Controversy exists about the maximum amount of protein that can be utilized for lean tissue-building purposes in a single meal for those involved in regimented resistance training. A long-held misperception in the lay public is that there is a limit to how much protein can be absorbed by the body. From a nutritional standpoint, the term “absorption” describes the passage of nutrients from the gut into systemic circulation. Based on this definition, the amount of protein that can be absorbed is virtually unlimited. Following digestion of a protein source, the constituent amino acids (AA) are transported through the enterocytes at the intestinal wall, enter the hepatic portal circulation, and the AA that are not utilized directly by the liver, then enter the bloodstream, after which almost all the AA ingested become available for use by tissues. While absorption is not a limiting factor with respect to whole proteins, there may be issues with consumption of individual free-form AA in this regard. Specifically, evidence shows the potential for competition at the intestinal wall, with AA that are present in the highest concentrations absorbed at the expense of those that are less concentrated [1].

It has been proposed that muscle protein synthesis (MPS) is maximized in young adults with an intake of ~ 20–25 g of a high-quality protein, consistent with the “muscle full” concept; anything above this amount is believed to be oxidized for energy or transaminated to form alternative bodily compounds [2]. The purpose of this paper is twofold: 1) to objectively review the literature in an effort to determine an upper anabolic threshold for per-meal protein intake; 2) draw relevant conclusions based on the current data so as to elucidate guidelines for per-meal daily protein distribution to optimize lean tissue accretion.

Speed of digestion/absorption on muscle anabolism

In a study often cited as support for the hypothesis that MPS is maximized at a protein dose of ~ 20–25 g, Areta et al. [3] provided differing amounts of protein to resistance-trained subjects over a 12-h recovery period following performance of a multi-set, moderate repetition leg-extension exercise protocol. A total of 80 g of whey protein was ingested in one of the following three conditions: 8 servings of 10 g every 1.5 h; 4 servings of 20 g every 3 h; or 2 servings of 40 g every 6 h. Results showed that MPS was greatest in those who consumed 4 servings of 20 g of protein, suggesting no additional benefit, and actually a lower rise in MPS when consuming the higher dosage (40 g) under the conditions imposed in the study. These results extended similar findings by Moore et al. [4] on whole-body nitrogen turnover.

Although the findings of Areta et al. [3] provide interesting insight into the dose-related effects of protein intake on muscle development, it is important to note that a number of factors influence dietary protein metabolism including the composition of the given protein source, the composition of the meal, the amount of protein ingested, and the specifics of the exercise routine [5]. In addition, individual variables such as age, training status, and the amount of lean body mass also impact muscle-building outcomes. A major limitation in the study by Areta et al. [3] is that total protein intake over the 12-h study period was only 80 g, corresponding to less than 1 g/kg of body mass. This is far below the amount necessary to maximize muscle protein balance in resistance-trained individuals who served as participants in the study [6, 7]. Furthermore, the ecological validity of this work is limited since habitual protein intakes of individuals focused on muscle gain or retention habitually consume approximately 2–4 times this amount per day [8, 9].

It also should be noted that subjects in Areta et al. [3] ingested nothing but whey protein throughout the post-exercise period. Whey is a “fast-acting” protein; its absorption rate has been estimated at ~ 10 g per hour [5]. At this rate, it would take just 2 h to fully absorb a 20-g dose of whey. While the rapid availability of AA will tend to spike MPS, earlier research examining whole body protein kinetics showed that concomitant oxidation of some of the AA may result in a lower net protein balance when compared to a protein source that is absorbed at a slower rate [10]. For example, cooked egg protein has an absorption rate of ~ 3 g per hour [5], meaning complete absorption of an omelet containing the same 20 g of protein would take approximately 7 h, which may help attenuate oxidation of AA and thus promote greater whole-body net positive protein balance. An important caveat is that these findings are specific to whole body protein balance; the extent to which this reflects skeletal muscle protein balance remains unclear.

Although some studies have shown similar effects of fast and slow proteins on net muscle protein balance [11] and fractional synthetic rate [12,13,14], other studies have demonstrated a greater anabolic effect of whey compared to more slowly digested sources both at rest [15, 16], and after resistance exercise [16, 17]. However, the majority of these findings were during shorter testing periods (4 h or less), whereas longer testing periods (5 h or more) tend to show no differences between whey and casein on MPS or nitrogen balance [18]. Furthermore, most studies showing greater anabolism with whey used a relatively small dose of protein (≤20 g) [15,16,17]; it remains unclear whether higher doses would result in greater oxidation of fast vs slow-acting protein sources.

