Leading Journal Highlights Oxaloacetate CFS research in Special ME/CFS Issue

Our Research Featured in Frontiers in Neuroscience: Advancing the Scientific Understanding of Chronic Fatigue

Terra Biological is pleased to announce that three of our peer-reviewed clinical research studies have been formally published as part of a special ME/CFS issue in Frontiers in Neuroscience entitled:

Exploring Chronic Fatigue: Neural Correlates, Mechanisms, and Therapeutic Strategies

This Research Topic brings together leading investigators from across disciplines to examine the neurobiological, physiological, and therapeutic dimensions of fatigue, with particular emphasis on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), long COVID, and related chronic disorders. The collection has garnered significant international attention, with more than 80,000 total views and downloads to date.

Our Contributions

Three randomized controlled trials conducted by researchers:

• RESTORE ME: A randomized controlled trial of oxaloacetate for improving fatigue in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

• REGAIN: A randomized controlled clinical trial of oxaloacetate for improving the symptoms of long COVID

• Relationships Between Fatigue, Cognitive Function, and Upright Activity in ME/CFS: Findings from a randomized controlled trial of oxaloacetate

Collectively, these studies investigate the role of metabolic modulation with oxaloacetate in addressing core features of post-viral and neuro-immune fatigue syndromes, including physical exhaustion, cognitive dysfunction, and impaired functional capacity.

Significance of the Research Topic

The Frontiers in Neuroscience Research Topic, Exploring Chronic Fatigue: Neural Correlates, Mechanisms, and Therapeutic Strategies, aims to advance understanding of both the physiological and neural mechanisms underlying fatigue and its pathological forms. The scope includes:

• Neural and autonomic nervous system dysfunction in ME/CFS

• Mechanisms of post-exertional malaise

• Brain and cognitive correlates of chronic fatigue

• The impact of sleep, aging, and autonomic regulation on fatigue

• Pharmacological and non-pharmacological treatment strategies

• Emerging analytical approaches, including machine learning and computational modeling

By synthesizing work across these domains, the collection seeks to address long-standing gaps in the understanding of fatigue and to inform the development of more effective, mechanism-based therapeutic strategies.

Advancing Evidence-Based Therapeutics

Terra Biological's inclusion in this volume reflects the rigor and clinical relevance of the research. Each of the studies employed randomized, placebo-controlled methodologies to evaluate the effects of oxaloacetate on fatigue severity, cognitive performance, and functional outcomes in populations with ME/CFS and long COVID, conditions that remain substantially underserved in both research and clinical care.

The publication of these trials within a high-impact neuroscience journal underscores the growing recognition that chronic fatigue is a complex, biologically grounded condition with identifiable neural and metabolic components, rather than a purely subjective or psychosomatic phenomenon.

Terra Biological is honored to contribute to this important body of work and to collaborate, through this special issue book, with an international community of scientists dedicated to advancing the understanding and treatment of chronic fatigue and related disorders.