Leucine is an amino acid that is used by the body mainly for building muscle and providing energy. It’s widely used to improve strength during exercise and muscle recovery times, which makes it a popular supplement among athletes and gym members. However, overconsumption of leucine does more harm than good. Keep reading to learn about the health benefits and side effects of leucine.
What Is Leucine?
Leucine is an amino acid that is regularly taken as a supplement. It is essential to the body, meaning that it cannot be produced and is needed to survive. Hence, leucine must be provided through food intake or supplements.
Leucine is a branched chain amino acid (BCAA). The other two BCAAs are valine and isoleucine, with leucine the most promising of the three when used as a bodybuilding supplement.
Similarly to many other amino acids, leucine is found in many foods that are high in protein. Examples include meats (such as fish, chicken, and turkey), dairy products (such as yogurt and cheese), and soybeans. Other foods like eggs, nuts, seeds, and fruit also contain leucine, but to a lesser extent.
Leucine can be classified in:
- L-leucine is the natural version of the amino acid, is found in the proteins of the body, and is the main form used as a supplement.
- D-leucine is the mirror image of L-leucine, which is created in the laboratory and is also used as a supplement.
Health Benefits of Leucine
1) Increases Energy Production
For the first 45 minutes, leucine supplementation increases energy production, but afterward, it produces a decrease in energy (most likely due to the restriction of pyruvate breakdown) .
Leucine breakdown produces two molecules that are used to obtain energy: acetyl-CoA and acetoacetate .
In rats, leucine also serves as a precursor to different fats (fatty acids, nonsaponifiable fats, and sterols) that are later broken down to produce energy .
Fasting leads to increased levels of leucine in the blood and increased activity of enzymes that convert leucine into ketone bodies and used for energy .
Patients with deficiencies in the molecule that breaks down leucine into acetyl-CoA and acetoacetate (3-Hydroxy-3-methylglutaryl-CoA lyase) develop acidosis (low blood pH) and hypoglycemia (low blood glucose) .
On the other hand, in rats, leucine increases blood levels of insulin, which causes glucose uptake by the cells and ultimately energy production. Together, leucine and glucose-induced a 4.5-fold increase in insulin (compared to 2.4-fold by glucose alone). Therefore, leucine plays a key role in maintaining glucose levels and producing energy .
Also Decreases Energy
Even though leucine increases insulin, which usually increases glucose uptake, leucine can also block glucose uptake.
Fasting increases blood levels of branched-chain amino acids (BCAAs) such as leucine. A study found that fasted animals with increased leucine concentrations did not uptake as much glucose as non-fasted animals thereby reducing energy production [R, R].
Leucine blocks pyruvate (a molecule that glucose is converted to produce energy) breakdown so that the glucose can’t be used for energy .
In people that fasted, leucine supplements also reduced energy production because it inhibited the insulin-mediated glucose uptake by the muscles .
Leucine supplementation increases blood insulin levels, which boosts the uptake of glucose in the muscles. However, leucine decreased the insulin-mediated glucose utilization by 50 to 83% in fasted rats [6, 7].
The inhibitory effect of leucine on energy production causes problems when it’s supplemented to increase energy. Therefore, it is advised that bodybuilders consume a meal prior to workouts. Otherwise, the supplementation could actually be hindering the workout.
Because of the inhibitory effect that leucine has on insulin-mediated glucose uptake, people with diabetes and those taking insulin should stay away from or not fast before leucine supplementation. This could possibly cause diabetic shock due to low levels of insulin and glucose.
2) Improves Muscles
Improves Muscle Recovery
BCAAs help protein synthesis and prevent protein degradation, which in turn helps prevent muscle fatigue and soreness .
In a study (DB-RCT) of 30 healthy adults, squat exercises caused muscle fatigue and soreness. Those that received BCAA supplementation had less soreness in the following days, while those that did not receive supplementation showed prolonged periods of soreness .
The muscle fatigue after exercise also decreased with BCAA supplementation .
Additional tests on individual BCAAs should be done to see if these amino acids can produce the desired effects individually (such as by leucine).
Furthermore, the same study also showed that leucine supplementation decreased muscle protein breakdown .
However, short-term amino acid supplementation (mostly L-leucine, but mixed with 13 other amino acids) showed no effect on 100km ultra-runners. Muscle soreness and race completion times did not improve with the supplementation .
Decreases Muscle Wasting
In studies on rats with cancer cachexia (a disease with heavy muscle wasting), leucine supplementation increased muscle mass (by 23% in the gastrocnemius, and by 22% in the tibialis anterior) .
Leucine also increased total amino acid concentration in blood, which is beneficial in creating more proteins and muscle .
In patients with either burns, trauma, or sepsis (infection in the tissues), branched chain amino acid (BCAA) supplementation, which includes leucine and two other amino acids, decreased muscle wasting .
Additionally, when humans age, they undergo sarcopenia, a natural decline of muscle and an increase in fat. This leads to an increased risk of injury and disability .
In younger adults, both high and low dosages of leucine supplements were able to increase protein synthesis .
However, in elderly patients, only those given high-content supplements increased protein synthesis .
