Glutamine is one of the most well-known amino acids in the supplement world because of the many roles it plays in the body. It’s an important component of protein, it nurtures good intestinal health, and your immune system depends on it.
While glutamine is produced naturally in the body and is found in various foods—meat, seafood, cabbage, beans, and eggs to name a few—glutamine supplements have become popular for boosting glutamine levels in the body, especially among people looking to build muscle mass. But should you take a glutamine supplement? Is it worth it? Let’s find out!
Glutamine’s Main Role in Muscle
As the most abundant free amino acid in muscle, glutamine is required for muscle protein synthesis (the building of new muscle tissue). Because it is made in the body and is available in abundance, there is never a shortage of glutamine for protein synthesis.
Glutamine’s main role in muscle is to detoxify the ammonia that is released when amino acids are metabolized.
Ammonia released from the metabolism of certain amino acids, including the branched-chain amino acids leucine, valine, and isoleucine, is transferred to the amino acid glutamate to form glutamine in muscle. Glutamine is then released by muscle and carried via the blood to the liver, where the toxic ammonia is converted into nontoxic urea and excreted in the urine. Glutamine is the main carrier of ammonia throughout the body.
Muscle Glutamine and Critical Illness
Depletion of muscle glutamine occurs in almost all diseases and illnesses. Glutamine depletion occurs at the same time as the net breakdown of muscle in disease states. It has therefore been widely postulated that glutamine depletion resulting from impaired production causes muscle protein breakdown, and, thus, the wasting away of muscle. However, this is not the case in critically-ill patients. Rather, glutamine synthesis in muscle is accelerated in critically-ill patients.
The reduction in glutamine concentration in muscle actually results from the rapid transport of glutamine out of the muscle and into the blood, where it is taken up at increased rates in other tissues and organs. Because of rapid use by other tissues and organs, the blood level of glutamine drops despite the accelerated release from muscle.
Accelerated glutamine production in muscle occurring at the same time as an increase in muscle protein breakdown is to be expected. Here’s why: when muscle protein breaks down, amino acids are released and metabolized, creating potentially toxic ammonia in the process.
Speed up protein breakdown, and you’re creating more need for resulting ammonia to be cleared away from the muscle and transferred to the liver for the purpose of urea production and eventual excretion. Urea excretion is increased in almost all forms of serious illness. As we’ve already discussed, glutamine plays a key role in this process. The concentration of glutamine in muscle falls, because it is being rapidly exported into the blood to deal with increased ammonia concentrations.
Muscle Glutamine and Overtraining Syndrome
Overtraining syndrome is a collection of responses that occur when a person isn’t sufficiently recovering from workouts, usually over several days. The main symptom is that performance deteriorates despite harder and harder training.
Although there is little doubt that overtraining can occur, the exact basis for the syndrome is still uncertain. It would be quite helpful to know why overtraining occurs, as this knowledge could presumably be used to avoid overtraining, as well as to do something about it once it occurs.
Reduced concentrations of glutamine in muscle and blood are markers of overtraining syndrome, but it is unclear if decreases in glutamine cause the syndrome or if glutamine depletion is merely a symptom of overtraining.
Supplementing with Glutamine During Critical Illness and Overtraining Syndrome
The relationship between decreases in the concentration of glutamine in muscle and the net loss of muscle protein (in critical illness) and deterioration of performance (in the overtraining syndrome) leads logically to the use of glutamine supplements in both circumstances. However, there is little evidence that glutamine supplements maintain muscle mass and function in any circumstance.
For one thing, the body normally makes in the range of 80 grams of glutamine per day, and the rate of glutamine production increases in pathological states. Also, glutamine is an abundant component of dietary protein, so daily consumption of glutamine may be as much as 80 grams per day as well. Therefore, it is very difficult to consume enough of a glutamine supplement to make a significant impact on the body’s glutamine levels relative to the amount that is normally produced and consumed through your normal diet.
Moreover, it is very difficult to get glutamine into the muscle cell when the response to increase the export of glutamine has been activated. Glutamine doesn’t move freely into and out of the muscle. Rather, there is a transporter specifically for glutamine that shepherds glutamine from the blood into the cell against a concentration gradient. That transport mechanism is reversed in critical illness and the overtraining syndrome, so rather than carrying glutamine into the muscle, it is carrying glutamine out of the muscle and into the blood. As a result, very little glutamine will enter the muscle, even when the blood concentration is increased significantly with glutamine supplementation. Consequently, taking a glutamine supplement has little impact on muscle mass or function.
Glutamine and Immune Function
Immune function involves a complex network of different cells and signaling molecules that are crucial for fighting infection. A variety of immune system functions are supported by glutamine metabolism, and the decrease in blood glutamine concentration in critical illness occurs in part because of the accelerated use of glutamine by the immune system.
