Leucine

Leucine is a nutrient belonging to the essential branch chained essential amino acid (BCAAs) class.

Leucine is also known as L-leucine, (S)-2-Amino-4-methylpentanoic acid, (S)-Leucine.

Leucine is vital for synthesising, developing, and repairing muscle proteins. It also supports blood sugar regulation and provides energy during exercise.

Leucine deficiency is very uncommon in humans. It may lead to hypoglycaemic characterised by fatigue, dizziness, and headaches.

Leucine can be obtained naturally in various protein-rich meals derived from both plant and animal sources. Examples of plant sources include oats, lentils, pea beans, spirulina, peanuts, and seeds. In contrast, chicken, pork, steak, tuna fish, salmon fish and cottage cheese are excellent sources of animal sources of leucine.

Leucine is absorbed in the small intestine, mainly distributed in muscles and tissues, metabolised for protein synthesis and energy and excreted in urine as metabolites.

The common side effects of Leucine include GI disturbances, imbalance of other amino acids like valine and isoleucine and low blood sugar.

Leucine is available in tablets, capsules and oral powders.

Biochemical action of Leucine

Leucine, belonging to the essential amino acid class, acts in several biological processes. It works via mTOR signalling pathway activation.

The complex network involved in cell growth, proliferation, and protein synthesis—the mechanistic target of the rapamycin (mTOR) signalling pathway—is activated. The leucine-sensing protein kinase mTOR, which exists in two different complexes called mTORC1 and mTORC2, is the enzyme that carries out the activity of leucine.

After consuming leucine, mTORC1 is activated, phosphorylating several downstream targets involved in translation initiation and ribosomal biogenesis. By stimulating ribosome formation and activating the translational machinery, this mechanism promotes protein synthesis. By modulating the phosphorylation of the essential regulators of protein synthesis, p70 ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), leucine also influences mRNA translation.

Leucine works by attaching to cell surface receptors, such as the leucine transporter LAT1, triggering a series of intracellular processes that eventually promote protein synthesis, cell division, and energy generation. As a result, leucine is an essential amino acid for maintaining muscle mass, boosting overall body composition, and supporting rapid recovery from exercise.

Leucine is available in tablets, capsules and oral powders.

• Tablets: To be swallowed whole with water/liquid, as applicable.
• Capsules: To be swallowed whole with water/liquid, as applicable.
• Powders, oral: Powders must be mixed thoroughly with the appropriate amount of liquid and stirred well to dissolve the powder, as applicable.

Leucine can be used as a supplement when the amount of leucine taken through diet is insufficient.

Taking leucine supplements effectively treats leucine deficiency caused by specific genetic diseases or other disorders.

Supplemental leucine may help to build and maintain bone health and density.

Leucine supplements may be necessary for wound healing and restoration after surgeries or injuries.

Leucine may help control blood sugar levels when used as a supplement.

Supplemental leucine's antioxidant abilities might help athletes and physically active people by reducing the oxidative stress produced by vigorous exercise.

Vitamins and natural supplements should not replace a balanced diet.

This product is not intended to diagnose, treat or prevent any disease(s).

Leucine can help to support as a supplement for the following health benefits:

• Protein Synthesis: Leucine supplements are used very commonly among bodybuilders as they promote protein synthesis, which benefits skeletal muscle building. It stimulates cell production by activating mTOR in two ways. Leucine supplementation improves muscle protein synthesis, according to research. Combining leucine with resistance exercises increases its efficacy, especially when taken pre-workout for maximal gains. The emphasis on skeletal protein production corresponds to increased muscle mass, which benefits bodybuilders.
• Athletic Performance: The significance of leucine in insulin synthesis provides an energy boost for productive workouts. Improved insulin management boosts muscle energy supply. Along with its ability to increase protein synthesis and limit breakdown, leucine's potential training benefits exceed those of other steroids. Daily pre-workout intake of leucine consumption boosts muscular strength and growth. Bodybuilders favoured leucine because of its ability to promote muscular development. It promotes muscle building by activating the mTOR signalling pathway. Short-term studies show increased protein synthesis but not consistently increased muscle mass. Long-term human study is required to validate leucine's effect on muscle building.
• Muscle Recovery: According to research, combining leucine supplementation with resistance training can help muscle recovery. The benefits seem to be enhanced when leucine is combined with essential amino acids. Recent research suggests that essential amino acids high in leucine can help decrease muscle damage after exercise. One study, however, found no evidence of significant changes in muscle protein synthesis. Another trial in young people found that leucine supplementation did not improve recovery after resistance training.
• Insulin Sensitivity: Taking leucine supplements over an extended period may improve insulin sensitivity. The supplements have been demonstrated in studies to prevent the development of insulin resistance even in a high-fat diet. This helps to prevent fat accumulation and increases muscular mass.
• Weight Control: According to animal research, leucine helps with weight control by influencing hunger regulation via leptin response augmentation. Its significance in the effectiveness of high-protein diets may include blood glucose management. Leucine promotes weight management by decreasing cravings, increasing fullness, maintaining muscle during weight loss, and preventing blood sugar rises.
• Burns fat: Leucine is an excellent supplement for increasing muscle building and fat burning. While not a magic cure, it does improve exercise results. Leucine may also inhibit fatty tissue accumulation, potentially counteracting age-related fat gain. A leucine supplement can help prevent the adverse effects of an imbalanced diet.