3) Increases the Amount of Protein
In studies on rat diaphragms, adding amino acids increased protein synthesis. Higher concentrations of amino acids produced greater effects .
However, these effects were solely due to the branch chained amino acids (BCAAs) and the other amino acids produced no effect on protein synthesis. Leucine, isoleucine, and valine are the three BCAAs .
When BCAAs were tested individually in rats, leucine was the most significant enhancer of protein synthesis. Valine by itself was unable to affect protein synthesis and isoleucine produced an inhibitory effect .
Excessive breakdown of these amino acids, which is common during fasting and in diabetic patients, leads to a limited supply of BCAAs, which in turn may decrease protein synthesis rates .
Only leucine was able to increase protein synthesis by 25% by itself .
These studies show that leucine is not only a crucial building block of proteins but also an important regulator in the production of proteins.
Proteins are the building blocks of muscles, so increasing protein synthesis would help build muscle in a similar way to how leucine supplementation increases muscle recovery .
4) May Increase Strength
A study performed on 26 men tested how leucine supplementation could lead to increased strength, measured through the maximum weight someone can lift five times .
Those that received L-leucine supplements were able to lift heavier weights .
However, leucine supplementation did not lead to increased muscle mass .
5) May Increase Longevity
Dairy-rich diets (which have a lot of amino acids such as leucine) increased the activation of the SIRT1 gene, which increased the number of mitochondria by 40% in muscle and fat cells. The increase in mitochondria is related to cell longevity .
Direct supplementation with leucine and its metabolites caused an increase in SIRT1 activity by 30 to 50%. Since high-calcium diets by themselves didn’t improve lifespan in rats, the observed effect may be attributed to leucine [19, 20].
6) Reduces the Risk of Hardening of the Arteries (Atherosclerosis)
Hardening of the arteries (atherosclerosis) is linked to high levels of low-density lipoproteins (LDL), while high-density lipoproteins (HDL) reduces the risk of atherosclerosis due to their role in reverse cholesterol transport (the process of returning cholesterol from the tissues to the liver) .
In rat studies, leucine supplementation decreased LDL by 41% and increased HDL by 40% .
Leucine supplementation also decreased atherosclerotic lesions (by 58%) .
Both high cholesterol levels and chronic inflammation are linked to atherosclerosis. Leucine supplementation reduced liver cholesterol by 52% and decreased inflammation .
7) May Help with Obesity
Rats given leucine-rich diets gained 32% less weight and decreased obesity by 25% .
Leucine also decreased cholesterol levels by 27% and LDL or “bad” cholesterol levels by 53%, thus reducing the risk of obesity .
BCAA Supplementation Is Not As Helpful As Leucine Only
Finally, some studies do not specifically test for leucine but for all the branch chained amino acids (BCAAs): leucine, isoleucine, and valine.
It was shown that leucine was the only BCAA that increased protein synthesis, while isoleucine actually had an inhibitory effect. Therefore, to maximize supplement efficiency, the patients should not be given BCAA supplements, but solely leucine .
However, some studies have shown that:
BCAA Supplementation May Improve Liver Cirrhosis
One study (DB-RCT) has shown that BCAA supplementation not only increased nutritional status but also the quality of life (improved sleep and decreased fatigue) in patients with liver cirrhosis .
BCAA Supplementation Helps Kidney Failure
BCAA supplementation is beneficial for those with chronic kidney failure because it provides the needed amino acids without increasing protein intake (known to increase kidney damage), which reduces the chances of kidney failure by 40% [24, 25].
Moreover, BCAA supplementation improved nutrition and appetite in patients undergoing dialysis .
Leucine Side Effects
1) May Decrease Serotonin
The blood-brain barrier competes for the absorption into the brain of branch chained amino acids (BCAA) and aromatic amino acids (ArAA), which are the precursors of serotonin. This competition decreases serotonin production .
Leucine absorption into the brain is influenced by diet; carbohydrate-rich, protein-poor diets increase BCAAs and decrease ArAAs in the brain, while a carbohydrate-poor, protein-rich diet does the opposite .
2) Excessive Supplementation Leads to Brain Damage and Liver Disease
The recommended dosage of leucine for everyday people is 50 mg/kgd, but for those who want to bolster their workouts, the dosage should not go over 500 mg/kgd. Overdose can lead to increased blood ammonia levels; therefore, brain damage and liver disease .
Contraindications of Leucine Supplementation
Leucine supplementation lowers glucose levels, which can lead to unhealthy levels in people with:
- Hypoglycemia (low blood sugar) 
- Diabetes, in those who take blood sugar-lowering medication [7, 29]
Leucine Supplement Reviews
Unlike some other amino acid supplements that are more cognitive function-based and might have mixed effects on different people, leucine is pretty constant in its beneficial effects.
Review boards stated that the leucine was very helpful and that it was crucial to them in maintaining the muscles after workouts. One user stated that the supplement helps him feel “recharged after an intense workout”.
People also notice more muscle gain after leucine supplementation.
One note of caution is that almost every review bemoaned the taste of the leucine supplement. Many said that leucine was very bitter, but that it was worth it due to its positive effects.
Some users saw some different side effects like loud ringing in her ears and increased anger that disappeared only after she stopped taking the leucine supplements .
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