Author(s): HAVERS, T., MARTINI, S., HILLGÄRTNER, M., RANA, G., SCHÖNFELDER, M., WITTING, M., LUTTER, D., ERDOGAN, G., BAUMERT, P., GEISLER, S., DREY, M., WACKERHAGE, H., Institution: IST UNIVERSITY OF APPLIED SCIENCES, Country: GERMANY, Abstract-ID: 2393

INTRODUCTION:
Sarcopenia, the age-related loss of muscle mass and function (1), is associated with 'anabolic resistance', a reduced muscle protein synthesis response to an anabolic stimulus, such as protein intake (2). We hypothesize that, analogously to an OGTT for glucose, the metabolome response after protein ingestion is a measure of protein digestion speed and anabolic sensitivity, since a rapid rise in amino acids indicates rapid digestion, while fast clearance suggests high protein synthesis or anabolism. To test this, we compared the metabolome response to 20 g of whey protein in young individuals and in individuals with sarcopenia.
METHODS:
Twenty-three participants, including young healthy adults (n = 12; 25.4 ± 2.0 years) and (pre-)sarcopenic elderly (n = 11; 82.9 ± 6.2 years), received a 20 g bolus of whey protein after overnight fasting. We collected venous blood at 0, 60, and 120 minutes post-ingestion and analyzed blood plasma using LC/MS untargeted metabolomics with HILIC separation in both positive and negative ionisation modes. Following log₁₀ transformation, median normalisation and ComBat batch correction, we applied a mixed effect ANOVA (time × group) with Benjamini–Hochberg FDR correction (q < 0.05).
RESULTS:
A total of 2,968 metabolites were detected, 201 of which were annotated. Data revealed no significant interaction (time x group) for any measured annotated metabolite (all ≈ 0.99), indicating that the kinetics of the whey protein response are similar across age groups. We identified significant time effects (q < 0.05) for a broad range of metabolites, including essential amino acids such as leucine (q < 10-10), valine (q = 5.06 x 10-6), and threonine (q = 6.15 x10-8), as well as various fatty acids (e.g., FA 16:1, q = 1.06 x 10-5). Significant group differences (q < 0.05) independent of protein intake were found in metabolites such as trimethylamine N-oxide (q = 0.019), tryptophan (q = 0.0038), and N(6)-methyladenosine (q= 0.019), highlighting distinct baseline metabolic profiles in (pre)sarcopenic adults. Next, we will perform additional analyses to test whether the metabolome's response to protein ingestion reflects digestion speed and anabolic sensitivity.
CONCLUSION:
Ingestion of whey protein not only causes a transient rise of amino acids but also of other metabolites. Additional analyses will ascertain whether this can be utilized to estimate the anabolic sensitivity of an individual. Furthermore, this data shows that protein ingestion not only affects plasma amino acids but also other metabolites.

References:
1 Cruz-Jentoft et al., Age Ageing, 2019
2 Aragon et al., Nutr Rev, 2023