Our systematic review incorporated randomized controlled trials (RCTs) that underwent peer review and were published between 1999 and February 2022. RCTs, including chronic eccentric training involving multiple joints and large muscle groups (e.g., walking, running, full body resistance training) having a treatment period of at least four weeks or more, intervention delivered a minimum once a week, designed to compare eccentric vs concentric exercise or traditional exercise were included in the review. Controlled trials involving sedentary healthy adults or those with an existing metabolic disease as a primary medical condition not engaged in structured exercise training in the past six months were included in this review. Trials on individuals with neurological conditions preventing safe exercise performance or with a primary medical condition other than metabolic disease were excluded.

For our review, we defined eccentric exercise as exercises with high eccentric contractions, i.e., downhill walking, descending stairs and lowering weights. Concentric exercises are defined as those with high concentric contractions, i.e., uphill walking, lifting but not lowering the weights. Traditional exercises are defined as movements with relatively even proportions of concentric and eccentric contractions. The PICOS (participants, interventions, comparators, outcomes, and study designs) detailed eligibility criteria are given in Table 1. This review covered studies that included at minimum one outcome measure from the following measures.

To identify relevant studies, an extensive search was conducted using free text terms and Medical Subject Headings (MeSH) in several web-based databases, including Cochrane Central Register of Controlled Trials, the Cochrane Library, Embase, PubMed, CINAHL, SPORTDiscus, Web of Science, MEDLINE, and SCOPUS. Human studies were considered only. Ongoing trials were searched for in clinicaltrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) up to February 2022. Further studies were also identified by searching selected articles’ reference lists. The complete search strategy is provided in Appendix 1. In case further information was needed, authors were contacted.

One reviewer (MA) identified published studies through an extensive literature search in seven major databases. According to individual databases, the search strategy was adapted. For a detailed search strategy, see Appendix 1. Covidence software (Covidence systematic review software, Veritas Health Innovation, Melbourne, Australia. Available at www.covidence.org) was used to screen and review articles. On the articles identified by the initial search, a pair of review authors (SM, SH, and MA) independently performed title and abstract screening. From the reviewed articles, duplicate references were removed, and conflicts were resolved by the fourth reviewer (AW). Studies included after the abstract screening were then full text reviewed by a pair of reviewers (MA, AW, SH, SM). From the full text, the authors assessed whether the studies met the inclusion criteria based on their methodology, participants, and interventions. In case of any disagreements, consensus meetings were held to resolve them.

The reasons for excluding articles after full-text review are outlined in the PRISMA flow chart (Figure 2), which shows the status of identified studies. The quality of included studies was assessed independently by two review authors (AW, MA) and data was extracted.

Two reviewers (AW, MA) independently extracted and cross-checked the data using a standardised data extraction form using Covidence software and the following criteria.

A pair of review authors (MA and AW) independently assessed the risk of bias in each included study across seven domains, using the criteria established in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins et al., 2022). Disputes were handled through debate in consensus meetings (Higgins et al., 2011). A 'Risk of Bias' table was prepared for each trial using the 'Risk of Bias' function in Review Manager 5 software (Review Manager (RevMan) [Computer program]. Version 5.4. The Cochrane Collaboration, 2020.) Review Manager 5 was used to calculate the total risk of bias for each of the seven areas listed below.

The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) profiler Guideline Development Tool software (GRADEpro GDT 2015) and the guidelines provided in Chapter 12.2 of the Cochrane Handbook for Systematic Reviews of Interventions were used to assess the quality of the evidence for each study (Higgins et al., 2011). The GRADE method assesses the quality of the body of evidence for each outcome by taking five factors into account (study limitations, consistency of effect, imprecision, indirectness, and publication bias). For allocating a grade, the following criteria were used.

The grade of evidence was downgraded once if:

Review Manager (RevMan) [Computer program]. Version 5.4. The Cochrane Collaboration, 2020. was used to perform meta-analyses on the following outcome measures: HbA1c, Glucose, Insulin, HOMA, LDLC, HDLC, 6 MWT, TUG, Strength. The outcomes of the intervention group (eccentric exercise) and the comparator intervention group (concentric or traditional exercise) were compared in each meta-analysis. Intervention group data were not compared with non-exercise control group data. To determine the effect size for continuous variables, the mean difference (MD) was computed using either fixed effects or random effects MD (depending on heterogeneity), along with 95% confidence intervals (CI). If outcome data were inconsistently reported or different units of measurement were used, standardised mean difference (SMD) was used to estimate effect size. To assess heterogeneity, the I² statistic was used in all meta-analyses, and the degree of heterogeneity was interpreted based on Deeks and colleagues' recommendations (Deeks et al., 2011), with an I² value greater than 30% indicating probable heterogeneity that needs further investigation.

For outcomes with low heterogeneity (P values higher than 0.1 and I² statistic less than 30% or not available), we utilised a fixed effect meta-analysis. We utilised a random effects model to account for heterogeneity where there was significant variability. The Review Manager calculator (Review Manager) was used to convert data reported as least-squares mean SE or 95% CI to SD. The analysis also included studies that offered mean change data. Where studies graphically published data, authors were contacted to obtain the specific mean and standard deviation figures. If summary information for averages, standard deviations, and the number of individuals assigned to each group were not available, they were excluded from the meta-analyses.

