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Effects of protein supplementation on muscle mass, muscle strength, and physical performance in older adults with physical inactivity: a systematic review and meta-analysis

BMC Geriatrics volume 25, Article number: 228 (2025) Cite this article

Abstract

Background

Maintaining skeletal muscle mass and function in older adults is of paramount importance for preserving both quality of life and overall health. Exercise is essential for muscle maintenance; however, for older individuals with comorbidities, engaging in physical exercise may pose challenges due to decreased endurance and the inability to reach optimal exercise intensities. Several studies have investigated the effects of protein supplementation on muscle mass, strength, and physical performance in older adults. However, the results are inconsistent. The objective of this study was to systematically review and synthesize the effects of protein supplementation on muscle mass, muscle strength, and physical performance in physically inactive older adults.

Methods

Four databases (PubMed, EMBASE, Web of Science and the Cochrane Central Registry of Controlled Trials) were systematically searched from inception to 31 January 2025. Two reviewers independently conducted the study screening, data extraction, risk of bias and GRADE assessments. In accordance with the PRISMA guidelines, the outcome data were synthesized using meta-analysis via RevMan5.4 software or a narrative method.

Results

Eight data groups from six randomized controlled trials(RCTs) were included in the analysis, stratifying participants into three physical activity(PA) trajectories: sustained low PA (n= 1), transition to structured training from low PA (n= 4), and a shift from moderate to low PA (n= 3). Protein supplementation had no statistically significant effect on total lean body mass (p> 0.05). Furthermore, secondary muscle mass parameters showed negligible intervention benefits, whereas heterogeneous outcomes were observed across muscle strength and physical performance metrics.

Conclusions

The influence of protein on muscle mass was not significantly efficacious, and mixed results were shown for muscle strength and physical performance. Further well-designed studies are needed to determine the effectiveness of protein supplementation to maximize its potential benefits in older individuals with physical inactivity.

Trial registration

This study was registered at www.crd.york.ac.uk/prospero/(registration no. CRD42024504443).

Peer Review reports

Background

Increased protein degradation and decreased protein synthesis accompanying the aging process, the consequences of inactivity, and inadequate nutrition are all important causes of muscle mass loss [1,2,3,4]. The presence of low muscle mass in individuals could predispose them to chronic diseases and lead to adverse clinical outcomes. These outcomes include poor metabolic health, reduced functional ability, increased risk of hospitalization, a negative impact on quality of life, and an association with mortality risk [5,6,7]. Thus, maintaining skeletal muscle mass and function during aging is crucial for preserving quality of life and health [1].

Combining nutritional supplementation with exercise to improve muscle mass and strength is currently internationally [8,9,10]. The previous studies revealed that exercise is the best strategy for maintain and increasing muscle mass [11,12,13]. However, for old people with unhealthy conditions such as decreased heart function, decreased lung function, and bone and joint diseases, it is likely that the ideal exercise intensity cannot be achieved. For these patients, nutritional supplementation is the only choice. However, the impact of anabolic resistance [14] (older individuals with low muscle mass often experience a reduced ability to synthesize muscle proteins in response to a given dose of protein or amino acids, leading to a negative protein balance) on muscle health cannot be ignored.

Several studies have revealed that protein supplements (including whey protein, essential amino acids (eaa), and other protein sources) have mixed effects on muscle mass, strength, and performance in people who are resting in bed and who are sedentary or limited in activity. Some studies reported beneficial effects of protein on muscle health [15,16,17], whereas others have not found significant effects [18,19,20,21,22]. The lack of consistent clinical evidence is still a challenge for recommending protein supplements.

Therefore, the purpose of this systematic review was to comprehensively evaluate the effects of protein supplementation on muscle health in older adults with physical inactivity.

Methods

Search strategy

We followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA- 2020) guidelines in this systematic review [23], and we registered the data at www.crd.york.ac.uk/prospero/(registration no. CRD42024504443). We searched PubMed, EMBASE, Web of Science, and the Cochrane Central Registry of Controlled Trials (CENTRAL), with the end date restricted to 31 January 2025. We restricted our systematic search to articles published in English. We combined four search themes relevant to sedentariness/limited mobility/bedrest, old people, protein/amino acid, and muscle mass/strength/function to find potentially relevant studies. The retrieval strategy is listed in Appendix 1.

