Psoriasis is an immune-mediated chronic inflammatory skin disorder with a global prevalence of approximately 2–3% (1, 2). It is distinguished by erythematous papules covered with silvery-white scales, commonly affecting the scalp, back, and extensor surfaces of the limbs. Beyond cutaneous manifestations, psoriasis can also impact multiple organ systems. Patients with psoriasis commonly have comorbidities, including psoriatic arthritis (3), diabetes (4), and cardiovascular diseases (5, 6). Psoriasis imposes significant physical and psychological trauma on patients, severely compromising their quality of life (7). It also imposes significant costs on individuals and healthcare systems. However, the pathogenesis of psoriasis remains incompletely understood. Current evidence indicates that its etiology is caused by genetic vulnerability, immune dysregulation, and environmental factors.

Magnesium, a crucial regulatory ion in numerous enzymatic reactions, is essential for human health and disease prevention (8). As the second common intracellular cation in the human body, magnesium ions are required for normal cellular activity and physiological homeostasis (9). Furthermore, magnesium participates in a variety of enzymatic reactions, having a crucial effect on energy metabolism, maintaining immune balance, and modulating oxidative stress and inflammatory responses (10). Magnesium deficiency or dysregulation of magnesium metabolism is implicated in the pathological processes of various diseases (11).

In recent years, the role of micronutrients in psoriasis has garnered increasing attention. Growing evidence suggests that micronutrients such as calcium, magnesium, zinc, and selenium influence the onset and progression of psoriasis through various biological mechanisms (12, 13). Previous studies have mainly examined the effect of serum magnesium levels and dietary magnesium intake on the disease. However, these evaluation criteria frequently ignore aspects such as renal excretion and intracellular storage, thereby failing to sufficiently capture magnesium level. Consequently, the prevalence of magnesium deficiency and its potential health effects may be significantly underestimated. The relationship between magnesium homeostasis and health or disease remains insufficiently explored. There is an urgent need to develop a precise, simple, and widely applicable tool for assessing magnesium bioavailability.

The magnesium depletion score (MDS) represents a newly proposed composite indicator that measures magnesium status in the body (14). MDS comprehensively evaluates four crucial risk factors, including proton pump inhibitor (PPI) and diuretic use, alcohol consumption, and renal disease. MDS takes into account renal reabsorption function, serving as a sensitive and reliable indicator for assessing magnesium deficiency status in the human body. A higher MDS means more severe magnesium insufficiency. MDS has been found to be strongly related to the risk and prognosis of several various diseases (15, 16). Nonetheless, the relationship between MDS and psoriasis remains to be explored. In view of this, this study evaluated the potential association between MDS and psoriasis based on data from the National Health and Nutrition Examination Survey (NHANES). The objective of this study was to reveal the relationship between magnesium homeostasis and psoriasis prevalence and mortality. These findings are expected to expand the understanding of environmental risk factors for psoriasis and open new perspectives for individualized nutritional management.

This study examined the relationship of MDS and the prevalence and all-cause mortality of psoriasis based on data from five NHANES cycles. The findings showed that MDS maintained significant and stable positive associations with psoriasis prevalence and all-cause mortality. These associations remained consistent across subgroups. The results provide new evidence supporting the environmental etiology of psoriasis from the perspective of systemic magnesium homeostatic imbalance, suggesting that systemic magnesium depletion may be directly involved in the pathological process of psoriasis. Our findings, if validated in future studies, could support the development of personalized dietary recommendations for psoriasis prevention. Similarly, the Dietary Inflammatory Index (DII), which quantifies the inflammatory potential of diet, has been linked to psoriasis incidence (19). Unlike the DII, which aggregates multiple dietary components, the MDS focuses specifically on magnesium status. It provides a more targeted assessment of magnesium depletion, potentially offering advantages in scenarios where magnesium deficiency is a hypothesized mechanistic driver of inflammation. Furthermore, serum vitamin D levels have been extensively studied in dermatological conditions, with deficiencies correlated with increased psoriasis severity (20). While serum vitamin D is a valuable biomarker, it represents a single snapshot. In contrast, the MDS combines both biochemical and dietary data, thereby providing a more comprehensive picture of nutrient status.

