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. 2023 Dec;20(1):2263409.
doi: 10.1080/15502783.2023.2263409. Epub 2023 Oct 6.

International Society of Sports Nutrition Position Stand: Effects of essential amino acid supplementation on exercise and performance

Arny A Ferrando  1 , Robert R Wolfe  1 , Katie R Hirsch  2 , David D Church  1 , Shiloah A Kviatkovsky  1 , Michael D Roberts  3 , Jeffrey R Stout  4 , Drew E Gonzalez  5 , Ryan J Sowinski  5 , Richard B Kreider  5 , Chad M Kerksick  6 , Nicholas A Burd  7 , Stefan M Pasiakos  8 , Michael J Ormsbee  9 , Shawn M Arent  2 , Paul J Arciero  10   11 , Bill I Campbell  12 , Trisha A VanDusseldorp  13   14 , Ralf Jager  15 , Darryn S Willoughby  16 , Douglas S Kalman  17 , Jose Antonio  18
Affiliations

International Society of Sports Nutrition Position Stand: Effects of essential amino acid supplementation on exercise and performance

Arny A Ferrando et al. J Int Soc Sports Nutr. 2023 Dec.

Abstract

Position Statement: The International Society of Sports Nutrition (ISSN) presents this position based on a critical examination of literature surrounding the effects of essential amino acid (EAA) supplementation on skeletal muscle maintenance and performance. This position stand is intended to provide a scientific foundation to athletes, dietitians, trainers, and other practitioners as to the benefits of supplemental EAA in both healthy and resistant (aging/clinical) populations. EAAs are crucial components of protein intake in humans, as the body cannot synthesize them. The daily recommended intake (DRI) for protein was established to prevent deficiencies due to inadequate EAA consumption. The following conclusions represent the official position of the Society: 1. Initial studies on EAAs' effects on skeletal muscle highlight their primary role in stimulating muscle protein synthesis (MPS) and turnover. Protein turnover is critical for replacing degraded or damaged muscle proteins, laying the metabolic foundation for enhanced functional performance. Consequently, research has shifted to examine the effects of EAA supplementation - with and without the benefits of exercise - on skeletal muscle maintenance and performance. 2. Supplementation with free-form EAAs leads to a quick rise in peripheral EAA concentrations, which in turn stimulates MPS. 3. The safe upper limit of EAA intake (amount), without inborn metabolic disease, can easily accommodate additional supplementation. 4. At rest, stimulation of MPS occurs at relatively small dosages (1.5-3.0 g) and seems to plateau at around 15-18 g. 5. The MPS stimulation by EAAs does not require non-essential amino acids. 6. Free-form EAA ingestion stimulates MPS more than an equivalent amount of intact protein. 7. Repeated EAA-induced MPS stimulation throughout the day does not diminish the anabolic effect of meal intake. 8. Although direct comparisons of various formulas have yet to be investigated, aging requires a greater proportion of leucine to overcome the reduced muscle sensitivity known as "anabolic resistance." 9. Without exercise, EAA supplementation can enhance functional outcomes in anabolic-resistant populations. 10. EAA requirements rise in the face of caloric deficits. During caloric deficit, it's essential to meet whole-body EAA requirements to preserve anabolic sensitivity in skeletal muscle.

Keywords: Protein; exercise.

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Conflict of interest statement

