Isoleucine

What is Isoleucine?

Isoleucine is an essential amino acid as the body cannot synthesise it and needs to be obtained from the diet. Isoleucine is one of the three branch chained amino acids (BCAAs). The two other BCAAs are luecine and valine.

BCAAs are needed in the synthesis of excitatory or inhibitory neurotransmitters which includes GABA.

Health Benefits of Isoleucine

Supports wound healing

Isoleucine can support blood clotting at wound sites and accelerate wound healing.

Blood clotting, or coagulation, is a complex process that involves the activation of various proteins in the blood, leading to the formation of a clot at the site of injury to prevent excessive bleeding.

One of the key proteins involved in blood clotting is called thrombin. Thrombin is produced from a precursor protein called prothrombin, which is made in the liver and released into the blood. Isoleucine is one of the amino acids that make up prothrombin, and it is important for the proper folding and function of the protein.

Helps build muscles and improves muscle health

Isoleucine is an essential amino acid and is a part of the branched-chain amino acid (BCAA) group. It is needed for building muscle mass. BCAAs are a common supplement taken by athletes and body builders.

Isoleucine is important for muscle growth, repair and recovery but much of its benefits for muscle maintenance comes from working synergistically with the other BCAAs valine and leucine. It is found to be low in athletes and body builders which is why BCAAs are a popular supplement for sports.

Improves stamina and endurance

Isoleucine along with the other BCAAs prevents breakdown of muscles from strenuous exercise by supplying extra glucose to the muscles. This provides a boost of energy during strenuous activity or workout and can reduce post-workout soreness, aches and pains.

BCAAs are useful for improving stamina and increasing endurance.

Sustains energy levels

BCAAs are not only important for tissue repair and muscle growth but needed to help regulate blood sugar levels to sustain energy levels. Isoleucine helps effectively use up glucose for energy during strenuous exercise.

Valine is the other BCAA that works synergistically with leucine which helps maintain glycogen and blood glucose levels. Valine is effective at this without taking the other two BCAAs leucine and isoleucine and should be taken together to maximize potential benefits for sustained energy levels. Leucine does not help with the synthesis of glycogen. [R]

The body produces energy by breaking down isoleucine in muscle tissue.

Helps with neurotransmitters

BCAAs are involved in the synthesis of excitatory or inhibitory neurotransmitters needed for cognitive function and depends on the genetic disposition of the person. Valine supports the central nervous system and cognitive function.

BCAAs are needed for the production of excitatory neurotransmitter glutamate and inhibitory neurotransmitter gamma-aminobutyric acid (GABA) within the brain due to the role of these amino acids as nitrogen donors. [R]

Regulate immune system function

Valine along with the other two BCAAs is essential for a healthy immune system.

BCAAs are important for the functions of lymphocytes and also needed for other immune cell functions. [R]

BCAAs are needed for the synthesis of RNA, DNA and protein by lymphocytes which have been observed in cell culture studies.

Improves sleep wake cycle

BCAAs may help with the sleep-wake cycle with studies showing improvement in people suffering from traumatic brain injury.

However excess BCAAs may not be as beneficial in healthy individuals. [R] [R]

Reduce stress and anxiety

Studies have shown BCAAs intake reduced the odds of depression and anxiety. A higher intake of valine, leucine and isoleucine is also linked to reduced odds of depression and anxiety. [R]

Agonist / Synergist

Vitamins B7

Amino acids BCAAs, threonine, methionine

BCAAs are catalyzed by propionyl-CoA carboxylase which is an enzyme that requires biotin (vitamin B7) for its functions.

Biotin (vitamin B7) is an essential cofactor for carboxylase enzymes. These enzymes are involved in the metabolism of fatty acids and amino acids

Carboxylase enzymes are essential for the utilisation of BCAAs for neurotransmitters synthesis and to produce energy

BCAAs are nitrogen donors and help with synthesis of inhibitory neurotransmitter glutamate and inhibitory neurotransmitter gamma-aminobutyric acid (GABA)

Valine meeds to be taken with leucine and isoleucine for muscle growth and development and will not work on its own

Threonine is converted into α-ketobutyrate for the synthesis of isoleucine. Threonine deaminase (also known as Threonine dehydratase) is an enzyme needed for this synthesis and is activated by valine.

