Skeletal muscle comprises about 30–40 % of total body mass of the average adult person(Reference Frontera and Ochala1), and is a multifunctional tissue(Reference Mukund and Subramaniam2), essential for force generation and movement, breathing, temperature control(Reference Frontera and Ochala1) and metabolism(Reference Merz and Thurmond3). Specifically, skeletal muscle regulates glucose homeostasis(Reference Merz and Thurmond3) and whole-body protein metabolism(Reference Wolfe4) – serving as the primary site for glucose uptake and storage, and as the principal, active reservoir of amino acids for protein synthesis in other tissues(Reference Wolfe4). Muscle health, described in terms of muscle mass and function (strength and physical performance), is affected by ageing processes(Reference Tieland, Trouwborst and Clark5–Reference Mitchell, Williams and Atherton8). After reaching a peak in the fourth decade of life(Reference Mitchell, Williams and Atherton8), muscle mass and strength start to decline gradually(Reference Dodds, Syddall and Cooper9,Reference Janssen, Heymsfield and Wang10) , with the rate estimated to accelerate to 1–3 % and 2·5–4 % per year, respectively in later life(Reference Mitchell, Williams and Atherton8).
Although not fully explained, changes in skeletal muscle with age are linked to multiple molecular mechanisms, such as inflammation, dysfunction in mitochondria, oxidative stress and deregulation of nutrient sensing(Reference Granic, Suetterlin and Shavlakadze7,Reference Sartori, Romanello and Sandri11–Reference Wiedmer, Jung and Castro13) . Declines in muscle strength and mass attributed to ageing characterise (primary) sarcopenia(Reference Cruz-Jentoft, Bahat and Bauer14,Reference Cruz-Jentoft and Sayer15) , a progressive and generalised muscle disorder with a complex aetiology(Reference Granic, Suetterlin and Shavlakadze7,Reference Wiedmer, Jung and Castro13,Reference Larsson, Degens and Li16,Reference Zhong, Zheng and Li17) that has increasing prevalence with advanced age(Reference Petermann-Rocha, Balntzi and Gray18). Depending on the definition and cut-offs applied for muscle mass and function, the global prevalence of sarcopenia varied from 10 % to 37 % in older adults aged ≥ 60 years, in a systematic evaluation of over 260 studies(Reference Petermann-Rocha, Balntzi and Gray18). These estimates may change with the adoption of an inclusive definition of sarcopenia worldwide led by the Global Leadership Initiative in Sarcopenia (GLIS)(Reference Kirk, Cawthon and Arai19). The presence of sarcopenia and its components (low muscle mass, muscle strength and poor physical performance) associate strongly with adverse health outcomes in older adults, such as disability, frailty, hospitalisation and premature death(Reference Cruz-Jentoft, Bahat and Bauer14,Reference Yuan and Larsson20,Reference Beaudart, Zaaria and Pasleau21) , accounting for a substantial health expenditure in the community and hospital settings(Reference Norman and Otten22).
Although new drugs for sarcopenia are in development and existing drugs are being explored(Reference Rolland, Dray and Vellas23), resistance exercise training (with/without nutritional supplementation) is considered the only effective non-pharmacological therapy for sarcopenia to date(Reference Hurst, Robinson and Witham24,Reference Shen, Shi and Nong25) . However, the anabolic response to exercise in older adults is less robust compared with younger adults(Reference Endo, Nourmahnad and Sinha26); the ability and willingness of older people to exercise may also be more limited(Reference Hurst, Robinson and Witham24). This has focused interest on other influences on healthy ageing such as high-quality diet and nutrition to be explored for their effectiveness in the prevention and treatment of sarcopenia – especially those that are cost-effective and feasible for the growing older adult population across different communities and health care settings.
Ageing processes show marked inter- and intraindividual differences (heterogeneity) at the tissue and cell level within different body systems(Reference Tian, Cropley and Maier27), including muscle(Reference Kirkeby and Garbarsch28), that are influenced by diverse internal and external factors(Reference Brook, Wilkinson and Phillips29). For example, skeletal muscle demonstrates plasticity in response to internal (e.g. inflammation(Reference Granic, Suetterlin and Shavlakadze7,Reference Liang, Zhang and Liu30) ) and external stimuli such as lifestyle, with exercise and nutrition playing important roles across the lifecourse(Reference Hurst, Robinson and Witham24,Reference Shen, Shi and Nong25,Reference Brook, Wilkinson and Phillips29,Reference Nunes, Colenso-Semple and McKellar31–Reference Calvani, Picca and Coelho-Júnior33) . The heterogeneity of muscle ageing and demonstrated muscle plasticity indicate the presence of modifiable factors that may influence the trajectory of muscle health with age and open the possibilities for the prevention and treatment of sarcopenia.
Since the conceptualisation of sarcopenia thirty years ago, research investigating nutrition-muscle relationships in observational and intervention studies in older adults has grown significantly, especially in the last decade(Reference Huang, Chen and Chen34). Three main approaches have been utilised to investigate the role of nutrition in preserving muscle health and ameliorating its decline with age: single nutrients, whole foods and whole diets effects (Fig. 1(A)), alone or combined with exercise training(Reference Shen, Shi and Nong25,Reference Nunes, Colenso-Semple and McKellar31–Reference Granic, Cooper and Robinson35) . However, despite the growth in research, there are still considerable gaps in understanding, especially for the links between nutrition and (incident) sarcopenia(Reference Robinson, Granic and Cruz-Jentoft32,Reference Calvani, Picca and Coelho-Júnior33) , and no consensus about nutrition recommendations for the prevention and/or treatment of sarcopenia exists across the sarcopenia working groups worldwide(Reference Chen, Arai and Assantachai36).
Summary of evidence from the three approaches applied in nutrition research for muscle health and sarcopenia. Created in BioRender. Granic, A. (2024) BioRender.com/x23y367 Recent evidence utilising a single nutrient, a whole food and a whole diet approach (panel A) was evaluated (panel B) from the latest qualitative and quantitative syntheses of observational and intervention studies in older adults with and without sarcopenia. Current evidence that may inform the development of preventive and intervention strategies for optimal muscle ageing and nutritional public policies aimed at combating sarcopenia is insufficient. Key: Red circles indicate evidence of no effect; yellow circles represent mixed, inconclusive evidence (i.e. evidence of effect/benefit or evidence of no effect); green circles indicate evidence of some effects/ benefits; purple circles indicate the absence of evidence or very scarce evidence of no effect for the selected outcomes. RE, resistance exercise; RCT, randomised controlled trial
The primary scope of this review is to evaluate the most recent evidence from qualitative and quantitative syntheses of findings from observational and intervention studies that applied these three approaches in investigating skeletal muscle ageing/sarcopenia-nutrition relationships in older adults. To aid this novel evidence synthesis, we used three exemplars. Protein supplementation with/without exercise in healthy and sarcopenic older adults was used as an exemplar of single nutrients approach. Fruits and vegetables were used as an exemplar of whole foods approach, and the Mediterranean diet served as an example of a whole diet approach applied in observational studies.
A single nutrient approach for the prevention and treatment of Sarcopenia
Investigations aimed at preventing or reducing age-related losses of muscle mass and function that utilised a single nutrient approach have greatly concentrated on finding the optimal nutrient levels for muscle health, applied either singly or combined with exercise training(Reference Shen, Shi and Nong25,Reference Nunes, Colenso-Semple and McKellar31–Reference Ganapathy and Nieves57) . These include protein (e.g. whey) and amino acids (e.g. leucine), n-3 fatty acids and vitamin D (Fig. 1(A)), with various combinations of protein supplementation with exercise being researched the most and systematically evaluated, including in meta- and network analyses(Reference Shen, Shi and Nong25,Reference Nunes, Colenso-Semple and McKellar31,Reference Cuyul-Vásquez, Pezo-Navarrete and Vargas-Arriagada40,Reference Gielen, Beckwée and Delaere42,Reference Ren, Lu and Wang44–Reference Thornton, Sim and Kennedy56) . In this section, we focus on protein. We briefly discuss the evidence for protein quantity, quality and timing for muscle health, summarising key findings from several recent quantitative syntheses of intervention studies (randomised controlled trials, RCTs) with protein, that were published in the last five years in older adults (aged ≥ 50 years) with and without sarcopenia.
