BCAAs are among the most studied amino acids in humans: in a Japanese trial involving 646 patients with cirrhosis, approximately half received 12 g per day for a planned duration of two years. Conversely, an Italian trial conducted in patients with amyotrophic lateral sclerosis was stopped in 1993: 24 deaths under BCAAs, compared to 13 under placebo. Between these two extremes, what risk does a healthy person who takes a few grams around their workout sessions run?
This guide reviews each risk based on studies identified via PubMed, with its actual frequency and a verdict on four levels: established, rare, theoretical, or misconception. Benefits and dosage are covered in our article BCAAs: benefits, dosage and usefulness.
What is reported : from 3 to 29 g per day for a few weeks in athletes, no tolerance problems are reported, but adverse effects have rarely been investigated. In cirrhotic patients treated for encephalopathy, orally or by infusion, nausea and diarrhea are more frequent in one of the two analyses, without an increase in serious adverse effects. Beyond 500 mg of leucine per kilogram per day, blood ammonia exceeds normal levels.
Signal or theory : elevated blood BCAAs are associated with diabetes, but genetic studies point to either a defect in BCAA degradation or insulin resistance itself, and none implicate supplementation; leucine alone as a supplement did not modify blood glucose at 3 and 6 months. Two clear contraindications exist: maple syrup urine disease and amyotrophic lateral sclerosis. Levodopa, pregnancy and kidney disease require medical advice.
- BCAAs: what we actually swallow
- Tolerance in trials
- Digestive disorders and sweeteners in powder
- Leucine and ammonia: where is the threshold
- BCAAs, insulin and diabetes: association or cause?
- The liver: a treatment, not a threat
- The kidneys: limited data, no signal
- Amyotrophic lateral sclerosis: the signal to know
- Brain, serotonin, sleep and mood
- Maple syrup, levodopa, pregnancy: the contraindications
- Isolated BCAAs or complete proteins
- Risk table and safety rules
- Frequently asked questions
BCAAs: what we actually swallow
BCAAs, for branched-chain amino acids, are leucine,isoleucine and valine, three essential amino acids that the body obtains from meat, fish, eggs, dairy products and legumes. A supplement therefore brings nothing foreign to the body, but a concentrated quantity, isolated from other amino acids.
Unlike most amino acids, they are first broken down in the muscle rather than in the liver, by an enzymatic complex called BCKAD. When this complex fails for genetic reasons, BCAAs accumulate and become toxic: this is maple syrup urine disease, discussed below.
When consumed alone, they quickly enter the bloodstream: in 10 trained young men, 5.6 g of BCAA increased blood leucine and isoleucine by approximately 300%, with a peak at 30 minutes. This is why competition with other amino acids to enter the brain concerns isolated BCAAs more than a steak.
Established : repeatedly observed in controlled trials. : isolated cases or infrequent effect, uncertain causality. : cas isolés ou effet peu fréquent, causalité incertaine. Theoretical : plausible or observed in animals, not demonstrated in humans at usual doses. Common misconception : tested and not confirmed.
Tolerance in trials
In athletes. The most recent meta-analysis on recovery, published in 2024, combined 18 randomized trials and 331 healthy participants, with 3.15 to 29.3 g of BCAA per day for 1 to 28 days. It reports no analysis of adverse effects, which recovery trials rarely describe: the absence of signal mainly reflects short-term exposures in young volunteers, predominantly men. Our BCAA 2.1.1 in capsules provide 3 g per day, near the lower end of this range.
In seniors. Two Dutch trials gave 2.5 g of leucine at each meal (7.5 g per day) to men aged 71 years. In 30 healthy men, 3 months changed neither insulin sensitivity, nor glycated hemoglobin, nor lipids; in 60 type 2 diabetics, 6 months did not change glycated hemoglobin (7.1% versus 7.2% under placebo), nor muscle mass or strength.