Several major databases were searched on 20^th February 2022 for studies from the inception of that database to 15^th February 2022. The PRISMA diagram (Figure 1) shows the record of studies in various steps. The literature search conducted initially yielded a total of 674 records, with an additional ten articles being identified through manual searching of reference lists of the screened articles. After identifying and eliminating 213 duplicate records, 468 studies were evaluated based on their title and abstract. Among these, 337 studies were excluded due to not meeting the selection criteria. For full-text eligibility, 131 studies were assessed, with 112 studies being rejected. Ultimately, 19 studies were included in this review. Reasons for exclusion are provided in Figure 1. The Covidence software, an online tool developed by Veritas Health Innovation Ltd located in VIC 3000, Australia, was used to screen and review the articles.

Table 2 presents the characteristics of the study participants, interventions, and results. This review includes 19 studies. Seventeen were conducted on healthy individuals (Chen et al., 2017a; Chen et al., 2017b; Drexel et al., 2008; Duncan et al., 1989; Franchi et al., 2014; Gault et al., 2012; Hortobagyi et al., 1996a; Hortobagyi et al., 1996b; Lewis et al., 2018; Miller et al., 2006; Nickols-Richardson et al., 2007; Pavone and Moffat, 1985; Raue et al., 2005; Regnersgaard et al., 2022; Rodio and Fattorini, 2014; Tomberlin et al., 1991; Zeppetzauer et al., 2013), and two included people with T2DM (Hajihasani et al., 2014; Kudiarasu et al., 2021). Included studies were RCTs with an exercise training intervention. The modes of performing eccentric exercise training differed in the trials. Out of the 19 studies, in nine studies, exercise training was performed on a dynamometer (Duncan et al., 1989; Hortobagyi et al., 1996a; Hortobagyi et al., 1996b; Kudiarasu et al., 2021; Miller et al., 2006; Nickols-Richardson et al., 2007; Pavone and Moffat, 1985; Raue et al., 2005; Tomberlin et al., 1991). In three studies, training was performed on a treadmill (Hajihasani et al., 2014; Gault et al., 2012; Rodio and Fattorini, 2014), hiking uphill and downhill in two studies (Drexel et al., 2008; Zeppetzauer et al., 2013), ascending and descending stairs in two studies (Chen et al., 2017a; Regnersgaard et al., 2022), two studies on leg press/extension machine (Chen et al., 2017b; Franchi et al., 2014), and one study on a cycle ergometer (Lewis et al., 2018).

Each study included in this review investigated the impacts of eccentric exercise training in comparison to concentric exercise training, except one study, in which downhill treadmill walking (eccentric exercise) was compared with flat walking (Gault et al., 2012). One study compared eccentric and concentric exercises with isometric training (Pavone and Moffat, 1985). A control group was also included in five studies, which did not perform any exercise (Duncan et al., 1989; Hortobagyi et al., 1996a; Hortobagyi et al., 1996b; Raue et al., 2005; Tomberlin et al., 1991). One study compared eccentric and concentric training with an additional group performing eccentric exercises and carrying a heavy load (Regnersgaard et al., 2022). In another study, in addition to the uphill and downhill walking group, two more groups exercised by walking on flat and mixed gradients (Rodio and Fattorini, 2014). The overall length of training intervention was variable among trials; the average duration of intervention was nine weeks, ranging from four to 20 weeks. The frequency of exercise sessions per week was found to vary across the studies; the average was 2.8 sessions per week from the range of one to five sessions every week. Depending on the study, the overall repetitions performed per session also varied.

In terms of participant number, there was variation among studies, ranging from 12 to 70. Overall, there were 618 participants in all included studies after adjusting for dropouts. Of the 19 studies, seven studies were on females only (Chen et al., 2017a; Hortobagyi et al., 1996a; Hortobagyi et al., 1996b; Miller et al., 2006; Nickols-Richardson et al., 2007; Pavone and Moffat, 1985; Rodio and Fattorini, 2014), five were on males only (Chen et al., 2017b; Duncan et al., 1989; Franchi et al., 2014; Lewis et al., 2018; Raue et al., 2005) and seven included both males and females (Hajihasani et al., 2014; Drexel et al., 2008; Gault et al., 2012; Kudiarasu et al., 2021; Regnersgaard et al., 2022; Tomberlin et al., 1991; Zeppetzauer et al., 2013). The distribution of gender was not proportional in included studies; there were 319 women and 163 men. Gender information was not supplied for 136 participants across four studies.

The meta-analyses included fifteen studies. The outcomes of the studies were typically reported as mean and standard deviation (SD) or 95% confidence interval or as mean and standard deviation (SD) or 95% confidence interval or as mean change and SD. Four studies that presented data in graphical format were not included in the meta-analyses. These papers were omitted from the analysis because the authors were approached for findings but never responded. Meta-analyses were carried out in Revman (Review Manager (RevMan) [Computer program]. Version 5.4.1, The Cochrane Collaboration, 2020.)

Six studies (Chen et al., 2017a; Chen et al., 2017b; Drexel et al., 2008; Kudiarasu et al., 2021; Regnersgaard et al., 2022; Zeppetzauer et al., 2013) provided information about the effects of eccentric exercise on glucose handling, five (Chen et al., 2017a; Chen et al., 2017b; Drexel et al., 2008; Kudiarasu et al., 2021; Zeppetzauer et al., 2013) reported about effects on lipids, six (Hajihasani et al., 2014; Chen et al., 2017a; Chen et al., 2017b; Gault et al., 2012; Kudiarasu et al., 2021; Regnersgaard et al., 2022) reported the effects on functional physical fitness, sixteen (Chen et al., 2017a; Chen et al., 2017b; Duncan et al., 1989; Franchi et al., 2014; Gault et al., 2012; Hortobagyi et al., 1996a; Hortobagyi et al., 1996b; Kudiarasu et al., 2021; Lewis et al., 2018; Miller et al., 2006; Nickols-Richardson et al., 2007; Pavone and Moffat, 1985; Raue et al., 2005; Regnersgaard et al., 2022; Rodio and Fattorini, 2014; Tomberlin et al., 1991) studies reported the effects on muscle strength. Two papers (Drexel et al., 2008; Zeppetzauer et al., 2013) reported results from the same study. However, due to possible duplication, only one of these studies was included in the meta-analysis (Drexel et al., 2008).

