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Leu4.5
Leucine Research
Too few graded studies
18 peer-reviewed studies
What the evidence says
Too few graded studies
Leucine doesn't have enough studies with structured effect-size data yet to pool a verdict. Browse the studies below for individual findings.
Most evidence is from high-quality meta-analyses and randomised trials published 2009–2026.
Based on 18 studies · 3 meta-analyses · 10 RCTs
Confidence
High confidence
By outcome
Lean body mass & muscle growthUncertain. Leucine triggers the muscle protein synthesis response, but the long-term RCT verified found no increase in muscle mass or strength in healthy elderly men taking it on top of a normal diet. Mapped at a low relevance deliberately. · Not established here
Too few graded studies8 studies
Muscle strength & powerUncertain. Leucine triggers the muscle protein synthesis response, but the long-term RCT verified found no increase in muscle mass or strength in healthy elderly men taking it on top of a normal diet. Mapped at a low relevance deliberately. · Not established here
Too few graded studies7 studies
Therapeutic & clinical
Too few graded studies6 studies
Weight management
Too few graded studies3 studies
Muscle cramps & function
Too few graded studies2 studies
Recovery
Too few graded studies1 study
Inflammation
Too few graded studies1 study
Respiratory & lung
Too few graded studies1 study
1 more outcome with fewer studies not shown.
Active research area
15 studies in the last 5 years · Latest meta-analysis: 2025
200920172026
1RCTCited 192×2009
In plain English: The paper's own title states the result: long-term leucine supplementation does not increase muscle mass or strength in healthy elderly men.
Verhoeven S et al. · Am J Clin Nutr (2009)
Randomised controlled trial of long-term leucine supplementation in healthy elderly men (PubMed publication types: Randomized Controlled Trial)
The result is stated in the title itself — no increase in muscle mass or strength — so it is grounded without reading the abstract
This is the central counter-evidence for leucine, and the reason its evidence score sits below 5
In plain English: RT with optimal protein intake significantly improved the Frailty Phenotype and increased basal MyoFSR along with type 1 and 2a myofiber CSA and total lean mass, with no added benefit of leucine supplementation.
Overall MyoFSR increased by 47%, with a concomitant increase in type 1 and 2a myofiber cross sectional area (CSA) (16% and 28%, respectively), and total lean mass (2%).
The number of Frailty Criteria was reduced by 64%, with improvements in physical function and strength.
RT with optimal protein intake significantly improved the Frailty Phenotype and increased basal MyoFSR along with type 1 and 2a myofiber CSA and total lean mass, with no added benefit of leucine supplementation.
In plain English: Both BLG and WPI effectively stimulated MPS doses in young healthy males, with BLG offering an advantage in EAA/BCAA/LEU bioavailability.
Ely IA, Paul M, Wall JJS, Cox J, Larsen MS, Scaife PJ, Lund JN, Breen L, Wilkinson DJ, Smith K, Phillips BE, Atherton PJ. · Nutrients (2025)
Plasma EAA, branched-chain amino acid (BCAA), and LEU concentrations increased rapidly following both protein supplements but exhibited a significantly greater EAA/BCAA/leucinemia following BLG (p < 0.05 for all).
MPS increased significantly in both FED (~52%) and FED-EX (~58%) states, with no significant differences between supplements.
Both BLG and WPI effectively stimulated MPS doses in young healthy males, with BLG offering an advantage in EAA/BCAA/LEU bioavailability.
In plain English: Advances in biomarker research may support earlier diagnosis and personalized nutrition-based therapeutic strategies.
Naas S et al. · Nutrients (2026)
Biomarkers such as GDF-15, CAF22, and specific microRNAs reflect nutritional status and correlate with muscle health in COPD.
Conclusions: Sarcopenia and frailty in COPD arise from a complex interplay of inflammatory, metabolic, nutritional, and lifestyle-related factors.
Integrating nutritional assessment and targeted dietary interventions with exercise and pulmonary rehabilitation is essential to counteract anabolic resistance and improve functional outcomes.
In plain English: Dileucine-supplemented EAA and BCAA support greater whole-body anabolism compared with COL after resistance exercise independent of attenuation in urinary estimates of myofibrillar protein breakdown.
