Glutamine Supplementation for Exercise

There are a number of people, myself included, that at one point consumed glutamine, separate from their usual protein intake. However, is this truly necessary? Why would one want to engage in this behavior? Let us find out, together.

What is Glutamine?

Glutamine is a non-essential amino acid that is used in gluconeogenesis, eradicating free radicals, and the formation of complete proteins for your cells to use for various cellular structures and functions [1].

Should I Supplement with Glutamine?

The reasons touted for supplementation are typically around increased immune function. When we exercise for extended periods of time, our immunity is acutely decreased (yet chronically elevated), and this is thought to be, at least partly, due to decreases in glutamine [2]. It is also implicated in catabolic states, moving from a non-essential amino acid, to conditional (meaning, the skeletal muscle may not be able to produce enough of it to meet demand required by other organs) [1][3][4].

So, this raises the question – should we supplement?

No. The reason is, because it is not held up in the research.

Glutamine supplementation does not help with immune function post-exercise, especially anything below one hour [1]. Even in chronic overtraining, there is little to no evidence glutamine supplementation is necessary, or even effective [1].

As for its impact in protein synthesis, the research is associative and cannot be used to come to any conclusions – especially when total protein was used, not glutamine supplementation [4]. As for direct evidence, it does not seem to show any mechanistic impact on increasing muscle protein synthesis, even as mTOR rises, other regulators stay depressed [5][7].

Finally, it’s impact in catabolic states is weak. Most studies have investigated its effect in relation to serious injury and illness leading to a person being bed ridden [3]. Glutamine does decrease with extended exercise, but if this is physiologically relevant is unlikely – albeit seemingly relevant in pathology (i.e. healthy? No impact, seriously ill? May help) [6]. Also, there is mechanistic evidence against the notion glutamine plays any major role in reducing degradation [5].

Interestingly, in vitro (controlled environment) studies show a blunted degradation and increased synthesis with glutamine supplementation, while others show increases in degradation pathways, but we will understand why this does not matter in the next section [9][10].

There is, however, some evidence glutamine may help ameliorate soreness and increase performance recovery from set to set within a training [8].

 

Understanding the Physiology

Some of the results are self-explanatory – glutamine does decrease with exercise, but not enough to be a limiting factor in immune cell proliferation. As for protein synthesis, in sedentary, glutamine does nothing to our major protein synthetic regulator, mTOR. Interestingly, it does increase its presence post-exercise, which might imply a rise in protein synthesis; however, downstream regulators of protein synthesis were not upregulated, making it a tricky scenario that might mislead a reader to believe it has an impact. Then, how does it rise mTOR?

While I do not know for sure, I imagine it increases energy available to the cell via glutamate and therefor the TCA cycle – as well as offering gluconeogenic substrate, if need be. Increased energy levels in the cell would activate mTOR.

As for its impact on catabolism, it may supply some benefit in extreme cases, for the same reason outline above – more energy, or possibly through its antioxidant-like effects. However, while many have touted a decrease in catabolism – a measure of two primary catabolic pathways (muRF and MaF-bx), show no depression with supplementation in sedentary. So, while this does not eliminate all scenarios, like autophagy, in which glutamine induced mTOR activation increase autophagy, it does punch the argument in the gut. At least, we can say with some strength that glutamine likely does not blunt degradation through the proteasome. Interestingly, it may through the autophagosome [10].

These seemingly confusing in vitro studies throw a wrench in the rest of the literature, as mechanistically, they do not add up to the rest – or do they [9][10]?

We established that glutamine does not increase protein synthesis, although it does increase mTOR activation, yet in this study, protein synthesis is elevated, through and through [9]. However, I will have you notice that with glutamine supplementation, leucine and alanine decrease, yet aspartate levels increase substantially. This implies the cell may be running the TCA cycle to create gluconeogenic substrate (although a muscle cell and therefore cannot export this material), lending to the hypothesis the cell is increasing energy levels. This also might imply the cell is not importing as much non-glutamine energy substrate (glucose, for example) from the serum and is relying heavily on glutamine, or that there is substantial protein turn over (seen in decreased leucine) which bears out as when tyrosine (another amino acid) is eliminated from the cell, protein synthesis drops significantly [9].

