In the scientific fields of nutrition and supplementation, all products and theories tend to wax and wane dependent upon the particular focus of the evidence base. In the last few years one dietary compound has been riding high on a wave of positive research: Leucine.
Leucine is a singular amino acid, which is deemed to be special; particularly by its proponents in the USA, such as Dr Victor Prisk, board-certified orthopaedic surgeon and author of the book Leucine Factor Diet. If sugar is kryptonite, then Dr Prisk would describe Leucine as “anti-kryptonite” (1).
This article will dive beneath the waves in the leucine ocean and hopefully shed some light on what makes this particular amino acid so special.
What Is Leucine?
Leucine is one of the branched-chain amino acids (BCAAs) which are so important in assisting muscular health. It is also a noteworthy component of whey protein which many believe gives this form of protein its power to augment muscle growth (2).
Essential Amino Acids
There are 9 essential amino acids, and 3 branched chain amino acids. The BCAAs are isoleucine, valine and, of course, leucine. These three amino acids are special as they are not degraded by enzymes in the liver, and have greater freedom to enter the body’s tissues.
The group of BCAAs provide a number of postulated benefits including assistance in reducing resistance exercise-based muscle damage (3). However, what about this singular amino acid? What makes this compound so essential?
Leucine specially is even more special because of the potency of function it brings to the table, one reason why it has garnered more research evaluation as a singular supplement than isoleucine or valine.
The functions include a special ability to:
✓ Stimulate muscle growth,
✓ It’s ability to modulate insulin sensitivity,
✓ A catabolic effect on fat – and the fact it is one of the two amino acids which cannot be converted to sugar!
How Does Leucine Work?
The maintenance of lean muscle mass is the underlying secret to managing weight, improving performance and sustaining health and wellness. Being able to facilitate greater muscle protein synthesis allows the body to recover from exercise, perform better and counteract the negative effects of aging.
Leucine has a key role in a variety of functions including hormone control, stabilising blood glucose levels, preventing muscle protein breakdown AND facilitating muscle protein synthesis (MPS).
The predominant function of leucine is in the latter of the two benefits mentioned above; namely being a building block for muscle protein development and facilitating the appropriate signals to facilitate growth. Remember more protein synthesis, means more skeletal muscle development.
The Science Behind Leucine
In order to understand how leucine benefits muscle protein synthesis it is important to understand some of the biology which underlies muscle protein development. Protein synthesis is not growth of current muscle, instead it is the construction of new proteins:Read The Science Behind Leucine.
Once covered, we can move onto the benefits of Leucine on a range of factors!
Leucine | Effects On Muscle Mass
Another added benefit of leucine goes beyond its benefit on augmenting MPS.
Leucines role in regulating the activity of various proteins which assist skeletal muscle translation lead it to be examined also as an anti-wasting agent.
At higher concentrations than required for muscle protein synthesis, even if MPS rates begin to plateau, if leucine concentration remains sufficient, a muscle preserving effect can be seen in atrophic conditions (19).
This means that in circumstances where muscle wasting (atrophy) is expected, high concentrations of leucine are able to protect the lean muscle mass of the person consuming the supplement in a dose dependent manner (20). In fact this has been seen in cancer (21,22); as well as during blood poisoning or traumatic injuries such as burns (23).
Can Leucine Prevent Muscle Breakdown?
Similar studies also showed that disuse atrophy (as seen during injury or with bed rest) can also be attenuated by leucine supplementation (24-25); as could age related muscle loss (sarcopenia) (26-29).
It is postulated that sufficient concentrations of leucine in normal circumstances may saturate the centres of proteidegradation in the muscle cells to slow down muscle wasting (30-31).
Leucine | Performance Benefits
One particular study examined the effect of 6 weeks of leucine supplementation on a number of physical and performance characteristics in canoeists (Crowe).
This randomised, double blind trial examined the influence of 45mg of leucine per kg of bodyweight (vs 45mg/kg of corn flour placebo) on VO2 max, upper body anaerobic power and time to exhaustion in a 70-75% maximal intensity row. The researchers also ensured that both the normal training regimes of the participants, and their dietary intakes were sufficiently similar throughout the trial.
The results indicated that the group given leucine supplementation had improved upper body power output (P=0.045), reduced rate of perceived exhaustion (P=0.031) and longer exercise time to fatigue (P=0.036) (compared to placebo).
The researchers initially theorised that these changes were indicative of a decrease in central fatigue (due to increases in plasma leucine and total BCAA concentrations). However, this was contradicted by no significant reduction in the plasma ratio of free tryptophan. Instead they suggest that the mechanism of performance improvement is through direct effect on skeletal muscles, including improvements in muscle synthesis (33) and reduced muscle damage (34).
✓ The benefits of a high-leucine-content BCAA supplement on signs of muscle damage following an acute bout of 85% 1RM resistance training also indicate reduced damage markers following supplementation to support these results (35).
Leucine | Effects On Lean Mass
In preliminary animal studies the change in lean body mass with a 50% increase in leucine intake, alongside a 50% reduction in food, was examined (36).
This study showed that in rats supplemented with leucine, a significantly greater percentage of lean body mass was preserved during a 6 week period of calorie restricted diet.
These results were also replicated when the rats were given a restricted diet for one week, followed by a 2 week period where they could eat as they liked (37).