Leucine supplementation may be administered orally.

Orally: Leucine supplements are available as tablets, capsules and powders that can be taken orally. Leucine supplements should be taken between meals to increase absorption and decrease the risk of gastrointestinal discomfort, especially if combined with other amino acids or protein sources. Leucine supplements should also be taken before bed to promote overnight muscle repair and development.

Taking it before, during or after exercise may boost its impact on growth hormone release for goals associated with exercise.

The dosage and duration of treatment should be as per the clinical judgment of the treating healthcare professional).

Vitamins and natural supplements should not replace a balanced diet

This product is not intended to diagnose, treat or prevent any disease(s).

• Tablets: 3000mg, 4000 mg
• Capsules: 500mg, 1000mg
• Powder, oral: 125g

Dosage Adjustment for Adult Patients

There are no specific dosage adjustments provided.

Leucine is available in tablets, capsules and oral powders.

Leucine should be a supplement that helps in several biochemical processes and appropriate dietary restrictions.

• Avoid alcoholic beverages.

• Stay within your daily calorie needs.

• Keep away from high-protein meals and beverages, especially those that include other amino acids, since these may hinder the absorption of leucine.

• While taking leucine supplements, limit the consumption of leucine-rich foods to avoid excessive intake.

Recommended Daily Allowance (RDA)

As per FSSAI, the estimated RDA of leucine is 39 mg/kg body weight per day.

Upper Tolerable Intake (UTL):

The UTL of leucine is not established.

Leucine supplementation may be contraindicated in the following conditions:

• Hypersensitivity: sensitive to leucine-related allergies
• Chronic liver disease
• Chronic kidney disease (CKD)
• Kidney failure
• Maple syrup urine disease (MSUD): A condition in which the body cannot break down branched amino acids like leucine, causing them to accumulate in the blood.
• Diabetes
• Active bleeding disorders
• Active ulcers or gastritis

High-dose supplements should be used cautiously in children and the elderly.

Before taking leucine, individuals with renal or liver disorders should see a physician since the dosage may need to be adjusted to prevent adverse effects.

Leucine supplements should be cautiously administered in pre-existing diabetic individuals as it may cause a lowering of the blood sugar levels, i.e hypoglycaemia.

Individuals taking high cholesterol or thyroid conditions may use leucine supplements cautiously as it can cause unwanted interactions.

To avoid potential interactions, it is recommended to use only one amino acid supplement or dietary supplements.

High dosages of leucine supplementation should be avoided since it may interfere with the production of niacin from tryptophan, worsening pellagra symptoms.

There is no sufficient scientific evidence traceable regarding the use and safety of leucine for breastfeeding populations.

There is no sufficient scientific evidence traceable regarding the use and safety of leucine for pregnant populations.

While taking leucine supplements, limit the consumption of foods that are leucine-rich foods to avoid excessive intake.

The adverse reactions related to leucine can be categorised as:

• Common: GI disturbances like bloating, gas, nausea, diarrhoea and vomiting
• Less Common: Allergic reactions like rash and itching.
• Rare: Hyperammonemia and hyperglycemia.