Figure 2 summarises the risk of bias assessment for each included study. Nineteen studies (Hajihasani et al., 2014; Chen et al., 2017a; Chen et al., 2017b; Drexel et al., 2008; Duncan et al., 1989; Franchi et al., 2014; Gault et al., 2012; Hortobagyi et al., 1996a; Hortobagyi et al., 1996b; Kudiarasu et al., 2021; Lewis et al., 2018; Miller et al., 2006; Nickols-Richardson et al., 2007; Pavone and Moffat, 1985; Raue et al., 2005; Regnersgaard et al., 2022; Rodio and Fattorini, 2014; Tomberlin et al., 1991; Zeppetzauer et al., 2013) were at high risk of bias for blinding participants and personnel criteria as in these exercise studies participants were not blinded to the intervention they received. In one study (Raue et al., 2005), the risk of bias was high for random sequence generation and allocation concealment (selection bias). In one study (Franchi et al., 2014), the risk of bias was high for random sequence generation. In another study (Lewis et al., 2018) risk of bias was high for allocation concealment (selection bias). For other categories, the bias was often low or not clear. Figure 2 represents the results of the risk of bias assessment. Figure 3 shows the review authors’ judgements about each risk of bias item for the review presented as percentages across included studies.

Six studies reported the effectiveness of eccentric exercise intervention on glycaemic control. Five studies were conducted on healthy people (Chen et al., 2017a; Chen et al., 2017b; Drexel et al., 2008; Regnersgaard et al., 2022; Zeppetzauer et al., 2013), and one was on people with T2DM (Kudiarasu et al., 2021). The modality of training used in these studies was a leg extension machine (Chen et al., 2017b), hiking upwards and downwards (Drexel et al., 2008; Zeppetzauer et al., 2013), resistance exercises (bicep curl, chest press, latissimus dorsi, triceps extension, leg extension, leg curl, calf raise, abdominal crunch) (Kudiarasu et al., 2021), and descending and ascending stairs (Chen et al., 2017a; Regnersgaard et al., 2022).

In two studies (Chen et al., 2017a; Chen et al., 2017b), glycaemic control was measured through fasting glucose, insulin, HOMA, HbA1C, and Oral glucose tolerance test (OGTT). Two studies (Drexel et al., 2008; Zeppetzauer et al., 2013) measured HOMA, Serum fasting insulin and glucose area under the curve in response to an OGTT. In one study (Regnersgaard et al., 2022), only fasting blood glucose was measured. In one study on people with T2DM (Kudiarasu et al., 2021), glycaemic control was measured through fasting plasma glucose, serum insulin, HbA1c and HOMA.

In four studies (Chen et al., 2017a; Chen et al., 2017b; Drexel et al., 2008; Zeppetzauer et al., 2013), the HOMA index of insulin resistance and fasting serum insulin were lowered by eccentric exercise. In one study (Drexel et al., 2008), a decrease in the area under the glucose curve after a standardised oral glucose load was seen after performing both concentric and eccentric exercise training; however, only the difference acquired through eccentric exercise was statistically significant. In one study (Kudiarasu et al., 2021), HbA1c decreased significantly (p < 0.05) after twelve weeks of concentric training only and not after eccentric training. In another study, no statistically significant difference was observed in glucose after intervention in any group (Regnersgaard et al., 2022).

HbA1c was measured in three studies (Chen et al., 2017a; Chen et al., 2017b; Kudiarasu et al., 2021) (74 participants). All studies reported results as mean and SD. A random effects meta-analysis using SMD showed eccentric exercise led to non-significant decreases in HbA1c level (SMD - 0.99; 95% CI, -2.96 to 0.98; n = 74; P = 0.32; Figure 4) across all studies in the meta-analysis with high and significant (I² = 92%, p = 0.00001) heterogeneity observed. The evidence for eccentric exercise to decrease HbA1c as compared to concentric exercise was graded as very low. The quality of evidence was downgraded thrice; once for the high risk of bias in included studies due to lack of blinding for participants and assessors; once for small sample size, and once due to more than 40% heterogeneity. HOMA was measured in four studies (116 participants). A random-effects meta-analysis using SMD showed eccentric exercise led to non-significant decreases in HOMA (SMD -0.92; 95% CI, -1.98 to 0.15; n = 116; P = 0.09; Figure 4) across all studies in the meta-analysis with high and significant (I2 = 85%, p = 0.0002) heterogeneity observed. These findings represent an approximate decrease of 0.42 in HOMA (95% CI -0.90 to 0.07). The quality of evidence for eccentric exercise to decrease HOMA was graded as very low. The quality of evidence was downgraded thrice, once for the high risk of bias in the included studies due to lack of blinding for participants and assessors, once for a small sample size, and once due to more than 40% heterogeneity.

