A combined team of researchers from Nanfang Hospital, Southern Medical University, in China, and the Tulane University School of Public Health and Tropical Medicine in the U.S. has found that time restricted diets offer no benefits toward weight loss.
In their paper published in The New England Journal of Medicine, the group describes their year-long study that involved monitoring obese volunteers observing two versions of the same diet and what it showed about the benefits of time restrictions.
Blandine Laferrère and Satchidananda Panda, with Columbia University Irving Medical Center and the Salk Institute for Biological Studies, respectively, have published an editorial piece in the same journal edition outlining the work by the team.
Some prior evidence, mostly with animals, has suggested that restricting eating to certain windows of time during the day might help people lose weight. The idea was that eating only during such periods would coincide with important parts of the circadian rhythm resulting in higher metabolic activity burning more calories.
But other studies have shown no such benefit. In this new effort, the combined team from China and the U.S. conducted the longest and largest study done to date on the topic: a year-long study of such a diet that involved the cooperation of 139 obese volunteers who agreed to go on a reduced calorie diet for one year.
A randomized number of the volunteers were also asked to limit their eating to the hours of 8am to 4pm. The calorie restrictions were divided by gender; women were to eat between 1200 and 1500 kcal per day, and men 1500 to 1800 kcal per day. All of the volunteers were monitored throughout the study to measure body weight and other weight loss attributes such as a decreasing waistline. Each was also tested to ensure they were suffering no negative health effects.
At the end of the year, the researchers found that while the volunteers in the eating-window did lose more weight on average than the other group, it was not statistically large enough to be meaningful. They also found that restricting eating to a time-window did not make any difference in weight loss attributes such as smaller waistlines. They suggest their study shows that time-restricted diets do not help people lose more weight than they would have otherwise.
The present study has shown that 5 weeks of eTRF, but not mTRF, improves insulin sensitivity, reduces fasting plasma glucose, reduces body mass and adiposity, ameliorates inflammation, and increases gut microbial diversity. However, there were no significant differences among the three groups with respect to blood pressure, circulating lipid concentrations, HbA1c, hsCRP, sleep quality, or appetite.
The good compliance with the two TRF protocols in the present study implies that TRF is an easy-to-execute fasting regimen, and the similar compliance with each suggests that they are similarly feasible. The participants in both TRF groups were instructed to eat ad libitum during their daily 8 h eating periods and no specific nutritional guidance was given to them, such that the trial conditions were similar to real-life situations.
However, there were reductions in energy intake in both of the TRF groups, which implies that energy intake can be limited just by shortening the daily duration of food consumption. Furthermore, the lack of a significant difference in the change in energy intake between the two TRF groups suggests that the differences in the improvements in metabolic health were not caused by differences in energy intake.
The benefits of improving insulin sensitivity are numerous34. Consistent with the results of previous studies3,14,35, we found that eTRF, but not mTRF, improved insulin sensitivity. Remarkably, this is the first trial to show that eTRF is superior to mTRF with respect to its ability to improve insulin sensitivity by directly comparing these two TRF regimens.
Although similar changes in energy intake occurred in both TRF groups, only the eTRF group showed a reduction in body mass versus the control group, which was accompanied by reductions in both the percentage body fat and fat mass. These may indicate an improvement in fat deposition, which requires further visceral fat measuring parameters in future trials.
Besides, the weight loss in eTRF group was relatively modest compared with prior eTRF studies3,36, which may be the result of different inclusion criteria of participants, with normal weight humans included in this trial, while mostly overweight participants or individuals with obesity were included in prior eTRF studies3,36.
Only one trial by Courtney Peterson et al. has previously reported the effect of eTRF on blood pressure, with participants showing markedly reduced blood pressure after eTRF3. In contrast, no significant changes in blood pressure were noticed in the eTRF group in the present trial. The baseline blood pressure levels might be the reason for the different effects of eTRF between these two trials, because the trial by Courtney Peterson et al. was carried on those with a mean blood pressure within prehypertensive range3, while the present trial on healthy participants. The reported effects of mTRF on blood pressure have been inconsistent, and only one previous study showed a reduction on blood pressure, which was assumed to be an “add-on” effects of anti-hypertensive drugs14,21,26. In addition, there was no effect of either TRF regimen on circulating lipid concentrations, but this was not unexpected, because the blood concentrations of most of the participants were within the normal range.
Excess nutrient intake usually induces an inflammatory response, which has been causally linked to the dysregulation of glucose and lipid metabolism37. Previous studies have shown beneficial effects of TRF to reduce inflammation in individuals with obesity or metabolic diseases3,22,38, and we have shown that eTRF reduces inflammation in individuals without obesity, in the form of reductions in the plasma concentrations of TNF-α and IL-8.