Eligibility and study selection

All titles and abstracts of the articles obtained for inclusion were reviewed by two authors (He FQ and Zhang LY). We identified pivotal studies in the article lists on the basis of eligibility and exclusion criteria.

Eligibility criteria: (1) adult participants aged 60 years or older; (2) demonstrating a state of physical inactivity (defined on the basis of descriptions in the original studies, specifically characterized as “sedentary, bedridden, restricted in mobility, inactive, or similar terminology”) either prior to the commencement of the study or throughout the study intervention period; (3) study design: randomized controlled trials (RCTs), both randomized controlled crossover and parallel trials were considered; (4) intervention: amino acid, derivative and protein intake; (5) comparator: placebo or no intervention; (6) outcomes: muscle mass, muscle strength and physical performance; (7) the selection of the studies was restricted to full-text articles and the English language.

The exclusion criteria were as follows: (1) opinion letters, editorials, conference abstracts, and comments; (2) duplicate reports; and (3) intervention with other potential active ingredients to change muscle fitness (e.g., omega- 3 fatty acids, anabolic steroids and so on).

Data extraction and outcome measures

Two evaluators (He FQ and Zhang LY) screened the documents and extracted information independently. If there were disagreements, a third party (Huang XL) was consulted to resolve the difference. First, we screened the title and abstract to exclude irrelevant literature. We then screened the whole text carefully. The data extracted included the following: (1) Basic information, such as title, first author, publication year, and country. (2) Basic characteristics of the subjects: study design, study duration, age, sample size, gender, and setting. (3) The key elements of the bias assessment. (4) Body composition, quantity and type of intervention, type of protein, total amount of protein, comparator, isocaloric, exercise, and measured outcomes were measured.

For each outcome, we collected the following information when available. Body composition outcomes were extracted as changes in any variable related to muscle mass, such as total lean body mass (LBM), appendicular lean mass (ALM), leg lean mass, arm lean mass, truck lean mass, total mid-thigh cross-sectional area (CSA), total muscle CSA, and lower limb muscular volume. Methods applied to measure body composition include dual energy X-ray absorptiometry (DEX) and peripheral quantitative computed tomography (pQCT). The strength testing outcomes were repetition-maximum (isotonic) strength (measured by 1-RM or 12-RM strength tests) or any isometric strength testing. Upper body strength was obtained from handgrip strength and chest press exercise testing data. For lower body strength, leg press, leg extension, leg flexion, knee extension, or similar exercises were used for data extraction. The physical performance tests included time up and go (TUG), chair stand test, alternate-step test, balance test, 4-meter walking test (4MWT), 6-minute walking test (6MWT), short physical performance battery (SPPB), 5-item physical performance battery, and tests involving activities of daily living. Data available only in figures were extracted via Plot Digitizer software (V.2.6.11; http://plotdigitizer.sourceforge.net) [24].

Assessment of study quality

The methodological quality of the included studies was independently assessed for risk of bias following the Cochrane Collaboration’s Risk of Bias 2 (ROB2) by two reviewers (He FQ and Zhang LY). Then, we cross-check the evaluation score results. The risk of bias was categorized as “low risk”, “high risk”, or “some concerns”. Two reviewers (He FQ and Zhang LY) used the GRADE approach to assess the quality of evidence in the included reviews. Any disagreements or discrepancies were resolved through discussion or by a third reviewer (Huang XL). Given that the number of included studies was fewer than 10, we did not perform a funnel plot analysis to assess potential publication bias.

