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L-Leucine
The branched-chain amino acid that triggers muscle protein synthesis — and the one whose only long-term supplementation RCT we could verify found NO gain in muscle mass or strength in healthy elderly men.
What the evidence says
Most Leucine studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from high-quality meta-analyses and randomised trials published 2009–2025 with a typical study size of 302 participants.
Based on 4 studies · 3 meta-analyses · 1 RCT · 302 total participants
Confidence
High confidenceBy outcome
Leucine's role as the trigger for muscle protein synthesis is well established mechanistically. Its value as a SUPPLEMENT is not: the only long-term randomised trial identified for this entry states in its own title that it does not increase muscle mass or strength in healthy elderly men, and the pooled estimates from the sarcopenia meta-analyses have not been transcribed here. The score reflects what has been verified, not what the mechanism suggests.
Our research database did not respond in time, so the studies and count above cover only our curated set. This refreshes automatically.
L-Leucine (C6H13NO2, PubChem CID 6106, CAS 61-90-5) is one of the three branched-chain amino acids and an indispensable — dietarily essential — amino acid, meaning the body cannot synthesise it (Recommended Dietary Allowances 10th edition, NCBI Bookshelf NBK234922).
It is sold on its own, rather than as part of a BCAA or EAA blend, because it is the specific amino acid that triggers the muscle protein synthesis response: a controlled human trial found that a high proportion of leucine is required for optimal stimulation of muscle protein synthesis by essential amino acids in the elderly (PMID 16507602).
HMB, which has its own entry here, is a leucine metabolite. The WHO/FAO/UNU expert consultation sets the adult leucine requirement at 39 mg/kg/day (WHO Technical Report Series 935, section 8.1.2 and Table 23); the IOM's 2005 figures are an EAR of 34 mg/kg/day and an RDA of 42 mg/kg/day.
What is much less clear is whether supplementing ON TOP of an adequate protein intake does anything: the one long-term randomised trial identified for this entry reported in its own title that leucine supplementation does not increase muscle mass or strength in healthy elderly men (PMID 19321567), and the systematic reviews that pool the sarcopenia literature have not had their pooled estimates transcribed here.
Leucine is the amino acid that switches on the muscle protein synthesis response to a protein feed. A controlled human trial found that a high proportion of leucine is required for optimal stimulation of muscle protein synthesis by essential amino acids in the elderly (PMID 16507602).
Leucine, isoleucine and valine share a degradation pathway whose second step is the branched-chain alpha-ketoacid dehydrogenase complex (GeneReviews, NCBI Bookshelf NBK1319). A deficiency of that complex is maple syrup urine disease, which is why leucine is restricted rather than supplemented in that condition.
HMB (beta-hydroxy-beta-methylbutyrate) is a leucine metabolite and is sold as a separate supplement with its own entry here. A meta-analysis found HMB does not improve resistance-exercise-induced changes in body composition or strength in young subjects (PMID 32456217).
Do not supplement. Treatment of MSUD consists of dietary leucine restriction, branched-chain-amino-acid-free medical foods and frequent biochemical monitoring (GeneReviews, NCBI Bookshelf NBK1319).
No data. No authoritative source consulted for this entry — WHO Technical Report Series 935, the NCBI Bookshelf collection, or the FDA GRAS notice — makes a statement about supplemental leucine in pregnancy. That is an absence of evidence, not a clean bill of health, and it is recorded here rather than left blank.
No data. As above: no authoritative source consulted for this entry addresses supplemental leucine during breastfeeding.
No data. No authoritative source consulted for this entry addresses supplemental leucine in under-18s. The FDA GRAS notice for L-leucine (GRN 308) covers food-category uses at 0.5-3 g per serving and does not speak to paediatric supplementation.
The WHO/FAO/UNU expert consultation recommends that the indispensable amino acid requirement pattern for elderly people is the same as for adults in general (WHO Technical Report Series 935, section 8.5). That is a requirements statement, not a supplementation one: the long-term randomised trial verified for this entry found no increase in muscle mass or strength in healthy elderly men taking supplemental leucine (PMID 19321567).
Leucine has an evidence score of 4.5/10 — emerging evidence based on 4 indexed studies, including 3 meta-analyses. The branched-chain amino acid that triggers muscle protein synthesis — and the one whose only long-term supplementation RCT we could verify found NO gain in muscle mass or strength in healthy elderly men. Representative study: PMID 25234223.
The commonly studied dose of Leucine is Requirement 39 mg/kg/day (WHO/FAO/UNU 2007) or RDA 42 mg/kg/day (IOM 2005) — met by ordinary protein intake. Supplemental servings are documented at 0.5-3 g in the FDA GRAS notice for L-leucine (GRN 308).. Individual needs vary — start at the lower end of the range and adjust based on how you respond.
The best time to take Leucine is with meals. Take it with food. Leucine is studied as part of a protein feed rather than in isolation between meals — the trial behind the leucine-threshold idea tested the proportion of leucine within an essential amino acid mixture (PMID 16507602).
Leucine is generally safe at recommended doses, with a few precautions worth noting. Use caution if any of these apply to you: Maple syrup urine disease (MSUD) — its treatment consists of dietary leucine RESTRICTION and branched-chain-amino-acid-free medical foods (GeneReviews, NCBI Bookshelf NBK1319), so a leucine supplement runs directly against the treatment.
Creatine
Likely helpsIncreases phosphocreatine stores for faster ATP regeneration, boosting strength, power output, and cognitive function under stress.
Whey Protein
Likely helpsComplete protein with high leucine content that maximizes muscle protein synthesis — most researched protein supplement worldwide.
Beta-Alanine
Likely helpsIncreases muscle carnosine to buffer acid during high-intensity exercise, extending endurance for 1-4 minute efforts.
Casein Protein
Likely helpsForms a stomach gel for 6-8 hours of sustained amino acid release — ideal for overnight muscle recovery and anti-catabolism.
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Reviewed by Dr. Baher Al Hakim · Last reviewed September 2026 · evidence from 4 studies · how we score · editorial policy
This information is for educational purposes only. It is not a substitute for professional medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication.