SynthesisFrontiers in oncology2025
Hydrated proton complexes supplementation for tumor microenvironment reprogramming: a bioenergetic strategy targeting the Warburg effect and mitochondrial dysfunction.
Synthesis in Frontiers in oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
4 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- A scalable outpatient framework for BI-RADS 2-4B breast nodule management: an iodine-DMSO transdermal protocol.Frontiers in health services · 2026Pooled it
- Stabilized adaptive states in microbiome-human integrated physiology: reframing health and chronic disease as symbiotic biological states.Frontiers in medicine · 2026Pooled it
- Construction and validation of risk prediction model for glioblastoma associated with cancer stem cells and disulfidptosis.Translational cancer research · 2026Article
- Membrane-decisional architecture: a framework for multigenomic signal prioritization in the plasma membrane nanobiome.Frontiers in physiology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: The tumor microenvironment (TME) is characterized by a reversed pH gradient-acidic extracellular and alkaline intracellular conditions-arising from mitochondrial dysfunction, metabolic reprogramming, and dysregulated proton transport. These alterations establish a permissive niche for tumor progression, immune evasion, and resistance to therapy. Although the TME is increasingly recognized as a key determinant of cancer behavior, effective and targeted strategies for its bioenergetic reprogramming remain scarce. Objectives: This study introduces and evaluates Eigen/Zundel Complexes-Rich Water (EZC-Rich Water) as a novel hydrated proton supplementation strategy capable of targeting Warburg-induced proton dysregulation and restoring mitochondrial function, while stabilizing electrochemical membrane dynamics within the TME. Methods: A structured translational research design was implemented, combining Work Breakdown Structure (WBS), Open Innovation, and Design Thinking methodologies. This approach enabled the identification of Fundamental Points of View (FPV's)-physiological targets underlying TME dysfunction-and Critical Success Factors (CSF's)-mechanistic requirements for therapeutic efficacy. Multicriteria decision analysis was applied to integrate findings from oncology, bioenergetics, and physical chemistry, linking hydrated proton supplementation to improved zeta potential, electrosmotic flow, mitochondrial coupling, and redox regulation. Results: Integrative analyses demonstrated that EZC-Rich Water delivers metastable hydrated proton clusters (H Conclusion: Hydrated proton supplementation through EZC-Rich Water represents an innovative bioenergetic intervention with potential to reprogram the tumor microenvironment. By targeting core metabolic dysfunctions such as the Warburg effect and mitochondrial uncoupling, this clinically adaptable and low-risk strategy introduces a new paradigm in nutritional oncology. Further preclinical and clinical studies are warranted to validate its efficacy, safety, and translational applicability in oncology and related metabolic disorders. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?, identifier CRD420251065137; https://www.crd.york.ac.uk/prospero/display_record.php?, identifier CRD420251022205.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.