Data analysis

The principal summary measures of interest were between-group differences in interventions for outcomes of muscle mass, muscle strength and physical performance. When more than 2 studies provided data on the same outcome, these data were quantitatively pooled. The data are uniformly represented by the mean and standard deviation. The qualitative synthesis was conducted via RevMan5.4 software, with the mean difference (MD) serving as the effect indicator, and point estimates and 95% confidence intervals (CIs) were provided. Heterogeneity among studies was assessed via the X2 test (a= 0.1), and the I2 statistic was used for quantitative evaluation. I2 values were categorized as low (< 25%), moderate (50%), or high (≥ 75%) heterogeneity. The data were analysed via the fixed-effects model and inverse variance method when I2< 50%. Otherwise, the random-effects model and DS-L method were employed. When there were insufficient data for meta-analysis, a narrative synthesis method was employed, utilizing the reported P values or 95% CIs to evaluate the effectiveness of the intervention. We performed subgroup analysis to carry out further studies when significant heterogeneity existed. We will conduct sensitivity analysis in cases such as the presence of moderate heterogeneity among studies (I2 is close to 50%, with a P value slightly greater than 0.05) or when the results of syntheses are statistically significant (if the P value is close to 0.05).

Results

Study selection

The details of the study selection process are shown in Figure 1. A total of 1641 pieces of literature were selected from the 4 databases. A total of 486 records were removed because of duplication. A total of 1116 irrelevant records were excluded after screening the titles and abstracts. The full texts of 39 records were assessed for eligibility. Thirty-three studies were excluded after we screened the full text. Finally, 8 groups of data from 6 studies [15,16,17, 19, 22, 25] with a total of 214 participants(intervention group: n= 105, control group: n= 99) were selected for the systematic review. This is because the study by Deutz et al. [17] and Bermon et al. [25]. We have separately integrated the data from each phase (Deutz, 2013 A and Deutz, 2013B; Bermon, 1998 A and Bermon, 1998B) into the analysis.

Fig 1
figure 1

The flow diagram of studies selection

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Study characteristics

Table 1 presents the general characteristics of the included 6 studies. Among these studies, 1 study was conducted in the Netherlands [19], 1 study in France [25], 1 study in Canada [15], and 3 studies in the USA [16, 17, 22]. The study duration was between 1 week and 6 months. One study included only male participants [19], and another 5 studies included both sexes [15,16,17, 22, 25]. The composition of the nutritional support used varied across studies, but all the nutrients contributed protein. The dose and type of protein supplementation ranged from approximately 3 g/day to 45 g/day, provided in the form of amino acids, their derivatives and proteins. The control treatments included a blank control or placebo supplements containing maltodextrin, carbohydrate or noncaloric diet soda. A portion of the data (leg press, chest press) from the study[25]was extracted via Plot Digitizer software.

Table 1 The characteristics of included 6 studies
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Five studies reported measures of muscle mass [15,16,17, 22, 25]. Among these studies, four investigated changes in total lean body mass measured via dual-energy X-ray absorptiometry (DXA) [16, 17, 22], or computed tomography (CT) [15, 16] (Table 2), and 5 sets of data from four studies were subjected to meta-analysis [15,16,17, 22].

Table 2 The total lean body mass changes across 4 studies
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The analysis stratified data from 8 subsets across 6 RCTs into three groups on the basis of pre- and during-study physical activity levels: maintained low physical activity (PA), transitioned from low PA to trained, and shifted from moderate to low PA, to evaluate the effects of protein supplementation on muscle mass, strength, and physical performance. The evidence synthesis from the included studies [15,16,17, 25] revealed four independent datasets documenting participants who were physically inactive at baseline and subsequently underwent structured training programs, either alone or in combination with protein supplements during the intervention phase (from low PA to trained). Three experimental groups from distinct studies [17, 19, 22] demonstrated a transition from moderately active baseline status to physical inactivity following intervention implementation(from moderate to low PA). Notably, one study cohort [25] maintained consistently inactive physical activity levels throughout both the pre- and post-intervention periods.

Risk of bias in studies

We employed the ROB2 test to assess the risk of bias in all studies. Three of the 6 RCTs had a low risk of bias [15,16,17]. Three studies had a high risk of bias [19, 22, 25]. The details of the assessment of the studies are shown in Figure 2.

Fig 2
figure 2

The risk of bias of the 6 studies

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Effects of protein supplementation (sustained low PA)

Only one study [25] included participants who maintained a physically inactive state. In terms of muscle mass, the results of this study revealed no significant changes in lower limb muscle volume within the groups. Similarly, regarding muscle strength, the study noted the absence of statistically significant differences within the groups for the 1-RM and 12-RM for leg press, as well as the 1-RM for leg extension.

