NEW STUDY! 

By Steve Blechman

Beta-hydroxy-beta-methylbutyrate (HMB) is a metabolite of the essential amino acid leucine that is produced in skeletal muscle. Alpha-hydroxyisocaproic acid (alpha-HICA) is also a metabolite of the amino acid leucine. It is often sold as a purported muscle-building supplement. Animal research has shown that HMB can increase body mass in animals. As a supplement for humans, HMB is marketed as an anti-catabolic nutrient that decreases protein breakdown. A dose of 3 grams of HMB daily has been recommended to augment resistance training-induced changes in body composition and performance. Two most recent studies published in the European Journal of Sports Science in July 2019 and also published in Medicine Science & Sport in January 2019 showed that the leucine metabolite HMB and HICA don’t improve muscle growth or strength in young adult men. Another recent study published in Journal of Sports Science on May 12^th, 2019 found that HICA, HMB free acid and CaHMB don’t lower exercise-induced inflammation.

Below is a review of the study:

“Purpose: We aimed to conduct a double-blind randomized controlled pragmatic trial to evaluate the effects of off-the-shelf leucine metabolite supplements of alpha-HICA, HMB-FA, and HMB-Ca on resistance training-induced changes in muscle thickness and performance.

Methods: Forty men were randomly assigned to receive alpha-HICA (n = 10, fat-free mass [FFM] = 62.0 ± 7.1 kg), HMB-FA (n = 11, FFM = 62.7 ± 10.5 kg), HMB-Ca (n = 9, FFM = 65.6 ± 10.1 kg), or placebo (PLA; n = 10, FFM = 64.2 ± 5.7 kg). The training program consisted of whole-body, thrice- weekly resistance training for 8 wk (seven exercises per session, three to four sets per session, at 70%-80% one repetition maximum). Skeletal muscle thickness by ultrasound, performance measures, and blood measures (creatine kinase, insulin-like growth factor 1, growth hormone, cortisol, and total testosterone) were evaluated at baseline and at the end of weeks 4 and 8.

Results: Time-dependent changes were observed for muscle thickness (P < 0.001), one repetition maximum bench press and squat (P < 0.001), Wingate peak power (P = 0.02), countermovement jump height (P = 0.03), power (P = 0.006), creatine kinase, insulin-like growth factor-1, growth hormone, and cortisol (all P < 0.001). No significant between-group or time-group interactions were observed.

Conclusions: No leucine metabolite resulted in any ergogenic effects on any outcome variable. Supplementation with leucine metabolites— alpha-HICA, HMB-FA, or HMB-Ca— is not a supplementation strategy that improves muscle growth and strength development in young adult men.” 

WHY LEUCINE IS STILL KING?

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.

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. Ingestion of leucine alone can independently activate mTOR and muscle protein synthesis. 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 clearly 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.)

Increase in muscle protein synthesis is dependant on leucine concentration. Research has shown that leucine stimulates the anabolic effect of protein synthesis on its own (Wilkinson et al, J Physiol, 2013). When leucine is taken on an on an empty stomach, it has a powerful anabolic switch that turns on protein synthesis. 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. Additionally, 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.

In conclusion, the research shows that leucine is king and 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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