Easy-made soy protein hydrolysate increases the forced swimming time of rats independent of increased blood amino acid levels

Abstract Anti-fatigue effects of protein hydrolysates are often attributed to low-molecular-weight peptides which are thought to rapidly increase plasma amino acids level. Typically, these peptides are produced using time consuming and labor-intensive procedures to isolate them. Here, we found that a soy protein isolate hydrolysate (SPIH), composed of a complex mixture of peptides with an average molecular weight of ~ 6 kDa, significantly increased endurance in a rat weight-loaded swimming test, prolonging the swimming time by 511%. This shows that a potent anti-fatigue effect can be achieved without isolating low-molecular-weight fractions. Nuclear Magnetic Resonance (NMR) analysis of the concentrations of more than 50 blood metabolites revealed that the anti-fatigue mechanism of SPIH is not correlated with, nor dependent on, an increase in proteinogenic amino acids. This contrasts with whey protein, for which an amino acid-mediated mechanism remains plausible. Furthermore, a principal component analysis (PCA) of the metabolomic data showed that the SPIH group clustered together with the free amino acid-administered group, which showed the poorest endurance. Based on this study, we propose a hypothesis for the anti-fatigue action of this soy protein hydrolysate, suggesting a mechanism distinct from simply increasing circulatory amino acids.