Aguilera JA, Tinline-Goodfellow CT, Lees MJ, Kortebi I, West DWD, Abou Sawan S, Sharma M, Bashir R, Barnes TM, Ulanov AV, Burd NA, Moore DR. · Journal of the International Society of Sports Nutrition (2025)
Results Total exogenous leucine retention were similar ( p = 0.68) between DIEAA (215.72 ± 42.45 μmol·kg -1 ) and BCAA conditions (219.15 ± 45.26 μmol·kg -1 ), with both DIEAA and BCAA being greater ( p < 0.0001) than COL (37.25 ± 8.16 μmol·kg -1 ).
There were no differences ( p = 0.58) in 3MH:Cr between supplement conditions.
Conclusions Dileucine-supplemented EAA and BCAA support greater whole-body anabolism compared with COL after resistance exercise independent of attenuation in urinary estimates of myofibrillar protein breakdown.
In plain English: The paper's own title states both the relationship and the result: supplementation with the leucine metabolite HMB does not improve resistance-exercise-induced changes in body composition or strength in young subjects.
Jakubowski JS et al. · Nutrients (2020)
Systematic review and meta-analysis of HMB in young subjects (PubMed publication types: Meta-Analysis, Systematic Review)
About HMB, NOT leucine itself — included as adjacent counter-evidence because HMB is the leucine metabolite, which the title states explicitly
The null result is stated in the title, so it is grounded without reading the abstract
In plain English: The first systematic review and meta-analysis of leucine specifically, pooling muscle protein synthesis, lean body mass and leg lean mass accretion in older people.
Xu ZR et al. · Br J Nutr (2015)
Systematic review and meta-analysis of leucine in older people (PubMed publication types: Meta-Analysis, Systematic Review)
Pools three distinct outcomes — muscle protein synthesis, lean body mass and leg lean mass accretion — rather than a single endpoint
Cited as a top-of-pyramid synthesis for the sarcopenia indication
In plain English: Leucine-rich high protein supplementation did not produce significant changes in body composition or muscle function in older adults with sarcopenia.
Chung SX, Shahar S, Ajit Singh DK, Malek Rivan NF, Abdul Karim N, Nik Fuad NF, Ong YQ, Arifin A, Abd Rahni AA. · European journal of nutrition (2026)
Results Participants were mostly women (89.4%) with a mean age of 69.3 ± 7.1 years.
However, genes responsible for adenosine triphosphate (ATP) production (GBA, MLYCD), cell proliferation (STAT5A) and DNA repair (BRCC3) were significantly up-regulated in intervention group (p < 0.05).
Conclusion Leucine-rich high protein supplementation did not produce significant changes in body composition or muscle function in older adults with sarcopenia.
In plain English: Eight weeks of this multi-ingredient MCT-leucine-creatine-based supplement induced a modest increase in muscle mass and attenuated the decline in handgrip strength observed in the placebo group among sarcopenic older adults without a structured exercise program, supporting further investigation as a safe and practical nutritional adjunct in geriatric care.
Chan DC et al. · Life (Basel, Switzerland) (2026)
ASM increased significantly in the TLN-01 group (+0.42 kg, +3.2%; p < 0.001) but remained unchanged in controls (p = 0.785), with a significant between-group difference (ANCOVA p < 0.01); this absolute change was below the commonly cited minimal clinically important difference.
Handgrip strength did not differ significantly between groups (p = 0.32); within-group analysis showed a significant decline in the placebo group (-7.0%; p < 0.001) that was not observed in the intervention group (p = 0.537).
In plain English: Full-fat dairy stimulated postprandial myofibrillar protein synthesis less effectively than a matched isolated blend and increased intramuscular NF-κB phosphorylation without modulating other markers of systemic inflammation.
Barnes TM, Zupančič Ž, Deutz MT, Askow AT, McKenna CF, Aguilera JA, Tinline-Goodfellow CT, Ulanov AV, Willard JW, West DWD, De Lisio M, Moore DR, Burd NA. · Clinical nutrition ESPEN (2026)
Myofibrillar protein synthesis was elevated above baseline during the 0-300 min postprandial periods for both ISO (P < 0.001) and MILK (P = 0.05), with a more significant increase in ISO compared to MILK (P = 0.011).
Acute intramuscular NF-κB phosphorylation was elevated at 300 min postprandially in MILK (P = 0.002), with no other changes in systemic or muscle inflammatory markers in either group (all, P < 0.05).
There was no change in postprandial mitochondrial protein synthesis from baseline regardless of condition (P > 0.05).
In plain English: Ingestion of 20 g of protein alone, independent of its quality, is not enough to increase muscle protein synthesis rates in older males.