In patients. In a 6-month trial in 95 patients with amyotrophic lateral sclerosis, of whom 31 received BCAA, 26.4 g per day were judged "well tolerated," despite a lower detailed respiratory signal. In Japan, 28 dialyzed patients took 12 g per day for 6 months, and in a trial involving 646 cirrhotic patients, approximately half received 12 g per day for a planned duration of 2 years, with good adherence.
| Population | Dose and duration | What was observed |
|---|---|---|
| 331 healthy athletes, 18 trials | 3.15 to 29.3 g per day, 1 to 28 days | Adverse effects not analyzed |
| 30 men aged 71 years healthy | 7.5 g of leucine per day, 3 months | Insulin, blood sugar and lipids unchanged |
| 60 men aged 71 years type 2 diabetics | 7.5 g of leucine per day, 6 months | Glycated hemoglobin 7.1% versus 7.2% under placebo |
| 28 dialyzed patients over 70 years of age | 12 g per day, 6 months | Appetite and albumin improved |
| 646 randomized cirrhotic patients | 12 g per day, up to 2 years | Fewer serious events, good adherence |
| 95 patients with ALS, of whom 31 received BCAA | 26.4 g per day, 6 months | Well tolerated, but faster respiratory decline |
Trials in athletes report no problems, but last a few weeks at most. Data over several months concern leucine alone in seniors, or patients monitored by a physician.
Digestive disorders and sweeteners in powder form
This is the best documented adverse effect, but in patients. The Cochrane review on hepatic encephalopathy, a cerebral complication of cirrhosis, pooled 16 trials and 827 participants: in the fixed-effects model, BCAAs multiplied the risk of nausea and vomiting by 5.56 (from 2.93 to 10.55); in the more conservative random-effects model, the difference was no longer significant. According to the authors, BCAAs did not increase serious adverse effects, but were associated with nausea and diarrhea.
In 827 patients, cirrhotic in 15 of 16 trials, BCAAs improved encephalopathy (relative risk of 0.73), with no effect on mortality.
Gluud LL, Dam G, Les I, et al. Cochrane Database Syst Rev 2017;5(5):CD001939. DOI : 10.1002/14651858.CD001939.pub4
In the one-year Italian trial in 174 patients with advanced cirrhosis, "long-term adherence was poor," write the authors, who call for new formulations. In athletes, these effects are poorly documented, due to lack of research.
What about sweeteners? In a trial published in 2022, 120 healthy adults took saccharin, sucralose, aspartame, or stevia for two weeks: each modified the microbiota, and saccharin and sucralose impaired the glycemic response, with large differences between individuals. Clinical consequences remain to be established. Our BCAA 2.1.1 powder contains natural flavors and a sweetener, at 5 g per serving; the HPMC vegetable capsule version is taken with a large glass of water.
Nausea, vomiting, and diarrhea are documented in cirrhotic patients treated for encephalopathy, by oral route or infusion, with a significant increase in only one of two analyses. In healthy individuals, they are possible but poorly described.
Leucine and ammonia: where is the threshold
No threshold is established for the three BCAAs together, but a Canadian team sought that of leucine, by increasing the dose in increments.
In 5 men aged 20 to 35 receiving up to 25 times the average leucine requirement, blood ammonia exceeded normal beyond 500 mg per kilogram per day. The authors propose this figure, approximately 35 g per day, as a prudent estimate of the threshold in acute conditions.
Elango R, Chapman K, Rafii M, et al. Am J Clin Nutr 2012;96(4):759-767. DOI : 10.3945/ajcn.111.024471
In 6 men aged 72, ammonia exceeded normal by 35 µmol/L beyond 550 mg per kilogram per day. In their review, researchers recommend for seniors 500 mg per kilogram, or cautiously 351 mg per kilogram, approximately 24.5 g per day for 70 kilos. These studies are acute and involve a few men: long-term studies remain necessary.
The 6 daily capsules of our BCAA 2.1.1 provide 1.5 g of leucine, approximately 23 times less than 35 g. Two servings of our powder, or 10 g in the lemon version, provide 4.3 g, nearly 6 times less than the prudent estimate of 24.5 g.
