By Steve Blechman

The branched-chain amino acids (BCAA) leucine, isoleucine and valine are essential amino acids that serve as the building blocks for muscle protein synthesis. Of the three BCAAs, leucine is the key regulator of muscle protein synthesis. Protein synthesis is mainly controlled by the mechanistic target of rapamycin (mTOR). Leucine is a powerful anabolic trigger – it is the most potent branched-chain amino acid (BCAA) of the mTOR pathway that is critical for muscle protein synthesis that promotes muscle growth. Leucine has many growth benefits preventing muscle loss, increasing insulin sensitivity, enhancing fat metabolism, and enhancing recovery.

A randomized control study published in the Journal of the American College of Nutrition found that taking 3 grams of pure leucine after resistance training exercise increased muscle insulin-like growth factor 1 (IGF-1). IGF-1 is a potent anabolic hormone derived from growth hormone. Increased IGF-1 in muscle can increase muscle protein synthesis and muscle growth. 

DO BRANCHED-CHAIN AMINO ACIDS CAUSE INSULIN RESISTANCE, DIABETES AND OBESITY?

It has been implicated that the branched-chain amino acids isoleucine and valine, but not leucine, are positively associated with increase of insulin resistance diabetes and obesity in animals as well as humans.

Over 70% of Americans are overweight. Medical researchers have projected that by 2030, one in two adults will be obese. A major health concern!

A new study published May 4, 2021 in the Journal Cell Metabolism reported, “The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine.” The researchers found that “reduced isoleucine or valine, but not leucine, promotes metabolic health in mice” Also, that “dietary levels of isoleucine are positively associated with BMI in humans.” Body mass index or BMI is defined to help measure healthy weight or obesity in men and women. Also, by specifically reducing isoleucine in the diet, you can improve insulin sensitivity and increase energy expenditure. The researchers concluded that results suggest that reducing isoleucine, “May be a novel therapeutic and public health strategy to combat the twin epidemics of obesity and diabetes.”

A study that was presented at the 40th European Society for Clinical Nutrition and Metabolism (ESPEN) Congress in Madrid, Spain on September 1-4, 2018 further confirmed that elevated branched-chain amino acids are associated with obesity.

In a previous article, I mentioned that branched-chain amino acids (BCAAs) had been identified in 2009 as a robust marker of obesity and insulin resistance in humans by Duke researchers led by Christopher Newgard, the director of the Duke Molecular Physiology Institute. This according to ScienceDaily on May 17, 2018 in addition to findings by Duke University researchers in Cell Metabolism, also on May 17, 2018. “The association between BCAA and insulin resistance had been present in the literature dating back to a 1969 study that appeared in the New England Journal of Medicine. And they have since been shown to be highly predictive of future diabetes development by the landmark Framingham Heart study,” the researchers concluded.

This study included 80 obese participants. High circulating BCAAs were negatively associated with free fatty acid concentrations. High blood levels of free fatty acids have been correlated in insulin resistance and type 2 diabetes (Diabetes, Obesity & Metab, June 2018). Elevated BCAA levels were significantly positively associated with deep visceral (abdominal fat) and hepatic (liver) fat. Liver fat content was assessed through magnetic resonance spectroscopy imaging (MRS), while visceral and subcutaneous adipose tissue were evaluated by magnetic resonance imaging (MRI). High visceral fat is strongly associated with the metabolic syndrome including inflammation, insulin resistance, diabetes, high triglycerides, high cholesterol, hypertension, and fatty liver.

Research has shown that elevated levels of valine are present in the blood of diabetic rats, mice and humans (Nat Rev Endocrinol, 2014). It was reported in the journal Nature Medicine in 2015 that valine catabolite 3-hydroxyisobutyrate (3-HIB) promoted the accumulation of fat within muscle tissue by directly stimulating fatty uptake in the muscle. Scientists have discovered that 3-hydroxyisobutyrate (3-HIB), one of the intermediate products in the breakdown of the BCAA valine, plays a role in the transport of fatty acids into skeletal muscle cells, which creates fatty muscles — a contributor to insulin resistance. Could an increase in insulin resistance cause skeletal muscle breakdown and increase valine catabolite 3-HIB in the blood, and also increase abdominal (visceral) and liver fat as well as muscle fat? Is valine catabolite 3-HIB the metabolic culprit? Is that why high BCAAs are linked to obesity and diabetes. 

