Does time-restricted eating impair muscle protein synthesis? Original paper

Time-restricted eating (TRE), which typically involves restricting the duration of the daily eating window to 6–10 hours, is an increasingly popular dietary strategy shown to promote weight loss and improve cardiometabolic risk factors.^[1] However, a potential downside is that it may promote reductions in lean mass compared to other diets.^[2][3] Evidence suggests that consuming a bolus of protein every few hours maximizes daily rates of muscle protein synthesis (MPS).^[4] A shorter eating window may compromise the capacity to stimulate MPS, thus reducing daily MPS rates.

In this 10-day randomized trial, 18 healthy men (average age of 46 and average BMI of 30) consumed an isocaloric, protein-matched (1.0 grams per kilogram of body mass per day) diet following either a TRE or control diet. Both groups ate three meals per day, and all meals were provided to the participants. In the TRE group, meals were eaten at 10 a.m., 2 p.m., and 6 p.m., while the control group ate at 8 a.m., 2 p.m., and 8 p.m.

Before the start of the intervention, the participants underwent a 3-day period that involved eating a standardized diet, a 6-hour deuterated water loading protocol, fitting of a continuous glucose monitor, and a muscle biopsy from the vastus lateralis. The participants were then randomized to a dietary intervention group. Deuterated water was ingested daily, and another muscle biopsy was obtained on day 11 to assess MPS rates over the 10-day intervention.

The primary outcome was the daily MPS rate. The secondary outcomes were measures of body composition assessed via DXA and glycemic control assessed via continuous glucose monitoring.

MPS did not differ between groups, and both groups lost a similar amount of total body mass compared to baseline. However, reductions in fat mass were greater in the control group, and reductions in lean mass (trunk lean mass, specifically) were greater in the TRE group. Consequently, body fat percentage was reduced to a greater extent in the control group.

In addition, 24-hour blood glucose total area under the curve was reduced in the TRE group compared to the control group. After lunch, blood glucose levels (i.e., 2-hour incremental area under the curve and peak glucose level) were reduced in the TRE group compared to the control group, and the peak blood glucose level after dinner was reduced in the TRE group compared to the control group.

Evidence suggests that there is an optimal dose of protein per feeding that maximizes the MPS response, beyond which amino acids are broken down to be used for energy and the construction of other compounds. Evidence also suggests that the MPS response to protein ingestion is relatively short-lived, particularly in the rested state (i.e., not post-exercise). In combination, these data provide evidence for a blueprint on how to distribute protein intake to maximize daily MPS rates.

In younger adults, approximately 0.24–0.40 grams of protein per kilogram of body weight appears to maximize the MPS response to feeding.^[5] The exact amount needed is influenced by factors like the source of protein consumed — because a sufficient amount of leucine is needed to trigger MPS and a sufficient amount of the other essential amino acids are needed to sustain MPS^[6] — and whether exercise was recently performed and what type of exercise was performed, among other factors.^[7]

Following the ingestion or infusion of a sufficient dose of protein, MPS peaks at approximately 90–120 minutes afterward^[8][9] and returns to baseline levels by the 180-minute mark.^[10]

This mechanistic grounding is important background for discussing different protein distribution strategies.

Two separate studies have reported that in a 12-hour period following resistance exercise, consuming 20 grams of protein every 3 hours produced greater MPS rates than consuming 10 grams of protein every 1.5 hours and 40 grams of protein every 6 hours.^[4][11]

Another study, which had participants refrain from strenuous exercise for 72 hours and measured 24-hour MPS rates, found greater MPS rates after participants consumed 30 grams of protein at each meal compared to 10 grams at breakfast, 15 grams at lunch, and 65 grams at dinner.^[12]

Adequate vs. inadequate protein distribution

Collectively, these data provide convincing evidence that a bolus of protein should be consumed every 3–5 hours to maximize daily MPS rates.^[6][13]

This brings us to the relatively unsurprising results of the current study, considering its design. Both groups consumed 1.0 grams of protein per kilogram of body weight per day, which was distributed in the following pattern: 25 grams at breakfast, 35 grams at lunch, and 40 grams at dinner. Considering that the participants were generally healthy and had an average body mass of roughly 95 kilograms, each dose of protein (which was primarily from animal-based foods) was about sufficient to stimulate a robust MPS response. Additionally, there were at least 4 hours between each protein feeding in both groups. So, even though the daily eating window was shorter in the TRE group, similar daily MPS rates between groups were to be expected.

Although total lean mass was reduced in the TRE group, there were no differences between groups in appendicular lean mass, only trunk lean mass. According to the researchers, this finding, in combination with the possibility that fluid intake was reduced in the TRE group (fluid intake was not reported, so this cannot be said with certainty), suggests that differences in total lean mass between groups were due to changes in fluid, organ, and/or digestive system mass, as opposed to skeletal muscle mass. This hypothesis seems plausible, especially given the similar daily MPS rates between groups.

In contrast to the current study, other studies that reported reductions in lean mass following TRE had the participants consume an ad libitum diet,^[3][2] which resulted in a decrease in energy intake and the consumption of a hypocaloric diet, whereas the control group consumed a roughly eucaloric or weight-maintaining diet. In this context, a decrease in lean mass in the TRE group isn’t exactly surprising because an energy deficit reduces MPS rates.^[14] Additionally, neither study featured a high-protein diet or a resistance exercise intervention, both of which can counteract reductions in MPS rates following the consumption of a hypocaloric diet.^[15][16]

Studies that involved a high-protein (1.8–1.9 grams of protein per kilogram of body weight per day), hypocaloric diet consumed within an 8-hour eating window and a resistance exercise intervention have not reported negative effects of TRE on lean mass compared to a diet with a longer eating window,^[17] even when the diet was eucaloric.^[18]

Therefore, the potentially negative effects of TRE on muscle mass appear to stem from the promotion of inadequate total daily energy and protein intake. When these factors are controlled between groups, it doesn’t appear that TRE has unique, detrimental effects on lean mass, at least in the context of an 8-hour eating window. It may be the case that a more narrow eating window (e.g., 4 hours) would have detrimental effects on lean mass compared to a diet with a longer eating window, even with similar total daily energy and protein intake between diets. This feat, however, is much easier said than done.

As outlined, the anabolic effect of protein is not unlimited. There is a ceiling to MPS, and consuming more protein beyond that which generates a maximal MPS response will not confer further benefit. In a hypothetical experiment comparing two high-protein diets, one featuring a 4-hour eating window (TRE) and the other featuring a typical 12–14-hour eating window (control), the TRE group would only be able to take advantage of the anabolic effects of one (possibly two) protein-rich meals, whereas the control group could feasibly consume four protein-rich meals, likely resulting in superior daily MPS rates in the control group.

Additionally, the catabolic nature of prolonged fasting may become more apparent in the context of a 20-hour fasting window.^[19] For these reasons, it’s possible that an eating window shorter than 8 hours would be inferior to a diet with a longer eating window for long-term changes in lean mass. However, further research is needed to confirm this hypothesis.