Key Takeaways (expand)
- Isoleucine is one of the nine essential amino acids, and one of the 20 amino acids that the body uses to create protein.
- Along with valine and leucine, isoleucine is a branched-chain amino acid, or BCAA—meaning it possesses a unique molecular structure with a branched side-chain.
- As a BCAA, isoleucine plays a particularly important role in muscle tissue repair, lean mass preservation, and protein synthesis.
- Isoleucine is both ketogenic and glucogenic—meaning the body can metabolize it into either ketone bodies or glucose.
- This amino acid can actually increase glucose uptake and utilization (especially during exercise), without directly stimulating insulin secretion!
- Isoleucine is key for the production of hemoglobin—the oxygen-carrying pigment in red blood cells.
- Its role in hemoglobin production makes isoleucine beneficial for recovering from anemia and blood loss.
- Due to being highly incorporated into immune cells and increasing the expression of host defense peptides, isoleucine is critical for the function of the immune system.
- Isoleucine also plays an important metabolic role in detoxing nitrogenous waste, especially ammonia.
- Although animal studies suggest isoleucine could have a beneficial effect on blood sugar regulation, energy metabolism, and diabetes, evidence in humans is mixed.
- Isoleucine is abundant in high-protein foods like eggs, poultry, beef, pork, seafood, dairy, and legumes (particularly soybeans).
Isoleucine (symbol Ile) is one of the 20 amino acids used by the body to create protein, and one of only nine that are essential (meaning we must obtain them from food). As its name implies, isoleucine is an isomer of leucine, meaning it has the same chemical formula but a different arrangement of atoms. It was first discovered in hemoglobin in 1903, by a German chemist named Felix Ehrlich.
Along with being used for protein biosynthesis, isoleucine plays an important role in immune function, energy regulation, and hemoglobin production.
The best sources of isoleucine are high-protein foods like eggs, poultry, beef, pork, seafood, dairy, and legumes (particularly soybeans). It can also be produced by some microorganisms in the gut microbiome.
The Biological Roles of Isoleucine
Broadly, amino acids are molecules with the molecular formula of R-CH(NH2)-COOH-NH2, where -NH2 is the basic amino group, COOH is an acidic carboxyl group, and R represents a molecular unit called a side chain. That side chain is unique for each amino acid, and its chemical properties create different classes of amino acids: nonpolar and neutral, polar and neutral, polar and acidic, and polar and basic.
Although hundreds of amino acids exist, only 20 of them are used for what amino acids are arguably most known for: forming the building blocks of proteins. Proteins are not only an essential macronutrient in the human diet; they’re molecules that perform most of the various functions of life. In addition to being major structural components of cells and tissues, proteins have incredibly diverse roles that range from driving chemical reactions (e.g., enzymes) to signaling (e.g., some types of hormones) to transporting and storing nutrients. Proteins are synthesized within cells through a two-phase process of transcription and translation, during which amino acids get linked together to form long chains (spanning anywhere from 20 to over 2,000 amino acids in length!).
So, while all proteins are made of amino acids, not all amino acids are used for making proteins! We use the term proteinogenic amino acids to refer specifically to the amino acids that get encoded into our DNA and incorporated into proteins. Meanwhile, non-proteinogenic amino acids do neither of these things (although they still have some very important biological roles!).
Amino acids can be further classified based on whether we can create them in our bodies, or need them from our diet. Essential amino acids are amino acids that can only be obtained from foods; these include histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. Non-essential amino acids are amino acids our bodies can synthesize metabolically from other molecules; these include alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, proline, serine, and tyrosine. And, some amino acids are conditionally essential, meaning our bodies can normally make them, but some circumstances (like illness or stress) can limit their synthesis and create a dietary requirement. These include arginine, cysteine, glutamine, tyrosine, glycine, ornithine, proline, and serine.
As both a proteinogenic and essential amino acid, isoleucine can be incorporated into proteins, and must be consumed from foods in order to meet our body’s needs. Isoleucine is both glucogenic and ketogenic, meaning it can be metabolized into either glucose or ketone bodies.
Isoleucine is one of three branched-chain amino acids, or BCAAs—the other two being leucine and valine. BCAAs possess a unique molecular structure with a branched side-chain (hence their name!), and play a particularly important role in muscle protein synthesis. They also comprise a significant portion of muscle tissue and body protein.
Like other BCAAs, isoleucine’s role in muscle protein synthesis means it can help repair muscle tissue and preserve muscle mass. Its ability to stimulate protein synthesis is higher than that of valine, but lower than that of leucine.
