How to Get Into Ketosis Fast
The low-carb, high-fat keto diet has been shown to improve body composition and increase endurance performance. But getting into ketosis is difficu...
“Eat breakfast like a king, lunch like a prince, and dinner like a pauper."
Does this old saying have scientific merit?
Welcome to the HVMN Research Roundup — a series where we explore some of the newest and most interesting studies in nutrition, metabolism, and human performance. Today, we take a look at how having an earlier intermittent fasting window (via early time-restricted feeding) can boost fat burning capacity, reduce appetite, and even enhance metabolic flexibility.
Our regulars know that intermittent fasting and how to apply it for health and human optimization is one of our key focus areas.
However, fasting can be made complicated as there are a myriad of variations of how to fast. You've heard me talk about 16:8, OMAD or one-meal-a-day, a 36 hour monk fast, or extended 3-7 day water fasts. Basically, any pattern that increases the pause of eating, versus the constant eating and grazing prevalent in modern culture, can be considered to be intermittent fasting.
Time restricted feeding, or TRF, is one term commonly used in scientific literature. The feeding is not restricted by types of foods nor the types of macronutrients, but restricted by time.
A variation of time restricted feeding is early time restricted feeding — eTRF. eTRF is what we'll be discussing so I'll be using this acronym a lot. eTRF differs from other TRF regimens by shifting the majority of food consumption to earlier in the day. Many people skip breakfast and have a late TRF window for example a late lunch and dinner, say 2 pm lunch and a 7 pm dinner. This is the pattern I often use. With eTRF, the fasting window starts and ends earlier: one eTRF example is 8 am start and 2 pm end.
Why could eTRF be better than other time-restricted feeding protocols? There are several theories, but one of the best contenders revolves around circadian rhythm. In short, circadian rhythms are the sunrise and sunset clocks present in our cells — nearly every organ in our body operates on a circadian rhythm. Throughout the day, changes in gene expression determine how we feel, how we perform, and how our body metabolizes energy. We have circadian rhythms in energy expenditure, appetite, and in the release of hormones like insulin, cortisol, and other metabolic regulators.
In particular, we observe that insulin and other metabolic processes peak earlier in the day. This suggests that shifting food intake to earlier in the day, when metabolism is more geared to the task, may improve metabolic control. Some research has shown that eating a large breakfast and a smaller dinner leads to a decrease in appetite and food intake. Other data suggests that restricting the window of eating to an earlier window can increase the body’s energy expenditure.
In contrast to the benefits of proper meal timing, studies also support the consequences that eating “out of sync” with circadian rhythms, for instance, munchies late at night, promotes weight gain and metabolic dysfunction.
So, the adage to eat breakfast like a king might be good. However, the specific mechanisms as to why early time restricted feeding might be more beneficial than other meal timing interventions or the standard way of eating is unclear. Is it appetite, metabolic hormones, energy expenditure, or metabolic flexibility or something else that gets the credit for the benefits of eTRF?
A new study sought to help answer this question. The study, titled “Early time restricted feeding reduces appetite and increases fat oxidation but does not affect energy expenditure in humans” was published in July 2019 in the scientific journal “Obesity”. The study was the first randomized, controlled trial to investigate whether meal timing has an influence on energy expenditure and other factors important for weight loss. The researchers hypothesized that early time restricted feeding would increase 24 hour energy expenditure and other metabolic variables when compared to a meal schedule that resembled the “typical” American pattern of eating.
Let's go over the experiment structure.
The two eating patterns studied were this: an eTRF protocol of 6 hour eating window — with meals eaten at 8 am, 11 am, and 2 pm versus the standard American eating pattern of a 12 hour eating window — with meals at 8 am, 2 pm, and 8 pm. Each pattern was done for 4 days.
The study was a randomized, crossover study — this means that the order in which the participants would receive each of two eating patterns would be determined by chance, but each person would do both patterns. So we have a 18 hour fasting window vs. a 12 hour fasting window.
After participants finished the first eating pattern, there was a washout period of 3 and a half to 5 weeks where everyone ate their usual pattern, before returning and starting the alternate diet.
On days 1 - 2 of each pattern, participants were studied in “free living” conditions — meaning they didn’t report to the lab and were told to eat their meals at home while still complying to their meal timing schedule. On days 3 - 4, all study meals were provided to the participants and eaten in the lab under supervision. Dietary composition was 50% carbohydrate, 35% fat, and 15% protein — but this was only validated for the meals that each participant was provided, not what they ate on their own at home.
Day 4, the last day, was the big day. Participants were studied for 24 hours inside of a respiratory chamber — basically a room-sized box that gathers information about participant’s metabolism using a technique known as indirect calorimetry. This measures how much carbon dioxide is produced and how much oxygen is consumed by sampling the air that is expired, which can then be used to determine things like energy expenditure, energy consumption, and substrate oxidation or the different metabolic fuels someone is using.
