The effects of radiofrequency electromagnetic field exposure on biomarkers of oxidative stress in vivo and in vitro: A systematic review of experimental studies (WHO SR 9)

Abstract

Overview

Oxidative stress is associated with a variety of diseases and is believed to be affected by radiofrequency electromagnetic fields (RF-EMF). This systematic review (SR) aimed to summarize and evaluate experimental studies investigating the effects of RF-EMF (100 kHz to 300 GHz) on biomarkers of oxidative stress in vivo and in vitro.

Methods

• The systematic review framework followed WHO and NTP/OHAT guidelines, using the GRADE approach for environmental health assessments.
• Database searches included PubMed, Embase, Web of Science Core Collection, Scopus, and EMF-Portal up to June 30, 2023, with supplemental manual searches of reference lists.
• Risk of Bias (RoB) was assessed using the OHAT RoB Rating Tool, and publication bias was analyzed via funnel plots.
• Certainty of evidence for RF-EMF and oxidative stress association was graded as high, moderate, low, or inadequate using an adapted GRADE framework.
• Data from 56 studies (45 in vivo, 11 in vitro) were extracted, with 51 studies and 168 results included in meta-analysis.

Findings

• The majority of studies used frequencies between 800 and 2450 MHz, predominantly in rodents and rabbits, measuring biomarkers for modified proteins/amino acids, oxidized DNA bases, and other markers.
• Results were highly inconsistent across studies and samples, with standardized mean differences (SMDs) pointing to both increases and decreases in biomarkers for oxidized DNA bases and other markers in various organs and species.
• Noteworthy increases in biomarkers of oxidative stress were found in the testis, serum, and thymus of rodents, though evidence remains of very low certainty.
• Overall, outcomes measured in the brain, liver, blood, plasma, female reproductive system, and in vitro studies showed no consistent or definitive trend, with high heterogeneity and low certainty.
• Most studies suffered from high risk of bias, primarily from poor blinding and inaccurate exposure or outcome measurement.

Conclusion

The association between RF-EMF exposure and biomarkers of oxidative stress remains highly uncertain due to heterogeneity and high risk of bias in the literature. Evidence points to potential increases in oxidative stress markers — especially in certain organs — but the data quality is insufficient for definitive conclusions. The findings underline the urgent need for improved study designs, rigorous exposure assessments, and validated biomarker measurements in future research. Importantly, there remains a plausible connection between RF-EMF exposure and oxidative stress, which is implicated in numerous health conditions, and cannot be dismissed given the current evidence base.

Funding: This review was partially funded by the World Health Organization. Protocol registered in PROSPERO and published in Environment International.