But, isoleucine also has some attributes that make it unique among the BCAAs! For one, unlike leucine and valine (which tend to suppress glucose uptake in cells), isoleucine is able to increase glucose uptake and utilization, especially during exercise. These actions depend on the activation of phosphoinositide 3-kinases (PI3K) and protein kinase C (PKC), rather than the classical signaling pathways involving the insulin receptor or AMP-activated protein kinase activation. In fact, unlike leucine, isoleucine doesn’t directly stimulate insulin secretion from the pancreas. Its only impact on insulin comes indirectly, following its conversion to glucose.
Isoleucine is a key player in the creation of hemoglobin—the oxygen-carrying pigment in red blood cells. It’s also highly incorporated into immune cells such as lymphocytes, eosinophils, and neutrophils, making it critical for the function of the immune system. Some experiments even show it can induce the expression of host defense peptides (such as beta-defensins) involved in regulating innate and adaptive immunity.
Isoleucine also plays an important metabolic role in detoxing nitrogenous waste, especially ammonia. More specifically, isoleucine helps provide the carbon skeleton for the synthesis of glutamate and glutamine, which are then used for the detoxification of ammonium.
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Isoleucine in Health and Disease
Evenidence suggests that isoleucine could play a helpful role in metabolic conditions and immunity, though its effects in humans aren’t fully confirmed.
Isoleucine and Diabetes
Given its ability to increase the uptake of glucose by cells, isoleucine has been studied for its effects on blood sugar regulation, energy metabolism, and diabetes. Animal models suggest a beneficial role here: in rodents, ongoing isoleucine supplementation can help prevent diet-induced weight gain and slightly improve insulin sensitivity, while short-term supplementation appears to improve glucose tolerance.
However, human studies haven’t shown a clear benefit! For example, observational research shows that higher isoleucine intake is associated with increased BMI, while higher blood levels of isoleucine are associated with higher risk of type 2 diabetes (of course, cause and effect can’t be determined from these findings alone). Similarly, controlled trials have been mixed: some have found that isoleucine has no effect on blood sugar levels after a high-carbohydrate meal, while others suggest it can reduce them by slowing gastric emptying. In all, there isn’t sufficient evidence that isoleucine is specifically beneficial for improving blood sugar regulation or protecting against diabetes.
Isoleucine and Anemia
Due to its importance in hemoglobin production, isoleucine can play a beneficial role in recovering from blood loss and anemia, helping the body more quickly rebuild red blood cells.
Isoleucine and Immunity
Although individual BCAAs haven’t been studied specifically here, studies suggest that BCAAs in general could improve immune function—especially under circumstances that normally suppress it. For example, studies of triathletes show that BCAA supplementation helps prevent the reduction in plasma glutamine concentrations usually seen after intense long-duration exercise, while also increasing the body’s lymphocyte response and cytokine production (which are usually suppressed after exercise). Similarly, BCAA-supplemented athletes report lower incidence of infection, suggesting these changes in post-exercise immunity really are protective. However, it’s hard to say whether these effects are owed to individual BCCAs or their synergistic activity; more research is needed!
Isoleucine and Maple Syrup Urine Disease
For some people, even normal intakes of any of the branched-chain amino acids can be problematic. A rare genetic disorder called maple syrup urine disease (MSUD)—named for the sweet, maple-syrup-like odor it produces in the urine and sweat—occurs due to a deficiency of enzymes in the branched-chain alpha-keto acid dehydrogenase complex. Normally, the body uses these enzymes to break down the branched-chain amino acids. When a deficiency in this enzyme complex occurs, it leads to an abnormal buildup of leucine, isoleucine, and valine (as well their toxic byproducts) in the blood and urine. In people born with severe maple syrup urine disease (little to no enzyme activity), this buildup happens so quickly that symptoms begin manifesting in the first few days after birth! In infants, this includes neurological dysfunction, irritability, poor feeding, abnormal movements, spasticity, and an eventual progression to seizures and coma; if left untreated, brain damage occurs, and the condition becomes fatal within weeks or months. In some forms of this disorder, branched-chain alpha-keto acid dehydrogenase activity is slightly higher, and maple syrup urine disease may go undiagnosed until later in childhood. In any case, people born with this particular enzyme deficiency must strictly monitor their branched-chain amino acid intake for life.
Didn’t know isoleucine was this important? Maybe your friends will enjoy this too!
Health Effects of Isoleucine Deficiency
Although fairly uncommon, isoleucine deficiency can result due to malabsorption issues, chronically low protein intake, or advanced age. When it occurs, deficiency shows up as symptoms such as muscle wasting and tremors.
How Much Isoleucine Do We Need?
The recommended intake for isoleucine is 20 mg per kg (9.1 mg per lb) of body weight daily for most adults. In order to achieve the health benefits seen in some studies, consuming 48 to 72 mg per kg (22 to 33 mg per lb) of body weight may be necessary!
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