Isoleucine inhibits the Threonine deaminase enzyme [R]

Methionine and threonine has some effects on BCAAs [R]

Antagonists

Amino acidsPhenylalanine, tryptophan

BCAAs (branched chain amino acids includes leucine, isoleucine and valine) compete with phenylalanine and tyrosine which can impact levels of neurotransmitters found in the brain that follow the catecholamines pathway which include dopamine, epinephrine and norepinephrine.

BCAAs compete for transport across the blood-brain barrier (BBB) with tryptophan and can impact serotonin levels.

Elevated blood levels of BCAA deplete tryptophan in the brain, which causes low serotonin

BCAAs compete with phenylalanine and tyrosine for transport across the blood-brain barrier

Food Sources of Isoleucine

Amino acids are found in abundance in animal food sources.

Isoleucine can be found in a variety of foods. Animal food sources of this amino acid include beef, chicken pork, tuna, and yoghurt.

Plant based food sources of isoleucine include lentils, soy protein, tofu, navy beans, podded peas peanuts, sesame seeds, pumpkin seeds, oatmeal, mushrooms, leafy greens and squash.

Recommended Daily Allowance

Adults need around 19mg or 20mg of isoleucine per kg of body weight per day from dietary intake for optimal functioning.

Children need more amino acids that adults as their body is still developing. The recommended daily amount for children over the age of three increases by 10% to 20% more than what is needed by adults. For infants the amount required increases by 150% more than what is needed by adults.

The requirements may change on individual basis and highly dependent on existing health.

Isoleucine Supplementation

Isoleucine is available as capsules, tablets or powders. This amino acid can be found in many full spectrum amino acid supplement. Isoleucine is not widely available as a single supplement and is found in supplements providing all three BCAAs which includes leucine and valine. BCAA supplements are often advertised as a sports supplement as they are beneficial for athletes and body builders.

Taking isoleucine in a BCAA supplement is more convenient than taking it as a singular amino acid as all three BCAA work synergistically for the health benefits and functions of the body.

BCAAs as powdered supplement do not taste good and are commonly found with added flavour. For this reason it is better to take capsule or tablet forms.

Only recommended dosage should be taken which may be found on supplement label or if in doubt ask a health professional. Excessive or high amounts of BCAA should be avoided.

BCAAs have to be taken in the correct ratio for better absorption and to achieve the health benefits from these amino acids. The recommended ratio is 2:1:1 which would equate to about 2 mg of leucine and 1mg each of isoleucine and valine. Most BCAA supplements are available in the correct ratio but various other ratios are also available and may require some experimentation. Another reason for this ratio is because it has shown to be most effective for stamina and endurance.

BCAA supplements can be taken at any time which includes before, during, or after exercise and at any other times. They can also be taken at bedtime however it is best to take at least an hour before bed.

BCAAs taken at bedtime may help with the synthesis of muscle protein over the period of sleep, however this has not been studied.

Taking single amino acid supplements are not always recommended and may be harmful for those with damaged liver or kidneys.

Deficiency Symptoms of Isoleucine

Isoleucine deficiency is uncommon because BCAAs are readily available in a variety of foods. Deficiency is likely from excessive exercise and without replenishing BCAA levels either through diet or appropriate supplementation.

Signs and symptoms of valine deficiency include;

Degenerative neurological conditions*
Low GABA levels
Anxiety
Hypoglycaemia

Isoleucine deficiency may cause degenerative neurological conditions as it is needed protecting the myelin sheath. The myelin sheath acts as an insulation for nerve cells which covers and protects nerve cells. The myelin sheath is implicated in many degenerative health conditions which includes Alzheimer’s disease and Parkinson’s disease. Multiple Sclerosis (MS) is also another health condition where problems with myelin sheath has been linked.

