Magnesium (Mg2+) is an essential mineral that supports normal cellular metabolism, optimal musculoskeletal and neuronal functions, the immune response, and cardiovascular health. The regulation of magnesium is a complex process, and during pregnancy, it becomes even more challenging because of increased magnesium needs. Magnesium inadequacy during pregnancy can lead to severe complications, including preeclampsia in the mother, intrauterine growth restriction, preterm birth, low birth weight, insulin resistance, heart disease, and developmental delays in the neonate, due in part to its critical role in fetal musculoskeletal and nervous development. Magnesium deficiency during pregnancy is a global health concern, and raising awareness about the importance of maintaining magnesium balance, improving dietary intake, and promoting supplementation, when needed, could help reduce associated risks. This chapter discusses the impact of altered magnesium homeostasis on maternal health and fetal development while also addressing the need for global awareness and interventions to improve maternal and child health.

IntroductionSugar-sweetened beverages (SSBs) represent a modifiable dietary factor that promotes oral dysbiosis by supplying fermentable sugars and generating low-pH conditions that favor acidogenic and acid-tolerant biofilms. Vitamin D plays a biologically significant role in oral host defense through regulation of the epithelial barrier, induction of antimicrobial peptides, immune modulation, inflammatory control, and mineral metabolism. However, the extent to which vitamin D modifies the SSB -oral microbiome -disease pathway in humans remains unclear.MethodsThis narrative-conceptual review employed structured evidence mapping. Relevant literature was identified through PubMed/MEDLINE, Scopus, and Web of Science Core Collection, with additional sources obtained via citation and hand searching. Evidence was categorized into predefined domains: SSB/free-sugar exposure and oral outcomes; sugar exposure and oral microbiome characteristics; vitamin D status and oral health outcomes; vitamin D-related host-defense mechanisms; vitamin D and human oral microbiome evidence; and proposed SSB × vitamin D interaction pathways. A PRISMA-ScR-style flow diagram documented the process of evidence identification and selection, resulting in the inclusion of 90 sources. Evidence interpretation followed a tiered approach.ResultsThe most robust evidence indicates an association between frequent SSB/free-sugar exposure and caries-related outcomes. Human microbiome studies suggest that high sugar intake may be linked to dysbiotic shifts, although results differ depending on sampling site, study design, and analytical methods. Evidence connecting vitamin D to caries and periodontal outcomes is suggestive but remains heterogeneous. Direct human evidence relating 25(OH)D status to oral microbiome trajectories or SSB × vitamin D interaction models is limited. Mechanistic studies support biological plausibility but do not establish causality in humans.DiscussionVitamin D should be considered a candidate susceptibility factor and a potential proxy marker for broader behavioral, socioeconomic, metabolic, and inflammatory risk environments. Future longitudinal studies are needed to jointly assess SSB exposure, standardized 25(OH)D levels, plaque-site microbiome trajectories, confounders, and incident oral outcomes. Current practice recommendations continue to emphasize reducing SSB consumption, encouraging non-sugary alternatives, promoting fluoride use, maintaining oral hygiene, and supporting preventive dental care.

Phosphate (Pi) and calcium (Ca2+) are essential mineral ions that play coordinated roles in maintaining normal cellular functions. While various steps of calcium signaling are well characterized, emerging evidence suggests the critical role of both intracellular and extra cellular phosphate in regulating intracellular Ca2+. In the cytoplasm, phosphate influences ATP production and organelle calcium buffering and influences the activity of calcium pumps, such as sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) and the plasma membrane Ca2+-ATPase (PMCA). Extracellular phosphate, taken up via sodium-dependent phosphate transporters, triggers signaling cascades that affect the processes of calcium influx, storage, and release. Additionally, high extracellular phosphate levels can disrupt calcium homeostasis through the systemic interactions of hormones such as fibroblast growth factor 23 (FGF23), vitamin D and parathyroid hormone (PTH), especially under pathological conditions such as chronic kidney disease (CKD). This article briefly summarizes the current understanding of the bidirectional influence of intra- and extracellular phosphate on calcium dynamics at the cellular level, with a focus on the underlying mechanisms.

