Introduction

Sarcopenia, an age-related condition characterized by progressive decrease in muscle mass, strength, and function, currently affects an estimated 10–40% of community-dwelling older adults [1, 2]. Additionally, sarcopenia is associated with increased risk of falls by 60%, increased fractures by 84%, and adverse health outcomes such as functional decline, decreased quality of life, mortality, and increased healthcare costs [1, 3, 4].

Modifiable risk factors including low physical activity and protein intake have been targeted for the prevention and treatment of sarcopenia [5]. In 2018, the International Conference on Sarcopenia and Frailty Research (ICSFR) guideline for the management of sarcopenia recommended progressive resistance training (RT) and a protein-rich diet or protein supplementation [6]. Recent systematic reviews and meta-analyses have demonstrated desirable effects of various forms of exercise with or without nutrition interventions on muscle strength and physical performance, as measured by gait speed (GS) or short physical performance battery (SPPB) [7,8,9]. However, the evidence for increasing muscle mass is less consistent. One meta-analysis focusing on sarcopenic older adults found no improvement after exercise, nutrition, and mixed exercise (aerobic training (AT) plus RT) and nutrition [8], while another meta-analysis published in the same year determined that mixed exercise with nutrition resulted in significantly increased muscle mass among people with sarcopenia [10]. Discrepancies in study results may be due to varied inclusion criteria, different definitions of sarcopenia used, and inconsistent exercise protocols in exercise type, frequency, intensity, and duration.

More importantly, exercise intensity, especially for RT, has not been fully taken into consideration in previous systematic reviews and meta-analyses. ACSM guidelines suggest moderate-to-vigorous RT intensity (60–80% one-repetition maximum, 60–80%1RM) of resistance exercise for older adults [11]. Recent systematic reviews and meta-analyses suggest that progressive RT may reduce mortality and produce greater gains in muscle strength in a linear fashion among older adults in general [12,13,14]. On the other hand, one meta-analysis focusing on older adults reported that high-load RT only produced marginal gains in muscle mass and insignificant improvements in muscle strength [15]. According to Csapo et al. because muscle hypertrophy plateaus above a certain point in high intensity training, high frequency low intensity training may be required to continue increasing muscle mass [15]. Additionally, high-intensity exercise might decrease adherence and lead to decline in total exercise [16]. Thus, clarification of the effects of RT intensity on muscle mass, strength, and physical performance is needed to make precise exercise prescriptions for older adults with sarcopenia.

The objective of this study is to compare the effectiveness of interventions for sarcopenia, with a particular focus on determining the optimal intensity of RT for older adults with sarcopenia. We conducted a network meta-analysis of randomized controlled trials (RCTs) in older adults with sarcopenia and pooled data of intervention effects on muscle mass (appendicular skeletal muscle, leg muscle mass, and skeletal muscle mass), muscle strength (handgrip strength (HG), chest press, and leg press), and physical function (5 times sit to stand (5TSTS), number of repetitions done in the 30-s chair stand test, timed up and go test (TUG), SPPB, GS, and 6-min walk test).

Methods

This network meta-analysis was performed according to the standards described in the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement [17]. The study was registered in PROSPERO under the ID CRD42021287114.

Search strategy and selection process

Using Pubmed, Embase, Central Register of Controlled Trials (CENTRAL), and ClinicalTrials (Clinicaltrials.gov), we identified RCTs on sarcopenia from database inception until October 20, 2022. The keywords used for the search were “sarcopenia” or “sarcopeni*” and “randomized controlled trial.” To identify pertinent studies, we utilized the search terms: “train*”, “physical activity”, “exercise”, “diet”, “nutr*”, and “drug therapy”. Additionally, we incorporated the associated MeSH terms: “sarcopenia”, “exercise”, “diet, food, and nutrition”, “nutrition therapy”, and “drug therapy”. "We integrated the search terms using the Boolean operators “AND” and “OR”. The complete search terms and search string can be found in Supplementary S1. To ensure comprehensive inclusion of potentially relevant articles, we refrained from applying filters related to publication type, age, or language. Additional studies were identified by reviewing the reference lists of papers found through the database search. Study protocol paper and conference abstracts were not included. The inclusion criteria for studies were: (1) community-dwelling adults aged over 18 years, (2) participants diagnosed with either sarcopenia (characterized by low muscle mass and low muscle strength, and/or reduced physical performance) or dynapenia (manifested as low muscle strength and/or reduced physical performance but with normal muscle mass) [18, 19], and (3) RCT. Since severe illness such as cancer, liver cirrhosis, or end stage renal failure could induce cachexia and decrease physical function, studies involving patients with these comorbidities were excluded.

