Successful endodontic Tx tied to cardiometabolic benefits

In a self-controlled, longitudinal cohort study on individuals with apical periodontitis (AP), successful endodontic treatment is associated with improvements in glucose tolerance and lipid profile, suggesting a potential role in alleviating cardiometabolic disease risk.

Using nuclear magnetic resonance spectroscopy on serum samples, the researchers evaluated metabolic improvements associated with successful endodontic treatment in 65 individuals with AP undergoing endodontic treatment (including nonsurgical root canal retreatment and periapical surgery). The samples were collected at baseline (preop) and during their review appointments (3 and 6 months, 1 year, and 2 years postop). [J Transl Med 2025;23:1195]

Of the 44 serum metabolites analysed, 24 showed significantly altered levels during follow-up compared with baseline. “These metabolites were primarily involved in amino acid, glucose, and lipid metabolism,” the researchers said.

Changes in amino acid profile

There were significant reductions in the levels of leucine, valine, glutamic acid, asparagine, ornithine, glycine, and histidine at one or more timepoints during follow-up compared with baseline (mixed-effects analysis with Greenhouse-Geisser correction, p<0.05).

Conversely, tryptophan levels increased progressively across all review appointments vs baseline (p<0.001), highlighting its unique role in the healing of periapical lesions. According to the researchers, the constant and significant increase in serum tryptophan levels suggests reduced risks of systemic inflammation and cardiovascular disease (CVD).

“[B]ranched-chain amino acids (BCAAs), including valine, leucine, and isoleucine, made a higher contribution to the compositional dissimilarity in the amino acid profile,” the researchers noted.

Changes in glucose metabolism

Looking at the metabolites involved in glucose metabolism and energy production, citric acid levels increased (p=0.0006 and p=0.0273 at 3 and 6 months, respectively), while glutamic acid levels decreased (p<0.0001 at 1 year), as did BCAA levels, specifically leucine and valine (p<0.0001 and p=0.0296 at 3 months), compared with pretreatment levels.

The researchers attributed the BCAA reductions to alterations in BCAA metabolism that may have occurred after periapical healing and remodeling following endodontic treatment. “[T]he post-treatment decrease in BCAAs may indicate improved glucose tolerance and lipoprotein metabolism.”

There were also reductions in lactic acid levels at 6 months and 1 year (p=0.0020 and p<0.0001, respectively) and glucose (p=0.0079) and pyruvate (p<0.0001) levels at 2 years.

“[T]here is a mutually reinforcing relationship between hyperglycaemia and systemic inflammation,” researchers said. The significant progressive reductions in glucose and pyruvate post-endodontic treatment, especially at 2 years, underscore the link between successful endodontic treatment and improved glucose tolerance and reduced systemic inflammatory burden.

Serum glucose level was not associated with any inflammatory markers or metabolic syndrome indicators at 2 years. According to the investigators, this suggests that improved glucose metabolism was associated with a reduced inflammatory burden post-endodontic treatment.

Changes in lipid metabolism

There were significant reductions in cholesterol levels at 3 months (p=0.0314) and 6 months (p=0.0007), and choline levels at 6 months (p=0.0004) compared with baseline. Fatty acid levels also dropped significantly at 3 months (p=0.0180) but recovered later. There was a trend toward reductions in triglyceride levels at 3 months, but increases were observed at 1 year and 2 years.

“Together, these findings highlight a link between successful endodontic treatment and a short-term benefit on lipid metabolism,” the researchers explained.

Potential prognostic markers

The investigators noted that the metabolic improvements may be tied to energy production and bone remodeling during post-treatment healing, possibly by restoring the tricarboxylic acid cycle function.

“Notably, serum tryptophan, triglyceride, and glucose levels emerge as potential AP prognostic biomarkers for monitoring post-treatment healing and assessing AP-related cardiometabolic disease risks,” they said.

“Taken together, this study highlights the broader systemic benefits of successful endodontic treatment beyond oral health, suggesting a potential role in mitigating cardiometabolic disease risk and the clinical significance of metabolic monitoring in AP patients undergoing endodontic treatment,” the researchers concluded.