Leucine

Overview

What is it?

Leucine is an essential branched-chain amino acid (BCAA) that is naturally found in protein-rich foods like meat, fish, dairy, soy, and nuts . It is one of the three BCAAs, the others being isoleucine and valine, and it plays a crucial role in muscle protein synthesis [1, 3]. Leucine cannot be synthesized by the body, and must be obtained from diet . It's also naturally found within the body, being a building block for muscle protein .

How does it work?

Leucine is a key regulator of muscle protein synthesis. It primarily works by activating a pathway called the mammalian target of rapamycin (mTOR) . When leucine is present in sufficient amounts, it stimulates mTOR, which in turn increases the production of muscle proteins. This process is essential for muscle growth and repair. Leucine also helps to decrease muscle protein breakdown, contributing to a net increase in muscle mass . Leucine is also involved in energy metabolism, promoting glucose uptake and fatty acid oxidation . The body converts a portion of leucine into other compounds like α-ketoisocaproate (α-KIC) and β-hydroxy-β-methylbutyrate (HMB), which may also contribute to muscle growth .

What are the benefits?

The primary benefit of leucine, particularly for those interested in fitness and muscle growth, is its ability to stimulate muscle protein synthesis and reduce muscle protein breakdown [2, 4]. This process is crucial for building muscle mass and maintaining it over time [4, 15]. Leucine supplementation has been shown to improve physical performance, particularly in elderly individuals with sarcopenia (age-related muscle loss), by enhancing muscle function and walking time . Leucine also has a positive effect on energy metabolism, and can help with fatty acid oxidation . Moreover, it can improve respiratory muscle function, essential for overall physical capacity . Leucine-enriched essential amino acids have also shown to improve muscle density and quality of life in patients with knee osteoarthritis . Tyrosine, when combined with leucine, can enhance the muscle anabolic response . The intake of Leucine during exercise can also help prevent muscle protein degradation .

Effectiveness

3.0

What does the research say?

Research indicates that leucine is essential for muscle protein synthesis, and its amount in ingested proteins or amino acid mixtures determines the extent of the muscle protein synthesis (MPS) response . Leucine activates the mTORC1 signaling pathway, which increases protein synthesis . While acute studies have shown that leucine supplementation can increase muscle protein synthesis in both younger and older adults, the long-term benefits for muscle growth are less consistent . Some studies suggest that higher doses or specific timing of supplementation may be necessary to see benefits in muscle accretion . Supplementing with leucine may be more beneficial when combined with resistance training, and may also prevent the decrease in serum levels of leucine that can occur with intensive training . Some studies suggest that adding extra leucine to a diet that already has sufficient essential amino acids might not provide additional benefit , and the positive effects of leucine supplementation are more apparent when the total daily intake of protein is low . Leucine supplementation can help to maintain lean muscle mass over time, but it may not significantly increase muscle strength or mass on its own, particularly in elderly individuals . Research suggests that leucine-enriched essential amino acids are more effective in stimulating muscle protein synthesis in older people than standard amino acid mixtures, especially when combined with exercise . Leucine also helps to reduce muscle breakdown . Leucine supplementation also appears to help maintain muscle mass and function during aging . It can also enhance the overall anabolic response in muscle, and help to alleviate muscle protein loss during aging .

Side Effects

Minimal

Elevated plasma ammonia concentrations

Short-term elevated plasma ammonia concentrations have been observed at higher doses of leucine supplementation, but these do not appear to have serious health consequences .

Evidence

Strong

Clinical Studies & Trials

[1] Isolated Leucine and Branched-Chain Amino Acid Supplementation for Enhancing Muscular Strength and Hypertrophy: A Narrative Review.

This review examines the effectiveness of branched-chain amino acid (BCAA) and leucine supplementation for enhancing muscle strength and hypertrophy. While leucine plays a key role in stimulating muscle protein synthesis, the benefits of BCAA or leucine supplementation on muscle strength and hypertrophy require further study.

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[2] The role of leucine and its metabolites in protein and energy metabolism.

This article discusses the role of leucine in protein and energy metabolism, focusing on its ability to activate mTOR signaling, promote protein synthesis, and enhance energy metabolism. It also discusses the roles of leucine's metabolites, alpha-ketoisocaproate and beta-hydroxy-beta-methylbutyrate.

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[3] Leucine supplementation and intensive training.

This paper reviews the effects of leucine supplementation during intensive training. Leucine stimulates muscle protein synthesis and may prevent protein degradation and glycogen depletion during exercise. Supplementation can also help maintain serum leucine levels in athletes.

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[4] Effects of Leucine Administration in Sarcopenia: A Randomized and Placebo-controlled Clinical Trial.

This clinical study investigates the effects of leucine supplementation in elderly individuals with sarcopenia. Leucine improved functional performance and respiratory muscle function but did not significantly increase muscle strength or mass.