Effects of protein supplementation (from low PA to structured training)

Muscle mass

In terms of total lean body mass, the results showed no significant difference between the intervention group and the control group (mean difference − 0.01 kg, 95% CI: − 3.23—3.20, p = 0.95, I2= 0%, Figure 3).

Fig 3
figure 3

The forest plot of total lean body mass across 3 studies (Low PA to trained)

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Two studies [15, 17] reported no significant differences in appendicular lean mass in within-group comparisons, with one study [15] further indicating no significant differences in between-group comparisons (− 4.2± 12.1 vs. − 4.6± 10.4, P= 0.45). Regarding leg lean mass, the study by Bermon et al. [25] revealed that there was no statistically significant difference in the change in lower limb muscular volume before and after supplementation with protein supplements in the experimental group. Furthermore, other body composition indicators, such as the mid-thigh cross-sectional area (CSA) and total muscle CSA, significantly increase in the within-group comparisons, whereas no significant difference was detected in the between-group comparisons [16].

Muscle strength

Upper body strength

The impact of protein supplementation on upper body strength was evaluated through handgrip strength and chest press tests. The findings of one study [15] indicated that handgrip strength did not significantly change either within or between groups. The number of bench press repetitions measured by the 1-RM and 12-RM strength tests did not significantly increase within either group, except for a 6.7% increase in the 1-RM value in the control group (P < 0.05). In contrast, the study by Bermon et al. [25] revealed that there were significant improvements in the 1-RM and 12-RM of the bench press within the groups, and these improvements were statistically significant.

Lower extremity strength

Similarly, study by Bermon et al. [25] reported significant increases in the 1-RM and 12-RM of the leg press and leg extension within groups. Another study [16] showed significant differences within groups but did not observe statistically significant differences between groups. Furthermore, Chalé et al. [16] reported that peak power measurements at both 40% and 70% of the 1-RM increased over time for the double leg press, but there was no significant difference in the change between groups.

Knee extensor muscles

The results of the study by Chalé et al. [16] revealed that the whey protein concentrate group presented more significant increases in peak power at both 40% and 70% knee extensors than the control group (protein group: 28–38% vs. control group: 8–21%), and this intergroup difference was statistically significant. In contrast, a study by Deutz et al. [17] indicated that isokinetic knee extensor strength (60°) significantly increased in the protein supplementation group, but no significant difference between groups was observed.

Physical performance

In terms of the effectiveness of the timed up and go (TUG) test, the study by Buckinx et al. [15] revealed significant improvements within groups, and the intergroup differences were also highly significant.

The findings of the study by Buckinx et al. [15] further indicated that in physical function tests such as the alternate-step test, balance test, 4-meter walk test, and 6-minute walk test, there were significant improvements within groups, and the intergroup differences were also statistically significant.

Two studies [15, 16] noted that there were significant improvements in the effectiveness of the chair stand test within groups. However, while the study by Buckinx et al. [15] revealed significant intergroup differences, the study by Chalé et al. [16] did not reveal such differences.

Effects of protein supplementation (from moderate to low PA)

Muscle mass

For total lean body mass, the results showed no significant difference between the groups (mean difference 0.61 kg, 95% CI: − 0.34—1.56, p = 0.78, I2= 0%, Figure 4).

Fig 4
figure 4

The forest plot of total lean body mass across 2 studies (Moderate to low PA)

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Research on leg lean muscle mass conducted by Dirks et al.[19] has indicated that there are no significant differences within groups. Similarly, another study [22] revealed that there are no significant differences between groups. Findings from a previous study [17], that explored whether HMB could attenuate muscle atrophy during total bed- rest in healthy older adults reported that the average loss in the HMB group was − 0.08 ± 0.17 kg (P = 0.65) versus that in the control group (− 1.01 ± 0.35, P = 0.02), and the change in value over the bed rest period was statistically significant between-group comparison (P = 0.02). Additionally, one study [17] reported that there were no significant effects on arm or trunk lean muscle mass in either the HMB or control groups, and no differences between groups were reported.

