Isoleucine: An Amino Acid for Exercise Recovery and More
A Branched-Chain Amino Acid for Exercise Recovery and Key Bodily Processes
Medically reviewed by Elizabeth Barnes, RDN
Isoleucine is one of the three branched-chain amino acids (BCAAs). It is named after its chemical structure.
It is considered an essential amino acid because the body cannot produce it, and it must be obtained through diet or supplementation.
Protein-containing foods such as meat and dairy products contain isoleucine. As a supplement, isoleucine is available by itself or with other BCAAs.
Isoleucine has been studied to treat post-exercise muscle soreness.
Branched-chain amino acids have also been studied to reduce postexercise muscle damage and maintain or improve muscle function.
Not only does isoleucine serve as a building block for proteins, but it also serves as a signaling molecule that regulates the following:
Sugar metabolism
Fat synthesis
Intestinal health
Immunity
This article discusses some of the potential uses and safety of isoleucine.
Isoleucine Supplement Facts
Active Ingredient(s): Isoleucine
Alternate Names(s): l-Isoleucine, (2S,3S)-2-Amino-3-methylpentanoic acid
Legal Status: Over-the-counter (OTC) dietary supplement (United States)
Suggested Dose: The dose of isoleucine varies depending on the indications or uses.
Safety Considerations: Isoleucine should not be used in the setting of maple syrup urine disease (MSUD), a condition in which the body cannot process certain amino acids or if you are pregnant or breastfeeding. Caution should be taken in people with kidney disease, insulin resistance, type 2 diabetes, obesity, heart disease, and in children.
Isoleucine vs. Leucine
While isoleucine and leucine are both BCAAs, leucine is the potent stimulator of muscle protein synthesis (the process by which cells make proteins).
However, preliminary data suggest that isoleucine and valine alongside leucine enhances protein synthesis to a greater extent than leucine alone.
Yet, ingesting BCAAs and other essential amino acids (i.e., amino acids that the body cannot produce) remains necessary for maximal muscle protein synthesis following resistance exercise training.
PatrÃcia Monteiro / Getty Images
Female stretching after exerciseUses of Isoleucine
Explainer
Supplement use should be individualized and vetted by a healthcare professional, such as a registered dietitian nutritionist (RD) or registered dietitian nutritionist (RDN), pharmacist, or healthcare provider. No supplement is intended to treat, cure, or prevent disease.
Blood Sugar
In one study, isoleucine was prepared as a suspension and given to 12 healthy and lean subjects via a nasogastric tube. Fifteen minutes later, the study subjects consumed a mixed-nutrient drink consisting of 56 grams (g) of carbohydrates, 15 g of protein, and 12 g of fat. Isoleucine lowered blood sugar levels by slowing gastric emptying (when contents move out of the stomach).
Further studies looking at the effect of isoleucine in people with type 2 diabetes are needed to determine how it may affect people with this condition.
Taking isoleucine by mouth has decreased blood sugar concentrations without changing levels of insulin (a hormone that regulates blood sugar levels).
On the contrary, high dietary intake of BCAAs has been associated with an increased risk of type 2 diabetes.
However, it is unclear if an increased level of BCAAs causes type 2 diabetes.
Muscle Damage and Soreness
An analysis of a collection of studies found that BCAAs reduced muscle damage biomarkers (measurable indicators) and muscle soreness following muscle-damaging exercises.
Because BCAAs were examined collectively, it is unclear if isoleucine alone affects muscle damage and soreness.
Exercise Fatigue
A study to determine the effect of BCAA supplementation on fatigue and muscle damage biomarkers (indicators) was conducted in 26 male subjects who used a type of exercise equipment called a bicycle ergometer. The study found that BCAAs decreased serotonin concentration (a chemical messenger contributing to fatigue) during endurance exercise.
The decreased serotonin concentration then reduced the concentration of muscle damage markers (e.g., creatinine kinase and lactate dehydrogenase) and enhanced exercise performance.
Since the study used a combination of three BCAAs, the effect of isoleucine alone on fatigue and muscle damage biomarkers remains unclear.
Further studies with larger sample sizes solely looking at isoleucine are needed to clarify the results.
Blood Flow in the Brain
In a study of 27 people with cirrhosis (scarring of the liver) and hepatic encephalopathy (toxin buildup in the brain due to liver disease), supplementation with isoleucine for one year improved blood flow in the brain.
Despite the positive finding, larger sample sizes are needed to confirm the results.
Immune System
Results from a review of a group of studies showed that BCAA intake in people with cancer undergoing surgery decreased the risk of postoperative (after surgery) infections as well as the risk of ascites (fluid buildup in the abdomen) compared to the control group.
Since the majority of the clinical studies looked at individuals with liver cancer, it is unclear if the results applied to individuals with other types of cancer.
Dosage
Explainer
Always speak with a healthcare provider before taking a supplement to ensure that the supplement and dosage are appropriate for your individual needs.
The following dosages were used in clinical trials:
Blood sugar: Two hundred milliliters (mL) of intragastric infusion consisting of 10 g of crystalline isoleucine and 58 milligrams (mg) of calcium chloride and water were given via a feeding tube that goes through the nose and into the stomach.
Muscle damage and soreness: Studies examining the effect of BCAA supplementation on muscle damage and soreness used a BCAA ratio of 2-to-1-to1 (leucine-to-isoleucine-to-valine). The dosage of BCAAs was between 0.20 and 1.76 grams per kilogram (g/kg) of body weight and between 12 and 260 g. The duration of BCAA supplementation ranged from one to 28 days.
Supplementing with BCAAs for at least seven days before muscle-damaging exercise may effectively limit exercise-induced muscle damage from exercise.