Kuin LM et al. · The Journal of nutrition (2026)
WHEY increased plasma essential amino acid concentrations more than PLANT and PLANT+LEU over the 4 h postprandial period (incremental area under curve: 135 ± 20 compared with 99 ± 21 and 105 ± 21 mmol·240 min·L‒1, respectively; P < 0.001).
Plasma peak leucine concentrations were higher after PLANT+LEU ingestion compared with PLANT and WHEY (567 ± 74 compared with 310 ± 49 and 471 ± 74 μmol·L‒1, respectively; P < 0.001).
Postprandial muscle protein synthesis rates averaged 0.034 ± 0.010, 0.035 ± 0.012, and 0.034 ± 0.010 %·h‒1 following PLANT, PLANT+LEU, and WHEY ingestion, respectively (treatment P = 0.828), and were not increased when compared with postabsorptive values.
In plain English: LEU supplementation had no significant effect on muscle strength in patients with cirrhosis.
Chaves Santos B et al. · Nutrition (Burbank, Los Angeles County, Calif.) (2026)
The sample comprised 49 patients, 77.6% male, with a median age of 53.0 (47.0-60.0) years.
However, dry body mass index (Δ 0.2 [-0.5 to 1.1] kg/m²), mid-arm circumference (Δ 0.5 [0.0-1.5] cm), triceps skinfold thickness (Δ 1.6 [0.0-2.7] mm), and adductor pollicis muscle thickness (Δ 0.7 [-0.8 to 2.8] mm) significantly increased over time, regardless of group allocation.
LEU supplementation had no significant effect on muscle strength in patients with cirrhosis.
In plain English: In healthy males, although combining QHCl with Leu or Ile, in the doses used, did not enhance their glucose-lowering effects, even small changes in the early gastric emptying rate and insulin stimulation appear to contribute to postprandial glucose-lowering.
Sajjad M, Ghorbaninejad P, Bitarafan V, Anjom-Shoae J, Rose BD, Fitzgerald PC, Horowitz M, Feinle-Bisset C. · The Journal of nutrition (2026)
QHCl, QHCl + Leu, and QHCl + Ile delayed the early rise in plasma glucose compared with control, Leu, and Ile (all P < 0.05).
QHCl + Leu and QHCl + Ile stimulated insulin compared with QHCl, Leu, and control (all P < 0.05), but did not affect gastric emptying.
The early glucose response [area under the curve (AUC), t = 0‒30 min (AUC0‒30 min)] was related directly to early gastric emptying (AUC0‒30 min) (R > 0.41, P < 0.01).
In plain English: Metabolomic changes were not related to protein type.
Martinsen T, Wirth J, Brennan L. · Metabolomics : Official journal of the Metabolomic Society (2026)
Results ASCA revealed no significant main effect of group (p = 0.23) or group × time interaction (p = 1.00), while time had a significant effect on the metabolomic profile (p < 0.05).
Baseline levels of leucine, isoleucine, PCaeC322 and SMOHC222 were associated with positive changes in handgrip strength (p < 0.05).
Conclusions Metabolomic changes were not related to protein type.
In plain English: In older adults, adding LEU to an EAA mixture suppresses intracellular catabolism of the other BCAAs and their keto acids, possibly negatively affecting anaplerotic flux into the tricarboxylic acid cycle and thus muscle health.
Data are expressed as percentage change after intake of EAA + LEU vs EAA [95%CI].
Intracellular disposal of LEU (43% [30%, 56%]; p < 0.001) and KIC (28% [4%, 52%]; p = 0.006) increased more after EAA + LEU mixture intake (LEU p < 0.0001, KIC p = 0.020), but those of ILE and VAL did not change.
The intracellular pool sizes of KMV (19% [-35%, -4%],p = 0.019) and KIV (-25% [-43%, -7%]; p = 0.019) decreased.
In plain English: Improvement in hand grip strength was observed only in the non-dominant hand, warranting further investigation to clarify the effect of supplementation combined with exercise.
Thavonlun C, Limsapjaroen J, Yoosuk P, Mahaisavariya C. · JBMR plus (2026)
The results of this study show no significant improvement in ASMI in either group after 6 mo.
Gait speed showed a positive association with supplementation and daily exercise regardless of regimen.
Improvement in hand grip strength was observed only in the non-dominant hand, warranting further investigation to clarify the effect of supplementation combined with exercise.