# Oral amino acid tracer delivery detects feeding and exercise changes in myofibrillar protein synthesis rates in male adults

**Authors:** Michael Mazzulla, Nathan Hodson, Paula J. Scaife, Kenneth Smith, Philip J. Atherton, Nicholas A. Burd, Dinesh A. Kumbhare, Daniel R. Moore

PMC · DOI: 10.14814/phy2.70776 · Physiological Reports · 2026-03-03

## TL;DR

This study shows that oral amino acid tracers can effectively measure muscle protein synthesis rates in response to feeding and exercise, offering a practical alternative to intravenous methods.

## Contribution

The study introduces oral amino acid tracers as a viable alternative to intravenous methods for measuring myofibrillar protein synthesis in humans.

## Key findings

- Oral amino acid tracers showed elevated plasma enrichment and effective incorporation into myofibrillar proteins.
- Myofibrillar protein synthesis rates were significantly higher in fed and exercise-fed conditions compared to fasted conditions.
- The method demonstrated physiological differences in protein synthesis rates across experimental conditions.

## Abstract

The efficacy of oral administration of leucine and phenylalanine tracers to measure MyoPS (LEUMyoPS and PheMyoPS, respectively) in response to varying anabolic stimuli was investigated. Participants were randomized to a rested‐fasted (FAST), rested‐fed (FED), or exercise‐fed (EXFED) condition. FED and EXFED consumed a mixed carbohydrate and AA beverage enriched with L‐[1‐13C]leucine (25%) and L‐[ring‐2H5]phenylalanine (30%) at rest or after a bout of resistance exercise, while FAST consumed only the equivalent tracer dose. Blood samples were obtained every 30 min for 300 min to determine tracer precursor enrichment with muscle biopsies obtained before and at 120 and 300 min after tracer ingestion to determine MyoPS by the precursor‐product method. LEUMyoPS over 300 min was greater (p < 0.01) in EXFED (0.090 ± 0.024%/h; mean ± SD) and FED (0.067 ± 0.028%/h) compared to FAST (0.024 ± 0.015%/h). PHEMyoPS over 300 min was greater (p < 0.01) in EXFED (0.128 ± 0.034%/h) and FED (0.098 ± 0.020%/h) compared to FAST (0.056 ± 0.012%/h). There was a positive correlation (r = 0.81, p < 0.0001) between LEUMyoPS and. Oral essential amino acid tracer ingestion can be used as an alternative method to detect changes in MyoPS in response to mixed macronutrient feeding and feeding plus exercise and may be an option for the study of human muscle protein synthesis where intravenous isotope administration is logistically difficult or prohibitively expensive.

Male participants were randomly assigned to consume [13C]leucine and [D5]phenylalanine tracers alone (FAST) or with a complete mixture of amino acids (0.25 g/kg) and carbohydrate (0.75 g/kg) at rest (FED) or after a bout of resistance exercise (EXFED). Plasma enrichment of both tracers increased rapidly after ingestion and remained elevated for up to 4–5 h. Muscle biopsies detected incorporation into myofibrillar proteins, which resulted in expected physiological differences in myofibrillar protein synthetic rates between conditions (EXFED > FED > FAST) regardless of tracer. Our study demonstrates that oral essential amino acid tracer ingestion can be used as an alternative method to traditional intravenous infusion to detect changes in myofibrillar protein synthesis rates in humans.

## Linked entities

- **Chemicals:** leucine (PubChem CID 857), phenylalanine (PubChem CID 994), [D5]phenylalanine (PubChem CID 56634323)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** FASTK (Fas activated serine/threonine kinase) [NCBI Gene 10922] {aka FAST}, JTB (jumping translocation breakpoint) [NCBI Gene 10899] {aka HJTB, HSPC222, PAR, hJT}
- **Diseases:** FED (MESH:D014202), MyoPS (MESH:C536766), EXFED (MESH:D000092202)
- **Chemicals:** PTFE (MESH:D011138), formic acid (MESH:C030544), acetonitrile (MESH:C032159), N2 (MESH:D009584), EDTA (MESH:D004492), water (MESH:D014867), Leucine (MESH:D007930), D2O (MESH:D017666), t-bdmcs (MESH:C103256), essential amino acid (MESH:D000601), caffeine (MESH:D002110), lidocaine (MESH:D008012), CLM-468-PK (-), carbohydrate (MESH:D002241), MTBSTFA (MESH:C059151), Phenylalanine (MESH:D010649), AA (MESH:D000596), alcohol (MESH:D000438)
- **Species:** Homo sapiens (human, species) [taxon 9606], Bos taurus (bovine, species) [taxon 9913], Gallus gallus (bantam, species) [taxon 9031]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12956835/full.md

## References

44 references — full list in the complete paper: https://tomesphere.com/paper/PMC12956835/full.md

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Source: https://tomesphere.com/paper/PMC12956835