Dietary protein and supplements: quantity, quality and timing
Protein quantity
An adequate intake of dietary protein supplying essential amino acids is vital for muscle protein synthesis (MPS) and the maintenance of whole-body protein mass throughout the lifecourse(Reference Calvani, Picca and Coelho-Júnior33,Reference Ispoglou, Witard and Duckworth37–Reference Campbell, Deutz and Volpi39,Reference Nishimura, Højfeldt and Breen58) . Daily protein requirements for a healthy person aged ≥ 18 years, irrespective of sex and age, are estimated to range between 0·8–0·9 g/kg body weight (BW) based on nitrogen balance studies(Reference Campbell, Deutz and Volpi39) and are the basis of international nutritional guidelines. However, debate continues about the optimal protein intake for muscle health in older adults and whether it should be higher than 0·8 g/kg BW/d(59), whilst considering other age-related changes influencing nutrition and skeletal muscle. These include changes in body composition(Reference Westbury, Syddall and Fuggle60), digestive system (e.g. dysphagia and reduced gastric emptying)(Reference Soenen, Rayner and Jones61), sensory system (taste and smell)(Reference Ho, Gupta and Fenwick62), energy requirements and expenditure(Reference Porter, Nguo and Collins63,Reference Cooper, Manini and Paton64) , appetite(Reference Cox, Morrison and Ibrahim65) and the presence of ill health(Reference Dodds, Granic and Robinson66,Reference Ye, Liang and Liu67) . Additionally, it has been demonstrated that older adults are less sensitive to anabolic stimuli from protein for MPS in response to protein feeding compared with young adults, a process termed ‘anabolic resistance’(Reference Aragon, Tipton and Schoenfeld68). For example, in a stable isotope tracer study older adults (aged 75 years) had a 16 % lower post-prandial MPS rate after 20 g protein (casein) intake compared with young adults (aged 34 years), but comparable post-absorptive (basal) MPS rates(Reference Wall, Gorissen and Pennings69). However, in a study using the same methodology with healthy and sarcopenic older men (aged ≥ 70 years), similar basal and post-prandial MPS rates were observed after 21 g bolus intake of enriched (whey) protein(Reference Kramer, Verdijk and Hamer70), indicating that the anabolic response in older sarcopenic muscle is not impaired.
Based on these and other evidence from cohort studies of ageing populations, several expert groups have increased dietary protein recommendations for older adults for the maintenance of muscle health, which may also prevent sarcopenia. For example, the recommendations of the PROT-AGE Study Group considered the health state and activity levels of an older person, proposing 1·0–1·2 g/kg BW/d of protein for healthy older adults, 1·2–1·5 g/kg BW/d for those with either chronic or acute illness, and 2·0 g/kg BW/d for malnourished older adults, and those with severe illnesses(Reference Bauer, Biolo and Cederholm71). At least 1·2 g/kg BW of protein post-exercise has been recommended for active older adults to stimulate MPS(Reference Bauer, Biolo and Cederholm71). However, in a meta-analysis conducted by the PROMISS (PRevention Of Malnutrition In Senior Subjects) consortium with four cohort studies and four national surveys from the EU and Canada in ∼8100 older adults (aged ≥ 55 years), the prevalence of low protein intake was high, especially for the higher recommendations (e.g. 46·7 % and 70·8 % for 1·0 and 1·2 g/kg BW/d of protein, respectively)(Reference Hengeveld, Boer and Gaudreau72). Similarly, according to the 2020–2025 Dietary Guidelines for Americans recommendations, about 30 % of men and 50 % of women aged ≥ 71 years do not consume enough protein-rich foods to meet the 0·8 g/kg BW/d requirement(Reference Berner, Becker and Wise73).
Protein quality
Another aspect of dietary protein intake to be considered for recommendations to support muscle health is protein quality. Different measures have been used to characterise the biological value of protein needed to meet the metabolic demands of muscle tissue(Reference Calvani, Picca and Coelho-Júnior33). Lately, the Digestible Indispensable Amino Acid Score (DIAAS) methodology has been implemented for measuring digestibility of each amino acid in supplements, foods and diets, based on their ileal tract digestibility and accounting for the effect of food processing(Reference Calvani, Picca and Coelho-Júnior33,Reference Bailey and Stein74) . Current recommendations consider animal-based proteins as high-quality proteins with DIAAS of 100 because of their high content of essential amino acids, such as leucine, and higher digestibility compared with plant-based proteins (DIAAS range 80–85)(Reference Calvani, Picca and Coelho-Júnior33,Reference Domić, Grootswagers and van Loon75) . However, production of plant-based proteins has lower environmental impact(Reference Lynch, Johnston and Wharton76) compared with animal-based proteins, and their anabolic properties for muscle could be enhanced by several strategies. These include having a higher protein intake, mixing different plant-based protein sources, or adding other anabolic stimuli (e.g. branched-chain amino acids such as leucine, n-3 fatty acids and exercise) to overcome their apparent inferiority to animal-based proteins for MPS(Reference Berrazaga, Micard and Gueugneau77,Reference Gorissen and Witard78) . Leucine and one of its metabolites, β-hydroxy-β-methyl butyrate are potent stimulators of MPS via, in part, the Akt-mTORC1-dependent (protein kinase B/mechanistic target of the rapamycin complex 1) signalling pathway and phosphorylation of 4E-BPs (the eukaryotic initiation factor 4E-binding proteins) and S6K1 (the ribosomal S6 protein kinase 1)(Reference Duan, Li and Li79,Reference Schiaffino, Reggiani and Akimoto80) . It has been shown that the anabolic potential of protein-rich foods is largely influenced by their leucine content (i.e. when leucine is not delivered as a supplement), especially affecting the post-prandial MPS response in older adults(Reference Cholewa, Dardevet and Lima-Soares81,Reference Rondanelli, Nichetti and Peroni82) . However, the effects of protein supplements enriched with leucine or food fortification with leucine (with/without exercise) on muscle health (mass and function) were equivocal(Reference Murphy, McCarthy and Roche38,Reference Rondanelli, Nichetti and Peroni82) . Overall higher leucine content of animal-based protein foods compared with plant-based foods(Reference Murphy, McCarthy and Roche38,Reference Rondanelli, Nichetti and Peroni82) should be considered when recommending myoprotective whole foods(Reference Granic, Cooper and Robinson35,Reference Granic, Dismore and Hurst83) and the foods-first strategy for sarcopenia(Reference Rondanelli, Nichetti and Peroni82,Reference Burd, Beals and Martinez84) .
Protein timing
The importance of protein timing and pattern of intake within a healthy diet (with/without exercise) has been researched lately, especially with the interest in chrono-nutrition and precision medicine approaches(Reference Calvani, Picca and Coelho-Júnior33,Reference Aoyama, Nakahata and Shinohara85,Reference Mao, Cawthon and Kritchevsky86) . Skeletal muscle does not have an inactive reservoir for protein (amino acids) such as for glucose (via glycogen)(Reference Merz and Thurmond3) but acts as an active protein store by incorporating dietary amino acids post-prandially(Reference Wolfe4), which is used in response to stress (fasting, starvation, critical illness, traumatic injury)(Reference Wolfe4). Thus, it has been suggested that per-meal protein intake and adequate anabolic response to each feed, as well as the distribution of protein across the meals, may be more important than total protein intake for muscle health in older adults(Reference Hudson, Iii and Campbell87). Although various strategies have been tested to find the optimal protein distribution for ageing muscle (e.g. even, or skewed protein feeding across the meals), evidence to date is inconclusive(Reference Hudson, Iii and Campbell87). A narrative review published in 2020 identified 12 observational and five intervention studies and concluded that even protein distribution may be an effective strategy to achieve a moderately high total protein intake in older adults who have low intakes (< 0·8 g/kg BW/d). For those with higher intake (0·8–1·3 g/kg BW/d), consumption of at least one meal with protein quantity sufficient to maximally stimulate MPS (30–40 g) is recommended for muscle health(Reference Hudson, Iii and Campbell87). Breakfast could be considered as a high-protein meal based on the findings from a 2024 scoping review showing that higher protein consumption at breakfast may be beneficial for muscle mass but not for muscle strength in middle-aged and older adults(Reference Khaing, Tahara and Chimed-Ochir88). Similarly, the PROMISS study findings from the longitudinal cohorts of older adults indicate benefits of consuming at least one meal with 30 g of protein/day to reach the minimum of 1·0 g/kg BW/d protein intake for muscle health(Reference Hengeveld, Chevalier and Visser89), regardless of the level of physical activity(Reference Mendonça, Hengeveld and Visser90).
