By Robert Schinetsky

Leucine is regarded as the “king” of amino acids, primarily due to its potent activation of the mechanistic target of rapamycin (mTOR) -- the anabolic signal that stimulates protein synthesis. Considerable amounts of research have been devoted to leucine’s anabolic properties over the past several decades, finding that not only does it help support muscle recovery and growth, it also combats muscle breakdown.

Over the past several years, a growing body of research has focused on the other beneficial aspects of leucine, particularly as it relates to cardiometabolic health and weight loss.

Today, we highlight the newest research findings regarding how leucine increases lean mass. We’ll also recap some of leucine’s weight loss support and cardiometabolic support, too!^†

Study #1

First up is a new randomized, double-blind, placebo-controlled study published in the European Journal of Clinical Nutrition that investigated the effects of 8 weeks of leucine supplementation on calorie-restricted individuals (i.e. people on a diet) at risk for metabolic syndrome.[1]

Participants were given biweekly meals plan that included six meals each day (3 main meals + 3 snacks) with daily calorie intakes varying between 1000-2800 kcal/day. Energy requirements for the participants were based on 75% of measured resting metabolic rate (RMR) multiplied by an activity factor of 1.5 for men and 1.3 for women.

However, the researchers also restricted the participants intake of dairy (one serving per day) and meat (3 per week for men and 2 per week for women). This was done to keep the total daily leucine intake at 3 grams per day (prior to supplementation). Calorie-calculated recipes with standard measurements of ingredients were provided to each participant for consistency, and to assist in controlling portion sizes.

While both groups lost weight (as expected) during the 8-week study, those supplementing with 3g leucine retained higher amounts of fat-free mass and lean tissue mass than the individuals who consumed a placebo alongside a reduced-calorie diet.[1]

Why is this noteworthy?

We know that weight loss is ultimately driven by a calorie deficit, which is most effectively/sustainably achieved using a combination of calorie restriction and exercise. While calorie deficits are good for fat loss, they’re not great for preserving lean muscle mass.

Also take into account that new highly-coveted weight loss pharmaceuticals (including GLP-1 agonists like Ozempic) lead to fat loss as well as significant amounts of muscle loss.[2]

Lower levels of fat-free mass are a strong independent predictor of increased insulin resistance, which in turn increases the risk for several chronic diseases. Skeletal muscle is key contributor to fat-free mass. It is essential for glucose clearance and is responsible for over 80% of glucose uptake following ingestion.[3]

Additionally, insulin resistance disrupts both the amount of glucose uptake into skeletal muscle and the timing of that uptake.[4]

The good news is that lean muscle can be preserved during a diet by two things: resistance training and adequate protein/leucine intake.

In fact, research shows that high protein diets are particularly effective for muscle preservation when dieting, and whey protein is beneficial for increasing protein synthesis (especially when paired with resistance training).[5,6] Leucine is naturally present in high quantities in whey protein. It enhances protein anabolism, cell growth and metabolism due its role as an anabolic “trigger” of protein synthesis, as we mentioned at the outset.

The above study found that leucine supplementation in the presence of energy restriction resulted in a greater preservation of fat-free mass and lean tissue mass particularly in men, but did not impact glucose metabolism.

Study #2

The other notable study published this year assessed the potential benefits of leucine supplements in men with various forms of GI cancer. As you may or may not be aware, cachexia (a form of muscle loss) is common in cancer patients as well as those with various other health conditions. It alters the function of mitochondria and energy metabolism.[7] Muscle tissue is also broken down and used as a source of energy by cancer cells.[8]

Previous research showed that leucine supplementation may alleviate cancer-cachexia damage and improve energy production, protein synthesis, and maintenance of normal metabolism, mainly through the glycolytic pathway.[9]^†

This recently published study found that a balanced diet enriched with free-Leucine supplementation was able to promote gains in body weight and lean mass in older men diagnosed with gastrointestinal and appendix organs of digestion cancer after 8 weeks.[10] ^†

Specifically, the men in this study supplemented with either 7.2 g/day of L-leucine or the control of 7.2 g/day of hydrolyzed collagen (which is extremely low in leucine).

