What is isoleucine?
Isoleucine is an amino acid that is found in most proteins. Its structure makes it a branched-chain amino acid (BCAA). Isoleucine is one of the nine essential amino acids.
It has a role in hemoglobin synthesis and the production of red blood cells. It has been shown to help control blood sugar levels. Isoleucine is also associated with the detoxification of nitrogenous waste like ammonia. One of the main effects of isoleucine is its ability to stimulate protein synthesis and muscle growth.
People often get isoleucine mixed up with leucine which is also a branched-chain amino acid. Isoleucine is best described as the middle BCAA because it is more potent than Valine in stimulating protein synthesis but not as strong as leucine. It falls in the middle in terms of effects on muscle and performance improvements. Even though it is less potent than leucine, it should not be ignored, as it has some very powerful effects on the body and muscle.
Benefits of isoleucine
There are many benefits to taking isoleucine supplements or ensuring adequate intake from your diet. Many benefits are backed up by solid scientific research and not just anecdotal reports. L-isoleucine supplements are inexpensive, easy to take and offer many benefits. The growing list of benefits backed up by research is why many athletes and bodybuilders supplement with it. The increased production of protein and muscle and glucose uptake are just a few of the many benefits of this branched-chain amino acid. If you want to increase your training efficiency or improve post-workout muscular recovery, isoleucine and BCAAs may be just the supplement you have been in need of.
The following section will break into more detail the many benefits of supplementing with isoleucine.
Isoleucine by itself is not commonly known for its muscle-building properties. It is common knowledge that isoleucine, in combination with the other BCAA Leucine and Valine, is anabolic and can significantly enhance protein synthesis and muscle growth. Evidence is starting to come to light that isoleucine on its own has anabolic properties and can help increase muscle growth. A study using mice showed that isoleucine increased muscle mass and fat mass significantly.  Researchers showed that isoleucine stimulated myogenesis in the skeletal muscle. 
Other studies done with isoleucine have shown that it can shuttle glucose into the muscle cells.  The increased glucose uptake by the skeletal muscles helps with muscle growth by enabling the muscles to work harder for longer and fueling the muscle recovery process.
Some exciting studies with isoleucine demonstrate its benefits for the immune system. Several studies showed that isoleucine could increase the production of B-defensin.  B-defensins are peptides with antimicrobial properties produced by epithelial cells in the lungs, intestines, and skin. The epithelial cells produce these antimicrobial peptides, and they sit on the surface of the cells and kill pathogens that land on the cell surface.  B-defensins can kill bacteria that are Gram-negative or Gram-positive, enveloped viruses, and fungi.
Isoleucine has been linked in studies to the production of hemoglobin by the body.  Hemoglobin is a globular protein structure that is the component of red blood cells that carries oxygen. More studies are needed to establish if supplementing with isoleucine can increase hemoglobin and lead to a performance boost or benefit.
Glucose Uptake and blood sugar control
Improve performance and reduce fatigue
Isoleucine can benefit performance by increasing the muscle cell’s uptake of glucose. when the working muscle cells can get more glucose, they can work hard for longer and not rely on fat or amino acids for fuel.
These exact mechanisms of increased glucose uptake can help speed recovery from workouts by providing the muscle with the needed glucose to replenish glycogen stores and provide the required cellular energy to repair and build new proteins.
Side effects of isoleucine
There is no known toxicity for isoleucine in healthy individuals. Toxicity is only seen in individuals who have a genetic condition referred to as maple syrup urine disease. This is a condition in which the body cannot break down branched-chain amino acids.
There are very few if any side effects with isoleucine supplementation for most users. The most commonly experienced side effects are gastrointestinal in nature, such as:
Other less common side effects include:
- Skin whitening
- Blood pressure changes
The most effective dosage for isoleucine supplementation is between 3 to 6 grams. Some users adjust this up or down based on their needs, weight and activity level. Dosage is also often adjusted based on any gastrointestinal side effects. For new users, it is often recommended that lower doses be tried first and titrated upward if no side effects are seen.
Most athletes take multiple daily doses to maintain a steady supply of the amino acid to the body to reap the most benefit in performance, recovery or protein synthesis.
When is the best time to take isoleucine?
The general consensus is that isoleucine should be taken with meals. It should also be taken pre-workout and post-workout to get the greatest performance, and muscle growth benefits possible. Some users also supplement with it during their workouts or intra-workout. The timing of isoleucine is very user-specific, and you need to test what works best for you, your body and your specific goals.
- Red Meat
- Whey protein
- Black beans
- Pinto beans
- Lima beans
- Sunflower seeds
- Sesame seed
- Pumpkin seeds
Summary of Isoleucine
As you can see from the many benefits this amino acid has, it is very compelling as something you might want to take as a supplement. Even with all of its benefits, it is probably not beneficial to supplement with it alone. Isoleucine should be taken in combination with the other BCAAs to get the most benefit in terms of performance and muscle repair, and growth. Not to mention if you take all the branched-chain amino acids, you get all the benefits of isoleucine plus all the benefits of the other two BCAAs.
- Isoleucine increases muscle mass through promoting myogenesis and intramyocellular fat deposition – PubMed (nih.gov)
- Effects of isoleucine on glucose uptake through the enhancement of muscular membrane concentrations of GLUT1 and GLUT4 and intestinal membrane concentrations of Na+/glucose co-transporter 1 (SGLT-1) and GLUT2 | British Journal of Nutrition | Cambridge Core
- An essential amino acid induces epithelial beta -defensin expression – PubMed (nih.gov)
- Albumin and amino acids upregulate the expression of human beta-defensin 1 – PubMed (nih.gov)
- A peptide antibiotic from human skin | nature
- Specialization of Rabbit Reticulocyte Transfer RNA Content for Hemoglobin Synthesis (science.org)
- Isoleucine, a blood glucose-lowering amino acid, increases glucose uptake in rat skeletal muscle in the absence of increases in AMP-activated protein kinase activity – PubMed (nih.gov)
- Isoleucine, a potent plasma glucose-lowering amino acid, stimulates glucose uptake in C2C12 myotubes – PubMed (nih.gov)
- Effects of Leucine and Isoleucine Infused Intrapancreatically on Glucagon and Insulin Secretion | Endocrinology | Oxford Academic (oup.com)
The information in this article is not intended to be taken as medical advice. Always consult with your doctor before taking any supplements.