Advertisement

Evidence-Based Recommendations for Optimal Dietary Protein Intake in Older People: A Position Paper From the PROT-AGE Study Group

Open AccessPublished:July 18, 2013DOI:https://doi.org/10.1016/j.jamda.2013.05.021

      Abstract

      New evidence shows that older adults need more dietary protein than do younger adults to support good health, promote recovery from illness, and maintain functionality. Older people need to make up for age-related changes in protein metabolism, such as high splanchnic extraction and declining anabolic responses to ingested protein. They also need more protein to offset inflammatory and catabolic conditions associated with chronic and acute diseases that occur commonly with aging. With the goal of developing updated, evidence-based recommendations for optimal protein intake by older people, the European Union Geriatric Medicine Society (EUGMS), in cooperation with other scientific organizations, appointed an international study group to review dietary protein needs with aging (PROT-AGE Study Group). To help older people (>65 years) maintain and regain lean body mass and function, the PROT-AGE study group recommends average daily intake at least in the range of 1.0 to 1.2 g protein per kilogram of body weight per day. Both endurance- and resistance-type exercises are recommended at individualized levels that are safe and tolerated, and higher protein intake (ie, ≥1.2 g/kg body weight/d) is advised for those who are exercising and otherwise active. Most older adults who have acute or chronic diseases need even more dietary protein (ie, 1.2–1.5 g/kg body weight/d). Older people with severe kidney disease (ie, estimated GFR <30 mL/min/1.73m2), but who are not on dialysis, are an exception to this rule; these individuals may need to limit protein intake. Protein quality, timing of ingestion, and intake of other nutritional supplements may be relevant, but evidence is not yet sufficient to support specific recommendations. Older people are vulnerable to losses in physical function capacity, and such losses predict loss of independence, falls, and even mortality. Thus, future studies aimed at pinpointing optimal protein intake in specific populations of older people need to include measures of physical function.

      Keywords

      Guidelines for dietary protein intake have traditionally advised similar intake for all adults, regardless of age or sex: 0.8 grams of protein per kilogram of body weight each day (g/kg BW/d).

      World Health Organization. Protein and amino acid requirements in human nutrition: Report of a joint WHO/FAO/UNU expert consultation. Geneva: WHO Press; 2007. Report 935.

      Institute of Medicine
      Dietary Reference Intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids (macronutrients).

      European Food Safety Authority (EFSA). Outcome of a public consultation on the draft scientific opinion on the EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA) on dietary reference values for protein. Parma, Italy: EFSA; 2012.

      The one-size-fits-all protein recommendation does not consider age-related changes in metabolism, immunity, hormone levels, or progressing frailty.
      • Clegg A.
      • Young J.
      • Iliffe S.
      • et al.
      Frailty in elderly people.
      Indeed, new evidence shows that higher dietary protein ingestion is beneficial to support good health, promote recovery from illness, and maintain functionality in older adults (defined as age >65 years).
      • Walrand S.
      • Guillet C.
      • Salles J.
      • et al.
      Physiopathological mechanism of sarcopenia.
      • Gaffney-Stomberg E.
      • Insogna K.L.
      • Rodriguez N.R.
      • Kerstetter J.E.
      Increasing dietary protein requirements in elderly people for optimal muscle and bone health.
      • Kurpad A.V.
      • Vaz M.
      Protein and amino acid requirements in the elderly.
      • Morse M.H.
      • Haub M.D.
      • Evans W.J.
      • Campbell W.W.
      Protein requirement of elderly women: Nitrogen balance responses to three levels of protein intake.
      • Chernoff R.
      Protein and older adults.
      • Morley J.E.
      • Argiles J.M.
      • Evans W.J.
      • et al.
      Nutritional recommendations for the management of sarcopenia.
      The need for more dietary protein is in part because of a declining anabolic response to protein intake in older people; more protein is also needed to offset inflammatory and catabolic conditions associated with chronic and acute diseases that occur commonly with aging.
      • Walrand S.
      • Guillet C.
      • Salles J.
      • et al.
      Physiopathological mechanism of sarcopenia.
      In addition, older adults often consume less protein than do young adults.
      • Rousset S.
      • Patureau Mirand P.
      • Brandolini M.
      • et al.
      Daily protein intakes and eating patterns in young and elderly French.
      • Fulgoni 3rd, V.L.
      Current protein intake in America: Analysis of the National Health and Nutrition Examination Survey, 2003–2004.
      • Vikstedt T.
      • Suominen M.H.
      • Joki A.
      • et al.
      Nutritional status, energy, protein, and micronutrient intake of older service house residents.
      A shortfall of protein supplies relative to needs can lead to loss of lean body mass, particularly muscle loss.
      • Houston D.K.
      • Nicklas B.J.
      • Ding J.
      • et al.
      Dietary protein intake is associated with lean mass change in older, community-dwelling adults: The Health, Aging, and Body Composition (Health ABC) Study.
      As a result, older people are at considerably higher risk for conditions such as sarcopenia and osteoporosis than are young people.
      • Cederholm T.E.
      • Bauer J.M.
      • Boirie Y.
      • et al.
      Toward a definition of sarcopenia.
      • Cruz-Jentoft A.J.
      • Baeyens J.P.
      • Bauer J.M.
      • et al.
      Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People.
      • De Souza Genaro P.
      • Martini L.A.
      Effect of protein intake on bone and muscle mass in the elderly.
      In turn, sarcopenia and osteoporosis can take a high personal toll on older people: falls and fractures, disabilities, loss of independence, and death.
      • Clegg A.
      • Young J.
      • Iliffe S.
      • et al.
      Frailty in elderly people.
      • Cruz-Jentoft A.J.
      • Baeyens J.P.
      • Bauer J.M.
      • et al.
      Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People.
      • De Souza Genaro P.
      • Martini L.A.
      Effect of protein intake on bone and muscle mass in the elderly.
      • Landi F.
      • Cruz-Jentoft A.J.
      • Liperoti R.
      • et al.
      Sarcopenia and mortality risk in frail older persons aged 80 years and older: Results from ilSIRENTE study.
      These conditions also increase financial costs to the health care system because of the extra care that is needed.
      • Janssen I.
      • Shepard D.S.
      • Katzmarzyk P.T.
      • Roubenoff R.
      The healthcare costs of sarcopenia in the United States.
      With the goal of developing updated evidence-based recommendations for optimal protein intake by older people, the European Union Geriatric Medicine Society (EUGMS), in cooperation with other scientific organizations, appointed an International Study Group led by Jürgen Bauer and Yves Boirie, and including 11 other members, to review dietary protein needs with aging (PROT-AGE Study Group). Expert participants from around the world were selected to represent a wide range of clinical and research specialties: geriatric medicine, internal medicine, endocrinology, nutrition, exercise physiology, gastroenterology, and renal medicine. This PROT-AGE Study Group reviewed evidence in the following 5 areas:
      • 1.
        Protein needs for older people in good health;
      • 2.
        Protein needs for older people with specific acute or chronic diseases;
      • 3.
        Role of exercise along with dietary protein for recovering and maintaining muscle strength and function in older people;
      • 4.
        Practical aspects of providing dietary protein (ie, source and quality of dietary proteins, timing of protein intake, and intake of protein-sparing energy);
      • 5.
        Use of functional outcomes to assess the impact of age- and disease-related muscle loss and the effects of interventions.

      PROT-AGE Methods

      The PROT-AGE Study Group first met in July 2012, followed by numerous e-mail contacts. The group followed a Delphi-like process for consensus decision making: structured discussions, evidence-based reasoning, and iterative steps toward agreement. The PROT-AGE Study Group represented the EUGMS, the International Association of Gerontology and Geriatrics (IAGG), the International Academy on Nutrition and Aging (IANA), and the Australian and New Zealand Society for Geriatric Medicine (ANZSGM). The recommendations developed by the PROT-AGE Study Group and represented here have been reviewed and endorsed by these participating organizations.

      Recommended Protein Intake for Healthy Older People: Current Recommendations and Evolving Evidence

        PROT-AGE recommendations for dietary protein intake in healthy older adults

      • To maintain and regain muscle, older people need more dietary protein than do younger people; older people should consume an average daily intake in the range of 1.0 to 1.2 g/kg BW/d.
      • The per-meal anabolic threshold of dietary protein/amino acid intake is higher in older individuals (ie, 25 to 30 g protein per meal, containing about 2.5 to 2.8 g leucine) in comparison with young adults.
      • Protein source, timing of intake, and amino acid supplementation may be considered when making recommendations for dietary protein intake by older adults.
      • More research studies with better methodologies are desired to fine tune protein needs in older adults.
      Existing guidelines for dietary protein intake specify the same recommended dietary allowance (RDA) for all adults: 0.8 g/kg BW/d.

      World Health Organization. Protein and amino acid requirements in human nutrition: Report of a joint WHO/FAO/UNU expert consultation. Geneva: WHO Press; 2007. Report 935.

      Institute of Medicine
      Dietary Reference Intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids (macronutrients).

      European Food Safety Authority (EFSA). Outcome of a public consultation on the draft scientific opinion on the EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA) on dietary reference values for protein. Parma, Italy: EFSA; 2012.

      In the view of the PROT-AGE working group, this recommendation is too low for older people. Evolving evidence supports the concept that lean body mass can be better maintained if an older person consumes dietary protein at a level higher than the general RDA.
      • Gaffney-Stomberg E.
      • Insogna K.L.
      • Rodriguez N.R.
      • Kerstetter J.E.
      Increasing dietary protein requirements in elderly people for optimal muscle and bone health.
      • Kurpad A.V.
      • Vaz M.
      Protein and amino acid requirements in the elderly.
      • Morse M.H.
      • Haub M.D.
      • Evans W.J.
      • Campbell W.W.
      Protein requirement of elderly women: Nitrogen balance responses to three levels of protein intake.
      • Chernoff R.
      Protein and older adults.
      • Morley J.E.
      • Argiles J.M.
      • Evans W.J.
      • et al.
      Nutritional recommendations for the management of sarcopenia.
      • Houston D.K.
      • Nicklas B.J.
      • Ding J.
      • et al.
      Dietary protein intake is associated with lean mass change in older, community-dwelling adults: The Health, Aging, and Body Composition (Health ABC) Study.
      • Walrand S.
      • Guillet C.
      • Boirie Y.
      Nutrition, protein turnover and muscle mass.
      • Campbell W.W.
      • Trappe T.A.
      • Wolfe R.R.
      • Evans W.J.
      The recommended dietary allowance for protein may not be adequate for older people to maintain skeletal muscle.
      Recent research results also suggest other specific nutritional strategies to promote protein absorption and its efficient use in older people; such strategies deal with protein source, timing of intake, and specific amino acid content or supplementation.
      • Walrand S.
      • Boirie Y.
      Optimizing protein intake in aging.
      • Paddon-Jones D.
      • Rasmussen B.B.
      Dietary protein recommendations and the prevention of sarcopenia.
      • Yang Y.
      • Breen L.
      • Burd N.A.
      • et al.
      Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men.
      • Wall B.T.
      • Hamer H.M.
      • de Lange A.
      • et al.
      Leucine co-ingestion improves post-prandial muscle protein accretion in elderly men.
      • Smith G.I.
      • Atherton P.
      • Reeds D.N.
      • et al.
      Dietary omega-3 fatty acid supplementation increases the rate of muscle protein synthesis in older adults: A randomized controlled trial.
      • Pannemans D.L.
      • Wagenmakers A.J.
      • Westerterp K.R.
      • et al.
      Effect of protein source and quantity on protein metabolism in elderly women.
      • Katsanos C.S.
      • Kobayashi H.
      • Sheffield-Moore M.
      • et al.
      A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly.
      • Jordan L.Y.
      • Melanson E.L.
      • Melby C.L.
      • et al.
      Nitrogen balance in older individuals in energy balance depends on timing of protein intake.
      • Burd N.A.
      • Yang Y.
      • Moore D.R.
      • et al.
      Greater stimulation of myofibrillar protein synthesis with ingestion of whey protein isolate v. micellar casein at rest and after resistance exercise in elderly men.
      • Arnal M.A.
      • Mosoni L.
      • Boirie Y.
      • et al.
      Protein pulse feeding improves protein retention in elderly women.
      The current dietary reference intake (DRI) for protein is based on nitrogen balance studies.
      • Rand W.M.
      • Pellett P.L.
      • Young V.R.
      Meta-analysis of nitrogen balance studies for estimating protein requirements in healthy adults.
      The concept underlying nitrogen balance studies is that protein is the major nitrogen-containing substance in the body. Therefore, gain or loss of nitrogen from the body represents gain or loss of protein; the amount of protein required to maintain nitrogen balance reflects the amount of protein required for optimal health.

      World Health Organization. Protein and amino acid requirements in human nutrition: Report of a joint WHO/FAO/UNU expert consultation. Geneva: WHO Press; 2007. Report 935.

