Systematic Review Protocol Explores Intermittent Fasting as a Tool Against Chronic Pain

Chronic pain, defined as pain lasting or recurring for three months or more, is a major public health problem. In 2023, 24% of US adults (over 80 million people) had chronic pain, and 8% had high-impact pain that limited work or daily activities. Globally, about 20% of people, over 1.5 billion, are affected, with older adults and women disproportionately burdened. Standard care includes drugs, physical therapy and surgery, yet many patients get incomplete relief. Opioid-involved deaths topped 80,000 in the US in 2022, which increases the need for safer non-drug options.

The authors point to diet as one such option, and to intermittent fasting (IF) in particular. IF alternates periods of fasting with normal eating and includes time-restricted eating, alternate-day fasting and 5:2 regimens. Studies in healthy people suggest IF can improve self-reported physical and mental health and reduce inflammation, fatigue and body pain. Narrative reviews note that fasting alters insulin, cytokines, neurotransmitters, endogenous opioids and brain-derived neurotrophic factor. A preliminary search found no existing or ongoing systematic review of IF in adults with chronic pain, which is the gap this protocol targets.

The review follows Cochrane guidance and PRISMA reporting and was registered in PROSPERO (CRD420261395061) in May 2026. It will search PubMed/MEDLINE, Embase, Web of Science and LILACS, including Portuguese and Spanish terms. It will also search Google Scholar (up to 300 results), ClinicalTrials.gov, PROSPERO, the Open Science Framework and MedRxiv, with no language or date limits. Eligible studies are randomized controlled trials in adults (18+) with chronic pain of any type, including musculoskeletal, neuropathic, headache, endometriosis, fibromyalgia and rheumatoid arthritis. Ramadan fasting studies are not excluded in advance. Comparators may be placebo, waitlist, education, standard care or active treatment.

Primary outcomes are self-reported pain (intensity, interference, disability) or function, analyzed separately, plus pain-related cognitions. Rescue medication use is the secondary outcome. Two reviewers will screen, extract data and assess risk of bias independently, using the PICOPortal software and Cochrane Risk of Bias 2. The INSPECT-SR tool will assess trial trustworthiness. Effects will be pooled with random-effects models in R (meta and metafor), using Hedges' g for standardized mean differences. Heterogeneity will be measured with I², and publication bias with funnel plots and Egger's test when there are 10 or more studies.

A distinctive feature is the handling of rescue medication. Patients who take more analgesics may mask a treatment's effect on pain. The team will run mean-difference analyses of medication use and, for studies using the Numerical Rating Scale, compute a QPAC1.5-adjusted pain score, varying its weight (1.0, 2.0) and correlation (0, 0.16) in sensitivity checks. All pain scales will also be converted to a 1–10 scale for interpretability. Leave-one-out analyses and exclusion of implausible pre-post correlations (r<0.5) will test robustness.

Planned subgroups are pain type (inflammatory pain is hypothesized to respond most), pain duration (longer duration, smaller effect) and baseline intensity (NRS 0–3 vs ≥4), with credibility judged by ICEMAN. GRADE will rate the certainty of evidence. The authors expect heterogeneity across pain conditions to be the main limitation. The review is due by July 2027, so it offers no efficacy findings yet.