# Clinical Performance of REAC-Based ACT, CO, and MO-IBZ Protocols in Routine Practice: A Prospective Real-World Observational PMCF Study

**Authors:** Vania Fontani, Arianna Rinaldi, Bruna Lombardi, Salvatore Rinaldi

PMC · DOI: 10.3390/jcm15052048 · 2026-03-07

## TL;DR

This study shows that a non-invasive treatment approach significantly reduces pain and improves symptoms in people with chronic low-grade inflammation.

## Contribution

The study provides real-world evidence of the clinical effectiveness of REAC-based protocols for chronic inflammation.

## Key findings

- Pain scores decreased significantly after treatment and remained reduced at follow-up.
- 78% of participants met criteria for a clinically meaningful improvement.
- Symptoms like sleep disturbance and fatigue improved with no adverse events.

## Abstract

Background/Objectives: Chronic low-grade inflammation underlies persistent pain, sleep disturbance, fatigue, and reduced perceived well-being. ACT (anti-inflammatory cellular treatment), CO (circulatory optimization), and MO (metabolic optimization) are non-invasive REAC-based biomodulation protocols within the Inside Blue Zone (IBZ) framework, yet real-world evidence on patient-reported outcomes remains limited. The aim of this study was to evaluate pain intensity and symptom burden (sleep disturbance, fatigue, perceived well-being) in subjects undergoing ACT, CO, and MO within a Post-Market Clinical Follow-Up (PMCF) framework. Methods: This prospective observational PMCF study enrolled 50 subjects receiving sequential ACT, CO, and MO in routine practice. Pain was assessed at baseline (T0), end of treatment (T1), and follow-up (T2) using a Visual Analog Scale (VAS). Secondary outcomes were analyzed through clinically meaningful severity categories. Results: VAS scores decreased significantly from T0 to T1 (t(49) = 21.37, p < 0.001, Cohen’s d = 3.02) and remained reduced at T2. Seventy-eight percent met responder criteria. Secondary outcomes shifted toward lower severity categories at both timepoints. No adverse events occurred. Conclusions: Sequential ACT, CO, and MO produced clinically meaningful pain reductions and favorable symptom severity shifts with good tolerability, supporting clinical performance of this REAC-based approach in chronic low-grade inflammatory conditions.

## Full-text entities

- **Diseases:** MO (MESH:D008659), fatigue (MESH:D005221), inflammation (MESH:D007249), sleep disturbance (MESH:D012893), Pain (MESH:D010146)
- **Chemicals:** CO (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12985770/full.md

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Source: https://tomesphere.com/paper/PMC12985770