While inside the chamber, everyone was given 3 identical meals at times that corresponded to the particular pattern they were in at the time — 8 am, 11 am, and 2pm for the eTRF group and 8 am, 2 pm, and 8 pm for the control group. The standard meal used was a strawberry yogurt smoothie with whey protein and skim milk along with a peanut butter and jelly sandwich. It wasn’t designed for maximal nutritional density, just to enable measurement of post-meal energy expenditure and metabolism, which were measured in between 60 and 85 minutes following each meal.
The chamber also measured something called metabolic flexibility. This is a hot buzz word that you've heard me reference before. Metabolic flexibility refers to the body’s ability to switch between oxidizing different substrates (mainly, fat and carbohydrates). Someone who is “metabolically flexible” might increase their reliance on glucose after a high-carb meal since they are insulin sensitive and readily burn carbs. At the same time, their ability to utilize fat is also superb, and the body readily metabolizes fat in a scenario where endurance or fasting is at play.
Along with the measures of energy expenditure and substrate oxidation inside the chamber, the study measured several other biomarkers. These included blood levels of hunger-related hormones like ghrelin, leptin, peptide YY, and glucagon-like peptide. Throughout the study, participants were also asked about the appetite and energy and asked to rate things like hunger, the desire to eat, the capacity to eat, fullness, stomach fullness, energy levels, awakeness, and perceived body temperature.
Now that we have the experiment details down, let’s dig into the results.
A total of 11 people completed this study, 7 men and 4 women. On average, they were 32 years old and had a BMI of 30. Everyone ate the same amount of food on each pattern — about 2,200 calories per day. Neither group experienced a change in body weight on either pattern, suggesting energetic balance was mostly achieved. The authors also noted 100% compliance with the meal timing schedules and eating the laboratory-provided meals. That removes some possible confounders and builds confidence in the data fidelity.
First, let’s talk about energy expenditure. The overarching finding here was that early TRF did not influence total 24 hour energy expenditure compared to the control pattern. However, energy expenditure did fluctuate during the feeding and fasting windows.
eTRF increased energy expenditure during the daytime — where participants burned 56 extra calories than they did while on the control pattern. However, this was accompanied by a lower energy expenditure at night — where eTRF resulted in 46 fewer calories burned compared to the control. Therefore, overall energy expenditure during 24 hours basically evened out.
However, eTRF did seem to increase the thermic effect of food after meals. Particularly, TEF was higher after the second and third meals of the day in the eTRF group compared to the control pattern. This was probably one of the reasons for the higher energy expenditure during the day in the early TRF group. Again, while energy expenditure was higher at these specific times of day, no difference was seen when the patterns were compared over 24 hours.
Next, let’s look at metabolic flexibility. In this study, fuel utilization was measured using non-protein respiratory quotient, or RQ, which measures the ratio of volume of carbon dioxide expelled vs. oxygen consumed. A ratio of 0.7 means 100% fat oxidation. A ratio of 1.0 means 100% carbohydrate oxidation. The difference between the largest and smallest value of RQ was used to determine metabolic flexibility — with a greater difference indicating better metabolic flexibility.
Early time restricted feeding led to a reduced 24 hour RQ. This indicates that participants were oxidizing more fat for fuel during the eTRF regimen compared to the control. The main differences in RQ were observed between 8 pm and 8:30 am — which makes sense, because during this time, participants were well into their fasting period.
Metabolic flexibility also improved on the eTRF pattern — there was a larger, statistically significant difference between the highest and lowest value of the respiratory quotient over 24 hours that it was measured.
There were also several significant differences in metabolic hormones between the groups. In the morning, those following the eTRF pattern had lower levels of ghrelin, leptin, and glucagon-like peptide. In the evening, ghrelin was also reduced while a hormone known as peptide YY increased. When morning and evening values were averaged, the eTRF regimen lowered levels of ghrelin and tended to increase levels of leptin, while no changes were seen in the control group.
But how did the participants actually feel throughout the study — this is potentially the most important factor. Early time restricted feeding decreased several measures of appetite in the middle of the day. For instance, participants on eTRF reported lower subjective ratings for the “desire to eat” while increasing their ratings of fullness during the day. All this is to suggest that restricting the feeding window and extending the fasting period didn’t adversely affect hunger or make participants any more hungry than usual, which would have been reflected in increased hunger and decreased satiety throughout the day and night.
Several things stand out about this study that should be discussed. The first is that, this study found no difference in overall energy expenditure when early time restricted feeding was compared to a standard eating schedule. This suggests that when meal frequency and energy intake are kept equal, time restricted feeding (at least for a 4 day period) might not provide an overall “metabolic advantage” compared to a standard eating regimen.
However, the study did find that early time restricted feeding (in a 4 day period) influenced fat metabolism and metabolic flexibility. Even when no differences in energy expenditure were observed, early TRF resulted in enhanced fat oxidation over a 24 hour period. This was indicated by a low respiratory quotient: indicating that more fat and fewer carbohydrates were being used for energy. This finding makes sense, given that participants in eTRF had a substantially longer fasting period compared to the control group — 18 hours compared to just 12. We know that fasting for even a moderate duration leads to increased fat oxidation and a lower reliance on carbohydrates for energy. This study supports that fact and indicates that, especially throughout the night, eTRF enhances your fat-burning capacity.