Glucose was measured as fasting serum glucose (Chen et al., 2017a; Chen et al., 2017b; Kudiarasu et al., 2021; Regnersgaard et al., 2022) and as Glucose (Area under the curve) in OGTT(Drexel et al., 2008). Fasting glucose was measured in four studies (Chen et al., 2017a; Chen et al., 2017b; Kudiarasu et al., 2021; Regnersgaard et al., 2022) (88 participants). A random-effects meta-analysis using SMD showed eccentric exercise led to non-significant decreases in fasting glucose level (SMD - 0.84; 95% CI, -1.95 to 0.27; n = 14; P = 0.14; Figure 4). The quality of evidence for eccentric exercise to decrease fasting glucose was graded as low. The quality of the evidence was rated as low because of the high risk of bias due to a lack of blinding for participants and assessors and once due to the small sample size.

Serum insulin was measured in four studies (119 participants) as fasting serum insulin (Chen et al., 2017a; Chen et al., 2017b; Drexel et al., 2008; Kudiarasu et al., 2021). A random-effects meta-analysis using SMD showed eccentric exercise led to non-significant decreases in insulin (SMD -0.93; 95% CI, -1.97 to 0.12; n = 119; P = 0.08; Figure 4) across all studies in the meta-analysis with high and significant (I2 = 85%, p = 0.0002) heterogeneity observed. This represents an approximate decrease of 17.98 pmol/L in insulin (95% CI -38.1 to 2.32). The quality of evidence for eccentric exercise to decrease insulin was graded as very low. The quality of evidence was downgraded thrice; once for the high risk of bias in the included studies due to lack of blinding for participants and assessors; once for a small sample size, and once due to more than 40% heterogeneity.

Five studies have reported the effects of eccentric exercise on lipids (Chen et al., 2017a; Chen et al., 2017b; Drexel et al., 2008; Kudiarasu et al., 2021; Zeppetzauer et al., 2013). Four studies were conducted on Healthy sedentary people (Chen et al., 2017a; Chen et al., 2017b; Drexel et al., 2008; Zeppetzauer et al., 2013) and one on people with T2DM(Kudiarasu et al., 2021). Exercise training was performed by hiking uphill and downhill (Drexel et al., 2008; Zeppetzauer et al., 2013), ascending and descending stair walking(Chen et al., 2017a), using a leg extension machine(Chen et al., 2017b) and Cybex dynamometer(Kudiarasu et al., 2021). TG, TC, LDLC, and HDLC were measured in all studies. In one paper Apolipoprotein B and apolipoprotein B/apolipoprotein A1 (apo B/apo A1), the ratio was also calculated (Drexel et al., 2008).

In two studies (Chen et al., 2017a; Chen et al., 2017b), TC, TG, and LDLC decreased significantly after eccentric and concentric training. However, the eccentric group's lowered magnitude was substantially greater than the concentric groups. In HDLC, a significant increase after only eccentric exercise was observed. In other studies, (Drexel et al., 2008; Zeppetzauer et al., 2013), HDLC, LDLC, TC, and apo B/apo A1 ratio were reduced in both eccentric and concentric groups, but only the diference for LDLC was statistically significant. There were no significant changes in the lipid profile for either group from pre- to post-intervention in the study on people with T2DM (Kudiarasu et al., 2021).

A meta-analysis was performed on the results of four studies (Chen et al., 2017a; Chen et al., 2017b; Drexel et al., 2008; Kudiarasu et al., 2021; Regnersgaard et al., 2022) as two papers reported the same study and had similar results (Drexel et al., 2008; Zeppetzauer et al., 2013), so data from only one study (Drexel et al., 2008) was included. The results show eccentric exercise is associated with non-significant LDLC reduction (SMD -0.52; 95% CI, -1.57 to 0.52; n = 116, P = 0.33; Figure 5) with high and significant (I² = 85%, P = 0.0002) heterogeneity observed and increased HDLC (SMD 0.74; 95% CI, -0.29 to 1.76; n = 116; P = 0.16; Figure 6) with high and significant (I² = 84%, P = 0.0003) heterogeneity observed as compared with concentric exercise. This represents an approximate decrease of 0.25 mmol/L (95% CI -0.77 to 0.25) in LDLC and an increase of 0.22 mmol/L (95% CI -0.09 to 0.52) in HDLC. The quality of evidence for eccentric exercise to decrease LDLC and increase HDLC was graded as very low. The quality of evidence was downgraded thrice; once for the high risk of bias in the included studies due to lack of blinding for participants and assessors; once for a small sample size, and once due to more than 40% heterogeneity.

Two studies (Chen et al., 2017a; Lewis et al., 2018) reported the effect of chronic eccentric exercise training compared to concentric training on cardiovascular outcome measures. Both these studies reported the effect of chronic eccentric training on resting brachial blood pressure, and only one (Chen et al., 2017a) reported an effect on resting heart rate. None of the studies measured central (aortic) blood pressure or arterial health.

Two studies on healthy participants measured brachial systolic and diastolic blood pressure (SBP and DBP) (Chen et al., 2017a; Lewis et al., 2018). The results of one study (Chen et al., 2017a) in which the training modality was walking up and down stairs showed SBP decreased more after eccentric exercise (-9%) than after concentric exercise (-4%). In the case of DBP, significant decreases were found in both groups following the training intervention, with no substantial differences between them. Another study (Lewis et al., 2018) showed a non-significant decrease in SBP and DBP among both training groups after training. At baseline, there was no difference in resting blood pressure between the groups, and this remained the same following training.