Ammonia during exercise. The breakdown of BCAAs in muscle releases nitrogen. In 9 trained cyclists over 100 km, ammonia was higher with glucose and BCAA than with glucose alone or placebo, for identical performance (157.2 minutes versus 160.1 and 159.8). In 8 men cycling in the heat, a beverage with 12 g of BCAA per liter increased ammonia throughout the effort, without endurance gain. None of these studies report symptoms related to this increase.
The increase in ammonia is established at very high doses and during prolonged exercise, without demonstrated clinical consequence. Doses of 3 to 10 g per day remain well below the measured thresholds.
BCAA, insulin, and diabetes: association or cause?
A meta-analysis of 8 cohorts comprising 8,000 people, of which 1,940 developed type 2 diabetes, associates an increase of one standard deviation in blood leucine, isoleucine, or valine with a risk approximately 35% higher (relative risk of 1.36 for leucine). A 2022 update, involving 71,196 participants, finds BCAAs among numerous metabolites associated with diabetes, with strong heterogeneity for some metabolites.
In three American cohorts followed for up to 32 years, with 16,097 diabetes cases, the fifth of participants who ate the most BCAAs had a risk 11 to 13% higher than those who ate the least. These are dietary intakes and associations: a high meat eater differs from a low meat eater on many other points.
A cohort observes that two phenomena occur together, without saying which causes the other: elevated BCAAs could promote insulin resistance, or could simply be a sign of it if the latter slows their breakdown.
Genetic studies, called Mendelian randomization, attempt to settle this. An analysis involving 47,877 diabetes cases and 267,694 controls concludes results compatible with a causal role of metabolism of BCAAs: the variants involved, especially near the PPM1K gene, slow their breakdown. The message concerns less efficient breakdown, not intake.
In 1,321 Danish participants and in genetic data from over 70,000 people, variants that elevate BCAAs were not associated with insulin resistance, whereas insulin resistance variants elevated BCAAs. Conclusion of the authors: insulin resistance increases BCAAs, not the other way around.
Mahendran Y, Jonsson A, Have CT, et al. Diabetologia 2017;60(5):873-878. DOI : 10.1007/s00125-017-4222-6
And the trials? The two leucine trials described above neither impaired insulin sensitivity nor glycated hemoglobin, and after 5.6 g of BCAA insulin did not differ from placebo. In well-controlled diabetics, a diet depleted in BCAAs for 4 weeks did not change insulin sensitivity measured by clamp, the reference method, but reduced postprandial insulin secretion by 28% and improved postprandial glucose sensitivity index by 24%; the authors request longer-term studies.
In mice, very high BCAA diets caused hyperphagia, obesity, and shorter lifespan, effects that disappeared if mice were prevented from overeating: not necessarily a direct toxicity, according to the authors. To act on your blood sugar, our article on elevated blood sugar reviews the mechanisms studied.
Elevated blood BCAAs are a marker of diabetes risk. Genetics point to a defect in degradation or insulin resistance itself, and two trials of leucine alone, 7.5 g per day for 3 and 6 months in elderly men, did not worsen blood glucose levels. The risk for a healthy adult is theoretical.
The liver: a treatment, not a threat
The question is posed in reverse: BCAAs have been studied for decades as nutritional treatment for liver disease.
In 646 patients with decompensated cirrhosis, approximately half receiving BCAAs, 12 g of BCAAs per day for a planned duration of 2 years (median follow-up of 445 days), reduced by one-third serious events (death, liver cancer, variceal rupture, worsening hepatic insufficiency) compared to a controlled diet, with a hazard ratio of 0.67.
Muto Y, Sato S, Watanabe A, et al. Clin Gastroenterol Hepatol 2005;3(7):705-713. DOI: 10.1016/s1542-3565(05)00017-0
In the Italian trial of 174 patients, BCAAs reduced serious events over one year compared to lactalbumin (odds ratio of 0.43), decreased hospitalizations and improved Child-Pugh score. We identified no published cases of liver damage attributed to BCAAs alone in a healthy person: the risk is not documented. In case of liver disease, BCAAs are part of medical management, including dosing and monitoring.
