Puta et al. (2026)
- Authors: Christian Puta, Cornelia Ellert, Philipp Reuken, Andreas Stallmach, Bio-SIG PEM Study Group
- Institutes: Department of Sports Medicine and Health Promotion, Friedrich Schiller University Jena, Jena, Germany, Jena University Hospital, Jena, Germany
- Publisher: International ME/CFS Conference 2026 (Berlin)
- Link: DOI
Summary
This research provides preliminary evidence that lactate recovery patterns can serve as an objective biological signature for Post-Exertional Malaise (PEM). By identifying distinct metabolic trajectories, the study suggests that ME/CFS and other post-infectious syndromes (PAIS) may be divided into biologically different phenotypes. For patients and caregivers, this work highlights the potential for a measurable test to validate the severity of PEM and could lead to more personalized pacing protocols based on individual metabolic thresholds. While currently a research-level finding, it moves the field toward a quantifiable diagnostic marker for exercise intolerance.
What was researched?
The study investigated the biopathological signatures of Post-Exertional Malaise (PEM) by analyzing metabolic recovery patterns and lactate trajectories in patients with ME/CFS and Post-Acute Infection Syndromes (PAIS).
Why was it researched?
Researchers aimed to identify objective biomarkers that could explain the biological basis of PEM and distinguish between different clinical phenotypes of the disease. The investigation sought to move beyond subjective symptom reporting toward quantifiable metabolic dysfunctions.
How was it researched?
The team employed a repeated measures design using short-duration protocols such as hand-grip strength tests and sit-to-stand tests, as well as Cardiopulmonary Exercise Testing (CPET). They measured metabolic markers including resting and active lactate levels, glucose, and succinate, while also utilizing Raman spectroscopy to examine cellular metabolic changes.
What has been found?
The study identified distinct ‘lactate recovery trajectories’ that support the existence of biologically different phenotypes among ME/CFS and PAIS patients. Key findings included significantly elevated resting and active lactate levels, along with disrupted lipid metabolism and amino acid depletion. These metabolic disturbances suggest that patients reach an anaerobic threshold much earlier than healthy individuals, impairing their recovery from exertion.
Discussion
The findings indicate that PEM is associated with a specific immune-metabolic signature that can be tracked through lactate kinetics. Limitations include the preliminary nature of the pilot data, though the use of multiple metabolic markers strengthens the observation of bioenergetic inflexibility. The study emphasizes that the ‘metabolic threshold’ for these patients is significantly lower than for healthy controls.
Conclusion & Future Work
Lactate monitoring and the analysis of recovery trajectories offer a promising way to subtype patients and objectively measure PEM severity. Future research will focus on validating these phenotypes to refine diagnostic criteria and therapeutic interventions.