A random-effects meta-analysis using MD showed eccentric exercise led to significant decreases in SBP (MD -6.84; 95% CI, -9.84 to -3.84; P = 0.00001 n = 47; Figure 7) with no (I² = 0%; P = 0.90) heterogeneity observed. The quality of evidence for eccentric exercise to decrease SBP was graded as low. The quality of evidence was downgraded twice, once for the high risk of bias in the included studies due to lack of blinding for participants and assessors and once for a small sample size.

A random-effects meta-analysis using MD performed on the results of two studies showed eccentric exercise led to a significant decrease in DBP (MD -6.39; 95% CI -9.62 to -3.15; P = 0.0001, n = 47; figure 7) with high and non-significant (I² = 70%; P = 0.07) heterogeneity observed. The quality of evidence for eccentric exercise to decrease DBP was graded as very low. The quality of evidence was downgraded thrice; once for the high risk of bias in the included studies due to lack of blinding for participants and assessors; once for a small sample size, and once due to more than 40% heterogeneity.

One study (Chen et al., 2017a) on a healthy population reported the effects of concentric and eccentric exercise training on resting heart rate. Results showed that resting heart rate was significantly decreased after eccentric exercise (-9.8 + 4.3%) compared to concentric exercise (-4.0% + 3.7%) after a 12-week intervention.

Six studies have reported the effects of eccentric exercise on functional physical fitness. Four studies (Chen et al., 2017a; Chen et al., 2017b; Gault et al., 2012; Regnersgaard et al., 2022) were conducted on a healthy population and two studies (Hajihasani et al., 2014; Kudiarasu et al., 2021) on people with T2DM. The training was performed by walking on a treadmill (Hajihasani et al., 2014; Gault et al., 2012), ascending and descending stairs (Chen et al., 2017a; Regnersgaard et al., 2022), using a leg extension machine (Chen et al., 2017b) and a Cybex dynamometer (Kudiarasu et al., 2021). The studies included in our review assessed a range of functional fitness tests, including tests for aerobic fitness/endurance (6MWT) and tests for mobility/flexibility, balance, and strength such as (TUG, 30-sec chair stand, 8 foot up and go, 6 m tandem walk, 2 min- step test). All but one study assessed functional fitness through 6MWT (Hajihasani et al., 2014; Chen et al., 2017a; Chen et al., 2017b; Kudiarasu et al., 2021; Regnersgaard et al., 2022). The remaining study (Gault et al., 2012) assessed functional physical fitness through TUG, and five repetitions sit to stand test. TUG was also performed in two other studies (Hajihasani et al., 2014; Kudiarasu et al., 2021). Two studies (Chen et al., 2017a; Chen et al., 2017b) performed other measures of functional physical fitness in addition to 6MWT, such as 30 seconds sit-to-stand test (30STS), 2 min- step test, 8 foot up and go test, and 6 m tandem walk test.

In the three studies which measured functional physical fitness through TUG, two studies (Hajihasani et al., 2014; Kudiarasu et al., 2021) compared eccentric exercise to concentric exercise, whereas one compared eccentric exercise (downhill walking) with traditional exercise (flat-level walking) (Gault et al., 2012). Results of two studies (Hajihasani et al., 2014; Gault et al., 2012) indicated that both types of exercise training decreased TUG time (sec) pre- to post-training significantly; however, in between group analysis, there was no significant difference observed. The third study showed that only eccentric training decreased time (sec) after training for TUG significantly (Kudiarasu et al., 2021). Meta-analysis was not performed on results because, in two studies, data was graphically presented (Hajihasani et al., 2014; Gault et al., 2012).

Among five studies that performed 6MWT, distance walked in 6 minutes increased post-training intervention in both groups. In two studies (Hajihasani et al., 2014; Chen et al., 2017a), the increase in 6MWT distance was significantly more for the eccentric training group than the concentric training group. Three studies (Chen et al., 2017b; Kudiarasu et al., 2021; Regnersgaard et al., 2022) reported no significant difference between groups, functional physical fitness increased in both groups because of training. A random effects meta-analysis using MD was performed on the results of four studies, as data was graphically presented in one paper (Hajihasani et al., 2014). The distance walked post-intervention was greater in both intervention groups in all studies. Results showed a non-significant increase in distance walked in meters in 6MWT following the eccentric versus concentric intervention (MD 13.91; 95%CI -18.44 to 46.27; p = 0.40; Figure 8) across all studies in the meta-analysis with a high and significant level of heterogeneity (I² = 81%, p = 0.001). The evidence for eccentric exercise to increase the distance walked in 6MWT was graded as very low. The quality of evidence was downgraded thrice; once for the high risk of bias in the included studies due to lack of blinding for participants and assessors; once for a small sample size, and once due to more than 40% heterogeneity.

Results from one (Chen et al., 2017a) of the two studies(Chen et al., 2017a; Chen et al., 2017b), which performed a 30-s chair stand, 8 foot up and go, 2 min- step test, and 6 m tandem walk, showed significant improvement in all these functional physical fitness parameters. However, the 30-s chair stand test and 6 m tandem walk showed more remarkable improvement for the eccentric than the concentric group. In the other study (Chen et al., 2017b), 8-foot up-and-go and 30-s chair stand test results were significantly better (P < 0.05) for the eccentric training group than concentric training group, but no significant diferences were found for other tests. Another study (Regnersgaard et al., 2022) also performed a 30-sec chair-stand test; results showed that the number of stands increased significantly after both types of exercise. A fixed-effects meta-analysis using MD was performed on the results of all studies. Results showed a significantly increased number of stands in the 30-sec chair-stand-test following the eccentric versus concentric intervention (MD 3.24; 95%CI -1.89 to 4.58; n = 70; p = 0.00001; Figure 9) across all studies in the meta-analysis with no heterogeneity observed (I2 = 0%, p = 0.52). The evidence for eccentric exercise to increase the number of stands in the 30-sec chair-stand test was graded as low. The quality of evidence was downgraded twice, once for study limitations due to the high risk of bias due to lack of blinding for participants and assessors and once due to small sample size.