In summary, protein as a single nutrient for muscle health in older adults has been well researched, however, findings are inconsistent and key recommendations are still lacking. Many narrative and systematic reviews, meta- and network analyses of observational and intervention studies have been published recently to understand the role of dietary protein and protein supplements (with/without exercise) in the prevention and treatment of sarcopenia in older adults(e.g.(Reference Shen, Shi and Nong25,Reference Nunes, Colenso-Semple and McKellar31–Reference Huang, Chen and Chen34,Reference Ispoglou, Witard and Duckworth37–Reference Ganapathy and Nieves57,Reference Wu, Huang and Chen91,Reference Tu, Kao and Tsai92)) . Here we summarise the main findings from most recent quantitative analyses of RCTs in healthy older adults and those with sarcopenia that may provide further insights about the protein-muscle health relationship and inform the strategies for sarcopenia treatment and prevention.
Protein supplementation, muscle health and sarcopenia
Intervention studies with protein in healthy older adults
Optimal protein quantity to support muscle mass and function (muscle strength and physical performance), as key components of sarcopenia, in healthy adults (aged < 65 and ≥ 65 years) was investigated in a 2022 systematic review and meta-analysis of 74 RCTs (published by September 2020)(Reference Nunes, Colenso-Semple and McKellar31). Most studies tested the effect of additional protein ingestion (by cut-offs of < 1·2 g/kg BW/d, 1·2–1·59 g/kg BW/d, and ≥ 1·6 g/kg BW/d) with resistance exercise. Notably, daily protein ingestion and their sources varied across the studies, from 1–4·4 g/kg BW/d in the intervention and 0·8–2·3 g/kg BW/d in the placebo groups. Overall, the results indicate that increasing protein intake during resistance exercise may result in gains in lean body mass in 62 RCTs, an approximately 0·5–0·7 kg gain difference between the intervention and placebo groups. In older adults (≥ 65 years), the benefits were seen if consuming 1·2–1·59 g of protein/kg BW/d with exercise, and ≥ 1·6 g/kg BW/d with resistance exercise in those aged < 65 years. A small effect of ingesting additional protein was observed on lower-body strength in 47 studies of participants subjected to resistance exercise. However, the effect of ingesting additional protein (with/without resistance exercise) was unclear for grip strength and physical performance in younger and older adults(Reference Nunes, Colenso-Semple and McKellar31). The authors concluded that protein intake > 1·0 g/kg BW/d with resistance exercise may have beneficial effects on muscle mass, but not on other components of sarcopenia. This is consistent with the findings of the review by the Health Council of the Netherlands that examined the health effects of protein quantity above the population reference intake proposed by the European Food Safety Authority of 0·83 g/kg BW/d(93) for muscle health and sarcopenia components (lean body mass, muscle strength and physical performance(Reference Hengeveld, de Goede and Afman41). This 2022 systematic review of 18 RCTs (published by April 2020) in older adults (aged ≥ 65 years), with an average habitual intake of ≥ 0·8 g/kg BW/d of protein from different sources and types (e.g. a mix of amino acids, protein supplementation), showed a possible beneficial effect of increased protein intake on lean body mass and muscle strength only when combined with exercise, and likely no effect on physical performance without exercise(Reference Hengeveld, de Goede and Afman41). Taken together, the authors concluded that the evidence for increasing protein intake above 0·8 g/kg BW/d to improve muscle health in the general older adult population is low and not convincing.
A 2020 systematic review and meta-analysis of 65 RCTs (published by March 2019) focused on the timing of protein intake for muscle-related outcomes in healthy adults (< 55 and > 55 years)(Reference Wirth, Hillesheim and Brennan48). The source and quantity of protein supplementation varied across the studies with whey protein (alone or in combination with other nutrients) being mostly used, and the timing of protein intake tied to exercise (e.g. immediately after, before and after). Daily protein intake ranged from 0·9 g–2·3 g/kg BW. There was some evidence that protein supplementation was effective in improving muscle mass in younger and older adults which was not dependent on protein timing. Removing RCTs without exercise in older adults did not alter the findings. No beneficial effects of protein supplementation were found for muscle strength (grip strength and leg press)(Reference Wirth, Hillesheim and Brennan48). Overall, this evidence summary supports a possible beneficial effect of protein supplementation with exercise for muscle mass in healthy older adults, independently of the timing of protein intake.
A dose-response relationship between protein intake and increase in lean muscle mass was further evaluated in a 2020 systematic review and meta-analysis of 105 RCTs (published by May 2019) in healthy adults (aged 19–81 years)(Reference Tagawa, Watanabe and Ito50). The multivariate-adjusted spline models revealed changes in lean muscle mass across a range of protein intake with or without exercise (e.g. a protein intake of 0·52–1·30 g/kg BW/d was associated with 0·06 kg (95 % CI: 0·03, 0·08) mean increase in muscle mass without resistance exercise, and 0·40 kg (95 % CI: 0·37, 0·43) with resistance exercise). An average effective dose of supplemental protein to increase muscle mass was determined as 0·17 g/kg BW/d. The results suggest that even a small increase in protein intake via supplementation may promote an increase in muscle mass with or without exercise(Reference Tagawa, Watanabe and Ito50). In comparison, another systematic review and meta-analysis of 29 RCTs (published in November 2017) with nutrition without exercise in older adults (aged ≥ 65 years) assessed the dose, duration, frequency, timing and adherence to interventions(Reference Martin-Cantero, Reijnierse and Gill53). The meta-analysis revealed an overall positive effect of amino acids, β-hydroxy-β-methyl butyrate, protein with amino acids supplementation on muscle mass, but not with protein alone, and protein with other nutrients. There was a great variability across the studies regarding the nutrition intervention characteristics and insufficient reporting about the treatment adherence, thus no conclusion could be drawn about the most effective intervention for muscle mass in older adults(Reference Martin-Cantero, Reijnierse and Gill53). A recent 2024 systematic review of 14 RCTs (published in 2013–2023) examined nutrition strategies on sarcopenia components (mass, strength, physical performance) in middle-aged and older women(Reference Thornton, Sim and Kennedy56). Six out of nine RCTs reported that protein supplementation alone or in combination with other (non)nutrients (e.g. vitamin D, resveratrol) had a beneficial effect on muscle mass and mixed evidence for an effect on muscle function(Reference Thornton, Sim and Kennedy56). Taken together, protein supplementation interventions in middle-aged and older adults may have positive but limited effect on muscle mass, whereas benefits for muscle strength and physical performance are less clear.
The latest umbrella review of systematic reviews of nutrition interventions to improve muscle health in older adults (aged ≥ 65 years) was conducted by the Sarcopenia Guidelines Development group of the Belgian Society of Gerontology and Geriatrics(Reference Gielen, Beckwée and Delaere42). Here, 15 reviews (published 2013–2017) were comprehensively assessed with the aim to generate recommendations based on the quality of evidence using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) method (i.e. certainty of evidence graded as very low, low, moderate and high). The supplements evaluated included protein supplementation, essential amino acids, leucine, β-hydroxy-β-methyl butyrate and others with or without exercise. Here we highlight the results for protein and leucine. Because of the low number and low quality of the reviews, the evidence supporting the recommendations was low to moderate. Specifically, there was a low level of evidence for a positive effect of protein supplementation for muscle mass, but no evidence for effects on muscle strength and physical performance. There was a moderate level of evidence for additive effect of protein supplementation in combination with resistance exercise for muscle mass in interventions lasting ≥ 24 weeks, and for muscle mass and strength in obese older adults, but no effects for physical performance. However, leucine supplementation alone has shown positive effects on muscle mass in older adults with sarcopenia (moderate level of evidence)(Reference Gielen, Beckwée and Delaere42). The authors concluded that there was some evidence of beneficial effects of protein supplementation in combination with resistance exercise for muscle mass and strength in obese older adults, and for interventions lasting longer than 24 weeks, and leucine for sarcopenia.
In summary, despite extensive research on the effect of protein and amino acids supplementation (with/without exercise) on muscle in healthy older adults (≥ 65 years), there is still lack of information to inform dietary recommendations. Protein supplementation in combination with resistance exercise may be beneficial for muscle mass, especially in the interventions of longer duration. Protein intake > 0·8 g/kg BW/d in combination with exercise has a possibly positive effect on muscle mass, but not on other sarcopenia components. It is also noted that heterogeneity in study designs (e.g. for intervention: protein quality, quantity, timing), duration, outcome measures and populations studied, limited collation and quantitative synthesis of evidence.
