ReviewUpdate on maximal anabolic response to dietary protein
Introduction
Dietary protein intake serves many physiological roles, but the most prominent is the maintenance or gain of body protein stores. This is accomplished by stimulation of protein synthesis, the inhibition of protein breakdown, or a combination thereof. A net gain in protein balance (i.e., synthesis minus breakdown) is called an anabolic response, as opposed to a catabolic response caused by the rate of protein breakdown exceeding the rate of protein synthesis. An anabolic response usually refers to gain of muscle protein, but can involve the entire body. Optimal protein nutrition in an individual meal could be defined as the minimal amount of protein intake that results in the maximal anabolic response, as that will be the most likely approach to maintaining or increasing lean body mass (LBM) over time. Consumption of dietary protein in excess of the amount needed to elicit the maximal anabolic response could be considered excessive, since no further stimulation of the net gain of body protein can occur. Consequently, determining the amount of dietary protein needed to elicit the maximal anabolic response is directly relevant to defining the “optimal” amount of dietary protein in a meal. Determining the optimal amount of dietary protein in a meal involves quantification of the rates of protein synthesis, breakdown, and the balance between synthesis and breakdown in response to dietary protein in the context of a complete mixed meal. There is presumably a limit to the extent to which protein synthesis can be stimulated by dietary protein intake, and protein breakdown cannot be suppressed to less than zero. Therefore, there must be some level of protein intake beyond which no further gains in net balance can occur, which we will define as the maximal anabolic response.
It has been postulated that the maximal anabolic response can be elicited with intake of 20–35 g of high quality protein solely based on the stimulation of muscle protein synthesis (MPS) [1]. If true, this would mean that the typical, uneven distribution of dietary protein intake in the American diet results in considerable excessive protein consumption in the dinner meal, as the average protein intake at dinner may be as much as 40 g or more [2]. As a consequence, it has been proposed that the anabolic response to protein intake would be improved if the traditional pattern of the American diet in which approximately half of dietary protein is consumed at dinner were altered so that daily intake of protein is more evenly distributed throughout breakfast, lunch and dinner. In this paper we will examine the validity of this perspective within the practical range of protein intake (i.e., the Acceptable Macronutrient Distribution Range or AMDR, 10–35% of daily calorie intake). In that context we will discuss if the maximal anabolic response to dietary protein is important physiologically, the physiological determinants of the net anabolic response, and the methodologies that have been used to evaluate the “even distribution” hypothesis. We will discuss relevant experimental data from studies performed in human subjects, including consideration of the difference between the responses to pure protein intake as opposed to intake of a protein-containing mixed meal. Finally, we will conclude that, based on currently-available data, there is no practical limit to the anabolic response to dietary protein intake at least within the range of AMDR in a single meal. Further, we conclude that the total amount of dietary protein over the day is more relevant to the total anabolic response to dietary protein than the distribution of intake over the course of the day. From a practical standpoint this conclusion can most readily be incorporated into daily nutritional pattern by increasing the amount of dietary protein as part of breakfast and lunch without diminishing the amount of dietary protein eaten at dinner.
Section snippets
Is a maximal anabolic response important? Implications for health and disease
The anabolic response in the fed state affects protein mass in many tissues and organs, but prominently involves repletion of skeletal muscle proteins lost in the post-absorptive or fasting state. The issue is thus important in maintaining or increasing skeletal muscle mass. In the fasted state the net breakdown of muscle protein (i.e., protein breakdown exceeding protein synthesis) provides amino acids into the circulation. The transient increase in muscle protein breakdown (MPB) in the
The balance between protein synthesis and breakdown: the metabolic determinants of the anabolic responses
Changes in muscle protein mass are a consequence of net changes in anabolic or catabolic responses to factors including nutritional intake, hormonal milieu, physical exercise, starvation, inflammation, and more serious physiological stress such as sepsis or trauma. Changes in muscle mass are most conventionally considered the primary target of anabolic and catabolic responses, although imbalances between protein synthesis and breakdown can occur in many body tissues and organs to some extent.
