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6 Benefits and Side Effects of BCAAs (8 Contraindications To Be Noted)

BCAAs are essential protein essential amino acids (proteinogenic essential amino acids) indispensable for skeletal muscle protein synthesis, glucose and lipid metabolism, muscle repair and ATP production, accounting for about 50% of the total amount of essential amino acids in food and 35% of the total essential amino acids of muscle protein. Note 12

What are the benefits of BCAAs in empirical medicine? Are there any side effects of BCAAs? See text analysis for details

What is BCAA (branched-chain amino acid)?

BCAA, Chinese as branched-chain amino acid, is an important essential amino acid in the human body, including valine, leucine and isoleucine, characterized by aliphatic-branched side chains.

Unlike most amino acids, the first step in BCAA catabolism does not occur in the liver because the first enzyme in the BCAA catabolic pathway: branched-chain amino acid aminotransferase (BCAT) has lower liver activity.

Thus, after protein intake, BCAAs increase rapidly in the systemic circulation and easily enter extrahepatic tissues (eg, muscle, kidney, heart, and adipose tissue, and brain).

This phenomenon gives BCAA-based nutritional formulas a unique advantage over other formulations, especially those that target muscle and brain.

In exceptional circumstances (e.g., sepsis, burns, trauma, and cancer), BCAAs are severely depleted and may require additional supplementation to maintain normal physiological levels.

What are the empirical benefits of BCAAs?

1. Beneficial for delayed onset muscle soreness

Delayed onset muscle soreness usually occurs within 24 hours of exhaustion or strenuous exercise, peaking between 24 and 72 hours, with muscle swelling and decreased muscle performance, as well as reduced range of motion.

Traditional physiotherapy strategies such as massage, cold water immersion, full-body vibration, compression garments, and stretching are often used to prevent or relieve symptoms of delayed onset muscle aches.

A meta-analysis (5 randomized controlled trials, 93 participants) suggested that BCAA supplementation was an effective way to reduce delayed onset muscle soreness, consistent regardless of sex and training status. Note 1

The mechanism behind it is related to BCAAs promoting skeletal muscle protein synthesis and regulating the attenuation of muscle protein breakdown in the recovery stage.

*Conclusion: BCAA supplementation may reduce delayed muscle soreness after exercise and positively help improve muscle tissue recovery rate.

2. It is beneficial to recover during surgery for hepatocellular carcinoma

Hepatocellular carcinoma is one of the most common cancers, chronic viral hepatitis is the most important risk factor, and other factors, such as excessive alcohol consumption, smoking, and environmental exposure to koji mycotoxins, can also affect disease progression and response to treatment.

Underlying cirrhosis often leads to malnutrition, usually caused by poor appetite, impaired nutrient intake, and disturbances in protein synthesis, and sometimes to ascites and edema, which are important factors affecting the prognosis of hepatocellular carcinoma.

A systematic literature review and meta-analysis (13 randomised controlled trials, 77% of cases associated with liver cancer) noted that BCAA (branched-chain amino acid) supplementation during cancer surgery reduced the risk of postoperative infection compared with controls, and also had benefits for ascites, weight, and length of hospital stay. Note 2

In addition, no differences were found between BCAAs and control groups in terms of mortality, recurrence, other postoperative complications (liver failure, oedema, pleural effusion), blood loss, quality of life, ammonia levels, and prothrombin time.

*Conclusion: m-BCAA (branched-chain amino acids) during tumor surgery may be positively helpful in reducing infection and ascites, but due to the high risk of bias of the included studies, more empirical confirmation is needed

3. Beneficial tardive dyskinesia

Tardive dyskinesia refers to slow or late involuntary movements of the face, lips, tongue, trunk, and extremities, which can be mild tremor or uncontrollable movements throughout the body, often occurring in individuals who take dopaminergic antagonists (antipsychotics) for a long time (occurring in about 15% to 30%).

Its pathophysiology lacks accepted theories and mechanisms. Several hypotheses have been proposed, including prolonged postsynaptic dopamine receptor blockade leading to dopamine receptor hypersensitivity, gamma-aminobutyric acid depletion, cholinergic deficiency, oxidative stress, altered synaptic plasticity, neurotoxicity, and defects in neuroadaptive signaling.

