Why people gain so differently from the same resistance programme
Summary of the 2025 Jyväskylä conference by the leading groups: the training variables matter (about 12 sets per muscle a week, at least 60 s rest and 2 min on multi-joint lifts, no more than 2 reps in reserve), but telling a true low responder from measurement noise takes repeat testing, and no gene test is shown to predict the response
The Inter-Individual Variation in Resistance Training Response conference (University of Jyväskylä, November 19-21, 2025) brought together the main laboratories studying why people gain such different amounts of muscle from the same programme; this paper summarises the talks in four themes.
(1) Muscle grows in cross-section mainly by adding myofibrils, and in length by adding sarcomeres along the whole fibre (mouse data).
(2) Programme variables matter in the general population: the authors' practical summary is about 12 sets per muscle a week, rests of at least 60 s (2 min on multi-joint lifts), and sets taken to within 2 reps of failure, while true failure adds nothing and machines grow muscle as well as free weights.
(3) Age and molecular signatures (ribosome biogenesis, satellite cells, the pre-training transcriptome) relate to the response; single genes, hormones in young adults, and diet do not separate high from low responders.
(4) The spread of observed responses is large, but much of it may be random variation, so the authors recommend repeat validation trials, one-leg-trained within-subject designs, minimum clinically important difference (MCID) thresholds and composite responder scores.
For practitioners: when someone is not gaining, check adherence, whether the load progressed, sleep and diet before blaming biology, and give genetic tests no weight. All numbers are second-hand; this is a summary of lectures, not a systematic review.
Themes
Format: a summary of lectures and discussion at a three-day conference; one speaker or laboratory per topic, cited to their published work. Submitted March 2026, published May 2026, open access (CC-BY 4.0).
Theme 1 — what grows: whole-muscle cross-section rises mainly through fibre cross-section; fibre growth in cross-section and length; myonuclear permanence; glycolytic metabolism in growing fibres (Hornberger, Mackey, Hulmi).
Theme 2 — programme variables that may reduce low responsiveness: load range, rest, proximity to failure, weekly sets, exercise selection, concurrent training, frequency, maintenance dose and the progression model (Schoenfeld, Bamman, Libardi).
Theme 3 — biological factors behind the spread: transcriptomics, epigenetics and microRNAs, ribosome biogenesis, satellite cells, capillaries and mitochondria, genetics and polygenic scores, fibre typology, sex and age (Ahtiainen, Bamman, Roberts, Nader, Hulmi, Sillanpää, Derave, Atherton, Mackey, Phillips).
Theme 4 — study design: separating true individual response from random variation; repeat validation trials, repeated testing within a programme, MCIDs, unilateral within-subject designs, meta-analysis of variance, composite scores (Hecksteden, Ahtiainen, Bamman, Libardi, Phillips, Roberts).
Practical applications section addressed to researchers and practitioners (programming, low responsiveness, genetics, age, supplements, measurement).
Key Findings — key points and the numbers the review gives
Muscle gain from the same programme varies widely between people, but a single before-and-after change says little about a person's true response: random variation (measurement error and biological day-to-day variation) and within-person variation must be separated from the true subject-by-training interaction, which takes repeated observations (Hecksteden's framework, [REF-441]).