Interventions with protein in older adults with sarcopenia
The following mixed conclusions have been obtained from the recent reviews and meta-analyses investigating the effectiveness of protein supplementation (with/without exercise) in older adults with sarcopenia(Reference Cuyul-Vásquez, Pezo-Navarrete and Vargas-Arriagada40,Reference Shi, Tang and Stanmore43,Reference Kamińska, Rachubińska and Grochans46,Reference Li, Zhang and Luo52,Reference Whaikid and Piaseu54,Reference Wu, Huang and Chen91) . Three meta-analyses evaluated RCTs investigating the effect of whey protein supplementation for improvements in sarcopenia components(Reference Cuyul-Vásquez, Pezo-Navarrete and Vargas-Arriagada40,Reference Kamińska, Rachubińska and Grochans46,Reference Li, Zhang and Luo52) . A 2023 meta-analysis of five RCTs (published by January 2023) in older adults with sarcopenia (average age 77·3 years) found a small increase in muscle mass and strength (grip strength) in interventions with whey supplementation and resistance exercise that did not reach the minimally important clinical difference. The qualitative synthesis of findings of whey supplementation for physical performance were mixed(Reference Cuyul-Vásquez, Pezo-Navarrete and Vargas-Arriagada40). Another 2023 meta-analysis of 10 RCTs (published by December 2022) concluded that whey supplementation with exercise had no effect on sarcopenia components in sarcopenic older adults (aged ≥ 74 years)(Reference Kamińska, Rachubińska and Grochans46). Positive results (effect sizes) for muscle strength were affected by the study durations and age of participants(Reference Kamińska, Rachubińska and Grochans46). However, different results were obtained in a 2024 meta-analysis of 10 RCTs (published by June 2023) of whey supplementation (with/without resistance exercise) in older adults (aged ≥ 60 years) with sarcopenia living in the community or hospitalised(Reference Li, Zhang and Luo52). Whey supplementation alone significantly increased muscle mass and physical performance (gait speed), and improved muscle strength (grip strength) when combined with resistance exercise in sarcopenic older adults, and promoted total protein and energy intake, and reduced inflammatory markers(Reference Li, Zhang and Luo52). Similarly, another 2024 meta-analysis of 7 RCTs (published by January 2023) of protein supplementation with resistance exercise in community-dwelling older adults (aged ≥ 60 years) with sarcopenia showed significant improvements in muscle mass and strength (grip strength but not in chair rises)(Reference Whaikid and Piaseu54). No improvements were seen in physical performance (gait speed)(Reference Whaikid and Piaseu54).
To investigate further whether the combination of protein and resistance exercise is more effective in improving all components of sarcopenia compared with each intervention alone, a 2023 scoping review evaluated 59 studies (70 % were RCTs; published in 2010–2023) in community-dwelling older adults (aged ≥ 60 years) with probable sarcopenia (low muscle mass or low muscle strength) or sarcopenia(Reference Shi, Tang and Stanmore43). The results revealed that nutrition (protein, protein diet, protein supplements) with resistance exercise was the most frequent multicomponent intervention studied. This type of intervention and exercise-only intervention showed positive results most frequently for physical performance (e.g. gait speed), muscle mass and strength (grip strength). However, most studies lacked post-trial follow-up, missing out on valuable information about long-term benefits and potential hazards of these interventions(Reference Shi, Tang and Stanmore43).
Lastly, several systematic reviews and meta-analyses combined RCTs with protein (with/without exercise) in healthy older adults and those with sarcopenia(e.g. (Reference Ren, Lu and Wang44,Reference Nasimi, Sohrabi and Nunes49,Reference Kirwan, Mazidi and Rodríguez García51,Reference Liao, Huang and Chen55,Reference Tu, Kao and Tsai92)) , and reported mixed results. For example, a 2023 systematic review and meta-analysis of 30 RCTs (published by June 2022) examined the effect of whey protein supplementation (with/without vitamin D, and in combination with resistance exercise or without) on sarcopenia components in older adults (aged ≥ 60 years)(Reference Nasimi, Sohrabi and Nunes49). In subgroup analyses by sarcopenia status, whey protein supplementation significantly improved muscle mass and physical function in sarcopenic and frail older adults but had no effect on muscle health in healthy individuals. A 2024 network meta-analyses of 78 RCTs (published by July 2023) examined the effectiveness of protein supplementation with resistance exercise on sarcopenia components in community-dwelling, hospitalised and institutionalised older adults (aged ≥ 50 years) with acute and chronic conditions(Reference Liao, Huang and Chen55). Of all protein sources identified, whey protein supplementation was the most efficient in enhancing the anabolic effect of resistance exercise on muscle mass, muscle strength (grip strength) and function (walking speed). These effects were moderated by sex, health conditions and supplement dose(Reference Liao, Huang and Chen55). However, in contrast, no effects of nutrition interventions with whey protein or β-hydroxy-β-methyl butyrate (without exercise) were found in 12 RCTs (published by May 2021) on any of the sarcopenia components in subgroup analyses of healthy and sarcopenic older adults(Reference Tu, Kao and Tsai92).
Taken together, quantitative syntheses of numerous RCTs investigating the effects of protein as a single nutrient on sarcopenia components in older adults with sarcopenia showed benefits for muscle mass and strength when combined with exercise, and a possible benefit for physical performance. Whey protein with resistance exercise has consistently shown some positive effects across the trials. However, these effects may be dependent on the setting (community v. clinical), age and health of participants and protein dose.
In summary, there is some evidence for beneficial effects of protein supplementation with exercise for muscle health and sarcopenia in older adults. However, the conclusions of the systematic reviews, meta- and network analyses presented here need to be interpreted with caution. All studies have indicated a high variation in the methodological quality of the included RCTs, publication bias and differences across the RCT protocols (e.g. heterogeneity in protein supplementation (quantity, source, timing), outcome measures (e.g. non-standardised measurement of muscle mass) and the availability of data on baseline protein intake). Thus, a definite protocol of specific nutrition strategy with optimal dosage and duration of the protein intervention for the prevention and treatment of sarcopenia cannot be determined.
A whole food approach for the prevention and treatment of Sarcopenia
Nutrient-rich foods with myoprotective potential: fruits and vegetables
Unlike the protein (amino acids)-muscle health relationship (a single nutrient approach) being examined in many qualitative and quantitative summaries of individual studies with older adults, the role of whole foods hypothesised to be beneficial for muscle health (myoprotective) has been rarely systematically evaluated(Reference Robinson, Granic and Cruz-Jentoft32,Reference Granic, Cooper and Robinson35,Reference Granic, Dismore and Hurst83) . Recently, we have summarised evidence from observational and intervention studies with nutrient-rich whole foods associated with the improvements in sarcopenia components in older adults(Reference Granic, Cooper and Robinson35,Reference Murphy, McCarthy and Roche38) and the risk reduction of incident sarcopenia in mid- and late adulthood(Reference Robinson, Granic and Cruz-Jentoft32). The foods most frequently researched were protein-rich foods (e.g. dairy)(Reference Granic, Hurst and Dismore94), and the foods consistently showing benefits for muscle health were antioxidant-rich foods (fruits and vegetables)(Reference Granic, Cooper and Robinson35,Reference Granic, Dismore and Hurst83,Reference Besora-Moreno, Llauradó and Valls95) . In predominantly observational studies these foods were evaluated either singly(Reference Granic, Hurst and Dismore94), or as multiple foods(Reference Park, Park and Won96), or their individual effects on sarcopenia components were assessed as a part of a heathy diet/dietary pattern(Reference Perälä, von Bonsdorff and Männistö97). Here, we have used fruits and vegetables as an exemplar of whole foods rich in nutrients (e.g. vitamins, minerals, fibre, proteins) and non-nutrients (e.g. biologically active phytonutrients such as lycopene and fisetin) implicated in general(Reference Martel, Ojcius and Ko98–Reference Yousefzadeh, Zhu and McGowan100) and muscle health(Reference Putra, Konow and Gage101,Reference Bagherniya, Mahdavi and Shokri-Mashhadi102) , through various cellular and molecular pathways, including antioxidative(Reference Bagherniya, Mahdavi and Shokri-Mashhadi102,Reference Fougere, van Kan and Vellas103) and anti-inflammatory pathways(Reference Prokopidis, Mazidi and Sankaranarayanan104).
