Effects of bcaa and l-glutamine supplementation on fatigue in juvenile athletes

[icon name=”user” class=”” unprefixed_class=””]  Swapnali Halder, Ph.D.

High-intensity exercise may lead to temporary fatigue because of a deficiency in adenosine triphosphate (ATP) i.e., body’s energy currency, and excessive production of hydrogen ions (H+) and ammonia. Together, these fatigue factors may reduce exercise performance. Moreover, intense exercise may cause muscle tissue damage that generates chronic inflammation (a burning sensation in the muscle), muscle pain, and high frequency of lesions, hence harms exercise performance.Exercise that consumes high levels of energy or involves high recurring rate such as rowing, releases intracellular proteins such creatine kinase (CK), lactate, cytokines in the bloodand this phenomenon is independent of the nature of the muscle damage. It is known that synthesis and release of cell signaling moleculessuch as cytokines in the blood activates inflammatory response. Though the entire mechanism of the inflammatory process is yet to be fully understood, several factors including training and nutrition seem to contribute toit.


Branched chain amino acid or BCAA (one of the building blocks of protein) is metabolized in skeletal muscles and serves as a precursor for glutamine synthesis.
There are contradictory results regarding the impacts of BCAA supplementation. For example, a study has shown that BCAA serves as the major fuel for the muscle energy along with other energy sources such as fat and carbohydrate,during long term exercises.In contrast, another study indicated that increased oxidation of BCAA causes a steady decrease in intermediates in tricarboxylic acid cycle or TCA cycle (a chain of chemical reactions in the cell that generates ATP and some amino acid precursors) and thus may cause fatigue due to energy scarcity.


Glutamine, an amino acid, is abundantly present in human skeletal muscle and blood and plays roles in different cellular mechanisms. Glutamine maintains acid-base balance, serves as a nitrogen precursor for nucleotide synthesis (nucleotides are subunits of DNA and RNA), and plays a regulatory role in protein formation and breakdown as well.Oral supplement of glutamine has shown beneficial effects in treating infections in athletes in an earlier study. This amino acid is also used as a fuel in muscles and as a substance that stimulates immune response. The glutamine level goes down following exhaustive exercise, which is a reason forexperiencingdiscomfort from overtraining in athletes. Therefore glutamine supplementation is vital for growing juvenile athletes. However, according to some studies oral supplementation of glutamine was not successful to enhance immune function or performance in athletes.A comparatively recent study conducted in rats reported that a glutamine containing solution was helpful in mitigating inflammation markers and plasma CK (one type of small protein involved in immune response) levels induced by exhaustive exercise. Koo and colleagues, a group of scientists in the Republic of Korea conducted a study to understand the impacts of BCAA and glutamine supplementation on the blood fatigue factors and cytokines in case of maximal intensity rowing performance.


In their study, Koo and colleagues examined effects of BCAA and glutamine supplementation on lactate, phosphorus, ammonia, CK, and cytokine concentrations in the blood of five male juvenile athletes, who had performed maximal intensity rowing exercise. The subjects were given placebo (PS), BCAA (BS) containing valine, leucine and isoleucine amino acids, or glutamine supplement (GS)or 7 days, three times a day. Doses for BCAA and glutamine were 3.15 g/day and 6g/day respectively. The participants were allowed to eat food or drink normally otherwise. For each type of supplementation, the rowing test was conducted 3 times using an indoor rowing machine. The athletes performed a 2000 m race at their own maximal paces such as 42-45pace for 0m~250m, 40 pace for 250m~500m, 36-38 pace for 500m~1500m, and over 42 pace for 1500m~2000m. Blood samples were collected from venous blood. Venous blood samples were drawn before, immediately after, and 30 minutes after the rowing exercise.

Lactate, phosphorous, ammonia concentrations and CK activity were measured in the blood samples through various biochemical analyses.Concentrations of different cytokines such as IL-6, IL-8, and IL-15 were also analyzed using modern assay techniques.


The results reflected significant variations in the blood lactate concentration at each stage of the exercise, which however remained similar between three groups. The blood lactate concentrations were higher in all three groups at the end of the exercise compared to that at the resting stage and recovery stage.