| Topic | What the review says | Source as the review cites it (second-hand) |
|---|---|---|
| Weekly sets | About 12 sets per muscle per week optimises growth in most trained individuals; above it the dose-response shows diminishing efficiency, with considerable variation between individuals. Practical summary: 12 sets per muscle group a week is "sufficient to most efficiently" promote hypertrophy for most people | Pelland 2026, meta-regressions of weekly volume and frequency (Sports Med) |
| Volume and low responders | Higher training volume reduced the prevalence of low responsiveness in older adults (frequency fixed at 2 days a week). In a four-arm trial in adults aged 60-75 (30 weeks after a 4-week pre-training period), 3 days a week of high-low-high variable intensity gave the largest total-body and thigh lean-mass gains and only 12% poor responders, against much higher proportions in the other three arms; arm lean mass grew most on high-high-high | Lixandrão; Bamman laboratory |
| Maintenance | After a 16-week programme, a 32-week trial of two maintenance prescriptions versus stopping suggested older adults need a higher volume than young adults to keep the muscle gained | One maintenance trial (Bamman laboratory) |
| Load range | Hypertrophy across roughly 5-30 reps per set; moderate loads (8-12 reps) for most sets may be practical; a spectrum of loads may favour fibre-type-specific growth | Schoenfeld lecture and cited meta-analyses |
| Rest intervals | Rests of 60 s or less tend to be suboptimal; 2 min or more may be needed on multi-joint exercises to maintain volume load. Practical summary: at least 60 s between sets, 2 min or more on multi-joint lifts (note: the evidence sentence counts 60 s itself as short) | Singer 2024 (Bayesian meta-analysis); Rosa 2023 |
| Proximity to failure | Train near failure (about 2 reps in reserve) to maximise hypertrophy; reaching true failure each set brings no additional benefit. Practical summary: no more than two reps in reserve | Robinson 2024 (meta-regressions); Refalo 2023 (REF-678) |
| Exercise selection | Exercise choice matters for which muscles are targeted, but machines grew muscle as well as free weights; this may not transfer to performance training (sprints, jumps), which is task-specific | Haugen 2023 meta-analysis |
| Frequency | In an 8-week within-subject comparison (one leg each), neither higher nor lower frequency prevailed — the optimum may differ by person | Damas (Libardi laboratory) |
| Progression model | Progressing by load or by reps: some individuals grew more under one model than under the other, and satellite-cell changes tracked the response | Libardi and Roberts laboratories |
| Concurrent training | Interference with hypertrophy is mixed and probably volume-dependent: 4-6 days a week of endurance work interferes more than 1-3; on the same day, lifting then aerobic exercise seems prudent | Cited reviews; the order is the authors' suggestion |
| Expected gains | 8-12 weeks of training gave 1.3-1.8 kg of lean mass in adults (the cited meta-analysis title says healthy adult males; 111 studies, 1,927 participants); "8-12 kg of muscle a year" gym lore is not realistic | Benito meta-analysis; Phillips lecture |
| Sex | On a relative scale women and men are about equally responsive from the untrained state, with no clear sex difference in responder distribution; male advantages appear with advanced training and on absolute scales | Several responder-classification studies |
| Age | Not all older adults are low responders; blunted acute protein synthesis in older adults did not translate into remarkable age differences in hypertrophy. Low testosterone in older hypogonadal men, and metformin (which inhibited hypertrophy in the MASTERS trial), may blunt it. Signs of fibre denervation were not reversed by 8-20 weeks but seemingly were by 6+ months to years of training | Atherton, Bamman, Mackey laboratories |
| Genetics | Of 500 polymorphisms tested after 12 weeks of arm training in 1,300 young adults, only 2 related to hypertrophy; of over 315,000 tested in 119 young men, one did. An 11-variant score explained 47% of the response in 440 untrained adults, at a liberal significance threshold. Heritability estimates run 30-70+%, yet a robust polygenic score would need more than 100,000 participants. In one-leg-trained designs, individual differences in fibre growth aligned more with intrinsic biology than with the protocol | FAMuSS; Roberts and Phillips laboratories; Yang; Libardi and Phillips laboratories |
| Fibre typology | "Fast twitchers" (high muscle carnosine) did not hypertrophy more than "slow twitchers", but performed fewer reps at a given %1RM and stayed fatigued longer after sessions | Derave laboratory (REF-307 for the recovery data) |
| Molecular markers | Ribosome biogenesis and satellite-cell expansion associated with higher responses across laboratories; the pre-training transcriptome looked more influential than molecular responses to exercise. rDNA copy number, extracellular-matrix proteins and sex-hormone markers in young adults did not separate responders; capillary and mitochondrial findings are mixed | Roberts, Bamman, Nader, Hulmi laboratories |