AAF is an inventor of EAA-based compositions (US11,273,138 B2, US20140343112, US20200253908). The results of some of these compositions are referred to under “EAAs and clinical conditions and outcomes (refs 40, 60, 89).” RRW is a shareholder in the Amino Company, LLC. RRW is an inventor of EAA-based compositions (U.S. Patent 9,597,367 B2; US Patent 9,364,463 B2; US Patent 16/761,175, US20100179089, US20090252684, US20090203606, US8703725B2, ES2274299T3, EP1865944B1, US 2008/0268038 A1, US20200253908, US10022358B2, US11,273,138 B2, US20140343112, US11,241,399 B2). DDC has received honoria, consulting fees, and performed free-lance work related to protein metabolism. He currently serves on the Advisory Board for Shifted Supplements. SK has no conflict in terms of financial or business interests related to this manuscript. SK has received grants to conduct research on dietary supplements; has served as a paid consultant for industry; and has received honoraria for speaking engagements and conferences. MDR reports current research contracts and gifts from several industry sponsors. MDR also acts as a consultant for industry entities in accordance with rules established by Auburn University’s Conflict of Interest (COI) Policies. JRS has no conflict of interest related to this manuscript in terms of financial or business interests. Over the past 25 years, he has received grants and contracts to conduct research on dietary supplements; served as a paid consultant for industry; and received honoraria for speaking at conferences and writing lay articles about sports nutrition ingredients and topics. RJS has no conflict in terms of financial or business interests related to this manuscript. RJS has conducted research on dietary supplements. RBK has conducted sponsored research on nutritional supplements through grants and contracts awarded to the universities he has been affiliated, received honorarium for presenting research related to dietary supplements, served as an expert on cases related to dietary supplements, and consulted with industry on product development including dietary supplements containing essential amino acids. CK has no conflicts of interest to report on the content of this paper. CK has consulted with and received external funding from companies who sell certain amino acids and dietary ingredients and has received remuneration from companies for delivering scientific presentations at conferences. He has also been paid in an advisory capacity from companies that manufacture various dietary ingredients including protein. NAB has no conflict in terms of financial or business interests related to this manuscript. NAB has received research grants, consulting fees, and speaking honoraria from PepsiCo, the National Cattlemen’s Beef Association, The Pork Check Off, National Dairy Council, and Alliance for Potato Research and Education (APRE). SMP has no conflict in terms of financial or business interests related to this manuscript. Furthermore, the opinions expressed in this article are those of Dr. Pasiakos and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government. Any citations of commercial organizations and trade names in this report do not constitute an official NIH endorsement of approval of the products or services of these organizations. MJO has no conflict in terms of financial or business interests related to this manuscript. MJO is a member of the International Protein Board that disseminates knowledge on protein and protein products. MJO has received grants and contracts to conduct research on dietary supplements; has served as a paid and unpaid consultant for industry; has received honoraria for speaking at conferences and writing lay articles about sports nutrition ingredients and topics. SMA has no current conflicts of interest specifically related to EAAs/protein. He has received other funding from dietary supplement companies for research, honoraria for speaking at conferences or as an advisory board member, and consulting. PJA has no conflict in terms of financial or business interests related to this manuscript. PJA is Founder and CEO of PRISE LLC, a health and wellness company providing consulting services to organizations and individuals to enhance health and performance. He serves as a paid consultant for Isagenix International LLC, a health and wellness company providing nutrition supplements. He is an advisory board member of the International Protein Board (IPB) and receives funding to conduct research on dietary supplements; he receives honoraria for keynote presentations and financial compensation for books and lay articles about sports nutrition ingredients and topics. BIC has no conflict in terms of financial or business interests related to this manuscript. BIC has received grants and contracts to conduct research on dietary supplements; has served as a paid consultant for industry; has received honoraria for speaking at conferences and writing lay articles about sports nutrition ingredients and topics; is a member of the International Protein Board that disseminates knowledge on protein and protein products; and has served as an expert witness on behalf of the plaintiff and defense in cases involving dietary supplements; and receives compensation for writing and providing educational services related to exercise and nutrition-related topics. TAV has no current conflicts of interest specifically related to EAAs/protein. She has received other funding from dietary supplement companies for research, honoraria for speaking at conferences/writing lay articles, and consulting in industry. RJ has no conflict in terms of financial or business interests related to this manuscript. RJ is an inventor of patents on dipeptides (US patent US20230053297, US20230113817, US11026991). RJ has received grants and contracts to conduct research on dietary supplements; has served as a paid consultant for industry; has received honoraria for speaking at conferences and has served as an expert witness on behalf of the plaintiff and defense in cases involving dietary supplements. DW has no conflict in terms of financial or business interests related to this manuscript. DW has received grants and contracts to conduct research on dietary supplements; has served as a paid consultant for industry; has received honoraria for speaking at conferences and writing lay articles about sports nutrition ingredients and topics; and has served as an expert witness on behalf of the plaintiff and defense in cases involving dietary supplements. DSK has no conflicts of interest to declare. In the past, DSK has conducted research on amino acids and protein products, none currently. JA is the CEO of the ISSN. The ISSN receives occasional funding and support from companies the manufacture and sell amino-acid containing supplements.

The opinions expressed in this article are those of the authors and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government. Any citations of commercial organizations and trade names in this report do not constitute an official NIH endorsement of approval of the products or services of these organizations.

Figures

Figure 1a.
Figure 1a.
Protein synthesis: transcriptional initiation, elongation, and termination leading to the production of mRNA in the nucleus, then exported to the cytosol to undergo translational initiation, elongation, and termination; producing a polypeptide which is folded into a protein.
Figure 1b.
Figure 1b.
mTOR signaling: regulation of mTORC1 by upstream stimuli; insulin, exercise (resistance, endurance), glucose, and amino acids (Aa’s). Exercise leads to an energy deficit (increased AMP) stimulating AMPK, inhibiting mTORC1 whereas glucose consumption raises ATP, inhibiting AMPK. Insulin and resistance exercise activate the PI3K pathway, positively regulating mTORC1, while endurance exercise activates CaMK, mostly promoting mitochondrial biogenesis. AA’s primarily stimulate mTORC1 by promoting the phosphorylation and dephosphorylation of rag GTPases, rag A/B and rag C/D, respectively. AA’s generally stimulate FNIP1/FLCN, promoting dephosphorylation of rag C/D, however, some EAA’s (leucine, histidine, valine, threonine, isoleucine, methionine) act to promote phosphorylation of rag A/B; leading to an upregulation in mTORC1 and downstream translation as well as glucose and lipid metabolism. Figures are derived from [10–12].
Figure 2.
Figure 2.
The effect of 15 g of free-form EAA vs 70 g of lean beef protein and mixed meal ingestion on plasma EAA kinetics. Adapted from references [50,51].
Figure 3.
Figure 3.
Muscle net balance of phenylalanine (umol/kg/min) during fasting, resistance exercise alone (RE), complete amino acid administration/infusion alone (AA), and with combined AA and RE. An interactive effect between RE and AA administration is demonstrated. Data derived from references [9,66].
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