A randomized placebo-controlled trial (3-week trial of 36 men with tardive dyskinesia) noted that BCAA (branched-chain amino acids) supplementation helped improve symptoms. Note 3

In addition, a decrease in the symptoms of tardive dyskinesia is not associated with changes in antipsychotic drugs and glucose plasma levels.

*Conclusion: For tardive dyskinesia, oral BCAA may bring positive help, but limited by small sample sizes, more studies are needed to further validate

4. Increase muscle mass

Since BCAAs are indispensable for the action of enzymes needed to make muscles, most people start using them for this reason.

However, as far as the current study is concerned, no muscle gain effect of using BCAA products has been found to be better than whey protein supplements or natural diet.

On the contrary, whey protein combined with training will bring about muscle gain better than taking monoamino acids. Note 4

5. Reduce fatigue during exercise

Fatigue during exercise often makes exercise unsustainable, and fatigue varies according to an individual’s physical state (glycohydrate depletion, creatine phosphate changes, dehydration, hormonal changes), exercise intensity, duration, and environmental factors.

Several studies have pointed out that taking BCAAs during exercise can help reduce fatigue compared to placebo, and the mechanism behind BCAAs may be related to the reduction of muscle damage and inflammation caused by BCAAs. Notes 5-6

Another controlled study (13 men and women who participated in the cyclic stress test) showed that taking BCAAs reduced fatigue and improved exercise performance by 12%. Note 7

*Conclusion: Oral BCAAs may bring positive help to fatigue during exercise, but limited by small sample sizes, more studies are needed to further validate

6. Beneficial for traumatic brain injury

Traumatic Brain Injury (TBI) is mainly a neurological dysfunction caused by external forces such as impact, shock or vibration, and can be simply divided into mild (transient changes in mental status or consciousness) or severe (long-term loss of consciousness and permanent brain injury) according to severity, the most common form is concussion.

The extent of nerve damage is determined by evolving pathophysiology, during which brain swelling, increased intracranial pressure, and decreased cerebral blood flow contribute to the development of cognitive and functional deficits.

A systematic review of 11 studies suggests that BCAAs help improve severe traumatic brain injury, such as cognitive function, but the evidence for minor traumatic brain injury is insufficient and needs further confirmation. Note 8

The mechanism behind it is related to the increase of ATP formation and insulin regulation function of BCAA.

*Conclusion: For traumatic brain injury, oral BCAA may bring positive help, but limited by small sample sizes, more studies are needed for further verification

Are there any side effects of BCAAs (branched-chain amino acids)?

Oral BCAAs are safe in appropriate doses for most adults in good health, but side effects or adverse effects have been reported as nausea, vomiting, diarrhea, bloating, fatigue, and loss of coordination with exercise (mostly related to pre-existing medical conditions or overdose)

Safety precautions (8 contraindications for use)

1. Amyotrophic lateral sclerosis (also known as frozen man’s disease) should not be used (because it may increase lung failure and mortality). Note 10

2. Maple syrup urine disease (also known as branched-chain ketoaciduria) should not be used (may cause dystrophic physical retardation, seizures, opisthotonus and coma). Note 11

3. BCAA has hypoglycemic effect, so diabetic patients or those taking related glucose control drugs please pay attention to, common related drug names: glimepiride, glyburide (glycemic reduction), insulin, pioglitazone, rosiglitazone, chlorpropamide, glipizide, tolbutamide (methylene glycene) etc.

4. Do not use if you are pregnant, lactating and have poor liver and kidney function (due to unknown safety)

5. Do not use in infants (due to unknown safety)

6. Do not use in combination with Parkinson’s disease treatment drugs (Levodopa), which may affect the effect of the drug

7. Do not combine with diazoxide (drugs used to treat hypoglycemia), thyroid hormones, corticosteroids, which may affect BCAA metabolism

8. Discontinue use 2 weeks before surgery, as BCAAs may affect blood glucose levels

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