However, both of these studies indicated that increases in muscle were not achieved during calorie restriction- meaning if transferred to human diets, one should NOT expect mass gains whilst dieting. Rather leucine could theoretically be used for lean mass maintenance.
STUDY | Leucine On Lean Mass >>>
In a 16 study (999 subjects) systematic review of the available literature (38) similar findings were found for human trial results. The amalgamated results found that leucine supplementation significantly increased bodyweight gain (1.02kg greater) and lean body mass (0.99kg greater) compared to respective control groups. This was particularly apparent in older individuals who were at risk of age related muscle loss.
Leucine | Effects On Weight Loss
Alongside the anabolic effects of high leucine diets to prevent muscle loss (39-40), there have also been suggestions that leucine supplementation can assist weight loss.
These weight loss benefits have been ascribed to activation of mTOR in a part of the brain called the hypothalamus and release of a hormone which increases satiety (41-42).
Since the maximum saturation point of amino acids in the brain is low (43), it is instead suggested that the appetite reducing effect is through production of neurotransmitters, dopamine and serotonin (44).
Some suggest that this would mean that use of leucine may in fact reduce food intake, limiting its effectiveness to augment MPS and reduce muscle atrophy. However, it is likely that consumption of only 1.5 x greater amounts of dietary leucine are required to increase protein turnover, and such amounts are unlikely to effect food consumption (41).
STUDY | Leucine On Weight Loss >>>
Rodent studies support this effect of leucine on weight loss. In two such studies where rats were given a high fat diet, leucine supplementation helped reduce the amount of weight gained by up to 30% (45-46) via a decrease in body fat, whilst lean mass was maintained. These changes were explained to be due to a reduction in food intake or increase in energy expenditure.
Leucine | Post-Injury Recovery
Interesting for me as a physiotherapist is the role in leucine to assist muscle regeneration following injury. Studies suggest that following injury people do not use supplementation as readily, when really it may be of benefit to assist recovery (47).
In one animal study involving rats, it has been shown that following an acute muscle injury, whilst leucine supplementation didn’t allow for sufficient protein synthesis to increase the size of a regenerating muscle fibre, it did allow a reduction in collagen scar tissue.
It also minimised the accumulation of extracellular matrix components, indicative of improved healing (48).This improved healing response was alongside the prevention of a decrease in maximal strength in the regenerating muscle tissue!
LEUCINE On Healing Tissue >>>
A further exciting study by the same authors (49) focused more closely on the effect of leucine on muscle growth during regeneration of healing tissue. This study showed both an increase in muscle cell size and a reduction in collagen scar tissue expression following muscle injury. It also saw that leucine helped to reduce accumulation of ubiquitinated proteins (proteins genetically destined for degradation), meaning more protein available for synthesis.
These studies show the potential added benefit of leucine not only in healthy muscle, but also as an aid to rehabilitation.
How To Take Leucine
A good guideline to follow is that between 2.5g and 4.0 g of leucine per meal are required to maximize MPS (2). Less than 2g of leucine per meal and protein will predominantly be used as calories.
It is also advisable to think about what are planning to consume with your single leucine supplement or high leucine protein.
Combining 2.5g of leucine to 20g of casein protein significantly boosts insulin response and MPS (53).
Other Essential Amino Acids >>>
A mix of leucine AND a BCAA or essential amino acid supplement combination works to optimise the efficiency of leucine to increase muscle mass and performance gains (54-55).
One specific alpha amino acid to consider mixing with Leucine is citrulline. This compound has its own role in weakly assisting MPS and aiding muscle function (56-58), especially during aging. It is thought that the combination of leucine and citrulline may work synergistically to amplify leucines cellular signalling and activation of mTOR. However, this theory is yet to be tested in athletes.
When consumed with glucose, leucine works to promote the release of the hormone insulin from the pancreas (59-60). It seems again that combining leucine with another compound (this time glucose) may have a collaborative relationship. In this instance it is where the duo consumed together boosts the amount of insulin available to undertake its own anabolic increase of MPS.
Leucine | Dosage & Safety
It is suggested that BCAA requirements are underestimated in the formation of values of estimated average requirement (EAR) and recommended dietary allowance (RDA) (66-67).
However one study (67) recommends that to overcome this fact, one needs to increase the EAR value by 10% for BCAAs, including leucine.
They advise an EAR of 144mg/ kg per day of BCAAs and 210mg/ kg per day as the safe maximal intake for the average population. They also recognise this is significantly higher than the World Health Organisation estimates of BCAA requirements (34mg/ kg per day) (68).
A number of studies on humans have shown that there are no adverse effects of BCAA supplementation in both healthy (61-62) and those with disease (63-64).
There has also been studies on leucine specifically, one of which examined an intake of 1250mg per kg of body weight (which is 25 times the estimated average intake!) (65).
This study identified that the highest concentrations of leucine cause an increase in the amount of ammonia in the blood which can be a potentially serious complication. As such an upper maximum limit was established of 500mg per kg to prevent toxicity.
Take Home Message
Whether you want to increase muscle mass gain, maintain lean body mass or improve performance, if you supplement your diet- you have to think about leucine!
Make sure your current protein intake is sufficient to provide you with enough leucine to optimise your muscle protein synthesis post work out, and if its NOT, then dont be afraid of adding a bit of BCAA or single leucine powder to your post work out shakes.
Maybe go the whole way and add some carbs or citrulline to make the cocktail even more muscle potent!
Many thanks, Chris
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