This is the largest meta-analysis on interventions including dietary protein supplementation with muscle and strength-related outcomes during prolonged RET to date. Our main finding was that dietary protein supplementation augmented RET-induced increases in 1RM strength (figure 2) and FFM (figure 3). For changes in FFM, dietary protein supplementation was more effective in resistance-trained individuals (table 1 and figure 3), less effective with increasing chronological age (table 1 and figure 4) and did not increase beyond total protein intakes of ~1.6 g/kg/day (figure 5). Our data show dietary protein supplementation is both sufficient and necessary to optimise RET adaptations in muscle mass and strength.

Previous meta-analyses6–12 have reached varying conclusions when examining the impact of protein supplementation on changes in lean mass or FFM and 1RM strength during RET. The discrepancies are likely a consequence of differing study inclusion criteria. For example, previous meta-analyses have included only trained participants,8 only older adults,9 11 supplements containing more than just protein,8 10 only one source of protein,8 12 shorter RET interventions,10 12 frail/sarcopenic participants7 9 11 and/or participants who were energy-restricted.6 7 12 Previously, the largest comprehensive meta-analysis to date on protein supplementation during RET included 22 studies and 680 participants7 and did show a significant effect of protein supplementation on RET-stimulated gains in strength and FFM. In agreement with this previous report,7 and strengthening the conclusion of that same report by including 49 studies and 1863 participants, we show that protein supplementation augmented gains in FFM and strength with RET.

The average RET-induced increase, with all measures of 1RM included, was 27 kg (mean±SD; 27±22 kg 22 32 ). Notably, dietary protein supplementation augmented the increase in 1RM strength by 2.49 kg (9%; figure 2 ; see online supplementary figure 4 ), which strongly suggests that the practice of RET is a far more potent stimulus for increasing muscle strength than the addition of dietary protein supplementation. None of our covariates (age, training status, postexercise protein dose or baseline protein intake) influenced the efficacy of protein supplementation on changes in 1RM strength. Improving performance of a specific task (eg, the 1RM of an exercise) is predominately determined by the practice of that task. 71 Though protein supplementation may slightly augment changes in 1RM (~9%), which may be important for those competing in powerlifting or weightlifting, it is pragmatic to advocate that if an increase in 1RM is the objective of an RET programme, a sufficient amount of work and practice at or around the 1RM is far more influential than protein supplementation.

Muscle mass

In addition to increasing changes in muscle strength, RET alone (≥6; 13±8 weeks) resulted in an increase in FFM (1.1±1.2 kg), an increase in fibre CSA (808±) and an increase in mid-femur CSA (52±30 mm2). Dietary protein supplementation augmented the increase in FFM by 0.30 kg (27%; figure 3; see online supplementary figure 4), fibre CSA by 310 µm2 (38%; see online supplementary figure 2: panel A) and mid-femur CSA by 7.2 mm2 (14%; see online supplementary figure 2: panel B). The postexercise protein dose did not affect the efficacy of protein supplementation on RET-induced changes in FFM whereas training status (positive), age (negative) and baseline protein intake (positive) did. Relative to untrained participants, resistance-trained participants have a smaller potential for muscle growth72 and an attenuated postexercise muscle protein turnover.73 As a result, we speculate that trained persons may have less ‘degrees of freedom’ to change with RET and therefore have a greater need for protein supplementation to see increases in muscle mass. Our thesis is supported by the observation of a more consistent impact of protein supplementation on gains in FFM in resistance-trained individuals than in novice trainees (figure 3).

Older individuals are anabolically resistant74 and require higher per-meal protein doses to achieve similar rates of MPS, the primary variable regulating changes in skeletal muscle mass,75 compared with younger participants.14 The average supplemental daily protein dose given to older participants was surprisingly low (20±18 g/day); thus, it is perhaps not surprising that we did not find that older individuals were responsive to protein supplementation (figure 4). Though age did not affect the RET-induced change in fibre CSA, the negative effect age had on changes in FFM leads us to speculate that even though exercise sensitises muscle to the effect of protein ingestion,3 older persons have an increased need for higher protein intakes to optimally respond to this effect and see gains in FFM.76

It has been theorised that the increased deviation from normal protein intake (g/kg/day) will positively affect the RET-induced gains in FFM.77 Contrary to this thesis, we found that a higher prestudy protein intake actually resulted in a greater effect of protein supplementation on changes in FFM (table 1); however, this was likely driven by the lower mean baseline protein intake (old: 1.2±0.2 g/kg/day, young: 1.5±0.4 g/kg/day) and daily protein dose (old: 20±18 g/day, young: 42±32 g/day) in the studies that included older participants (see online supplementary figure 3: panel B and D). Indeed, a sensitivity analysis that did not include older (>45; 65±14 years) versus younger (<45; 24±4 years) individuals found that baseline protein intake had no effect on the efficacy of protein supplementation in young individuals (see online supplementary figure 3, panel C). In an unadjusted meta-regression analysis, a higher baseline protein intake in young individuals actually attenuated the change in FFM (see online supplementary figure 3, panel D).