Leucine > Collagen for Lean Mass Gains

These lean mass-preserving benefits of leucine vs collagen were previously studied in 2022.[11]

A 10-week study involving untrained young adults following a resistance training program found that 35 grams of whey protein (which naturally contains 3 grams of leucine) was superior to a leucine-matched collagen supplement (1.0g occurring in collagen + 2g L-Leucine) for increasing muscle mass (but not power or strength) in untrained young adults.[11]

Additionally, a 2023 systematic review and meta-analysis published in Nutrients investigated the effects of whey protein, leucine and vitamin D on individuals with sarcopenia. The authors concluded that whey protein, leucine, and vitamin D supplementation significantly improves muscle mass, and combining those supplements with exercise can also improve muscle power and performance.[12]

Additional Benefits of Leucine

In addition to its lean mass benefits, leucine may also offer a host of other benefits, especially for those interested in weight loss as well as cardiovascular support.^†

Regarding weight loss, leucine may increase satiety with an additional impact on glucose metabolism and stimulate energy and lipid metabolism by regulating uncoupling protein-3 (UCP-3) expression in metabolically active tissues such as skeletal muscle, brown adipose tissue (BAT) and white adipose tissue (WAT).[13] FYI, BAT thermogenesis is a primary focal point of AML ThermoHeat and ThermoHeat Cocktail.

Other studies find that leucine possesses the ability to influence insulin secretion and improve insulin sensitivity.[14]^†

What About BCAA Supplements?

For well over a decade, BCAA supplements ranked among the most popular supplements for serious gym rats. This is due to the fact that the three BCAAs (leucine, isoleucine, and valine) were shown to activate mTOR and ignite protein synthesis in the body. As a result, supplement companies keen to make lots of easy bucks started cranking out BCAA products left and right under the guise of keeping fitness enthusiasts and athletes “anabolic.”

There are a few things left out, though, regarding the hype surrounding BCAAs.

As we already mentioned, leucine does a bang-up job of stimulating mTOR all by itself, and it’s more effective at doing so than either isoleucine or valine.

Second, BCAAs compete with each other for absorption, which is something that most of the supplement purchasing population doesn’t realize. Over-supplementing with individual amino acids would inhibit uptake of other critical amino acids due to the fact that they use the same transporters. 

Third, a growing body of research finds that elevated isolated valine and isoleucine may be associated with various health risks, including increased oxidative stress, type 2 diabetes, insulin resistance, obesity and cardiovascular disease.[15,16]

Note: the exact reason why elevated levels of BCAAs (which are essential) are associated with a number of poor health states is still being investigated. It’s also important to mention that many states of disease (such as diabetes and obesity) disrupt the body’s natural metabolism, which could partially explain the elevated BCAA levels found in research.

AML Post Workout: The Best Leucine Supplement

When looking for a premium quality leucine supplement, Advanced Molecular Labs Post Workout supplements has you covered.

Every serving delivers 5,000mg of pure L-Leucine to support protein synthesis, combat muscle breakdown, and kickstart muscle recovery. In addition to a full 5 grams of leucine, AML Post Workout also supplies 5 grams creatine monohydrate alongside 2 grams betaine to enhance training adaptations, improve energy recovery, and aid cell hydration.

For best results, Advanced Molecular Labs suggests taking AML Post Workout on an empty stomach immediately after training, before your post-workout meal.

Taking AML Post Workout by itself allows for a quicker, better spike of blood leucine to kickstart the recovery process and halt muscle breakdown. The ensuing post workout meal (consumed 30-45 minutes after the serving of AML Post Workout) provides all the essential amino acids to sustain protein synthesis.

Skip the overhyped BCAA supplements and supplement with the king of amino acids in L-Leucine!

^{† These statements have not been evaluated by the Food and Drug administration. This product is not intended to diagnose, treat, cure, or prevent any disease.}