CAN LEUCINE PROTECT AGAINST CARDIOVASCULAR DISEASE?

A study in the journal BioFactors (February 15, 2018) it was shown that leucine might be protective of cardiovascular disease in humans by “…attenuating macrophage foam-cell formation by mechanisms related to the metabolism of cholesterol, triglycerides and energy production.” “Foam cells are a type of macrophage that localize to fatty deposits on blood vessel walls, where they ingest low-density lipoproteins and become laden with lipids, giving them a foamy appearance. These cells secrete various substances involved in plaque growth and their death promotes inflammation, thereby contributing to cardiovascular disease.” (Nature, https://www.nature.com/subjects/foam-cells.) 

HOW TO TAKE LEUCINE FOR MAXIMIZING PROTEIN SYNTHESIS, MUSCLE GROWTH & RECOVERY

For best results to use as an anabolic trigger, take 5 grams of leucine (on an empty stomach) 15-30 minutes before a post-workout meal. A meta-analysis (Nutrition, 2017) that combined the results of seven studies showed that BCAA supplements are best taken after exercise, not before, or during exercise (intra-workout).

Leucine, not branched-chain amino acids (BCAAs), is the most important chemical that turns on the mTOR pathway, so it is likely that consuming leucine after exercise would be more effective (and cheaper) than consuming BCAAs. The BCAAs share the same active transport system into cells and muscle cells. Indeed, isoleucine and valine have been shown to inhibit absorption of leucine (Nutrition, 2017; Biochem J, 1966; Int J of Sp Nutr & Exer Metab, 2018).

Robert R. Wolfe, noted amino acid researcher, states in the Journal of the International Society of Sports Nutrition (2017) that “BCAAs also compete with other amino acids for transport, including phenylalanine, and this competition could affect the intramuscular availability of other EAAs. As a result of competition for transporters, it is possible that leucine alone, for example, could have a transitory stimulatory effect on muscle protein synthesis where the BCAAs fail to elicit such response.”

Timing of leucine ingestion is critical! By taking pure leucine on an empty stomach after your workout, you will get a better spike in blood levels than if you take leucine with food, because food can slow leucine’s absorption. The addition of isoleucine and valine may hinder the benefits of leucine due to competition for transport into muscle cells. When leucine is taken on an empty stomach, it’s a powerful metabolic switch that turns on protein synthesis.

Leucine increases mTOR activity for several hours after training. Leucine should be taken on an empty stomach, after resistance exercise, and as an anabolic trigger before a post-workout, protein-containing meal (or protein shake) rich in essential amino acids. This will trigger greater protein synthesis for improved recovery and greater gains.

WHY LEUCINE IS STILL KING

Based on the latest scientific research, leucine is still king, and the most potent anabolic/amino acid trigger! For added benefits, it is best taken with creatine monohydrate and betaine (found in AML PostWorkout™). Creatine stimulates muscle growth and recovery by increasing muscle cell formation and protein synthesis. Research has shown that creatine monohydrate combined with leucine can inhibit the production of wasting protein myostatin! Supplementing leucine post-exercise also enhances muscle creatine uptake via an insulin-stimulated effect. Betaine is an excellent post-workout supplement when combined with leucine and creatine. “2.5 grams of betaine reduces fatigue and increased power and strength after 15 days of high-intensity, high-volume bench press and squat training. Betaine is also an osmolyte, enhancing muscle cell swelling, stimulating protein synthesis and decreasing protein breakdown, resulting in muscle growth. Betaine also has been shown to increase growth hormone and insulin-like growth factor 1 (IGF-1).” (See my AML Article – Top 3 Post Workout Nutrients: Leucine, Creatine and Betaine.)

There is no need to take supplements of BCAAs-isoleucine and valine that interfere with leucine and share the same active transport system into cells and muscle cells! Like I said earlier, isoleucine and valine have been shown to inhibit the absorption of leucine. Your diet and your post-workout meal will give you all the isoleucine, valine and other essential amino acids that you need!

References:

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