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Amino Acids as Metabokines in Hypercatabolic States: Rethinking Nutritional Protein-Based Strategies Beyond Caloric
Giovanni Corsetti1, Evasio Pasini1,2
1Department of Clinical and Experimental Sciences, Università di Brescia, 25128 Brescia, Italy.
Nutrients
|June 12, 2026
Summary
In hypercatabolic states, essential amino acids (EAAs) are crucial signaling molecules for muscle preservation, not just protein building blocks. Optimal nutrition requires a quality-focused approach, integrating metabolic status and EAAs, rather than solely focusing on calories or protein quantity.
Area of Science:
- Metabolic Regulation
- Nutritional Biochemistry
- Clinical Nutrition
Background:
- Hypercatabolic states (HCS) in acute and chronic diseases involve inflammation and neuroendocrine activation.
- HCS accelerates skeletal muscle proteolysis, leading to sarcopenia and cachexia.
- Skeletal muscle amino acids (AAs) are mobilized for energy and organ function, compromising lean body mass.
Purpose of the Study:
- To review the roles of calories, proteins, and AAs in metabolic regulation, focusing on HCS.
- To examine AAs as signaling molecules (metabokines) in anabolic and catabolic pathways.
- To advocate for a shift towards quality-oriented, signal-based nutrition strategies.
Main Methods:
- Narrative review of existing literature.
- Analysis of the distinct roles of calories, proteins, and AAs.
- Focus on signaling pathways like mTORC1 and AMPK.
Main Results:
- Calories permit protein utilization; proteins and essential amino acids (EAAs) are substrates and signaling molecules.
- Energy alone cannot prevent muscle loss without adequate EAA availability.
- High protein intake without sufficient energy leads to anabolic resistance.
Conclusions:
- Protein quality and balanced EAA availability are critical for lean mass preservation.
- Calorie- or protein-quantity-based strategies are limited in HCS.
- Targeted EAA supplementation and personalized, quality-oriented nutrition can improve outcomes.
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