose weight, but it is certainly also possible that it is partly explained by real differences in how much weight people lose when they follow TRE. That makes me wonder whether TRE may be a valuable tool with a potentially major effect on body weight for some people, while it does very little to nothing for others.
My best guess would be that those people who benefit the most are those who have a long eating window of 14, 15, or more hours every day, and who have a habit of eating a lot of junk food or drinking a lot of alcohol in the evening hours. I would guess that if these folks can succeed in making, say, 8-10h-TRE work as a regular part of their lifestyle at least 5 or 6 days of the week it may make a real difference in their weight all by itself.
For those who are already eating within a 10, 11, or 12- hour window, though, I think the benefits of further restricting their eating window may very well be minimal. Unless those folks were able to reduce their eating window very dramatically to less than 6 hours or so, which most people would not be willing to do for an extended period of time.
I cannot give any personal recommendations here, but if you are someone who is really motivated to lose weight, and you wanted to give TRE a try, I don’t see any reason in the literature why you shouldn’t (after discussing it with your doctor). It may well help a little bit, or maybe you are one of the people who benefit a lot. However, you should have the right expectations and not blame yourself if you don’t lose weight. There’s nothing wrong with you, and you are in good company, as all of these studies show in which a lot of participants lost no or only very small amounts of weight on TRE interventions.
Let me just add that in this blog post, we only discussed the effects of TRE on weight loss. TRE has also been suggested to improve health independent of any effect on body weight. That though is a topic for a separate article.
I’d like to finish with that New York Times headline that “Scientists Find No Benefit to Time-Restricted Feeding”. Allow me to fix that title a little bit to bring it more in line with what the new study really showed:
What the newspaper headline was clearly missing was what we call qualifiers. Rather than stating that time-restricted eating has no benefit, it is important to clarify that it has no major benefit, because a smaller weight loss benefit is still possible, I would say even likely particularly if we were to reduce the eating window more substantially. It is also critical to emphasize that the Chinese study found no benefit with regard to body weight, and not other endpoints, and that the results cannot be generalized beyond this particular population that was studied here. Looking at the other published studies, it seems possible to me that a similar study of 8h-early TRF in the United States, for example, may well show a larger additional weight loss benefit because the eating window would be more substantially reduced, and also because the general diet of the US population may well include more ultra-processed foods, snacks, fast food, and alcoholic beverages.
I hope this article clarified your questions around the new paper, or where the field stands in terms of the impact of TRE on weight loss. If anything remains unclear, please feel free to leave a comment, and I will do my best to respond in a timely fashion.
Take care!
References
- Manoogian et al.; Time-restricted eating for the prevention and management of metabolic diseases. Endocrine Reviews 2022; 43: 405-36.
- Hatori et al.; Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metabolism 2012; 15: 848-60.
- Liu et al.; Calorie restriction with or without time-restricted eating in weight loss. The New England Journal of Medicine 2022; 386: 1495-504.
- Peeke et al.; Effect of time restricted eating on body weight and fasting glucose in participants with obesity: results of a randomized, controlled, virtual clinical trial. Nutr. Diab. 2021; 11:6.
- Phillips et al.; The effects of time-restricted eating versus standard dietary advice on weight, metabolic health and the consumption of processed food: a pragmatic randomized controlled trial in community-based adults. Nutrients 2021; 13: 1042.
- Lowe et al.; Effects of time-restricted eating on weight loss and other metabolic parameters in women and men with overweight and obesity: the TREAT randomized controlled clinical trial. JAMA Int. Med. 2020; 180: 1491-9.
- Chow et al.; Time-restricted eating effects on body composition and metabolic measures in humans who are overweight: a feasibility study. Obesity 2020; 28: 860-9.
- Cienfuegos et al.; Effects of 4- and 6-h time-restricted feeding on weight and cardiometabolic health: a randomized trial in adults with obesity. Cell Metab. 2020; 32: 366-78.
- Gill and Panda. A smartphone app reveals erratic diurnal eating patterns in humans that can be modulated for health benefits. Cell Metab. 2015; 22: 789-98.
One Response
From my experience 8 hours is too long and freedom to eat anything didn’t work for me. Studying TRF like that is, I feel, a study for the purpose of demonstrating failure. I aim for 4 hours starting at 1700 hrs and I blend it with LCHF and moderate exercise. But… I haven’t satisfactorily managed to maintain it yet. Extended fasting on the other hand, for me, really does work astoundingly. At the time of writing I’m about to complete day 7 of what I hope will be 14 days (which I’ve done before) and I’m I’m feeling alert and energetic. For me I either fast or eat till I’m full.