Douglas Paddon-Jones

Dietary protein recommendations and the prevention of sarcopenia

Purpose of reviewTo draw attention to recent work on the role of protein and the amount of protein needed with each meal to preserve skeletal muscle mass in ageing. Recent findingsAgeing does not inevitably reduce the anabolic response to a high-quality protein meal. Ingestion of approximately 25–30 g of protein per meal maximally stimulates muscle protein synthesis in both young and older individuals. However, muscle protein synthesis is blunted in elderly when protein and carbohydrate are coingested or when the quantity of protein is less than approximately 20 g per meal. Supplementing regular mixed-nutrient meals with leucine may also enhance the muscle protein synthetic response in elders. SummaryOn the basis of recent work, we propose a novel and specific dietary approach to prevent or slow down muscle loss with ageing. Rather than recommending a large, global increase in the recommended dietary allowance (RDA) for protein for all elderly individuals, clinicians should stress the importance of ingesting a sufficient amount of protein with each meal. To maximize muscle protein synthesis while being cognizant of total energy intake, we propose a dietary plan that includes 25–30 g of high quality protein per meal.

A moderate serving of high-quality protein maximally stimulates skeletal muscle protein synthesis in young and elderly subjects.

Ingestion of sufficient dietary protein is a fundamental prerequisite for muscle protein synthesis and maintenance of muscle mass and function. Elderly people are often at increased risk for protein-energy malnutrition, sarcopenia, and a diminished quality of life. This study sought to compare changes in muscle protein synthesis and anabolic efficiency in response to a single moderate serving (113 g; 220 kcal; 30 g protein) or large serving (340 g; 660 kcal; 90 g protein) of 90% lean beef. Venous blood and vastus lateralis muscle biopsy samples were obtained during a primed, constant infusion (0.08 mumol/kg/min) of L-[ring-(13)C(6)] phenylalanine in healthy young (n=17; 34+/-3 years) and elderly (n=17; 68+/-2 years) individuals. Mixed muscle fractional synthesis rate was calculated during a 3-hour postabsorptive period and for 5 hours after meal ingestion. Data were analyzed using a two-way repeated measures analysis of variance with Tukeys pairwise comparisons. A 113-g serving of lean beef increased muscle protein synthesis by approximately 50% in both young and older volunteers. Despite a threefold increase in protein and energy content, there was no further increase in protein synthesis after ingestion of 340 g lean beef in either age group. Ingestion of more than 30 g protein in a single meal does not further enhance the stimulation of muscle protein synthesis in young and elderly.

Protecting muscle mass and function in older adults during bed rest

Purpose of reviewTo highlight the losses in muscle mass, strength, power, and functional capacity incurred in older adults during bed rest-mediated inactivity and to provide practical recommendations for both the prevention and rehabilitation of these losses. Recent findingsIn addition to sarcopenic muscle loss, older adults lose lean tissue more rapidly than the young during prolonged periods of physical inactivity. Amino acid or protein supplementation has the potential to maintain muscle protein synthesis and may reduce inactivity-induced muscle loss, but should ideally be part of an integrated countermeasure regimen consisting of nutrition, exercise, and, when appropriate, pharmacologic interventions. SummaryIn accordance with recent mechanistic advances, we recommend an applied, broad-based two-phase approach to limit inactivity-mediated losses of muscle mass and function in older adults: (i) Lifestyle: consume a moderate amount (25–30 g) of high-quality protein with each meal and incorporate habitual exercise in close temporal proximity to protein-containing meals; (ii) Crises: react aggressively to combat the accelerated loss of muscle mass and function during acute catabolic crises and periods of reduced physical activity. As a base strategy, this should include nutritional support such as targeted protein or amino acid supplementation and integrated physical therapy.

Amino acid supplementation increases lean body mass, basal muscle protein synthesis, and insulin-like growth factor-I expression in older women.

CONTEXT Inadequate dietary protein intake has been implicated in sarcopenia. OBJECTIVE AND DESIGN The objectives of this study were to determine whether: 1) chronic essential amino acid (EAA) supplementation improves postabsorptive muscle protein fractional synthesis rate (FSR), lean body mass (LBM), and one-repetition maximum muscle strength, and androgen receptor and IGF-I muscle protein expression; and 2) the acute anabolic response to EAA ingestion is preserved after a 3-month supplementation period. Using a randomized, double-blinded, placebo-controlled design, older women (68 +/- 2 yr) were assigned to receive either placebo (n = 7), or 15 g EAA/d [supplemented treatment group (SUP)] (n = 7) for 3 months. Metabolic outcomes were assessed in association with stable isotope studies conducted at 0 and 3 months. SETTING The study was performed at The University of Texas Medical Branch General Clinical Research Center. RESULTS Ingestion of 7.5 g EAA acutely stimulated FSR in both groups at 0 months (P < 0.05). Basal FSR at 3 months was increased in SUP only. The magnitude of the acute response to EAA was unaltered after 3 months in SUP. LBM increased in SUP only (P < 0.05). One-repetition maximum strength remained unchanged in both groups. Basal IGF-I protein expression increased in SUP after 3 months (P = 0.05), with no changes in androgen receptor or total and phosphorylated Akt, mammalian target of rapamycin, S6 kinase, and 4E-binding protein. CONCLUSIONS EAA improved LBM and basal muscle protein synthesis in older individuals. The acute anabolic response to EAA supplementation is maintained over time and can improve LBM, possibly offsetting the debilitating effects of sarcopenia.