Methodological considerations in determination of the anabolic response
There are various methods that estimate anabolic responses to dietary protein at the muscle and the whole body levels in response to a single meal or over the course of an entire day [5], [7]. We will discuss representative stable isotope tracer methods for exploring anabolic responses at the muscle and the whole-body levels. It has been shown that the tracer methods to quantify protein kinetics (protein synthesis, protein breakdown, and net protein balance) in response to dietary protein in
Relation of the anabolic response at the muscle level to the total whole body response
The determination of the anabolic response to dietary protein intake at the muscle level is obviously important, since muscle is a major fate of EAAs absorbed from dietary protein. However, tissues other than muscle account for more than half of the total protein turnover [21], [22]. Consequently, determination of the anabolic response at the muscle level could underestimate total anabolic response. Figure 1 illustrates schematically the potential role of protein turnover in the gut on the
Role of insulin in the anabolic response
The maximal anabolic response at the muscle level has been determined in many studies in response to the consumption of a pure protein [26], [27], [28]. The maximal anabolic response to dietary protein is complicated when considered in the context of a mixed meal, in part because of the impact of an increase in insulin concentration resulting from the meal intake. Ingestion of certain proteins and amino acids can stimulate insulin release, but the effect of carbohydrate intake on insulin
Role of intracellular EAA availability in the anabolic response
Although insulin suppresses protein breakdown, it is likely that there is an upper limit to this response. In accordance with this notion, it has been shown that no further suppression of leg muscle protein breakdown occurred at insulin concentration beyond 30 μ IU/ml [32]. However, it is likely that insulin cannot entirely explain the suppression of protein breakdown in response to a meal. We have previously shown that consumption of 70 g of dietary protein resulted in a greater reduction in
Is there a maximal anabolic response?
We previously presented data supporting the perspective that the maximal total anabolic response increases linearly in relation to the amount of amino acid or protein intake [18], [19], [33], [34], [35]. These data did not show a plateauing in the gain in the net balance between protein synthesis and breakdown as the amount of intake increased. It is reasonable to assume that there must be some upper limit to the anabolic response to the amount of dietary protein in one meal. There is some
Does meal distribution of dietary protein matter?
Consumption of dietary protein or EAA stimulates MPS in a dose-dependent manner to a point, but at higher levels of intake the extent of stimulation of MPS plateaus (e.g., Refs. [26], [27], [28]). The minimum dose of dietary protein (eaten as pure protein) that stimulates a near maximal stimulation of MPS is 20–35 g protein [41], [42] or more specifically 0.24–0.40 g/kg/meal depending on the quality of protein and individuals' age [25]. The conclusion that these values represent the maximal
Summary and conclusions
The limit of the stimulation of MPS has been studied extensively, but little attention has been given to the suppression of protein breakdown at higher rates of protein intake. It has been reported that a maximal MPS response is achieved with 20–35 g of a high quality protein [41], [42], or more specifically 0.24 g/kg/meal for young and 0.40 g/kg/meal for older adults [25]. This has been promoted as the maximal anabolic response [1]. However, this conclusion ignores the potential contribution
Author contributions
I.-Y.K. and R.R.W. drafted manuscript; I.-Y.K., N.E.D., and R.R.W. discussed, edited and approved the final manuscript.
Conflicts of interest
Dr. Wolfe has received research grants and/or honoraria from the National Cattleman's Beef Checkoff program, Abbott Nutrition Pronutria, and PepsiCo; Dr. Deutz has received research grants and honoraria from Abbott Nutrition. Dr. Kim has no potential conflicts of interest.
Acknowledgements
This project was financially supported by Pepper Center Grant PG30-AG-028718 and Award Number UL1-TR-000039 and KL2-TR-000063 from the National Center for Advancing Translational Sciences (NCATS).
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