A high plasma AST activity is a feature of obesity-induced hepatic steatosis 39,40, and we have also shown a potential protective effect of eTRF against high liver enzyme activity, which is consistent with the results of most previous studies of animal models of liver steatosis, non-alcoholic fatty liver disease4,6,41,42,43,44,45,46,47, or hepatic ischemia-reperfusion5; only one previous study showed that TRF does not affect the activities of the liver enzymes ALT, ALP, and GGT48.
The increase in pTregs in the eTRF group may also contribute to the beneficial effects of eTRF on metabolism, because a low pTreg count is associated with obesity, insulin resistance, and inflammatory responses49,50,51,52,53. Although the mechanism of the effect of TRF on pTregs is still under investigation, intermittent fasting has been shown to increase the number of pTregs in rodent intestines, where they have an immunoregulatory effect54. We also found that the α-diversity of the gut microbiota increased in the eTRF group, and this has been reported to be associated with a healthier gut microbiota55, whereas low gut microbial diversity is associated with metabolic diseases56.
Our finding that eTRF has superior effects to mTRF may be the results of different effects on mediators of the peripheral daily rhythm. Disturbances in the daily rhythms of secreted substances are associated with obesity and metabolic health57,58,59, and diet influences these60,61,62,63.
A previous study conducted in rodents showed that food restriction within an active period influences the daily rhythm of these substances and improves metabolic health64. Although in the present study TRFs seemed to have no effects on the fasting plasma concentrations of these substances, eTRF influenced the daily rhythms of ghrelin and resistin.
Although the daily variations in the circulating concentration of resistin has been reported to be related to feeding rhythm in rats65, and TRF has been reported to influence the circulating concentration of resistin in men66, the effect of a change in the feeding window on the daily rhythm of resistin had not been previously reported.
This change might merely be a reaction to the change in feeding rhythm. The daily rhythm in circulating ghrelin concentration has been reported to synchronize with TRF in mice, with the concentration increasing before the feeding period67, and it should be noted that ghrelin has an important role in the feeling of hunger68.
Therefore, the higher concentration of ghrelin that was identified at 23:00 in the eTRF group might be at least in part the results of a longer period of fasting in this group at that time point.
Cosinor analysis has been reported to accurately reflect the rhythmic changes in clock gene expression69; therefore, we used this to compare clock gene expression among the groups. Because not all the expression data for every participant fitted Cosinor curves, the parameters were calculated just for exploratory purposes, to provide clues for future investigations.
Previous studies identified a positive relationship between the amplitude of oscillation of rhythmic components and metabolic health70. We found that eTRF might enhance the daily rhythms in human clock genes, on the basis of the findings that all the participants in the eTRF group showed increases in the amplitude of SIRT1 expression and the MESORs of BMAL1, PER2, and SIRT1 expressions in PBMCs.
In contrast, mTRF had diverse effects on the daily rhythms of expression of several clock genes: it increased the amplitude and MESOR of PER2 expression, but reduced the amplitude and MESOR of PER1 expression in all the participants. This suggests that mTRF has relatively complex effects on daily rhythms, which will be further investigated in the future.
However, it is worth noting that the timing of food intake on the test day might influence the results of the analyses of daily rhythm-related parameters. Although it has been shown in rodent models that peripheral concentrations of secreted substances and PBMC gene expression can be influenced by changes in feeding rhythm, rather than just by recent food intake 65,71, it is unclear at present which of these has a greater effect on the daily rhythms of secreted substances and PBMC clock gene expression in humans.
The present study had several limitations. Firstly, although it was a randomized trial, the participants could not be blinded to the intervention. Secondly, the people who applied to join the trial might already have been interested in TRF or wished to improve their health through making a dietary change, and most were women.
Thirdly, the number of participants in the trial was relatively small and they may not have been representative of the wider population. Fourthly, the potential barriers to TRF were not analyzed. Fifthly, the participants in the TRF groups were required to consume their meals within an 8 h period, but the specific timing and duration of their meals varied within each group, which may have influenced the results. The influence of the duration of food consumption on the effects of TRF requires further investigation.
Sixthly, the changes in the eating periods that were made in the TRF groups may have caused changes in the duration of fasting prior to testing, which might have influenced the results. Lastly, daily rhythm-related parameters were measured in limited numbers of participants and few time points were assessed.
To better assess the effects of TRFs on daily rhythms, further, larger studies should be conducted that include shorter intervals between measurements and more than one diurnal cycle.
reference link : https://www.nature.com/articles/s41467-022-28662-5
More information: Deying Liu et al, Calorie Restriction with or without Time-Restricted Eating in Weight Loss, New England Journal of Medicine (2022). DOI: 10.1056/NEJMoa2114833
Blandine Laferrère et al, Calorie and Time Restriction in Weight Loss, New England Journal of Medicine (2022). DOI: 10.1056/NEJMe2202821