Differential stimulation of muscle protein synthesis in elderly humans following isocaloric ingestion of amino acids or whey protein

To counteract the debilitating progression of sarcopenia, a protein supplement should provide an energetically efficient anabolic stimulus. We quantified net muscle protein synthesis in healthy elderly individuals (65-79 yrs) following ingestion of an isocaloric intact whey protein supplement (WY; n=8) or an essential amino acid supplement (EAA; n=7). Femoral arterio-venous blood samples and vastus lateralis muscle biopsy samples were obtained during a primed, constant infusion of L-[ring-2H5]phenylalanine. Net phenylalanine uptake and mixed muscle fractional synthetic rate (FSR) were calculated during the post-absorptive period and for 3.5 h following ingestion of 15 g EAA or 15 g whey. After accounting for the residual increase in the intracellular phenylalanine pool, net post-prandial phenylalanine uptake was 53.4+/-9.7 mg phe leg-1 (EAA) and 21.7+/-4.6 mg phe leg-1 (WY), (P<0.05). Postabsorptive FSR values were 0.056+/-0.004% h-1 (EAA) and 0.049+/-0.006% h-1 (WY), (P>0.05). Both supplements stimulated FSR (P<0.05), but the increase was greatest in the EAA group with values of 0.088+/-0.011% h-1 (EAA) and 0.066+/-0.004% h-1 (WY), (P<0.05). While both EAA and WY supplements stimulated muscle protein synthesis, EAAs may provide a more energetically efficient nutritional supplement for elderly individuals.

Dietary Protein Distribution Positively Influences 24-h Muscle Protein Synthesis in Healthy Adults

The RDA for protein describes the quantity that should be consumed daily to meet population needs and to prevent deficiency. Protein consumption in many countries exceeds the RDA; however, intake is often skewed toward the evening meal, whereas breakfast is typically carbohydrate rich and low in protein. We examined the effects of protein distribution on 24-h skeletal muscle protein synthesis in healthy adult men and women (n = 8; age: 36.9 ± 3.1 y; BMI: 25.7 ± 0.8 kg/m2). By using a 7-d crossover feeding design with a 30-d washout period, we measured changes in muscle protein synthesis in response to isoenergetic and isonitrogenous diets with protein at breakfast, lunch, and dinner distributed evenly (EVEN; 31.5 ± 1.3, 29.9 ± 1.6, and 32.7 ± 1.6 g protein, respectively) or skewed (SKEW; 10.7 ± 0.8, 16.0 ± 0.5, and 63.4 ± 3.7 g protein, respectively). Over 24-h periods on days 1 and 7, venous blood samples and vastus lateralis muscle biopsy samples were obtained during primed (2.0 μmol/kg) constant infusion [0.06 μmol/(kg⋅min)] of l-[ring-13C6]phenylalanine. The 24-h mixed muscle protein fractional synthesis rate was 25% higher in the EVEN (0.075 ± 0.006%/h) vs. the SKEW (0.056 ± 0.006%/h) protein distribution groups (P = 0.003). This pattern was maintained after 7 d of habituation to each diet (EVEN vs. SKEW: 0.077 ± 0.006 vs. 0.056 ± 0.006%/h; P = 0.001). The consumption of a moderate amount of protein at each meal stimulated 24-h muscle protein synthesis more effectively than skewing protein intake toward the evening meal.

Bed rest impairs skeletal muscle amino acid transporter expression, mTORC1 signaling, and protein synthesis in response to essential amino acids in older adults