The health benefits of higher consumption of variety of fruits and vegetables have been well established, with moderate to strong effects being reported for cardiovascular diseases, cancer and mortality risk reduction in numerous qualitative and quantitative synthesises(Reference Wallace, Bailey and Blumberg105–Reference Hu108). As an essential part of a healthy, balanced diet across the lifecourse, fruits and vegetables are indorsed as a component of food-based dietary guidelines in over 100 countries to promote healthy eating habits and combat diet-related diseases in the population(109). Compared with single nutrients, there is a greater understanding of a food-first approach among the general public to foster healthy ageing and longevity(Reference Hu108). Biologically, whole foods such as fruits and vegetables may provide health benefits beyond the sum of those obtained from each constituent, in which nutrient and non-nutrient within the foods act synergistically and cumulatively on health outcomes. For example, higher habitual consumption of fruits and vegetables may increase the antioxidative capacity of the diet and counteract systemic low-grade inflammation (i.e. inflammaging) that arises through multiple molecular mechanisms, including oxidative stress and compromised antioxidative defence system that, in turn, activate pro-inflammatory signalling cascades(Reference Chung, Kim and Kim110). Chronic inflammation is an established hallmark of ageing(Reference Schmauck-Medina, Molière and Lautrup111,Reference López-Otín, Blasco and Partridge112) that, in connection with other hallmarks such as altered nutrient sensing(Reference Baechle, Chen and Makhijani113), drives many age-related processes and diseases(Reference Franceschi and Campisi114), including the inflammatory response in ageing muscle and sarcopenia(Reference Granic, Suetterlin and Shavlakadze7,Reference Liang, Zhang and Liu30,Reference Jimenez-Gutierrez, Martínez-Gómez and Martínez-Armenta115,Reference Wang116) . Importantly, the Dietary Inflammation Index®(Reference Shivappa, Steck and Hurley117) have shown anti-inflammatory potential in reducing the risk of musculoskeletal diseases(Reference Su, Yeung and Chen118), including sarcopenia(Reference Diao, Yan and He119,Reference Xie, Wang and Wu120) . Thus, promoting higher habitual consumption of fruits and vegetables within a healthy diet for their antioxidative and anti-inflammatory properties may be one of the nutrition strategies to counteract detrimental effects of many age-related diseases with inflammaging and oxidative stress as underlying causes, such as sarcopenia.
Fruits and vegetables for the prevention and treatment of sarcopenia
In a 2020 systematic review, we evaluated evidence from 28 studies (19 observational and 9 interventional; published by March 2020) examining the relationship between individual whole foods (meat, fish, eggs, fruits and vegetables and non-liquid dairy with/without exercise), sarcopenia and sarcopenia components in adults aged ≥ 50 years(Reference Granic, Dismore and Hurst83). The myoprotective potential of these foods was further examined in the most recent prospective studies and RCTs (without exercise) assessing later risk of sarcopenia and/or decline in sarcopenia components in mid- (< 60 years) and late adulthood in a 2024 narrative review (60–70 years)(Reference Robinson, Granic and Cruz-Jentoft32). We also evaluated the latest scientific evidence (published between April 2022–November 2023) from studies of whole foods (protein-rich and antioxidant-rich foods; with/without exercise) in older adults aged ≥ 55 years(Reference Granic, Cooper and Robinson35). The main conclusions from these qualitative syntheses were that largely consistent positive associations were observed between higher consumption of fruits and vegetables (total intake, fruits, or vegetable total intake) and measures of muscle health. These were based on observational studies (mostly cross-sectional), and evidence from RCTs was limited. Here we summarise key findings from these reviews and give examples of individual studies, concentrating on relevant prospective studies and RCTs that examined fruits and vegetables in relation to sarcopenia/sarcopenia components (with/without exercise) in older adults.
Our 2020 systematic review of individual myoprotective foods found positive associations between fruits and vegetables intake and physical performance, and moderate evidence for a role in preventing loss of muscle strength and sarcopenia, based solely on observational studies(Reference Granic, Dismore and Hurst83). For example, an inverse dose-response relationship was found between baseline fruits and vegetables consumption and the risk of slow walking speed over 2·5 years in three independent cohorts of over 2900 community-dwelling older adults (aged ≥ 60 years) from Spain and France(Reference García-Esquinas, Rahi and Peres121). For participants consuming 1, 2, or ≥ 3 portions of fruits a day (1 portion = 120 g) compared with 0 portions, the odds of walking speed decline were 0·59 (95 % CI: 0·27, 0·90), 0·58 (0·29, 0·86) and 0·48 (0·20, 0·75), respectively. Similarly, the corresponding odds for vegetables consumption (1 portion = 150 g) were 0·69 (0·42, 0·97), 0·56 (0·35, 0·77) and 0·52 (0·13, 0·92). However, no associations were found between fruits and vegetables consumption and muscle strength(Reference García-Esquinas, Rahi and Peres121). In a longitudinal study of over 1400 Australian post-menopausal women (aged ≥ 70 years), higher total vegetables (1 serving = 75 g) or fruits intake (1 serving = 150 g) was associated with reduced odds of muscle strength (grip strength) or physical performance decline (Timed Up-and-Go test) over 14·5 years of follow-up(Reference Sim, Blekkenhorst and Lewis122). Compared with low vegetables intake (< 2 servings/d), a higher intake (≥ 3 servings/d) was associated with 31 % lower odds of weak grip strength, whereas every 75 g increase in vegetables intake was associated with 12 % lower odds of decline in Timed Up-and-Go test. For fruits, high (≥ 2 servings/d) compared with low (< 1 serving/d) intake was associated with 30 % lower odds of grip strength, but not physical performance decline. Similar dose-response relationship between fruits and vegetables consumption and shared components of sarcopenia and frailty (low muscle strength and physical performance) was observed in a recent 2021 systematic review and meta-analysis of 14 observational studies (10 prospective)(Reference Ghoreishy, Asoudeh and Jayedi123). Mixed results were obtained in a study of over 430 middle-aged African American adults (aged ≥ 49 years) with low intake of fruits and vegetables at baseline(Reference Ribeiro, Morley and Malmstrom124). At 6-year follow-up, higher intake of vegetables other than carrots, salads and potatoes was associated with stronger grip strength, whereas fruit juice was associated with grip strength decline(Reference Ribeiro, Morley and Malmstrom124).
Further evidence for the role of fruits and vegetables in muscle health in mid-life was summarised in our 2023 review, specifically suggesting harmful effects of habitual low fruits and vegetables consumption in middle-aged individuals for the risk of muscle health decline in later life(Reference Robinson, Granic and Cruz-Jentoft32). A longitudinal study of British civil servants, the Whitehall II study, assessed fruits and vegetables consumption on three occasions (1991–1993) when the participants were, on average, 50, 55 and 61 years old, before being assessed for muscle strength (GS) and physical performance (walking speed) in 2007–2009 at age of 66(Reference Sabia, Elbaz and Rouveau125). Low fruits and vegetables consumption (< 2 times/d) at every dietary assessment in mid-adulthood was associated with slower walking speed at follow-up. Furthermore, the accumulation-of-risk model with a cumulative fruits and vegetables score (i.e. the number of times low fruits and vegetables intake was reported over the three occasions) revealed the best model fit for longitudinal data, suggesting greater effects on muscle function with a longer duration of low fruits and vegetables consumption. These cumulative associations were independent of other unhealthy behaviours (smoking, low physical activity and nonmoderate alcohol drinking). In contrast, the cumulative associations with low fruits and vegetables and GS were weaker and attenuated by adjustment for other behavioural risk factors(Reference Sabia, Elbaz and Rouveau125).
Several studies examined the prospective associations between sarcopenia components and fruits and vegetables included in a dietary pattern (e.g. the Nordic Diet Score, Mediterranean diet) in older adults (aged ≥ 60 years), but found mixed results(e.g. (Reference Perälä, von Bonsdorff and Männistö97,Reference Perälä, von Bonsdorff and Männistö126–Reference Bruyère, Reginster and Beaudart128)) . For example, in the Helsinki Cohort Study of over 1000 older adults (born 1934–1944), habitual diet was assessed at mean age of 61 (2001–2004) to calculate the Nordic Diet Score score that included Nordic fruits (apples, pears and berries) and Nordic vegetables (tomatoes, cucumber, leafy vegetables, roots, cabbages and peas)(Reference Perälä, von Bonsdorff and Männistö126). Individual foods were examined for the prospective associations with physical performance (the Senior Fitness Test), muscle mass and strength (GS and leg strength) in men and women at age 71 years (2011–2013). Only consumption of Nordic fruits was positively associated with the Senior Fitness Test score in women, but not in men(Reference Perälä, von Bonsdorff and Männistö126). However, in another examination of the protective effects of Nordic fruits and vegetables on muscle mass and function in the same cohort, no associations were found at 10-year follow-up(Reference Perälä, von Bonsdorff and Männistö97).