During the initial selection process, two independent authors reviewed the title, abstract, and full text of each reference to determine its suitability for inclusion. In cases of uncertainty regarding the study’s relevance, a third author was consulted to achieve consensus. When multiple studies on the same population were conducted by the same research group and reported identical outcomes of interest, we only chose the results from the study with the longest follow-up duration. The process of selection is detailed in Fig. 1. Finally, the included studies underwent a comprehensive assessment of bias risk using the Cochrane Risk of Bias Tool 2.0 (RoB 2.0) [20], accessible at https://methods.cochrane.org/risk-bias-2. This tool evaluates each study’s susceptibility to potential bias across multiple domains, including randomization procedures, adherence to intended interventions, handling of missing outcome data, measurement of outcome variables, and selection bias. We categorized the overall risk of bias in each domain as “Low risk of bias,” “Some concerns,” or “High risk of bias.”

Fig. 1
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PRISMA flow diagram

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Data extraction

RCTs with at least one intervention (e.g., nutrition, exercise, whole body electrical muscle stimulation [WB-EMS], whole body vibration [WBV], electrical puncture, Taichi, global sensorimotor training, focused vibrational therapy, and drug treatment [bimagrumab, MK-0773, perindopril, oxytocin]) were included. One researcher entered the following data for each paper into a standardized table: authors, publication year, location of study, number of participants, baseline characteristics of participants, inclusion criteria, exclusion criteria, intervention(s), comparison group, duration of intervention, intensity of resistance exercise, and outcomes of interest. Outcome measures included 5TSTS, number of repetitions done in the 30-s chair stand test, TUG, SPPB, GS, 6-min walk test, appendicular skeletal muscle index (ASMI), leg muscle mass, skeletal muscle mass, HG, chest press, leg press. Since the quality of life (QOL), as measured by either the Short Form 36 or Short Form 12, is divided into physical and mental components, the combined QOL is represented using overall, physical, and psychological scores.

Grading of exercise intensity

Exercise was initially classified as either AT or RT. According to ACSM guidelines, the intensity of RT was categorized into five levels: very light, light, moderate, vigorous, and near-maximal to maximal intensity, based on repetition maximum (RM) and/or rating of perceived exertion (RPE) [11]. The term “1RM” refers to the maximum weight an individual can lift for a single repetition. Relative intensity, indicated as percentage of 1RM (%1RM), was calculated by converting from the repetition numbers implemented in the RT program [21]. The Borg RPE is a subjective scale and reliable measure of RT intensity [22]. However, the sarcopenia management guidelines advocate for RT of at least moderate intensity [23]. Accordingly, we stratified RT intensity into 3 distinct levels: light-to-moderate (LMRT), moderate (MRT), and moderate-to-vigorous intensity RT (MVRT). Specifically, LMRT corresponds to scores of 6–11 on the Borg RPE scale (whose full range is 6–20), 0–4 on the Modified Borg’s scale (with a complete range of 0–10), or less than 49% of 1RM [11]. MRT is represented by ratings of 12–13 on the Borg RPE scale, 5–6 on the Modified Borg’s scale, or 50% ~ 69% of 1RM [11]. MVRT is characterized by scores of 14–17 on the Borg RPE scale, 7–8 on the Modified Borg’s scale, or 70% ~ 84% of 1RM [11]. To ensure accuracy, both a sports medicine physician and a geriatrician meticulously reviewed all included studies. They then determined the RT intensity through mutual consensus.