Skeletal muscle atrophy during bed rest is attributed, at least in part, to slower basal muscle protein synthesis (MPS). Essential amino acids (EAA) stimulate mammalian target of rapamycin (mTORC1) signaling, amino acid transporter expression, and MPS and are necessary for muscle mass maintenance, but there are no data on the effect of inactivity on this anabolic mechanism. We hypothesized that bed rest decreases muscle mass in older adults by blunting the EAA stimulation of MPS through reduced mTORC1 signaling and amino acid transporter expression in older adults. Six healthy older adults (67 ± 2 yr) participated in a 7-day bed rest study. We used stable isotope tracers, Western blotting, and real-time qPCR to determine the effect of bed rest on MPS, muscle mTORC1 signaling, and amino acid transporter expression and content in the postabsorptive state and after acute EAA ingestion. Bed rest decreased leg lean mass by ∼4% (P < 0.05) and increased postabsorptive mTOR protein (P < 0.05) levels while postabsorptive MPS was unchanged (P > 0.05). Before bed rest acute EAA ingestion increased MPS, mTOR (Ser(2448)), S6 kinase 1 (Thr(389), Thr(421)/Ser(424)), and ribosomal protein S6 (Ser(240/244)) phosphorylation, activating transcription factor 4, L-type amino acid transporter 1 and sodium-coupled amino acid transporter 2 protein content (P < 0.05). However, bed rest blunted the EAA-induced increase in MPS, mTORC1 signaling, and amino acid transporter protein content. We conclude that bed rest in older adults significantly attenuated the EAA-induced increase in MPS with a mechanism involving reduced mTORC1 signaling and amino acid transporter protein content. Together, our data suggest that a blunted EAA stimulation of MPS may contribute to muscle loss with inactivity in older persons.

Whey protein ingestion in elderly persons results in greater muscle protein accrual than ingestion of its constituent essential amino acid content

It is recognized that both whey protein (WY) and essential amino acids (EAA) are stimuli for muscle protein anabolism. The aim of the present study was to determine if the effects of WY ingestion on muscle protein accrual in elderly persons are due solely to its constituent EAA content. Fifteen elderly persons were randomly assigned to ingest a bolus of either 15 g of WY, 6.72 g of EAA, or 7.57 g of nonessential amino acids (NEAA). We used the leg arteriovenous model to measure the leg phenylalanine balance, which is an index of muscle protein accrual. Phenylalanine balance (nmol x min(-1) kg lean leg mass(-1)) during the 3.5 hours after the bolus ingestion improved in the WY (-216 +/- 14 vs -105 +/- 19; P < .05) but not in the EAA (-203 +/- 21 vs -172 +/- 38; P > .05) or NEAA groups (-203 +/- 19 vs -204 +/- 21; P > .05). The insulin response (uIU x mL(-1) 210 min(-1)) during the same period was lower in both the NEAA (48 +/- 40) and EAA (213 +/- 127) when compared to the WY (1073 +/- 229; P < .05). In conclusion, WY ingestion improves skeletal muscle protein accrual through mechanisms that are beyond those attributed to its EAA content. This finding may have practical implications for the formulation of nutritional supplements to enhance muscle anabolism in older individuals.

Leucine supplementation chronically improves muscle protein synthesis in older adults consuming the RDA for protein

BACKGROUND & AIM Protein-energy supplementation is routinely employed to combat muscle loss. However, success is often compromised by increased satiety, poor palatability, high costs and low compliance. METHODS For 2-weeks we supplemented meals of older individuals with leucine (4 g/meal; 3 meals/day; days 2-14). Metabolic studies were performed prior to (Day 1) and following (Day 15) supplementation. Leucine was not provided on metabolic study days. Venous blood and vastus lateralis muscle biopsies were obtained during a primed constant infusion of L-[ring-(13)C(6)] phenylalanine. Mixed muscle fractional synthesis rate (FSR), body composition and markers of nutrient signaling (mTOR, 4E-BP1 and p70S6K1 phosphorylation) were measured before and after a low protein/carbohydrate simulated meal. RESULTS The meal modestly increased FSR on Day 1 (postabsorptive: 0.063 ± 0.004 vs. postprandial: 0.075 ± 0.006%/h; p = 0.03), however, two weeks of leucine supplementation increased postabsorptive FSR (p = 0.004) and the response to the meal (p = 0.01) (postabsorptive: 0.074 ± 0.007 vs. postprandial: 0.10 ± 0.007%/h). Changes in FSR were mirrored by increased phosphorylation of mTOR, 4E-BP1 and p70S6K1 (p ≤ 0.1). No change in fat free mass was observed (p > 0.05). CONCLUSIONS In older adults, leucine supplementation may improve muscle protein synthesis in response to lower protein meals.

Dietary protein and muscle in older persons.

Purpose of reviewThe purpose of this study is to highlight recent advances in nutrition and protein research that have the potential to improve health outcomes and status in ageing adults. Recent findingsThe beneficial effects of dietary protein on muscle health in older adults continue to be refined. Recent research has bolstered support for moderately increasing protein consumption beyond the current Recommended Dietary Allowance by adopting a meal-based approach in lieu of a less specific daily recommendation. Results from muscle protein anabolism, appetite regulation and satiety research support the contention that meeting a protein threshold (approximately 30 g/meal) represents a promising strategy for middle-aged and older adults concerned with maintaining muscle mass while controlling body fat. SummaryOptimizing dietary protein intake to improve health requires a detailed consideration of topics including muscle protein anabolism, appetite control and satiety. Although each area of research continues to advance independently, recent collaborative and translational efforts have highlighted broad, translational consistencies related to the daily distribution and quantity of dietary protein.