The measurement of the effects of dietary protein consumption on the whole-body protein kinetic models

The idea that “we are what we are eat” has been widespread for hundreds of years, and the relationship between body composition and food consumption has been investigated for a long time. The synthesis and breakdown of body protein (whole-body protein kinetics)  in response to dietary consumption has been studied for almost a century.  Nonetheless, controversies persist regarding the optimal approach for determining whole-body protein kinetics.  

Herein, scientists from the University of Arkansas: Professor Robert Wolfe, Professor Arny Ferrando, Dr. David Church in collaboration with Professor Il-Young Kim, Professor Sanghee Park from Gachon University and Professor Paul Moughan from Massey University (New Zealand), have provided a critical review of the most widely-used approaches for determining the response of whole-body protein kinetics to dietary protein consumption, which is published in the journal of Clinical Nutrition Open Science 36 (2021): 78-90. https://doi.org/10.1016/j.nutos.2021.02.006

According to the review of Professor Wolfe and colleagues,  the general principles of whole-body protein models focus on the overall processes of protein synthesis and breakdown rather than on the components and various pools.  Basically, labeled molecules are used as tracers, which enable the quantification of the endogenous tracee’s rate of appearance from the breakdown of body protein and the rate of uptake of the tracee in the process of protein synthesis.  Tracers are usually administered intravenously but also orally in some cases. The estimation of the net protein balance of the entire body (i.e., the anabolic response) is equal to protein synthesis minus breakdown. Lead author Professor Wolfe said: “Quantifying the anabolic response to dietary protein intake is an essential application. There are different models with which to accomplish this goal, each with advantages and limitations.”

The nitrogen (N)-flux method has an outstanding advantage of requiring only oral administration of the tracer, so the method is non-invasive.  Moreover, the model enables the calculation of all aspects of whole-body protein kinetics with minimal assumptions.  However,  it is difficult to quantify changes in response to a single meal with this approach.  Professor Wolfe emphasizes that despite the advantages of this method when used over a prolonged period of time, “rapid changes in protein kinetics, such as occur after a single meal of dietary protein, cannot be reliably determined with the N-flux method.”

The primed-constant infusion of an essential amino acid tracer can be used to quantify the rapid changes from the basal state in whole-body protein kinetics that occur after ingestion of a single meal containing dietary protein. Professor Wolfe mentioned to Science Featured that expressing the data as the response from the basal state has the distinct advantage of taking account of differences in basal rates of protein kinetics between individual subjects.  The rapid time frame in which a model based on an intravenously infused essential amino acid tracer can be used is also an important advantage.  The major challenge with models based on essential amino acid tracers following a meal is to distinguish how much of the unlabeled tracee in the blood has arisen from the release from protein breakdown in the body as opposed to absorption of digested dietary protein.  Consumption of an intrinsically labelled protein helps distinguish whether the observed tracee in the blood has arisen from the ingested protein or body protein breakdown. However, lack of availability of intrinsically-labeled proteins is a limitation of this approach.  More fundamentally, unmeasured dilution of the intrinsically labeled protein can lead to significant underestimation of the rate of absorption of dietary protein, with the consequence of an overestimation of the rate of breakdown of body protein.

An alternative approach to the use of an intrinsically-labeled protein is called the “bioavailability” approach,  whereby the absorption of the tracee essential amino acid is calculated from the known amount of protein ingested, the amount of the tracee amino acid contained in the dietary protein, and the true ileal digestibility of the protein. “An advantage of the bioavailability approach is that the response to a combination of a variety of proteins that are likely to be included in a normal meal can be quantified. In addition, a physiological steady state is not required, meaning that the method is well suited for quantifying the response to a meal,” said Professor Wolfe. He added: “On the other hand, only the total anabolic response can be determined because only the total contribution of exogenous phenylalanine to the peripheral circulation can be estimated, not the rate at which it is absorbed.  Also, the method often must rely on literature values for true ileal digestibility, which may be inaccurate in some cases”.  On the other hand, the figure above demonstrates that use of either the upper or lower bounds of the likely true ileal digestibility often does not significantly affect conclusions.   

In summary, the most appropriate method with which to quantify whole-body protein kinetics depends on the degree of uncertainty in the required assumptions in a given situation.  In this review, it has been shown that all approaches for obtaining total body protein have some limits. Professor Wolfe and colleagues recommend for all methods upper and lower bounds for whole-body protein kinetics be calculated using realistic maximum and minimum values for assumed parameters. Simultaneous use of two models that require different assumptions can also assist in validating the calculated results. 

Journal Reference and Image Credits:

Wolfe, Robert R., Il-Young Kim, David D. Church, Paul J. Moughan, Sanghee Park, and Arny A. Ferrando. “Whole-body protein kinetic models to quantify the anabolic response to dietary protein consumption.” Clinical Nutrition Open Science 36 (2021): 78-90. https://doi.org/10.1016/j.nutos.2021.02.006

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