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AMAZING ANABOLIC AND FAT-LOSS POWERS OF LEUCINE

Brian Turner

Posted on November 28 2018

By Steve Blechman

 

Leucine is an essential amino acid that serves as a building block for muscle protein synthesis. Leucine is a powerful anabolic trigger— it’s the most potent branched-chain amino acid (BCAA) and a key activator 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.

Increases Muscle Protein Synthesis. Muscles increase in size when muscle protein synthesis is greater than muscle breakdown. Protein balance is influenced by muscle tension, physical activity, calories, protein and amino acids. High protein intake temporarily increases protein synthesis in the muscles by activating key biochemical pathways in the cells. When combined with protein, leucine triggers protein synthesis for greater gains.

Leucine, not branched-chain amino acids, 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 addition of isoleucine and valine may hinder the benefits of leucine due to competition for transport into muscle cells. 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.

Robert R. Wolfe, noted amino acid researcher, said 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.”

Studies indicate increases in muscle protein synthesis are dependent on leucine concentration! Leucine stimulates the anabolic effects of muscle protein by itself. A Japanese study published on October 18, 2018 in the journal Nutrients found that taking leucine supplements alone may be better for muscle protein synthesis and more anabolic than leucine from food! Japanese researchers found that blood levels of leucine were higher from pure, free leucine taken alone compared to the same amount of leucine in a meal. Increase in muscle protein synthesis is dependent on leucine concentration. Research has shown that leucine stimulates the anabolic effect of muscle protein on its own (Wilkinson et al., J Physiol, 2013). The Nutrients study showed that, “based on these findings, it is presumed that compared to the intake of protein alone or free amino acids alone, the intake of dietary protein from mixed meals may result in a lower maximum plasma leucine concentration. However, no study to date has investigated the changes in amino acid concentrations after the ingestion of mixed meals in comparison to those after the intake of a similar amount of free amino acids.”

In a randomized crossover study, 10 healthy, young Japanese men underwent tests under different conditions: consuming 2 grams of leucine alone; a mixed meal with 2.15 grams of leucine without any additional leucine supplementation; 2 grams of leucine right after a meal; and the final serving consisted of 2 grams of leucine, 180 minutes after a meal.

The study concluded that “based on the aforementioned discussions, the intake of free leucine alone markedly increased the plasma leucine concentration. However, the increase in leucine concentration after the intake of a mixed meal containing the same amount of leucine was significantly less than that of free leucine intake alone. Moreover, when free leucine was ingested after a mixed meal with the purpose of increasing the plasma leucine concentration, the maximum plasma concentration was attenuated when it was ingested immediately after the mixed meal, despite the fact that the total leucine content was doubled. These results suggest that when free amino acids ingested with the purpose of increasing plasma amino acid concentrations, the timing in relation to the mixed meal intake needs to be considered.”

For best results to use as an anabolic trigger, take 5 grams of leucine (on an empty stomach) 30 minutes before a post-workout meal, or protein shake. 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.) (Nutrition 2017, 42: 30-36; American Journal of Clinical Nutrition 2016; 104:1594-606; Med Sci Sports Exercise 2011, 43: 2249-2258; Nat Med 2015, 22: 421-426; Biochemical Journal 1996, 100: 7-11; International Journal of Sport Nutrition and Exercise Metabolism, March 2018, 28: 170-177; Amino Acids, June 2008, 35: 147-155; Amino Acids, July 2015, 47: 1389-98).

By taking pure leucine on an empty stomach, 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. When leucine is taken after resistance exercise and before a post-workout, protein-containing meal rich in essential amino acids, it triggers greater protein synthesis for improved recovery and greater gains.  

There’s an overwhelming amount of evidence over the years that elevated branched-chain amino acids are associated with obesity and insulin resistance. A most recent meta-analysis study (Acta Diabetologica, November 9, 2018) found that oral BCAA elevates circulating dietary BCAA intake and were positively and inversely related to type 2 diabetes, mellitus and overweight/obesity risk respectively! The researchers said, “Eight articles on randomized clinical trials of oral BCAA supplementation and seven articles on dietary BCAA intake and type 2 diabetes/obesity risks were eligible for inclusion in our meta-analysis.”

A study in the Journal of Physiology (February 2018) suggests that a diet low in BCAAs may help weight loss and prevent the metabolic problems that occur in diabetes and obesity. “We’ve identified an unanticipated role for dietary BCAAs in the regulation of energy balance, and we show that a diet with low levels of BCAAs promotes leanness and good control of blood sugar,” according to an article in Nutraingredients-USA.com, dated December 21, 2017.