| Nutrition and supplements | Protein insufficiency is not a key feature of anabolic resistance; self-reported diet did not appreciably affect the spread; supplements are the least important factor, though creatine and chronic protein supplementation gave modest gains (0.5-1.0 kg lean mass over 12+ weeks) | Atherton lecture (protein); Bamman and Roberts groups (self-reported diet); Phillips lecture (supplements least important); authors' practical section (0.5-1.0 kg) |
| Low responsiveness in practice | Before attributing it to intrinsic factors, first examine adherence, progressive overload, and (when possible) sleep quality and dietary habits; habitual progressive training over years is the key external factor | Authors' practical recommendation |
| Responders vs random variation | Three components: random variation (measurement error and biological variation), within-subject variation in the response to the same programme on another occasion, and the subject-by-training interaction, the true individual response. A control group estimates the first; the second stays hypothetical in common designs | Hecksteden framework (REF-441); Hopkins |
| Repeat validation trials | The theoretical standard is two training periods with a washout, checking whether the same people respond high and low; but washout length and "muscle memory" carry-over (DNA methylation, proteome, myonuclei; strength and fibre carry-over before retraining) threaten it. Repeated testing within one programme (baseline, 3, 6 and 9 months), as Hecksteden did for endurance training, may approximate it. A large repeat-validation trial in Jyväskylä has run 3 years and ends within 1-2 years | Hecksteden, Ahtiainen; Robinson (replicated unilateral trial, preprint) |
| Unilateral within-subject designs | Train one limb and leave the other untrained as the person's own control, with confidence intervals from measurement error and natural variability; drawbacks are cross-education (10-15% strength gains in the untrained limb) and lower ecological validity than whole-body training | Chaves (Libardi laboratory) |
| MCID thresholds | Needs repeated run-in tests (pre-test 1, pre-test 2, post); methods disagree and no established MCID exists for hypertrophy. Proposed starting points, not norms: 0.5-1.0 kg of DXA appendicular lean mass over 12-16 weeks (DXA error generally under 1-2%); about 700 µm² (10-15%) of fibre cross-sectional area; 2-3% in ultrasound muscle thickness or cross-section (0.24 cm and 0.60 cm² for vastus lateralis). Thresholds are context-specific and error can scale with baseline | Bamman; cited reliability studies |
| Composite responder classification | A multivariate composite score is a better classifier than one outcome: several measures of muscle size at minimum, or a wider model adding strength, function, metabolic adaptation, cognition, mood and stress | Phillips, Bamman, Roberts groups |
Mechanisms
Radial growth by more myofibrils — Measured-in-cited-studies: a fluorescence imaging method (FIM-ID) showed that fibre growth in cross-section after resistance training in humans and mechanical overload in mice comes mainly from an increased number of myofibrils, not only bigger ones; myofibrils occupy 80-85% of the fibre.
Longitudinal growth by sarcomere addition along the fibre — Measured-in-cited-studies (mice only): synergist ablation in mice lengthened fibres by adding sarcomeres in series; labelling of newly made proteins suggests new sarcomeres are added throughout the fibre's length (not at its ends) by transverse splitting of Z-lines, through signalling insensitive to rapamycin. Authors' interpretation: this growth is likely independent of mTORC1; human data are awaited.
Fibre length as a hidden driver of cross-section — modelling, then Authors' interpretation: in a geometric (Maxwell) model of pennate muscle applied to rodent overload data, a roughly 13% rise in fibre length could raise mid-belly whole-muscle cross-section by about 50% and the fibres counted per cross-section by about 50%; training that emphasises lengthened contractions can lengthen fibres (measured in a cited study).The authors read this as shrinking the role of hyperplasia or fibre splitting, which cohort data on long-term lifters still leave open.
Myonuclei — Measured-in-cited-studies: in mice, detraining after training can lose the newly gained nuclei, so myonuclear permanence is not absolute; across 27 human studies (903 participants) fibre growth of 10% or less already added myonuclei, and clearly more were added when growth exceeded 20%. Authors' interpretation: apparent fibre splitting may instead be branch fusion during regeneration after severe damage.
Ribosome biogenesis and satellite cells — Measured-in-cited-studies (associations): higher responders accrued more ribosomal RNA and more myonuclei, especially in type II fibres, and had more satellite cells at baseline; blocking RNA polymerase I abolished hypertrophy in human myotubes in vitro. Authors' interpretation: ribosome capacity is a key driver of the spread; causality in humans is not shown.
Glycolysis in growing muscle — Measured in humans (glucose uptake, glycolytic enzymes) and in cells and flies (PHGDH, TRIM32); Authors' interpretation: growing muscle takes up much glucose and glycolytic branches (PHGDH, serine synthesis) support growth in vitro; the authors caution this does not make lactate a central cause of hypertrophy.