Sixteen studies reported the effects of eccentric exercise training on muscle strength (Chen et al., 2017a; Chen et al., 2017b; Duncan et al., 1989; Franchi et al., 2014; Gault et al., 2012; Hortobagyi et al., 1996a; Hortobagyi et al., 1996b; Kudiarasu et al., 2021; Lewis et al., 2018; Miller et al., 2006; Nickols-Richardson et al., 2007; Pavone and Moffat, 1985; Raue et al., 2005; Regnersgaard et al., 2022; Rodio and Fattorini, 2014; Tomberlin et al., 1991). Among these, 15 studies were conducted on healthy people, and one included people with T2DM (Kudiarasu et al., 2021). Fifteen studies compared eccentric exercise with concentric exercise (Chen et al., 2017a; Chen et al., 2017b; Duncan et al., 1989; Franchi et al., 2014; Hortobagyi et al., 1996a; Hortobagyi et al., 1996b; Kudiarasu et al., 2021; Lewis et al., 2018; Miller et al., 2006; Nickols-Richardson et al., 2007; Pavone and Moffat, 1985; Raue et al., 2005; Regnersgaard et al., 2022; Rodio and Fattorini, 2014; Tomberlin et al., 1991) and one study (Gault et al., 2012) compared eccentric exercise with mixed training. Five studies also included a non-exercise control group (Duncan et al., 2016; Hortobagyi et al., 1996a; Hortobagyi et al., 1996b; Raue et al., 2005; Tomberlin et al., 1991). One study (Rodio and Fattorini, 2014) included two additional comparison groups (level and mixed walking group), while another study(Pavone and Moffat, 1985) included an isometric training comparison group. A single study included two eccentric training groups (downhill walking and downhill walking while carrying additional weight in a backpack) (Regnersgaard et al., 2022). In nine studies, training was performed on an isokinetic dynamometer (Duncan et al., 1989; Hortobagyi et al., 1996a; Hortobagyi et al., 1996b; Kudiarasu et al., 2021; Miller et al., 2006; Nickols-Richardson et al., 2007; Pavone and Moffat, 1985; Raue et al., 2005; Tomberlin et al., 1991), two studies involved climbing or descending stairs (Chen et al., 2017a; Regnersgaard et al., 2022), two studies used a leg extension machine (Chen et al., 2017b; Franchi et al., 2014), two included treadmill walking (Gault et al., 2012; Rodio and Fattorini, 2014) and one study involved training on a cycle ergometer(Lewis et al., 2018). Strength was measured through an isokinetic dynamometer(Chen et al., 2017b; Duncan et al., 1989; Franchi et al., 2014; Gault et al., 2012; Hortobagyi et al., 1996a; Hortobagyi et al., 1996b; Lewis et al., 2018; Miller et al., 2006; Nickols-Richardson et al., 2007; Pavone and Moffat, 1985; Raue et al., 2005; Tomberlin et al., 1991), leg extension device (Chen et al., 2017a), force plate(Regnersgaard et al., 2022), using free weights (Kudiarasu et al., 2021), and an experimental strength measurement device based on a load cell (Rodio and Fattorini, 2014). Strength was measured as one repetition maximum (RM) (Chen et al., 2017b; Franchi et al., 2014; Kudiarasu et al., 2021; Raue et al., 2005), 3 RM (Regnersgaard et al., 2022), 6 RM(Lewis et al., 2018), Maximum voluntary isometric contraction (MVC-Iso) (Chen et al., 2017a; Chen et al., 2017b; Hortobagyi et al., 1996a; Hortobagyi et al., 1996b; Lewis et al., 2018; Pavone and Moffat, 1985; Rodio and Fattorini, 2014), concentric isokinetic torque (Duncan et al., 1989; Gault et al., 2012; Hortobagyi et al., 1996a; Hortobagyi et al., 1996b; Miller et al., 2006; Nickols-Richardson et al., 2007; Tomberlin et al., 1991) and eccentric isokinetic torque (Duncan et al., 1989; Gault et al., 2012; Hortobagyi et al., 1996a; Hortobagyi et al., 1996b; Miller et al., 2006; Nickols-Richardson et al., 2007; Tomberlin et al., 1991).

Eccentric training increased isometric(Chen et al., 2017a; Chen et al., 2017b; Franchi et al., 2014; Hortobagyi et al., 1996a; Hortobagyi et al., 1996b; Lewis et al., 2018; Rodio and Fattorini, 2014), concentric(Chen et al., 2017b; Franchi et al., 2014; Kudiarasu et al., 2021; Miller et al., 2006; Nickols-Richardson et al., 2007; Pavone and Moffat, 1985) and eccentric strength(Duncan et al., 1989; Gordon et al., 2019; Hortobagyi et al., 1996b; Miller et al., 2006; Nickols-Richardson et al., 2007; Tomberlin et al., 1991). Concentric training also increased isometric(Franchi et al., 2014; Hortobagyi et al., 1996b; Lewis et al., 2018), concentric (Duncan et al., 1989; Franchi et al., 2014; Hortobagyi et al., 1996b; Kudiarasu et al., 2021; Miller et al., 2006; Nickols-Richardson et al., 2007; Raue et al., 2005; Regnersgaard et al., 2022; Tomberlin et al., 1991) and eccentric strength (Hortobagyi et al., 1996a; Miller et al., 2006; Nickols-Richardson et al., 2007; Tomberlin et al., 1991). A single study reported no change in eccentric and concentric strength after downhill and flat-level Walking (Gault et al., 2012).

