Give it a rest: a systematic review with Bayesian meta-analysis on the effect of inter-set rest interval duration on muscle hypertrophy.

We systematically searched the literature for studies with a randomized design that compared different inter-set rest interval durations for estimates of pre-/post-study changes in lean/muscle mass in healthy adults while controlling all other training variables. Bayesian meta-analyses on non-controlled effect sizes using hierarchical models of all 19 measurements (thigh: 10; arm: 6; whole body: 3) from 9 studies meeting inclusion criteria analyses showed substantial overlap of standardized mean differences across the different inter-set rest periods [binary: short: 0.48 (95%CrI: 0.19-0.81), longer: 0.56 (95%CrI: 0.24-0.86); Four categories: short: 0.47 (95%CrI: 0.19-0.80), intermediate: 0.65 (95%CrI: 0.18-1.1), long: 0.55 (95%CrI: 0.15-0.90), very long: 0.50 (95%CrI: 0.14-0.89)], with substantial heterogeneity in results. Univariate and multivariate pairwise meta-analyses of controlled binary (short vs. longer) effect sizes showed similar results for the arm and thigh with central estimates tending to favor longer rest periods [arm: 0.13 (95%CrI: -0.27 to 0.51); thigh: 0.17 (95%CrI: -0.13 to 0.43)]. In contrast, central estimates closer to zero but marginally favoring shorter rest periods were estimated for the whole body [whole body: -0.08 (95%CrI: -0.45 to 0.29)]. Subanalysis of set end-point data indicated that training to failure or stopping short of failure did not meaningfully influence the interaction between rest interval duration and muscle hypertrophy. In conclusion, results suggest a small hypertrophic benefit to employing inter-set rest interval durations >60 s, perhaps mediated by reductions in volume load. However, our analysis did not detect appreciable differences in hypertrophy when resting >90 s between sets, consistent with evidence that detrimental effects on volume load tend to plateau beyond this time-frame. Systematic Review Registration: OSF, https://doi.org/10.17605/OSF.IO/YWEVC.

Exploring the Dose-Response Relationship Between Estimated Resistance Training Proximity to Failure, Strength Gain, and Muscle Hypertrophy: A Series of Meta-Regressions.

BACKGROUND: The proximity to failure in which sets are terminated has gained attention in the scientific literature as a potentially key resistance training variable. Multiple meta-analyses have directly (i.e., failure versus not to failure) or indirectly (e.g., velocity loss, alternative set structures) evaluated the effect of proximity to failure on strength and muscle hypertrophy outcomes categorically; however, the dose-response effects of proximity to failure have not been analyzed collectively in a continuous manner. OBJECTIVE: To meta-analyze the aforementioned areas of relevant research, proximity to failure was quantified as the number of repetitions in reserve (RIR). Importantly, the RIR associated with each effect in the analysis was estimated on the basis of the available descriptions of the training interventions in each study. Data were extracted and a series of exploratory multilevel meta-regressions were performed for outcomes related to both strength and muscle hypertrophy. A range of sensitivity analyses were also performed. All models were adjusted for the effects of load, method of volume equating, duration of intervention, and training status. RESULTS: The best fit models for both strength and muscle hypertrophy outcomes demonstrated modest quality of overall fit. In all of the best-fit models for strength, the confidence intervals of the marginal slopes for estimated RIR contained a null point estimate, indicating a negligible relationship with strength gains. However, in all of the best-fit models for muscle hypertrophy, the marginal slopes for estimated RIR were negative and their confidence intervals did not contain a null point estimate, indicating that changes in muscle size increased as sets were terminated closer to failure. CONCLUSIONS: The dose-response relationship between proximity to failure and strength gain appears to differ from the relationship with muscle hypertrophy, with only the latter being meaningfully influenced by RIR. Strength gains were similar across a wide range of RIR, while muscle hypertrophy improves as sets are terminated closer to failure. Considering the RIR estimation procedures used, however, the exact relationship between RIR and muscle hypertrophy and strength remains unclear. Researchers and practitioners should be aware that optimal proximity to failure may differ between strength and muscle hypertrophy outcomes, but caution is warranted when interpreting the present analysis due to its exploratory nature. Future studies deliberately designed to explore the continuous nature of the dose-response effects of proximity to failure in large samples should be considered.

Similar muscle hypertrophy following eight weeks of resistance training to momentary muscular failure or with repetitions-in-reserve in resistance-trained individuals.

