Branched-chain amino acids Natural Standard Bottom Line Monograph, Copyright © 2014 (www.naturalstandard.com). Commercial distribution prohibited. This monograph is intended for informational purposes only, and should not be interpreted as specific medical advice. You should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions. While some complementary and alternative techniques have been studied scientifically, high-quality data regarding safety, effectiveness, and mechanism of action are limited or controversial for most therapies. Whenever possible, it is recommended that practitioners be licensed by a recognized professional organization that adheres to clearly published standards. In addition, before starting a new technique or engaging a practitioner, it is recommended that patients speak with their primary healthcare provider(s). Potential benefits, risks (including financial costs), and alternatives should be carefully considered. The below monograph is designed to provide historical background and an overview of clinically-oriented research, and neither advocates for or against the use of a particular therapy Related Terms 2-Amino-3-methylbutanoic acid, 2-amino-3-methylbutyric acid, 2-amino-3-methylvaleric acid, 2-amino-4methylvaleric acid, 2-aminoisovaleric acid, (2S,3S)-2-amino-3-methylpentanoic acid, alpha-amino-betamethylvaleric acid, alpha-aminoisocaproic acid, alpha-aminoisovaleric acid, Aminoleban®, Amino-Mel hepa® + L-valine, BCAA, hard body BCAA (MLO Products), hepatic aid, hi-test muscle octane BCAA's (Anabol Naturals), Ile, isoleucine, large neutral amino acids, Leu, leucine, L-isoleucine, L-leucine, LNAAs, L-valine, (S)-2-amino-3-methylbutanoic acid, (S)-2-amino-4-methylpentanoic acid, Val, valine. Background Branched-chain amino acids (BCAAs) consist of three amino acids: leucine, isoleucine, and valine. BCAAs may be converted to glucose and therefore may be used as an energy source during exercise. Also, some evidence suggests that BCAAs may be used in making protein during muscle repair following exercise. BCAAs are most often used as a supplement for increased athletic performance and endurance. Preliminary research suggests that BCAAs may be helpful for muscle atrophy associated with bed rest, neurological disorders, in particular spinocerebellar degeneration, and tardive dyskinesia. However, more research is needed to confirm this. Scientific Evidence Uses These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified Grade healthcare provider. Chronic obstructive pulmonary disease (COPD) Supplementation with BCAAs may benefit patients with chronic obstructive pulmonary disease (COPD). However, more high-quality research is needed in this area. C Enhanced athletic performance BCAAs may increase athletic performance and endurance. Further high-quality research is needed. C Hepatic encephalopathy BCAAs may serve as a treatment for hepatic encephalopathy (confusion caused by liver failure). Further high-quality research is needed. C Hepatitis (alcoholic hepatitis) BCAAs have been suggested as a treatment for hepatitis (alcoholic hepatitis). Further high-quality research is needed. C Hormone regulation BCAAs may serve to regulate hormones. In preliminary research, BCAA supplementation was shown to prevent exercise-induced decreases in human growth hormone and testosterone concentrations. Further high-quality research is needed. C Immunomodulation BCAAs may regulate immune functioning. In preliminary research, BCAA supplementation during exercise affected white blood cells and immune cytokines after exercise. Further research is needed. C Liver cancer (hepatocellular carcinoma) BCAAs may serve as a treatment for liver cancer (hepatocellular carcinoma). In preliminary research, BCAA supplementation resulted in an improvement in clinical symptoms associated with resectioning in patients with hepatocellular carcinoma. However, more clinical trials are needed that study this effect in a larger sample size. C Liver cirrhosis BCAAs may improve symptoms associated with cirrhosis of the liver (scarring of the liver and poor liver function). However, due to various methodological issues, conclusive evidence for or against BCAA supplementation for this indication is lacking. More clinical trials are needed that study this effect in a larger sample size. C Muscle atrophy BCAAs may prevent muscle atrophy (wasting) associated with prolonged bed rest. In preliminary research, BCAA supplementation during bed rest decreased nitrogen loss during short-term bed rest. More clinical trials are needed. C Neurological disorders (spinocerebellar degeneration) BCAAs may improve brain disorder symptoms. However, more clinical trials are needed. C Phenylketonuria BCAAs may improve symptoms associated with phenylketonuria (PKU; a metabolic genetic disorder). Preliminary research suggests that BCAA supplementation increased brain function in patients with PKU. More clinical trials are needed. C Tardive dyskinesia BCAAs may improve symptoms associated with tardive