Editorial: Endocrine Imbalances of Mineral Ions and Vitamins in Chronic Diseases Pathogenesis

Mor-Li Hartman¹Hosam Gharib Abdelhady²Mohammed S. Razzaque^3*

• ¹The Forsyth Institute, Cambridge, United States
• ²Sam Houston State University College of Osteopathic Medicine, Conroe, United States
• ³The University of Texas Rio Grande Valley, Edinburg, United States

Chronic diseases represent a major global health burden, accounting for nearly two-thirds of all deaths worldwide (1). In the United States, poor dietary habits and insufficient physical activity, both strongly associated with obesity, are leading contributors to this burden (1). Among the many factors implicated in the onset and progression of chronic diseases, disruptions in mineral and vitamin homeostasis play a critical yet often underappreciated role. Essential mineral ions such as calcium, magnesium, phosphate, zinc, selenium, and iron are fundamental to human physiology. They participate in metabolic regulation, immune responses, neuromuscular function, and bone health (2,3). Both deficiency and excess of these micronutrients can lead to significant health complications. For example, dysregulation of calcium and phosphate levels is linked to osteoporosis, cardiovascular events, and neuromuscular dysfunction (2,4,5). Similarly, chronic kidney disease (CKD) is influenced by imbalances in minerals, vitamins, and other metabolites, with evidence supporting their potential therapeutic roles in modulating inflammation and oxidative stress (5). Micronutrient deficiencies are also frequently observed in metabolic disorders such as type 2 diabetes, obesity, cardiovascular disease, and metabolic syndrome. Notably, patients with type 2 diabetes often exhibit reduced levels of zinc, magnesium, and chromium, which may exacerbate insulin resistance and impair glucose metabolism (6)(7)(8)(9). Recent work also suggests that salivary phosphate levels could serve as early biomarkers for obesity risk in children, linking oral biomarkers with systemic metabolic changes (10). Despite these insights, the mechanistic relationships between micronutrient status and chronic disease progression remain incompletely understood. Emerging evidence further highlights the protective effects of a nutrient-rich diet, particularly in younger populations.Adolescents consuming diets high in fruits, vegetables, legumes, and whole grains show significantly lower risk of developing chronic diseases compared to those adhering to Western dietary patterns (11). These findings underscore the importance of early dietary interventions and the need to investigate how micronutrient dynamics contribute to disease etiology, prevention, and treatment across the lifespan. National Health and Nutrition Examination Survey (NHANES). They introduced the Magnesium Depletion Score (MDS) as a novel marker of magnesium status and found that higher MDS was significantly associated with increased prevalence of hyperuricemia, suggesting a potential contributory role of magnesium deficiency. The authors emphasize the need for prospective studies to confirm these results. Moreover, they noted magnesium's role in vitamin D biosynthesis, an essential hormone for glucose metabolism and insulin sensitivity. China to examine the relationship between Asprosin, an adipokine associated with insulin resistance (13), and vitamin D. Previous studies have shown that Asprosin levels correlate positively with insulin resistance (14). In this study, the authors found an inverse relationship between serum Asprosin and 25hydroxyvitamin D, the primary circulating form of vitamin D. These findings underscore the need for further research into vitamin D metabolism and its broader implications for human health (6,15,16). Hakeem et al. examined the metabolism of vitamin D and the various factors influencing its levels, with a particular focus on validating a novel LC-MS/MS method for analyzing vitamin D and its metabolites in mouse hair samples. The use of hair as a biomatrix for assessing vitamin D status represents an innovative approach.Their findings highlight the roles of dietary intake, light exposure, and metabolic regulation in maintaining adequate vitamin D levels in mice. The study supports the importance of sufficient vitamin D and sunlight exposure for optimal vitamin D status. This complements existing research emphasizing the critical role of vitamin D in bone health, particularly in calcium and phosphate homeostasis (15,17,18). progression and may serve as potential therapeutic targets. As DKD resulting from metabolic disease poses a major global health challenge, further research is needed to better understand its underlying mechanisms (24), emphasizing consequences of abnormal regulation of FGF23, vitamin D and phosphate metabolism in chronic diseases (25,26). Lin and Yang investigated the association between serum Klotho levels and the risk of CKD in middle-aged and older adults with metabolic syndrome. Using crosssectional data from NHANES, they identified a non-linear, L-shaped relationship between Klotho levels and CKD risk, with an inflection point at 9.88 pg/mL. Their findings suggest that both abnormally low and high Klotho concentrations are associated with increased CKD risk, underscoring the importance of maintaining Klotho within an optimal range. The study highlights the potential of Klotho as both a serum biomarker and a target for preventive strategies in this high-risk population. levels and all-cause mortality, addressing the current lack of a defined normal reference range for this biomarker (27). Their analysis revealed a U-shaped association, with an inflection point at 2.89 pg/mL, indicating that both low and high alpha-Klotho levels may be linked to increased mortality risk.However, further research is needed to elucidate the underlying mechanisms driving this relationship. Xia et al. reported a U-shaped association between dietary niacin intake and CKD, with an inflection point at 38.83 mg/day, indicating that both low and high dietary niacin levels may be linked to disease burden of CKD. Drawing on cross-sectional data from the 2003-2018 NHANES, the study investigated the link between niacin, recognized for its renal protective effects, and CKD in the elderly U.S. population. The findings underscore the importance of early prevention and intervention strategies in this at-risk group. However, due to the cross-sectional design, causality cannot be established, emphasizing the need for confirmation through largescale prospective cohort studies. Liver health is a critical concern due to the liver's central role in metabolism, detoxification, and biochemical synthesis (28). Selenium, an essential micronutrient obtained through the diet, has garnered attention for its potential impact on liver function, given its key role in enzymatic activity and antioxidant defense mechanisms (29). Liang et al.described the relationship between selenium intake, blood selenium levels, and liver function to inform future dietary guidelines and interventions. Their cross-sectional study focused on a population with relatively high selenium intake and blood concentrations, but without significant liver impairment. The findings suggest that both dietary and circulating selenium levels influence liver function parameters. The authors emphasize the need for further research to clarify the interplay between selenium status and liver health across diverse populations, to improve preventive care strategies.