This study examined the influence of resistance training (RT) proximity-to-failure, determined by repetitions-in-reserve (RIR), on quadriceps hypertrophy and neuromuscular fatigue. Resistance-trained males (n = 12) and females (n = 6) completed an 8-week intervention involving two RT sessions per week. Lower limbs were randomised to perform the leg press and leg extension exercises either to i) momentary muscular failure (FAIL), or ii) a perceived 2-RIR and 1-RIR, respectively (RIR). Muscle thickness of the quadriceps [rectus femoris (RF) and vastus lateralis (VL)] and acute neuromuscular fatigue (i.e., repetition and lifting velocity loss) were assessed. Data was analysed with Bayesian linear mixed-effect models. Increases in quadriceps thickness (average of RF and VL) from pre- to post-intervention were similar for FAIL [0.181 cm (HDI: 0.119 to 0.243)] and RIR [0.182 cm (HDI: 0.115 to 0.247)]. Between-protocol differences in RF thickness slightly favoured RIR [-0.036 cm (HDI: -0.113 to 0.047)], but VL thickness slightly favoured FAIL [0.033 cm (HDI: -0.046 to 0.116)]. Mean volume was similar across the RT intervention between FAIL and RIR. Lifting velocity and repetition loss were consistently greater for FAIL versus RIR, with the magnitude of difference influenced by the exercise and the stage of the RT intervention.

Terminating RT sets with a close proximity-to-failure (e.g., 1- to 2-RIR) can be sufficient to promote similar hypertrophy of the quadriceps as reaching momentary muscular failure in resistance-trained individuals over eight weeks, but the overall influence of proximity-to-failure on muscle-specific hypertrophy may also depend on other factors (e.g., exercise selection, order, and subsequent musculature targeted).Due to high repetition loss (from the first to final set) when sets are terminated at momentary muscular failure, performing RT with 1- to 2-RIR allows for similar volume load and repetition volume accumulation as reaching momentary muscular failure across eight weeks, possibly influencing the overall RT stimulus achieved.Performing RT to momentary muscular failure consistently induces higher levels of acute neuromuscular fatigue versus RT performed with 1- to 2-RIR; however, improved fatigue resistance overtime may attenuate acute neuromuscular fatigue and subsequent repetition loss (but may depend on the exercise performed).

Accuracy of Intraset Repetitions-in-Reserve Predictions During the Bench Press Exercise in Resistance-Trained Male and Female Subjects.

ABSTRACT: Refalo, MC, Remmert, JF, Pelland, JC, Robinson, ZP, Zourdos, MC, Hamilton, DL, Fyfe, JJ, and Helms, ER. Accuracy of intraset repetitions-in-reserve predictions during the bench press exercise in resistance-trained male and female subjects. J Strength Cond Res 38(3): e78-e85, 2024-This study assessed the accuracy of intraset repetitions-in-reserve (RIR) predictions to provide evidence for the efficacy of RIR prescription as a set termination method to inform proximity to failure during resistance training (RT). Twenty-four resistance trained male ( n = 12) and female ( n = 12) subjects completed 2 experimental sessions involving 2 sets performed to momentary muscular failure (barbell bench press exercise) with 75% of 1 repetition maximum (1RM), whereby subjects verbally indicated when they perceived to had reached either 1 RIR or 3 RIR. The difference between the predicted RIR and the actual RIR was defined as the "RIR accuracy" and was quantified as both raw (i.e., direction of error) and absolute (i.e., magnitude of error) values. High raw and absolute mean RIR accuracy (-0.17 ± 1.00 and 0.65 ± 0.78 repetitions, respectively) for 1-RIR and 3-RIR predictions were observed (including all sets and sessions completed). We identified statistical equivalence (equivalence range of ±1 repetition, thus no level of statistical significance was set) in raw and absolute RIR accuracy between (a) 1-RIR and 3-RIR predictions, (b) set 1 and set 2, and (c) session 1 and session 2. No evidence of a relationship was found between RIR accuracy and biological sex, years of RT experience, or relative bench press strength. Overall, resistance-trained individuals are capable of high absolute RIR accuracy when predicting 1 and 3 RIR on the barbell bench press exercise, with a minor tendency for underprediction. Thus, RIR prescriptions may be used in research and practice to inform the proximity to failure achieved upon set termination.