Exercise fatigue: BCAAs containing isoleucine (20%), valine (24%), and leucine (46%) were dissolved in 500 milliliters (mL) of reverse osmosis water and 80 milligrams per kilogram (mg/kg) BCAA of weight was given. Five hundred milliliters of the BCAA mixture was consumed by mouth 50 minutes before exercise.
Hepatic encephalopathy: The dose was three packets (each containing 5 g of maltodextrin, 1.8 g of maltitol, 1.2 g of flavoring, and 10 g of L-isoleucine) by mouth daily mixed in 200 mL of juice or dairy drinks and ingested during breakfast, lunch, and an evening snack for 12 months.
Postsurgical morbidity (disease) from infections and ascites: The dose is 4.74 g of BCAAs by mouth three times daily, one month before and one year after surgery.
Safety
Side Effects
Branched-chain amino acids given through the veins were associated with increased blood sugar levels and urine production post-surgery.
Although no side effects were reported in some studies, other studies have reported the following side effects of BCAAs:
While these side effects are associated with BCAAs, it is unclear if isoleucine alone would have such side effects.
Interactions
The following interactions should be noted when taking isoleucine:
Diabetes medications: Since isoleucine has been shown to lower blood sugar levels, using isoleucine in combination with diabetes medications may cause blood sugar levels to drop too low.
Levodopa: In general, proteins can interfere with the absorption of levodopa, a medication used to treat Parkinson's disease. Therefore, isoleucine may theoretically affect the absorption and, thus, the efficacy of levodopa.
It is essential to carefully read a supplement's ingredients list and nutrition facts panel to know which ingredients and how much of each ingredient is included. Review this supplement label with your healthcare provider to discuss potential interactions with foods, other supplements, and medications.
Precautions
The following precautions should be noted when taking isoleucine:
Severe allergic reaction: Avoid using isoleucine if you have a known allergy to it or its ingredients. Ask your pharmacist or healthcare provider for a complete list of the ingredients if you're unsure. If you're having a severe allergic reaction or if any of your symptoms feel life-threatening, call 911 and get medical help right away.
Pregnancy and breastfeeding: Since people who are pregnant and breastfeeding were excluded from the studies, the safety of isoleucine in such a population is unknown.
Children: Supplementation with a single amino acid may cause growth problems in children.
MSUD: Maple sugar urine disease is a metabolic disorder in which the body lacks the enzyme that breaks down the three BCAAs (isoleucine, leucine, and valine). Consequently, the levels of these BCAAs, along with their toxic byproducts, build up, causing brain and nerve disorders, such as cognitive impairments, mood and anxiety disorders, and attention deficit hyperactivity disorder (ADHD). One of the strategies to manage MSUD consists of dietary restriction of BCAAs.
Liver disease: Although BCAAs have been shown to improve blood flow in the brain in people with hepatic encephalopathy, higher BCAA levels were found in people with nonalcoholic fatty liver disease (NAFLD) and obesity. The therapeutic role of BCAAs in the setting of liver disease seems to be unclear due to the contradictory results.
Kidney disease: A high-protein diet was associated with a faster decline in kidney function in people with poor kidney function. If you have kidney problems, such as chronic kidney disease, consult with your healthcare provider or RD before starting amino acid supplements.
Other medical conditions: Increased isoleucine levels have been associated with a higher cholesterol level, liver fat content, insulin resistance, type 2 diabetes, obesity, and cardiovascular disease. Further studies are needed to determine if increased isoleucine levels were the cause or an effect of certain medical conditions.
Similar Supplements
Like isoleucine, leucine and valine are also BCAAs.
However, out of the three BCAAs, leucine is the primary activator of muscle protein synthesis. It has been suggested that isoleucine and valine compete for the same site as leucine in the intestinal and muscle cells. Therefore, using isoleucine and valine in combination with leucine can lower leucine uptake by intestinal and muscle cells.
How isoleucine and leucine work to lower blood sugar levels also differs. Whereas isoleucine lowered blood sugar levels without affecting insulin levels, leucine increased insulin levels.
Explainer
In the United States, the Food and Drug Administration (FDA) does not regulate supplements the way it regulates prescription drugs. That means some supplement products may not contain what the label says.
When choosing a supplement, look for third-party tested products and consult a healthcare provider, an RD or RDN, or a pharmacist.
Summary
Isoleucine is a BCAA crucial in protein synthesis and blood sugar regulation.
Some studies suggest a potential use for isoleucine and BCAAs in lowering blood sugar levels, reducing muscle damage and soreness, improving exercise fatigue, improving hepatic encephalopathy, and decreasing the risk of infections post-surgery.
Before starting isoleucine supplements, be sure to consult with your healthcare provider to determine if it is appropriate for you.
Frequently Asked Questions
What is isoleucine?
Protein has 20 amino acids; out of the 20, nine are essential amino acids. Essential amino acids are amino acids that cannot be produced by the body and must be acquired through dietary intake or supplementation. Three of the nine essential amino acids are classified as branched-chain amino acids (BCAAs) due to their chemical structure. Isoleucine is one of the three BCAAs (the other two are leucine and valine).
What does isoleucine do?
Isoleucine serves as a building block for protein synthesis or energy production and plays a role in regulating the following:
Blood sugar metabolism
Fat synthesis
Intestinal health
Immunity
Who should avoid isoleucine?
Isoleucine should be avoided in people who are pregnant or breastfeeding due to the lack of safety data in such a population. It should be used with caution in children.
People with maple syrup urine disease (MSUD), an inherited disorder affecting the proper breakdown of BCAAs, should avoid isoleucine due to the risk of the accumulation of toxic BCAAs byproducts that can lead to nerve and brain symptoms.
Caution should be taken for the following medical conditions:
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