Researchers analyzed the ability of a glutamine supplement to enhance immune function, as reflected by infectious complications and length of hospital stay in surgical or critically-ill patients, in a review of 14 different clinical trials of glutamine supplementation. This analysis showed that there may be an association between glutamine supplementation and a reduction in infectious complications and shorter hospital stays, although the associations were not very strong.
The importance of immune function in hospitalized patients is evident, as the resistance to infection is crucial in recovery. It is less well appreciated that exhaustive exercise also stresses the immune system. According to a study published in the journal Nutrition, glutamine supplementation may also decrease the incidence of infections following exhaustive exercise in endurance athletes.
Glutamine and Intestinal Health
In addition to the intestine’s role in digestion and nutrient absorption, there are intestinal cells involved in a variety of other functions, including the immune response and the secretion of hormones.
Amino acids, particularly glutamine and other nonessential amino acids that can be produced in the body, have an important metabolic role in the intestines. Glutamine metabolism contributes an important portion of energy generation in the intestine and is a precursor for a number of important metabolic pathways, especially those leading to the production of the amino acids ornithine, citrulline, proline, and arginine.
Because of the specific role of glutamine in the intestine, as well as its protective function in the intestine, many clinical trials have been conducted assessing the benefits of glutamine supplementation on intestinal health, particularly in clinical states in which normal intestinal function is disrupted. The results of these trials have been confusing and inconclusive. This is in part due to the fact that the amino acids glutamate and proline can readily substitute for many of the metabolic roles of glutamine, including energy production and amino acid synthesis. Whether or not glutamine supplementation benefits intestinal health is, at best, “equivocal.”
Glutamine and Neurotransmitters
Glutamine has several roles in the brain and central nervous system (CNS). The principle action of glutamine is as a precursor for the production of glutamate and aspartate, which are both excitatory neurotransmitters. Glutamine is also the precursor of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
Much of the production of glutamate and GABA from glutamine occurs via a metabolic pathway within the CNS. Glutamine is produced from glutamate and ammonia in specialized cells within the CNS called astrocytes. Newly produced glutamine is transferred to neurons, where it is converted to glutamate and GABA, and may also be converted to aspartate. The relationship between glutamine and glutamate in the astrocyte is cyclic in that glutamine metabolism forms glutamate, which, in turn, combines with ammonia to re-form glutamine. For this reason, it is referred to as the glutamine/glutamate cycle in astrocytes.
Glutamate, GABA, and aspartate produced from glutamine function as neurotransmitters. Since glutamate and aspartate work to counteract the influence of GABA, the balance of these neurotransmitters is crucial for healthy brain activity. The metabolic reactions regulating the glutamine/glutamate cycle are under tight control to ensure that the appropriate balance of neurotransmitters is maintained.
Glutamine Supplementation and Brain Function
Glutamine can pass through the blood-brain barrier by a specialized transporter, so in theory, taking a glutamine supplement can increase glutamine in the brain. However, most of the glutamine in the brain comes from glutamate combining with ammonia in the astrocytes in the brain.
Glutamine supplementation is often advocated to improve brain health, particularly when blood levels of glutamine are low, but evidence to support this claim is minimal. It is very difficult to increase the concentration of glutamine in the blood and ensure it enters the brain because a typical glutamine supplement provides such a small fraction of the total amount of glutamine in the body. Further, the entry of glutamine into the brain is regulated to maintain a proper balance of glutamate aspartate and GABA. The primary source of glutamine in the brain is derived from the glutamine/glutamate cycle rather than from the blood, so the failure to demonstrate glutamine’s beneficial effect on brain health in an amount greater than what is normally consumed in the diet is not surprising.
So…Should You Take a Glutamine Supplement?
Glutamine is the most abundant free amino acid in the body and plays many metabolic roles. It serves as a shuttle to transfer ammonia from muscle to liver, as an energy source for the intestine and immune system, and as a precursor for key neurotransmitters in the brain.
Because of the many diverse roles of glutamine, taking glutamine supplements has been promoted extensively, particularly in stressful or pathological situations when glutamine concentration in the blood is depleted. There is some evidence that glutamine supplementation may aid immune function when the blood glutamine concentration is decreased. However, in most circumstances, glutamine supplementation has shown minimal beneficial effects in other regards, including muscle building and brain function.
In large part, the ambiguous results of glutamine supplementation can be attributed to the rate of glutamine production in the body, as well as normal dietary consumption. Glutamine production is already so great that the incremental increase in glutamine availability resulting from a dietary supplement will usually be of minimal significance.