A high-protein diet.

L-Leucine Benefits to Support Nervous System Health*

Leucine is one of the essential branched-chain amino acids (BCAAs) necessary for protein synthesis and metabolism.* It is also involved in several other cellular processes, including tissue regeneration and metabolism.* Leucine supplementation promotes various health functions, including the nervous system, musculoskeletal system, and cellular health. 

This post discusses the benefits of L-leucine, particularly highlighting its effect on the nervous system. Use the links below to jump ahead to different topics on the page.

L-Leucine and Its Dietary Sources

Food for brain

The BCAAs–leucine, isoleucine, and valine–account for approximately one-third of muscle protein. A distinctive feature of BCAAs is that, unlike most other amino acids, they bypass first-pass metabolism in the liver after intestinal absorption. Instead of being extensively metabolized in the gut or liver, BCAAs enter the body’s systemic circulation largely intact, leading to a significant postprandial increase in plasma levels. This allows various tissues, particularly skeletal muscle, to directly sense and utilize BCAAs for protein synthesis, energy production, and metabolic signaling.* 

The recommended daily intake for leucine ingestion in healthy young adults is 55 mg per kg.

Chemically, L-leucine is the L-enantiomer of leucine, the biologically active form utilized in protein synthesis and metabolic processes. Leucine is widely available in dietary protein sources and is one of the most abundant amino acids in a high-protein diet. The leucine content of protein typically varies between 5 to 10 percent, depending on the source. Dietary protein intake stimulates muscle protein synthesis (MPS), with MPS peaking approximately 2-3 hours post-ingestion.Foods rich in leucine to keep stocked in your fridge and pantry include cheese, soybeans, oats, lentils, beans, tofu, fish, egg, yogurt, nuts, sesame seeds, pumpkin seeds, and animal meat.    

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L-Leucine Benefits  

Leucine plays a key role in protein synthesis and metabolism.* It is not only a substrate for protein synthesis, it is also a potent signal nutrient that regulates protein metabolism.* In addition to protein synthesis and metabolism, L-leucine promotes energy metabolism to provide energy for protein synthesis. Approximately 80 percent of leucine is normally used for protein synthesis, with the rest being converted to metabolic intermediates. Some of the functions of leucine are thought to be modulated by its metabolites.   

The following table highlights key L-leucine benefits in promoting various physiological processes:

Key L-Leucine Benefits to Promote Health Functions
  • It helps regulate glucose homeostasis.* Several studies indicate that leucine supplementation enhances glucose homeostasis.* Although the underlying mechanism of leucine on glucose control remains unknown, it is hypothesized that leucine targets the pancreas and affects glucose homeostasis. 

    It has been found that leucine stimulates protein synthesis in pancreatic cells through the mTOR signaling pathway.* Leucine also displays insulinotropic properties, stimulating the body’s insulin secretion.*2 These pathways are likely to be involved in leucine’s beneficial effects on glucose control and healthy weight management.*;

    Leucine supplementation also affects glucose metabolism and glycogen synthesis in insulin-sensitive tissues, such as the liver and skeletal muscle, which can influence whole-body glucose homeostasis.*
  • It helps improve muscle protein synthesis.* BCAAs have been shown to increase skeletal muscle protein synthesis and net balance.* Leucine, in particular, plays a role in muscle anabolism — the process of building and maintaining muscle mass.* In skeletal muscle, a dip in leucine level and a reduction in glycogen stores are observed during exhaustive aerobic exercise. Consumption of BCAA before or during endurance exercise.

    Lower blood levels of leucine are associated with lower values of the skeletal muscle index, grip strength, and performance. Leucine supplementation has been found to be useful in addressing the age-related decline in muscle mass in elderly individuals because it increases the muscle protein fractional synthetic rate.*3 The role of leucine in enhancing muscle protein anabolism and, potentially, muscle size and function helps address reduced muscle mass and strength in the elderly.*

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How L-Leucine Promotes Neurological Health 

The central nervous system is vital for regulating food intake, energy balance, and glucose homeostasis. Research indicates that leucine enters the brain from the blood more rapidly than any other essential amino acid. The following table highlights how L-leucine promotes brain functions and supports the nervous system:* 

How L-Leucine Benefits Brain Health*
  • It helps limit the potentially toxic accumulation of high glutamate concentrations.* Although glutamate is critical for learning and memory, an excessive concentration of glutamate in the brain can cause brain cell damage or cell death (autophagy). 

    Leucine participates in glutamate-branch amino acid shuttling between neurons and astrocytes (the star-shaped glial cells in the brain), which limits the toxic accumulation of high glutamate concentrations.*4 It also helps maintain the nitrogen balance in the glutamate/glutamine cycle.*   
  • It helps regulate the mammalian target of rapamycin (mTOR) activity.* mTOR is a critical cell signaling pathway that modulates several integrated physiological functions of the nervous system, including synaptic plasticity, neuronal development, memory storage, and cognition. Leucine is the most effective amino acid for regulating mTOR activity, influencing energy balance and glucose homeostasis, and regulating food intake.*5
  • It is involved in regulating autophagy.* Autophagy is the beneficial process of cellular self-digestion that results in the degradation of dysfunctional proteins and organelles. Although autophagy plays a critical role in physiological conditions, excessive autophagy can disrupt cellular functions. It has been found that a leucine deficiency induces elevated autophagy with damaging effects on neurons.*6  

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L-Leucine Metabolism 

Oral L-leucine supplementation has been found to increase protein synthesis in the skeletal muscle, white adipose tissue, heart, liver, kidney, and pancreas.* To understand the effects of L-leucine supplementation, let’s look at how BCAAs are metabolized in the body.7

  • Transamination by the branched-chain amino acid transaminase (BCAT): The BCAT enzyme catalyzes the first and reversible transamination step of leucine degradation. The cytosolic form of BCAT metabolizes leucine in the brain, whereas the mitochondrial form of the enzyme is expressed in multiple tissues, including skeletal muscle, white adipose tissue, and the pancreas.
  • Catalyzation by the branched-chain alpha-ketoacid dehydrogenase complex (BCKDK): BCCA oxidation has been found to be self-regulated. Increased BCAA levels induce higher BCAT and BCKDK complex activities to limit excessive BCAA levels that could be toxic.

