INTRODUCTION

Glutamine is the most common non-essential amino acid found in skeletal muscle, making up approximately 60% of the intramuscular amino acid pool. It is claimed that during intense resistance exercise, intramuscular and plasma glutamine stores become depleted and cause declines in muscle mass, strength and muscle endurance. Glutamine acts as the primary transporter of nitrogen between muscle cells and other tissues, leading to suggestions of glutamine playing a critical role in maintaining muscle protein synthesis levels and a net anabolic state. Although glutamine is found naturally occurring in most plant and animal protein sources, these claims have lead to the marketing of supplemental glutamine to bodybuilders, weightlifters and athletes. Suggested benefits include accelerated gains in muscle mass, elevated growth hormone levels, increased rates of protein synthesis and decreased rates of protein breakdown. In April 2018, an article by bodybuilding.com, the world’s largest distributor of online supplements with over 25 million orders dispatched, listed glutamine as number 5 on the “Top 5 Supplements for Faster Muscle Gain” list.

During periods of severe physiological stress, such as critical illnesses (cachexia, infection) and injuries (burns, trauma), plasma glutamine concentrations can fall by up to 50%, causing the depletion of intramuscular glutamine stores. Under these conditions glutamine is considered to change from a non-essential to a “conditionally essential” amino acid, meaning the ability to synthesise glutamine isn’t sufficient to meet physiological demands. Prior to suggestions as a bodybuilding aid, glutamine supplementation was shown to maintain muscle glutamine content under such conditions. This prevention of glutamine depletion reduced muscle wastage and attenuated the decline in protein synthesis associated with these catabolic states. The relationship between maintaining muscle glutamine content and net positive protein synthesis lead to the recommendations of glutamine supplementation for bodybuilders concerned with maintaining a sustained net muscle protein synthesis level beyond protein breakdown to cause muscle hypertrophy. It was further suggested that strenuous strength training workouts could induce a similar catabolic state as seen following injury or during illness, and therefore supplementing with glutamine could prevent the depletion of intramuscular stores and this would consequently have positive effects on protein synthesis levels, muscle growth and recovery.

Glutamine, along with alanine are the major compounds that transport amino nitrogen from muscle cells to different organs and tissues. With glutamine being composed of 19% nitrogen it is considered to have positive effects on nitrogen balance and retention. This concept particularly appeals to bodybuilders, as a positive nitrogen balance is viewed as the optimal state for muscle growth, where nitrogen uptake is greater than nitrogen loss. A relationship between glutamine levels and muscle protein synthesis is further supported by the observation that in vitro, glutamine administration increases the rate of protein synthesis in a dose-dependent manner. Additionally, glutamine infusion to rats reduced rates of muscle protein breakdown.

An additional muscle-building claim is that supplementation with glutamine can increase growth hormone levels. This claim is supported by the basis that oral glutamine ingestion can increase plasma arginine and glutamate concentrations, with these amino acids being previously implicated with increased growth hormone secretion. It is widely held in the bodybuilding community that increased growth hormone levels cause increased rates of muscle growth and fat loss.

THE SCIENTIFIC EVIDENCE

A premise for glutamine supplementation is supported by a number of biochemical principles and physiological concepts, and upon first glance this supplement strategy appears scientifically plausible. As discussed, the theoretical basis for supplementing with glutamine originated from trauma studies, which demonstrated that severely depleted glutamine stores were associated with muscle wastage and a catabolic protein state. Glutamine supplementation attenuated this depletion effect and consequently prevented a decline in protein synthesis levels. Going beyond the literature, it was then suggested that intense resistance training workouts could induce a similar physiological stress as seen following trauma or illness, and therefore the subsequent depletion of glutamine stores and catabolic effects would occur. However, a study by Gleeson and colleagues (1998) showed that following severe eccentric resistance exercise, there were no significant changes in plasma glutamine levels. This suggests that resistance exercise does not induce the same physiological stress or glutamine demand as observed following critical injury or illness, which raises questions surrounding the usefulness for glutamine supplementation among healthy individuals.

