After cross-sectional analysis of 3405 participants, this large, nationally representative study found no statistically significant associations between serum zinc, copper, and selenium levels, nor the copper/zinc ratio, and psoriasis.
The available evidence regarding the relationship between zinc and psoriasis is limited and conflicting. Our results are consistent with some studies showing no independent association between serum zinc and psoriasis[17, 21]. However, other investigations indicate that individuals with psoriasis exhibit lower serum zinc ion concentrations than healthy controls[14, 15, 16]. A negative relation also was observed between PASI score and zinc ion concentration in the IMQ-induced psoriasis mouse model[22]. Taken together, The findings from these studies imply that inadequate levels of zinc ions could be a pivotal factor contributing to the onset of psoriasis. Both zinc deficiency and excess are known to produce redox stress[23]. In addition, severe zinc deficiency has been associated with a decreased proportions of T helper and cytotoxic T cells, heightened monocyte cytotoxicity, and decreased natural killer cell activity[24]. SLC35E1 has been found to play a role in psoriasis by promoting proliferation of keratin-forming cells through regulation of zinc ion concentration[22].In addition, supplementation with zinc ions may alleviate psoriasis symptoms. Currently, topical formulations of zinc pyrithione are proving to be therapeutic in limited psoriasis[25]. Zinc chloride (ZnCl2), zinc disodium ethylenediaminetetraacetate (Zn-EDTA), and zinc gluconate (Zn-GLU) significantly inhibited mitosis in the vaginal epithelium of mice by affecting antioxidant enzyme activities and interleukin (ILs) levels in psoriatic mice[26].The hypothesis is that zinc ion supplementation could be a potential treatment for psoriasis.
Copper stands out as a crucial trace metal, and multiple studies have underscored elevated blood copper levels in psoriasis patients compared to their healthy counterparts [19–21]. Furthermore, a positive correlation exists between copper levels and the severity scores of psoriasis [19, 24]. The surplus of copper is recognized for its ability to trigger reactive oxygen species, culminating in oxidative stress and inflammatory responses [27]. Consequently, the heightened serum copper levels observed in our study may merely serve as an indicator of inflammation.Earlier research has illuminated that individuals following a high-copper diet exhibit increased cytokine production and peripheral blood lymphocyte counts [28, 29]. Notably, copper levels also show a correlation with rheumatoid arthritis (RA) disease activity and serum cytokine levels [30, 31]. Serum copper predominantly mirrors serum copper cyanin [32], with cuprocyanin levels known to surge by 50% or more in various physical stress conditions, including trauma, inflammation, or disease [33]. The parallel elevation in serum cuprocyanin and copper levels has been substantiated in psoriasis patients by Hinks et al [34].Remarkably, studies have brought to light that tetrathiomolybdate (TM), a copper chelator, effectively inhibits imiquimod-induced psoriasis-like skin inflammation in mice [35]. TM induces a reduction in cumulative score, epidermal thickness, and ki-67 expression, alongside lowering cytokine levels in the skin by impeding the activation of keratinocytes and splenocytes. This underscores the potential of a copper chelator, such as TM, as a promising agent for psoriasis treatment. However, it is imperative to conduct further studies to elucidate the precise role of copper in the pathogenesis of psoriasis.
Although our results did not show that serum selenium is associated with the risk of psoriasis, according to a part of previous studies, serum selenium concentrations are decreased in patients with psoriasis[17, 18]. Several reviews have emphasized the potential of Se as an antioxidant for the treatment of diseases by exerting an immunostimulatory effect enhancing the function of immune and thyroid cells[36, 37, 38]. Selenium deficiency induces higher levels of inflammatory cytokines and immune responses, thereby augmenting vulnerability to infections[39]. A case-control study involving 60 psoriasis patients and 58 healthy subjects revealed lower serum selenium concentrations in individuals with psoriasis (71.89 ± 16.90 µg/L) compared to controls (79.42 ± 18.97 µg/L), even following NB-UVB treatment[40]. However, selenium supplementation remains controversial given the small gap between beneficial and harmful intakes of selenium.
Elevated serum copper and reduced serum zinc levels are commonly observed in patients with psoriasis, and therefore the Cu/Zn ratio is significantly higher than that of controls.Wacewicz et al. found significant correlation coefficients between CRP and Cu/Zn, and therefore serum Cu/Zn may be useful as an indicator of the extent of acute inflammatory tissue damage and the efficacy of treatment in psoriasis[41].Gao et al. identified a marked rise in serum zinc levels and a pronounced decline in serum copper in patients with psoriatic arthritis after intravenous methotrexate administration[42].In conclusion, treatment that normalizes serum copper and zinc levels improves the prognosis of patients with psoriasis.
This study boasts a significant strength in utilizing a sizable, nationally representative sample of adults in the United States. It is the largest cross-sectional study investigating the association between serum zinc, copper, and selenium and psoriasis to date. We recognize some limitations of this study. The first is reverse causality caused by the cross-sectional design of NHANES. Second, the definition of psoriasis patients was based on a validated questionnaire that was not confirmed by linkage to a dermatologic registry. In addition, other covariates not considered in this analysis may be of concern. Finally, the association between dietary intake of zinc, copper, and selenium and risk of psoriasis was not considered in this analysis.
In conclusion, the study found no substantial association between serum zinc, copper and selenium levels and psoriasis in US adults.Furthermore, large longitudinal studies should be needed to confrm these fndings.