The trials, conducted in cirrhotic patients, show no liver damage; none involved healthy individuals.
The kidneys: limited data, no signal
No identified trial measured renal function in healthy people taking BCAAs alone. The closest data concerns protein: a meta-analysis of 28 trials and 1,358 adults without kidney disease found no difference in glomerular filtration rate decline between high-protein diets (at least 1.5 g per kilogram, 20% of energy or 100 g per day) and normal or low-protein diets. These are dietary proteins, not BCAA supplements.
In 28 hemodialyzed patients over 70 years old, malnourished, 12 g of BCAAs per day for 6 months improved appetite; in the 14 patients treated first, albumin increased from 3.31 to 3.93 g/dL.
Hiroshige K, Sonta T, Suda T, et al. Nephrol Dial Transplant 2001;16(9):1856-1862. DOI: 10.1093/ndt/16.9.1856
No adverse signal is reported, but these patients were under medical supervision: in case of chronic kidney disease, the decision is up to the nephrologist.
Nothing indicates that BCAAs damage healthy kidneys.
Amyotrophic lateral sclerosis: the signal to know about
Amyotrophic lateral sclerosis, or ALS, destroys motor neurons. BCAAs were tested at high dose in two controlled trials without success.
Patients with ALS received daily 12 g of leucine, 6 g of isoleucine and 6 g of valine, or placebo. After enrollment of 126 patients, there were 24 deaths under BCAAs compared to 13 under placebo: this excess mortality, with no effect on disability, led the safety committee to stop the trial.
The Italian ALS Study Group. Neurology 1993;43(12):2466-2470. DOI: 10.1212/wnl.43.12.2466
The second trial, American, compared in 95 patients over 6 months BCAAs (26.4 g per day, 31 patients), threonine and placebo. No benefit appeared, and respiratory capacity declined approximately 2.5 times faster under BCAAs and threonine than under placebo. According to the authors, chance is possible, but a harmful effect "cannot be excluded".
In 24 patients from the Italian trial, blood BCAAs were multiplied by 3 to 6 under treatment, their entry into the brain increased by 10 to 40% and that of aromatic amino acids decreased. Researchers suggest that this imbalance "could" worsen symptoms, an unproven hypothesis.
This signal concerns patients with ALS, at 24 to 26.4 g of BCAAs per day, eight times or more a typical dose of 3 g. It says nothing about healthy people. But in case of ALS, two unfavorable trials and no benefit are sufficient: BCAA supplements should be avoided, except on the neurologist's recommendation.
Brain, serotonin, sleep and mood
To enter the brain, BCAAs use the same transporter as tryptophan, a precursor of serotonin, and tyrosine, a dopamine precursor. This is the basis of the central fatigue hypothesis: during prolonged exercise, the ratio between free tryptophan and BCAAs increases, which would favor serotonin and fatigue. A 2001 review reports a decrease in perceived effort and mental fatigue in some trials, with physical benefit only in a few situations. In 10 endurance athletes, drinks containing 6 or 18 g of BCAAs per liter reduced the estimated tryptophan entry into the brain by 8 to 12%, without changing time to exhaustion; in 13 men and women cycling in heat, this time increased from 137.0 to 153.1 minutes.
Sleep. Less tryptophan in the brain could theoretically impact serotonin, then melatonin. But we identified no trials measuring sleep after BCAA intake, and the estimated reduction of 8 to 12% with high doses suggests not to overstate concerns. Taking them around training rather than at bedtime sidesteps the issue; our guide when to take BCAAs details the timing.
In 25 manic phase patients, 60 g of BCAAs per day for 7 days reduced symptoms within the first 6 hours compared to placebo; the authors attribute this to reduced tyrosine availability to the brain.
Scarna A, Gijsman HJ, McTavish SF, et al. Br J Psychiatry 2003;182:210-213. DOI: 10.1192/bjp.182.3.210
This trial does not describe a danger, but shows that at 60 g per day, 20 times a typical dose, BCAAs can have a measurable psychic effect. In case of monitored mood disorder or treatment affecting serotonin or dopamine, it's better to discuss it with your doctor, as with Griffonia (see our article on 5-HTP risks).
