Since we are in the season of making and breaking resolutions, one of the most broken resolutions appears to be – ‘lose weight’. As we approach the new year, I wanted to share research findings by Amanda Chaix and others from Salk Institute’s Satchindananda Panda’s lab. This paper, published timely in December 2014 explores ‘Time Restricted Feeding or TRF’ and its possible use in obesity therapy (1). A previous paper by this same lab was published in The Cell two years earlier and showed that in mice, if feeding was restricted to 8 hours of their active phase (i.e in the night), even if they ate high fat food, they were protected from weight gain and other obesity induced metabolic disorders. Recently, it has also come to light that many metabolic pathways and even drug targets designed to deal with metabolic disorders have diurnal rhythms (2). In light of these observations, in this study the authors extend their previous findings and undertake a more comprehensive study to include different diets and feeding patterns that might possibly mimic human food consumption patterns.

In this paper they investigate the beneficial effect of Time Restricted Feeding (TRF) under different diets, the legacy effect of TRF on different time-scales and the possible therapeutic effect of TRF on diet induced obesity and overall metabolism.

For the experiments, two feeding patterns were followed

1) Adlibitum Feeding (ALF) – food is available at all times with the quantity and frequency of consumption being the free choice of the animal and 2) Time Restricted Feeding (TRF) –  food is available only during their active time i.e in the night (9 hours)

In both cases the food provided was isocaloric (same amount of calories) in content but varied in the percentage of energy the mice get from each of the macronutrients (fats, carbs and protein). Just as a reference, regular chow that is fed to lab mice is composed of agricultural byproducts, such as ground wheat, corn, or oats, alfalfa and soybean meals, a protein source such as fish, and vegetable oil and is supplemented with minerals and vitamins. Chow is inexpensive to manufacture and is palatable to rodents.

So let me dive into what they tested one by one. First, what is/are the beneficial effects of Time Restricted Feeding (TRF) and is it irrespective of diet composition. They take 10 week old mice and feed them with normal chow for two weeks adlibitum. Then they start the experiment. The experiment is carried out for 12 weeks and the gain in weight is measured. So at the start of the experiment, they gave mice different types of diets either adlibitum (ALF) or time restricted for 9 hours (TRF). The types of diets included sucrose + fat, high fructose, normal chow feed and high fat diet. For the high fat diet alone, they also tested the effects of increasing TRF times – 9 hours, 12 hours and 15 hours.

In every case, irrespective of the diet composition, mice fed by TRF gained less weight compared to ALF. Secondly, mice on a fatty diet showed increasing weight gain with increase in the time of feeding (9hrs, 12hrs and 15 hrs) but it was still much lower compared to mice on fat diet adlibitum. An important side note, mice on normal chow diet whether on ALF or TRF regiments did not show any significant difference in the amount of weight gained during the course of the experiment. So they suggest that overall TRF does restrict weight gain irrespective of the composition of the diet (some diets are slightly better than others).

Coming to the second question – What happens if you give TRF a break and do ALF for whatever reason? They liken this to a human consuming TRF(9hrs) 5 days a week and going ALF in the weekend! True to their expectations, they found that even if there is a break in TRF when the mice were feeding ad libitum in the weekend, the weight gain was similar to the ones that were on TRF the whole time for 9 hours. So we can take comfort in the fact that at least in the short term, it is ok to occasionally binge :).  They also wanted to test the long term effect on changing feeding regimens (they call this legacy effect). For this 25 week long experiment, mice began by eating high fat food TRF(9hrs) for 12 weeks and then half of them continued in the TRF regimen and half were shifted to ALF for the reminder of the experiment.  They also tested the converse regimen (Start with ALF, half continued in ALF and half were shifted to TRF).

Obviously, the animals that started out on an ALF regimen of high fat diet and continued in the same regimen for the entire period of the experiment (25 weeks) showed the maximum weight gain, a whopping 111% increase. However, among the other half that were switched to TRF mid way (after the 12th week), the weight gain was much more reduced compared to the mice on ALF for 25 weeks. Conversely, the animals that were on TRF throughout showed the lowest weight gain. But among the TRF mice that were switched to ALF, weight gain was rapid. They control the experiments with a normal chow diet and show that irrespective of the feeding regimen and any changes midway, the animals gained about the same weight. So of course a balanced diet is the best 🙂

Thirdly and not surprisingly, the metabolic effects usually associated with obesity and Type II diabetes were seen in mice on a high fat ALF regimen (fat accumulation in liver, serum glucose level accumulation, glucose tolerance). However, these effects were less pronounced in mice that were on the TRF regimen throughout and were reversed to a significant extent when the feeding regimen was changed from ALF to TRF. They suggest that switching to the TRF regimen improves the motor coordination ability of the high fat diet consuming mice by measuring their rotarod and treadmill performance. They find that overall, TRF improves metabolic rhythms (making proteins, burning carbs and fat) and the metabolic capacity irrespective of diet.

Based on this study, you are not just what you eat but also when you eat. Obese mice that consume high fat diet in a time restricted manner are obese but fit and better protected from metabolic pathway perturbations and obesity associated outcomes. One important suggestion of this study based on their short term and long term cross over studies is that the earlier obese mice were switched to TRF, the better the outcome. When I presented this paper at Carnegie, some of the experts working on metabolism shared how different the metabolisms of humans were from mice; especially lab mice. For us, practicing TRF by restricting eating to 8-9 hrs in 24 hours might be a little hard although recent studies are showing that it is beneficial in humans as well (4). More research is needed to understand how TRF can be effectively translated to humans and tweaked to be truly beneficial. It is an exciting paper though!