      A nitrogen-balance study uses careful documentation of nitrogen intake, a diet adjustment period of 5+ days for individuals for each test level of intake, and a precise accounting of all nitrogen excreted. There are several limitations to nitrogen-balance studies, including the difficulty of quantifying all routes of nitrogen intake and loss, and the practical challenge of managing research studies with extended adaptation times; such limitations are likely to result in underestimation of protein requirements.
      • Gaffney-Stomberg E.
      • Insogna K.L.
      • Rodriguez N.R.
      • Kerstetter J.E.
      Increasing dietary protein requirements in elderly people for optimal muscle and bone health.
      In addition, a neutral nitrogen balance may not reflect subtle changes in protein redistribution (eg, shifts between muscle and splanchnic tissues in older subjects).
      • Boirie Y.
      • Gachon P.
      • Beaufrere B.
      Splanchnic and whole-body leucine kinetics in young and elderly men.
      Moreover, given the relatively slower rate of protein turnover in muscle, it is unlikely that significant changes in muscle mass, particularly in older persons, could be detected in short-term balance studies. These limitations underscore the challenges of determining protein intake requirements for all adults, as well as the difficulty in differentiating needs for men versus women or for older adults versus younger adults.
      • Rand W.M.
      • Pellett P.L.
      • Young V.R.
      Meta-analysis of nitrogen balance studies for estimating protein requirements in healthy adults.
      Although other methods, including carbon balance
      • Waterlow J.C.
      Lysine turnover in man measured by intravenous infusion of L-[U-14C]lysine.
      and amino acid indicator studies,
      • Brunton J.A.
      • Ball R.O.
      • Pencharz P.B.
      Determination of amino acid requirements by indicator amino acid oxidation: Applications in health and disease.
      • Kurpad A.V.
      • El-Khoury A.E.
      • Beaumier L.
      • et al.
      An initial assessment, using 24-h [13C]leucine kinetics, of the lysine requirement of healthy adult Indian subjects.
      • Kurpad A.V.
      • Regan M.M.
      • Varalakshmi S.
      • et al.
      Daily methionine requirements of healthy Indian men, measured by a 24-h indicator amino acid oxidation and balance technique.
      have been used to estimate protein requirements, they are still not currently considered as robust as the nitrogen balance method.

      World Health Organization. Protein and amino acid requirements in human nutrition: Report of a joint WHO/FAO/UNU expert consultation. Geneva: WHO Press; 2007. Report 935.

      Protein Intake and Utilization Affect Functionality in Older Adults

      Determining the appropriate protein intake for older adults is important because inadequate intake contributes to increased risk for common age-associated problems, such as sarcopenia, osteoporosis, and impaired immune responses.
      • Cederholm T.E.
      • Bauer J.M.
      • Boirie Y.
      • et al.
      Toward a definition of sarcopenia.
      • Cruz-Jentoft A.J.
      • Baeyens J.P.
      • Bauer J.M.
      • et al.
      Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People.
      • De Souza Genaro P.
      • Martini L.A.
      Effect of protein intake on bone and muscle mass in the elderly.
      • Castaneda C.
      • Dolnikowski G.G.
      • Dallal G.E.
      • et al.
      Protein turnover and energy metabolism of elderly women fed a low-protein diet.
      The following 3 factors variously influence protein use in older individuals: inadequate intake of protein (eg, anorexia or appetite loss, gastrointestinal disturbances), reduced ability to use available protein (eg, insulin resistance, protein anabolic resistance, high splanchnic extraction, immobility), or a greater need for protein (eg, inflammatory disease, increased oxidative modification of proteins), all of which point to a need to understand the role of dietary protein in maintaining functionality in older people (Figure 1).
      Figure thumbnail gr1
      Fig. 1Aging-related causes of protein shortfall. Such protein deficits have adverse consequences, including impairment of muscular, skeletal, and immune function.

      Benefits of Higher Protein Intake for Older Adults

      Epidemiological studies and clinical trials support the need for higher protein intake by older adults. Several epidemiological studies have found a positive correlation between higher dietary protein intake and higher bone mass density
      • Promislow J.H.
      • Goodman-Gruen D.
      • Slymen D.J.
      • Barrett-Connor E.
      Protein consumption and bone mineral density in the elderly: The Rancho Bernardo Study.
      • Kerstetter J.E.
      • Looker A.C.
      • Insogna K.L.
      Low dietary protein and low bone density.
      • Rapuri P.B.
      • Gallagher J.C.
      • Haynatzka V.
      Protein intake: Effects on bone mineral density and the rate of bone loss in elderly women.
      ; slower rate of bone loss
      • Hannan M.T.
      • Tucker K.L.
      • Dawson-Hughes B.
      • et al.
      Effect of dietary protein on bone loss in elderly men and women: The Framingham Osteoporosis Study.
      ; and muscle mass and strength.
      • Scott D.
      • Blizzard L.
      • Fell J.
      • et al.
      Associations between dietary nutrient intake and muscle mass and strength in community-dwelling older adults: The Tasmanian Older Adult Cohort Study.
      One epidemiological study showed a positive association between higher dietary protein intake and fewer health problems in older women.
      • Vellas B.J.
      • Hunt W.C.
      • Romero L.J.
      • et al.
      Changes in nutritional status and patterns of morbidity among free-living elderly persons: A 10-year longitudinal study.
      With data from the Health, Aging, and Body Composition (Health ABC) Study, Houston et al
      • Houston D.K.
      • Nicklas B.J.
      • Ding J.
      • et al.
      Dietary protein intake is associated with lean mass change in older, community-dwelling adults: The Health, Aging, and Body Composition (Health ABC) Study.
      were able to assess the association between dietary protein intake and changes in lean body mass (LBM) over a 3-year period in healthy, older adults (n = 2066). In this study, dietary protein intake was assessed by using a food-frequency questionnaire; changes in LBM were measured using dual-energy x-ray absorptiometry (DEXA). After adjustment for potential confounders (eg, demographic characteristics, smoking status, alcohol consumption, physical activity), energy-adjusted protein intake was associated with 3-year changes in LBM (P = .004); participants in the highest quintile of protein intake lost approximately 40% less LBM than did those in the lowest quintile of protein intake. These results remained significant even after adjustment for changes in fat mass. Although causality cannot be established, these results do suggest a close relationship between higher protein intake and maintenance of skeletal muscle mass in older adults.
      Several short-term metabolic studies investigated the differences in protein synthesis and breakdown (both whole-body and skeletal muscle) between younger and older adults.
      • Volpi E.
      • Mittendorfer B.
      • Wolf S.E.
      • Wolfe R.R.
      Oral amino acids stimulate muscle protein anabolism in the elderly despite higher first-pass splanchnic extraction.
      • Guillet C.
      • Prod'homme M.
      • Balage M.
      • et al.
      Impaired anabolic response of muscle protein synthesis is associated with S6K1 dysregulation in elderly humans.
      • Dangin M.
      • Guillet C.
      • Garcia-Rodenas C.
      • et al.
      The rate of protein digestion affects protein gain differently during aging in humans.
      Given the complex nature of the aging process,
      • Cesari M.
      • Vellas B.
      • Gambassi G.
      The stress of aging.
      it is not surprising that the combined results of these studies are inconclusive, and sometimes contradictory, for the fasted state. In the fed state, however, most researchers now agree that there is an impairment of the muscle protein anabolic response to meal intake in older adults,
      • Guillet C.
      • Prod'homme M.
      • Balage M.
      • et al.
      Impaired anabolic response of muscle protein synthesis is associated with S6K1 dysregulation in elderly humans.
      • Volpi E.
      • Mittendorfer B.
      • Rasmussen B.B.
      • Wolfe R.R.
      The response of muscle protein anabolism to combined hyperaminoacidemia and glucose-induced hyperinsulinemia is impaired in the elderly.
      • Paddon-Jones D.
      • Van Loon L.J.
      Nutritional approaches to treating sarcopenia.
      although some studies found no difference between older and younger adults, especially when high amounts of amino acids or proteins were administered. Abnormal muscle protein anabolism may result from inadequate nutritional intake (lower anabolic signal) or from impaired response to nutrients and hormones (lower sensitivity), that is, anabolic resistance.
      • Walrand S.
      • Guillet C.
      • Salles J.
      • et al.
      Physiopathological mechanism of sarcopenia.
      For such anabolic resistance, several new strategies aim to improve postprandial anabolic signaling or sensitivity to nutrients. These include providing sufficient protein/amino acid intake to maximize muscle protein anabolism and/or using exercise to improve sensitivity to nutrients and hormones (particularly insulin).
      • Timmerman K.L.
      • Dhanani S.
      • Glynn E.L.
      • et al.
      A moderate acute increase in physical activity enhances nutritive flow and the muscle protein anabolic response to mixed nutrient intake in older adults.
      • Fujita S.
      • Rasmussen B.B.
      • Cadenas J.G.
      • et al.
      Aerobic exercise overcomes the age-related insulin resistance of muscle protein metabolism by improving endothelial function and Akt/mammalian target of rapamycin signaling.
      • Cermak N.M.
      • Res P.T.
      • de Groot L.C.
      • et al.
      Protein supplementation augments the adaptive response of skeletal muscle to resistance-type exercise training: A meta-analysis.
      Additionally, supplementation of anabolic nutrients, such as specific amino acids (eg, leucine), different distribution of the protein intake over the daily meals, or selection of proteins with different digestion profiles (“slow” and “fast” proteins concept), are new strategies. These innovative strategies, especially those combining nutritional and physical preventive strategies, are discussed later in this article.
      Longer-term protein intake studies in older adults are scarce. In one intervention study of intermediate length, Campbell et al
      • Campbell W.W.
      • Trappe T.A.
      • Wolfe R.R.
      • Evans W.J.
      The recommended dietary allowance for protein may not be adequate for older people to maintain skeletal muscle.
      found that consuming the RDA for protein resulted in the loss of mid-thigh muscle area over a 14-week period in healthy older adults (n = 10). Although whole body composition (% body fat, fat-free mass, and protein + mineral mass) and weight did not change over the course of the intervention, mid-thigh muscle area was significantly decreased (P = .019), suggesting that metabolic adaptation may have occurred and the RDA for protein was not adequate to meet the metabolic and physiological needs of these individuals. These findings highlight how changes in muscle tissue are not always reflected at the whole-body level.
      Concerns are frequently raised regarding the impact of high-protein diets on renal function, particularly in older persons. However, reviews of research studies reveal little or no evidence that high-protein diets cause kidney damage in healthy individuals, including those who are older.
      • Gaffney-Stomberg E.
      • Insogna K.L.
      • Rodriguez N.R.
      • Kerstetter J.E.
      Increasing dietary protein requirements in elderly people for optimal muscle and bone health.
      • Surdykowski A.K.
      • Kenny A.M.
      • Insogna K.L.
      • Kerstetter J.E.
      Optimizing bone health in older adults: The importance of dietary protein.
      • Martin W.F.
      • Armstrong L.E.
      • Rodriguez N.R.
      Dietary protein intake and renal function.
      Given the available data, a recommendation of protein intake at 1.0 to 1.2 g/kg BW/d is expected to help maintain nitrogen balance without affecting renal function, especially until results of additional studies are available.
      • Gaffney-Stomberg E.
      • Insogna K.L.
      • Rodriguez N.R.
      • Kerstetter J.E.
      Increasing dietary protein requirements in elderly people for optimal muscle and bone health.
      Protein intake recommendations for individuals with kidney disease are presented later in this article.