Blood phosphorous concentration varied from one stage to another; though within a stage the differences were not significant between PS, BS, and GS groups.For all the three groups, the blood phosphorous concentrations at the end of exercise stage were significantly higher than those in the resting stage. Phosphorous levels of the PS group at the recovery stage were similar to those at the end of exercise period, but the levels in the BS and GS groups in the recovery stage were significantly smaller than those at the end of the exercise.

The blood ammonia concentrations also showed similar trend like phosphorous, i.e., different levels in each stage of exercise but no significant differences between PS, BS and GS groups. Ammonia concentrations at the end of exercise stage were higher than those of resting and recovery stages.

For all 3 groups, the blood CK activity levels were higher at the end of the exercise stage compared to the resting stage. Though CK levels from the PS and BS groups in the recovery stage were similar to those at the end of exercise, however the levels in the GS group were lower than that at the end of exercise stage.Among the cytokines, IL-6 and IL-8 did not reflect any significant differences among the groups and stages, however IL-15 showed differences between testing stages.


Improvement of exercise performance is highly associated with body’s capacity to constantly generate anaerobic ATPalong with delaying fatigue. Intensity of fatigue depends on external factors such as exercise intensity, exercising periods etc., as well as on internal factors such as muscle mass, muscle fiber type, and energy storage. During high intensity exercise, decrease in the muscle contraction occurs due to stimulation of fatigue causing metabolites, for example lactate, phosphate and ammonia.An appropriate supply of ergogenic aids (a substance that increases the capacity for physical or mental labor by eliminating fatigue symptoms)can play an important role in improving exercise performance.


BCAA is a dietary component that supplements the energy requirement in the skeletal muscle. Studies conducted on the application of BCAA to minimize fatigue and provide energy source, have shown contradictory results. Some of those reported positive outcomes i.e., enhancement of performance through an increased body concentration of BCAA. In those studies, increased BCAA concentrations led toan enhanced ATP resynthesisand promoted hormone release to stimulate protein synthesis in muscles and increased muscle power.

Glutamine,an amino acid present in muscles and blood is considered crucial for proper immune function since it supplies fuel for nucleotide biosynthesis. Blood glutamine levels were reported to be low in situations of fasting, prolonged exercise or recovery period followed by high intensity exercises. A state of exercise-induced stress consumes an increased amount of glutamine for gluconeogenesis (glucose synthesis from non-carbohydrate precursors), thus plasma glutamine is rapidly diminished. Also, lower levels of blood glutamine may be a reason for causing discomfort in athletes’bodies following overtraining. Therefore right amount of glutamine intake is vital for juvenile athletes in their growing age.

In the study described here, glutamine supplementation did not seem to be effective in reducing blood lactate stimulation during the recovery stage. Lactate production exceeds its removal rate during the high intensity exercise, which in turn impairs ATP synthesis and leads to fatigue. A study informed that glutamate was transformed into other intermediates in the TCA cycle and α-ketoglutarate, and glutamate levels decreased promptly with the decrease in glutamine. Reduction in the TCA cycle intermediates would eventually led to lack in the energy supply. Since carbon skeletons required for glutamine synthesis come from muscle glycogens, glycogen depletion occurs following high intensity exercise. Therefore replenishing the TCA cycle intermediates by supplementing glutamine would decrease the lactate stimulation, giving benefit to the athletes.

An increase in the phosphorous, another fatigue factor, decreases the ratio of cross-bridges in fiber fibers, and prevents the catalysis of ATPase. Besides, hydrogen ion stimulation forms inorganic phosphates, leading to decrease in muscle power supply. In the present study, phosphorous concentrations were significantly lower in BS and GS groups than that of PS group in the recovery stage. Presumably, BCAA or glutamine supplied intermediate substrates of the TCA cycle and thereby helped preservation of ATP, which might otherwise be reduced to inorganic phosphates.

The rate of amino acid metabolism may heighten due to a steady rise in the blood ammonia levels during high intensity exercise, a majority of which is created in thepurine nucleotide cycle or PNC cycle to maintain the adenine nucleotide levels. Glutamine can be interchanged to glutamate and vice versa by release or acceptance of the ammonium ion.