Research indicates that leucine regulates several cellular processes through various signaling pathways, including the (mTOR) in skeletal muscles, adipose tissues, and placental cells.* L-leucine’s potential role in regulating energy balance and glucose homeostasis translates to its health-promoting benefits in brain health, the musculoskeletal system, and healthy weight management.*

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Safety of L-Leucine

55 mg/kg is the daily recommended intake for leucine ingestion in healthy young adults. The popularity of leucine supplements raises concerns about the potential adverse effects of excessive leucine intake. In a study to determine the metabolic and adverse effects of a very high intake of leucine supplements, it was found that:8 

  • The plasma leucine concentrations increased beyond an intake of 500 mg/ kg per day. 
  • The metabolic limit to oxidize leucine was between 550 and 700 mg/ kg per day. 
  • An increase in blood ammonia concentrations was observed at a leucine intake of more than 500 mg/kg per day. Elevated plasma ammonia concentrations can increase brain ammonia levels, which could lead to adverse neurologic consequences. However, the plasma ammonia concentrations returned within normal ranges the day after the leucine intervention.
  • Glucose concentrations dropped but remained within the normal range and without any change in insulin. 

The advantages and safety of leucine supplementation over the long term are still being investigated. Also, similar safety studies of L-leucine effects in the elderly have not yet been conducted. Therefore, it is recommended to consult with your healthcare provider to determine the right amount of leucine intake and its potential contraindications with prescription medications.   

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Including An Advanced L-Leucine Supplement in Your Diet

The benefits of L-leucine make it a commonly used supplement for promoting nervous system health, metabolic health, and overall wellness.* When considering a leucine supplement, it is essential to select a formulation that optimizes the amino acid’s absorption and bioavailability to achieve its desired benefits.  

N-Acetyl-L-leucine, developed by Tesseract Medical Research, enhances the absorption and bioavailability of the active nutrient through the proprietary CyLoc® – DexKey® nutrient delivery nanotechnology. The CyLoc® technology encases each L-leucine molecule in its own dextrin fiber delivery cage. The DexKey® technology accompanies each CyLoc® molecule and breaks the dextrin fiber cage at the desired point in the intestinal tract for the optimal absorption and bioavailability of L-leucine molecules.   

Tesseract’s innovative leucine supplement has been manufactured following Good Manufacturing Practices (GMPs), including advanced analytical techniques and a well-designed quality control system to provide optimal support for your nervous system.*  

The power of Tesseract supplements lies in enhancing palatability, maximizing solubility, absorption and bioavailability, and micro-dosing a single or multiple nutrients in a single, highly effective capsule. Shop products on our website and learn more about how they support neurological health/strong>.*

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References 

1,7Pedroso JAB, et al. Reviewing the effects of L-leucine supplementation in the regulation of food intake, energy balance, and glucose homeostasis. Nutrients vol. 7,5 3914-37. 22 May. 2015, doi:10.3390/nu7053914

2Binder E, et al. Leucine supplementation protects from insulin resistance by regulating adiposity levels. PloS One vol. 8,9 e74705. 25 Sep. 2013, doi:10.1371/journal.pone.0074705

3Xu Z, et al. The effectiveness of leucine on muscle protein synthesis, lean body mass and leg lean mass accretion in older people: a systematic review and meta-analysis. The British Journal of Nutrition vol. 113,1 (2015):25-34. doi:10.1017/S0007114514002475

4Yudkoff M, et al. Astrocyte leucine metabolism: significance of branched-chain amino acid transamination. Journal of Neurochemistry vol. 66,1 (1996):378-385. doi:10.1046/j.1471-4159.1996.66010378.x

5Rehman SU, et al. Research progress in the role and mechanism of Leucine in regulating animal growth and development. Frontiers in Physiology vol. 14 1252089. 17 Nov. 2023, doi:10.3389/fphys.2023.1252089

6Wang X, et al. Leucine mediates cognitive dysfunction in early life stress-induced mental disorders by activating autophagy. Frontiers in Cellular Neuroscience vol. 16 1060712. 4 Jan. 2023, doi:10.3389/fncel.2022.1060712

8Pencharz PB, et al. Determination of the tolerable upper intake level of leucine in adult men. The Journal of Nutrition vol. 142,12 (2012):2220S-2224S. doi:10.3945/jn.112.160259

Al Czap, Founder | Tesseract

Al Czap has more than four decades of professional experience in preventative medicine. He founded Thorne Research in 1984 (sold in 2010) and he published Alternative Medicine Review for 17 years beginning in 1996. AMR was a highly acclaimed, peer-reviewed, and indexed medical journal. Al was the first to recognize the need for hypoallergenic ingredients and to devise methods of manufacture for and delivery of hypoallergenic products to underserved patient populations. His work has greatly impacted those with impaired immune and digestive systems and compromised health due to environmental exposures.

The advanced formulations based on our revolutionary, patented, and patent-pending technology are only available through Tesseract. No other medical, pharmaceutical, or supplement company is licensed to utilize our proprietary technology.
*These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.
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