      Specific Nutritional Strategies to Achieve Optimal Protein Utilization

      Specific feeding strategies represent advancing refinement in our understanding of protein synthesis in older adults. Strategies include feeding to optimize protein digestion and absorption by specifying the type of protein, addition of specific amino acids or fatty acids to enhance protein synthesis, and specifying per-meal protein quantity and timing of intake (Table 1).
      Table 1Some Examples of Nutritional Strategies to Enhance Optimal Protein Synthesis
      StrategyReferenceOutcomes
      Protein source: animal-based vs vegetable-based proteinPannemans 1998
      • Pannemans D.L.
      • Wagenmakers A.J.
      • Westerterp K.R.
      • et al.
      Effect of protein source and quantity on protein metabolism in elderly women.
      Net protein synthesis was lower with a high vegetable-protein diet than with a high animal-protein diet.
      Luiking 2011
      • Luiking Y.C.
      • Engelen M.P.
      • Soeters P.B.
      • et al.
      Differential metabolic effects of casein and soy protein meals on skeletal muscle in healthy volunteers.
      Moderate-nitrogen casein and soy protein meals affected leg amino acid uptake differently but without significant differences in acute muscle protein metabolism.
      Protein source: whey vs caseinBoirie 1997
      • Boirie Y.
      • Dangin M.
      • Gachon P.
      • et al.
      Slow and fast dietary proteins differently modulate postprandial protein accretion.
      The speed of protein digestion and amino acid absorption from the gut had a major effect on whole body protein anabolism after one single meal. “Slow” and “fast” proteins thus modulate the postprandial metabolic response.
      Dangin 2002
      • Dangin M.
      • Boirie Y.
      • Guillet C.
      • Beaufrere B.
      Influence of the protein digestion rate on protein turnover in young and elderly subjects.
      A “fast” protein was more effective than a “slow” protein for limiting body protein loss in older subjects.
      Pennings 2011
      • Pennings B.
      • Boirie Y.
      • Senden J.M.
      • et al.
      Whey protein stimulates postprandial muscle protein accretion more effectively than do casein and casein hydrolysate in older men.
      Whey protein stimulated postprandial muscle protein accretion more effectively than either casein or casein hydrolysate in older men.
      Protein source & exercise: whey vs caseinBurd 2012
      • Burd N.A.
      • Yang Y.
      • Moore D.R.
      • et al.
      Greater stimulation of myofibrillar protein synthesis with ingestion of whey protein isolate v. micellar casein at rest and after resistance exercise in elderly men.
      Ingestion of isolated whey protein supported greater rates of myofibrillar protein synthesis than micellar casein both at rest and after resistance exercise in healthy older men.
      Protein feeding patternPaddon-Jones 2009
      • Paddon-Jones D.
      • Rasmussen B.B.
      Dietary protein recommendations and the prevention of sarcopenia.
      Review article proposes a dietary plan that includes 25–30 g of high-quality protein per meal (spread feeding) in order to maximize muscle protein synthesis.
      Arnal 1999
      • Arnal M.A.
      • Mosoni L.
      • Boirie Y.
      • et al.
      Protein pulse feeding improves protein retention in elderly women.
      A protein pulse-feeding pattern (most protein at midday) was more efficient than a spread-feeding pattern in improving whole-body protein retention in older women.
      Bouillane 2013
      • Bouillanne O.
      • Curis E.
      • Hamon-Vilcot B.
      • et al.
      Impact of protein pulse feeding on lean mass in malnourished and at-risk hospitalized elderly patients: A randomized controlled trial.
      A protein pulse-feeding pattern (midday) had a positive and greater effect on lean mass in malnourished and at-risk hospitalized elderly patients than a protein spread-feeding pattern.
      Amino acid supplementation: essential amino acidsVolpi 2003
      • Volpi E.
      • Mittendorfer B.
      • Wolf S.E.
      • Wolfe R.R.
      Oral amino acids stimulate muscle protein anabolism in the elderly despite higher first-pass splanchnic extraction.
      Essential amino acids were primarily responsible for the amino acid–induced stimulation of muscle protein anabolism in older adults.
      Amino acid supplementation: leucineWall 2012
      • Wall B.T.
      • Hamer H.M.
      • de Lange A.
      • et al.
      Leucine co-ingestion improves post-prandial muscle protein accretion in elderly men.
      Co-ingestion of leucine with a bolus of pure dietary protein further stimulated postprandial muscle protein synthesis rates in older men.
      Katsanos 2006
      • Katsanos C.S.
      • Kobayashi H.
      • Sheffield-Moore M.
      • et al.
      A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly.
      Increasing the proportion of leucine in a mixture of essential amino acids reversed an attenuated response of muscle protein synthesis in older adults, but did not result in further stimulation of muscle protein synthesis in young subjects.
      Rieu 2006
      • Rieu I.
      • Balage M.
      • Sornet C.
      • et al.
      Leucine supplementation improves muscle protein synthesis in elderly men independently of hyperaminoacidaemia.
      Leucine supplementation during feeding improved muscle protein synthesis in older adults independently of an overall increase of other amino acids. It is not known whether high leucine intake can limit aging-related loss of muscle protein.
      Fatty acid supplementation: omega-3 fatty acid & insulin sensitivity of protein synthesisSmith 2011
      • Smith G.I.
      • Atherton P.
      • Reeds D.N.
      • et al.
      Dietary omega-3 fatty acid supplementation increases the rate of muscle protein synthesis in older adults: A randomized controlled trial.
      Omega-3 fatty acid supplementation augmented the hyperaminoacidemia-hyperinsulinemia–induced increase in the rate of muscle protein synthesis, which was accompanied by greater increases in muscle mTOR (mammalian target of rapamycin) (P = .08) and p70s6k (P < .01) phosphorylation.
      Timing of protein and exerciseJordan 2010
      • Jordan L.Y.
      • Melanson E.L.
      • Melby C.L.
      • et al.
      Nitrogen balance in older individuals in energy balance depends on timing of protein intake.
      Older individuals were better able to maintain nitrogen balance by consuming a high-quality protein source following exercise as opposed to consuming the identical protein several hours before exercise.
      Esmark 2001
      • Esmarck B.
      • Andersen J.L.
      • Olsen S.
      • et al.
      Timing of postexercise protein intake is important for muscle hypertrophy with resistance training in elderly humans.
      Immediate intake of an oral protein supplement after resistance training increased muscle mass as well as dynamic and isokinetic strength in older men, whereas delayed intake improved only dynamic strength.
      Cermak 2012
      • Cermak N.M.
      • Res P.T.
      • de Groot L.C.
      • et al.
      Protein supplementation augments the adaptive response of skeletal muscle to resistance-type exercise training: A meta-analysis.
      Protein supplementation increases muscle mass and strength gains during prolonged resistance-type exercise training in both younger and older subjects
      For timing and amount of intake, older individuals appear to have a higher per-meal protein threshold to promote anabolism (ie, 25 to 30 g protein per meal containing about 2.5 to 2.8 g leucine).
      • Paddon-Jones D.
      • Van Loon L.J.
      Nutritional approaches to treating sarcopenia.
      This evidence suggests benefits to even distribution of protein at breakfast, lunch, and supper; however, recent studies have also shown anabolic benefits from pulse feeding (ie, a main high-protein meal, usually at midday).
      • Bouillanne O.
      • Curis E.
      • Hamon-Vilcot B.
      • et al.
      Impact of protein pulse feeding on lean mass in malnourished and at-risk hospitalized elderly patients: A randomized controlled trial.
      • Deutz N.E.
      • Wolfe R.R.
      Is there a maximal anabolic response to protein intake with a meal?.
      Additional clinical studies are needed to determine whether both feeding patterns are effective or whether one is clearly favored over the other. Such strategies should be tested in both long- and short-term clinical interventions.

      Specific Recommendations on Dietary Protein Intake by Healthy Older People

      Current guidelines for protein intake in older adults are identical to those for younger adults. In particular, the most commonly used benchmark for dietary recommendations, the RDA, is defined by the minimum amount of daily protein necessary to prevent deficiency in 97% of the population. However, present recommendations (0.8 g/kg BW/d), are based on adult studies and do not take into account the many body changes that occur with aging, so they may not be adequate to maintain, or help regain, muscle mass in the older population. Although longer-term studies are needed, research to date supports increasing this recommendation from the current 0.8 g/kg BW/d to a range of at least 1.0 to 1.2 g/kg BW/d (Table 2). Although this change represents a significant increase, this value, which is approximately 13% to 16% of total calories, is still well within the acceptable macronutrient distribution range (AMDR) for protein (10%–35% of total daily calories) according to the Institute of Medicine.
      • Gaffney-Stomberg E.
      • Insogna K.L.
      • Rodriguez N.R.
      • Kerstetter J.E.
      Increasing dietary protein requirements in elderly people for optimal muscle and bone health.
      Table 2Summary of Recommendations for Dietary Protein Intake in Healthy Older Adults
      ReferenceRecommendationAuthors’ Comment
      Paddon-Jones 2012
      • Paddon-Jones D.
      • Van Loon L.J.
      Nutritional approaches to treating sarcopenia.
      1.0–1.3 g/kg BW/d… we argue that while a modest increase in dietary protein beyond the RDA may be beneficial for some older adults (perhaps 1.0–1.3 g/kg per day), there is a greater need to specifically examine the quality and quantity of protein consumed with each meal.
      Wolfe 2012
      • Wolfe R.R.
      The role of dietary protein in optimizing muscle mass, function and health outcomes in older individuals.
      >0.8 g/kg BW/d, but no specific value givenSince there is no evidence that a reasonable increase in dietary intake adversely affects health outcomes, and deductive reasoning suggests beneficial effects of a higher protein intake, it is logical to recommend that the optimal dietary protein intake for older individuals is greater than the recommend dietary allowance of 0.8 g protein/kg/d.
      Volpi 2012
      • Volpi E.
      • Campbell W.W.
      • Dwyer J.T.
      • et al.
      Is the optimal level of protein intake for older adults greater than the recommended dietary allowance?.
      >0.8 g/kg BW/d, but no specific value givenAlthough the RDA of protein is probably sufficient for most sedentary or low-active adults to avoid protein inadequacy, it may not provide a measure of optimal intake to maintain health and maximize function in older adults. Avoidance of net nitrogen losses may be an inadequate outcome for older sarcopenic individuals, for whom net lean mass gains are desirable.
      Morley 2010
      • Morley J.E.
      • Argiles J.M.
      • Evans W.J.
      • et al.
      Nutritional recommendations for the management of sarcopenia.
      1.0–1.5 g/kg BW/dAs 15% to 38% of older men and 27%–41% of older women ingest less than the recommended daily allowance for protein, it is suggested that protein intake be increased.
      Gaffney-Stomberg 2009
      • Gaffney-Stomberg E.
      • Insogna K.L.
      • Rodriguez N.R.
      • Kerstetter J.E.
      Increasing dietary protein requirements in elderly people for optimal muscle and bone health.
      1.0–1.2 g/kg BW/dGiven the available data, increasing the RDA to 1.0 to 1.2 g/kg per day (or approximately 13%–16% of total calories) would maintain normal calcium metabolism and nitrogen balance without affecting renal function and still be well within the acceptable range according to the IOM.
      Institute of Medicine
      Dietary Reference Intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids (macronutrients).
      Therefore, increasing the RDA to 1.0 to 1.2 g/kg per day for elderly people may represent a compromise while longer term protein supplement trials are still pending.
      Morais 2006
      • Morais J.A.
      • Chevalier S.
      • Gougeon R.
      Protein turnover and requirements in the healthy and frail elderly.
      1.0–1.3 g/kg BW/dData from published nitrogen balance studies indicate that a higher protein intake of 1.0–1.3 g/k/d is required to maintain nitrogen balance in the healthy elderly, which may be explained by their lower energy intake and impaired insulin action during feeding compared with young persons.

      Protein Recommendations in Acute and Chronic Diseases

        PROT-AGE recommendations for protein levels in geriatric patients with specific acute or chronic diseases

      • The amount of additional dietary protein or supplemental protein needed depends on the disease, its severity, the patient’s nutritional status prior to disease, as well as the disease impact on the patient’s nutritional status.
      • Most older adults who have an acute or chronic disease need more dietary protein (ie, 1.2–1.5 g/kg BW/d); people with severe illness or injury or with marked malnutrition may need as much as 2.0 g/kg BW/d.
      • Older people with severe kidney disease (ie, estimated glomerular filtration rate [GFR] < 30 mL/min/1.73m2) who are not on dialysis are an exception to the high-protein rule; these individuals need to limit protein intake.

      Protein Needs and Recommendations in Older Populations With Disease or Injury

      Many healthy older adults fail to eat enough dietary protein, but the situation is worsened when they are sick or disabled. When older adults have acute or chronic diseases, their activities are more limited, they are less likely to consume adequate food, and they fall farther behind in energy and protein intake.
      • Covinsky K.E.
      • Martin G.E.
      • Beyth R.J.
      • et al.
      The relationship between clinical assessments of nutritional status and adverse outcomes in older hospitalized medical patients.
      • Inzitari M.
      • Doets E.
      • Bartali B.
      • et al.
      Nutrition in the age-related disablement process.
      As a result, malnourished older people recover from illness more slowly, have more complications, and are more frequently admitted to hospitals for longer stays than are healthy older adults.
      • Covinsky K.E.
      • Martin G.E.
      • Beyth R.J.
      • et al.
      The relationship between clinical assessments of nutritional status and adverse outcomes in older hospitalized medical patients.
      • Inzitari M.
      • Doets E.
      • Bartali B.
      • et al.
      Nutrition in the age-related disablement process.
      Most experts agree that when a person has an acute or chronic disease, his or her needs for protein increase. Guidelines for critically ill adults
      • Fürst P.
      • Deutz N.
      • Boirie Y.
      • et al.
      Proteins and amino acids.
      • McClave S.A.
      • Martindale R.G.
      • Vanek V.W.
      • et al.
      Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.).
      • Singer P.
      • Berger M.M.
      • Van den Berghe G.
      • et al.
      ESPEN guidelines on parenteral nutrition: intensive care.
      advise that adequate energy should be provided along with protein for a protein-sparing effect. Energy requirements are preferably determined by indirect calorimetry. When calorimetry is unavailable, an estimation (eg, 25 kcal/kg/d) or appropriate predictive equation taking into account resting energy expenditure plus factors for activity level and stress is recommended.
      The American Society for Parenteral and Enteral Nutrition (ASPEN) standards for critically ill adults call for adjusting both protein and energy level for obese patients.
      • McClave S.A.
      • Martindale R.G.
      • Vanek V.W.
      • et al.
      Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.).
      In the European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines, Weijs et al
      • Weijs P.J.
      • Sauerwein H.P.
      • Kondrup J.
      Protein recommendations in the ICU: g protein/kg body weight—which body weight for underweight and obese patients?.
      propose using “ideal body weight” to more accurately estimate protein requirements for underweight (body mass index [BMI] <20 kg/m2) and obese (BMI >30 kg/m2) patients. Some recommendations are specific to protein, whereas others recommend protein as part of an oral nutrition supplement (ONS) or enteral nutrition formula.
      With increased protein intake, older people may experience improved bone health, cardiovascular function, wound healing, and recovery from illness.
      • Cawood A.L.
      • Elia M.
      • Stratton R.J.
      Systematic review and meta-analysis of the effects of high protein oral nutritional supplements.
      These benefits also have the potential to help older people meet the health challenges of illness. The latest Cochrane update from 2009 indicates that protein-energy supplementation reduces mortality, especially in older, undernourished subjects and in patients with geriatric conditions.
      • Milne A.C.
      • Potter J.
      • Vivanti A.
      • Avenell A.
      Protein and energy supplementation in elderly people at risk from malnutrition.
      Table 3 summarizes studies and recommendations for protein intake in older people who are hospitalized in ward or critical care settings.
      Table 3Summary: Recommendations and Evidence on Dietary Protein Intake in Older Adults With Illness or Other Complicating Medical Conditions
      ReferenceProtein RecommendationDescription
      General
       Cawood 2012
      • Cawood A.L.
      • Elia M.
      • Stratton R.J.
      Systematic review and meta-analysis of the effects of high protein oral nutritional supplements.
      High protein ONS: >20% kcal from protein
      • Meta-analysis of 11 RCTs in community patients aged 65 years and older with hip fracture, leg and pressure ulcers, and acute illness
      • High protein given as part of multinutrient ONS
      • Significant reduction in the incidence of complications
       Gaillard 2008
      • Gaillard C.
      • Alix E.
      • Boirie Y.
      • et al.
      Are elderly hospitalized patients getting enough protein?.
      1.06 ± 0.28 g/kg BW /d (minimum requirement) so that

      1.3-1.6 g/kg/d as safe protein intake
      • Mean safe protein intake needed to reach neutral nitrogen balance in 36 older patients (age 65–99) hospitalized in short-stay geriatric wards and rehabilitation care units
       Morais 2006
      • Morais J.A.
      • Ross R.
      • Gougeon R.
      • et al.
      Distribution of protein turnover changes with age in humans as assessed by whole-body magnetic resonance image analysis to quantify tissue volumes.
      >1.0–1.3 g/kg BW/d
      • Nitrogen balance studies indicate that healthy older people require 1.0–1.3 g/kg BW/d; even higher protein-intake levels may help restore muscle and function for older people who have become frail.
      Critical illness
       Weijs 2012
      • Weijs P.J.
      • Stapel S.N.
      • de Groot S.D.
      • et al.
      Optimal protein and energy nutrition decreases mortality in mechanically ventilated, critically ill patients: A prospective observational cohort study.
      1.2–1.5 g/kg preadmission BW/d
      • Study of 886 critically ill patients with various medical or surgical conditions who required extended mechanical ventilation; average age, 63 ± 16 years
      • 245 patients who reached predefined protein and energy targets experienced nearly a 50% decline in 28-day mortality
       Singer 2009
      • Singer P.
      • Berger M.M.
      • Van den Berghe G.
      • et al.
      ESPEN guidelines on parenteral nutrition: intensive care.