Magnesium is necessary for life and health (21). As a key cofactor of adenosine triphosphate, it plays an indispensable role in cellular energy metabolism. Furthermore, magnesium influences the metabolism of proteins, lipids, and carbohydrates in addition to serving as a cofactor for a variety of enzyme activities. Magnesium deficiency is a common nutritional deficiency state. Magnesium deficiency is influenced by various factors, including inadequate dietary intake, gastrointestinal absorption disorders, increased renal excretion, as well as medication use and chronic diseases. Due to unhealthy dietary patterns, many individuals often fail to meet the daily recommended intake of magnesium, leading to magnesium deficiency. The 2015–2020 Dietary Guidelines for Americans recommend an optimal dietary magnesium requirement of 320 mg per day for females and 420 mg per day for males under physiologic conditions. Importantly, the demand for magnesium may be higher under pathological conditions. Unfortunately, many Americans do not consume sufficient magnesium in their daily diets (22).

Although the precise mechanisms linking magnesium depletion to psoriasis pathogenesis remain to be fully elucidated, several plausible biological pathways, informed by the known role of magnesium in cellular functions, may explain our observed association. First, magnesium deficiency has been linked to elevated levels of substance P and neurogenic inflammation, which are known contributors to psoriasis flare-ups and pruritus (23). Moreover, magnesium deficiency is associated with inflammatory responses mediated by calcium, N-methyl-D-aspartate, and tumor necrosis factor-alpha, as well as increases in C-reactive protein (CRP) (24, 25). Besides, low magnesium levels trigger the activation of nuclear factor kappa B (NF-κB), a primary driver of the chronic inflammation characteristic of psoriasis (26). Magnesium modulates inflammatory signaling through multiple pathways and inhibits the generation of inflammatory mediators, thereby attenuating psoriasis. A meta-analysis that included 17 randomized controlled trials found that magnesium supplementation significantly reduced several inflammatory markers, particularly CRP (27). These findings indicate that the protective impact of magnesium supplementation in psoriasis is partially attributable to inflammation suppression effects. Interestingly, a recent study identified that a high-magnesium diet enhanced the number of regulatory T cells (Treg) in an IL-10-dependent manner through the mediation of the gut microbiota (28). Treg cells exert a protective role in psoriasis by suppressing inflammatory responses and maintaining immune homeostasis (29). Furthermore, magnesium ions specifically suppress the antigen-presenting function of human epidermal Langerhans cells in vivo and in vitro, contributing to the enhancement of psoriasis efficacy (30).

Second, magnesium has been demonstrated to inhibit oxidative stress and reduce impairment due to free radicals (31). Persistent magnesium deficiency exacerbates oxidative stress. Low magnesium levels trigger oxidative DNA modifications and impaired DNA repair, worsen skin inflammation, and stimulate hyperproliferation of keratinocytes (32). Psoriasis patients show abnormally elevated concentrations of reactive oxygen species (ROS) in areas of skin lesions (33). Mitochondria are the main site of intracellular ROS generation. When intracellular magnesium is deficient, magnesium translocation to mitochondria is suppressed, which in turn results in lower magnesium levels in mitochondria. Mitochondrial magnesium deficiency impairs the activity of the electron transport chain and interferes with the coupling efficiency of the respiratory chain, ultimately causing increased ROS generation (10). Interestingly, dietary magnesium supplementation significantly increased erythrocyte superoxide dismutase levels (34).

Third, magnesium has a significant effect in lipid metabolism, which is closely related to the pathomechanism of psoriasis by regulating sebum metabolism. Magnesium participates in fatty acid synthesis and cholesterol metabolism as a cofactor for several enzymes. Importantly, magnesium regulates phospholipase A2 (PLA2) activity. PLA2 is a vital enzyme involved in inflammatory responses and cellular signaling. Additionally, PLA2 is responsible for chronic epidermal hyperplasia and hyperkeratosis (35). Specifically, magnesium ions indirectly inhibit PLA2 activity by modulating intracellular calcium ion concentrations, reducing the release of arachidonic acid and its downstream production of proinflammatory lipid mediators, such as prostaglandin E2 and leukotriene B4 (36). It was found that magnesium supplementation contributed to lowering blood lipid levels (37). Magnesium ions reduce skin damage from external stimuli by regulating epidermal lipid composition and enhancing skin barrier function (38).