dyskinesia (a disorder of involuntary movements). Preliminary research provides good indication that BCAAs may be beneficial for this indication. However, more clinical trials are needed. C Total parenteral nutrition (TPN) BCAAs may provide additional support to patients on TPN. However, clinical trials with a larger sample size are still required. C Amyotrophic lateral sclerosis (ALS) ALS is a neurodegenerative disease characterized by the degeneration of motor neurons. There seemed to be a lack of an effect after BCAA supplementation, and increased death and reduced lung function. Evidence is lacking for or against the use of BCAAs in treating ALS. D Tradition/Theory The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below. Anorexia (associated with cancer), burns, concentration enhancement, depression, diabetes, fatigue, liver disease (hypoalbuminemia), metabolic disorders (subacute necrotizing encephalopathy, maple syrup urine disease), muscle wasting (sarcopenia). Dosing The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy. Adults (18 years and older) General: The daily dosage of BCAAs is 25-65 milligrams per kilogram of body weight. Amyotrophic lateral sclerosis (ALS): BCAA packets containing 1.2g of L-leucine, 0.6g of L-isoleucine, and 0.6g of L-valine (Friliver®, Bracco S.p.A) have been given as two packets by mouth five times daily before meals for 12 months. BCAA 26.4 grams (12 grams of leucine, eight grams of isoleucine, 6.4 grams of valine powder) has been taken by mouth daily for six months. BCAA (12 grams of leucine, eight grams of isoleucine, and 6.4 grams of valine) has been taken for eight days. BCAA powder (three grams of leucine, two grams of isoleucine, and 1.6 grams of valine) has been taken by mouth four times daily for 12 months. Enhanced athletic performance: BCAAs (Roeder 1956 Pharmaceuticals; 0.3 grams of leucine, 0.15 grams of isoleucine, and 0.15 grams of valine), at 0.2 grams per kilogram of body weight, half before and half after training, have been taken by mouth daily for eight weeks. Six grams or 18 grams of BCAAs as a single dose during exercise has been taken by mouth. Seven grams of BCAAs (MLO, United States) in vanilla pudding has been taken one hour prior to exercise. The following dosages have been used: 1,500 milliliters of a drink containing 0.4% BCAAs and 4% carbohydrate for six days; four 250-milliliter aliquots of a 12 grams per liter BCAA solution at 30-minute intervals prior to exercise, with an additional 150 milliliters consumed every 15 minutes throughout exercise, by mouth; BCAA packets containing 1.2g of L-leucine, 0.6g of L-isoleucine, and 0.6g of L-valine (Friliver®, Bracco, Italy) have been given as two packets by mouth three times daily for 21 days (an average of 4.8 envelopes daily were taken by mouth); 22.4 grams of BCAAs (7.8 grams of leucine, 3.4 grams of isoleucine, and 11.2 grams of valine) once daily for six days, by mouth; BCAA supplementation daily for six weeks (16, two, and two grams of leucine, isoleucine and valine, respectively), by mouth; 150 milliliters of BCAA solution (45% leucine, 30% valine, and 25% isoleucine) at a concentration of 100 milligrams per 1.5 liter, at different times, by mouth; 2,500 milliliters of BCAAs (0.8% BCAAs in a 3.5% carbohydrate solution) daily for three days, by mouth; a 6% carbohydrate solution containing seven grams of L-1 BCAAs, by mouth; 0.2 grams per kilogram of Friliver® (Bracco Industria Chimica SpA Milano, Italy) twice daily for one month, providing four kilocalories of energy per gram and containing 12% leucine, 6% isoleucine, and 6% valine, by mouth; a BCAA beverage containing 480 milligrams of isoleucine, 1.22 grams of leucine, and 730 milligrams of valine (10 kilocalories) before and at 60 minutes of exercise; a BCAA beverage every 30 minutes during peak exercise to exhaustion; 77 milligrams per kilogram of BCAAs by mouth prior to exercising the knee extensor muscles of one leg for 60 minutes; 300 milliliters of artificially sweetened and flavored water with BCAAs (3.5 grams of leucine, 2.1 grams of isoleucine, and 1.7 grams of valine) mixed into water for three days; 3.5 liter of a 5% carbohydrate drink with 18 grams of BCAAs (50% valine, 35% leucine, 15% isoleucine); and 7.5-16 grams of BCAAs total (50% valine, 35% leucine, 15% isoleucine in a 5% carbohydrate solution), by mouth. Hepatic encephalopathy: BCAAs, at 0.24 grams per kilogram (1.2 grams of leucine, 0.6 grams of isoleucine, 0.6 grams of valine), divided into three doses, has been taken by mouth daily for three months. Thirty grams of BCAAs has been taken by mouth for two 14-day periods. One gram per kilogram of an amino acid mixture with 40% branched-chain contents has been taken by mouth daily for a maximum of 16 days. BCAAs, at 0.25 grams per kilogram, have been taken by mouth daily for one week. BCAA solution in 20% glucose has been taken intravenously. BCAAs, at 20 grams per liter in 5% glucose, have been taken intravenously for 20 hours daily for up to five days. Hepatitis (alcoholic hepatitis): 60-80 grams of total amino acids containing 51% BCAAs have been taken daily by mouth. Two thousand kilocalories and 10 grams of nitrogen (either from a conventional protein source or a BCAA-enriched formulation resulting in 20 grams of BCAAs daily) have been by mouth daily for up to three weeks or until death or discharge. Two thousand kilocalories and 10 grams of nitrogen (either from a conventional protein source or a BCAA-enriched formulation resulting in 20 grams of BCAAs daily) have been taken daily for up to three weeks via feeding tube or until death or discharge. Two thousand kilocalories and 10 grams of nitrogen (either from a conventional protein source or a BCAA-enriched formulation resulting in 20 grams of BCAAs daily) have been taken intravenously daily for up to three weeks or until death or discharge. 60-80 grams of total amino acids containing 51% BCAAs has been taken intravenously daily. Hepatocellular cancer: BCAA-enriched TPN (30% BCAA) (Amiparen® 10% solution, Otsuka Pharmaceuticals, Osaka, Japan) has been used parenterally from day of surgery to six days after. Liver cancer (hepatocellular carcinoma): Aminoleban® EN (Otsuka Pharmaceutical Company, Tokyo, Japan) 100 grams has been taken by mouth daily for a minimum of one year. Liver cirrhosis: BCAA granules (LIVACT, Ajinomoto Co., Inc., Tokyo, Japan) (4.15 grams) have been taken by mouth three times daily for least one year. A BCAA-enriched nutrient mixture (210 kilocalories of energy, 13.5 grams of protein, 3.5 grams of fat, and trace minerals and vitamins) has been taken by mouth for three months. BCAA granules (14.22 grams) have been taken by mouth daily for two years. BCAAs (Friliver; Bracco spa, Milan, Italy) (14.4g) has been taken by mouth daily for one year. Muscle atrophy: 30 millimoles of BCAAs (Sigma Inc., St. Louis, MO) has been taken by mouth daily for six days. Neurological disorders (spinocerebellar degeneration): Two hundred milliliters of BCAA solution has been taken for seven days (the form and frequency are unclear). Also, 1.5, three, or six grams of BCAAs (Livact®, Ajinomoto, Tokyo) has been taken three times daily for four weeks. Tardive dyskinesia: Up to 222 milligrams of BCAAs per kilogram of body weight, three times daily by mouth for three weeks. Children (under 18 years old) Not enough scientific data available. Safety The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects. Allergies BCAAs appear to be well tolerated. Side Effects & Warnings Use cautiously in patients with amyotrophic lateral sclerosis (ALS), due to possible increases in death in ALS patients. Use cautiously in patients with diabetes or hypoglycemia, as glucose and amino acid together increased insulin production and changed blood glucose. Use cautiously in patients using thyroid agents, as thyroid hormone medications may decrease the rate of branched-chain amino acid metabolism. Increased T3 levels and an increased T3-to-T4 ratio have been shown. Use cautiously in amounts greater than those commonly found in the diet in pregnant and nursing women, due to a lack of safety data. Use cautiously in amounts greater than those commonly found in the diet in children, due to a lack of safety data. Pregnancy & Breast Feeding Branched-chain amino acids are likely safe when taken by mouth in levels normally found in proteincontaining foods. There is not enough reliable information about the safety of medicinal use during pregnancy or lactation. Possible significant uptake from the umbilical cord has been shown. Information on BCAA's effects on lactation is lacking in the National Institute of Health's Lactation and Toxicology Database (LactMed). Interactions Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Interactions with Drugs Branched-chain amino acids may change blood sugar levels. Caution is advised when using medications that may also change blood sugar. People taking drugs for diabetes by mouth or taking insulin should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary. Branched-chain amino acids may also interact with agents that suppress the immune system, analgesics, anesthetics, caffeine, cancer agents, corticosteroids, diazoxide, epinephrine, exercise performanceenhancing agents, human growth hormone, insulin, recombinant human erythropoietin, and thyroid agents. Interactions with Herbs & Dietary Supplements Branched-chain amino acids may change blood sugar levels. Caution is advised when using medications that may also change blood sugar. People taking drugs for diabetes by mouth or taking insulin should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary. Branched-chain amino acids may also interact with agents that affect the immune system, analgesics, caffeine, cancer agents, creatine, exercise performance-enhancing agents, glutamine, and thyroid agents. Natural Standard Monograph (www.naturalstandard.com) Copyright © 2014 Natural Standard. Commercial distribution or reproduction prohibited. The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.