      Fürst 2011
      • Fürst P.
      • Deutz N.
      • Boirie Y.
      • et al.
      Proteins and amino acids.


      All adults
      1.3–1.5 g/kg ideal BW/d
      • ESPEN Guidelines for parenteral nutrition for all adults in intensive care–not specific to older adults
      • Provide energy adequate to meet the patient’s measured expenditure (without indirect calorimetry, use 25 kcal/kg/d)
       McClave 2009
      • McClave S.A.
      • Martindale R.G.
      • Vanek V.W.
      • et al.
      Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.).


      All adults
      1.2–2.0 g/kg BW/d
      • ASPEN Guidelines for patients with BMI <30; may be higher in patients with burns or multiple traumas
      • Provide energy adequate to meet the patient’s measured expenditure (without indirect calorimetry, use predictive equations unless patient is obese)
      • Critically ill obese adult: reduced energy and higher protein is recommended; refer to guideline for details
      ASPEN, American Society for Parenteral and Enteral Nutrition; BMI, body mass index; BW, body weight; ESPEN, European Society for Clinical Nutrition and Metabolism; ONS, oral nutrition supplement; RCT, randomized controlled trial.

      Hospitalized older adults

      Results of a retrospective study of undernourished older people in a Dutch hospital (n = 610) showed that only 28% met protein targets (n = 172).
      • Leistra E.
      • Willeboordse F.
      • van Bokhorst-de van der Schueren M.A.
      • et al.
      Predictors for achieving protein and energy requirements in undernourished hospital patients.
      For the study, subjects were identified by nutrition screening on admittance. Of those screened, 15% were malnourished and included in the study; 40% of patients older than 65 had multiple diseases. Energy targets were determined with the Harris-Benedict equation, then adjusted by +30% for activity or disease; protein targets were 1.2 to 1.7 g protein/kg BW/d.
      In a French study, the sickest patients in a group of older adults in short- or long-stay care settings were found to be the most undernourished, and fell particularly short of protein targets (intake of 0.9 g protein/kg BW/d, compared with 1.5 g/kg BW/d goal). Patients categorized to be at a nutritional “steady state” were able to meet their energy and protein goals (25–30 kcal/kg BW/d and 1.0 g protein/kg BW/d).
      • Perier C.
      • Triouleyre P.
      • Terrat C.
      • et al.
      Energy and nutrient intake of elderly hospitalized patients in a steady metabolic status versus catabolic status.

      Frailty

      The frailty syndrome has a place on the continuum between the normal physiological changes of aging and the final state of disability and death.
      • Clegg A.
      • Young J.
      • Iliffe S.
      • et al.
      Frailty in elderly people.
      • Abellan van Kan G.
      • Rolland Y.M.
      • Morley J.E.
      • Vellas B.
      Frailty: Toward a clinical definition.
      Frailty worsens age-related changes in protein metabolism, further increasing muscle protein catabolism and decreasing muscle mass.
      • Chevalier S.
      • Gougeon R.
      • Nayar K.
      • Morais J.A.
      Frailty amplifies the effects of aging on protein metabolism: Role of protein intake.
      Higher protein consumption has been associated with a dose-responsive lower risk of incident frailty in older women.
      • Beasley J.M.
      • LaCroix A.Z.
      • Neuhouser M.L.
      • et al.
      Protein intake and incident frailty in the Women's Health Initiative observational study.
      Incorporating more protein into the diet is thus a rational strategy for frailty prevention.

      Hip fracture

      Older adults (average age 84) with hip or leg fracture who entered the hospital undernourished did not meet estimated energy or protein targets. Individual energy requirements were estimated by age, gender, activity level, and disease-related metabolic stress; protein requirements were estimated at 1.0 g protein/kg BW/d. With diet alone, patients were able to meet only 50% of energy and 80% of target protein intake.
      • Miller M.D.
      • Bannerman E.
      • Daniels L.A.
      • Crotty M.
      Lower limb fracture, cognitive impairment and risk of subsequent malnutrition: A prospective evaluation of dietary energy and protein intake on an orthopaedic ward.
      Considerable evidence supports the concept that supplemental protein or higher dietary protein intake by older people hospitalized for hip fracture could reduce risk for complications,
      • Milne A.C.
      • Potter J.
      • Vivanti A.
      • Avenell A.
      Protein and energy supplementation in elderly people at risk from malnutrition.
      • Avenell A.
      • Handoll H.H.
      Nutritional supplementation for hip fracture aftercare in older people.
      • Botella-Carretero J.I.
      • Iglesias B.
      • Balsa J.A.
      • et al.
      Perioperative oral nutritional supplements in normally or mildly undernourished geriatric patients submitted to surgery for hip fracture: a randomized clinical trial.
      improve bone mineral density,
      • Schurch M.A.
      • Rizzoli R.
      • Slosman D.
      • et al.
      Protein supplements increase serum insulin-like growth factor-I levels and attenuate proximal femur bone loss in patients with recent hip fracture. A randomized, double-blind, placebo-controlled trial.
      • Tengstrand B.
      • Cederholm T.
      • Soderqvist A.
      • Tidermark J.
      Effects of protein-rich supplementation and nandrolone on bone tissue after a hip fracture.
      and reduce rehabilitation time (Table 4).
      • Schurch M.A.
      • Rizzoli R.
      • Slosman D.
      • et al.
      Protein supplements increase serum insulin-like growth factor-I levels and attenuate proximal femur bone loss in patients with recent hip fracture. A randomized, double-blind, placebo-controlled trial.
      Table 4Summary: Recommendations and Evidence on Dietary Protein Intake by Older People With Hip Fracture or Osteoporosis
      ReferenceProtein RecommendationDescription
      Hip fracture
       Avenell 2010
      • Avenell A.
      • Handoll H.H.
      Nutritional supplementation for hip fracture aftercare in older people.
      Not specified
      • Review of patients recovering from hip fracture; most were > 65 years old
      • Based on 4 studies addressing protein intake, protein supplementation may reduce the number of long-term complications
       Botello-Carretero 2010
      • Botella-Carretero J.I.
      • Iglesias B.
      • Balsa J.A.
      • et al.
      Perioperative oral nutritional supplements in normally or mildly undernourished geriatric patients submitted to surgery for hip fracture: a randomized clinical trial.
      1.4 g/kg BW/d compared to

      1.0 g/kg BW/d
      • RCT of 60 normal or mildly undernourished older patients (age 85.0 ± 4.4 years) undergoing surgery for hip fracture
      • High protein given perioperatively as part of multinutrient ONS
      • Tendency for fewer complications in the supplemented group
       Milne 2009
      • Milne A.C.
      • Potter J.
      • Vivanti A.
      • Avenell A.
      Protein and energy supplementation in elderly people at risk from malnutrition.
      Not specified
      • Review of 62 trials of protein-energy supplementation in older people (≥ 65 years old)
      • 24 studies looked at morbidity; meta-analysis found there may be a reduced risk of complications with supplementation for hip fracture patients (RR 0.60; 95% CI 0.40 to 0.91)
       Tengstrand 2007
      • Tengstrand B.
      • Cederholm T.
      • Soderqvist A.
      • Tidermark J.
      Effects of protein-rich supplementation and nandrolone on bone tissue after a hip fracture.
      20 g extra/d
      • RCT for 6 months in lean women after hip fracture showing improved BMD with protein supplementation
       Schurch 1998
      • Schurch M.A.
      • Rizzoli R.
      • Slosman D.
      • et al.
      Protein supplements increase serum insulin-like growth factor-I levels and attenuate proximal femur bone loss in patients with recent hip fracture. A randomized, double-blind, placebo-controlled trial.
      20 g extra/d
      • RCT with 82 patients with recent hip fracture, 20 g proteins day for 6 months increased IGF-1, decreased loss of BMD and reduced hospital stay.
      Osteoporosis
       Darling 2009
      • Darling A.L.
      • Millward D.J.
      • Torgerson D.J.
      • et al.
      Dietary protein and bone health: A systematic review and meta-analysis.
      Not specified
      • A systematic review indicating a small positive effect of protein supplementation on lumbar spine BMD
       Meng 2009
      • Meng X.
      • Zhu K.
      • Devine A.
      • et al.
      A 5-year cohort study of the effects of high protein intake on lean mass and BMC in elderly postmenopausal women.
      1.6 g/kg BW/d vs 0.85 g/kg BW/d
      • 5-year prospective cohort study showing higher BMD with higher protein intake
       Devine 2005
      • Devine A.
      • Dick I.M.
      • Islam A.F.
      • et al.
      Protein consumption is an important predictor of lower limb bone mass in elderly women.
      >0.84 g/kg BW/d vs <0.84 g/kg BW/d
      • 1- year prospective cohort study showing higher BMD with higher protein intake
       Dawson-Hughes 2004
      • Dawson-Hughes B.
      • Harris S.S.
      • Rasmussen H.
      • et al.
      Effect of dietary protein supplements on calcium excretion in healthy older men and women.
      High protein diet (24% of energy) vs low protein diet (16% of energy)
      • RCT in 32 old subjects for 9 weeks, BMD increased in the higher protein group
      BMD, bone mass density; BW, body weight; CI, confidence interval; IGF-1, insulin-like growth factor 1; ONS, oral nutrition supplement; RCT, randomized controlled trial; RR, relative risk.

      Osteoporosis

      In older people with osteoporosis, findings from a systematic review,
      • Darling A.L.
      • Millward D.J.
      • Torgerson D.J.
      • et al.
      Dietary protein and bone health: A systematic review and meta-analysis.
      several prospective cohort studies,
      • Devine A.
      • Dick I.M.
      • Islam A.F.
      • et al.
      Protein consumption is an important predictor of lower limb bone mass in elderly women.
      • Meng X.
      • Zhu K.
      • Devine A.
      • et al.
      A 5-year cohort study of the effects of high protein intake on lean mass and BMC in elderly postmenopausal women.
      and a randomized, controlled trial
      • Dawson-Hughes B.
      • Harris S.S.
      • Rasmussen H.
      • et al.
      Effect of dietary protein supplements on calcium excretion in healthy older men and women.
      (RCT) all found higher bone mineral density when protein intake was at levels higher than 0.8 g/kg BW/d or was 24% of total energy intake (Table 4).

      Stroke

      In patients with stroke (69.0 ± 11.3 years), Foley et al
      • Foley N.
      • Finestone H.
      • Woodbury M.G.
      • et al.
      Energy and protein intakes of acute stroke patients.
      found that the actual intake failed to meet energy or protein targets, reaching just 80% to 90% of either target in the first 21 days of hospitalization. Energy targets were set using measured energy expenditure (plus 10% for bedridden or 20%–40% for ambulatory patients); protein targets were 1.0 g/kg BW/d, above the healthy adult level to allow for the additional physiological demands of stroke. Enterally fed patients in the study, unlike patients on regular or dysphagia diets, were able to meet or exceed energy or protein goals at some of the 5 evaluation points.

      Pressure ulcer

      Results of an observational study in a small group of older patients (71 ± 10 years) hospitalized for surgical repair of chronic pressure ulcers, showed that intake from normal hospital meals covered only 76% of patients’ energy requirements. Oral nutrition supplements were necessary to achieve both energy and protein requirements.
      • Raffoul W.
      • Far M.S.
      • Cayeux M.C.
      • Berger M.M.
      Nutritional status and food intake in nine patients with chronic low-limb ulcers and pressure ulcers: Importance of oral supplements.
      A report from Health Quality Ontario (2009) indicated that protein supplementation improved healing score when compared with a placebo.
      Health Quality Ontario
      Management of chronic pressure ulcers: An evidence-based analysis.
      A Japanese cross-sectional nitrogen balance survey of older adults with pressure ulcers (n = 28) found that the average daily protein requirement for these subjects to achieve nitrogen balance was 0.95 g/kg BW/d, but protein requirements varied according to an individual’s condition and wound severity and ranged from 0.75 to 1.30 g/kg BW/d.
      • Iizaka S.
      • Matsuo J.
      • Konya C.
      • et al.
      Estimation of protein requirements according to nitrogen balance for older hospitalized adults with pressure ulcers according to wound severity in Japan.

