Copper and Iron Associated With Fibromyalgia Risk

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Copper (Cu) and iron (Fe) are associated with fibromyalgia (FM) risk according to new research with trace elements, warranting further study.¹

“There is evidence suggesting that abnormalities in trace element metabolism may be associated with the development and progression of the disease.² For example, Fe deficiency has been linked to fatigue and cognitive impairments in FM patients; zinc deficiency is associated with inflammatory responses and oxidative stress, both relevant to the pathophysiology of FM; and magnesium deficiency can lead to muscle pain and increased neural excitability, aligning with FM’s symptomatic pain. However, these associations are primarily based on cross-sectional or case-control studies, making it challenging to establish causality and potentially subject to confounding and reverse causation effects,” lead investigator Wenxing Zeng, First Clinical College of Guangzhou University of Chinese Medicine, and First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China, and colleagues wrote.¹

Zeng and colleagues analyzed trace elements using inverse-variance weighting (IVW), Mandelian randomization Egger, weighted median, weighted mode, and simple mode methods. They also used multivariable analysis to control for selenium as a potential confounder to evaluate the independent associations of Cu and Fe with FM risk. Using 2-sample MR analysis, they found a positive association between Cu and increased risk of FM (IVW: OR, 1.095 [95% CI, 1.015 -1.181]; P = .018), and a negative association between Fe and FM risk (IVW: OR, 0.440 [95% CI, 0.233-0.834]; P = .011). The investigators found that these associations remained significant in the multivariable analysis and there were no other significant associations with other trace elements such as selenium and zinc.¹

“Our findings provide new insights for future research, particularly in exploring how Cu and Fe influence the onset and progression of FM. Future studies need to delve into the molecular level to reveal how these trace elements influence the pathological processes of FM through specific molecular pathways and signaling routes. This includes detailed studies on the impact of inflammatory mediators, oxidative stress markers, and neurotransmitter systems,” Zeng and colleagues wrote.¹

“Considering the potential interactions between genetic and environmental factors, future work should evaluate how genetic variations interact with factors like diet, lifestyle, and occupational exposures to affect individual susceptibility to FM. Large-scale epidemiological studies will help validate the associations between trace element status and FM risk and explore dose-response relationships. Comparative studies across different populations will assess the consistency of these associations across various ethnicities, genders, and age groups. Overall, future research will provide a deeper understanding, helping to develop new prevention and treatment strategies, and offer more targeted interventions for individuals at high risk for FM,” Zeng and colleagues concluded.¹

Other research recently found that people with fibromyalgia syndrome (FMS) had impaired bioenergetic health index (BHI), a proxy of mitochondrial function, which also had a slight correlation with pain.³ People with FM had a lower median BHI (−22.1%, P =.03) than healthy controls.

REFERENCES
1. Zeng, W., Hu, M., Ma, L. et al. Copper and iron as unique trace elements linked to fibromyalgia risk. Sci Rep 15, 4019 (2025). https://doi.org/10.1038/s41598-025-86447-4

2. Chen, L., Min, J. & Wang, F. Copper homeostasis and cuproptosis in health and disease. Signal. Transduct. Target. Therapy. 7 (1), 378. https://doi.org/10.1038/s41392-022-01229-y (2022)

3. Macchi C, Giachi A, Fichtner I, et al. Mitochondrial function in patients affected with fibromyalgia syndrome is impaired and correlates with disease severity. Sci Rep (2024): 14(30247). doi: 10.1038/s41598-024-81298-x