Competition with tryptophan and tyrosine is established, an effect on mania was observed in a small trial at 60 g per day, and no trial measured sleep. At typical doses, the risk remains theoretical.
Maple syrup, levodopa, pregnancy: contraindications
Maple syrup urine disease. This is the clearest contraindication. Genetic and recessive, it affects approximately one birth per 185,000 worldwide, up to one per 200 in some Mennonite communities in Pennsylvania, according to a 2017 review. The complex that breaks down BCAAs functions at less than 2% of normal in the classic form. The intermittent form goes unnoticed in good health, even with unrestricted diet, and decompensates during fever, infection, exertion, or surgery. In adults, excess leucine manifests as stomach pain, vomiting, muscle fatigue, or disturbances in consciousness or gait. Treatment relies on dietary restriction of BCAAs and close metabolic monitoring: a supplement is therefore contraindicated.
In a study involving 9 patients, high-protein meals or leucine, isoleucine, or phenylalanine at 100 mg per kilo canceled the effect of infused levodopa without lowering its blood level, unlike glycine and lysine: these amino acids compete with levodopa to enter the brain.
Nutt JG, Woodward WR, Hammerstad JP, et al. N Engl J Med 1984;310(8):483-488. DOI: 10.1056/NEJM198402233100802
Levodopa. The interaction is demonstrated in a small study at high dose: 100 mg of leucine per kilo is 7 g in a single dose for 70 kilos. One serving of our powder provides 2.15 g of leucine, but 5 g of BCAAs which all three compete with levodopa. This dose has not been tested: on levodopa, the decision rests with the neurologist.
Antidiabetic drugs. We identified no study describing an interaction, and leucine did not modify blood glucose in 60 diabetics over 6 months. A treated diabetic person can mention the intake to their doctor.
Pregnancy and breastfeeding. We identified no trials on BCAA supplements during pregnancy or breastfeeding, and a 2017 review notes that in pregnant women with maple syrup urine disease, data are lacking on the effect of elevated blood BCAAs on the fetus. Adequate protein intake covers needs; an isolated supplement has no reason to be used without medical advice.
Maple syrup urine disease: established contraindication. Levodopa: established interaction at high dose. Pregnancy and breastfeeding: no data, abstain unless advised by a doctor.
Isolated BCAAs or complete proteins
BCAAs activate muscle protein synthesis, with leucine playing a signaling role. But to build muscle, all nine essential amino acids are needed, and BCAAs provide only three.
In 10 trained young men, 5.6 g of BCAAs after weight training increased muscle protein synthesis by 22% compared to placebo, about half the increase reported in earlier studies with a whey dose providing similar BCAA quantities, according to the authors, due to the lack of other essential amino acids. The drinks were provided by an industry manufacturer.
Jackman SR, Witard OC, Philp A, et al. Front Physiol 2017;8:390. DOI: 10.3389/fphys.2017.00390
A 2017 review goes further: without the other essential amino acids, the increase is theoretically limited to approximately 30%, and its author judges the idea that BCAAs alone produce an anabolic response to be unfounded. On recovery, results are more favorable but uneven: the 2024 meta-analysis finds less muscle soreness 24 to 96 hours after traumatic exertion, whereas an earlier meta-analysis of 8 trials found an effect only on creatine kinase, a marker of muscle injury.
To meet protein needs, a complete protein provides BCAAs along with other essential amino acids: the 5.6 g of BCAAs in the study corresponded to the typical content of 20 g of whey. Our 100% Whey Isolate provides 22.9 g of protein per 30 g serving. BCAAs retain their value for targeted intake around exercise, as our article compares BCAA or Creatine ; our guide on whey details its effects.