      Chronic obstructive pulmonary disease

      Chronic obstructive pulmonary disease (COPD) presents multiple nutritional challenges. People with COPD have a need for greater supplies of energy and protein to meet higher energy expenditure, in part from the increased work of breathing and the inflammatory process of the disease, and, when also insulin-resistant, decreased protein anabolism.
      • Aniwidyaningsih W.
      • Varraso R.
      • Cano N.
      • Pison C.
      Impact of nutritional status on body functioning in chronic obstructive pulmonary disease and how to intervene.
      • King D.A.
      • Cordova F.
      • Scharf S.M.
      Nutritional aspects of chronic obstructive pulmonary disease.
      In the face of these challenges, patients with COPD are generally underweight, and several studies show they have a lower fat-free mass than healthy people.
      • Aniwidyaningsih W.
      • Varraso R.
      • Cano N.
      • Pison C.
      Impact of nutritional status on body functioning in chronic obstructive pulmonary disease and how to intervene.
      Aniwidyaningsih and colleagues
      • Aniwidyaningsih W.
      • Varraso R.
      • Cano N.
      • Pison C.
      Impact of nutritional status on body functioning in chronic obstructive pulmonary disease and how to intervene.
      recommended high-protein ONS with 20% kcal from protein. However, evidence is limited, so further studies are necessary, especially in older people with COPD.

      Cardiac disease

      Guidelines from Spain recommended protein intake at 1.2 to 1.5 g/kg ideal BW/d for all adult critically ill patients with cardiac disease who are hemodynamically stable.
      • Jimenez Jimenez F.J.
      • Cervera Montes M.
      • Blesa Malpica A.L.
      Guidelines for specialized nutritional and metabolic support in the critically-ill patient: Update. Consensus SEMICYUC-SENPE: Cardiac patient.
      They also recommended adequate energy, 20 to 25 kcal/kg/d.
      In addition, Aquilani et al
      • Aquilani R.
      • Viglio S.
      • Iadarola P.
      • et al.
      Oral amino acid supplements improve exercise capacities in elderly patients with chronic heart failure.
      found that cardiac patients given supplemental amino acids had improved exercise capacity and shortened postexercise recovery time. The RCT involved 95 community-living patients with chronic heart failure (74 ± 5 years) who received supplemental amino acids twice a day (8 g amino acids per day) for 30 days along with standard pharmacologic therapy.

      Diabetes

      For older people with diabetes, dietary recommendations, including protein recommendations, depend on the individual’s nutritional status, as well as on comorbid conditions. However, diabetes is associated with a faster loss of muscle strength and a higher rate of disability. An older person with diabetes and sarcopenic obesity may benefit from increased dietary protein intake, whereas someone with diabetes and severe kidney nephropathy may need to follow a protein-restricted diet. In developed countries, diabetes is the leading cause of chronic kidney disease, and in the United States, accounts for nearly half of all kidney failure.
      KDOQI
      KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease.
      Recent guidelines from the American Geriatrics Society stress the importance of an individualized treatment approach for diabetic adults who are frail or have multiple comorbid conditions.
      • Kirkman M.S.
      • Briscoe V.J.
      • Clark N.
      • et al.
      Diabetes in older adults.
      Table 5 summarizes protein recommendations and study results for older people with diabetes.
      Table 5Summary: Recommendations and Evidence Supporting Dietary Protein Intake in Older Adults With Diabetes
      ReferenceProtein RecommendationDescription
      Diabetes without nephropathy
       Larsen 2011
      • Lacson Jr., E.
      • Wang W.
      • Zebrowski B.
      • et al.
      Outcomes associated with intradialytic oral nutritional supplements in patients undergoing maintenance hemodialysis: A quality improvement report.
      High-protein diet (30% of kcal from protein)
      • RCT of 99 older adults (≥60 years old) with type 2 diabetes, HbA1c 7.9%
      • Those who ate a diet with about 30% of kcal from protein required 8% fewer diabetes medications (primarily insulin and sulfonylurea therapies) after 1 year, compared to baseline medication levels
      Diabetes with nephropathy
       Robertson 2007
      • Robertson L.
      • Waugh N.
      • Robertson A.
      Protein restriction for diabetic renal disease.
      Low-protein diet

      (0.8 g/kg BW/d)
      • Systematic review of low protein diets in adults with Type 1 or 2 diabetes and diabetic nephropathy (few were ≥65 years).
      • Results of 7 studies of Type 1 diabetes were combined in a meta-analysis; a low protein diet appears to slow the progression of diabetic nephropathy, but not significantly
      • 4 studies of Type 2 diabetes noted small but nonsignificant reductions in the rate of kidney function decline in 3 of them
      RCT, randomized controlled trial.

      Diabetes without kidney disease

      The American Diabetes Association recommends normal protein intake (15%–20% of daily energy) as long as kidney function is normal. Not enough is known about the effect of high-protein diets (>20% of daily energy) to evaluate their safety.
      American Diabetes Association
      Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications.
      However, a recent study of older patients (upper age limit: 75 years) with moderate Type 2 diabetes (HbA1c about 7.9%) but no kidney disease, showed that those who ate a high-protein diet (about 30% kcal from protein) tended to require fewer glucose-lowering medications after 1 year, compared with their baseline medication levels.
      • Larsen R.N.
      • Mann N.J.
      • Maclean E.
      • Shaw J.E.
      The effect of high-protein, low-carbohydrate diets in the treatment of type 2 diabetes: A 12 month randomised controlled trial.

      Diabetes with kidney disease

      Robertson et al
      • Robertson L.
      • Waugh N.
      • Robertson A.
      Protein restriction for diabetic renal disease.
      conducted a systematic review of the effects of low-protein diets in people with Type 1 or 2 diabetes and diabetic nephropathy (very few older adults included). When possible, RCT results were combined for meta-analysis. In 7 studies of Type 1 diabetes, a low-protein diet appeared to slow the progression of diabetic nephropathy, but not significantly. A review of 4 studies among people with Type 2 diabetes again noted small but insignificant reductions in the rate of declining kidney function in 3 of them. Accordingly, the Kidney Disease Outcomes Quality Initiative of the American National Kidney Foundation (KDOQI) guidelines call for adults with chronic kidney disease (CKD) and diabetes to follow the same low-protein diets (0.8 g protein/kg BW/d) as people with CKD, although there is little evidence for adults older than 75.
      KDOQI
      KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease.
      Other experts argue that low-protein diets may not be appropriate for all people with Type 2 diabetes. Koya et al
      • Koya D.
      • Haneda M.
      • Inomata S.
      • et al.
      Long-term effect of modification of dietary protein intake on the progression of diabetic nephropathy: A randomised controlled trial.
      conducted a clinical trial in 88 people (average age approximately 57 ± 8 years) with Type 2 diabetes and nephropathy, randomizing patients to follow a diet with low protein (0.8 g/kg BW/d) or higher protein (1.2 g/kg BW/d) for 5 years. Findings showed that the low-protein diet did not appear to slow the rate of progression of nephropathy. Researchers noted it was extremely difficult for patients to maintain the low-protein diet,
      • Meloni C.
      • Morosetti M.
      • Suraci C.
      • et al.
      Severe dietary protein restriction in overt diabetic nephropathy: Benefits or risks?.
      • Pijls L.T.
      • de Vries H.
      • van Eijk J.T.
      • Donker A.J.
      Protein restriction, glomerular filtration rate and albuminuria in patients with type 2 diabetes mellitus: A randomized trial.
      and they concluded that uncertain renal protection may not be worth the risk of malnutrition.
      • Meloni C.
      • Morosetti M.
      • Suraci C.
      • et al.
      Severe dietary protein restriction in overt diabetic nephropathy: Benefits or risks?.
      For older adults with diabetes and mid- to late-stage CKD, some experts
      • Abaterusso C.
      • Lupo A.
      • Ortalda V.
      • et al.
      Treating elderly people with diabetes and stages 3 and 4 chronic kidney disease.
      argue that the effect of the modest delay in progression of diabetic CKD is too small, with a benefit that accrues across a term that may be longer than an older patient’s available time horizon. Furthermore, people frequently reduce their protein intake spontaneously as they age.

      Kidney Function and Kidney Disease

      Increased protein intake can help improve muscle health and functionality in older people. However, aging is associated with decline in kidney function; thus, clinicians are concerned that high-protein diets will stress kidney function. The key question is, “At what level of kidney impairment does higher protein intake do more harm than good?”
      Recent evidence from a large, 5-year prospective cohort study found that older women (most older than 60, but not older than 79) with normal or slightly impaired kidney function and consuming higher protein than the RDA (an average of 1.1 g protein/kg BW/d), did not experience a reduction in renal function.
      • Beasley J.M.
      • Aragaki A.K.
      • LaCroix A.Z.
      • et al.
      Higher biomarker-calibrated protein intake is not associated with impaired renal function in postmenopausal women.
      Similarly, among older women in the Nurses’ Health Study (56.0 ± 6.6 years at start of study, but not older than 68) who had normal renal function, protein intake was not associated with declining GFR over 11 years.
      • Knight E.L.
      • Stampfer M.J.
      • Hankinson S.E.
      • et al.
      The impact of protein intake on renal function decline in women with normal renal function or mild renal insufficiency.
      However, among women with mild kidney insufficiency at the start of the study, high protein intake (particularly nondairy animal protein) was associated with more rapid GFR decline than expected.
      • Knight E.L.
      • Stampfer M.J.
      • Hankinson S.E.
      • et al.
      The impact of protein intake on renal function decline in women with normal renal function or mild renal insufficiency.
      In patients with nondiabetic CKD stages 3 and 4 (moderate to severe) up to age 70, there is evidence that low-protein diets can slow the progression of CKD.
      • Eyre S.
      • Attman P.O.
      • Haraldsson B.
      Positive effects of protein restriction in patients with chronic kidney disease.
      • Fouque D.
      • Pelletier S.
      • Mafra D.
      • Chauveau P.
      Nutrition and chronic kidney disease.
      • Fouque D.
      • Aparicio M.
      Eleven reasons to control the protein intake of patients with chronic kidney disease.
      Compared with a non–protein-limited diet, a low-protein diet of 0.6 g/kg BW/d can prevent a decline in GFR of approximately 1 mL/min per year per 1.73 m2 and is associated with a 30% decrease in reaching a dialysis-dependent stage.
      • Fouque D.
      • Aparicio M.
      Eleven reasons to control the protein intake of patients with chronic kidney disease.
      • Klahr S.
      • Levey A.S.
      • Beck G.J.
      • et al.
      The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group.
      However, there are concerns about the safety of low-protein diets, in particular when patients are not adequately monitored regarding nutritional indicators. In patients with well-controlled CKD enrolled in an RCT, a small but significant decline in nutrition indicators, essentially muscle mass, has been observed.
      • Kopple J.D.
      • Levey A.S.
      • Greene T.
      • et al.
      Effect of dietary protein restriction on nutritional status in the Modification of Diet in Renal Disease Study.
      When a low-protein diet is prescribed, nutritional counseling advocating an energy intake of 30 kcal/kg BW/d is necessary to maintain a neutral nitrogen balance. In addition, a regular nutritional follow-up by a renal dietician is recommended to detect early signs of malnutrition. Under those conditions, the development of malnutrition during a low-protein diet is an extremely rare event.
      • Klahr S.
      • Levey A.S.
      • Beck G.J.
      • et al.
      The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group.
      As a safety precaution, malnourished patients and patients under stress conditions (eg, hospitalization or surgery) should not follow a protein-restricted diet.
      An Italian RCT of older (≥70 years) patients with CKD who were close to starting dialysis
      • Brunori G.
      • Viola B.F.
      • Parrinello G.
      • et al.
      Efficacy and safety of a very-low-protein diet when postponing dialysis in the elderly: A prospective randomized multicenter controlled study.
      showed that a very low protein diet with 0.3 g/kg BW/d, supplemented with keto-analogues, amino acids, and vitamins, delayed the start of dialysis by approximately 11 months compared with a control group who followed a nonrestricted protein diet and immediately started dialysis. Compared with the control group, patients who were prescribed a very low protein diet had similar mortality rates and their nutritional status was maintained. It is important to mention that patients enrolled in the study were not malnourished at baseline, and that they received nutritional counseling and follow-up nutritional care to maintain intake at 35 kcal/kg BW/d.
      In a retrospective Dutch study of older patients (average age 65) with uncomplicated advanced CKD, a diet of 0.6 g protein/kg BW/d with nutritional counseling helped delay the start of dialysis by 6 months, with no difference in mortality compared with a control group not receiving a low-protein diet.
      • Eyre S.
      • Attman P.O.
      • Haraldsson B.
      Positive effects of protein restriction in patients with chronic kidney disease.
      Nonetheless, some experts remain concerned about prospects for survival in older patients with CKD with sarcopenia, or depleted muscle mass. These experts call for 0.8 g protein/kg BW/d as a measure to help maintain fat-free mass and improve survival prospects (Table 6).
      • Fouque D.
      • Pelletier S.
      • Mafra D.
      • Chauveau P.
      Nutrition and chronic kidney disease.
      • Wolfe R.R.
      • Miller S.L.
      • Miller K.B.
      Optimal protein intake in the elderly.
      Table 6Recommended Energy and Protein Intakes for Patients With CKD
      Nondialysis CKDHemodialysisPeritoneal Dialysis
      PROT-AGE recommendations for older people with kidney disease
      • Severe CKD, GFR <30
        GFR is measured in mL/min/1.73 m2.
        : Limit protein intake to 0.8 g/kg BW
        Recommendations are based on ideal body weight. Regular follow-up supports compliance.
        /d
      • Moderate CKD, 30 <GFR <60: Protein >0.8 g/kg BW
        Recommendations are based on ideal body weight. Regular follow-up supports compliance.
        /d is safe, but GFR should be monitored 2x/year
      • Mild CKD, GFR >60: Increase protein intake per patient needs
      >1.2 g/kg BW
      Recommendations are based on ideal body weight. Regular follow-up supports compliance.
      /d or, if achievable, 1.5 g/kg BW
      Recommendations are based on ideal body weight. Regular follow-up supports compliance.
      /d
      Prospective studies targeting these high protein intakes in older hemodialysis/peritoneal dialysis patients are not available.
      >1.2 g/kg BW
      Recommendations are based on ideal body weight. Regular follow-up supports compliance.
      /d or, if achievable, 1.5 g/kg BW
      Recommendations are based on ideal body weight. Regular follow-up supports compliance.
      /d
      Prospective studies targeting these high protein intakes in older hemodialysis/peritoneal dialysis patients are not available.
      BW, body weight; CKD, chronic kidney disease; GFR, glomerular filtration rate.
      GFR is measured in mL/min/1.73 m2.
      Recommendations are based on ideal body weight. Regular follow-up supports compliance.
      Prospective studies targeting these high protein intakes in older hemodialysis/peritoneal dialysis patients are not available.
      The International Society of Renal Nutrition and Metabolism (ISRNM) has recently developed new dietary recommendations for people with CKD, including patients not on dialysis as well as those on peritoneal or hemodialysis.

