Branched-chain amino acids

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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.
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