“… branched-chain amino acids, or BCAA, 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,” according to ScienceDaily on May 17, 2018 and most recently published, 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.”

“This helps to explain how and why BCAAs are associated with disordered fat metabolism that can lead to type 2 diabetes,” said Newgard, who has worked on BCAA in metabolic disease for more than a decade.

Research has shown that elevated levels of valine are present in the blood of diabetic rats, mice and humans (Nat Rev Endocrinol, 2014). When the mice were fed a diet without valine, insulin sensitivity improved after only one day. Mice on the valine-free diet lasting an entire week showed decreased blood glucose levels, indicating that there was improved insulin function (Metabolism, 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. The intramuscular fat activates certain signaling cascades within the muscle cell that diminish insulin signaling, leading to insulin resistance. This study also found that inhibiting the production of 3-HIB prevented the uptake of fat. Other studies support the negative effect of 3-HIB on insulin signaling with elevated 3-HIB in the muscle of human subjects with diabetes (J Lipid Res, 1989; Diabetologia, 2015). An article titled Insulin Resistance, And What May Contribute To It by Lila Abassi and published on the American Council on Science and Health website on March 14, 2016 reported on “… a study published in Nature Medicine, [that] 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.” Abassi also states, “Thus far, it has been a relative mystery as to how BCAAs play a role in insulin resistance. Skeletal muscles display resistance to insulin when there is excess fat inside their cells.” In her closing of the article, Abassi said, “What the researchers found was that 3-HIB acted as a shuttle in muscle cells, allowing blood vessels in skeletal muscle tissue to move fat into skeletal muscle. The more 3-HIB, the more fat was transported — and conversely, when scientists blocked 3-HIB from being made, there was less uptake of fat into skeletal muscle.”

One of the authors of the study, Dr. Zoltan Arany, said to Abassi: “In this study we showed a new mechanism to explain how 3-HIB, by regulating the transport of fatty acids in and out of muscle, links the breakdown of branched-chained amino acids with fatty acid accumulation, showing how increased amino acid flux can cause diabetes.”

More recent studies have confirmed that the branched-chain amino acid valine metabolite 3-HIB is involved in the pathogenesis of insulin resistance in skeletal muscle and might be involved in insulin resistance in humans (Diabetes, July 2017; EbioMedicine, 2018; J Diab Rsch, 2018). Unlike valine, leucine has been shown to improve insulin function. Leucine consumption alone has been shown to rescue insulin-signaling deficiency (PLOS, 2011). A most recent study (Exp Clin Endocrinol Diabetes, 2018) has found that oral administration of leucine improved endothelial function in healthy individuals when infused with glucose. Acute hyperglycemia impairs endothelial function in healthy individuals. This study found that leucine administration prevented hyperglycemia-mediated endothelial function. Unlike leucine, which avoids insulin resistance by increasing mitochondrial-driven fat loss, valine does not encourage mitochondrial biogenesis. Impaired mitochondrial function in skeletal muscle is one of the major predisposing factors to metabolic diseases, such as insulin resistance, type 2 diabetes and cardiovascular disease. Leucine supplementation increases insulin sensitivity by activating SIRT1 activity. SIRT1 is known to “promote mitochondrial biogenesis and oxidative capacity and prevent the mitochondrial dysfunction in skeletal muscle.” (Journal of Nutrition and Metabolism, 2014) Leucine may also attenuate adiposity and promote weight loss during energy restriction (Nutrition 2006, Diabetes, 2007). These effects are in part by activating the SIRT1-dependent pathway, stimulating mitochondrial biogenesis and increased oxygen consumption (Nutrition Metabolism, 2008). Mitochondrial biogenesis and SIRT1 expression in skeletal muscle has also been shown to increase lifespan in middle-aged mice (Cell Metabolism, 2010). As far as isoleucine is concerned, unlike valine, it has been shown to improve insulin sensitivity by increasing glucose into muscle cells (Am J Physiol Endocrinol Metab, 2007).

In conclusion, the research shows that leucine is a powerful anabolic trigger and enhances protein synthesis and can promote muscle growth and recovery. Also, leucine supplementation can improve mitochondrial biogenesis and function, increase insulin sensitivity and may also enhance fat loss and improve lean body mass.

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