Risk Table and Safety Guidelines
| Risk | What studies show | Verdict |
|---|---|---|
| Nausea, diarrhea | Relative risk of 5.56 in fixed effects, non-significant in random effects, in cirrhotic patients | Probable in patients, rarely described otherwise |
| Elevated ammonia | Beyond 500 mg of leucine per kg per day, and during prolonged exercise | Theoretical at common doses |
| Diabetes, insulin | Association in cohorts, causality disputed, two trials of leucine alone, 3 and 6 months, neutral | Theoretical for supplements |
| Liver damage | Used as a treatment for cirrhosis, no cases identified | Not documented |
| Kidney damage | No specific data, high protein without effect on filtration | Theoretical, medical advice if kidney disease |
| ALS | 24 deaths versus 13, then respiratory decline 2.5 times faster | Unfavorable signal, to be avoided |
| Maple syrup urine disease | Toxic accumulation of leucine, treatment by restriction | Established contraindication |
| Levodopa | Effect canceled by leucine at 100 mg per kilogram, in a study involving 9 patients | Interaction established at high dose |
| Sleep, mood | Competition with tryptophan and tyrosine, no trials on sleep | Theoretical |
| Pregnancy, breastfeeding | No trials identified | Unknown, abstention |
Stop and consult without delay in case of repeated vomiting, of confusion, unusual drowsiness or balance problems, ofworsening of neurological symptoms or of breathing difficulties in a person with a neuromuscular disease, or if treatment with levodopa appears less effective. Persistent digestive issues despite meal splitting are also a reason to stop. These benchmarks are practical advice, drawn from effects described in studies.
Leucine, isoleucine and valine in a 2:1:1 ratio, in HPMC vegetable capsules. Six capsules per day provide 3,000 mg of BCAAs, including 1,500 mg of leucine. The formula is also available in powder form, at 5 g per serving.
View BCAAsFor complete protein intake, discover our 100% Whey Isolate, 22.9 g of protein per serving.
Frequently Asked Questions
Are BCAAs dangerous?
Not for a healthy adult at typical doses of 3 to 10 g per day, according to trials lasting a few weeks in athletes and up to six months for leucine in seniors. However, certain diseases and treatments require avoiding them or seeking medical advice.
What are the side effects of BCAAs?
The best documented are nausea, vomiting and diarrhea, especially in cirrhotic patients treated for encephalopathy. Beyond 500 mg of leucine per kilogram per day, and during prolonged exercise, blood ammonia increases, without demonstrated clinical consequences.
Are BCAAs bad for the kidneys?
No study shows an effect of BCAAs on healthy kidneys, and 28 trials found no effect of high-protein diets on renal filtration in healthy adults. In case of kidney disease, consultation with a nephrologist is essential.
Do BCAAs damage the liver?
Nothing indicates this: they are used in cirrhotic patients, and in a trial involving 646 patients, 12 g per day, planned for two years, reduced serious events. In case of liver disease, their use is a matter for a physician.
Do BCAAs raise insulin or promote diabetes?
High blood BCAAs are associated with diabetes in cohorts, but genetic studies point to either a defect in BCAA breakdown or insulin resistance itself, and none incriminate supplementation. In trials, 7.5 g of leucine per day for three and six months altered neither insulin nor glycated hemoglobin.
Do BCAAs prevent sleep?
No trial has shown this. They slightly inhibit tryptophan entry into the brain, by 8 to 12% at high doses during exercise, but no study has measured sleep. As a practical precaution, take them around your workout rather than at bedtime.
What is the maximum daily dose of BCAAs?
No threshold is established for BCAAs combined. For leucine, it is around 500 mg per kilogram per day, approximately 35 g for 70 kilos, or 24.5 g cautiously in seniors, far removed from typical doses of 3 to 10 g of BCAAs.
Who should not take BCAAs?
People with maple syrup urine disease or another hereditary amino acid metabolism disorder, and those with amyotrophic lateral sclerosis. Medical advice is necessary with levodopa, in case of liver or kidney disease, treated mood disorder, pregnancy or breastfeeding.
Can BCAAs be taken during pregnancy?