A randomised controlled trial assessing the potential of palmitoylethanolamide (PEA) to act as an adjuvant to resistance training in healthy adults: a study protocol.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics are used frequently by athletes either prophylactically for the prevention of pain, or to accelerate recovery following an injury. However, these types of pain management strategies have been shown to inhibit signalling pathways (e.g., cyclooxygenase-2) that may hinder muscular adaptations such as hypertrophy and strength. Nutraceuticals such as palmitoylethanolamide (PEA) have analgesic properties that act via different mechanisms to NSAIDS/analgesics. Furthermore, PEA has been shown to have a positive effect on sleep and may contribute positively to muscle hypertrophy via PKB activation. Although PEA has not been widely studied in the athletic or recreationally active population, it may provide an alternative solution for pain management if it is found not to interfere with, or enhance training adaptations. Therefore, the study aim is to investigate the effects of daily PEA supplementation (Levagen + ®) with resistance training on lean body mass, strength, power and physical performance and outcomes of recovery (e.g., sleep) compared to placebo. METHODS: This double-blind, randomised controlled study will take place over an 11-week period (including 8-weeks of progressive resistance training). Participants for this study will be 18-35 years old, healthy active adults that are not resistance trained. Participants will attend a familiarisation (week 0), pre-testing (week 1) and final-testing (week 11). At the pre-testing and final-testing weeks, total lean body mass (dual-energy X-ray absorptiometry; DXA), total mid-thigh cross sectional area (pQCT), maximal muscular strength (1 repetition maximum bench press, isometric mid-thigh pull) and power (countermovement jump and bench throw) will be assessed. Additionally, circulating inflammatory cytokines and anabolic hormones, sleep quality and quantity (ActiGraph), pain and subjective wellbeing (questionnaires) will also be examined. DISCUSSION: This study is designed to investigate the effects that PEA may have on pre-to post intervention changes in total body and regional lean muscle mass, strength, power, sleep, subjective wellbeing, and pain associated with resistance training and menstruation compared with the placebo condition. Unlike other NSAIDs and analgesics, which may inhibit muscle protein synthesis and training adaptations, PEA which provides analgesia via alternative mechanisms may provide an alternative pain management solution. It is therefore important to determine if this analgesic compound interferes with or enhances training adaptations so that athletes and active individuals can make an informed decision on their pain management strategies. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR: ACTRN12621001726842p).

Influence of Resistance Training Proximity-to-Failure, Determined by Repetitions-in-Reserve, on Neuromuscular Fatigue in Resistance-Trained Males and Females.

BACKGROUND: This study examined the influence of proximity-to-failure in resistance training (RT), using subjective repetitions-in-reserve (RIR) prediction, on neuromuscular fatigue and perceptual responses. METHODS: Twenty-four resistance-trained males (n = 12) and females (n = 12) completed three experimental trials in a randomised order, each involving six RT sets (barbell bench press) with 75% 1-RM performed to either momentary muscular failure (FAIL), 1-RIR, or 3-RIR. Changes in lifting velocity with a fixed load were assessed from pre-exercise to post-exercise with the aim of quantifying acute neuromuscular fatigue (4 min post-exercise) and the associated time course of recovery (24 and 48 h post-exercise), and from the first to final set performed. Perceptual responses to RT were assessed at multiple time points during and following RT. RESULTS: Decreases in lifting velocity at 4 min post-exercise were greater for FAIL ( - 25%) versus 1-RIR ( - 13%) and 3-RIR ( - 8%), with greater decreases for male ( - 29%) versus female ( - 21%) participants following FAIL. At 24 h post-exercise, decreases in lifting velocity were greater for FAIL ( - 3%) and 1-RIR ( - 3%) versus 3-RIR (+ 2%), with all between-protocol differences diminishing at 48 h post-exercise. Loss of lifting velocity from the first to final set was greater for FAIL ( - 22%) versus 1-RIR ( - 9%) and 3-RIR ( - 6%), with a greater lifting velocity loss from the first to final set for males ( - 15%) versus females ( - 9%). As proximity-to-failure neared, ratings of perceived discomfort, exertion, and muscle soreness increased, general feelings worsened, and perceived recovery decreased. CONCLUSION: These findings support a linear relationship between RT proximity-to-failure and both acute neuromuscular fatigue and negative perceptual responses, which may influence long-term physiological adaptations and adherence to RT.

Influence of Resistance Training Proximity-to-Failure on Skeletal Muscle Hypertrophy: A Systematic Review with Meta-analysis.

BACKGROUND AND OBJECTIVE: This systematic review with meta-analysis investigated the influence of resistance training proximity-to-failure on muscle hypertrophy. METHODS: Literature searches in the PubMed, SCOPUS and SPORTDiscus databases identified a total of 15 studies that measured muscle hypertrophy (in healthy adults of any age and resistance training experience) and compared resistance training performed to: (A) momentary muscular failure versus non-failure; (B) set failure (defined as anything other than momentary muscular failure) versus non-failure; or (C) different velocity loss thresholds. RESULTS: There was a trivial advantage for resistance training performed to set failure versus non-failure for muscle hypertrophy in studies applying any definition of set failure [effect size=0.19 (95% confidence interval 0.00, 0.37), p=0.045], with no moderating effect of volume load (p=0.884) or relative load (p=0.525). Given the variability in set failure definitions applied across studies, sub-group analyses were conducted and found no advantage for either resistance training performed to momentary muscular failure versus non-failure for muscle hypertrophy [effect size=0.12 (95% confidence interval -0.13, 0.37), p=0.343], or for resistance training performed to high (>25%) versus moderate (20-25%) velocity loss thresholds [effect size=0.08 (95% confidence interval -0.16, 0.32), p=0.529]. CONCLUSION: Overall, our main findings suggest that (i) there is no evidence to support that resistance training performed to momentary muscular failure is superior to non-failure resistance training for muscle hypertrophy and (ii) higher velocity loss thresholds, and theoretically closer proximities-to-failure do not always elicit greater muscle hypertrophy. As such, these results provide evidence for a potential non-linear relationship between proximity-to-failure and muscle hypertrophy.

