Systematic literature study on possible effects of exposure to radiofrequency electromagnetic fields on biomarkers of oxidative stress

Background

The WHO has been studying the potential health effects of exposure to electromagnetic fields (EMF) for decades. The Environmental Health Criteria (EHC) monographs are the WHO’s risk assessments for chemical, biological, and physical health factors. They are drawn up by independent scientists and are the result of a thorough and critical review of the entire body of research on a specific chemical or physical factor such as EMF¹. To date, the WHO has published three EHC monographs on these fields, including static², extremely low frequency (ELF) fields³ and radiofrequency (RF) fields. The last EHC monograph on RF-EMF was published in 1993⁴. In view of the large number of new publications in this field, this monograph is being comprehensively updated and thus lead to a new EHC monograph on this area.

To ensure that the EHC monograph is based on the most up-to-date knowledge and includes all available scientific evidence on particularly relevant diseases and symptoms (endpoints), the WHO has commissioned a series of systematic literature reviews dedicated to specific questions (see Spotlight on EMF Research of 24 April 2024⁵). One of these questions is whether possible effects of exposure to RF-EMF on biomarkers of oxidative stress can be deduced from the experimental animal and cell culture studies available. The term “oxidative stress” describes an imbalance between the production of certain chemical particles and their detoxification. It is about the relationship between the production of reactive (oxidising/electrophilic) chemical species, which also occur naturally in processes such as energy production or pathogen defence, and the degradation of these by antioxidant defence mechanisms.

Radiofrequency electromagnetic fields are used by radio applications to transmit information. The introduction of the 5G mobile communications standard and the integration of digital technologies into almost all areas of daily life are changing the exposure conditions of the population and the environment to these fields in all frequency ranges. This raises concerns about possible health effects. In scientific and public debates, oxidative stress is often cited as a possible mechanism by which EMF could affect biological systems.

Objective

The WHO has commissioned expert scientists from the BfS and other institutions to carry out a systematic assessment of the scientific literature on the possible effects of short-term exposure to RF-EMF on changes in biomarkers for oxidative stress in experimental human, animal, and cell culture studies. To this end, all available peer-reviewed scientific literature relevant to this issue was to be systematically identified, evaluated, and analysed.

Methods and implementation

A protocol in which the methodology and evaluation criteria for conducting the study were transparently defined was drawn up and published in a peer-reviewed scientific journal⁶. The research question was formulated according to the PECO(S) scheme, which defines the population (P), exposure (E), comparator (C), outcome (O), and study type (S) as follows: What are the effects of exposure to RF-EMF in the frequency range of 100 kHz to 300 GHz (E) on the most important, validated biomarkers for oxidative stress (O) compared with non-exposed or sham-exposed control groups (C) in experimental studies (S) on animals, humans, and cells (P)?

Experimental human, animal, and cell culture studies in which at least two exposure levels (including sham exposed or control group) were tested under controlled laboratory conditions were included. Only studies that used biomarkers for oxidative stress considered valid by the experts involved were considered. Also excluded were studies with insufficient exposure contrast, lack of exposure characterisation, or co-exposure to other substances or to EMF outside the specified frequency range.

Between June 2021 and June 2023, electronic searches were carried out in the PubMed (NLM), Embase, Scopus, Web of Science, and EMF-Portal databases with no restrictions on publication date and language. The studies identified in this way were subjected to a multi-stage assessment procedure to check whether they met the defined inclusion criteria. This procedure was used to compile the final set of studies from which the data relevant for the systematic review were then extracted.

The quality of these studies was assessed using an evaluation procedure established for clinical studies, and the degree of various risks of falsification and bias was determined. For different animal species, organ systems, and cell types, the data available were summarised in comparable groups, and meta-analyses were carried out if the database permitted this. It was assessed whether there were changes in the biomarkers of oxidative stress. The confidence in these results was then assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) concept recommended by the non-profit organisation Cochrane. The results were published in the special issue "WHO assessment of health effects of exposure to radiofrequency electromagnetic fields: systematic reviews" of the journal Environment International, which specialises in systematic reviews⁷.

Results

After removing duplicates, the database search yielded 12,409 studies. After checking the inclusion criteria, 56 studies that contained the level of knowledge relevant to the research question were identified. Measured values for biomarkers of oxidative stress in human and animal cells and various organ systems, including the brain, liver, and blood of test animals such as mice, rats and rabbits, were extracted from the studies and analysed. Overall, there was no reliable evidence of a connection between exposure to RF-EMF and changes in the biomarkers for oxidative stress. However, confidence in the evidence is quite low because the study designs and results are inconsistent overall, and most studies included show some serious deficits in the characterisation of the exposure, the measurement of the endpoints, and the blinding.

Literatur

1) World Health Organization. Radiation and health - Health risk assessment 2024

2) World Health Organization. Static fields: World Health Organization; 2006.

3) World Health Organization. Extremely low frequency fields: World Health Organization; 2007.

4) World Health Organization. Electromagnetic fields (300 Hz to 300 GHz): World Health Organization; 1993.

5) Spotlight on “WHO assessment of health effects of exposure to radiofrequency electromagnetic fields: systematic reviews”, a special series in Environment International.

6) Henschenmacher, Bernd, et al. "The effect of radiofrequency electromagnetic fields (RF-EMF) on biomarkers of oxidative stress in vivo and in vitro: A protocol for a systematic review." Environment international 158 (2022): 106932.

7) Meyer, Felix, et al. "The effects of radiofrequency electromagnetic field exposure on biomarkers of oxidative stress in vivo and in vitro: A systematic review of experimental studies." Environment International (2024): 108940.