A few studies examining the role of fruits and vegetables in muscle health in older adults have been published more recently and summarised in(Reference Granic, Cooper and Robinson35). This latest qualitative synthesis for myoprotective roles of protein-rich (dairy) and antioxidant-rich (fruits and vegetables foods noted the dominance of observational studies (cross-sectional) and the lack of evidence from RCTs(Reference Besora-Moreno, Llauradó and Valls95). For example, in a 2020 systematic review and meta-analysis of 28 studies (19 observational (13 cross-sectional) and 9 RCTs; published between 2000–2020), the effect of antioxidant-rich foods (fruits and vegetables, beans, nuts, seeds, tea, cacao and oils) and antioxidant supplements on muscle health was investigated in adults aged ≥ 55 years(Reference Besora-Moreno, Llauradó and Valls95). Based on largely cross-sectional evidence, the authors found positive associations between higher fruits and vegetables consumption for muscle mass, strength, measures of muscle agility and mobility. Of five observational studies (four cross-sectional) examining the risk of sarcopenia in relation to antioxidant-rich foods (fruits and vegetables) or dietary patterns with higher consumption of these foods, only three found significant inverse associations. However, no RCTs examining the effect of fruits and vegetables in people with sarcopenia were reported(Reference Besora-Moreno, Llauradó and Valls95).
The lack of intervention studies with whole foods (fruits and vegetables), with/without exercise, for muscle health was also discussed in a 2022 review investigating lifestyle factors for the prevention and treatment of sarcopenia published between 2012–2022(Reference Bruyère, Reginster and Beaudart128). We have found one recent 6-month feasibility trial with 91 older adults (aged years ≥ 50 years) with habitually low fruits and vegetables consumption who were instructed to add 100 g/d (4 servings/d) of dried fruit to their diet to improve muscle mass and function(Reference Ceglia, Shea and Rasmussen129). No significant changes in physical performance, lean non-fat and non-bone lean muscle mass were observed after 6 months. Further examination of the RCTs registries for intervention studies with fruits and vegetables for muscle heath and sarcopenia revealed only a few new entries (e.g. Clinical Trial gov. NCT05863507, a trial of freeze-dried grape powder, a rich source of polyphenols, to mitigate sarcopenia in post-menopausal women), indicating that higher level of evidence is still absent. Taken together, there is a need for well-designed intervention studies, of sufficient duration, with whole foods (with/without exercise) to better validate their efficacy and mechanisms of action for the prevention and treatment of sarcopenia in a diverse population of older adults(Reference Granic, Cooper and Robinson35,Reference Granic, Dismore and Hurst83,Reference Granic, Hurst and Dismore94,Reference Bruyère, Reginster and Beaudart128) .
In summary, there is reasonably consistent evidence mainly from observational studies showing benefits of higher consumption of fruits and vegetables for healthy muscle ageing. Higher daily intake of fruits and vegetables as a part of habitual diet may be beneficial for physical performance (in cross-sectional studies) and in preventing physical performance and muscle strength decline (in prospective studies) in middle-aged and older adults. Inconclusive evidence was found for their role in muscle mass. However, interventions with whole foods (fruits and vegetables) for muscle health are scarce, and those in older adults diagnosed with sarcopenia are lacking.
Potential health benefits of whole foods for ageing muscle should be considered in the context of other foods consumed within the diet/dietary pattern and the inevitable collinearity of individual foods (nutrients) in observational studies, which complicates the detection of an association (effect) of a single food and health outcomes. Because foods are consumed in combination, a low or high consumption of one (e.g. fruits and vegetables) could be an indicator of overall diet quality and the consumption of other foods that are either detrimental or beneficial for muscle heath. Therefore, a growing number of observational studies have used a whole diet approach to account for a complex interaction of foods and (non)nutrients and in diets and their influence on healthy ageing(Reference Hu108).
A whole diet approach for the prevention and treatment of Sarcopenia
Mediterranean diet
Of all healthy diets/dietary patterns investigated in nutritional epidemiology in relation to muscle ageing and sarcopenia in older adults, the Mediterranean diet has gained most scientific attention for potential health benefits. However, evidence is predominantly from observational studies(Reference Robinson, Granic and Cruz-Jentoft32,Reference Craig, Bunn and Hayhoe130–Reference Trichopoulou142) . Here we summarise evidence from several narrative and systematic reviews (with a few meta-analyses) of cross-sectional and prospective studies published recently (2017–2024), that investigated the Mediterranean diet in relation to sarcopenia in Mediterranean and non-Mediterranean populations(Reference Craig, Bunn and Hayhoe130–Reference Cailleaux, Déchelotte and Coëffier139). These mostly qualitative syntheses assessed studies that used the Mediterranean diet-style indices only(Reference Craig, Bunn and Hayhoe130–Reference Silva, Pizato and da Mata132,Reference Coelho-Júnior, Trichopoulou and Panza136–Reference Andreo-López, Contreras-Bolívar and García-Fontana138) or evaluated the Mediterranean diet with other healthy dietary patterns(Reference Robinson, Granic and Cruz-Jentoft32,Reference Bloom, Shand and Cooper133–Reference Jang, Han and Jang135,Reference Cailleaux, Déchelotte and Coëffier139) . Evidence from prospective studies was scarce(Reference Jang, Han and Jang135), especially studies with repeat dietary assessments(Reference Robinson, Granic and Cruz-Jentoft32,Reference Serra-Majem, Tomaino and Dernini143) , whereas RCTs were lacking(Reference Granic, Sayer and Robinson134,Reference Papadopoulou, Detopoulou and Voulgaridou137) . Only two included meta-analyses because of a high heterogeneity across the studies (e.g. differences in the Mediterranean diet indices (exposure), muscle-related outcomes, and their measurements, low number of studies with sarcopenia, and variations in adjustments for confounding). Overall, reasonably consistent positive results were found between a higher Mediterranean diet adherence and muscle function (walking speed, mobility) in cross-sectional studies and less decline over time in prospective studies. Mixed results were found for other sarcopenia components, muscle strength (grip strength) and muscle mass, and inconclusive evidence for sarcopenia in a few observational studies. Without RCTs, cause and effect conclusions for the Mediterranean diet in muscle health (prevention and treatment of sarcopenia) with ageing cannot be determined.
Characteristics of Mediterranean diet
The Mediterranean diet represents a healthy dietary pattern that has been extensively studied in relation to various health outcomes(Reference Trichopoulou142), including healthy ageing and longevity(Reference Mazza, Ferro and Pujia141). The original Mediterranean diet represents a traditional diet of populations living in the Mediterranean Basin during the 50s and 60s in the last century(Reference Trichopoulou142). Despite changes in the diet composition in the last decades, the Mediterranean diet, as a plant-based diet, is considered environmentally sustainable(Reference Serra-Majem, Tomaino and Dernini143). The traditional Mediterranean diet is characterised by a low consumption of red meats and meat products, moderate consumption of fish, eggs, poultry, fermented dairy (cheese and yoghurt) and high consumption of plant foods (fruits, vegetables, legumes, tree nuts and cereals) and extra-virgin olive oil as the main source of fat. Red wine is consumed moderately during meals.
To measure adherence to the Mediterranean diet-style diet in different populations, various indices/scores have been developed. For example, there were 22 indices by 2015 that differed in their scoring systems and composition (e.g. Mediterranean Diet Scale: 9 components, range 0–9; Mediterranean Lifestyle Index: 28 components, range 0–28)(Reference Hernández-Ruiz, García-Villanova and Guerra Hernández144). However, the main principles of the Mediterranean diet – its plant-based core and a low red meat consumption (positive components) – have been preserved across the indices(Reference Hernández-Ruiz, García-Villanova and Guerra Hernández144).
