Systems Modeling Reveals Shared Metabolic Dysregulation and Potential Treatments in ME/CFS and Long COVID.
Li, Gong-Hua, Han, Fei-Fei, Kalafatis, Efthymios et al. · International journal of molecular sciences · 2025 · DOI
Quick Summary
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.
Why It Matters
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.
Observed Findings
Downregulation of alanine and aspartate metabolism pathway in muscle tissue of ME/CFS patients.
Downregulation of arginine and proline metabolism pathway in ME/CFS muscle.
Significant aspartate downregulation in both muscle and blood during post-exertional malaise in Long COVID patients.
In silico modeling suggested that aspartate or asparagine supplementation could theoretically restore metabolic balance.
Metabolic patterns overlap between ME/CFS and Long COVID patient cohorts.
Inferred Conclusions
ME/CFS and Long COVID share common metabolic dysfunctions in amino acid metabolism that manifest particularly during exertional stress.
L-ornithine and l-aspartate (LOLA) combination supplementation may potentially address identified metabolic deficiencies.
Amino acid metabolism dysregulation may be a tractable therapeutic target in these conditions.
Remaining Questions
Will LOLA supplementation actually improve symptoms or exercise tolerance in clinical trials, and at what dose?
Do the identified metabolic changes occur in all ME/CFS and Long COVID patients, or only specific subgroups?
What This Study Does Not Prove
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.