Li, Gong-Hua, Han, Fei-Fei, Kalafatis, Efthymios et al. · International journal of molecular sciences · 2025 · DOI
This study found that both ME/CFS and Long COVID may share similar problems with how muscles process certain amino acids (building blocks of proteins). Using computer modeling, researchers identified that two specific metabolic pathways are underactive in muscle tissue. They then tested whether adding supplements containing aspartate and a related compound could help restore normal muscle metabolism, and suggest a combination treatment called LOLA as a potential future therapy.
This study suggests a potential biological mechanism linking two conditions that affect millions globally and may identify a specific, testable intervention. If validated clinically, LOLA supplementation could offer patients a relatively low-risk therapeutic option that addresses underlying metabolic dysfunction rather than just symptom management.
This study does not prove that aspartate or LOLA supplementation will actually help ME/CFS or Long COVID patients—it only predicts this possibility using mathematical models and observational data. It does not establish whether the identified metabolic changes cause the illness or are simply a consequence of it, nor does it account for the heterogeneity of these conditions across different patients.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Li, Gong-Hua, Han, Fei-Fei, Kalafatis, Efthymios, Kong, Qing-Peng, & Xiao, Wenzhong (2025). Systems Modeling Reveals Shared Metabolic Dysregulation and Potential Treatments in ME/CFS and Long COVID.. International journal of molecular sciences. https://doi.org/10.3390/ijms26136082
BibTeX
@article{mecfsatlas-li-2025-systems-modeling,
author = {Li, Gong-Hua and Han, Fei-Fei and Kalafatis, Efthymios and Kong, Qing-Peng and Xiao, Wenzhong},
title = {Systems Modeling Reveals Shared Metabolic Dysregulation and Potential Treatments in ME/CFS and Long COVID.},
journal = {International journal of molecular sciences},
year = {2025},
doi = {10.3390/ijms26136082},
note = {PubMed: 40649860},
url = {https://www.mecfsatlas.com/evidence/li-2025-systems-modeling},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-25. https://www.mecfsatlas.com/evidence/li-2025-systems-modeling
Contribute
Private, reviewed by a human. Not a public comment thread.