Muscle strength

The findings of Dirks et al. [19] have shown that the changes in maximal leg muscle strength (1-RM) are statistically significant within groups, but not between groups.

With respect to isokinetic knee extensor strength at 60° and 180°, a study by Deutz [17] reported a significantly greater decline in strength during bed rest in the control group than in the HMB group. However, the changes within each group, compared with the baseline values, were not statistically significant. Additionally, there were no significant differences in the changes during bed rest between the treatment groups.

Physical Performance

A previous study [22] revealed significant differences in physical performance, including stair ascent power, stair descent power, and floor transfer, between groups. However, Deutz et al. [17] reported no significant changes within or between groups in this battery of physical performance tests, including the short physical performance battery (SPPB), the Get-Up-&-Go test, or the 5-item physical performance test.

Quality of the evidence

We used the GRADE tool to evaluate the results of the meta-analysis (Fig. 5). The results revealed that our outcomes were of moderate quality (in the analysis of three studies from low PA to structured training) and low quality (from moderate to low PA).

Fig 5.
figure 5

Quality of the evidence

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Discussion

In this systematic review, we performed a systematic review of randomized controlled trials on the effects of protein supplementation on muscle mass, muscle strength and physical performance in physically inactive older adults. The results demonstrated that for older adults transitioning from low PA to structured training or from moderate to low PA, protein supplementation did not have a statistically significant effect on total muscle mass. The results of the systematic review of three distinct trajectories of physical activity revealed that protein supplementation had no significant effect on appendicular or arm lean mass. Protein supplementation resulted in significant within-group differences in other parameters (such as mid-thigh CSA and total muscle CSA), but not significant between-group comparison. The results of studies on the effects of protein supplementation on leg lean mass, muscle strength, and physical performance are inconsistent.

Proteins and amino acids are crucial for a multitude of body functions, including structural support, metabolism, and growth. A deficiency in protein intake could lead to an imbalance in protein metabolism, predominantly affecting skeletal muscles. This results in conditions such as muscle wasting, hindered muscle development or repair, and reduced physical performance. Special groups, such as older individuals, are at a greater risk of suffering from inadequate protein levels. Anabolic resistance is considered a primary factor in the development of sarcopenia. It has been reported that older individuals (mean age 71 years) may require almost twice as much protein intake per meal to stimulate muscle protein synthesis to the same degree as their younger counterparts (mean age 22 years) [26]. Anabolic resistance is also instrumental in the skeletal muscle atrophy that occurs during periods of muscle disuse [14, 27]. For older individuals, immobility through bed rest for just a week can lead to a significant loss of lean tissue. Sedentary behavior is associated with a loss of muscle mass and strength and negatively impacts the efficiency of EAA in stimulating protein metabolism, which requires the consumption of more protein or high-quality proteins [28]. Two weeks of inactivity (reduce their daily step count to ≤ 750 steps/d, which is a daily step count similar to what is observed in older hospitalized patients) resulted in the loss of leg lean mass and a decrease in muscle protein synthesis [29]. Muscle loss due to a lack of physical activity results from chronic negative protein balance driven by unequal contributions of muscle protein synthesis and breakdown [2].

Protein is a key driver of muscle protein synthesis and may be critical for maintaining skeletal muscle health in older adults with physically inactive. The classical mechanisms of protein nutritional support for alleviating sarcopenia include the regulation of the ubiquitin‒proteasome system, oxidation reactions, and autophagy, as well as potential novel mechanisms, including alterations in miRNA profiles and the gut microbiota [30]. Although the impact of protein on muscle health (i.e., quality and function) is mediated through several pathways, the mechanisms of intervention involve an increase in muscle protein synthesis and a decrease in muscle protein breakdown. A sufficient amount of protein is central to muscle health, as it stimulates protein synthesis and prevents anabolic resistance [14, 27].

