title: Calcium homeostasis and low-frequency magnetic and electric field exposure: A systematic review and meta-analysis of in vitro studies.
abstract: Low frequency magnetic field (LF MF) exposure is recurrently suggested to have the ability to induce health effects in society. Therefore, in vitro model systems are used to investigate biological effects of exposure. LF MF induced changes of the cellular calcium homeostasis are frequently hypothesised to be the possible target, but this hypothesis is both substantiated and rejected by numerous studies in literature. Despite the large amount of data, no systematic analysis of in vitro studies has been conducted to address the strength of evidence for an association between LF MF exposure and calcium homeostasis. Our systematic review, with inclusion of 42 studies, showed evidence for an association of LF MF with internal calcium concentrations and calcium oscillation patterns. The oscillation frequency increased, while the amplitude and the percentage of oscillating cells remained constant. The intracellular calcium concentration increased (SMD 0.351, 95% CI 0.126, 0.576). Subgroup analysis revealed heterogeneous effects associated with the exposure frequency, magnetic flux density and duration. Moreover, we found support for the presence of MF-sensitive cell types. Nevertheless, some of the included studies may introduce a great risk of bias as a result of uncontrolled or not reported exposure conditions, temperature ranges and ambient fields. In addition, mathematical calculations of the parasitic induced electric fields (IEFs) disclosed their association with increased intracellular calcium. Our results demonstrate that LF MF might influence the calcium homeostasis in cells in vitro, but the risk of bias and high heterogeneity (I(2)>75%) weakens the analyses. Therefore any potential clinical implications await further investigation.
authors.affiliation: Cell Biology and Immunology Group, Wageningen University, P.O.Box 338, 6700AH Wageningen, The Netherlands.
authors.forename: Lieke A
authors.initials: LA
authors.lastname: Golbach
authors.affiliation: The Foundation for Research on Information Technologies in Society (IT'IS), Zeughausstrasse 43, CH-8004 Zurich, Switzerland.
authors.forename: Lucas A
authors.initials: LA
authors.lastname: Portelli
authors.affiliation: Cell Biology and Immunology Group, Wageningen University, P.O.Box 338, 6700AH Wageningen, The Netherlands.
authors.forename: Huub F J
authors.initials: HF
authors.lastname: Savelkoul
authors.affiliation: Cell Biology and Immunology Group, Wageningen University, P.O.Box 338, 6700AH Wageningen, The Netherlands.
authors.forename: Sofie R
authors.initials: SR
authors.lastname: Terwel
authors.affiliation: The Foundation for Research on Information Technologies in Society (IT'IS), Zeughausstrasse 43, CH-8004 Zurich, Switzerland; Department of Information Technology and Electrical Engineering, Swiss Federal Technical Institute (ETHZ), Gloriastrasse 35, CH-8092 Zurich, Switzerland.
authors.forename: Niels
authors.initials: N
authors.lastname: Kuster
authors.affiliation: SYRCLE, Central Animal Laboratory, Radboud University Medical Center, The Netherlands.
authors.forename: Rob B M
authors.initials: RB
authors.lastname: de Vries
authors.affiliation: Cell Biology and Immunology Group, Wageningen University, P.O.Box 338, 6700AH Wageningen, The Netherlands. Electronic address: lidy.vankemenade@wur.nl.
authors.forename: B M Lidy
authors.initials: BM
authors.lastname: Verburg-van Kemenade
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D004560:Electricity / Q000009:adverse effects*; D004574:Electromagnetic Fields / Q000009:adverse effects; D006706:Homeostasis / Q000528:radiation effects*; D006801:Humans; D060526:Magnetic Fields / Q000009:adverse effects*
chemical_list: D002118:Calcium
keywords: Calcium oscillations; Imposed magnetic field; Induced electric field; Intracellular calcium; LF EMF; Risk of bias