Successfully treating apical periodontitis with endodontic therapy may improve glucose and lipid metabolism as well as systemic inflammatory markers.
In a 2-year longitudinal metabolomic study, researchers at King's College London analyzed 44 serum metabolites using nuclear magnetic resonance (NMR) spectroscopy in 65 adult patients with apical periodontitis (AP) undergoing endodontic treatment. Samples were collected at five time points: preoperative baseline and at 3, 6, 12, and 24 months.
The researchers revealed postoperative changes in 24 metabolites (55%). Most notably, branched-chain amino acids leucine and valine decreased significantly at 3 months following treatment, suggesting improved glucose tolerance and lipoprotein metabolism. Glucose and pyruvate levels decreased significantly at the 2-year review.
"The results suggested improved glucose and lipid metabolism as well as reduced inflammatory burdens, as evidenced by a significant reduction in branched-chain amino acids at the 3-month review; a significant decrease in glucose and pyruvate at the 2-year review; a short-term reduction in cholesterol, choline, and fatty acid levels; and a progressive increase in tryptophan," reported lead study author Yuchen Zhang, of the Centre for Oral, Clinical & Translational Sciences in the Faculty of Dentistry, Oral & Craniofacial Sciences at King’s College London, and colleagues.
Dynamic Bayesian network modeling identified key regulatory metabolites throughout the review period, with the top 10 including lysine, valine, glutamine, alanine, ornithine, and threonine. These metabolites demonstrated strong associations with the tricarboxylic acid (TCA) cycle, suggesting a central role in cellular energy production during periapical healing.
"[W]e hypothesize that successful endodontic treatment may restore impaired TCA cycle function by improving glucose and lipid metabolism. The restoration of TCA cycle activity may, in turn, promote periapical bone regeneration via the mTOR signaling pathway," the study authors stated.
Lipid metabolism improvements were characterized by transient reductions in cholesterol at 3 months and 6 months, decreased choline levels at 6 months, and reduced fatty acid levels at 3 months. Tryptophan levels demonstrated a sustained increase throughout follow-up, with 2-year levels nearly double the baseline measurements. The researchers suggested serum tryptophan could serve as a prognostic biomarker for AP outcomes and AP-related cardiovascular disease risk.
The researchers identified statistically significant correlations between serum metabolites and cardiovascular disease risk biomarkers. Matrix metalloproteinase (MMP)-8 demonstrated consistent negative correlations with glucose levels at baseline and through 1 year of follow-up. At the 2-year review, when glucose levels decreased, serum glucose showed no statistically significant associations with inflammatory markers or metabolic syndrome indicators, suggesting a reduced inflammatory burden.
Microbiome analysis revealed strong correlations between preoperative blood and intracanal bacterial genera and serum metabolites. Acinetobacter, Ralstonia, Delftia, Micrococcus, and Mycobacterium demonstrated the most extensive associations with metabolic profiles. Specifically, blood Rothia correlated perfectly with cholesterol levels, while Mycobacterium showed strong positive associations with cholesterol, polyunsaturated fatty acids, and unsaturated fatty acids.
Correlation analyses revealed robust associations between metabolic profiles and clinical parameters. Triglyceride levels showed the strongest correlations with the overall metabolomic profile, demonstrating positive associations with acetone, mannose, cholesterol, and fatty acids; whereas exhibiting negative correlations with multiple amino acids, including asparagine, citric acid, glutamine, glycine, histidine, lysine, and ornithine.
The cohort comprised patients over 18 years without diabetes, cardiovascular disease, or metabolic syndrome according to NCEP ATP III criteria. All of the patients underwent either nonsurgical root canal retreatment or periapical surgery. Exclusion criteria included smoking, pregnancy, uncontrolled periodontal disease with pockets deeper than 4 mm, systemic inflammatory conditions, medications altering bone metabolism, and recent antibiotic use.
Radiographic assessment using periapical radiographs and cone beam computed tomography confirmed treatment success in all patients by the 2-year review (though 4 of the patients showed failure at 1 year), with reduced or fully resolved periapical lesions.
The researchers demonstrated that demographic and clinical factors like age, body mass index, blood pressure, waist circumference, lesion size, and HbA1c levels didn't show statistically significant associations with metabolite profiles following multiple testing correction, suggesting these variables didn't act as confounding factors. However, the total cholesterol/high-density lipoprotein (HDL) ratio demonstrated a positive association with serum fatty acid levels.
"Successful endodontic treatment in [patients with] AP is associated with improved glucose and lipid metabolic profiles, and a reduction in systemic inflammation, suggesting a potential role in mitigating cardiometabolic disease risk," concluded the study authors.
The findings paralleled established evidence from periodontal therapy studies, where meta-analyses have demonstrated improvements in glycemic control, endothelial function, and lipid profiles following treatment of generalized periodontitis. This study extended similar systemic metabolic benefits to the endodontic treatment of AP.
Study limitations included its modest sample size (n = 65), absence of control groups comprising healthy patients or cases with unsuccessful treatment, and potential residual confounding from unmeasured factors such as dietary habits. The researchers emphasized that while the data supported an association between successful endodontic treatment and metabolic improvements, they didn't establish causation. Definitive conclusions will require well-powered, controlled epidemiologic studies and mechanistic experiments in animal models.
The authors declared that they have no competing interests.