Glucagon-like peptide-1 (GLP-1) is a key metabolic hormone secreted by intestinal L-cells in response to nutrient ingestion. It plays a central role in regulating glucose homeostasis by enhancing insulin secretion, inhibiting glucagon release, delaying gastric emptying, and suppressing appetite. While glucose, fat, and protein are established stimulators of GLP-1 release, calcium has emerged as a key modulator of this enteroendocrine axis. Recent studies have shown that extracellular calcium, acting through the calcium-sensing receptor (CaSR) and voltage-gated calcium channels, triggers intracellular calcium influx, which is essential for GLP-1 exocytosis from L-cells. This highlights the role of calcium not merely as a dietary mineral but as a signaling ion that links nutrient sensing in the gastrointestinal tract to the hormonal regulation of blood glucose homeostasis. This chapter briefly explains how calcium influences the GLP-1-mediated gut-glucose axis.

Vitamin D–mediated regulation of antimicrobial peptides (AMPs) is an important focus in innate immunology and is aimed at elucidating the role of vitamin D in enhancing antimicrobial defense. AMPs are short protein chains that serve as a first line of defense against invading pathogens, including fungi, bacteria and viruses. Unlike conventional antibiotics, AMPs are produced endogenously and are less likely to induce antimicrobial resistance, making them promising candidates for treating infections caused by drug-resistant pathogens. Studies indicate that optimal vitamin D levels are essential for activating antimicrobial pathways and regulating AMPs that target multiple fungal pathogens. This article summarizes recent findings on vitamin D-induced AMPs in the context of invasive fungal infections. It also distinguishes vitamin D as a host immune modulator from vitamin D3 as a putative active antifungal compound, given that direct antifungal use is limited by supraphysiologic dosing requirements, pharmacologic impracticality, and risks of hypercalcemia and hyperphosphatemia, especially in patients with granulomatous diseases. Model limitations and species differences are also discussed, including primate-specific CAMP vitamin D response element regulation, which constrains direct translation of rodent vitamin D-to-LL-37 findings to human fungal disease. Current global fungal priority frameworks and resistance surveillance support emphasizing Candida, Aspergillus, and Cryptococcus in this review of invasive fungal disease and translational host-defense evidence, underscoring the relevance of these pathogens.

Viral infectious diseases rank among the leading causes of mortality globally. The rise of drug resistance mechanisms puts the effectiveness of all existing antimicrobial drugs at risk, several of which have become ineffective. Consequently, there is an acute need for novel antimicrobial agents. Host defense antimicrobial peptides (AMPs) are naturally occurring, evolutionarily conserved peptides that contribute to innate immunity and exhibit broad activity against viruses, bacteria, and fungi. They can also exert immunomodulatory and adjuvant activities by serving as chemotactic agents for immune cells and promoting cytokine and chemokine production. Vitamin D is a fat-soluble steroid hormone essential for regulating calcium and phosphorus metabolism to preserve bone homeostasis. Recent research has indicated that vitamin D has immunomodulatory effects on both the innate and adaptive immune systems, suggesting that it is a vital regulator of immunological homeostasis. Vitamin D stimulates the development of robust AMPs found in natural killer cells, monocytes, neutrophils, and epithelial cells of the respiratory tract. This chapter explains the evidence suggesting that vitamin D can reduce viral survival and replication by inducing AMPs.

Nutrients frequently act in coordination with the absorption and metabolism of one nutrient often interdependent on the presence of others. For example, magnesium is essential for the activation of vitamin D, which, in turn regulates calcium and phosphate homeostasis, both of which are critical for cellular and organ function. A comprehensive understanding of disorders arising from disruptions in vitamin D and mineral ion metabolism is essential for explaining the pathophysiological mechanisms associated with their imbalance. The chapters of this book are selected to provide in-depth insights and highlight important areas of bidirectional relationship between vitamin D and mineral ions for future research to advance the understanding of the delicate interactions between nutrients and overall health.

