Magnesium acts as an important catalyst as the fourth most active element in a human body and the second most in cells (1).It is specifically present in bones and soft tissue among others. It not only plays a key role in energy metabolism, nucleic acid, and protein synthesis, which ensure the survival of all tissues and cells in the human body, but it is also an indispensable nutrient necessary for maintaining human life. Despite the fact that the biomarker of magnesium concentration in serum does not reflect the magnesium levels existing inside the cell, there is ample evidence associating the content of this metal with the various pathological conditions including cardiovascular diseases, diabetes, hypertension, and osteoporosis, which are systemic conditions as a result of the periodontal disease (2, 3). Chronic inflammation of the periodontal supporting tissues is known as periodontitis (4). Prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and other pathogenic factors can be secreted by periodontal bacteria and metabolites, which can activate immune cells and cause persistent inflammation that damages periodontal tissue and absorbs bone from the alveolar bone (5). Furthermore, injury to periodontal tissue might be caused by the endotoxin of several gram-negative bacteria found in periodontal microorganisms (6). The hard and soft tissues that surround teeth are affected by the frequent oral illness known as periodontitis. Gum edema, the development of periodontal pockets (7), the absorption of alveolar bone that follows, and ultimately the loosening and shedding of teeth are the key symptoms of the early stages of periodontal disease, which have a major negative impact on people’s lives and health. The adult tooth loss rate can range from 10 to 15%, whereas the incidence rate can reach up to 90% (8). Thus, the current focus of research in mouth-related domains is on regeneration of periodontal tissue. Controlling inflammation, halting the spread of the disease, and restoring the architectural structure and functionality of healthy periodontal tissue are the goals of periodontal therapy (9). Currently, basic treatment, surgical treatment, and adjuvant medication treatment are the typical ways to treat periodontitis (10). However, these treatments have their own advantages and disadvantages. Basic treatment and drug treatment can alleviate inflammation and temporarily stop the development of lesions, but bone regeneration cannot be achieved yet. Since the 1980s, researchers have gradually explored the cellular and molecular mechanisms related to magnesium and inflammation through in vivo and in vitro experiments. However, there is limited literature summarizing the correlation between magnesium and periodontitis, despite the fact that periodontitis is also associated with magnesium (11). Therefore, this review aims to provide a preliminary summary of the relationship between magnesium and periodontitis as well as to infer the pathogenic mechanism of magnesium on periodontitis based on current research.

