A new Mendelian randomization study identified copper and iron as key trace elements potentially influencing fibromyalgia risk, with elevated copper levels associated with increased risk and higher iron levels showing a protective effect.
The research, published in Scientific Reports, analyzed genetic data from 400,197 individuals (2689 fibromyalgia patients and 397,508 controls) to examine potential causal relationships between 15 trace elements and fibromyalgia (FM) risk. Using multivariate analysis that controlled for selenium as a potential confounder, the study found higher copper levels were associated with a 9.5% increased risk of FM, and higher iron levels corresponded to a 56% reduced risk.
The protective effect of iron remained significant even after adjusting for selenium, strengthening the findings' reliability. The data came from FinnGen release R10, with data collection completed in the third quarter of 2022.
Mechanistically, the researchers found that "excessive accumulation of Cu in the body's soft tissues can cause damage, and high levels can be toxic, especially in its cuprous form. Cuprous ions catalyze the conversion of hydrogen peroxide to hydroxyl radicals through the Fenton reaction, generating highly reactive free radicals that cause lipid peroxidation, leading to damage to cellular membranes and functions."
The study authors noted that "chronic oxidative stress is considered a potential biological basis for the fatigue and hypersensitivity to pain observed in FM patients." Furthermore, "oxidative stress can activate various cellular signaling pathways, inducing the release of cytokines and inflammatory mediators, thereby promoting inflammatory responses."
Regarding iron's protective effect, the researchers noted that "abnormalities in iron metabolism are closely associated with neurotransmitter dysregulation." The study found that Fe-deficient mice, "had lower pain thresholds and were more sensitive to pain, which parallels the pathophysiological traits of FM."
Iron deficiency may have broader implications, as "Fe is also vital for the normal functioning of the immune system. Fe deficiency can lead to impaired immune cell functions, such as reduced activity of T cells and natural killer cells, which may affect the body's overall immune defense capabilities."
Background on fibromyalgia reveals that it "affects between 2 and 8% of the global population, with prevalence rates 3 to seven 7 higher in women than in men." Patients "frequently exhibit a range of symptoms including widespread musculoskeletal pain, fatigue, sleep disturbances, and cognitive impairments, significantly impacting their daily lives and work capabilities."
The study was supported by the Academic Reserve Talent Cultivation Programme for Double First-class High-level Universities and the National TCM Expert Workshop Construction Project of Guangzhou University of Traditional Chinese Medicine.
The authors declared having no competing interests.