A random effects meta-analysis using SMD performed on the results of five studies showed eccentric exercise led to a significant increase in isometric strength (SMD 0.84; 95% CI 0.03 to 1.65; n=120; P = 0.04, figure 10) with significant and high (I² = 76%; P=0.002) heterogeneity observed. This represents an approximate 7.8 Nm increase in isometric strength (95% CI 0.27 to 15.25). The quality of evidence for eccentric exercise to increase isometric strength was graded as very low. The quality of evidence was downgraded thrice, once due to the high risk of bias in included studies due to lack of blinding for participants and assessors, once for small sample size and once for more than 40% heterogeneity.

Meta-analysis was performed on the results of ten studies as data were presented graphically in one study (Hortobagyi et al., 1996b). A random effects meta-analysis using SMD showed eccentric exercise led to a non-significant increase in concentric strength (SMD 0.16; 95% CI -0.26 to 0.58; n = 292; P = 0.45, figure 10) with high and significant (I² = 64%; P = 0.003) heterogeneity observed. This represents an approximate 5.8 Nm increase in concentric strength (95% CI -9.43 to 21.04). The quality of evidence for eccentric exercise to increase concentric strength was graded as very low. The quality of evidence was downgraded thrice, once due to the high risk of bias in included studies due to lack of blinding for participants and assessors, once for a small sample size and once for more than 40% heterogeneity.

Meta-analysis was performed on the results of six studies as results were in graphical form in one study(Hortobagyi et al., 1996b). A random effects meta-analysis using SMD performed on the results of six studies showed eccentric exercise led to a significant increase in eccentric strength (SMD 1.37; 95% CI 0.21 to 2.53; n = 224; P = 0.02, figure 10) with high and significant (I² = 93%; P = 0.00001) heterogeneity observed. This represents an approximate 70.82 Nm increase in eccentric strength (95% CI 10.85 to 130.79). The quality of evidence for eccentric exercise to increase eccentric strength was graded as very low. The quality of evidence was downgraded thrice, once due to the high risk of bias in included studies due to lack of blinding for participants and assessors, once for a small sample size and once for more than 40% heterogeneity.

Each of these analyses shows a trend towards greater strength gains among those who exercise eccentrically versus concentrically.

The health-related risk factors explored in this review included glucose handling, lipids, and blood pressure. Only six RCTs compared the effects of eccentric exercise to concentric exercise on glucose handling. Results indicated that eccentric exercise led to similar or better glucose handling by decreasing HbA1c, HOMA, fasting glucose and insulin compared to concentric exercise. The mechanism related to better glucose handling during eccentric exercise is based on the type of contractions. During lengthening eccentric contractions, there is greater microdamage sustained by muscle fibres. Hence, more energy is required to repair the damaged muscle fibres, which leads to better blood glucose handling (Proske and Morgan, 2001). Although the overall effect size favoured eccentric exercise over concentric exercise, but there were very few studies, and significant heterogeneity was observed across studies; consequently, these findings require further investigation.

Similarly, limited research studies have investigated the effects of eccentric exercise training on lipids, and none of the previous reviews has examined these effects. Among the 19 studies, five examined the effects of eccentric exercise training on lipid levels. LDLC levels are directly and HDLC levels are inversely related to the risk of cardiovascular disorders. Meta-analyses performed on the results of four studies in our review represent a non-significant decrease in LDLC and an increase in HDLC after eccentric exercise training. A possible explanation is that oxidation of fatty acid increases after eccentric contractions (Peñailillo et al., 2014). Reduction in LDLC that occurred following eccentric resistance training may be caused by the flow of cholesterol into the muscle from plasma. This provides a platform for synthesising new cell membranes (Paschalis et al., 2011). The rise in HDLC that occurs after eccentric exercise may be attributable to an increase in lipoprotein lipase activity, an enzyme which accelerates the breakdown of TG derived from very low-density lipoproteins (VLDL) and reduces the size of lipoprotein particles. Consequently, an excess of shell lipids are produced, the majority of which are transferred to HDLC (Frayn et al., 2003; Paschalis et al., 2010). Two studies analysed the effects of eccentric exercise training on HR and BP. Results showed that eccentric exercise significantly lowered both SBP and DBP.

Based on our findings, eccentric exercise is as or more effective than concentric exercise for the management of health-related risk factors. Furthermore, our review indicates the trend of eccentric exercise towards better glucose handling than traditional or concentric exercise. This finding has important potential implications linked to the effective management of conditions involving impaired glucose handling, such as T2DM. Obesity and a sedentary lifestyle are key risk factors for developing T2DM (Qin et al., 2010). In sedentary individuals at risk of metabolic disease, adopting eccentric exercises could delay the development of metabolic disease and may be more attractive due to lower cardiovascular demand and reduced perceived effort associated with the exercise (Lewis et al., 2018). Nevertheless, additional high-quality studies with minimal risk of bias are necessary to validate these results.