Towards an improved understanding of proximity-to-failure in resistance training and its influence on skeletal muscle hypertrophy, neuromuscular fatigue, muscle damage, and perceived discomfort: A scoping review.

While proximity-to-failure is considered an important resistance training (RT) prescription variable, its influence on physiological adaptations and short-term responses to RT is uncertain. Given the ambiguity in the literature, a scoping review was undertaken to summarise evidence for the influence of proximity-to-failure on muscle hypertrophy, neuromuscular fatigue, muscle damage and perceived discomfort. Literature searching was performed according to PRISMA-ScR guidelines and identified three themes of studies comparing either: i) RT performed to momentary muscular failure versus non-failure, ii) RT performed to set failure (defined as anything other than momentary muscular failure) versus non-failure, and iii) RT performed to different velocity loss thresholds. The findings highlight that no consensus definition for "failure" exists in the literature, and the proximity-to-failure achieved in "non-failure" conditions is often ambiguous and variable across studies. This poses challenges when deriving practical recommendations for manipulating proximity-to-failure in RT to achieve desired outcomes. Based on the limited available evidence, RT to set failure is likely not superior to non-failure RT for inducing muscle hypertrophy, but may exacerbate neuromuscular fatigue, muscle damage, and post-set perceived discomfort versus non-failure RT. Together, these factors may impair post-exercise recovery and subsequent performance, and may also negatively influence long-term adherence to RT.KEY POINTS This scoping review identified three broad themes of studies investigating proximity-to-failure in RT, based on the specific definition of set failure used (and therefore the research question being examined), to improve the validity of study comparisons and interpretations.There is no consensus definition for set failure in RT, and the proximity-to-failure achieved during non-failure RT is often unclear and varies both within and between studies, which together poses challenges when interpreting study findings and deriving practical recommendations regarding the influence of RT proximity-to-failure on muscle hypertrophy and other short-term responses.Based on the limited available evidence, performing RT to set failure is likely not superior to non-failure RT to maximise muscle hypertrophy, but the optimal proximity to failure in RT for muscle hypertrophy is unclear and may be moderated by other RT variables (e.g., load, volume-load). Also, RT performed to set failure likely induces greater neuromuscular fatigue, muscle damage, and perceived discomfort than non-failure RT, which may negatively influence RT performance, post-RT recovery, and long-term adherence.

Influence of resistance training load on measures of skeletal muscle hypertrophy and improvements in maximal strength and neuromuscular task performance: A systematic review and meta-analysis.

This systematic review and meta-analysis determined resistance training (RT) load effects on various muscle hypertrophy, strength, and neuromuscular performance task [e.g., countermovement jump (CMJ)] outcomes. Relevent studies comparing higher-load [>60% 1-repetition maximum (RM) or <15-RM] and lower-load (≤60% 1-RM or ≥ 15-RM) RT were identified, with 45 studies (from 4713 total) included in the meta-analysis. Higher- and lower-load RT induced similar muscle hypertrophy at the whole-body (lean/fat-free mass; [ES (95% CI) = 0.05 (-0.20 to 0.29), P = 0.70]), whole-muscle [ES = 0.06 (-0.11 to 0.24), P = 0.47], and muscle fibre [ES = 0.29 (-0.09 to 0.66), P = 0.13] levels. Higher-load RT further improved 1-RM [ES = 0.34 (0.15 to 0.52), P = 0.0003] and isometric [ES = 0.41 (0.07 to 0.76), P = 0.02] strength. The superiority of higher-load RT on 1-RM strength was greater in younger [ES = 0.34 (0.12 to 0.55), P = 0.002] versus older [ES = 0.20 (-0.00 to 0.41), P = 0.05] participants. Higher- and lower-load RT therefore induce similar muscle hypertrophy (at multiple physiological levels), while higher-load RT elicits superior 1-RM and isometric strength. The influence of RT loads on neuromuscular task performance is however unclear.