Enhanced metabolic flexibility in the eTRF group is suggestive that this pattern might be better at teaching the body to efficiently use different energy sources in response to supply and demand. During the day, the eTRF group had a respiratory quotient that indicated a mix of carbs and fat were being used — this makes sense because they were in the “fed” state between 8 am and 2 pm. However, the respiratory quotient in this group steadily declined well into the fasting period and throughout the night, indicating that when fuel ran low, they began to rely on fat oxidation to a greater extent than those who were consuming food in the larger eating window.
Improved metabolic flexibility is an important aspect of preventing and treating metabolic conditions like type 2 diabetes and obesity, as well as being an important aspect of peak human health and performance. Thus, eTRF may be particularly beneficial or conditions that involve metabolic dysfunction.
Another valuable finding is the modulation of appetite by the eTRF regimen. A common argument against intermittent fasting is that it will increase hunger, making this strategy unfeasible or unbearable for most people. Won’t skipping a big dinner just make me ravenous later at night? This study provided evidence that the desire to eat was actually reduced throughout the day, and fullness increased in the restricted eating group. The appetite regulation may have been due to the reduced levels of ghrelin in the morning. Ghrelin is known as the “hunger hormone” — and lower levels would somewhat indicate a lower desire to eat. Furthermore, peptide YY, a hormone involved in satiety signaling, was increased in the middle of the day. Each of these changes likely contributed to the beneficial lack of hunger experienced by the eTRF group. Finally, the eTRF group experienced reduced hunger swings, meaning that hunger levels were more even keeled throughout the day, despite only consuming food during a 6-hour window.
This was a nice study, but we should call out its limitations. First of all, this was a small study of 11 subjects, with the pool skewed towards men. Larger n will help affirm the generalizability.
Secondly, this was a very short study — only 4 days for each eating pattern. This is likely not enough time for many metabolic adaptations to take place. General practice talks about 2-4 weeks of adaptation, so a longer trial of a few weeks to months may observe different changes, or perhaps more significant ones. However, still very cool to see results in just 4 days.
One confounding variable is the lack of control over dietary intake during the first two days of each pattern, where participants were told to eat their habitual diet. We know little about WHAT participants ate during this period, only when. We all know that macronutrient composition is important, but this wasn't looked at in this study. Eating keto vs. the 50% carbohydrate diet used in the study would create very different ketone, glucose, and insulin loads on the body over the experimental periods. For example, I would want to see if people were ketogenic at the tail end of the fasting window. 18 hours is just around the border where I expect ketones to start rising and be present at substantial levels if the people were eating a ketogenic diet in a 18:6 eating pattern.
I believe the ultimate questions that all these studies are beginning to unpack is this: how does fasting work and what's the best way to reap its benefits ? Is being in ketosis the main metabolic driver or is the pause in consumption is the main metabolic driver. How do these two interplay ?
Another question is how important the timing of the eating window really is. Is the early eating window dominant or simply having an eating window even one later in the evening for example 2 pm - 8 pm good enough ?
I have a few key takeaways here. This study shows how powerful time restricted feeding can be. Even a fasting pattern of 4 days was able to show improvements in metabolic flexibility and fat oxidation. Increased fat oxidation can ultimately result in more weight and fat loss, if that is your goal. Otherwise, fans of early time restricted feeding just got another brick of evidence supporting this eating pattern. Being a better fat-burner, without requiring severe dietary changes, is nice and has applications for both health and performance.
As I mentioned at the top, there's a lot of variations on the timing a fast (whether you fast in the morning or in the evening), the length of fasting (how many hours fasted), and the macronutrient consumption of food when you do eat.
If I were to speculate on the rank order of importance between the three, my ranking is this: longer fasting window is most important, the macronutrient consumption of food when you do eat is secondary, and then the timing of the eating window is tertiary. If it works for your routine, it may be a good idea to shift a majority of your eating to earlier in the day. But if not, fasting and the type of macros you do eat probably captures the majority of the benefit as seen in this particular study.
My suspicion is that getting into ketosis is the important trigger point that sets off much of the metabolic benefit of fasting. Thus, the levers of timing, length, and meal macros are just different toggles to control in order to get into periodic ketosis. The way to confirm this is to 1) understand the variations of different fasting routines and determine whether they share the same underlying mechanism of action, 2) determining whether that mechanism of action is simply becoming ketogenic and therefore the end state of ketosis is driving most of the metabolic benefit, 3) and lastly while in ketosis, does consuming non-insulinogenic calories from fat or ketone esters blunt some of the benefits of fasting or not ? Another way to ask the question is whether being in ketosis enough or must one fully stop consumption to maximize the benefit.
There's a lot more research to be done in this space, and when its published, we’ll be here to break down the studies.
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