Targeting mitochondrial metabolism with combined metabolic activators, 2026, Hong Yang et al

[Mij]

Highlights​

Mitochondrial dysfunction is a common feature of many human diseases and is emerging as a therapeutic target.

Systems biology and multiomics approaches have revealed that deficits in glutathione and NAD+ metabolism, impaired fatty acid oxidation, and disrupted redox balance are key drivers of disease pathogenesis.

Combined metabolic activators (CMA) were developed to address these metabolic deficits through the complementary actions of serine, N-acetylcysteine, l-carnitine, and NAD+ precursors.

CMA have been shown to lower hepatic fat, reduce systemic inflammation, accelerate recovery from infection, and improve cognitive performance in clinical studies.

Abstract​

Mitochondria play a central role in energy metabolism, redox balance, and cellular homeostasis, and their dysfunction has been implicated in the pathogenesis of complex human diseases.

Advances in systems biology and omics technologies have elucidated the mechanisms underlying these conditions, including metabolic dysfunction, mitochondrial impairment, inflammation, and redox imbalance.

Preclinical and early clinical studies of combined metabolic activators (CMA), a formulation of bioactive metabolites, have demonstrated improvements in mitochondrial function and systemic metabolic profiles across multiple diseases.

In this review, we provide a comprehensive overview of the mechanistic rationale for CMA, summarize evidence from preclinical models and clinical studies investigating CMA and its components, and evaluate its translational potential and challenges as a mitochondrial-targeted therapeutic strategy for complex human diseases.
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[Creekside]

A reliable set of CMAs would be useful. Not just for people with mitochondrial dysfunction, but also if it doesn't provide improvements, it's evidence that mitochondrial dysfunction isn't responsible for a particular symptom or a disease.