^{© Published by Advanced Research Media, Inc. 2024}

^{© Reprinted with permission from Advanced Research Media, Inc.}

References

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2. Mechanick JI, Butsch WS, Christensen SM, et al. Strategies for minimizing muscle loss during use of incretin-mimetic drugs for treatment of obesity. Obesity Reviews. 2024;e13841. doi:1111/obr.13841
3. Merz KE, Thurmond DC. Role of Skeletal Muscle in Insulin Resistance and Glucose Uptake. Compr Physiol. 2020 Jul 8;10(3):785-809. doi: 10.1002/cphy.c190029. PMID: 32940941; PMCID: PMC8074531.
4. DeFronzo RA, Jacot E, Jequier E, Maeder E, Wahren J, Felber JP. The effect of insulin on the disposal of intravenous glucose. Results from indirect calorimetry and hepatic and femoral venous catheterization. Diabetes 30: 1000–1007, 1981.
5. Azadbakht L, Izadi V, Surkan PJ, Esmaillzadeh A. Effect of a High Protein Weight Loss Diet on Weight, High-Sensitivity C-Reactive Protein, and Cardiovascular Risk among Overweight and Obese Women: A Parallel Clinical Trial. Int J Endocrinol. 2013;2013:971724.
6. Burd NA, Yang Y, Moore DR, Tang JE, Tarnopolsky MA, Phillips SM. Greater stimulation of myofibrillar protein synthesis with ingestion of whey protein isolate v. micellar casein at rest and after resistance exercise in elderly men. Br J Nutr. 2012;108:958–62.
7. Beaudry A.G., Law M.L. Leucine Supplementation in Cancer Cachexia: Mechanisms and a Review of the Pre-Clinical Literature. Nutrients. 2022;14:2824. doi: 10.3390/nu14142824.
8. Argilés J.M., Busquets S., Stemmler B., López-Soriano F.J. Cancer cachexia: Understanding the molecular basis. Nat. Rev. Cancer. 2014;14:754– doi: 10.1038/nrc3829
9. Cruz B., Oliveira A., Viana L.R., Lopes-Aguiar L., Canevarolo R., Colombera M.C., Valentim R.R., Garcia-Fóssa F., de Sousa L.M., Castelucci B.G., et al. Leucine-rich diet modulates the metabolomic and proteomic profile of skeletal muscle during cancer cachexia. Cancers. 2020;12:1880. doi: 10.3390/cancers12071880
10. Soares JDP, Siqueira JM, Brito FDSB, Pimentel GD. A Randomized Controlled Trial on the Effects of Leucine-Supplement Combined with Nutritional Counseling on Body Composition in Mix Cancer Older Men. Nutrients. 2024 Jan 9;16(2):210. doi: 10.3390/nu16020210. PMID: 38257103; PMCID: PMC10818878.
11. Jacinto JL, Nunes JP, Gorissen SHM, Capel DMG, Bernardes AG, Ribeiro AS, Cyrino ES, Phillips SM, Aguiar AF. Whey Protein Supplementation Is Superior to Leucine-Matched Collagen Peptides to Increase Muscle Thickness During a 10-Week Resistance Training Program in Untrained Young Adults. Int J Sport Nutr Exerc Metab. 2022 May 1;32(3):133-143. doi: 10.1123/ijsnem.2021-0265. Epub 2022 Jan 17. PMID: 35042187.
12. Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis. Nutrients. 2023 Jan 19;15(3):521. doi: 10.3390/nu15030521. PMID: 36771225; PMCID: PMC9920795.
13. Zhang Y, Guo K, LeBlanc RE, Loh D, Schwartz GJ, Yu YH. Increasing dietary leucine intake reduces diet-induced obesity and improves glucose and cholesterol metabolism in mice via multimechanism Diabetes. 2007;56:1647–54.; McAllan L, Cotter PD, Roche HM, Korpela R, Nilaweera KN. Impact of leucine on energy balance. J Physiol Biochem. 2013;69:155–63.
14. Newsholme P, Brennan L, Bender K. Amino Acid Metabolism, β-Cell Function, and Diabetes. Diabetes. 2006;55(suppl 2):S39– Macotela Y, Emanuelli B, Bang AM, Espinoza DO, Boucher J, Beebe K, et al. Dietary leucine - An environmental modifier of insulin resistance acting on multiple levels of metabolism. PLoS One. 2011;6:0021187
15. Hu W, Yang P, Fu Z, Wang Y, Zhou Y, Ye Z, Gong Y, Huang A, Sun L, Zhao Y, Yang T, Li Z, Jiang XC, Yu W, Zhou H. High L-Valine Concentrations Associate with Increased Oxidative Stress and Newly-Diagnosed Type 2 Diabetes Mellitus: A Cross-Sectional Study. Diabetes Metab Syndr Obes. 2022 Feb 19;15:499-509. doi: 10.2147/DMSO.S336736. PMID: 35221701; PMCID: PMC8865866.
16. McGarrah, R.W., White, P.J. Branched-chain amino acids in cardiovascular disease. Nat Rev Cardiol 20, 77–89 (2023). https://doi.org/10.1038/s41569-022-00760-3