Isoleucine

Isoleucine is a nutrient belonging to the essential amino acid class.

Isoleucine is also known as Ile and L-Isoleucine.

Isoleucine is vital for stimulating muscular growth, controlling energy levels, boosting immune system health, and supporting the renewal of tissues and wound healing.

Isoleucine deficiency can cause symptoms including muscular atrophy, fatigue, impaired immune system response, and difficulties with blood sugar management.

Isoleucine can be obtained naturally in various protein-rich meals derived from plant and animal sources. Legumes like lentils, chickpeas, and soybeans; nuts and seeds like almonds, walnuts and pumpkin seeds; whole grains like quinoa and brown rice; and greens like spinach are plant sources of isoleucine. Lean meats (chicken and turkey), fish, eggs, and dairy products (cheese and yoghurt) are all animal sources of isoleucine.

Isoleucine is distributed to tissues after being absorbed through digestion and moving through circulation. It is metabolised via branched-chain amino acids (BCAAs) metabolism, which helps with protein synthesis and energy synthesis. Isoleucine in excess is either stored or excreted through urine.

The common side effects of Isoleucine include nausea, vomiting, diarrhoea, stomach bloating, fatigue and loss of coordination.

Isoleucine is available in tablets, capsules and oral powders.

Biochemical action of Isoleucine

Isoleucine, belonging to the essential amino acid class, acts in several biochemical processes. It works via the propionyl-CoA synthesis pathway.

Leucine, isoleucine, and valine are three essential amino acids, referred to as branched-chain amino acids (BCAAs), and they are needed for human nutrition. The health of muscles and energy metabolism benefit greatly from BCAAs. Since humans are unable to synthesise certain amino acids, they are crucial nutritional ingredients. BCAA catabolism in the muscle results in NADH and FADH2, which help to create ATP. The earliest stages of their catabolism, which include transamination with -ketoglutarate, are catalysed by common enzymes. As a result, diverse -keto acids are produced, which branched-chain -keto acid dehydrogenase oxidises to create various CoA derivatives. The breakdown of valine has propionyl CoA, a precursor to glucose. AcetylCoA and propionyl CoA are the products of isoleucine's catabolic process, which makes it both glucogenic and ketogenic. Leucine is purely ketogenic because it produces acetyl CoA and acetoacetyl CoA.

A common branched-chain -keto acid dehydrogenase enzyme deficiency causes Maple syrup urine disease, one of the genetic diseases connected to BCAA catabolism. As a result, urine begins to accumulate -keto acids, which have a characteristic odour. People who have this condition may likely have severe mental impairment. Unfortunately, BCAAs cannot be severely reduced from the diet since they are necessary amino acids. People who are affected have unusual development and a shorter lifespan. Failure CNS myelination is a primary neurological problem.

• 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.

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

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

Isoleucine supplements help in reducing post-workout soreness and accelerating muscle repair.

Isoleucine supplements enhance glucose uptake, providing energy during intense workouts and endurance activities.

Isoleucine supplements may help in synthesising haemoglobin and regulating blood sugar and energy levels.

The isoleucine supplement may help promote collagen formation, which supports wound healing and tissue repair.

Vitamins and natural supplements should not replace a balanced diet.

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

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

• Nutrient Deficiency: In cases of nutritional deficiency, isoleucine has significant benefits. It is a critical amino acid that facilitates protein synthesis, essential for tissue regeneration. It also improves energy generation by promoting glucose absorption and preventing tiredness brought on by deficits. Immune system performance is also enhanced, essential when shortages affect immunity. To address the slowed recovery caused by nutritional scarcity, the amino acid's function in collagen creation helps wound healing. Additionally, isoleucine helps overcome problems caused by deficiencies due to its role in controlling blood sugar, maintaining metabolism, and producing neurotransmitters.
• Athletic Performance: According to research, a combination of amino acids, including isoleucine, increased rugby players' training effectiveness and improved blood cell development and muscle integrity. This amino acid combination improved the blood's ability to transport oxygen and helped muscles recover from tiredness, improving athletic performance. It is also essential for after exercises as isoleucine promotes muscle recovery. While some research investigates the effects of amino acids and BCAAs on activity, scientific research varies on whether they can promote muscle synthesis after exercise. While isoleucine outperforms leucine and valine in improving glucose absorption into muscle cells, leucine is associated with more remarkable muscle-protein synthesis.
• Protein Synthesis: BCAAs have been found to have an anabolic effect on muscles, which slows down the rate of protein breakdown. According to studies, taking BCAAs before and after exercise causes changes in the signalling pathways that control protein synthesis. Leucine has the highest protein synthesis efficiency among the BCAAs. For the best results in protein synthesis, the study emphasises the importance of combining all three BCAAs.
• Haemoglobin: The production of haemoglobin, the protein responsible for carrying oxygen in the blood, requires isoleucine, a vital amino acid. The formation of haemoglobin is supported by an adequate intake of isoleucine, resulting in effective oxygen transport to body tissues. This addition shows the importance of isoleucine for sustaining healthy oxygenation levels and general well-being.
• Blood Sugar Regulation: Isoleucine supports blood sugar control by improving insulin sensitivity and facilitating glucose absorption into cells. It increases glucose metabolism and helps in maintaining stable blood sugar levels. Isoleucine's importance in promoting metabolic health and reducing implications from high blood sugar is shown by this effect, which is particularly beneficial for those with insulin resistance or diabetes.

Isoleucine supplementation may be administered orally.

Orally: Isoleucine supplements are available as tablets, capsules and powders that can be taken orally. Isoleucine supplements that include other amino acids should be taken between meals to ensure optimal absorption and utilization. Isoleucine 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 activity.

