Recent trends in weight loss diets have led to a substantial increase in protein intake by individuals. As a result, the safety of habitually consuming dietary protein in excess of recommended intakes has been questioned. In particular, there is concern that high protein intake may promote renal damage by chronically increasing glomerular pressure and hyperfiltration. There is, however, a serious question as to whether there is significant evidence to support this relationship in healthy individuals. In fact, some studies suggest that hyperfiltration, the purported mechanism for renal damage, is a normal adaptative mechanism that occurs in response to several physiological conditions. This paper reviews the available evidence that increased dietary protein intake is a health concern in terms of the potential to initiate or promote renal disease. While protein restriction may be appropriate for treatment of existing kidney disease, we find no significant evidence for a detrimental effect of high protein intakes on kidney function in healthy persons after centuries of a high protein Western diet.

A transient increase in local pro-inflammatory cytokine expression following skeletal muscle injury mediates the repair and regeneration of damaged myofibers through myogenesis. Regenerative capacity is diminished and muscle wasting occurs, however, when intramuscular inflammatory signaling is exceedingly high or persists chronically. An excessive and persistent inflammatory response to muscle injury may therefore impair recovery by limiting the repair of damaged tissue and triggering muscle atrophy. The concentration-dependent activation of different downstream signaling pathways by several pro-inflammatory cytokines in cell and animal models support these opposing roles of post-injury inflammation. Understanding these molecular pathways is essential in developing therapeutic strategies to attenuate excessive inflammation and accelerate functional recovery and muscle mass accretion following muscle damage. This is especially relevant given the observation that basal levels of intramuscular inflammation and the inflammatory response to muscle damage are not uniform across all populations, suggesting certain individuals may be more susceptible to an excessive inflammatory response to injury that limits recovery. This narrative review explores the opposing roles of intramuscular inflammation in muscle regeneration and muscle protein turnover. Factors contributing to an exceedingly high inflammatory response to damage and age-related impairments in regenerative capacity are also considered.

The effect of a 4-wk aerobic exercise training program (30–45 min, 3–5 d/wk, ≥65% maximal heart rate) on mixed skeletal muscle protein fractional synthetic rate (FSR), fractional breakdown rate (FBR), and net protein balance (FSR − FBR) (NET) was examined in 8 healthy, previously unfit men and women [21.0 ± 0.4 y, 163.7 ± 4.4 cm, 75.6 ± 5.7 kg, 33.5 ± 4.1% body fat, VO_2peak 38.6 ± 2.3 mL/(kg·min)] fed eucaloric diets providing 0.85 g protein/(kg·d) for the 6-wk study. Measurements were made at baseline after 2 wk of diet intervention only, and after 4 wk of aerobic exercise training and diet intervention. Primed continuous infusions of ring-[²H₅]-phenylalanine (2 μmol/kg; 0.05 μmol/(kg·min) and [¹⁵N]-phenylalanine (2 μmol/kg; 0.05 μmol/(kg·min) were used to assess skeletal muscle protein turnover at rest via the precursor-product method. Endurance training improved cardiovascular fitness, with a significant increase in VO_2peak (P < 0.01) and a significant decrease in running time on a standard course (P < 0.01). There were no significant changes in body mass or composition. There was a significant increase in FSR (0.077 ± 0.007 vs. 0.089 ± 0.006%/h, P < 0.05) and decrease in NET (FSR − FBR) (−0.023 ± 0.004 vs. −0.072 ± 0.012%/h, P < 0.05); FBR tended to increase (0.105 ± 0.014 vs. 0.143 ± 0.018%/h; P = 0.06) after training. Findings show that aerobic training for 4 wk increases skeletal muscle protein turnover in previously unfit subjects.

Muscle atrophy and weakness occur as a consequence of disuse after musculoskeletal injury (MSI). The slow recovery and persistence of these deficits even after physical rehabilitation efforts indicate that interventions designed to attenuate muscle atrophy and protect muscle function are necessary to accelerate and optimize recovery from MSI. Evidence suggests that manipulating protein intake via dietary protein or free amino acid–based supplementation diminishes muscle atrophy and/or preserves muscle function in experimental models of disuse (i.e., immobilization and bed rest in healthy populations). However, this concept has rarely been considered in the context of disuse following MSI, which often occurs with some muscle activation during postinjury physical rehabilitation. Given that exercise sensitizes skeletal muscle to the anabolic effect of protein ingestion, early rehabilitation may act synergistically with dietary protein to protect muscle mass and function during postinjury disuse conditions. This narrative review explores mechanisms of skeletal muscle disuse atrophy and recent advances delineating the role of protein intake as a potential countermeasure. The possible synergistic effect of protein-based interventions and postinjury rehabilitation in attenuating muscle atrophy and weakness following MSI is also considered.

This investigation evaluated the physiological impact of different dietary protein intakes on skeletal muscle protein synthesis postexercise in endurance runners. Five endurance-trained, male runners participated in a randomized, crossover design diet intervention, where they consumed either a low (0.8 g/kg; LP)-, moderate (1.8 g/kg; MP)-, or high (3.6 g/kg; HP)-protein diet for 4 wk. Diets were designed to be eucaloric with carbohydrate, fat, and protein approximating 60, 30, and 10%; 55, 30, and 15%; and 40, 30, and 30% for LP, MP, and HP, respectively. Substrate oxidation was assessed via indirect calorimetry at 3 wk of the dietary interventions. Mixed-muscle protein fractional synthetic rate (FSR) was measured after an endurance run (75 min at 70% V̇o_{2 peak}) using a primed, continuous infusion of [²H₅]phenylalanine. Protein oxidation increased with increasing protein intake, with each trial being significantly different from the other ( P < 0.01). FSR after exercise was significantly greater for LP (0.083%/h) and MP (0.078%/h) than for HP (0.052%/h; P < 0.05). There was no difference in FSR between LP and MP. This is the first investigation to establish that habitual dietary protein intake in humans modulates skeletal muscle protein synthesis after an endurance exercise bout. Future studies directed at mechanisms by which level of protein intake influences skeletal muscle turnover are needed.

Whereas diet and exercise have been shown to influence whole-body protein utilization, little is known about the impact of these factors on skeletal-muscle protein turnover. We highlight the role of dietary protein in modulating skeletal-muscle protein turnover in response to endurance exercise. Effects of endurance exercise on skeletal-muscle protein metabolism are presented and the influence of habitual protein intake on exercise-related protein responses is discussed. Skeletal-muscle protein turnover increases in response to endurance exercise training and following a single endurance exercise bout. Nutritional supplementation postexercise favorably affects skeletal-muscle protein synthesis and demonstrates amino acid availability as pivotal to the skeletal-muscle synthetic response following exercise. The level of habitual protein intake influences postexercise skeletal-muscle protein turnover. Dietary protein and exercise are powerful stimuli affecting protein turnover. Since variation in habitual protein intake influences skeletal-muscle protein turnover postexercise, investigations are needed to determine what role protein intake has in regulating skeletal-muscle protein metabolism. Long-term, well controlled diet and exercise intervention studies are essential for clarification of the relation between protein intake, endurance exercise, and skeletal-muscle protein turnover. Studies designed to characterize this relationship should be attentive to habitual macronutrient and energy intakes.