A goal of this meta-analysis was to deliver evidence-based recommendations that could be readily translated. A crucial point is that even though the mean baseline protein intake for the 1863 participants was ~1.4 g protein/kg/day, which is 75% greater than the current US/Canadian recommended dietary allowance (RDA),78 an average supplementation of ~35 g protein/day still augmented RET-stimulated gain in FFM (figure 3) and 1RM strength (figure 2). Thus, consuming protein at the RDA of 0.8 g protein/kg/day appears insufficient for those who have the goal of gaining greater strength and FFM with RET. This conclusion is emphasised for older men79 and women80 81 wishing to obtain strength and gain lean mass with RET and protein supplementation.

A recent retrospective analysis showed a ‘breakpoint’ for the stimulation of MPS when ingesting an isolated protein source at 0.24 g protein/kg and 0.40 g protein/kg in younger and older participants, respectively.14 Given the observation of a dose-responsive relationship between protein intake and MPS82–85 and the fact that MPS is aligned with muscle hypertrophy,13 we elected to use an identical two-segment regression approach between total daily protein intake and changes in FFM (figure 5) as has been done for changes in protein dose and MPS.14 Here we provide significant insight (using 42 study arms including 723 young and old participants with protein intakes ranging from 0.9 g protein/kg/day to 2.4 g protein/kg/day) by reporting an unadjusted plateau in RET-induced gains in FFM at 1.62 g protein/kg/day (95% CI: 1.03 to 2.20). These results are largely in congruence with previous narrative reviews that comment on the optimal nutritional strategies to augment skeletal muscle adaptation during RET.3 86 Given that the CI of this estimate spanned from 1.03 to 2.20, it may be prudent to recommend ~2.2 g protein/kg/d for those seeking to maximise resistance training-induced gains in FFM. Though we acknowledge that there are limitations to this approach, we propose that these findings are based on reasonable evidence and theory and provide a pragmatic estimate with an incumbent error that the reader could take into consideration.

Although the present analysis provides important and novel data, there are limitations that we acknowledge. First, the lack of RET research in older individuals has led to inconclusive recommendations from previous meta-analyses specifically focusing on older individuals.9 11 Indeed, in this manuscript there were only 13 studies that met our inclusion criteria in older (>45 years) individuals and only six of those studies reported baseline protein intakes with changes in FFM. In addition, only four studies27 29 33 45 in older individuals had participants that consumed what we consider to be close to optimal total protein intake (~1.2 g/kg/day to 1.6 g/kg/day) in non-exercising adults5. Furthermore, only two studies23 30 in older individuals provided a postexercise supplemental protein dose that we consider to be close to optimal (~35–40 g) to stimulate FFM accretion in elderly individuals.76 Given that older adults require more protein per day,79–81 consume less protein per day87 and that dietary protein ingestion and RET are effective strategies to maintain muscle mass and function with age,67 future RET research should focus on using higher protein doses (or potentially higher leucine), larger sample sizes and longer interventions in ageing populations. Second, we included a variety of additional covariates into univariate meta-regressions to elucidate the variables that may modify whether protein supplementation affects RET-induced changes in muscle mass and strength. Such an approach is generally considered to be hypothesis generating. The only significant findings we found were that if the RET sessions were whole-body (adjusted R2=76%, p=0.01) or supervised (adjusted R2=58%, p=0.047), protein supplementation was more effective at augmenting changes in 1RM. No variable affected changes in FFM (see online supplementary table 3). Given the relatively small effect that protein supplementation has on changes in FFM and 1RM, clearly other variables as a component of RET programmes are of much greater importance. Our meta-analyses also only included studies with participants that were at or above their energy requirements, which may have omitted the significant impact protein has during periods of weight loss with RET.88 Lastly, we found that the postexercise protein dose did not affect the efficacy of protein supplementation on RET-induced changes in FFM. Our analysis, and those from others,6 leads us to conclude that the specifics of protein supplementation (eg, timing, postexercise protein dose or protein source) play a minor, if any, role in determining RET-induced gains in FFM and strength over a period of weeks. Instead, our results indicate that a daily protein intake of ~1.6 g/kg/day, separated into ~0.25 g/kg doses,14 is more influential on adaptive changes with RET, at least for younger individuals.