The Mediterranean diet is a rich source of numerous nutrients and non-nutrients, such as vitamins (carotenoids, C, D, E, folate), minerals (K, Mg, Fe, Se, Ca), mono- and polyunsaturated fatty acids (MUFA and PUFA) and phytochemicals that have antioxidative and anti-inflammatory properties(Reference Granic, Sayer and Robinson134,Reference Davis, Bryan and Hodgson145) . We have hypothesised that these (non)nutrient may have a direct effect on the ageing muscle (i.e. myoprotective effect) by acting synergistically and cumulatively on the pathophysiological mechanisms of sarcopenia(Reference Granic, Suetterlin and Shavlakadze7,Reference Wiedmer, Jung and Castro13) , and an indirect effect by reducing the risk of age-related conditions related to sarcopenia(Reference Granic, Sayer and Robinson134). Other benefits of the Mediterranean diet may involve lesser acidity and favourable acid-base balance of the diet, which have been implicated in muscle health in older adults(Reference Gholami, Bahrampour and Samadi146,Reference Faure, Fischer and Dawson-Hughes147) .
Mediterranean diet for the prevention and treatment of sarcopenia
Evidence summary from narrative and systematic reviews
Here we summarise key findings and conclusions of several recent narrative and systematic reviews that investigated the associations between sarcopenia components and sarcopenia in various populations of middle-aged and older adults (aged ≥ 45 years)(Reference Craig, Bunn and Hayhoe130–Reference Cailleaux, Déchelotte and Coëffier139). Four reviews (published 2017–2018) have been described in detail in our 2019 systematic review of dietary patterns, muscle ageing and sarcopenia(Reference Granic, Sayer and Robinson134). Briefly, in a 2017 systematic review of observational studies (published in 2016) examining the role of the Mediterranean diet in musculoskeletal health across the lifecourse, only two studies (one cross-sectional and one prospective) in older adults were included(Reference Craig, Bunn and Hayhoe130). Positive cross-sectional associations were reported between the Mediterranean diet, muscle mass and leg power, but no associations were found in the prospective study(Reference Craig, Bunn and Hayhoe130). A 2017 narrative review of the role of the Mediterranean diet in frailty and sarcopenia, synthesised evidence from 12 observational studies (7 assessed sarcopenia or components of sarcopenia/sarcopenic symptomology; published 2008–2017) in older adults (aged ≥ 55 years)(Reference McClure and Villani131). All studies (cross-sectional and prospective) reported lower risks of sarcopenic symptomology with greater adherence to the Mediterranean diet (i.e. lower extremity functioning and mobility). A 2018 systematic review and meta-analysis of 12 studies (8 prospective; published 2011–2017) investigated the relationship between adherence to the Mediterranean diet, frailty, functional disability and sarcopenia in older adults (aged ≥ 60 years)(Reference Silva, Pizato and da Mata132). Only two prospective studies of sarcopenia were included and showed no association between the Mediterranean diet and sarcopenia risk. However, cross-sectional studies indicated better sarcopenia components with higher Mediterranean diet scores. Also, higher adherence to the Mediterranean diet was associated with a lower risk of frailty and functional impairment (e.g. assessed by physical component sub-scale of SF-12)(Reference Silva, Pizato and da Mata132). Another 2018 systematic review of the association between diet quality (pre-defined or data-driven dietary indices) and sarcopenia in middle-aged and older adults (aged ≥ 50 years), included 26 studies (published by 2016) and found strong observational evidence for the association between ‘heathier’ diets (including the Mediterranean diet) and lower risk of decline in physical performance (e.g. walking speed), but not for decline in muscle strength(Reference Bloom, Shand and Cooper133). Evidence from cross-sectional studies for other sarcopenia components and sarcopenia was weak(Reference Bloom, Shand and Cooper133).
In our 2019 systematic review, along with the summary of evidence from previous reviews(Reference Craig, Bunn and Hayhoe130–Reference Bloom, Shand and Cooper133), we have included additional studies (published 2017–2019) that further corroborated the positive associations between the Mediterranean diet scores and better physical performance (walking speed and Timed Up-and-Go test) in cross-sectional but not in prospective studies(Reference Granic, Sayer and Robinson134). The main conclusions of this review were that only a few studies have investigated the role of the Mediterranean diet in the aetiology of sarcopenia, but a number of studies have explored the relationship between components of sarcopenia and a decline in physical function. Specifically, higher adherence to the Mediterranean diet was positively associated with lower extremity functioning, mobility and better walking speed over time. No associations were found for the measures of upper-body muscle strength in most of the studies. The results suggest that, whilst the Mediterranean diet may not improve muscle strength in older adults, higher adherence to the Mediterranean diet-style diets may be beneficial for mobility and general physical functioning. Based on this summary, the Mediterranean diet may have the greatest myoprotective potential compared with other healthy diets. However, prospective studies with longer duration are needed to support future clinical trials of myoprotective dietary patterns in older adults. Differences in findings could be explained by heterogeneity across the studies, especially in the Mediterranean diet indices used in different populations. To date, no univocal definition of the Mediterranean diet and its dietary score exists, which should be based on modern understanding of the Mediterranean diet(Reference Serra-Majem, Tomaino and Dernini143) to advance the field of nutritional epidemiology and sarcopenia(Reference Hu108).
Further evidence summary from a 2021 systematic review of diet quality and sarcopenia in middle-aged and older adults (age ≥ 45 years) was based on 14 prospective studies (7 with the Mediterranean diet; published by 2020)(Reference Jang, Han and Jang135). Mixed results were reported suggesting benefits of the Mediterranean diet for muscle mass, but inconclusive evidence for muscle strength (grip strength). The evidence for physical performance (walking speed, the risk of developing mobility disability) was also mixed, with some studies reporting positive and others no associations (especially in women). Only a few studies examined the associations between the Mediterranean diet and sarcopenia and found nil results(Reference Jang, Han and Jang135). The authors concluded that there is conflicting evidence for the association between the Mediterranean diet, sarcopenia components and sarcopenia(Reference Jang, Han and Jang135). Another 2021 systematic review and meta-analysis of 53 observational studies (19 cross-sectional, 35 prospective studies; published by May 2021), investigated the association between the Mediterranean diet adherence and cognitive and physical functioning in older adults (aged ≥ 60 years)(Reference Coelho-Júnior, Trichopoulou and Panza136). Eight cross-sectional and 10 prospective studies examined the link between the Mediterranean diet and components of sarcopenia (walking speed, Timed Up-and-Go test, grip strenght, Short Physical Performance Battery). In a meta-analysis of cross-sectional studies, a high adherence to the Mediterranean diet was associated with better walking speed (Standard Mean Difference 0·42 (95 % CI: 0·12, 0·72)) and knee muscle strength (0·26 (95 % CI: 0·17, 0·36)). No associations were found for GS and mobility. Equally, no prospective associations were found in meta-analysis of five studies linking the Mediterranean diet adherence to incidence of mobility problems(Reference Coelho-Júnior, Trichopoulou and Panza136). The latest 2023 systematic review of the role of the Mediterranean diet in the prevention of sarcopenia (components), included 10 studies (6 prospective; published 2000–2022) in healthy older adults (age ≥ 65 years)(Reference Papadopoulou, Detopoulou and Voulgaridou137). Both positive and negative associations were reported for muscle strength (grip strength) in four studies. Of six studies (five prospective) investigating the association between the Mediterranean diet and muscle function (walking speed, Short Physical Performance Battery, squat test), all but one reported positive association. No associations were observed between the Mediterranean diet and sarcopenia in a few included studies(Reference Papadopoulou, Detopoulou and Voulgaridou137).
None of the summarised reviews reported RCTs with the Mediterranean diet in healthy or sarcopenic older adults.