Clinical research by Meisel revealed a strong correlation between serum magnesium ion concentration and periodontal probing depth, which prevents attachment loss and tooth loss (12). Furthermore, magnesium shortage and the induction of pro-inflammatory cytokines may be the reason for the low periodontal bone mass in patients with periodontitis. Through a cross-sectional study, they looked further into the relationship between blood magnesium concentration and periodontal health in 4290 people and discovered that 35% of patients with periodontitis had hypomagnesemia. After that, they compared the periodontal-related parameters between the patients who took and did not take magnesium supplements. They discovered that patients who took drugs containing magnesium had a significant correlation between their serum magnesium levels and periodontal health, indicating that taking magnesium supplements could both prevent tooth loss and improve periodontal health (13). Furthermore, researchers have examined the serum magnesium levels of individuals with chronic periodontitis both before and after scaling and root planning, and they have discovered that the elevation of serum magnesium levels occurs following the resolution of inflammation during scaling (14). However, from a nutritional perspective, it has been discovered that trace minerals can influence the course of periodontitis, and a chronic deficiency in magnesium will result in weakening of the alveolar bone, swelling of the gingiva, loosening of the teeth, and early loss (15). However, the height of alveolar ridge and tooth loss caused by magnesium deficiency may reduce bone loss if magnesium supplements are taken orally in time (16). In rodents, pro-inflammatory cytokines, associated proteins, and gingival congestion will all rise in response to a drop in serum magnesium ion concentration (17). Nevertheless, other research likewise revealed no distinction in serum magnesium concentrations between individuals consuming magnesium supplements and those who did not (16). Because people with hypomagnesemia can only benefit from substantial doses of magnesium to raise their serum magnesium content (18). From a biological perspective, magnesium modulates immune cells to influence the onset and progression of periodontitis. A lack of magnesium will impair adaptive immune cells’ ability to respond, trigger the innate immune system, and so increase inflammation (3). Isolated from animals lacking in magnesium, macrophages and neutrophils exhibit hyperreactivity to a range of stimuli, maybe linked to the reduction in magnesium concentration in inflammatory responses (19). Neutrophils contribute to tissue degradation and preserve inflammation (20). Hypomagnesemia can be caused by activated neutrophils (21). Additionally, magnesium controls the immune system’s reaction (22). As a result, reduced magnesium concentration can intensify the bacterially-induced inflammatory response (23). Nevertheless, some research has shown that a drop in serum magnesium levels does not always translate into a drop in salivary magnesium concentrations. In fact, some investigations have shown that an increase in the magnesium content of calcified tissues can cause salivary magnesium concentrations to rise. Patients with gingivitis and periodontitis had, on average, higher concentrations of magnesium in their saliva, according to research by Shetty et al. (24). According to some researches, the variation in the amount of magnesium in saliva could be useful in assessing the severity of periodontal disease (25). Manea and Nechifor (26) did note, however, that periodontitis patients’ saliva did not exhibit a statistically significant rise in magnesium concentration (26). Based on similar studies, saliva contains more magnesium than 8 parts per milligram (ppm). This could be a sign of periodontal disease or a sign that therapy is working.

A great deal of research has already shown that there is a connection between inflammation and low magnesium levels. Other studies have even looked at the possible pathways that could connect low magnesium to periodontitis. Research has shown that the start of periodontitis and other trace elements like potassium, calcium, and phosphorus, which can cause inflammation, are somewhat related to magnesium insufficiency brought on by vitamin imbalances. In a cross-sectional epidemiological study where periodontal health was identified and associated with serum magnesium and calcium concentrations, magnesium intake was inversely associated with the prevalence of periodontitis (49). Magnesium, of its unique ability to reduce inflammation caused by bacterial toxins, may play an important role in preventing periodontal disease (50). A toothpaste containing magnesium salt can reduce the incidence of periodontitis (51). Mg was also found to have local analgesic and anti-inflammatory effects in previous studies, especially in the presence of alkaline pH (52). Periodontitis may develop as a result of immunological responses impacted by a magnesium imbalance, which could cause immune cells to release cytokines. A shortage in magnesium can also cause oxidative stress, and the reactive oxygen species (ROS) that come from this can take part in a number of inflammatory and periodontal bone resorption processes. The development and course of periodontitis are clearly influenced by magnesium deficiency in an indirect manner.

The exact cause of magnesium deficiency-induced periodontitis, the effects of magnesium on local periodontal microorganisms and their functions, the difference between the effects of magnesium on extracellular and intracellular periodontal tissue, the temporal and spatial influence of magnesium deficiency on other trace elements in the context of periodontitis, and the best ways to supplement with magnesium to treat periodontitis caused by magnesium deficiency are all subjects of further in-depth mechanistic studies that are necessary to clarify the matter. This covers issues like which form and use of magnesium supplements is best, as well as whether systemic or local supplementation is preferable. Biodegradable magnesium biomaterials have emerged as a possible treatment option for various human ailments, as biomaterials research continues to advance. Investigations into the possible application of biomaterials containing magnesium to improve and treat periodontitis have resulted from this. These results may provide more effective methods of treating and preventing periodontitis.

MW: Conceptualization. YC: Preparation and revision of the manuscript. YC and MY: Data curation. All authors participated in the manuscript’s revision process and gave their approval before it was submitted to this publication.