Practical Application
**Am I a strength non-responder?One flat block cannot show it: one before-and-after test cannot separate a low responder from noise and day-to-day biology (the paper), so retest first; changing one variable at a time is the base's practice.** The leading resistance-training groups (2026 conference summary, B-, mostly untrained and older non-athletes) agree that people gain very different amounts from the same programme, but say that telling true differences from random variation needs repeated tests.Before blaming biology, check adherence, whether the load actually progressed, sleep and food. If the repeat test is still flat, change one thing — weekly sets (toward about 12 per muscle), rest (at least 60 s, 2 min on multi-joint lifts), effort (no more than 2 reps in reserve) or the progression model (load versus reps) — and judge it on the same test after the next block."Retest, then one variable" is the base's practice, built on this paper and REF-441.
Give a genetic test for "muscle-building potential" no weight in programming (the authors: no undue weight; not acting on it is the base's practice). Of 500 variants tested in 1,300 adults only 2, and of over 315,000 in 119 men only 1, related to growth; one 11-variant score explained 47% in 440 adults, but at a liberal threshold and unreplicated; a robust polygenic score would need more than 100,000 people (SYNTH-13 says the same for endurance genotypes).
Set honest expectations: 8-12 weeks of training adds roughly 1.3-1.8 kg of lean mass in adults (the cited meta-analysis title says healthy adult males; 111 studies, 1,927 participants), not "8-12 kg a year"; creatine and chronic protein supplementation add a modest 0.5-1.0 kg over 12+ weeks (REF-1094 gives ~1.4 kg in 12 weeks for drug-free men).
Age and sex are not reasons to expect less. Women gain about as much as men in relative terms from the untrained state, and many older adults respond well; older adults may need more volume to keep what they gained (one maintenance trial; see REF-587), and higher volume reduced the share of low responders among older adults — while REF-1140 ranked the lowest weekly volume most effective for average muscle size in adults over 60.Group averages and individual non-response are different questions; the two are not yet reconciled (inference).
For a cyclist or runner, these are hypertrophy doses for non-athletes. The base's strength defaults for endurance athletes (heavy, few reps, 2-3 reps in reserve, about 3 min rest, twice a week) are in SYNTH-43 and SYNTH-44; they target force, not muscle size. Interference with muscle growth grows with endurance frequency (4-6 days a week more than 1-3, the review's reading), and where a lift sits in the week is SYNTH-31 and SYNTH-21.
Machines are fine for muscle size; for jumps, sprints and sport-specific force, choose task-specific lifts (the authors' caveat).
Reading a body-composition change: a DXA lean-mass change within about 1-2% can be test error, and an ultrasound muscle-thickness change needs roughly 2-3% to clear test-retest error; the authors' starting thresholds (0.5-1.0 kg appendicular lean mass over 12-16 weeks, 2-3% muscle thickness) are proposals, not norms, and only hold for the same device and protocol (inference).
Limitations
A conference summary, not a systematic review: no search strategy, no inclusion criteria, no risk-of-bias appraisal, no pooled estimate. Each paragraph reports one speaker's lecture, largely the speaker's own laboratory's work.
The authors are the field's main investigators and are invested in its questions and methods; several sections cite their own trials, and some data are preliminary (the Jyväskylä repeat-validation trial) or preprint (the replicated unilateral trial).
Every number is second-hand from the cited studies; this entry did not check them against the primary papers. The 12-set figure rests on one 2026 meta-regression.
Populations are mostly untrained young adults and older adults; hypertrophy is the main outcome and strength secondary; there are no endurance athletes and no performance outcomes.
Some symbols were lost in the PDF text extraction and were read from the PDF: ≤60 s, ≥2 min, ~12 sets, ~2 reps in reserve, ≤10%, ~700 µm², ~2–3%.
Conflicts disclosed: M.D.R. is a paid consultant to industry partners and routinely receives grants from industry and commodity groups; M.M.B. serves on the Science & Innovation Advisory Board of AG1 USA; S.M.P. has received grants from public funders and from Roquette Frères, Nestlé Health Sciences, FrieslandCampina, the US National Dairy Council, Dairy Farmers of Canada, Myos and Cargill, honoraria from Nestlé Health Sciences, Optimum Nutrition, Nutricia and Danone, and holds patents licensed to Exerkine (no reported financial gain); B.J.S. formerly sat on the scientific advisory board of Tonal (fitness equipment).The others declare none.
