# Carbohydrate restriction drives greater perturbations in circulating metabolites than low energy availability in elite male athletes

**Authors:** Kyle A. Dunlop, Nathan G. Lawler, Jamie Whitfield, Alannah K. A. McKay, Nicolin Tee, Megan L. Ross, Stacey N. Reinke, John A. Hawley, David Broadhurst, Louise M. Burke

PMC · DOI: 10.14814/phy2.70752 · Physiological Reports · 2026-02-03

## TL;DR

This study shows that restricting carbohydrates more strongly affects metabolites in elite athletes than simply reducing energy intake.

## Contribution

The study reveals that carbohydrate restriction, not just energy restriction, causes significant metabolic changes in athletes.

## Key findings

- LCHF diets caused greater metabolic changes, especially in fatty acid and acylcarnitine levels.
- LEA did not produce the same metabolic responses as carbohydrate restriction.
- Metabolic shifts were most evident after prolonged endurance exercise.

## Abstract

Periods of low energy availability (LEA) are common in elite athletes and typically arise from reduced energy intake, often involving some degree of carbohydrate (CHO) restriction. Whether the metabolic profile created by energy restriction per se is distinct compared to that driven by CHO restriction is unknown. Using untargeted metabolomics, we examined metabolic perturbations linked to CHO restriction and energy restriction in plasma from elite male endurance athletes. In a semi‐randomized controlled trial, athletes (n = 20) completed one of three 5‐day dietary interventions: high energy‐high CHO (HCHO); LEA (energy‐restricted, CHO‐reduced); or low‐CHO, high‐fat (LCHF; energy‐matched, CHO‐restricted). Plasma samples were taken at multiple timepoints pre‐ and post a standardized 25 km race walk protocol. Metabolomic analysis was performed using liquid chromatography–mass spectrometry (LC–MS), with multivariate analysis conducted using RM‐ASCA+ and hierarchical clustering. A total of 5391 metabolic features were detected and 138 metabolites annotated. LCHF induced substantial metabolic perturbations, especially after prolonged exercise, including elevations in fatty acyls, hydroxy acids, dicarboxylic acids and acylcarnitine intermediates, responses not seen under LEA. We conclude that CHO restriction concomitant with a high‐fat load induces a greater metabolic perturbation in selected lipid‐based metabolites than short‐term LEA exposure in elite athletes undergoing prolonged endurance exercise.

Elite male race walkers underwent a 5 d dietary intervention of either high carbohydrate (HCHO), low‐carbohydrate high‐fat (LCHF), or low energy availability (LEA) to evaluate their metabolomic response. Following a standardized 25 km endurance walk, blood samples were collected across five timepoints, ranging from a fasted state to 3 h post‐exercise. Following plasma processing and analysis via mass spectrometry, data interpretation revealed that carbohydrate restriction (LCHF) may serve as a potent driver of circulating metabolite shifts than LEA. This is evidenced by marked perturbations in pathways related to fatty acid β‐oxidation and increased acylcarnitine production, which distinguish the LCHF profile from both the LEA and HCHO conditions.

## Full-text entities

- **Genes:** PC (pyruvate carboxylase) [NCBI Gene 5091] {aka PCB}, SLC2A4 (solute carrier family 2 member 4) [NCBI Gene 6517] {aka GLUT4}, IRS1 (insulin receptor substrate 1) [NCBI Gene 3667] {aka HIRS-1}, PCSK1 (proprotein convertase subtilisin/kexin type 1) [NCBI Gene 5122] {aka BMIQ12, NEC1, PC1, PC1/3, PC3, SPC3}, PDP1 (pyruvate dehydrogenase phosphatase catalytic subunit 1) [NCBI Gene 54704] {aka PDH, PDP, PDPC, PDPC 1, PPM2A, PPM2C}, CBX4 (chromobox 4) [NCBI Gene 8535] {aka NBP16, PC2}
- **Diseases:** dysfunction of (MESH:D006331), impaired bone health (MESH:D001847), gastrointestinal dysfunction (MESH:D005767), Diabetes (MESH:D003920), REDs (MESH:D000080822), reproductive dysfunction (MESH:D060737)
- **Chemicals:** ornithine (MESH:D009952), guanidinosuccinic acid (MESH:C001318), acetyl-CoA (MESH:D000105), tricarboxylic acid (MESH:D014233), 3-hydroxycapric acid (MESH:C017552), blood glucose (MESH:D001786), oxaloacetate (MESH:D062907), bile acid (MESH:D001647), triglycerides (MESH:D014280), alkaloid (MESH:D000470), 3-hydroxydodecanoic acid (MESH:C022145), FA (MESH:D005492), ammonium acetate (MESH:C018824), water (MESH:D014867), hydroxy acid (MESH:D006880), alpha-aminobutyric acid (MESH:C012223), dicarboxylic acids (MESH:D003998), glycogen (MESH:D006003), isoleucine (MESH:D007532), caffeine (MESH:D002110), urea (MESH:D014508), hydroxyproline (MESH:D006909), CoASH (MESH:D003065), Carbohydrate (MESH:D002241), O-acetyl-L-carnitine (MESH:D000108), CHO (MESH:C034482), taurocholate (MESH:D013656), phenolic acids (MESH:C017616), succinic acid (MESH:D019802), acylcarnitine (MESH:C116917), ATP (MESH:D000255), steroid hormones (MESH:D013256), docosapentaenoic acid (MESH:C026219), LEA (-), acetonitrile (MESH:C032159), hexadecanedioic acid (MESH:C012346), fat (MESH:D005223), FFA (MESH:D005230), lactate (MESH:D019344), ascorbic acid (MESH:D001205), purines (MESH:D011687), carnitine (MESH:D002331), 10-hydroxydecanoic acid (MESH:C000621793), lipid (MESH:D008055), TCA (MESH:D014238), fatty acid (MESH:D005227), palmitoyl-CoA (MESH:D010171), nitrogen (MESH:D009584), ADP (MESH:D000244), alpha-linolenic acid (MESH:D017962), xylopyranose (MESH:C431715), 3-hydroxybutanoic acid (MESH:D020155), adrenic acid (MESH:C011395), glucose (MESH:D005947), methanol (MESH:D000432), formic acid (MESH:C030544), leucine (MESH:D007930), amino acid (MESH:D000596), palmitoylcarnitine (MESH:D010172), A (MESH:D001151)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

54 references — full list in the complete paper: https://tomesphere.com/paper/PMC12868390/full.md

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Source: https://tomesphere.com/paper/PMC12868390