AT primarily focuses on augmenting cardiovascular endurance and efficiency. Nonetheless, it also leads to discernible enhancements in muscular strength and endurance [24]. Given that 50% of 1RM is roughly equivalent to an average of 26 repetitions [25], AT, which typically involves over 100 repetitive movements, can be categorized as LMRT. Thus, the effects of AT on muscular strength and endurance might be more subtle compared to those elicited by RT. Consequently, we opted not to further classify AT.

Statistical analysis

Network meta-analysis was performed using changes in mean and standard deviation (SD) from baseline. 95% two-tailed credible intervals (CrI) were calculated, with p < 0.05 indicating statistical significance. When studies only reported 25% and 75% percentile of outcome values, we estimated SD based on interquartile range (IQR = 1.349*SD) [26]. If changes in SD were not available, it was estimated using the following equation: [SDpre2 + SDpost2-2 × CC × SDpre × SDpost]0.5 [9, 27]. SDpre represented the SD at baseline and SDpost was the SD after the intervention. CC was the correlation coefficient between baseline and post-intervention values for the same individual. If the correlation was not reported, CC was designated as 0.5. Network plots visually represented the number of study participants according to the size of nodes and the number of trials conducted according to the thickness of connecting lines. Forest plots depicted the intervention effects compared to the control group. Effectiveness of the interventions were ordered by rank probability and determined using the surface under the cumulative ranking curve (SUCRA), where larger surface areas equaled greater treatment effects [28].

We used the web‐based software MetaInsight V4.0.0 powered by Rshiny for network meta-analysis combining direct and indirect comparisons and figure plotting [11].

Surprisingly, MVRT was not associated with additional benefits compared to MRT in terms of TUG, which is a measure of overall functional mobility, including locomotion, static balance, and dynamic balance. Most MVRT trials increased intensity by elevating %1RM, but used the original exercise type, such as body weight workout and elastic band exercise, which mainly build limb strength. To improve agility and balance, power resistance training may provide benefits in addition to muscle power and physical performance. A 12-week RCT reported that high-speed RT program may bring greater improvement in walking sprint, 8-foot up-and-go test, and sit-to-stand test [91]. Another randomized within-subject trial demonstrated that power resistance training generated more increases in muscle power and movement velocity [92]. Considering the significance of rate-dependent mobility for fall prevention and functional maintenance in older adults [93, 94], velocity-based power training should be introduced and integrated into traditional RT programs.

According to our results, MVRT was not associated with greater gains in HG compared to MRT. Similarly, most MVRT programs tended to focus on reinforcing lower limb strength because gait and balance were more pertinent to all-cause mortality, activities of daily living (ADL) decline, and instrumental activities of daily living (IADL) worsening [95, 96]. Compared to gait and balance, HG has been proven to be equivalently essential in the concept of intrinsic capacity developed by the WHO [97]. In addition, grip strength was related to cognitive performance, mental health, and quality of life cross-sectionally and longitudinally [98], and grip training has been reported to improve cognitive function through increasing the local efficiency of brain white matter connectivity in minor acute ischemic stroke patients [11]. Third, many studies have failed to report on exercise adherence, potentially leading to an underestimation of the true effects of exercise interventions. Fourth, discordant advice on usual diet habits, lifestyle, and physical activity in control groups among studies might obscure the intervention effects.

Fifth, given the variety of metrics used to evaluate exercise, comparing results across different studies can be challenging. The ACSM recommends a holistic approach to evaluating exercise intensity, encompassing metrics such as 1-RM, VO2 max, and RPE. This approach offers both an objective measure and a subjective assessment of effort, streamlining the standardization of exercise intensity across various studies [11]. Detailed reporting on exercise intervention protocols should be emphasized in future studies.

Conclusions

This network meta-analysis suggests that RT with or without nutritional supplementation improves physical performance, ASMI, and handgrip strength in older adults suffering from sarcopenia. Higher RT intensity potentially generates more benefits on lower body strength and muscle mass compared to lower RT intensity. Further investigation is necessary to clarify the advantages and disadvantages of intensifying RT and give insight to future exercise program modifications.