Is there a limit to how much protein the body can use? Original paper

In this randomized controlled trial, ingesting 100 grams of protein led to greater muscle and whole-body protein synthesis rates than 25 grams of protein. These results support the idea that eating enough protein in a day is more important than how protein is distributed.

Whether there is a linear dose-response relationship between the amount of protein ingested and the muscle protein synthesis (MPS) response (the primary outcome).

The rates of whole-body protein synthesis and whole-body protein net balance were also assessed.

36 recreationally active young men without apparent health conditions (ages 18–40).

Individuals who engaged in sports or exercise less than once per week or more than 3 times per week were excluded.

In this randomized controlled trial, the participants performed a bout of whole-body resistance exercise and then consumed a drink containing 25 grams of milk protein (25PRO), 100 grams of milk protein (100PRO), or 0 grams of protein (placebo).

Two days before the experiment, the participants were instructed to refrain from exercise and to maintain a consistent diet. All of the participants consumed a standardized meal the evening before the experiment.

To assess rates of protein synthesis and breakdown, the milk protein was enriched with amino acid tracers, stable isotope amino acid tracers were administered via intravenous infusions, and blood and muscle tissue samples were collected throughout a 12-hour period.

Over the entire 12-hour postprandial (postmeal) period, the MPS rate was the greatest in 100PRO.

Also, the rate of whole-body protein synthesis and whole-body protein net balance was the greatest in 100PRO. There was a very strong correlation between whole-body protein net balance and protein intake relative to body mass (up to around 1.7 grams of protein per kilogram of body mass), meaning that greater amounts of protein corresponded to greater whole-body net protein balance.

The results of the summarized study suggest that there is no practical limit to the amount of protein the body can use in a single meal for anabolic purposes.

With respect to whole-body protein synthesis, the reported finding is in agreement with previous research indicating that ingesting larger amounts of protein in a single meal results in a greater whole-body protein synthesis rate and net protein balance.^[1] What makes the summarized study groundbreaking is that it is the first to demonstrate an apparent linear dose-response relationship between dietary protein intake and MPS.

It is traditionally assumed that MPS is a saturable process. In other words, ingesting a certain amount of protein maximizes the MPS response, and ingesting a larger amount of protein does not further benefit MPS.^[2] Evidence for this statement comes from a collection of studies that measured the MPS response to various amounts of whey protein over 3–4 hours. In these studies, it was shown that ingesting about 0.24 and 0.40 grams of protein per kilogram of body weight (g/kg) in younger and older adults, respectively, was sufficient, on average, to maximize the MPS response.^[3]

Based on this data, in combination with the idea that the MPS response is relatively short lived, it has been recommended that people with the goal of maximizing anabolism (i.e., gaining muscle mass or preserving what they already have) should consume a bolus of protein every few hours,^[2] as this would lead to several maximal MPS spikes throughout the day and thus maximize the cumulative 24-hour MPS rate.

However, although it may be the case that a given amount of protein maximizes the MPS response over 3–4 hours, and so consuming a larger amount of protein does not further benefit MPS within this period, that doesn’t necessarily mean that this finding can be extrapolated to longer durations. It may be the case that if postprandial MPS is measured over a longer duration, a larger amount of protein would produce a greater MPS rate.

The summarized study put this theory to the test. In accordance with previous data, the difference in MPS between 25PRO and 100PRO was not statistically significant from 0 to 4 hours. It wasn’t until after 4 hours that differences in MPS between 25PRO and 100PRO became statistically significant. Specifically, the MPS rate was 40% higher in 100PRO than 25PRO from 4 to 12 hours.

Collectively, the results challenge the notion that consuming a bolus of protein every few hours is the best strategy for maximizing anabolism, and they suggest that consuming larger amounts of protein less frequently is another viable option. Rather than protein in excess of what’s been shown to maximize the MPS response over 3–4 hours being “wasted”, larger amounts of protein require a prolonged period of time for complete digestion and amino acid absorption before being incorporated into tissue protein like muscle. So while larger, less frequent protein feedings result in less maximal postprandial MPS spikes throughout the day than smaller, more frequent feedings, it seems that the duration in which MPS is elevated is longer for each spike, which results in a comparable cumulative 24-hour MPS rate, when total daily protein intake is equal.

The relationship between protein intake and postprandial muscle protein synthesis

It’s traditionally assumed that consuming more protein than what’s been shown to maximize the postprandial MPS response over 3–4 hours will result in the excess protein being oxidized (broken down), thus not contributing to the synthesis or maintenance of muscle protein. The results of the summarized study suggest that this is not the case. Rather, ingesting larger amounts of protein will lead to a prolonged elevation in protein synthesis and subsequently a greater net protein balance. (Remember, for an increase in muscle mass to occur, MPS must exceed muscle protein breakdown, resulting in positive net protein balance.)

Given that a protein intake of approximately 1.6 grams per kilogram of body weight per day (g/kg/day) tends to maximize resistance exercise-induced gains in muscle mass,^[4] it may be the case that 2 protein feedings each containing about 0.8 g/kg is just as good as the current best practice recommendation of 4 protein feedings each containing about 0.4 g/kg for maximizing anabolism.^[5]

Research on time-restricted eating (TRE) provides some support for this hypothesis. In these studies, the participants consumed a high-protein diet (at least 1.6 g/kg/day), performed resistance exercise, and either consumed their daily calories over an 8-hour window (TRE) or an approximately 12–13 hour window (the control).^[6][7][8] Altogether, the results indicated no difference between groups for the change in muscle mass. Similarly, a study that had the TRE group restrict their eating window to 4 hours per day on 4 days per week also reported that the change in muscle mass did not significantly differ between groups.^[9]

A limitation of these studies is that the researchers didn’t report whether protein intake distribution differed between groups. It can only be assumed that a shorter eating window led to fewer protein feedings per day in the TRE group, although this may not have been the case. Nonetheless, the results collectively demonstrate that shorter eating windows do not pose a threat to muscle mass, as long as total daily protein intake is adequate and resistance exercise is performed, which provides support for the idea that protein doesn’t need to be consumed every few hours to maximize anabolism.

Until a proper randomized controlled trial is conducted, it cannot be said for certain whether less frequent, larger protein feedings have a comparable effect on muscle mass to the current best practice recommendation of consuming a protein bolus containing about 0.40 g/kg every few hours.^[5] In the meantime, people interested in maximizing anabolism, such as bodybuilders, may want to play it safe and stick to smaller, more frequent protein feedings. For people with less intense physique goals, the summarized study suggests that there is more than one path to gaining muscle, and as long as total daily protein intake is adequate, it probably doesn’t make a practical difference whether you have 2, 4, or 6 protein feedings per day.

In this study, young men with no apparent health conditions were evaluated after a bout of whole-body resistance exercise, so the results may not be generalizable to other populations and conditions, such as older adults with cardiometabolic disease. It’s possible that the performance of resistance exercise led to a heightened anabolic state, increasing the participants’ capacity to effectively utilize larger amounts of protein.