Vitamin D has long been accepted as a vital nutrient for bone health, with past guidelines supporting supplementation to maintain optimal levels. However, the recently updated 2024 Endocrine Society guidelines introduce a more conservative approach, shifting the focus away from widespread supplementation in healthy individuals and instead emphasizing use in high-risk populations. This chapter analyzes the key changes from the previous 2011 guidelines, including the removal of strict serum level thresholds for deficiency, revised daily intake recommendations, and screening criteria. The shift reflects growing evidence suggesting that excessive vitamin D supplementation may not provide additional health benefits and can contribute to risks such as hypercalcemia, kidney dysfunction, and eventual increased healthcare costs. The commentary explains the rationale behind said changes and the value for using evidence-based supplementation. Finally, we discuss the implications of these updated guidelines on paving clinicians' decision-making for their patients while highlighting the need for increased awareness and adherence to ensure safe and effective vitamin D consumption.

Owing to emerging global threats such as viral pandemics and the rise of antibiotic resistance, there is an urgent need for novel approaches to combat drug-resistant pathogens. Antimicrobial peptides (AMPs), also known as cationic host defense peptides (CHDPs), are considered promising candidates because of their ability to target various pathogenic microorganisms both directly and indirectly. These functionally versatile molecules modulate host immune responses by activating multiple signaling pathways simultaneously. The unique mechanisms of interaction within the pathogen-host system, combined with relatively straightforward biosynthesis, make AMPs viable alternatives to traditional antibiotics. Vitamin D is a key endogenous factor that regulates the biosynthesis and activity of AMPs, particularly cathelicidin and defensins. This chapter focuses on the interplay between vitamin D and antimicrobial peptides, highlighting recent advances in understanding their synergistic protective effects and potential clinical benefits.

Mpox, a zoonotic viral disease, has emerged as a global concern due to outbreaks in both endemic and non-endemic regions in 2022. Rodents, including African squirrels and Gambian pouched rats, are suspected key reservoirs, with human infections occurring through direct contact with infected animals or bushmeat consumption. Previously confined to rural Africa, mpox has spread via international travel and the exotic pet trade. Human-to-human transmission occurs mainly via respiratory droplets and direct contact with bodily fluids or lesions. The virus has a double-stranded DNA genome within a lipid envelope. Despite lower mutation rates in DNA viruses, mpox has developed mutations, particularly in genes like F8L, G9R, and F13L, facilitating viral replication and immune evasion. The virus targets immune cells such as monocytes and macrophages, weakening host defenses and prolonging infection. Immunocompromised individuals are at higher risk of severe complications. Although generally self-limiting, severe cases may require antiviral treatment. This article briefly summarizes the therapeutic and preventive strategies, and public health measures to combat zoonotic threats.

Minerals are essential nutrients that play critical roles in human health by regulating various physiological functions. Examples include bone development, enzyme function, nerve signaling, and the immune response. Both the deficiencies and toxicities of minerals can have significant health implications. Deficiencies in macrominerals such as calcium, magnesium, and phosphate can lead to osteoporosis (associated with falls and fractures), cardiovascular events, and neuromuscular dysfunction. Trace mineral deficiencies, such as iron and zinc. Selenium deficiency impairs oxygen transport, immune function, and antioxidant defenses, contributing to anemia, delaying wound healing, and increasing susceptibility to infectious diseases. Conversely, excessive intake of minerals can have severe health consequences. Hypercalcemia can cause kidney stones and cardiac arrhythmias as well as soft-tissue calcification, whereas excessive iron deposition can lead to oxidative stress and organ/tissue damage. Maintaining adequate mineral levels through a balanced diet, guided supplementation, and monitoring at-risk populations is essential for good health and preventing disorders related to deficiencies and toxicities. Public health interventions and education about dietary sources of minerals are critical for minimizing health risks and ensuring optimal well-being across populations. While a comprehensive analysis of all macro and micronutrients is beyond the scope of this article, we have chosen to focus on calcium, magnesium, and phosphate. We summarize the consequences of deficiency and the adverse events associated with the overconsumption of other minerals.

