U-shaped association between magnesium intake and all-cause and cancer mortality in patients with osteoarthritis

Abstract

BACKGROUND: Clarifying the relationship between dietary magnesium intake and mortality risk in patients with osteoarthritis can provide theoretical basis for optimizing dietary interventions, reducing all-cause mortality and cardiovascular disease mortality, and provide reference value for nutritional management in patients with osteoarthritis. OBJECTIVE: To assess the association between dietary magnesium intake and all-cause and etiological mortality in adults with osteoarthritis in the United States. METHODS: We enrolled data of adults with osteoarthritis from the National Health and Nutrition Examination Survey (conducted by the National Center for Health Statistics under the U.S. Centers for Disease Control and Prevention, it aims to assess the health and nutritional status of the civilian population in the United States) between 2003 and 2020. The association between dietary magnesium intake and mortality in patients with osteoarthritis was evaluated by Cox proportional hazard model and two-stage Cox model. To assess whether the association between dietary magnesium intake and all-cause mortality was consistent across the population and to identify potential high-risk groups, subgroup analyses in terms of age, sex, body mass index, hypertension, diabetes mellitus, physical activity, smoking status, and drinking status were performed and tested for interactions. RESULTS AND CONCLUSION: (1) A total of 2 868 patients with osteoarthritis were included, and 699 all-cause deaths, 281 cardiovascular disease deaths, and 143 cancer deaths were recorded during follow-up. After adjusting for multiple variables, higher dietary magnesium intake was significantly associated with reduced risk of cardiovascular disease mortality; each 1-unit increase in dietary magnesium intake was associated with a 78% reduction in cardiovascular disease mortality (P=0.022 2), and quartile analysis of dietary magnesium intake was consistent with this. Dietary magnesium intake showed a U-shaped association with all-cause mortality and cancer mortality, with thresholds for lowest mortality risk at 0.38 g/d and 0.40 g/d, respectively. When magnesium intake was below the threshold, higher intake was significantly associated with lower all-cause mortality [HR=0.17, 95%CI(0.06, 0.50)] and cancer mortality [HR=0.16, 95%CI(0.01, 1.50)]; but above the threshold, magnesium intake was significantly associated with increased all-cause mortality [HR=2.94, 95%CI(0.55, 15.84)] and cancer mortality [HR=26.30, 95%CI(1.46, 474.73)]. Subgroup analyses further verified the robustness of the results. (2) The results indicate that insufficient dietary magnesium intake may play an adverse role in cardiovascular health, and there is a U-shaped relationship between dietary magnesium intake and all-cause mortality and cancer mortality, with both too low and too high magnesium intake potentially increasing mortality risk. This finding provides new insights into the potential impact of dietary magnesium intake on cardiovascular disease, cancer, and all-cause mortality, provides scientific basis for nutritional intervention in patients with osteoarthritis, and provides theoretical support for the prevention and management of cardiovascular disease and cancer in China, especially in the context of high cardiovascular disease incidence, reasonable magnesium intake helps reduce related mortality.

1. Introduction

Osteoarthritis is a chronic orthopedic disease primarily caused by cartilage degeneration [1], often leading to pain during walking, limited mobility, and ultimately disability [2]. With the aging of the global population, the incidence of osteoarthritis has been increasing annually, making it an increasingly severe public health issue [3]. Meta-analyses and cohort studies have shown that patients with osteoarthritis have a significantly higher risk of cardiovascular disease and mortality compared to the general population [4-5]. Therefore, identifying biomarkers that can predict and reduce long-term mortality risk, especially cardiovascular-related deaths, is of great importance. Existing research indicates that genetic factors, obesity, and unhealthy dietary habits may increase the risk of developing osteoarthritis [3].

Magnesium, as a key trace element in the human body, participates in metabolic balance and energy regulation, and an increasing number of studies point to a close relationship between dietary magnesium and osteoarthritis [6]. VERONESE et al. [7] found that for every 100 mg increase in daily magnesium intake, knee cartilage thickness and volume significantly increased, suggesting that high magnesium intake may play a positive role in the prevention and treatment of osteoarthritis. However, KONSTARI et al. [8] reported results contrary to this hypothesis, failing to demonstrate a protective effect of high magnesium intake on knee osteoarthritis. A meta-analysis showed that increased daily magnesium intake was significantly associated with reduced fracture risk in patients with knee osteoarthritis, but this increase did not significantly reduce the risk of knee osteoarthritis itself; moreover, individuals with higher serum magnesium levels had a significantly lower risk of knee osteoarthritis [9]. BAI et al. [10] ...