Muscle Protein Synthesis and Muscle Mass in Healthy Older Men

See corresponding articles on pages 2252 and 2262.

The age-related loss of skeletal muscle mass and function is a major public health problem. These changes have been attributed to the blunted anabolic sensitivity of the response of muscle protein to protein intake due to a disruption in the regulation of muscle protein turnover and the imbalance between protein synthesis and breakdown. Sarcopenia, the age-related pathological loss of skeletal muscle mass and muscle function, is largely related to an impaired sensitivity of muscle protein synthesis to postprandial anabolic stimuli induced by amino acids, insulin, and other protein metabolism–related nutrients and hormones (1–5). In this issue of the Journal, the articles by Chanet et al. (6), “Supplementing breakfast with a vitamin D and leucine–enriched whey protein medical nutrition drink enhances postprandial muscle protein synthesis and muscle mass in healthy older men,” and Kouw et al (7), “Protein ingestion before sleep increases overnight muscle protein synthesis rates in healthy older men: a randomized controlled trial,” address 2 nutritional strategies to improve muscle protein synthesis and muscle mass and to reduce the rate of lean and muscle mass losses in older adults.

As discussed in these 2 studies, protein ingestion during meals stimulates muscle protein synthesis and represents a main nutritional component for the maintenance of body composition and skeletal muscle mass over the life span, but different feeding strategies can improve the anabolic effect of protein. The different strategies that aim to preserve muscle mass in adults and to reduce muscle losses during aging involve the supply of an adequate quantity of high-quality protein during meals according to different patterns between meals and during the day to optimize daily muscle protein anabolism. The optimal quantity of protein to be provided to older adults remains controversial, and it was shown in some studies that prolonged protein supplementation could significantly increase protein synthesis in various older populations (8–18), whereas other studies did not detect measurable increases in muscle mass or strength (19–22). The quality of the protein is also an important component, and nutritional strategies to reduce muscle protein losses in older adults also focused on the use of high-quality protein with a high content of bioavailable indispensable amino acids and high leucine content as an anabolic signal for protein synthesis (23–27). In addition, the pattern of distribution of protein over meals can also improve muscle protein synthesis and possibly lean mass in older adults (28–31).

In addition to the importance of the quantity and quality of the protein in promoting protein synthesis, fortification with free leucine, indispensable amino acids, and other indispensable nutrients has been studied to determine its effectiveness in improving postprandial muscle protein synthesis rates when lower amounts of dietary protein are consumed. Interestingly, the importance of vitamin D in the regulation of muscle protein metabolism also has been examined, because an inadequate vitamin D status in the older population has been related to impairment of different functional outcomes related to protein anabolism and muscle mass (32–35). Accordingly, the study by Chanet et al. (6) was a randomized, placebo-controlled, double-blind study that aimed to investigate the acute effect of a vitamin D– and leucine-enriched whey protein medical nutrition drink integrated into the habitual breakfast of healthy older adults on postprandial muscle protein synthesis. In addition, the longer-term effect on muscle mass, physical performance, and glucose and insulin response to meals was evaluated. The results showed that supplementing breakfast with a vitamin D– and leucine-enriched whey protein nutrition drink stimulated postprandial muscle protein synthesis and increased muscle mass after 24 wk in healthy older adults. As discussed by the authors, the observed longer-term increase in muscle mass with the intervention is in line with the acute stimulation of postprandial muscle protein synthesis.

Not only the quantity and the quality of protein and nutrient supply matter but the pattern of protein and nutrient distribution between meals and over the day is also important in improving protein synthesis and muscle mass. Different studies have shown that the consumption of multiple meals with adequate high-quality protein content more adequately stimulates muscle protein synthesis and is positively associated with muscle protein synthesis, lean mass, and muscle performance (30, 36–41). In addition, protein ingestion before sleep has been suggested as an effective strategy for increasing the anabolic response and to efficiently stimulate muscle protein synthesis in older adults (42). Accordingly, the study by Kouw et al. (7) evaluated the efficacy of presleep protein ingestion to improve muscle protein synthesis rates during the overnight period in older adults. This study assessed in older men the efficacy of presleep ingestion of 40 g casein, 20 g casein, 20 g casein + leucine, or placebo on protein digestion and absorption kinetics and overnight muscle protein synthesis rates. The results showed that these proteins were properly digested and absorbed throughout the night and that, compared with placebo, 40 g protein before sleep increased overnight muscle protein synthesis rates above values observed in the placebo group, whereas this effect was not observed with either 20 g casein or with 20 g casein + leucine. As discussed by the authors, a proper distribution (both timing and quantity) of protein intake is essential to allow protein supplementation to improve muscle mass in older adults; and presleep protein ingestion that is associated with physical activity represents an efficient strategy to stimulate muscle protein synthesis during a period in which muscle protein synthesis rates have been shown to be typically low (42–44).

These 2 studies provide interesting directions for additional nutritional strategies to support and maintain skeletal muscle mass in older individuals. In addition to the quantity and quality of protein provided to older adults, a combination that includes supplementation with indispensable amino acids and other nutrients, intake of an even pattern of distribution of protein over meals, and protein ingestion before sleep that is associated with physical activity performed in the evening could efficiently improve the efficacy of protein utilization in older adults. More work is needed on the impact of protein intake distribution, and a more precise upper threshold of protein intake remains to be established to improve muscle protein synthesis rates in older individuals. In addition, it has not been established whether there is a direct relation between protein synthesis and muscle mass, and additional results on the long- term effects of such a strategy on body composition, lean mass, and muscle function should be provided in older adults.