      Ikizler TA, Cano N, Franch H, et al. Prevention and treatment of protein energy wasting in chronic kidney disease patients: A consensus statement by the International Society of Renal Nutrition and Metabolism [published online ahead of print May 22, 2013]. Kidney Int http://dx.doi.org/10.1038/ki.2013.147.

      Because patients with kidney disease are at risk of protein-energy wasting, 30 to 35 kcal/kg BW/d is recommended. In patients not on dialysis, protein intake of 0.6 to 0.8 g/kg BW/d is recommended for people who are well and 1.0 g/kg BW/d for those with disease or injury. Once maintenance dialysis begins, a diet with higher protein is necessary to overcome nutritional depletion of the dialysis procedure. Experts currently recommend more than 1.2 g/kg BW/d to compensate for the spontaneous decline in protein intake and the dialysis-induced catabolism.

      Ikizler TA, Cano N, Franch H, et al. Prevention and treatment of protein energy wasting in chronic kidney disease patients: A consensus statement by the International Society of Renal Nutrition and Metabolism [published online ahead of print May 22, 2013]. Kidney Int http://dx.doi.org/10.1038/ki.2013.147.

      It is recommended that more than 50% of the protein consumed be of high biological value (ie, complete protein sources containing the full spectrum of amino acids).
      PROT-AGE recommendations for older people reflect the ISRNM guidelines, providing as much protein as possible for patients not no dialysis based on actual kidney function (measured as GFR).

      Ikizler TA, Cano N, Franch H, et al. Prevention and treatment of protein energy wasting in chronic kidney disease patients: A consensus statement by the International Society of Renal Nutrition and Metabolism [published online ahead of print May 22, 2013]. Kidney Int http://dx.doi.org/10.1038/ki.2013.147.

      In a recent year-long study of older people with CKD (65 ± 14 years) on hemodialysis, patients were offered high-protein, multinutrient ONS during their thrice-weekly dialysis sessions.
      • Lacson Jr., E.
      • Wang W.
      • Zebrowski B.
      • et al.
      Outcomes associated with intradialytic oral nutritional supplements in patients undergoing maintenance hemodialysis: A quality improvement report.
      The “as-treated” patients receiving ONS had a 34% reduced risk of 1-year mortality (hazard ratio 0.66; 95% confidence interval [CI] 0.61–0.71), a significant and important improvement.

      Combining Protein Intake and Exercise in Older People

        PROT-AGE recommendations for exercise and protein intake for older adults

      • Endurance exercise is recommended at 30 minutes per day or at individualized levels that are safe and tolerated. Include progressive resistance training when possible; consider 2 to 3 times per week for 10 to 15 minutes or more per session.
      • Increase dietary protein intake or provide supplemental protein, as needed, to achieve total daily intake of at least 1.2 g protein/kg BW; consider prescribing a 20-g protein supplement after exercise sessions.
      • Protein or amino acid supplementation is recommended in close temporal proximity of exercise; some evidence supports protein consumption after the exercise/therapy session.
      The anabolic effects of insulin and amino acids on protein synthesis are enhanced by physical activity and some nutrients (omega-3 fatty acids, vitamin D) and are impaired by sedentary lifestyle, bed rest, or immobilization (Figure 2).
      • Cermak N.M.
      • Res P.T.
      • de Groot L.C.
      • et al.
      Protein supplementation augments the adaptive response of skeletal muscle to resistance-type exercise training: A meta-analysis.
      • Boirie Y.
      Physiopathological mechanism of sarcopenia.
      • Attaix D.
      • Mosoni L.
      • Dardevet D.
      • et al.
      Altered responses in skeletal muscle protein turnover during aging in anabolic and catabolic periods.
      With aging, the normal balance between muscle protein synthesis and degradation is shifted toward net catabolism, the body’s anabolic response to dietary protein or amino acids is limited,
      • Guillet C.
      • Prod'homme M.
      • Balage M.
      • et al.
      Impaired anabolic response of muscle protein synthesis is associated with S6K1 dysregulation in elderly humans.
      • Boirie Y.
      Physiopathological mechanism of sarcopenia.
      • Koopman R.
      Dietary protein and exercise training in ageing.
      • Timmerman K.L.
      • Volpi E.
      Amino acid metabolism and regulatory effects in aging.
      and the normal antiproteolytic response to insulin is impaired.
      • Guillet C.
      • Prod'homme M.
      • Balage M.
      • et al.
      Impaired anabolic response of muscle protein synthesis is associated with S6K1 dysregulation in elderly humans.
      • Wilkes E.A.
      • Selby A.L.
      • Atherton P.J.
      • et al.
      Blunting of insulin inhibition of proteolysis in legs of older subjects may contribute to age-related sarcopenia.
      • Boirie Y.
      • Gachon P.
      • Cordat N.
      • et al.
      Differential insulin sensitivities of glucose, amino acid, and albumin metabolism in elderly men and women.
      At the same time, older people lead a less-active lifestyle, sometimes because of limitations imposed by chronic illnesses.
      • Matthews C.E.
      • Chen K.Y.
      • Freedson P.S.
      • et al.
      Amount of time spent in sedentary behaviors in the United States, 2003–2004.
      As a result, aging is associated with a progressive loss of skeletal muscle mass and strength, which leads to reduced functional capacity.
      • Boirie Y.
      Physiopathological mechanism of sarcopenia.
      • Koopman R.
      Dietary protein and exercise training in ageing.
      • Evans W.J.
      Protein nutrition, exercise and aging.
      Evidence shows that age-related muscle loss can be counteracted by exercise training
      • Liu C.J.
      • Latham N.K.
      Progressive resistance strength training for improving physical function in older adults.
      and by increased intake of protein or amino acids.
      • Walrand S.
      • Guillet C.
      • Salles J.
      • et al.
      Physiopathological mechanism of sarcopenia.
      • Boirie Y.
      Physiopathological mechanism of sarcopenia.
      Figure thumbnail gr2
      Fig. 2Anabolic effects of insulin and amino acids on protein synthesis are enhanced by physical activity and some nutrients and are impaired by sedentary lifestyle, bed rest, or immobilization.

      Physical Activity

      The amounts of physical activity and exercise that are safe and well tolerated depend on each individual’s general health. For all adults, physical activity can be accumulated as activities of daily living (ADLs); exercise is structured and repetitive. For older people, structured exercises are recommended to target health-associated physical benefits: cardiorespiratory fitness, muscle strength and endurance, body composition, flexibility, and balance.
      The American Heart Association (AHA) and the American College of Sports Medicine (ASCM) encourage older adults to accumulate 30 to 60 minutes of moderate intensity aerobic exercise per day (150–300 minutes per week) or 20 to 30 minutes per day of vigorous intensity (75–150 minutes per week).
      In addition, to counteract muscle loss and increase strength, resistance exercises are strongly recommended for 2 or more nonconsecutive days per week. For healthy older adults, exercise of 10 to 15 minutes per session with 8 repetitions for each muscle group is a reasonable goal.
      Considerable evidence shows that exercise, both as aerobic activity and as resistance training, is beneficial to older people.
      • Conn V.S.
      • Minor M.A.
      • Burks K.J.
      • et al.
      Integrative review of physical activity intervention research with aging adults.
      • Kruger J.
      • Buchner D.M.
      • Prohaska T.R.
      The prescribed amount of physical activity in randomized clinical trials in older adults.
      • Fielding R.A.
      Effects of exercise training in the elderly: Impact of progressive-resistance training on skeletal muscle and whole-body protein metabolism.
      With exercise, frail older people can gain muscle strength and function into their 9th and 10th decades of life, as shown in resistance-training studies.
      • Fiatarone M.A.
      • Marks E.C.
      • Ryan N.D.
      • et al.
      High-intensity strength training in nonagenarians. Effects on skeletal muscle.
      • Fiatarone M.A.
      • O'Neill E.F.
      • Ryan N.D.
      • et al.
      Exercise training and nutritional supplementation for physical frailty in very elderly people.
      • Serra-Rexach J.A.
      • Bustamante-Ara N.
      • Hierro Villaran M.
      • et al.
      Short-term, light- to moderate-intensity exercise training improves leg muscle strength in the oldest old: A randomized controlled trial.
      When their opinions were surveyed, older people reported positive perceptions of exercise, even during hospitalization.
      • So C.
      • Pierluissi E.
      Attitudes and expectations regarding exercise in the hospital of hospitalized older adults: A qualitative study.

      Protein or Amino Acid Supplementation

      Dietary protein or amino acid supplementation promotes protein synthesis in older people
      • Paddon-Jones D.
      • Sheffield-Moore M.
      • Zhang X.J.
      • et al.
      Amino acid ingestion improves muscle protein synthesis in the young and elderly.
      and can enhance recovery of physical function in older individuals. Tieland et al
      • Tieland M.
      • van de Rest O.
      • Dirks M.L.
      • et al.
      Protein supplementation improves physical performance in frail elderly people: A randomized, double-blind, placebo-controlled trial.
      showed that muscle strength and physical function improved when frail older people were given supplemental protein daily (15 g at breakfast, 15 g at lunch) for 24 weeks; such improvement occurred in the absence of measurable changes in muscle mass. These results suggest that protein feeding alone may improve muscle strength and function more readily than muscle mass.
      • Tieland M.
      • van de Rest O.
      • Dirks M.L.
      • et al.
      Protein supplementation improves physical performance in frail elderly people: A randomized, double-blind, placebo-controlled trial.