Funding: the conference was funded by the Federation of Finnish Learned Societies and the University of Jyväskylä's Faculty of Sport and Health Sciences; the lectures' data were funded by public bodies (NIH, US Department of Defense, Research Council of Finland, FWO, the São Paulo Research Foundation and others) and by industry or private sources including Hilmar, Dr. Chris Lockwood LLC, the Renaissance Research Fund, the Peanut Institute, Built with Science Holdings, Strcng Inc and Renaissance Periodization; the FinnGen project is funded by Business Finland and 13 pharmaceutical companies.
How this entry was checked and changed
Why this level
below the rubric's B+ "authoritative narrative review from the leading group" because a conference summary reports each speaker's lecture, largely their own laboratory's work and some preliminary or preprint data, with no search, weighting or synthesis across the field; above C+ because the 14 authors lead the field, it is peer-reviewed, and its programming numbers trace to named meta-analyses rather than to untraced composites. Every number below is second-hand from the cited studies, not re-analysed here; read from the full text
Full text (checked 2026-10-16)
Conference held at the University of Jyväskylä, November 19–21, 2025; four themes; submitted 26 March 2026, accepted 19 May 2026, first published May 22, 2026, CC-BY 4.0 (full text).
Benito meta-analysis: 111 studies and 1,927 participants; 8–12 wk interventions yield lean mass increases of 1.3–1.8 kg; gym lore of 8–12 kg of muscle per year is not realistic (full text).
Maxwell model: a 13% increase in fiber length could lead to a 50% increase in whole muscle CSA at the mid-belly; myofibrils occupy 80%–85% of the fiber (full text).
Hypertrophy across 5–30 repetitions; moderate loads 8–12 repetitions for most sets (full text).
Rest: short intervals (≤60 s) tend to be suboptimal, ≥2 min may be required for multijoint exercises to maintain volume load; practical: at least 60 s between sets (≥2 min for multijoint exercises); symbols read from the PDF (full text).
Failure: near failure, 2 repetitions in reserve per set; true failure each set does not elicit additional benefits; practical: no more than two repetitions in reserve (full text).
Volume: 12 sets per muscle per week optimizes growth in most trained individuals, with diminishing efficiency above this threshold (full text).
Concurrent interference volume-dependent: 4–6 days/wk interfere more than 1–3 days/wk (full text).
Older (60–75 yr) adults, four arms, 30 wk after a 4-wk pretraining period: 3 day/wk high-low-high best, only 12% poor responders on HLH (full text).
Damas: 8-wk unilateral within-subject frequency comparison, neither frequency prevailed; maintenance trial: 32 wk following a 16-wk program, older adults require higher volume to maintain (full text).
Genetics: 12 wk of unilateral arm training in 1,300 younger men and women, 500 polymorphisms, only MSTN and SPP1 associated; one SNP (GLI3) from over 315,000 in 119 college-aged males after 10–12 wk; 440 untrained adults, 11 polymorphisms, score explained 47%; heritability 30–70+%; robust PGS requires >100,000 participants (full text).
Repeated testing during a training period (baseline, 3 mo, 6 mo, and 9 mo) as implemented by Hecksteden for endurance training; the Jyväskylä trial has taken 3 yr and concludes within the next 1–2 yr (full text).
MCID starting points: 0.5–1.0 kg DXA appendicular lean mass over 12–16 wk (DXA error generally <1%–2%); 700 µm² (10%–15%) fiber CSA; 2%–3% ultrasound muscle thickness or CSA (0.24 cm and 0.60 cm2 for vastus lateralis) (full text).
Unilateral designs: cross-education gives 10%–15% strength increases in the untrained limb (full text).
Conceição: 27 studies (903 participants); myonuclear addition with muscle fiber hypertrophy of ≤10%, more myonuclei when hypertrophy is >20% (full text).
Creatine monohydrate and chronic protein supplementation: 0.5–1.0 kg lean tissue mass over a 12+ wk period (full text).
Low responsiveness: first examine adherence, progressive overload application, and (when possible) sleep quality and dietary habits before attributing it to intrinsic factors (full text).
Disclosures: M.D.R. paid consultant to industry partners; M.M.B. AG1 USA advisory board; S.M.P. industry grants, honoraria and patents licensed to Exerkine; B.J.S. formerly Tonal advisory board (full text).