The most significant claim relevant to bodybuilding relates to glutamine’s effect on the rates of muscle protein synthesis and breakdown, and subsequent muscle growth. A protein synthesis level exceeding protein breakdown is required for muscle hypertrophy to occur, and thus any intervention that can shift net protein balance in the positive direction is of value to bodybuilders. It is claimed that glutamine plays an important role in maintaining an “anabolic state” through its effect on protein and nitrogen balance, and indeed in vitro and animal studies have provided support for this concept. Of more concern is whether any measurable effects on muscle hypertrophy are observed in trained individuals following glutamine supplementation. A study by Candow and colleagues (2001) investigated the effects of glutamine supplementation combined with resistance training. Interestingly, the study showed no effect of glutamine on both lean muscle mass or protein breakdown when compared to placebo. A second study, by Wilkinson and colleagues (2006) attempted to evaluate the direct effects of glutamine ingestion on rates of muscle protein synthesis after exercise. Glutamine added to a post-workout shake failed to yield higher rates of muscle protein synthesis when compared to having the shake alone.

The final claim related to the muscle-building effects of glutamine is that supplementation can increase growth hormone levels acutely. Consulting the literature, a study by Welbourne and colleagues (1995) showed that a 2g oral dose of glutamine increased plasma growth hormone levels by 400%, remaining above baseline for 90 minutes. On face value this looks like an extremely encouraging result, but considering that 60 minutes of high intensity exercise alone can cause a 2000% increase in growth hormone levels, there doesn’t seem to be a convincing enough reason for bodybuilders to take this supplement when they are already involved in an exercise program. Perhaps a more relevant question would be whether glutamine has a measurable effect on growth hormone levels when combined with resistance exercise, compared to resistance exercise alone, however this is yet to be elucidated.

THE VERDICT

Although the theoretical basis for supplementing with glutamine for the purpose of bodybuilding seems plausible, the literature does not provide sufficient support for this practice. Glutamine was shown to increase rates of muscle protein synthesis in vitro, and decrease muscle protein breakdown in animal models, however in healthy trained males glutamine supplementation failed to show any beneficial effect. Indeed glutamine can increase serum growth hormone levels, but considering the magnitude of change compared to the standard response following a bout of high-intensity exercise, it is unlikely that this hormonal action will yield any measurable effects on muscle hypertrophy in already training athletes. A belief exists among bodybuilders that intense resistance training can induce a marked depletion in intramuscular glutamine levels, and that supplementation can yield the same anti-catabolic benefits as seen in clinical settings. However, the research has shown that this is a misconception, demonstrating that even following intense muscle- damaging resistance exercise, there is not sufficient physiological stress to cause changes to plasma glutamine concentrations, indicating that glutamine demand is remaining stable. In conclusion, despite the widespread use and extreme popularity of this supplement in the bodybuilding community, it does not appear that glutamine supplementation has any significant benefit to muscle growth in healthy individuals.

SCIENTIFIC REFERENCES

(1) Candow, D. G., Chilibeck, P. D., Burke, D. G., Davison, K. S., & Smith-Palmer, T. (2001). Effect of glutamine supplementation combined with resistance training in young adults. Eur J Appl Physiol, 86(2), 142-149. doi: 10.1007/s00421-001-0523-y

Shows glutamine supplementation to have no significant effect on muscle mass gains when combined with a training program, strongly disputing its major claim relevant to bodybuilding.

(2) Gleeson, M., Walsh, N. P., Blannin, A. K., Robson, P. J., Cook, L., Donnelly, A. E., & Day, S. H. (1998). The effect of severe eccentric exercise-induced muscle damage on plasma elastase, glutamine and zinc concentrations. Eur J Appl Physiol Occup Physiol, 77(6), 543-546. doi: 10.1007/s004210050373

Demonstrates how intense eccentric exercise isn’t sufficient to cause changes to plasma glutamine levels, disputing the bodybuilder’s misconception that it does.

(3) Welbourne, T. C. (1995). Increased plasma bicarbonate and growth hormone after an oral glutamine load. Am J Clin Nutr, 61(5), 1058-1061.

Demonstrates the acute effects of glutamine on growth hormone. This study is often cited when promoting glutamine supplements, relying on the fact that customers aren’t familiar with typical growth hormone responses following exercise.

(4) Wilkinson, S. B., Kim, P. L., Armstrong, D., & Phillips, S. M. (2006). Addition of glutamine to essential amino acids and carbohydrate does not enhance anabolism in young human males following exercise. Appl Physiol Nutr Metab, 31(5), 518- 529. doi: 10.1139/h06-028

Demonstrates that glutamine has no additional benefits to stimulating muscle protein synthesis levels, disputing one of its major claims in relation to protein and nitrogen balance.