No trial has evaluated BCAA supplements during pregnancy or breastfeeding. Lacking data, it is better to avoid them without medical advice and meet amino acid needs through adequate protein intake.
Is there an interaction between BCAAs and levodopa?
Yes. In a study of 9 Parkinson's patients, leucine or isoleucine at 100 mg per kilogram cancelled the effect of levodopa, because these amino acids compete with the drug for entry into the brain. A person treated with levodopa should discuss this with their neurologist before taking any.
Is it better to take whey or BCAAs?
To build muscle, a complete protein has the advantage: 5.6 g of BCAAs increased muscle protein synthesis by 22% compared to placebo, about half as much as in earlier whey studies. BCAAs remain an option for targeted intake around exercise.
Sources
The studies cited below were identified via PubMed.
- Muto Y, Sato S, Watanabe A, et al. Effects of oral branched-chain amino acid granules on event-free survival in patients with cirrhosis. Clinical Gastroenterology and Hepatology, 2005;3(7):705-713. DOI
- The Italian ALS Study Group. Branched-chain amino acids and amyotrophic lateral sclerosis: a therapeutic failure? Neurology, 1993;43(12):2466-2470. DOI
- Blackburn PR, Gass JM, Vairo FPE, et al. Maple syrup urine disease: mechanisms and management. The Application of Clinical Genetics, 2017;10:57-66. DOI
- Jackman SR, Witard OC, Philp A, et al. Branched-chain amino acid ingestion stimulates myofibrillar protein synthesis following resistance exercise in humans. Frontiers in Physiology, 2017;8:390. DOI
- Salem A, Ben Maaoui K, Jahrami H, et al. Attenuating muscle injury markers and delayed onset muscle soreness following damaging exercise with BCAAs: a systematic review and meta-analysis with meta-regression. Sports Medicine - Open, 2024;10(1):42. DOI
- Verhoeven S, Vanschoonbeek K, Verdijk LB, et al. Long-term leucine supplementation does not increase muscle mass or strength in healthy older men. The American Journal of Clinical Nutrition, 2009;89(5):1468-1475. DOI
- Leenders M, Verdijk LB, van der Hoeven L, et al. Long-term leucine supplementation does not increase muscle mass and does not modify glycemic control in older men with type 2 diabetes. The Journal of Nutrition, 2011;141(6):1070-1076. DOI
- Tandan R, Bromberg MB, Forshew D, et al. A controlled trial of amino acid therapy in amyotrophic lateral sclerosis: I. Clinical, functional, and maximum isometric torque data. Neurology, 1996;47(5):1220-1226. DOI
- Hiroshige K, Sonta T, Suda T, Kanegae K, Ohtani A. Oral supplementation with branched-chain amino acids improves the nutritional status of elderly patients undergoing chronic hemodialysis. Nephrology Dialysis Transplantation, 2001;16(9):1856-1862. DOI
- Gluud LL, Dam G, Les I, et al. Branched-chain amino acids for people with hepatic encephalopathy. Cochrane Database of Systematic Reviews, 2017;5(5):CD001939. DOI
- Marchesini G, Bianchi G, Merli M, et al. Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a randomized, double-blind controlled trial. Gastroenterology, 2003;124(7):1792-1801. DOI
- Suez J, Cohen Y, Valdés-Mas R, et al. Personalized, microbiota-dependent effects of non-nutritive sweeteners on glucose tolerance in humans. Cell, 2022;185(18):3307-3328.e19. DOI
- Elango R, Chapman K, Rafii M, Ball RO, Pencharz PB. Determination of the maximum tolerable leucine intake during acute dietary studies in young men. The American Journal of Clinical Nutrition, 2012;96(4):759-767. DOI
- Rasmussen B, Gilbert E, Turki A, Madden K, Elango R. Determination of the safety of leucine supplementation in healthy older men. Amino Acids, 2016;48(7):1707-1716. DOI
