What is leucine and what does it do?

How do I get stronger? A question echoed in gyms across the world! To get stronger, cross‐sectional area of muscle fibres, muscle strength, and muscle function must increase.

Muscles are made of protein, so to increase muscle mass we need to be making more protein (protein synthesis) than we are breaking down (protein degradation). Protein is made from building blocks called amino acids. There are two groups of amino acids, non-essential, which can be made within the body, and essential, which need to come from food sources. Three of the essential amino acids; leucine, isoleucine and valine are known collectively as branched chain amino acids (BCAAs). These have been identified as important in signalling within skeletal muscle for promotion of protein synthesis.

During exercise, carbohydrates are the initial source of fuel used by skeletal muscles to produce energy. Exercise does however cause an increase in protein breakdown. Endurance exercise causes inhibition of protein synthesis, and an increase in protein degradation. Resistance exercise actually causes an increase in protein synthesis, but also an increase in degradation, causing a net breakdown of protein. These changes persist until adequate protein and energy are available for recovery. (1)

The question is can this balance be altered to promote protein synthesis rather than degradation? The branched chain amino acids, and leucine in particular seem to be instrumental in this.

In isolated rat diaphragms, the addition of amino acids promoted protein synthesis and inhibited degradation of the diaphragm. A five times increased concentration of amino acids had larger effects, and the BCAAs alone had this effect, whilst the other amino acids without the BCAAs had no effect. (2)

In a group of 6 volunteers, ingestion of oral essential amino acids resulted in a change from net muscle protein degradation to net muscle protein synthesis after heavy resistance exercise. (3)

These results have then been shown using leucine alone, rather than in combination. Male rats fed leucine alone after exercise restored protein synthesis to pre-exercise levels. (4)

When tested separately, again in rat diaphragms, valine was ineffective, isoleucine was inhibitory, but 0.5 mM leucine increased the specific activity of muscle proteins, and the activity increased when leucine concentrations were raised from 0.1 to 0.5 mM. (5)

The injection of BCAAs or leucine into psoas muscles showed that administration of the three branched chain amino acids together or leucine alone significantly increased the proportion of polysomes (a building block for protein synthesis).(6)

Do we know how it works?

Ok, so this gets a bit science-ey. During exercise, protein synthesis is reduced by inhibition of factors involved in the synthesis of mRNA (building block for protein). This appears to be under the control of insulin signalling and leucine concentrations. So when we exercise, our skeletal muscle cells start using protein for energy, the activity of the enzyme which breaks down BCAAs (BCKDH) increases, and therefore leucine levels drop. This signals our body to stop building protein. This makes sense, as in a fight or flight situation, or during a marathon for example, the body wants all the energy available to be used to keep running, rather than to be used for building protein. After exercise, recovery of protein synthesis requires an increase in leucine levels to remove the inhibition and allow protein synthesis to start again. (7)

Does leucine actually improve performance?

The first thing to say is that leucine alone will not improve strength performance. Resistance training is the most efficient way to improve muscle strength. In a study of rats, the subjects were split into 5 groups, control groups with low or high dose leucine, and exercising groups with none, low or high dose leucine.  The exercising high dose leucine group showed higher numbers of positive embryonic myosin fibres and myonuclei than any of the other groups. The exercising groups increased the cross‐sectional area, the number of satellite cells and protein expression relative to the control groups. The leucine only group did not increase skeletal muscle hypertrophy and satellite cell activity, regardless of the dose. (8)

In a group of 13 outrigger canoeists, leucine supplementation (45mg/kg) resulted in significant increases in plasma leucine and total BCAA concentrations. Upper body power was significantly greater after leucine supplementation compared to the placebo. Rowing time significantly increased and average RPE significantly decreased with leucine supplementation while these variables were unchanged with the placebo. (9)

In a group of 10 cyclists eating 1.6g/kg/day protein, post exercise leucine-protein ingestion improved mean repeat sprint power by 2.5% and reduced perceived overall tiredness during the sprints by 13%, but perceptions of leg tiredness and soreness were unaffected.  (10)

One study investigated the effect of supplementation with HMB, a metabolite of leucine. Subjects were randomised to 2 protein levels, 117g/day or 175g/day and 3 levels of HMB, 0g, 1.5g or 3g per day. They then underwent a weightlifting program for 3 weeks.  HMB significantly reduced the exercise-induced muscle protein breakdown during the first 2 weeks of exercise. Plasma creatine phosphokinase (a breakdown product of muscle) was also decreased with HMB supplementation. Weight lifted was increased by HMB supplementation when compared with the unsupplemented subjects during each week of the study. Interestingly, no differences in the amount of weight lifted were seen between the different protein level  groups for any of the exercises. This may be because 117g protein/day is already above the recommended protein intake for most people. The total strength (combined upper and lower body weight totals) increased by 8% in the unsupplemented subjects during the 3-wk period, whereas in the 1.5- and 3.0-g HMB-supplemented groups, total strength increased by 13% and 18.4%, respectively. (11)

But do I need to take supplements?

This is where information becomes a bit more unclear. Recommended dietary intake for leucine seems to vary from anywhere from 14mg/kg/day to 60mg/kg/day in athletes. Protein contains 5-10% leucine. (12) So if a person is eating 2g/kg bodyweight of protein then this should be plenty of leucine. The above study however, showed strength increases with additional HMB despite subjects already eating 175g protein per day. The cyclists were also already eating protein 1.6g/kg/day.

In a study of 20 track and field athletes eating 1.26g/kg/day protein, supplementation of 50mg/kg/day leucine prevented decreases in blood leucine concentrations during training. (13)

This implies that supplementation would be beneficial, even on top of a high protein diet, although it is not clear why this would be the case. It would be interesting to know the leucine content of the protein used in the studies above, or to compare a high leucine protein diet to leucine supplementation. As always, there is plenty more research to be done!

Let me know your thoughts in the comments below!

References

1. https://academic.oup.com/jn/article/136/2/533S/4664398
2. http://www.jbc.org/content/250/1/290.short
3. https://www.physiology.org/doi/full/10.1152/ajpendo.1999.276.4.e628
4. https://academic.oup.com/jn/article/129/6/1102/4721899
5. https://www.jci.org/articles/view/108201
6. http://europepmc.org/abstract/MED/457032
7. https://academic.oup.com/jn/article/136/2/533S/4664398
8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021278/
9. https://www.ncbi.nlm.nih.gov/pubmed/16265600
10. https://www.ncbi.nlm.nih.gov/pubmed/21609286
11. https://www.physiology.org/doi/full/10.1152/jappl.1996.81.5.2095
12. https://www.ncbi.nlm.nih.gov/pubmed/1096762
13. https://www.ncbi.nlm.nih.gov/pubmed/9239992