The clinically relevant drug interactions of leucine are summarized here:

• Anti-diabetic drugs: Leucine has the potential to reduce blood sugar levels. When taken with insulin or other diabetes treatments, this can result in deficient blood sugar levels.
• Vitamins: Leucine, when used concurrently with vitamins like niacin (B3) and vitamin B6, can interfere with the production of niacin and vitamin B6.
• Antiplatelets: Potential interactions owing to the effect of leucine on platelet aggregation.
• Antiparkinson’s medications: These medications, such as levodopa, when used along with Leucine, may interfere with levodopa absorption, reducing its effectiveness.
• Sildenafil: Animal studies suggest that leucine may improve the efficacy of PDE5 inhibitors of erectile dysfunction medications such as Viagra (sildenafil).

The common side of Leucine include the following:

• Diarrhea
• Vomiting
• Bloating
• Gas
• Upset stomach
• Nausea
• Hypoglycemia
• Imbalance of other amino acids like valine and isoleucine

Leucine should be prudent in the following group of special populations.

• Pregnancy:

There is no sufficient scientific evidence traceable regarding the use and safety of leucine for pregnant populations. Avoid leucine supplements unless advised to do so by a healthcare professional while pregnant.

• Paediatrics:

Without specific health recommendations, leucine supplements are typically not advised for children. There is no sufficient scientific evidence traceable regarding the use and safety of leucine for paediatric populations.

Dosage Adjustment for Paediatric Patients

There are no specific dosage adjustments provided.

• Geriatrics:

There is no sufficient scientific evidence traceable regarding the use and safety of leucine for geriatric populations. Avoid supplements unless advised to do so by a healthcare professional.

• Lactating mothers:

There is no sufficient scientific evidence traceable regarding the use and safety of leucine for lactating mothers populations. Avoid leucine supplements unless advised by a healthcare professional while lactating.

Dosage Adjustment in Kidney Impairment

There are no specific dosage adjustments provided.

Dosage Adjustment in Hepatic Impairment

There are no specific dosage adjustments provided.

The physician should be vigilant about the knowledge pertaining to identifying and treating overdosage of Leucine. Overconsumption of Leucine may lead to symptoms that might include Nausea, diarrhoea, stomach pain and indigestion.

There is no specific antidote or treatment for excessive intake of supplemental Leucine.

Leucine supplements should be terminated immediately when an overdose is suspected or experience any unusual symptoms after Leucine supplement use or dietary intake. Supportive therapy should also be given, addressing any symptoms that persist or worsen. Physical treatment might be added if necessary.

Biochemistry profile of Leucine

Leucine, an essential amino acid, has a branching structure with a central carbon atom attached to an amino group, a carboxyl group, and a distinct side chain.

Leucine's actions extend beyond its role as a protein building block. It is powerfully held by a critical signalling route that regulates cell growth, proliferation, and protein synthesis, the mTOR (mammalian target of rapamycin) pathway. Leucine enters cells through amino acid transporters like LAT1 after absorption. Leucine, particularly in muscle tissues, stimulates the mTORC1 complex within the cell, activating translation and boosting the synthesis of new proteins. Its significance for muscle development, repair, and metabolic equilibrium is a result of its capacity to start anabolic processes and improve muscle protein synthesis. Leucine metabolism also helps generate energy since it may be transformed into acetyl-CoA, a crucial component in energy production and the synthesis of fatty acids.

Kinetic profile:

• Absorption: Leucine is absorbed in the small intestine via active transport pathways. It competes for transport with other branched-chain amino acids (BCAAs), which can alter its absorption rate.
• Distribution: Leucine is widely distributed throughout the body, with muscles serving as its primary reservoir due to its involvement in protein synthesis.
• Metabolism: Leucine is primarily metabolised in skeletal muscles, where it acts as a substrate for protein synthesis and energy production. It can also be broken down into other tissues, such as the liver. Leucine can be used to synthesize other amino acids that help with the production of glucose or be transformed into ketone bodies.
• Elimination: Leucine is not excreted in substantial quantities. Its metabolites, such as alpha-ketoisocaproate (KIC), can be eliminated in urine.

1. https://www.fssai.gov.in/upload/advisories/2021/07/60f1798019f94Direction_RDA_16_07_2021.pdf
2. https://examine.com/supplements/leucine/
3. https://www.verywellhealth.com/leucine-uses-benefits-side-effects-dosage
4. https://www.healthifyme.com/blog/leucine-benefits/
5. https://www.webmd.com/diet/foods-high-in-leucine
6. https://community.bulksupplements.com/l-leucine/