Hypoglycaemia symptoms include:

Dizziness
Fatigue
Headaches
Confusion
Irritability
Depression

Causes of low isoleucine include:

Inadequate dietary intake (low protein diets)
Excessive or strenuous exercise (as seen in athletes and body builders)*

*Athletes and body builders and people who generally exercise a lot to build muscle mass have an increased need for valine and the other BCAAs. BCAAs are a popular sports supplement.

Most people may not require supplementation of BCAAs if following a healthy diet however a severe deficiency will require supplementation. If a deficiency is suspected it is important to check levels with a health professional such as a doctor. [R]

Toxicity Symptoms of Isoleucine

Isoleucine is an essential amino acid, however excessive amounts can cause a host of symptoms. The signs and symptoms of excess isoleucine include:

Hallucinations and a skin crawling sensation
Impaired kidney function
Impaired liver function
High levels of toxic ammonia in the body
Disturbance in the sleep-wake cycle in healthy individuals
Branched-chain ketoaciduria also called maple syrup urine disease (MSUD)*
Reduced levels of serotonin – competes with serotonin precursor tryptophan
Reduced levels of dopamine – competes with dopamine precursor phenylalanine and tyrosine

BCAAs have been shown to be effective in the sleep-wake cycle in people suffering from traumatic brain cycle however it is not as beneficial in high amounts in healthy individuals and instead may cause a disturbance in the sleep-wake cycle.

It is not recommended to take BCAAs with impaired liver or kidney function and a person’s health will need to be assessed before considering therapy with BCAAs.

Toxicity causes of isoleucine:

Excessive supplementation of isoleucine
Branched-chain ketoaciduria – impaired metabolism of BCAAs
Vitamin B7 deficiency

Carboxylase enzymes are essential for the utilisation of branched-chain amino acids and are needed for neurotransmitter synthesis and providing energy.

Biotin (vitamin B7) is an essential cofactor for carboxylase enzymes. These enzymes are involved in the metabolism of fatty acids and amino acids. A deficiency of vitamin B7 is linked to cognitive decline, mood changes, depression, fatigue, hallucinations, and numbness and tingling of the extremities.

Toxicity is treated by restricting dietary intake of Isoleucine.

BCAAs “steal” tryptophan and compete with uptake in the brain which can lower serotonin levels. Low serotonin levels affects mood and may be a cause for low mood or depression. Serotonin also regulates appetite and when significantly reduced can cause binge eating especially of simple carbohydrates.

Studies have shown that low serotonin level from high BCAA intake in mice fed with twice as much as the normal amount resulted in the animals becoming obese from overeating. Obesity significantly increases poor health conditions and reduces lifespan. [R]

Excess BCAAs may cause the production of too much insulin which can lead to low blood sugar levels (hypoglycaemia) if glucose reserves are rapidly used up or not being replenished through the diet.

Branched-chain ketoaciduria is a metabolic disease characterized by impaired metabolism of BCAAs. It is also known as maple syrup urine disease (MSUD) as the odour from the urine is similar to maple syrup. Although this condition does not indicate low levels of BCAA it is a sign that the BCAAs are not being utilized by the body which will lead to toxic levels of BCAAs. This condition can cause delirium and neurological problems.

Amino acids are transported to the liver during digestion where protein is synthesised.

If there is too much protein the amino acids can convert into fat and stored in fat deposits or if needed made into glucose for energy by gluconeogenesis.

Excess amino acids from protein digestion can be excreted safely. The amino acids are deaminated in the liver where they are formed into ammonia which can be toxic if not eliminated. In healthy liver functioning the ammonia is converted to urea for safe excretion. [R]

Excess amino acids are excreted by the liver through liver cells releasing urea and water which are transported to the kidneys to filter the blood and then excreting urea through urine.

It is important to seek medical advice from medical practitioners such as a General Physician before taking any BCAA supplements as certain conditions such as an impaired kidney or liver function can worsen.