- Elango R, Rasmussen B, Madden K. Safety and tolerance of leucine supplementation in older men. The Journal of Nutrition, 2016;146(12):2630S-2634S. DOI
- Madsen K, MacLean DA, Kiens B, Christensen D. Effects of glucose, glucose combined with branched-chain amino acids, or placebo on performance during a 100-km cycling time trial. Journal of Applied Physiology, 1996;81(6):2644-2650. DOI
- Watson P, Shirreffs SM, Maughan RJ. Effect of acute branched-chain amino acid supplementation on endurance exercise capacity in the heat. European Journal of Applied Physiology, 2004;93(3):306-314. DOI
- Guasch-Ferré M, Hruby A, Toledo E, et al. Metabolomics of prediabetes and diabetes: systematic review and meta-analysis. Diabetes Care, 2016;39(5):833-846. DOI
- Morze J, Wittenbecher C, Schwingshackl L, et al. Metabolomics and type 2 diabetes risk: updated systematic review and meta-analysis of prospective cohort studies. Diabetes Care, 2022;45(4):1013-1024. DOI
- Zheng Y, Li Y, Qi Q, et al. Cumulative intake of branched-chain amino acids and incidence of type 2 diabetes. International Journal of Epidemiology, 2016;45(5):1482-1492. DOI
- Lotta LA, Scott RA, Sharp SJ, et al. Genetic predisposition to impaired branched-chain amino acid metabolism and type 2 diabetes risk: a Mendelian randomization analysis. PLoS Medicine, 2016;13(11):e1002179. DOI
- Mahendran Y, Jonsson A, Have CT, et al. Genetic evidence of a causal effect of insulin resistance on branched-chain amino acid levels. Diabetologia, 2017;60(5):873-878. DOI
- Karusheva Y, Koessler T, Strassburger K, et al. Short-term dietary reduction of branched-chain amino acids decreases postprandial insulin secretion and modifies the microbiota in type 2 diabetes: a randomized controlled crossover trial. The American Journal of Clinical Nutrition, 2019;110(5):1098-1107. DOI
- Solon-Biet SM, Cogger VC, Pulpitel T, et al. Branched-chain amino acids influence health and lifespan indirectly, through amino acid balance and appetite control. Nature Metabolism, 2019;1(5):532-545. DOI
- Devries MC, Sithamparapillai A, Brimble KS, et al. Renal function outcomes do not differ between healthy adults consuming high or low protein diets: a systematic review and meta-analysis. The Journal of Nutrition, 2018;148(11):1760-1775. DOI
- Bastone A, Micheli A, Beghi E, Salmona M. Imbalance of cerebral availability of large neutral amino acids in patients with amyotrophic lateral sclerosis treated with high doses of branched-chain amino acids. Neurochemistry International, 1995;27(6):467-472. DOI
- Blomstrand E. Amino acids and central fatigue. Amino Acids, 2001;20(1):25-34. DOI
- van Hall G, Raaymakers JS, Saris WH, Wagenmakers AJ. Ingestion of branched-chain amino acids and tryptophan during prolonged exercise in humans: no effect on performance. The Journal of Physiology, 1995;486(Pt 3):789-794. DOI
- Mittleman KD, Ricci MR, Bailey SP. Branched-chain amino acids prolong exercise in heat in men and women. Medicine and Science in Sports and Exercise, 1998;30(1):83-91. DOI
- Scarnà A, Gijsman HJ, McTavish SF, et al. Effects of a branched-chain amino acid drink in mania. The British Journal of Psychiatry, 2003;182:210-213. DOI
- Nutt JG, Woodward WR, Hammerstad JP, Carter JH, Anderson JL. The on-off phenomenon in Parkinson's disease: relation to the absorption and transport of levodopa. The New England Journal of Medicine, 1984;310(8):483-488. DOI
- Wolfe RR. Branched-chain amino acids and muscle protein synthesis in humans: myth or reality? Journal of the International Society of Sports Nutrition, 2017;14:30. DOI
- Rahimi MH, Shab-Bidar S, Mollahosseini M, Djafarian K. Branched-chain amino acid supplementation and exercise-induced muscle damage: meta-analysis of randomized clinical trials. Nutrition, 2017;42:30-36. DOI