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[5] The effects of branched-chain amino acids on muscle protein synthesis, muscle protein breakdown and associated molecular signalling responses in humans: an update.

This review examines the effects of branched-chain amino acids (BCAAs), including leucine, on muscle protein synthesis (MPS) and muscle protein breakdown (MPB). BCAAs can activate molecular pathways that regulate translation initiation, reduce indices of MPB, and transiently stimulate MPS rates, but are less effective than a complete protein source.

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[6] Low-protein intakes and protein turnover in elderly women.

This study examined the effects of low-protein diets in elderly women. Leucine oxidation reflected the nitrogen balance, showing that the women were unable to adapt to the low-protein intake, resulting in reduced body cell mass, immune response, and muscle function.

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[7] Protein dose requirements to maximize skeletal muscle protein synthesis after repeated bouts of resistance exercise in young trained women.

This study looked into protein requirements to maximize muscle protein synthesis in trained women after resistance training. The study used whey protein doses of 15g, 30g and 60g. The results help understand the protein needed to maximise MPS.

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[8] Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics.

This paper introduces the SILAC method, which uses isotopically labeled amino acids, such as deuterated leucine, to quantify protein expression. This approach can be used in cell culture to study muscle cell differentiation.

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[9] HMB and leucine supplementation during critical illness and recovery.

This review discusses the potential benefits of leucine and its metabolite beta-hydroxy-beta-methylbutyrate (HMB) in preventing muscle wasting during critical illness and recovery. The article details the mechanisms of action for both substances.

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[10] Regulation of Skeletal Muscle Function by Amino Acids, Especially Non-Proteinogenic Amino Acids.

This review article examines the impact of amino acids, including leucine, on the function of skeletal muscles. The text discusses how different amino acids affect muscle health and function.

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[11] Nutritional and regulatory roles of leucine in muscle growth and fat reduction.

This article reviews the metabolic roles of leucine in regulating protein and lipid metabolism. Leucine activates the mTOR pathway, promoting muscle protein synthesis, mitochondrial biogenesis, and fatty acid oxidation.

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[12] Efficacy and Safety of Leucine Supplementation in the Elderly.

This review examines the efficacy and safety of leucine supplementation in elderly individuals. While leucine can acutely stimulate muscle protein synthesis, long-term benefits for muscle growth are less clear. Leucine supplementation up to 1250 mg/kg/day appears to be safe.

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[13] Role of Exercise and Nutrition in the Prevention of Sarcopenia.

This review discusses the role of exercise and nutrition, particularly leucine, in the prevention of sarcopenia. Leucine and insulin stimulate muscle protein synthesis, and resistance exercise enhances muscle anabolism, especially when combined with nutritional support.

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[14] Tyrosine Is a Booster of Leucine-Induced Muscle Anabolic Response.

This clinical study investigates the interaction between leucine and tyrosine in muscle protein synthesis. The study shows that tyrosine enhances the leucine-induced mTORC1 signaling, making leucine more effective.

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[15] [Amino Acid Nutrition in the Prevention and Treatment of Sarcopenia].

This review discusses the role of amino acid nutrition, particularly leucine, in preventing and treating sarcopenia. Leucine-enriched essential amino acids help overcome anabolic resistance in elderly individuals and improve muscle health when combined with exercise.

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[16] Supplemental dietary leucine and the skeletal muscle anabolic response to essential amino acids.

This study examines whether supplemental leucine provides additional benefits for muscle protein synthesis (MPS) when added to a diet that already contains sufficient essential amino acids (EAAs). The study concludes that adding leucine may not provide additional benefit on resting MPS when sufficient EAAs are consumed.

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[17] The effects of catabolic and anabolic steroids on amino acid incorporation by skeletal-muscle ribosomes.

This study uses leucine incorporation by ribosomes to measure protein synthesis. It shows that catabolic steroids reduce leucine incorporation, while anabolic steroids can partially counteract this effect.

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[18] The efficacy and safety of leucine-enriched essential amino acids in knee osteoarthritis patients: A randomized controlled trial.

This clinical trial shows that leucine-enriched essential amino acids (LEAAs) can improve muscle density and quality of life in patients with knee osteoarthritis. LEAAs appear to be safe and well-tolerated.

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[19] Beta-hydroxy-beta-methylbutyrate and sarcopenia: from biological plausibility to clinical evidence.

This review discusses the role of leucine and its metabolite beta-hydroxy-beta-methylbutyrate (HMB) in maintaining muscle mass and function during aging. It compares the metabolism and effectiveness of leucine and HMB in older adults.

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[20] Safety and Tolerability of Leucine Supplementation in Elderly Men.

This review examines the safety and tolerability of leucine supplementation, with a focus on determining the Tolerable Upper Intake Level (UL). It discusses studies that use leucine oxidation to assess safe doses in young and elderly men.

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