Our findings are similar to those of one previous systematic review, which reported that protein supplementation alone did not significantly improve muscle mass, strength or function in prefrail or frail older people [31]. This systematic review specifically targets physically inactive older adults, encompassing a substantially broader population than the study restricted to frail/prefrail individuals. Epidemiologically, physical inactivity affects 67% of community-dwelling older individuals, whereas the prevalence of frailty is 11–15% [32, 33]. Diverging from frailty research emphasizing terminal outcomes such as falls and disability, we employed early-stage biomarkers, including muscle mass and strength [34], to demonstrate the efficacy of protein supplementation during the preclinical phase. These findings provide evidence for implementing nutritional interventions in community-based primary prevention programs [35]. However, it is common for hospitalized old patients to become bedridden due to the aggravation of chronic or acute diseases, which leads to a precipitous decline in functional status. One of the most prominent hazards of hospitalization is that older patients spend more than 80% of their hospital stay lying in bed and have significantly lower muscle strength and muscle mass, with physical inactivity [3, 36]. Moreover, older adults with reduced physical activity compounded with acute illness, postsurgical trauma, diseases, and medications are likely to experience catabolic effects on muscle that may further accelerate the loss of lean tissue [2]. Therefore, identifying the role of protein in the muscles of hospitalized old people is highly important. Bellanti et al. reported that amino acid supplementation during 7 d of low mobility had a significant effect on free fat mass and ALM in hospitalized older patients [37]. Although the study employed a non-RCT design, the study may still hold some reference value. Additionally, an RCT of the impact of protein supplementation with different protein sources during simulated hospital and convalescence in older men and women suggested that protein supplementation alone was insufficient to offset the absolute loss of muscle mass with acute inactivity but that supplementation with whey protein may be protective on leg lean mass from a bout of inactivity combined with a hypocaloric diet and even enhance recovery following return to habitual activity [29]. Protein therapy has potential, but further RCTs with more rigorous designs are needed. It would be interesting to assess the impact of protein supplementation on old inpatients with physical inactivity, who are at high risk of functional deterioration, with the goal of maintaining mass function in acute or chronic conditions.

Regarding protein supplementation for older individuals with low physical activity, several aspects should be considered. First, a protein intake ranging from 1.0–1.2 g/kg/day is recommended for healthy aging muscles, while 1.2–1.5 g/kg/day may be necessary for older patients with acute or chronic diseases, and older individuals with severe illness or malnutrition could require up to 2.0 g/kg/day [27]. Differences in protein dosage and findings among the studies included in this systematic review indicate that future research is needed to determine the optimal protein intake for older individuals with low physical activity. Second, in addition to quantity, the quality of consumed protein plays a critical role in the context of muscle health, which is determined by the EAA profile, digestibility, and bioavailability of specific protein sources [27]. Animal proteins contain a large quantity of EAAs, the main nutritional stimulus for protein synthesis, but their consumption may be impaired in older individuals due to poor dentition, reduced appetite, anorexia, solid dysphagia, taste alteration and cost [38,39,40]. Although plant proteins are good protein sources, they may exacerbate gastrointestinal problems such as slow gastric emptying and diarrhea. Dairy, which is high in muscle-building leucine, is often limited in intake owing to its fat content. The sources of protein in our included studies were diverse, which may have contributed to differences in therapeutic efficacy. Third, the timing of protein ingestion is a relevant factor to consider in enhancing muscle health. The opinion of some researchers is that proteins should be consumed uniformly throughout the day to ensure a more sustained 24-hour anabolic response [36]. However, previous studies reported similar negative results and suggested that protein timing might have no effect on mass gain [39, 41]. Thus, owing to the uncertainty of the current evidence, studies should be designed to specifically assess the effects of different patterns of protein ingestion. Fourth, regarding the synergistic effect between nutrients, studies have shown that a combination of whey protein with other nutrients significantly increases muscle strength and gait speed in older adults with limited mobility, an effect not observed with whey protein alone, potentially due to synergistic physiological benefits from the interaction of polyphenols, fish oil, and protein [18]. A recent RCT provided further insights: the effect of protein as a sole supplement on improving muscle health is minimal, whereas supplementation with a combination of nutrients may be more beneficial. Fifth, previous studies reported that the combination of exercise and protein supplementation seems to have a greater effect on attenuating the loss of muscle mass, strength and function in frail old people [31]. However, in our included studies [17, 25], there was no additional benefit observed from providing an exercise program and protein supplementation simultaneously in terms of muscle fitness outcomes compared with protein intake alone. Exercise interventions may have limited potential to improve muscle health in older individuals with physical inactivity, as it may not always be feasible for those with limited mobility or who are bedridden to supplement their protein with an increased exercise program.