Fibroblast growth factor 23 (FGF23) requires both αKlotho and heparan sulfate proteoglycans (HSPGs) as obligatory coreceptors to bind, dimerize, and activate its FGF receptors (FGFRs) in the kidney, thereby regulating mineral ion and vitamin D homeostasis. Cryogenic electron microscopy studies reveal that FGF23 signaling proceeds through an asymmetric 1:2:1:1 FGF23-FGFR-αKlotho-HS assembly. According to this structural model, αKlotho simultaneously anchors FGF23 and one FGFR chain, referred to as the primary receptor (FGFRP), to form a 1:1:1 FGF23-FGFRP-αKlotho triplex, which boosts FGF23-FGFRP interaction. Subsequently, the HS coreceptor aids the triplex in recruiting a second FGFR chain, or secondary receptor (FGFRS), leading to asymmetric receptor dimerization. This recruitment is driven by the interactions of FGF23 and FGFRP from the triplex with the secondary receptor, with no direct involvement from αKlotho. This model outlines the possibility of heterodimerization among the renal cognate receptors of FGF23 (namely, FGFR1c, FGFR3c, and FGFR4), which may introduce signaling diversity affecting phosphate and vitamin D regulation. In addition, it proposes that kidney-specific HS structures could cooperate with renal αKlotho to home FGF23 to renal tissues. The proposed FGF23 signaling assembly provides a framework for further investigation and may inform the development of FGF23 antagonists or partial agonists for treating disorders associated with phosphate and vitamin D dysregulation.

INTRODUCTION:Inexorable high serum phosphate levels in chronic kidney disease (CKD) patients deteriorate the functionality of the musculoskeletal, renal, and cardiovascular systems, thereby contributing to increased morbidity and mortality. Higher phosphate balance has also been correlated with increased mortality rates in individuals with normal renal function, independent of other comorbidities. Clinical and epidemiological studies of CKD patients and healthy subjects, alongside evidence of accelerated aging in murine models induced by excessive phosphate loading, indicate that phosphate toxicity is a driver of premature aging and age-related organ damage. AREA COVERED:This article briefly discusses the causes and consequences of phosphate toxicity in the context of organ damage and aging while also elaborating on the therapeutic potential of the fibroblast growth factor 23 (FGF23) hormone signaling system in alleviating phosphate toxicity in patients with normal kidney function and CKD. EXPERT OPINION:Human age-associated disorders may be delayed through dietary programs or pharmacological interventions capable of modulating the activity of FGF23 signaling to reduce the systemic phosphate burden.

Magnesium plays an essential role in glucose utilization and insulin signaling. Recent advances have revealed a greater prevalence of hypomagnesemia in general, and low intracellular magnesium levels in individuals with diabetes contribute to β-cell dysfunction and insulin resistance. This article describes the documented effects of magnesium on various aspects of β-cells and glucose homeostasis. Studies have demonstrated that magnesium deficiency is associated with reduced pancreatic β-cell activity and increased insulin resistance in patients with type 2 diabetes. Additionally, magnesium is involved in many cellular events, including energy homeostasis, protein synthesis, and DNA stability. Furthermore, magnesium is critical for proper glucose utilization and insulin signaling, and magnesium deficiency can lead to the dysregulation of ATP-sensitive potassium (KATP) channels in pancreatic β-cells, impairing insulin secretion. Therefore, maintaining adequate magnesium levels is crucial for maintaining overall health and preventing of metabolic disorders such as type 2 diabetes.

Introduction: SARS-CoV-2 infection and COVID-19 vaccination can both lead to serious cardiac conditions such as myocarditis, arrhythmia, acute myocardial infarction, and coagulopathy. Further studies are needed to better understand the risks and benefits of COVID-19 vaccination, and to determine the best course of action for individuals with preexisting heart conditions. Areas covered: The current knowledge and challenges in understanding vaccine-associated heart issues concerning the COVID-19 pandemic are briefly summarized, highlighting similar cardiac conditions caused by either SARS-CoV-2 infection or COVID-19 vaccination and the potential clinical impacts. Expert opinion: The short-term risks of severe cardiovascular side effects following COVID-19 vaccination are relatively low. However, further studies are needed to determine whether adverse vaccination events outweigh the long-term benefits in specific groups of individuals. Since cardiac inflammation, blood pressure dysregulation, coagulopathy, acute myocardial infarction, or arrhythmia could be the consequences of either SARS-CoV-2 infection or COVID-19 vaccination, clinical questions should be asked whether the COVID-19 vaccine worsens the condition in persons with preexisting heart diseases. It is important to carefully assess the potential risks and benefits of COVID-19 vaccination, especially for individuals with preexisting heart conditions, and to continue monitoring and studying the long-term effects of vaccination on cardiovascular health.