Compounding these equivocal findings, research examining the fate of intrinsically labeled whey and casein consumed within milk found a greater incorporation of casein into skeletal muscle [19]. The latter finding should be viewed with the caveat that although protein turnover in the leg is assumed to be mostly reflective of skeletal muscle, it is also possible that non-muscle tissues might also contribute. Interestingly, the presence versus absence of milk fat coingested with micellar casein did not delay the rate of protein-derived circulating amino acid availability or myofibrillar protein synthesis [20]. Furthermore, the coingestion of carbohydrate with casein delayed digestion and absorption, but still did not impact muscle protein accretion compared to a protein-only condition [21]. The implication is that accompanying macronutrients’ potential to alter digestion rates does not necessarily translate to alterations in the anabolic effect of the protein feeding – at least in the case of slow-digesting protein such as casein. More fat and/or carbohydrate coingestion comparisons need to be made with other proteins, subject profiles, and relative proximity to training before drawing definitive conclusions.

Higher acute ‘anabolic ceiling’ than previously thought?

More recently, Macnaughton et al. [22] employed a randomized, double-blind, within-subject design whereby resistance-trained men participated in two trials separated by ~ 2 weeks. During one trial subjects received 20 g of whey protein immediately after performing a total body resistance training bout; during the other trial the same protocol was instituted but subjects received a 40-g whey bolus following training. Results showed that the myofibrillar fractional synthetic rate was ~ 20% higher from consumption of the 40 g compared to the 20 g condition. The researchers speculated that the large amount of muscle mass activated from the total body RT bout necessitated a greater demand for AA that was met by a higher exogenous protein consumption. It should be noted that findings by McNaughton et al. [22] are somewhat in contrast to previous work by Moore et al. showing no statistically significant differences in MPS between provision of a 20 g and 40 g dose of whey in young men following a leg extension bout, although the higher dose produced an 11% greater absolute increase [23]. Whether differences between intakes higher than ~ 20 g per feeding are practically meaningful remain speculative, and likely depend on the goals of the individual.

Given that muscular development is a function of the dynamic balance between MPS and muscle protein breakdown (MPB), both of these variables must be considered in any discussion on dietary protein dosage. Kim et al. [24] endeavored to investigate this topic by provision of either 40 or 70 g of beef protein consumed as part of a mixed meal on two distinct occasions separated by a ~ 1 week washout period. Results showed that the higher protein intake promoted a significantly greater whole-body anabolic response, which was primarily attributed to a greater attenuation of protein breakdown. Given that participants ate large, mixed meals as whole foods containing not only protein, but carbohydrates and dietary fats as well, it is logical to speculate that this delayed digestion and absorption of AAs compared to liquid consumption of isolated protein sources. This, in turn, would have caused a slower release of AA into circulation and hence may have contributed to dose-dependent differences in the anabolic response to protein intake. A notable limitation of the study is that measures of protein balance were taken at the whole-body level and thus not muscle-specific. It therefore can be speculated that some if not much of anti-catabolic benefits associated with higher protein intake was from tissues other than muscle, likely the gut. Even so, protein turnover in the gut potentially provides an avenue whereby accumulated amino acids can be released into the systemic circulation to be used for MPS, conceivably enhancing anabolic potential [25]. This hypothesis remains speculative and warrants further investigation. It would be tempting to attribute these marked reductions in proteolysis to higher insulin responses considering the inclusion of a generous amount of carbohydrate in the meals consumed. Although insulin is often considered an anabolic hormone, its primary role in muscle protein balance is related to anti-catabolic effects [26]. However, in the presence of elevated plasma AAs, the effect of insulin elevations on net muscle protein balance plateaus within a modest range of 15–30 mU/L [27, 28]. Given evidence that a 45 g dose of whey protein causes insulin to rise to levels sufficient to maximize net muscle protein balance [29], it would seem that the additional macronutrients consumed in the study by Kim et al. [24] had little bearing on results.