This study has several limitations: First, although this study covered several key outcome measures, including muscle mass, muscle strength, and physical performance, it is limited by the number of studies currently available. We only performed quantitative meta-analyses for total lean mass, and systematic reviews for other measures. This limitation may have led to an incomplete understanding of these important outcomes. Second, the subjects in this study were all healthy older adults who were physically inactive before or during the study. Although this setting provides important data on the muscle response of older adults in inactivity status, it does not fully mimic inactivity in disease or pathological states. Therefore, extrapolating only from the effect of protein supplements on muscle health in healthy older adults during inactivity to conditions of disease or pathology may be subject to certain biases and limitations. Third, our results do not support the widely held belief that protein supplementation improves muscle health. This result may be related to differences in the type of protein used, the dose, and the duration of the study. Although, it should be noted that the I2 value was 0% in the meta-analysis, the very low heterogeneity may also be a superficial phenomenon and, in fact, may have prevented the detection of real heterogeneity due to the small number of studies, the small sample size, and other reasons. Therefore, these potential limitations need to be considered with caution when interpreting and applying the results of this study.

Conclusion

In physically inactive older adults, protein supplementation has limited effects on muscle mass, and studies of its effects on strength and fitness have yielded mixed results. Owing to the limited number of included studies and participants, and the inability to fully simulate the effect of protein supplementation on muscle in inactive older adults in the disease state, the findings need to be generalized with caution. In the future, rigorous research is needed to clarify the optimal type, dose, and duration of protein supplementation and explore its interactions with other nutrients to maximize the health benefits of protein supplementation in older individuals with physical inactivity.

Data availability

All the data generated or analysed during this study are included in these published articles [15,16,17, 19, 22, 25], Table 1 The studies’ characteristics, and Appendix 2.

Abbreviations

ALM:

Appendicular lean mass

BCAA:

Branched-chain amino acids

CENTRAL:

The Cochrane Central Registry of Controlled Trials

CIs:

Confidence intervals

CON:

Control group

CSA:

Cross-sectional area

DEX:

Dual energy X-ray absorptiometry

EAAs:

Essential amino acids

EXP:

Experiment group

HGS:

Handgrip strength

HMB:

β-hydroxy-β-methylbutyrate

IIE:

Isometric intermittent endurance

LBM:

Lean body mass

MD:

Mean difference

MM:

Muscle mass

MS:

Muscle strength

PLA:

Placebo

pQCT:

Peripheral quantitative computed tomography

PP:

Physical performance

PRISMA- 2020:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020

RCTs:

Randomized controlled trials

ROB2:

Risk of Bias 2

RM:

Repetition-maximum

SPPB:

Short physical performance battery

TUG:

Time up and go

1-RM:

One repetition maximum

4MWT:

4-meter walking test

6MWT:

6-minute walking test

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Acknowledgements

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Funding

This research was funded by the Sichuan Science and Technology Program (grant number 2023YFS0246) and Health and Scientific Research for Cadres in Sichuan Province (grant numbers 2022-- 102, 2024-- 105, 2024—106, and 2025-- 105).

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  1. The Center of Gerontology and Geriatrics, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Sichuan Province, Chengdu, 610041, China

    Liying Zhang, Gongxiang Liu, Xiaoli Huang & Fuqian He

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L.Z. drafted, and revised the review and edited the final manuscript. G.L. wrote and revised the review. X.H. revised the review. F.H. conceptualized the study, administered the project, supervised the study, revised the review, and edited the final manuscript. All the authors read and approved the final manuscript.

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Correspondence to Fuqian He.

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Zhang, L., Liu, G., Huang, X. et al. Effects of protein supplementation on muscle mass, muscle strength, and physical performance in older adults with physical inactivity: a systematic review and meta-analysis. BMC Geriatr 25, 228 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12877-025-05885-x

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Keywords

BMC Geriatrics

ISSN: 1471-2318

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