Conditions associated with inactive metabolites, hypoxia, stress, and dietary restriction create problems with internal energy supply. High intensity exercise decreases glycogen, α-ketoglutarate, and glutamate levels, which decreases the creation of glutamine. High level of ammonia formed during the exercise prevents glutamine transformation, elicits fatigue and hampers exercising capability.Though it was not identified in the current study, the similar levels of ammonia concentrations among three groups indicated a probable decrease in the internal BCAA levels by exercise and glutamine supplementation.

The CK, an enzyme that breaks down creatine phosphate to generate anaerobic ATP during high-intensity exercise, is used as a marker for tissue damage caused by exercise stress. Low levels of CK in the GS group at the end of exercise and recovery stages in the present study might reflect the effects of energy supplementation from glutamine supply, which acted as fuel in the muscle.Glutamine might have a positive impact in protecting muscles against exercise stress-induced tissue damages.

In addition to fatigue, intensive exercise may cause tissue damage through inflammatory responses and changes in cytokines.Cytokines are detectable in the plasma during and after strenuous exercise. There are pro- and anti-inflammatory cytokines that belong to the acute phase response to tissue damage. With the fast increase of pro-inflammatory cytokines like IL-1, anti-inflammatory cytokines such as IL-6 also increases accordingly to make a balance in cytokine secretion. IL-6 has been categorized as pro- and anti-inflammatory cytokine, and its main anti-inflammatory property has generated concerns. In the present study, IL-6 levels remained comparable between groups and exercise stages. Though a firm conclusion could not be drawn, these results of the present study indicate that glutamine supplementation might have prevented the increase of inflammation induced by exercise.However, IL-6 synthesis in the skeletal muscle activates AMP-kinase, an enzyme that stimulates glucose uptake and fat oxidation; on the other hand releaseof IL-6 from the muscle maintains glucose homeostasis. Therefore an increase in IL-6 might not occur due to glutamine supplementation.

IL-8, a type of cytokine called chemokineis produced by macrophages(a type of white blood cell that engulfs cellular debris and foreign substances) and epithelial cells (cells that form outer layer of many organs and structures),and causes inflammation by activating inflammatorycells. IL-15 is also created by macrophage and mononuclear phagocyte(another type of cell present in the body that degrades foreign particles). Though the study described here did not exhibit any significant differences in IL-8 for the 3 groups in the resting stage and end of exercise, however for IL-15 the PS and BS groups exhibited differences. The outcomes of examining IL-8 in the present study was different from those of another study, which likely happened due to the differences in exercise intensity and duration. Therefore it seems that an alteration of blood chemokine concentrations requires comparatively high intensity performance of exercise for long duration. IL-15 concentrations were different in the PS and BS groups for the resting stage and the end of exercise except in the GS group. This suggests a more sensitive reaction of IL-15 on exercise than IL-8. Glutamine supplementation seemed to cause a substantial increase in the saved glutamine amount. When the saved glutamine amount decreases, other key molecules or cells of immune system also decrease in their amount. Therefore, IL-15 concentrations in the PS and BS groups increased as a compensational effect of decreased glutamine level. In the GS group, on the other hand, the IL-15 concentration remained stable because the immune function and the inflammatory defense actions were not compromised.

In conclusion, the groups supplemented with BCAA or glutamine showed a decreased blood phosphorous levels compared to the placebo group during the recovery stage after maximal intensity exercise performance.The glutamine supplemented group seemed to have lower concentration of CK compared to other groups, which indicates positive impact of glutamine in attenuating fatigue factor stimulation at the recovery stage. IL-6 and IL-15 differed between the resting stage and the end of exercise for PS and BS groups, but not in the GS groups. Therefore pre-exercise glutamine supplementation is also effective in boosting the immune function and defensive inflammatory function in juvenile athletes compared to a BCAA supplementation or placebo.

Summarized from the article:


GaHee Koo, JinHee Woo, SunGWHun Kang, Ki oK Shin

J. Phys. Ther. Sci. 26: 1241–1246, 2014

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