      Synergistic Effects of Exercise and Protein or Amino Acids

      In young and old people alike, protein ingestion together with exercise training increased synthesis of skeletal muscle
      • Yang Y.
      • Breen L.
      • Burd N.A.
      • et al.
      Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men.
      • Burd N.A.
      • Yang Y.
      • Moore D.R.
      • et al.
      Greater stimulation of myofibrillar protein synthesis with ingestion of whey protein isolate v. micellar casein at rest and after resistance exercise in elderly men.
      • Fujita S.
      • Rasmussen B.B.
      • Cadenas J.G.
      • et al.
      Aerobic exercise overcomes the age-related insulin resistance of muscle protein metabolism by improving endothelial function and Akt/mammalian target of rapamycin signaling.
      • Cermak N.M.
      • Res P.T.
      • de Groot L.C.
      • et al.
      Protein supplementation augments the adaptive response of skeletal muscle to resistance-type exercise training: A meta-analysis.
      • Yang Y.
      • Churchward-Venne T.A.
      • Burd N.A.
      • et al.
      Myofibrillar protein synthesis following ingestion of soy protein isolate at rest and after resistance exercise in elderly men.
      ; effects were evident for both aerobic exercise
      • Timmerman K.L.
      • Dhanani S.
      • Glynn E.L.
      • et al.
      A moderate acute increase in physical activity enhances nutritive flow and the muscle protein anabolic response to mixed nutrient intake in older adults.
      • Fujita S.
      • Rasmussen B.B.
      • Cadenas J.G.
      • et al.
      Aerobic exercise overcomes the age-related insulin resistance of muscle protein metabolism by improving endothelial function and Akt/mammalian target of rapamycin signaling.
      and resistance exercise.
      • Yang Y.
      • Breen L.
      • Burd N.A.
      • et al.
      Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men.
      • Burd N.A.
      • Yang Y.
      • Moore D.R.
      • et al.
      Greater stimulation of myofibrillar protein synthesis with ingestion of whey protein isolate v. micellar casein at rest and after resistance exercise in elderly men.
      • Yang Y.
      • Churchward-Venne T.A.
      • Burd N.A.
      • et al.
      Myofibrillar protein synthesis following ingestion of soy protein isolate at rest and after resistance exercise in elderly men.
      Exercise consistently reduced the difference between muscle protein breakdown and synthesis; net positive protein balance (ie, synthesis greater than breakdown) was achieved only when protein or amino acid intake was supplemented.
      • Biolo G.
      • Tipton K.D.
      • Klein S.
      • Wolfe R.R.
      An abundant supply of amino acids enhances the metabolic effect of exercise on muscle protein.
      • Drummond M.J.
      • Marcus R.L.
      • Lastayo P.C.
      Targeting anabolic impairment in response to resistance exercise in older adults with mobility impairments: Potential mechanisms and rehabilitation approaches.
      In a clinical study, frail older people who engaged in resistance training and consumed supplemental dietary protein for 24 weeks showed significant muscle hypertrophy, together with increases in muscle strength and performance; study researchers concluded that protein intake was necessary for training-associated gains in muscle mass.
      • Tieland M.
      • Dirks M.L.
      • van der Zwaluw N.
      • et al.
      Protein supplementation increases muscle mass gain during prolonged resistance-type exercise training in frail elderly people: A randomized, double-blind, placebo-controlled trial.
      In addition, the quality of the protein consumed may exert an influence on the protein synthetic response. High-leucine–containing and rapidly digested whey proteins showed an advantage over isolated casein and soy proteins,
      • Yang Y.
      • Breen L.
      • Burd N.A.
      • et al.
      Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men.
      • Burd N.A.
      • Yang Y.
      • Moore D.R.
      • et al.
      Greater stimulation of myofibrillar protein synthesis with ingestion of whey protein isolate v. micellar casein at rest and after resistance exercise in elderly men.
      • Pennings B.
      • Boirie Y.
      • Senden J.M.
      • et al.
      Whey protein stimulates postprandial muscle protein accretion more effectively than do casein and casein hydrolysate in older men.
      • Yang Y.
      • Churchward-Venne T.A.
      • Burd N.A.
      • et al.
      Myofibrillar protein synthesis following ingestion of soy protein isolate at rest and after resistance exercise in elderly men.
      which was particularly evident in short-term experiments.
      • Rieu I.
      • Balage M.
      • Sornet C.
      • et al.
      Leucine supplementation improves muscle protein synthesis in elderly men independently of hyperaminoacidaemia.
      • Paddon-Jones D.
      • Sheffield-Moore M.
      • Katsanos C.S.
      • et al.
      Differential stimulation of muscle protein synthesis in elderly humans following isocaloric ingestion of amino acids or whey protein.
      As for the combination of protein and exercise, a recent RCT in 175 community-dwelling women with sarcopenia showed that the combination of exercise twice weekly and 3 g of leucine twice daily for 3 months was superior compared with either intervention alone.
      • Kim H.K.
      • Suzuki T.
      • Saito K.
      • et al.
      Effects of exercise and amino acid supplementation on body composition and physical function in community-dwelling elderly Japanese sarcopenic women: A randomized controlled trial.
      In another study, blends of whey and soy protein stimulated muscle protein synthesis after exercise to a similar extent as did whey protein alone.
      • Reidy P.T.
      • Walker D.K.
      • Dickinson J.M.
      • et al.
      Protein blend ingestion following resistance exercise promotes human muscle protein synthesis.
      Yet another trial compared resistance training in mobility-limited older adults in subgroups who received either whey protein supplementation or an isocaloric diet over 6 months; no statistically different changes were seen in lean body mass, muscle cross-sectional area, muscle strength, or stair-climbing.
      • Chale A.
      • Cloutier G.J.
      • Hau C.
      • et al.
      Efficacy of whey protein supplementation on resistance exercise-induced changes in lean mass, muscle strength, and physical function in mobility-limited older adults.
      More long-term studies are needed to confirm potential benefits of whey protein.

      When, How Much, and How?

      With combination exercise-protein therapy, the timing of protein or amino acid intake relative to exercise is central to muscle anabolism. Exercise enhances muscle protein synthesis by sensitizing muscle to insulin- or amino acid-mediated anabolic actions, an effect that appears to peak in the first 3 hours after exercise
      • Tang J.E.
      • Phillips S.M.
      Maximizing muscle protein anabolism: The role of protein quality.
      and may persist 18 to 24 hours after an exercise bout.
      • Fujita S.
      • Rasmussen B.B.
      • Cadenas J.G.
      • et al.
      Aerobic exercise overcomes the age-related insulin resistance of muscle protein metabolism by improving endothelial function and Akt/mammalian target of rapamycin signaling.
      • Burd N.A.
      • West D.W.
      • Moore D.R.
      • et al.
      Enhanced amino acid sensitivity of myofibrillar protein synthesis persists for up to 24 h after resistance exercise in young men.
      Such findings suggest that protein should be consumed close after exercise (or physical therapy) to take advantage of its sensitizing effect. The short-term complementary effects of exercise and protein supplementation were underscored in long-term studies as well. Results of a meta-analysis of 22 RCTs involving 680 young and old subjects demonstrated that prolonged resistance training (>6 weeks) combined with cotemporal protein supplement consumption led to significant muscle mass gains, which were associated with significant strength gains.
      • Cermak N.M.
      • Res P.T.
      • de Groot L.C.
      • et al.
      Protein supplementation augments the adaptive response of skeletal muscle to resistance-type exercise training: A meta-analysis.
      During and following hospitalization, a rehabilitation specialist usually makes individualized recommendations for duration and intensity of exercise. There is no global standard or recommendation, but physical activity during hospitalization and in posthospitalization rehabilitation sessions has reported benefits.

      World Health Organization. Protein and amino acid requirements in human nutrition: Report of a joint WHO/FAO/UNU expert consultation. Geneva: WHO Press; 2007. Report 935.

      Institute of Medicine
      Dietary Reference Intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids (macronutrients).

      European Food Safety Authority (EFSA). Outcome of a public consultation on the draft scientific opinion on the EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA) on dietary reference values for protein. Parma, Italy: EFSA; 2012.

      • Walrand S.
      • Guillet C.
      • Salles J.
      • et al.
      Physiopathological mechanism of sarcopenia.
      • Gaffney-Stomberg E.
      • Insogna K.L.
      • Rodriguez N.R.
      • Kerstetter J.E.
      Increasing dietary protein requirements in elderly people for optimal muscle and bone health.
      • Kurpad A.V.
      • Vaz M.
      Protein and amino acid requirements in the elderly.
      • Morse M.H.
      • Haub M.D.
      • Evans W.J.
      • Campbell W.W.
      Protein requirement of elderly women: Nitrogen balance responses to three levels of protein intake.
      • Chernoff R.
      Protein and older adults.
      • Morley J.E.
      • Argiles J.M.
      • Evans W.J.
      • et al.
      Nutritional recommendations for the management of sarcopenia.
      • Fürst P.
      • Deutz N.
      • Boirie Y.
      • et al.
      Proteins and amino acids.
      • McClave S.A.
      • Martindale R.G.
      • Vanek V.W.
      • et al.
      Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.).
      • Hauer K.
      • Rost B.
      • Rutschle K.
      • et al.
      Exercise training for rehabilitation and secondary prevention of falls in geriatric patients with a history of injurious falls.
      • Killey B.
      • Watt E.
      The effect of extra walking on the mobility, independence and exercise self-efficacy of elderly hospital in-patients: A pilot study.
      • Campbell W.W.
      • Leidy H.J.
      Dietary protein and resistance training effects on muscle and body composition in older persons.
      • Hoffer L.J.
      • Bistrian B.R.
      Appropriate protein provision in critical illness: A systematic and narrative review.
      Total daily dietary protein intake seems to influence the anabolic effects of exercise. In a study of body composition changes in 50- to 80-year-old adults who followed resistance training regimens for 3 months, net positive effects of protein occurred when protein intake was greater than 1.0 g protein/kg BW/d.
      • Campbell W.W.
      • Leidy H.J.
      Dietary protein and resistance training effects on muscle and body composition in older persons.

      Specific Patient Populations

      Evidence supports the combination of exercise and protein/amino acid supplementation for prevention and treatment of muscle loss in certain debilitating clinical conditions, including bed rest for acute critical illness or injury
      • Bamman M.M.
      • Clarke M.S.
      • Feeback D.L.
      • et al.
      Impact of resistance exercise during bed rest on skeletal muscle sarcopenia and myosin isoform distribution.
      • Biolo G.
      • Agostini F.
      • Simunic B.
      • et al.
      Positive energy balance is associated with accelerated muscle atrophy and increased erythrocyte glutathione turnover during 5 wk of bed rest.
      • English K.L.
      • Paddon-Jones D.
      Protecting muscle mass and function in older adults during bed rest.
      • Ferrando A.A.
      • Paddon-Jones D.
      • Hays N.P.
      • et al.
      EAA supplementation to increase nitrogen intake improves muscle function during bed rest in the elderly.
      • Ferrando A.A.
      • Tipton K.D.
      • Bamman M.M.
      • Wolfe R.R.
      Resistance exercise maintains skeletal muscle protein synthesis during bed rest.
      • Paddon-Jones D.
      • Sheffield-Moore M.
      • Urban R.J.
      • et al.
      Essential amino acid and carbohydrate supplementation ameliorates muscle protein loss in humans during 28 days bedrest.
      • Schweickert W.D.
      • Pohlman M.C.
      • Pohlman A.S.
      • et al.
      Early physical and occupational therapy in mechanically ventilated, critically ill patients: A randomised controlled trial.
      • Trappe T.A.
      • Burd N.A.
      • Louis E.S.
      • et al.
      Influence of concurrent exercise or nutrition countermeasures on thigh and calf muscle size and function during 60 days of bed rest in women.
      and also for chronic diseases, such as COPD
      • Dal Negro R.W.
      • Aquilani R.
      • Bertacco S.
      • et al.
      Comprehensive effects of supplemented essential amino acids in patients with severe COPD and sarcopenia.
      • Laviolette L.
      • Lands L.C.
      • Dauletbaev N.
      • et al.
      Combined effect of dietary supplementation with pressurized whey and exercise training in chronic obstructive pulmonary disease: A randomized, controlled, double-blind pilot study.
      • Reid W.D.
      • Yamabayashi C.
      • Goodridge D.
      • et al.
      Exercise prescription for hospitalized people with chronic obstructive pulmonary disease and comorbidities: A synthesis of systematic reviews.
      • Sugawara K.
      • Takahashi H.
      • Kasai C.
      • et al.
      Effects of nutritional supplementation combined with low-intensity exercise in malnourished patients with COPD.
      • van Wetering C.R.
      • Hoogendoorn M.
      • Broekhuizen R.
      • et al.
      Efficacy and costs of nutritional rehabilitation in muscle-wasted patients with chronic obstructive pulmonary disease in a community-based setting: A prespecified subgroup analysis of the INTERCOM trial.
      and congestive heart failure (CHF).
      • Aquilani R.
      • Viglio S.
      • Iadarola P.
      • et al.
      Oral amino acid supplements improve exercise capacities in elderly patients with chronic heart failure.
      • Reid W.D.
      • Yamabayashi C.
      • Goodridge D.
      • et al.
      Exercise prescription for hospitalized people with chronic obstructive pulmonary disease and comorbidities: A synthesis of systematic reviews.
      • Akner G.
      • Cederholm T.
      Treatment of protein-energy malnutrition in chronic nonmalignant disorders.
      The loss of muscle mass and strength associated with bed rest per se can be partly offset by protein or amino acid supplementation.
      • Paddon-Jones D.
      • Sheffield-Moore M.
      • Urban R.J.
      • et al.
      Essential amino acid and carbohydrate supplementation ameliorates muscle protein loss in humans during 28 days bedrest.
      • Paddon-Jones D.
      • Sheffield-Moore M.
      • Urban R.J.
      • et al.
      The catabolic effects of prolonged inactivity and acute hypercortisolemia are offset by dietary supplementation.
      Exercise is recognized to provide a potent anabolic stimulus to muscle, even among patients who are mostly limited to bed rest.
      • Bamman M.M.
      • Clarke M.S.
      • Feeback D.L.
      • et al.
      Impact of resistance exercise during bed rest on skeletal muscle sarcopenia and myosin isoform distribution.
      • Ferrando A.A.
      • Tipton K.D.
      • Bamman M.M.
      • Wolfe R.R.
      Resistance exercise maintains skeletal muscle protein synthesis during bed rest.
      • Connolly B.
      • Denehy L.
      • Brett S.
      • et al.
      Exercise rehabilitation following hospital discharge in survivors of critical illness: An integrative review.
      For patients with COPD, results of 2 studies clearly showed benefits from exercise training along with protein supplementation
      • Laviolette L.
      • Lands L.C.
      • Dauletbaev N.
      • et al.
      Combined effect of dietary supplementation with pressurized whey and exercise training in chronic obstructive pulmonary disease: A randomized, controlled, double-blind pilot study.
      • Sugawara K.
      • Takahashi H.
      • Kasai C.
      • et al.
      Effects of nutritional supplementation combined with low-intensity exercise in malnourished patients with COPD.
      ; whey protein served as an effective protein source. People with CHF likewise experienced benefits when treated with exercise and amino acid supplementation.
      • Aquilani R.
      • Viglio S.
      • Iadarola P.
      • et al.
      Oral amino acid supplements improve exercise capacities in elderly patients with chronic heart failure.
      Thus, a small number of trials have shown that modest physical activity is possible in people with chronic illnesses or those recovering from critical illness,
      • Burtin C.
      • Clerckx B.
      • Robbeets C.
      • et al.
      Early exercise in critically ill patients enhances short-term functional recovery.
      • Karatzanos E.
      • Gerovasili V.
      • Zervakis D.
      • et al.
      Electrical muscle stimulation: An effective form of exercise and early mobilization to preserve muscle strength in critically ill patients.
      • Skinner E.H.
      • Berney S.
      • Warrillow S.
      • Denehy L.
      Development of a physical function outcome measure (PFIT) and a pilot exercise training protocol for use in intensive care.
      but more and larger trials are needed to demonstrate the safety and efficacy of such strategies, especially because protein supplementation alone may not be sufficient to rescue very old people or those with severe muscle loss.
      • Trappe T.A.
      • Burd N.A.
      • Louis E.S.
      • et al.
      Influence of concurrent exercise or nutrition countermeasures on thigh and calf muscle size and function during 60 days of bed rest in women.

