Systemic inflammation mediates the association between docosahexaenoic acid/docosapentaenoic acid ratio and the risk of periodontitis.

Docosapentaenoic acid (DPA_ω6) and docosahexaenoic acid (DHA) are ω6 and ω3 polyunsaturated fatty acids (PUFAs), but their association with periodontitis is controversial. We hypothesize that a novel ratio incorporating these 2 PUFAs could provide a more reliable indicator of the relationship between serum PUFAs and the risk of periodontitis. To test this hypothesis, we examined the association between the DHA-to-DPA_ω6 ratio and the risk of periodontitis and explored the potential mechanism in human subjects. Logistic regression was employed to investigate the relationship between the DHA-to-DPA_ω6 ratio and periodontitis using data from the National Health and Nutrition Examination Survey. Restricted cubic spline analysis was performed to determine whether the association was linear or nonlinear, and mediation analyses were performed to identify the mediators of the association. Periodontitis was diagnosed in 1444 of 2937 participants. Unlike DHA or DPA_ω6 individually, the DHA-to-DPA_ω6 ratio was significantly associated with periodontitis risk (odds ratio: 0.99; 95% CI: 0.98-0.99; P = .03) and disease severity. This association was mediated by systemic inflammation (β = -0.004; 95% CI, -0.007 to -0.002; P < .001), rather than by oxidative stress, immunomodulation, or metabolic regulation. This novel omega-3-to-omega-6 polyunsaturated fatty acid ratio provides clinicians with a polyunsaturated fatty acid-based tool with which to evaluate the risk of periodontitis. It is therefore recommended that DHA intake be increased and DPA intake decreased to reduce the risk of the disease.