The Anabolic Response to Dietary Protein Is Not Limited by the Maximal Stimulation of Protein Synthesis in Healthy Older Adults: A Randomized Crossover Trial

Abstract

We have recently demonstrated in young adults that an anabolic response with mixed meal protein intake above ~35 g/meal, previously recognized as an “optimal” protein dose, was further stimulated. However, it is unknown if this applies to older adults. We therefore examined anabolic response to a mixed meal containing either 35 g (MOD, moderate amount of protein) or 70 g (HIGH, high amount of protein) in a randomized cross-over metabolic study in older adults (n = 8). Primed continuous infusions of L-[2H5] phenylalanine and L-[2H2]tyrosine were performed to determine whole-body protein kinetics and muscle protein fractional synthesis rate (MPS) in basal fasted and fed states. Whole-body protein kinetics (NB, net protein balance; PS, protein synthesis; PB, protein breakdown) and MPS was expressed as changes from the baseline post-absorptive state. Consistent with our previous findings in young adults, both feedings resulted in a positive NB, with HIGH being more positive than MOD. Furthermore, NB (expressed as g protein∙240 min) increased linearly with an increasing amount of protein intake, expressed relative to lean body mass. The positive NB was achieved due mainly to the suppression of PB in both MOD and to a greater extent HIGH, while PS was only increased in HIGH. Consistent with the whole-body data, MPS was significantly higher in HIGH than MOD. Plasma concentrations of essential amino acids and insulin were greater in HIGH vs. MOD. We conclude that in the context of mixed meals, whole-body anabolic response linearly increases with increasing protein intake primarily through the suppression of PB, and MPS was further stimulated with protein intake above the previously considered “optimal” protein dose in older adults.

High-Protein Energy-Restriction: Effects on Body Composition, Contractile Properties, Mood, and Sleep in Active Young College Students

“…However, following low energy availability, muscle protein synthesis is reduced leading to a negative net protein balance, and thus, finally culminates in muscle mass loss (Carbone et al, 2013 ; Pasiakos et al, 2013 ). In this context, it has been suggested that higher protein intake (2.4 vs. 1.2 g/kg) might restore muscle protein synthesis (Longland et al, 2016 ; Macnaughton et al, 2016 ) due to amino acids being preferentially used for muscle protein synthesis instead of gluconeogenesis (Walberg et al, 1988 ; Wackerhage and Rennie, 2006 ), with a concomitant decrease in protein breakdown (Kim et al, 2016 ; Park et al, 2020 ). Greater amino acid availability results in a more pronounced positive protein balance (Pikosky et al, 2008 ; Gwin et al, 2020 ), leads to a muscle sparing effect and is, therefore, recommended as an efficient strategy to increase the likelihood of lean mass retention (Phillips, 2008 , 2014 ; Manore, 2015 ; Murphy et al, 2015 ; Witard et al, 2019 ).…”

Dietary protein requirements and recommendations for healthy older adults: a critical narrative review of the scientific evidence

“…Deutz and Wolfe (85) advocated that there is no limit to in vivo whole-body protein anabolism when protein is consumed as a part of a mixed macronutrient meal (97,101) . More recently, Park et al (83) showed in healthy older adults (69•3 ± 1•8 years) that there is a higher MPS response following the consumption of a higher protein intake (70 g) compared with moderate (35 g) as part of a mixed macronutrient meal, and a greater whole-body net protein balance in the higher protein intake group due to the suppression of protein breakdown as well as increased protein synthesis (Fig. 1).…”

“…This shift is due to the interactive effects of protein contained in whole foods with other nutrients and bioactive compounds on muscle and whole-body protein turnover. Studies have primarily focused on MPS in response to beef (78,79) , eggs (80,81) and mixed macronutrient meals (82,83) . These studies highlighted the importance of considering complex food matrices in the regulation of muscle and whole-body protein turnover.…”

“…Previous studies investigating whole-body protein turnover in the context of mixed macronutrient meal intake demonstrated that anabolic response is not limited by protein synthesis (82)(83)(84) . Deutz and Wolfe (85) advocated that there is no limit to in vivo whole-body protein anabolism when protein is consumed as a part of a mixed macronutrient meal (97,101) .…”

In Vivo and In Vitro Quantification of Glucose Kinetics: From Bedside to Bench

“…In other words, the faster the tracee turnover, the lower the E p for a given F . The tracer dilution model can be applicable to assessments of in vivo kinetics of various metabolites including amino acids [ 26 , 44 – 46 ], palmitate [ 6 , 47 , 48 ], glycerol [ 49 – 51 ], pyruvate [ 52 ], lactate [ 53 – 55 ] as well as glucose [ 8 , 11 , 56 , 57 ] in steady states and non-steady states.…”