So, this means glutamine is important in protein synthesis and in protein degradation, but does not overcome an incomplete amino acid profile, regardless of the amount of glutamine added. Additionally, glutamine may still have no significant impact on downstream protein synthesis pathways (beyond mTOR), yet other amino acids might. However, there is an instance in which post-mTOR pathways (4E-BP1 and P70S6K) are upregulated in the presence of glutamine [10].

Highlighted in red is the failure my proposed failure of glutamine to act on downstream regulators of protein synthesis, even if it acts on mTOR.
Summary

In two instance glutamine supplementation helps; one, extreme physical trauma or illness that requires hospitalization for immune function deficiencies, and secondly, it may provide a slight benefit in recovery between sets in training. Other than those two scenarios, glutamine supplementation will not offer any benefit, yet glutamine still remains a vital amino acid for a variety of reasons.

Writer: Nicolas Verhoeven

References

[1] Gleeson, M. (2008). Dosing and Efficacy of Glutamine Supplementation in Human Exercise and Sport Training. The Journal of Nutrition, 138(10), 2045S-2049S. doi:10.1093/jn/138.10.2045s

[2] PARRY-BILLINGS, M., BUDGETT, R., KOUTEDAKIS, Y., BLOMSTRAND, E., BROOKS, S., WILLIAMS, C., … NEWSHOLME, E. A. (1992). Plasma amino acid concentrations in the overtraining syndrome. Medicine & Science in Sports & Exercise, 24(12), 1353???1358. doi:10.1249/00005768-199212000-00008

[3] Boelens, P. G., Nijveldt, R. J., Houdijk, A. P., Meijer, S., & Van Leeuwen, P. A. (2001). Glutamine Alimentation in Catabolic State. The Journal of Nutrition, 131(9), 2569S-2577S. doi:10.1093/jn/131.9.2569s

[4] Jepson, M. M., Bates, P. C., Broadbent, P., Pell, J. M., & Millward, D. J. (1988). Relationship between glutamine concentration and protein synthesis in rat skeletal muscle. American Journal of Physiology-Endocrinology and Metabolism, 255(2), E166-E172. doi:10.1152/ajpendo.1988.255.2.e166

[5] Lambertucci, A. C., Lambertucci, R. H., Hirabara, S. M., Curi, R., Moriscot, A. S., Alba-Loureiro, T. C., … Pithon-Curi, T. C. (2012). Glutamine Supplementation Stimulates Protein-Synthetic and Inhibits Protein-Degradative Signaling Pathways in Skeletal Muscle of Diabetic Rats. PLoS ONE, 7(12), e50390. doi:10.1371/journal.pone.0050390

[6] Rennie, M. J., Edwards, R. H., Krywawych, S., Davies, C. T., Halliday, D., Waterlow, J. C., & Millward, D. J. (1981). Effect of Exercise on Protein Turnover in Man. Clinical Science, 61(5), 627-639. doi:10.1042/cs0610627

[7] Wang, W., Choi, R. H., Solares, G. J., Tseng, H., Ding, Z., Kim, K., & Ivy, J. L. (2015). l-Alanylglutamine inhibits signaling proteins that activate protein degradation, but does not affect proteins that activate protein synthesis after an acute resistance exercise. Amino Acids, 47(7), 1389-1398. doi:10.1007/s00726-015-1972-7

[8] Legault, Z., Bagnall, N., & Kimmerly, D. S. (2015). The Influence of Oral L-Glutamine Supplementation on Muscle Strength Recovery and Soreness Following Unilateral Knee Extension Eccentric Exercise. International Journal of Sport Nutrition and Exercise Metabolism, 25(5), 417-426. doi:10.1123/ijsnem.2014-0209

[9] Wu, G., & Thompson, J. R. (1990). The effect of glutamine on protein turnover in chick skeletal musclein vitro. Biochemical Journal, 265(2), 593-598. doi:10.1042/bj2650593

[10] Tan, H. W., Sim, A. Y., & Long, Y. C. (2017). Glutamine metabolism regulates autophagy-dependent mTORC1 reactivation during amino acid starvation. Nature Communications, 8(1). doi:10.1038/s41467-017-00369-y

 

"CLICK" for Most Recent