      Other Dietary Supplements for Muscle Maintenance in Older People

      Several dietary supplements have been tested in combination with exercise in older adults, namely creatine
      • Trappe T.A.
      • Burd N.A.
      • Louis E.S.
      • et al.
      Influence of concurrent exercise or nutrition countermeasures on thigh and calf muscle size and function during 60 days of bed rest in women.
      • Bemben M.G.
      • Witten M.S.
      • Carter J.M.
      • et al.
      The effects of supplementation with creatine and protein on muscle strength following a traditional resistance training program in middle-aged and older men.
      • Brose A.
      • Parise G.
      • Tarnopolsky M.A.
      Creatine supplementation enhances isometric strength and body composition improvements following strength exercise training in older adults.
      • Candow D.G.
      • Chilibeck P.D.
      Effect of creatine supplementation during resistance training on muscle accretion in the elderly.
      • Chrusch M.J.
      • Chilibeck P.D.
      • Chad K.E.
      • et al.
      Creatine supplementation combined with resistance training in older men.
      and beta-hydroxy-beta-methylbutyrate (β-HMB).
      • Baier S.
      • Johannsen D.
      • Abumrad N.
      • et al.
      Year-long changes in protein metabolism in elderly men and women supplemented with a nutrition cocktail of beta-hydroxy-beta-methylbutyrate (HMB), L-arginine, and L-lysine.
      • Fitschen P.J.
      • Wilson G.J.
      • Wilson J.M.
      • Wilund K.R.
      Efficacy of beta-hydroxy-beta-methylbutyrate supplementation in elderly and clinical populations.
      • Jowko E.
      • Ostaszewski P.
      • Jank M.
      • et al.
      Creatine and beta-hydroxy-beta-methylbutyrate (HMB) additively increase lean body mass and muscle strength during a weight-training program.
      • Panton L.B.
      • Rathmacher J.A.
      • Baier S.
      • Nissen S.
      Nutritional supplementation of the leucine metabolite beta-hydroxy-beta-methylbutyrate (hmb) during resistance training.
      • Vukovich M.D.
      • Stubbs N.B.
      • Bohlken R.M.
      Body composition in 70-year-old adults responds to dietary beta-hydroxy-beta-methylbutyrate similarly to that of young adults.
      In general, these agents have positive effects on lean body mass and strength, but the effects tend to be small and are not consistent. Some authors have championed the benefits of creatine for outcomes other than skeletal muscle synthesis, including bone health and cognitive function.
      • Candow D.G.
      • Chilibeck P.D.
      Potential of creatine supplementation for improving aging bone health.
      • Rawson E.S.
      • Venezia A.C.
      Use of creatine in the elderly and evidence for effects on cognitive function in young and old.
      • Tarnopolsky M.A.
      • Safdar A.
      The potential benefits of creatine and conjugated linoleic acid as adjuncts to resistance training in older adults.
      However, at this time, it is not possible to state definitively whether creatine or β-HMB can enhance exercise responses in older people, as these agents have been shown to do in younger people.
      • Nissen S.L.
      • Sharp R.L.
      Effect of dietary supplements on lean mass and strength gains with resistance exercise: A meta-analysis.
      • Rowlands D.S.
      • Thomson J.S.
      Effects of beta-hydroxy-beta-methylbutyrate supplementation during resistance training on strength, body composition, and muscle damage in trained and untrained young men: a meta-analysis.
      Clearly this is an area for more clinical trials.

      Exercise and Protein Recommendations for Older People

      Because older people are at high risk for muscle loss and disability when immobilized, and because exercise has known prevention and recovery benefits for physical health, the PROT-AGE group recommends a combination of higher protein intake and exercise for older people. A usual intake of 20 g protein at least, probably just after physical exercise, is recommended as muscle sensitivity to amino acids may be increased after exercise.
      • Yang Y.
      • Breen L.
      • Burd N.A.
      • et al.
      Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men.
      Another aspect is the amino acid content of the protein source, as leucine has been reported as an interesting stimulating factor for muscle protein synthesis. From the available studies, it is accepted that 2.0 to 2.5 g of leucine intake should be contained in the amino acid mixture.
      • Yang Y.
      • Breen L.
      • Burd N.A.
      • et al.
      Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men.
      • Wall B.T.
      • Hamer H.M.
      • de Lange A.
      • et al.
      Leucine co-ingestion improves post-prandial muscle protein accretion in elderly men.
      Some individuals may not be able to tolerate exercise (eg, those with acute myocardial infarction, unstable angina, uncontrolled arrhythmia) or very high protein/amino acid supplementation (eg, nondialyzed late-stage kidney patients). As always, all treatment decisions are guided by clinical judgment and a full perspective of the patient’s health condition. In these situations, muscle electrical stimulation may be an effective therapy to help alleviate muscle loss.
      • Gibson J.N.
      • Smith K.
      • Rennie M.J.
      Prevention of disuse muscle atrophy by means of electrical stimulation: Maintenance of protein synthesis.
      • Parry S.M.
      • Berney S.
      • Koopman R.
      • et al.
      Early rehabilitation in critical care (eRiCC): Functional electrical stimulation with cycling protocol for a randomised controlled trial.
      • Kayambu G.
      • Boots R.J.
      • Paratz J.D.
      Early rehabilitation in sepsis: A prospective randomised controlled trial investigating functional and physiological outcomes The i-PERFORM Trial (Protocol Article).

      Protein Quality and Specific Amino Acids

        PROT-AGE recommendations on dietary protein and amino acid quality for older people

      • The list of indispensable amino acids is qualitatively identical for young and old adults.
      • There is no evidence that protein digestion and absorption capacities change significantly with aging.
      • “Fast” proteins may have some benefits over “slow” proteins in muscle protein metabolism.
      • Dietary enrichment with leucine or a mixture of branched-chain amino acids may help enhance muscle mass and muscle function, but further studies are needed to support specific recommendations.
      • β-HMB may attenuate muscle loss and increase muscle mass and strength in older people, but further studies are needed to support specific recommendations.
      • Creatine supplementation may be justified for older people, especially those who are creatine-deficient or at high risk of deficiency.
      For older people, a high-quality protein is one that has a high likelihood of promoting healthy aging or improving age-related problems and diseases. Protein quality was traditionally defined by amino acid composition, as measured by an essential amino acid score or by the ratio of essential to nonessential nitrogen. It was believed that a high-quality protein supplied all needed amino acids in quantities sufficient to satisfy demands for ongoing protein synthesis in the human body; however, the definition of protein quality has evolved in recent years. Protein quality still considers amino acid content but also includes new concepts: digestibility and absorption of the protein, as well as newly recognized roles of specific amino acids in regulation of cellular processes.
      • Tang J.E.
      • Phillips S.M.
      Maximizing muscle protein anabolism: The role of protein quality.
      • Millward D.J.
      • Layman D.K.
      • Tome D.
      • Schaafsma G.
      Protein quality assessment: Impact of expanding understanding of protein and amino acid needs for optimal health.
      The following section reviews state-of-the-art understanding of protein quality and relates these concepts to practical aspects of protein intake by older adults.

      Indispensable, Dispensable, and Conditionally Dispensable Amino Acids

      Nutritive amino acids were originally classified as essential (no endogenous synthesis pathway in humans possible) or non-essential (endogenous enzymatic synthesis possible). This simple classification did not take all physiological situations into account, so the classification was revised.
      • Reeds P.J.
      Dispensable and indispensable amino acids for humans.
      • Furst P.
      • Stehle P.
      What are the essential elements needed for the determination of amino acid requirements in humans?.
      Dispensable amino acids can be synthesized by the human body in sufficient amounts for all physiological situations. Indispensable amino acids are never synthesized in humans because enzymatic pathways are lacking; supplies must be provided from dietary sources. Conditionally-indispensable amino acids are synthesized by the human body under normal physiological conditions but must be supplied in part from dietary sources when needs are unmet. Unmet needs occur when protein synthesis increases, enzymatic pathways are limited by genetic factors, or endogenous supplies are insufficient due to decreased availability of precursor supplies.
      Using novel methodologies (eg, stable isotopes, long-term metabolic studies), metabolism and function of amino acids can be evaluated objectively. To date, research has not shown that aging has a significant impact on endogenous synthesis of amino acids. There is, thus, no scientific evidence to make a separate amino acid classification for older people. Consequently, there is no reason at this time to change indispensable amino acid requirements compared to those published for young adults.
      • Pillai R.R.
      • Kurpad A.V.
      Amino acid requirements in children and the elderly population.

      Protein Digestibility–Corrected Amino Acid Score

      Recent scoring systems, such as the Protein Digestibility–Corrected Amino Acid Score (PDCAAS), consider not only the chemical composition of a protein but also its digestibility rate.
      • Schaafsma G.
      Advantages and limitations of the protein digestibility-corrected amino acid score (PDCAAS) as a method for evaluating protein quality in human diets.
      The score is based on a comparison between the quantities of single indispensable amino acids in 1 g of a test protein with the quantities of these amino acids in the same amount of reference protein. The lowest ratio (first limiting indispensable amino acid) determines the quality of the protein. This calculated value is then corrected for the true fecal/ileal digestibility, which is evaluated by measuring the endogenous losses of amino acids after protein consumption in vivo. The PDCAAS is now widely used
      • Schaafsma G.
      Advantages and limitations of the protein digestibility-corrected amino acid score (PDCAAS) as a method for evaluating protein quality in human diets.
      ; it has been adopted by the Food and Agriculture Organization/World Health Organization as the preferred method for the measurement of protein quality in human nutrition.
      Although some age-related anatomical and physiological changes have been described in the gastrointestinal tract,
      • Pillai R.R.
      • Kurpad A.V.
      Amino acid requirements in children and the elderly population.
      these changes are relatively small and do not substantially impair amino acid availability from food.
      • Koopman R.
      • Walrand S.
      • Beelen M.
      • et al.
      Dietary protein digestion and absorption rates and the subsequent postprandial muscle protein synthetic response do not differ between young and elderly men.
      Consequently, there is no reason at this time to change amino acid requirements compared with those published for young adults.
      • Pillai R.R.
      • Kurpad A.V.
      Amino acid requirements in children and the elderly population.

      “Fast” and “Slow” Proteins

      After protein intake and digestion, the magnitude and duration of changes in amino acid availability have been shown to regulate protein gain.
      • Boirie Y.
      • Dangin M.
      • Gachon P.
      • et al.
      Slow and fast dietary proteins differently modulate postprandial protein accretion.
      • Dangin M.
      • Boirie Y.
      • Guillet C.
      • Beaufrere B.
      Influence of the protein digestion rate on protein turnover in young and elderly subjects.
      The concept of “fast” proteins means a faster, higher, and more transient elevation of postprandial plasma amino acid appearance from dietary protein than for “slow” proteins, even when the amino acid content is similar.
      • Dangin M.
      • Boirie Y.
      • Garcia-Rodenas C.
      • et al.
      The digestion rate of protein is an independent regulating factor of postprandial protein retention.
      Such different kinetic patterns influence the subsequent amino acid metabolism.
      • Boirie Y.
      • Dangin M.
      • Gachon P.
      • et al.
      Slow and fast dietary proteins differently modulate postprandial protein accretion.
      In older men, whey protein (a “fast” milk-derived protein) stimulated postprandial muscle protein accretion more effectively than casein (a “slow” milk-derived protein), an effect that is attributed to a combination of whey's faster digestion and absorption kinetics and possibly to its higher leucine content.
      • Burd N.A.
      • Yang Y.
      • Moore D.R.
      • et al.
      Greater stimulation of myofibrillar protein synthesis with ingestion of whey protein isolate v. micellar casein at rest and after resistance exercise in elderly men.
      • Pennings B.
      • Boirie Y.
      • Senden J.M.
      • et al.
      Whey protein stimulates postprandial muscle protein accretion more effectively than do casein and casein hydrolysate in older men.
      • Paddon-Jones D.
      • Sheffield-Moore M.
      • Katsanos C.S.
      • et al.
      Differential stimulation of muscle protein synthesis in elderly humans following isocaloric ingestion of amino acids or whey protein.
      However, because ingestion of 15 g of whey protein appeared to be better than ingestion of its equivalent in essential amino acids (6.72 g),
      • Katsanos C.S.
      • Chinkes D.L.
      • Paddon-Jones D.
      • et al.
      Whey protein ingestion in elderly persons results in greater muscle protein accrual than ingestion of its constituent essential amino acid content.
      whey protein does appear to have some anabolic benefit beyond its essential amino acid content.
      The whey/casein difference has not been found universally. When taken in immediately after resistance exercise, whey and casein resulted in equally increased protein synthesis despite temporal differences in postprandial insulin and amino acid concentrations.
      • Reitelseder S.
      • Agergaard J.
      • Doessing S.
      • et al.
      Whey and casein labeled with L-[1–13C]leucine and muscle protein synthesis: Effect of resistance exercise and protein ingestion.
      Milk-derived proteins (whey, casein) were both more efficient for improving muscle protein anabolism than soy proteins.
      • Phillips S.M.
      • Tang J.E.
      • Moore D.R.
      The role of milk- and soy-based protein in support of muscle protein synthesis and muscle protein accretion in young and elderly persons.
      Studies are therefore needed to ascertain whether such benefits are characteristic of milk proteins or are more generally related to animal versus plant differences.
      Taken together, research findings generally suggest that “fast” proteins provide greater benefit to muscle protein accretion than do “slow” proteins. However, evidence from small experimental trials needs to be confirmed in larger patient populations before precise recommendations can be made on the choice of “fast” versus “slow” proteins.
      • Jordan L.Y.
      • Melanson E.L.
      • Melby C.L.
      • et al.
      Nitrogen balance in older individuals in energy balance depends on timing of protein intake.