The capability to perform one's daily living (ADL) activities without undue fatigue or difficulty is typically considered an indicator of functional fitness. Functional fitness assessment tests are carried out to determine the individual's mobility, strength, flexibility and endurance (Rikli and Jones, 2013). As individuals age, functional fitness decreases. A low level of fitness in elderly is linked to excessive lean muscle loss, an abnormal metabolic profile, increases in blood pressure, poor balance and reduced muscle strength, all of which lead to increased dependence on others, which negatively impacts the quality of life and leads to increased risk of morbidity and mortality (Jae et al., 2010; Koster et al., 2010; Sui et al., 2012). Maintaining functional physical fitness from a young age is essential to delay mortality and dependency associated with ageing. Studies included in this review had a mix of young and older adult populations. Various tests, including 6MWT, assessed functional fitness. The ability to walk as far as possible in a given time reflects individuals' functionality and quality of life (Enright et al., 2003). Meta-analysis showed eccentric exercise led to a non-significant increase of 14 m in 6 MWT compared to concentric exercise. A previous review has shown that a change of 14.0 to 30.5m in 6MWT distance is clinically meaningful across multiple chronic disease groups (Bohannon and Crouch, 2017); this indicates that the increase reported in this review may represent a meaningful improvement in physical fitness. However, given that changes were not statistically significant, further research is required to support this contention. TUG and 30STS tests frequently assess fall risk and overall function (Bennell et al., 2011). All three studies that analysed the effects of eccentric exercise on TUG showed improvement after eccentric exercise training compared to pre-training scores (Hajihasani et al., 2014; Gault et al., 2012; Kudiarasu et al., 2021). There was a significant improvement in 30STS after eccentric exercise training compared to traditional or concentric exercise. The conclusions of this review align with a recent review (Čretnik et al., 2022) conducted on older healthy adults (greater than 55 years) and patients with metabolic and cardiovascular diseases, which reported eccentric exercise elicited more significant improvements in TUG, 2-min sit-stand test and 30STS, but not significantly in 6MWT. Our findings build on this previous review by including a more diverse age group and additional studies.

With age, people experience a simultaneous deterioration in their strength and the quality of their muscles, both of which lead to lower exercise tolerance and an increased risk of impairment, significantly decreasing their life quality (Hughes et al., 2001; Manini et al., 2007). The cardiovascular function also declines with age (Gault and Willems, 2013). Less cardiovascular stress is caused by eccentric actions (Vallejo et al., 2006) and the perceived exertion is also low (Hollander et al., 2003). Our review confirms that eccentric exercise training significantly increases isometric and eccentric strength more than traditional/concentric exercise. Eccentric exercise training also indicated a trend towards greater gains in concentric strength than concentric exercise, even though the difference was not statistically significant. In conclusion, this systematic review suggests that eccentric exercise may be more beneficial for people with lower exercise tolerance due to greater improvements in strength with lower perceived effort compared to concentric exercise (Vallejo et al., 2006). The meta-analyses conducted on strength showed a positive finding for heterogeneity. This variation could be due to disparities in training modalities, training duration and intensity, methods used for testing strength, and participant characteristics. Our results align with a previous review (Roig et al., 2009), showing increased strength with eccentric exercise. In contrast to our results, a systematic review of older people demonstrated that isometric strength gains were greater following eccentric training than concentric/traditional training. Although the overall effect favoured the eccentric group, it was not statistically significant (Čretnik et al., 2022). The difference between the previous and our review is due to the difference in studies included in both reviews. The previous review encompassed studies involving older individuals (greater than 55 years) only, whereas this review included studies conducted on both young and ageing populations. As eccentric contractions can enhance muscle strength and mass without imposing undue stress on the cardiopulmonary system, they merit exploration as a potential exercise option for individuals with low exercise tolerance, including frail elderly individuals or those with chronic illnesses (Roig et al., 2008; Vallejo et al., 2006).

There are several strengths of this review. Before conducting the searches, the decisions related to the selection of studies, data extraction and analyses were made, and the study protocol was registered on Prospero. We used certified tools like Covidence and Grade Pro to screen studies and grade the evidence quality and adhered to the PRISMA-P guidelines. Data were extracted by two reviewers independently in Covidence. Two reviewers conducted an independent risk of bias assessment, and the findings were utilized to evaluate the quality of the evidence. Since RCTs are part of the review, it is considered to have the highest possible level of evidence. Another important strength is that the included studies were not limited to a specific population but included diverse populations, so the findings of this review are widely applicable.

However, we recognise that this review has some limitations. Few studies have been conducted to examine the chronic effects of eccentric exercise programmes in contrast to concentric/traditional exercise on health risk factors such as glucose handling, lipids, heart rate, blood pressure and arterial health. Furthermore, limited studies were conducted on people with metabolic disease, so meta-analyses were conducted on these limited studies, and subgroup analyses were not possible. Most of these studies received a "low" rating in methodological quality due to their failure to implement blinding procedures for participants, evaluators, and therapists responsible for delivering training in the study. It is vital to consider that blinding participants and therapists in exercise training type studies is difficult.

There was heterogeneity in exercise type and data measurement methods, for example, strength was measured using a range of equipment, making it difficult to compare outcomes. In some studies, participants engaged in aerobic training (i.e., walking or cycling); while in others, they engaged in resistance-type protocols (i.e., isokinetic). Because there were few studies, it was impossible to categorise them based on the sort of training technique used. In future studies, it may be possible to eliminate these disparities by utilizing more exact descriptors to characterise each mode of training.