Magnesium condition was assessed by MDS in this study. MDS combines several major factors that influence magnesium reabsorption in the body, involving prescription medications, kidney function, and lifestyle habits. We discovered that greater MDS was associated with higher prevalence and all-cause mortality in psoriasis. Previous research has demonstrated that kidney failure acts as an independent risk factor for death (39). Notably, patients with psoriasis have a significantly elevated risk of chronic kidney disease (CKD) and end-stage renal disease compared to individuals without psoriasis (40, 41). Meanwhile, kidney diseases are likely to exacerbate psoriasis and significantly raise mortality risk from psoriasis (42). Hence, changes in eGFR-related markers in psoriasis patients need to be monitored to minimize renal damage. Additionally, people who use diuretics often have a combination of multiple underlying diseases, including cardiovascular disease, hypertension and diabetes, and other chronic disorders. Given this factor, people taking diuretics tend to face a higher risk of death. Moreover, excessive alcohol consumption hinders intestinal magnesium absorption, which is one of the key factors contributing to magnesium deficiency (43). Numerous evidences revealed that alcohol intake aggravates psoriasis progression (44). Besides, alcohol might also influence the absorption and metabolism of medications, reducing the efficacy of psoriasis and making it difficult to control (45). Therefore, it is essential to emphasize the negative effects of alcohol consumption on psoriasis to patients in clinical health education.

One effective way to enhance the management of psoriasis is to increase intake of protective key nutrients through dietary changes. The association between MDS and psoriasis may provide new perspectives on the prevention and treatment of psoriasis. First, psoriasis risk may be reduced by modifying diet to increase consumption of foods rich in magnesium. Green leafy vegetables, healthy grains, legumes, and nuts are excellent sources of magnesium. The Mediterranean diet focuses on legumes, fish, whole grains, olive oil, vegetables, fruits, and nuts high in B vitamins and magnesium. It has been demonstrated that following Mediterranean diet contributes to alleviating psoriasis (46). Second, magnesium supplementation may represent an effective tool to manage psoriasis, especially in high-risk populations such as patients taking PPIs and diuretics, and CKD patients. Serum vitamin D levels were found to be significantly lower in psoriasis patients compared to healthy controls (47). The severity of psoriasis was negatively correlated with serum vitamin D levels (48). Magnesium supplementation may indirectly benefit psoriasis patients by improving serum vitamin D levels.

This study utilized data from the NHANES database. The sample selected was representative and large. Secondly, potential confounding factors were adjusted, ensuring the reliability of the study findings. Furthermore, sensitivity analyses confirmed the robustness of the results. Nevertheless, this study has several limitations that need to be addressed. First, the cross-sectional design restricts causal inference, making it unable to demonstrate a causal association between MDS and psoriasis. Second, while several covariates were considered in this study, it cannot be guaranteed that all potential confounding variables have been completely excluded. Factors such as genetic predisposition, stress levels, or specific medications may influence outcomes. Third, the MDS is an indirect estimate of magnesium status. The lack of direct biomarker correlation means we cannot confirm a true cellular deficit or fully delineate the potential biological mechanisms linking magnesium status to psoriasis pathogenesis. Additionally, a key limitation of this study is its reliance on the U. S.-based NHANES database. Therefore, our findings may have limited generalizability to populations in other regions, particularly non-Western countries. Differences in genetic backgrounds, dietary patterns, environmental exposures, and healthcare systems could significantly influence both magnesium status and psoriasis, limiting the direct applicability of our results to these populations. To validate the universality of the results, large-scale prospective cohort studies in other populations are still needed. Finally, psoriasis was diagnosed based on self-reported data, which is susceptible to recall bias and misclassification. Although self-report is a practical for large surveys like NHANES, the absence of validation against clinical examinations or review of medical remains a limitation. Overall, although the current study lacks a clear biological mechanism to explain the interaction between MDS and psoriasis, these findings may provide new perspectives for the prevention and treatment of psoriasis.

This study revealed a positive association between MDS and the prevalence and all-cause mortality of psoriasis, suggesting that magnesium deficiency may be a risk factor for psoriasis and influence its prognosis. Therefore, early monitoring and management of MDS might benefit the prevention and treatment of psoriasis. Increasing dietary magnesium intake may serve as a simple and potentially beneficial adjunctive approach for managing psoriasis. Future studies should further examine the specific mechanisms by which magnesium homeostasis affects the physiopathological processes of psoriasis, particularly its role in T cell activation, cytokine release, and skin barrier function. Combined analysis of multi-omics data likely contributes to a more comprehensive understanding of the complex relationship between MDS and psoriasis. Furthermore, the observed results need to be further validated by prospective cohort studies and randomized controlled trials to facilitate their translation into clinical practice.