Isoleucine

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    Last Updated: October 13, 2023

    Isoleucine is one of the three branched-chain amino acids (BCAAs). It is an essential amino acid. Isoleucine is required for muscle protein synthesis, and it may help to reduce post-exercise muscle soreness and markers of muscle damage when taken as part of a BCAA supplement. However, whether isoleucine holds any special merit as a supplement on its own is unclear.

    Isoleucine is most often used for Muscle Gain & Exercise.

    What is isoleucine?

    Isoleucine is one of the three branched-chain amino acids (BCAAs), along with valine and leucine. As an essential amino acid, isoleucine needs to be consumed regularly and can be found naturally in dietary proteins like meat, fish, soy, and dairy.[4][5] Isoleucine serves as a building block for proteins, but it’s also thought to function as a signaling molecule in the body, involved in the regulation of protein, glucose, and lipid metabolism; glucose transport; and immune function.[6]

    What are isoleucine’s main benefits?

    Isoleucine is essential for muscle growth and may play a role in muscle recovery, similar to other essential amino acid, but it’s unclear whether supplementing isoleucine alone above the RDA provides any particular benefits.

    Isoleucine is necessary for the process of muscle protein synthesis, and BCAAs in general are thought to be particularly important for stimulating this process while also minimizing protein breakdown.[7][8] However, compared to leucine, isoleucine does not stimulate muscle protein synthesis to a significant degree, and ultimately, research suggests that optimal muscle protein synthesis is achieved when all nine essential amino acid are present.[9][10] In terms of muscle recovery, when isoleucine is taken as part of a BCAA supplemen,t it seems to reduce post-exercise muscle soreness and markers of muscle damage, but may not impact the recovery of muscle performance.[11][12][13]

    Animal studies suggest that isoleucine enhances the uptake of glucose by muscle cells and increases the breakdown of glucose into energy.[2] While theoretically this might be beneficial for exercise performance, studies providing isoleucine as part of a BCAA supplement have not consistently found a positive effect on performance, and isoleucine has generally not been studied alone.[13]

    What are isoleucine’s main drawbacks?

    Isoleucine is usually well-tolerated, but some people may experience gastrointestinal upset (e.g., nausea, diarrhea).[14] Importantly, these side effects have been observed when isoleucine was taken as part of a BCAA supplement; the potential side effects of isoleucine when supplemented alone are undetermined.

    Observational studies have found that increased levels of isoleucine in the blood are associated with certain health conditions, including insulin resistance,[15] type 2 diabetes,[16][15] cardiovascular disease,[17][18] and obesity.[19][20] Further research is needed to determine whether these elevated levels of isoleucine are a cause or an effect of these conditions.

    How does isoleucine work?

    Isoleucine is an amino acid used by the body during protein synthesis, which is required for muscle growth and recovery. In terms of glucose metabolism and transport, research in rodents suggests that isoleucine reduces blood glucose levels by enhancing the uptake of glucose by skeletal muscle cells, increasing the overall breakdown of glucose into energy, and reducing the amount of glucose produced by the liver (hepatic gluconeogenesis).[2][3]

    Dosage information

    The recommended daily allowance (RDA) of isoleucine established by the Institute of Medicine is 19 mg of isoleucine per kilogram of bodyweight (mg/kg) daily. This is the average amount of isoleucine that meets the nutritional requirements of most people.[1]

    Isoleucine can be supplemented individually, but it is more commonly taken as part of a BCAA or complete protein supplement (e.g., whey protein, soy protein). There is currently no strong evidence to support the use of isoleucine as a supplement alone and no well-established dosing.

    In rat studies, dosages of 0.3–0.45 mg/kg were effective for reducing blood glucose and increasing muscle cell glucose uptake.[2][3] This could be extrapolated to a human dose of 48–72 mg/kg (for a 150 lb person, 3.3–4.9 g), but these beneficial effects have not yet been clearly established in clinical trials.

    Frequently asked questions

    What is isoleucine?

    Isoleucine is one of the three branched-chain amino acids (BCAAs), along with valine and leucine. As an essential amino acid, isoleucine needs to be consumed regularly and can be found naturally in dietary proteins like meat, fish, soy, and dairy.[4][5] Isoleucine serves as a building block for proteins, but it’s also thought to function as a signaling molecule in the body, involved in the regulation of protein, glucose, and lipid metabolism; glucose transport; and immune function.[6]

    What are isoleucine’s main benefits?

    Isoleucine is essential for muscle growth and may play a role in muscle recovery, similar to other essential amino acid, but it’s unclear whether supplementing isoleucine alone above the RDA provides any particular benefits.

    Isoleucine is necessary for the process of muscle protein synthesis, and BCAAs in general are thought to be particularly important for stimulating this process while also minimizing protein breakdown.[7][8] However, compared to leucine, isoleucine does not stimulate muscle protein synthesis to a significant degree, and ultimately, research suggests that optimal muscle protein synthesis is achieved when all nine essential amino acid are present.[9][10] In terms of muscle recovery, when isoleucine is taken as part of a BCAA supplemen,t it seems to reduce post-exercise muscle soreness and markers of muscle damage, but may not impact the recovery of muscle performance.[11][12][13]

    Animal studies suggest that isoleucine enhances the uptake of glucose by muscle cells and increases the breakdown of glucose into energy.[2] While theoretically this might be beneficial for exercise performance, studies providing isoleucine as part of a BCAA supplement have not consistently found a positive effect on performance, and isoleucine has generally not been studied alone.[13]

    What are isoleucine’s main drawbacks?

    Isoleucine is usually well-tolerated, but some people may experience gastrointestinal upset (e.g., nausea, diarrhea).[14] Importantly, these side effects have been observed when isoleucine was taken as part of a BCAA supplement; the potential side effects of isoleucine when supplemented alone are undetermined.

    Observational studies have found that increased levels of isoleucine in the blood are associated with certain health conditions, including insulin resistance,[15] type 2 diabetes,[16][15] cardiovascular disease,[17][18] and obesity.[19][20] Further research is needed to determine whether these elevated levels of isoleucine are a cause or an effect of these conditions.

    How does isoleucine affect blood glucose and metabolic health?

    Isoleucine has a regulatory effect on glucose transport and metabolism in the body and has been suggested to have a hypoglycemic (blood sugar lowering) effect when taken before glucose/carbohydrates. While this has been observed in animals,[21] human clinical trials so far have shown inconsistent results, and the clinical relevance of this effect is questionable.[22][23][24]

    Alternatively, in vitro and animal studies suggest that BCAAs can induce insulin resistance[25] and that BCAA-restricted diets (especially isoleucine-restricted ones) can improve insulin sensitivity and weight status.[26][27] While some human observational data reports that increased consumption of BCAAs is associated with increased body mass index (BMI),[26] other research has found the opposite effect.[28][29] The long-term effects (both potentially positive and negative) of a BCAA-restricted diet in humans have been largely unexplored, and the few small and short-term trials that have been done have found inconclusive effects.[30][31]

    How does isoleucine work?

    Isoleucine is an amino acid used by the body during protein synthesis, which is required for muscle growth and recovery. In terms of glucose metabolism and transport, research in rodents suggests that isoleucine reduces blood glucose levels by enhancing the uptake of glucose by skeletal muscle cells, increasing the overall breakdown of glucose into energy, and reducing the amount of glucose produced by the liver (hepatic gluconeogenesis).[2][3]

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