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: 67 mg
• Capsules: 500 mg, 1000 mg, 1030 mg, 2000 mg, 3000 mg
• Powder, oral: 3.25 mg/sachet

Dosage Adjustment for Adult Patients

By Mouth:

Taking 1 to 2 grammes up to three times a day is the best way to begin taking supplements. When trying to gain muscle, you should take BCAAs or isoleucine with leucine and valine.

Isoleucine supplements are available in tablets, capsules and oral powders.

Isoleucine should be a supplement that helps in several physiological processes and appropriate dietary restrictions.

• Avoid alcoholic beverages.
• Stay within your daily calorie needs.
• Since these may hinder absorption, keep away from food, especially foods high in other branched-chain amino acids (BCAAs) like Leucine and valine.
• While taking Isoleucine supplements, limit the consumption of Isoleucine-rich foods to avoid excessive intake.

Recommended Daily Allowance (RDA)

As per FSSAI, the estimated RDA of Isoleucine is 20 mg/kg body weight per day.

Upper Tolerable Intake (UTL):

The UTL of Isoleucine needs to be established.

Isoleucine supplementation may be contraindicated in the following conditions:

• Hypersensitivity: sensitive to Isoleucine-related allergy.
• 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 isoleucine, causing them to accumulate in the blood.
• Alcoholics
• Hyperammonemia
• ALS or Lou Gehrig's disease
• Post-surgery
• Diabetes
• Electrolyte disorder

Isoleucine supplements should be cautiously taken in pregnant and breastfeeding mothers and under the supervision of a healthcare professional.

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

Isoleucine supplements should be given cautiously to people with preexisting medical conditions or taking medications.

Individuals with a history of allergies or sensitivities to amino acids should be vigilant and used cautiously.

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

Caution is advised when consuming alcohol with isoleucine.

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

The adverse reactions related to Isoleucine can be categorised as:

• Common: GI disturbances like nausea or stomach upset
• Less common: Allergic Reactions and hypoglycemia
• Rare: Elevated Blood Urea Nitrogen (BUN) and Neurological symptoms.

There is no sufficient scientific evidence traceable regarding the use and safety of isoleucine in concurrent use with any particular drugs.

The common side of Isoleucine include the following:

• Nausea
• vomiting
• Diarrhea
• Stomach bloating
• Fatigue
• Need for coordination.
• Upset stomach
• Muscle incoordination.
• Gastrointestinal discomfort
• Headache
• Dizziness
• Allergic reactions (rare)
• Increased insulin levels

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

• Pregnancy:

Without specific health recommendations, Isoleucine supplements are typically not advised for children. There is no sufficient scientific evidence traceable regarding the use and safety of Isoleucine for pregnant populations. Avoid Isoleucine supplements unless advised by a healthcare professional while pregnant.

• Paediatrics:

Without specific health recommendations, isoleucine supplements are typically not advised for children. There is no sufficient scientific evidence traceable regarding the use and safety of isoleucine 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 isoleucine 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 isoleucine for lactating mothers populations. Avoid isoleucine 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 about identifying and treating overdosage of Isoleucine. Overconsumption of Isoleucine could lead to symptoms like nausea, vomiting, diarrhoea and difficulty breathing.

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

Isoleucine supplements should be terminated immediately when an overdose is suspected or experience any unusual symptoms after Isoleucine 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 Isoleucine

Isoleucine is an α-amino acid with a side chain comprised of straight hydrocarbons. It has a central carbon atom attached to an amino group, a carboxyl group, and a side chain of three carbon atoms.

The human body cannot produce isoleucine, a branched-chain amino acid (BCAA). Hence, it must be consumed through food. Isoleucine has a role in protein synthesis and energy production during metabolism. Muscle tissues are where its catabolism begins, producing chemicals like NADH and FADH2 that help make ATP. Enzymes that catalyse transamination and oxidative decarboxylation processes, which have a number of intermediates, are part of the isoleucine catabolic pathway. Particularly, isoleucine can contribute to the production of both glucose and ketone bodies since it can be both glucogenic and ketogenic. Its importance in maintaining energy balance is increased by its dual metabolic function. Measuring isoleucine levels is crucial for people with metabolic disorders to ensure their nutritional and physiological well-being.

Kinetic profile:

• Absorption: Isoleucine 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: Isoleucine is widely distributed throughout the body, with muscles serving as its primary reservoir due to its involvement in protein synthesis.
• Metabolism: Isoleucine is primarily metabolised through the branched-chain amino acid (BCAA) route. Isoleucine, valine, and leucine are broken down into intermediates through a series of enzyme activities via this process, which can be used to produce energy. Acetyl-CoA, a crucial molecule for making energy in the form of ATP, is one of the main byproducts of isoleucine catabolism.
• Elimination: Isoleucine that is not immediately needed for metabolism can either be transformed into other molecules or stored for later use. The body subsequently eliminates the breakdown products from isoleucine metabolism through the urine.

1. https://www.fssai.gov.in/upload/advisories/2021/07/60f1798019f94Direction_RDA_16_07_2021.pdf
2. https://pubchem.ncbi.nlm.nih.gov/compound/l-Isoleucine

3. https://www.fssai.gov.in/upload/advisories/2021/07/60f1798019f94Direction_RDA_16_07_2021.pdf

4. Tessari P. 2019. Nonessential amino acid usage for protein replenishment in humans: a method of estimation; American Society for Nutrition. Department of Medicine, University of Padova, Padova, Italy

5. National Institute of Nutrition. 2011. Dietary guidelines for Indians; 2nd Edition. Hyderabad. India