Additional evidence from individual studies
We have identified three recent individual studies that investigated the associations between the Mediterranean diet and sarcopenia(Reference Cacciatore, Calvani and Marzetti148–Reference Mazza, Ferro and Maurotti150) classified with the European Working Group on Sarcopenia in Older People (EWGSOP2) definition(Reference Cruz-Jentoft, Bahat and Bauer14). A cross-sectional study of 2963 participants (mean age 72·8 ± 5·7 years) enrolled in the Longevity Check-up 7+ project, investigated the associations between the Mediterranean diet (a modified Medi-Lite categorised as low (≤ 8), good (9–11), or high (≥ 12)) and probable sarcopenia (low GS; < 27 kg in men, and < 16 kg in women)(Reference Cacciatore, Calvani and Marzetti148). Those with lower Mediterranean diet score (low adherence) had higher prevalence of probable sarcopenia (25·9 %) compared with those with good and high scores (19·1 % and 15·5 %, respectively). In the fully adjusted models, good (OR 0·71 (95 % CI: 0·55, 0·92)) and high (0·60 (95 % CI: 0·44, 0·81) adherence to the Mediterranean diet was associated with lower odds of probable sarcopenia(Reference Cacciatore, Calvani and Marzetti148). Further analyses of a combined effect of aerobic training and the Mediterranean diet score in 491 participants (mean age 72·7 ± 5·7 years) with sarcopenia (low grip strength and appendicular muscle mass), revealed no associations with sarcopenia or sarcopenia components(Reference Coelho-Júnior, Calvani and Picca149). In a cross-sectional study of 528 Italian adults (aged ≥ 50 years) attending health screening checks at a local hospital, diets in the lowest third of the Mediterranean diet pattern (detected by principal components analysis) were associated with increased odds of probable sarcopenia (2·38 (95 % CI: 1·05, 5·37)) and sarcopenia (9·69 (95 % CI: 1·41, 66·29)) compared with the highest third(Reference Mazza, Ferro and Maurotti150). Because of wide confidence intervals (CI), the result for sarcopenia needs to be interpreted with caution.
Taken together, although the evidence for the benefits of a higher adherence to the Mediterranean diet for sarcopenia (sarcopenia components) in prospective studies of older adults are emerging(Reference Jang, Han and Jang135,Reference Coelho-Júnior, Trichopoulou and Panza136) , positive associations summarised in recent reviews (2017–2024) come largely from cross-sectional studies, and their limitations must be considered when interpreting the results (e.g. reverse causality). Higher adherence to the Mediterranean diet was associated with lower extremity functioning, mobility and better walking speed. The associations with sarcopenia were mostly non-significant, although evidence is limited. The heterogeneity of evaluated studies was high, and only a few meta-analyses of cross-sectional studies with the Mediterranean diet were conducted. No clinical trials were reported.
Summary and future direction
In this review, we have evaluated the most recent evidence from qualitative and quantitative syntheses of observational and intervention studies that used a single nutrient (protein supplementation), a whole food (fruits and vegetables), or a whole diet (the Mediterranean diet) approach to investigate nutrition-muscle ageing relationships in older adults with and without sarcopenia (Fig. 1(A)). Key findings are summarised in Fig. 1(B).
Overall, there is some evidence of associations between protein and amino acids (leucine) supplementation and muscle in healthy older adults (aged ≥ 65 years). Protein intake above 0·8 g/kg BW/d in combination with exercise may be beneficial for muscle mass, especially in the interventions of longer duration(Reference Nunes, Colenso-Semple and McKellar31,Reference Hengeveld, de Goede and Afman41,Reference Gielen, Beckwée and Delaere42,Reference Wirth, Hillesheim and Brennan48,Reference Martin-Cantero, Reijnierse and Gill53,Reference Thornton, Sim and Kennedy56) , but not for other sarcopenia components(Reference Hengeveld, de Goede and Afman41). In older adults with sarcopenia, protein (whey) supplementation in combination with exercise training showed benefits for muscle mass and muscle strength(Reference Shi, Tang and Stanmore43,Reference Nasimi, Sohrabi and Nunes49,Reference Kirwan, Mazidi and Rodríguez García51,Reference Li, Zhang and Luo52,Reference Whaikid and Piaseu54) , and physical performance in some meta-analyses(Reference Shi, Tang and Stanmore43,Reference Li, Zhang and Luo52) . However, there is considerable heterogeneity in study protocols and in the quality of trials and limited quantitative syntheses of evidence and, key recommendations for protein are still lacking. Debate continues about the quantity, quality, frequency and timing of protein consumption for the prevention and treatment of sarcopenia(Reference Nunes, Colenso-Semple and McKellar31,Reference Murphy, McCarthy and Roche38,Reference Campbell, Deutz and Volpi39) . Future high-quality intervention studies are needed to inform the development of nutrition strategies that specify optimal levels of protein intake for the prevention and treatment of sarcopenia in older adults.
There is reasonably consistent evidence from predominantly observational studies of associations between higher consumption of fruits and vegetables and better physical performance in cross-sectional studies(Reference Granic, Cooper and Robinson35,Reference Granic, Dismore and Hurst83) and the prevention of physical performance and muscle strength decline in prospective studies(Reference Robinson, Granic and Cruz-Jentoft32,Reference Sabia, Elbaz and Rouveau125) . These observational results need to be tested in interventions with whole foods (fruits and vegetables) in older adults with and without sarcopenia as there are still considerable gaps in nutrition research about the role of whole foods in heathy muscle ageing. This is especially as focusing on whole foods as a strategy to promote overall(Reference Wallace, Bailey and Blumberg105,Reference Rosell and Fadnes106) and muscle health may be more acceptable to older adults and health professionals compared with single nutrients(Reference Hayes, Granic and Hurst151,Reference Mahony, Shea and O’Connor152) .
For a whole diet approach with the Mediterranean diet as an exemplar of healthy and sustainable diet(Reference Dominguez, Di Bella and Veronese140–Reference Serra-Majem, Tomaino and Dernini143), reasonably consistent positive results were found between the adherence to the Mediterranean diet and better muscle function (e.g. lower-body function) in cross-sectional studies(Reference McClure and Villani131,Reference Silva, Pizato and da Mata132) , and slower decline in function in a few prospective studies(Reference Bloom, Shand and Cooper133,Reference Granic, Sayer and Robinson134) . Mixed results were found for other sarcopenia components, muscle strength and muscle mass and there was inconclusive evidence for sarcopenia in a few observational studies(Reference Jang, Han and Jang135–Reference Papadopoulou, Detopoulou and Voulgaridou137). Importantly, there were few prospective studies with repeated dietary assessments across adulthood to inform preventive strategies(Reference Robinson, Granic and Cruz-Jentoft32,Reference Serra-Majem, Tomaino and Dernini143) , and no clinical trials(Reference Granic, Sayer and Robinson134,Reference Papadopoulou, Detopoulou and Voulgaridou137) . Therefore, there are still big gaps in knowledge and a need for long-term RCTs to unravel the associations between the Mediterranean diet and muscle health with ageing. Additionally, scientific consensus on defining compliance with the Mediterranean diet (indices) based on the latest understanding of the Mediterranean diet(Reference Serra-Majem, Tomaino and Dernini143) is needed, with external validation in different populations(Reference Hernández-Ruiz, García-Villanova and Guerra Hernández144) in well-conducted observational studies to reduce heterogeneity across studies.
In conclusion, since the conceptualisation of sarcopenia approximately thirty years ago, the three approaches to the characterisation of diet (from single nutrients to whole diets) described here have amassed a large body of literature aimed at the development of preventive and intervention strategies for healthy muscle ageing. However, we have found considerable gaps in knowledge as required to achieve full consensus about nutrition recommendations for sarcopenia that can inform public policy(Reference Chen, Arai and Assantachai36,Reference Ganapathy and Nieves57) . There was some evidence for the benefits of protein supplementation ≥ 0·8 g/kg BW/d with exercise for muscle mass in intervention studies with healthy older adults and those with sarcopenia. However, this evidence is still insufficient for recommending a nutrition strategy with optimal protein intakes for the prevention and/or treatment of sarcopenia. There was reasonably consistent evidence for benefits of higher consumption of fruits and vegetables and higher adherence to the Mediterranean diet for physical functioning in predominantly observational studies, but a substantial lack of interventions, particularly in adults with sarcopenia (Fig. 1(B)). Current efforts to harmonise the operational definition of sarcopenia by GLIS(Reference Kirk, Cawthon and Arai19) will greatly contribute to advancing our understanding of nutrition-sarcopenia relationships to inform public health recommendations for optimal skeletal muscle ageing in the future.
Acknowledgements
The author (A.G.) would like to that the Nutrition Society for the invitation to present parts of this review at the Nutrition Society Winter Conference 2023, London.
Financial support
This work was supported by the National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre (BRC) (grant number: NIHR203309). All authors are supported by the NIHR Newcastle BRC. The views expressed are those of the authors and not necessarily those of the National Health services, the NIHR, or the Department of Health and Social Care. The NIHR had no role in the design, analysis or writing of this article.
Conflicts of interest
There are no conflicts of interest.
Authorship
Conceptualisation, Writing – Original draft, and Visualisation: A.G. Writing – review and editing: all authors. Supervision and Funding Acquisition: A.A.S. All authors critically reviewed the manuscript and approved the final version submitted for publication.
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