Docosahexaenoic Acid and Periodontitis in Adults

Abstract

Periodontitis is a common chronic inflammatory disease initiated by bacteria, resulting in bone resorption, tooth loss, and systemic inflammation. Long-chain omega-3 fatty acids such as docosahexaenoic acid (DHA) reduce periodontitis in animals. We aimed to determine whether DHA supplementation with low-dose aspirin would reduce periodontitis in humans. We conducted a double-blind placebo-controlled parallel trial lasting 3 mo. Fifty-five adults with moderate periodontitis were randomized to 2,000 mg of DHA or identical soy/corn oil capsules. All participants received 81 mg of aspirin but received no other treatments. We analyzed the primary outcome of per-pocket change in pocket depth using mixed models among teeth with pocket depth ≥5 mm. Secondary outcomes assessed with generalized estimating equations included gingival index, plaque index, and bleeding on probing. Gingival crevicular fluid samples were analyzed for changes in high-sensitivity C-reactive protein (hsCRP) and interleukins 6 and 1β (IL-6 and IL-1β). Plasma was analyzed for changes in systemic inflammatory markers, including hsCRP. We confirmed adherence with erythrocyte fatty acid measurement. Forty-six participants completed the trial. While similar at baseline, the proportion of DHA in red blood cell plasma membranes increased from 3.6% ± 0.9% to 6.2% ± 1.6% in the intervention group but did not change among controls. DHA supplementation decreased mean pocket depth (-0.29 ± 0.13; p = .03) and gingival index (-0.26 ± 0.13; p = .04). Plaque index and bleeding on probing did not change. Significant adjusted differences were found between DHA and control for both gingival crevicular fluid hsCRP (-5.3 ng/mL, standard error [SE] = 2.4, p = .03) and IL-1β (-20.1 pg/mL, SE = 8.2, p = .02) but not IL-6 (0.02 pg/mL, SE = 0.71, p = .98) or systemic hsCRP (-1.19 mg/L, SE = 0.90, p = .20). In this randomized controlled trial, aspirin-triggered DHA supplementation significantly improved periodontal outcomes in people with periodontitis, indicating its potential therapeutic efficacy (clinicaltrials.gov NTC01976806).

Impact of Docosahexaenoic Acid Therapy on Subgingival Plaque Microbiota

“…This investigation was designed as a substudy of a recently published randomized controlled trial which showed that oral DHA + aspirin therapy reduces periodontal PD and local inflammation in GCF compared with placebo + aspirin among patients with untreated chronic periodontal disease 14 . A total 560 adults, aged ≥40 years, with moderate periodontitis according to American Association of Periodontology World Workshop criteria, were recruited from the greater Boston metropolitan region via advertisements and prescreening telephone interviews; of them, 128 (age and sex data unavailable) were evaluated at the study site (Beth Israel Deaconess Medical Center, Boston, MA) from June 2009 to December 2011 18 .…”

“…Two randomized controlled trials of DHA with low‐dose aspirin as an adjunct treatment to surgical and non‐surgical therapies have demonstrated improved therapeutic outcomes 12 , 13 . A recently completed randomized controlled trial of DHA + aspirin versus placebo + aspirin as a monotherapy showed improvement in clinical attachment level (CAL), probing depth (PD), and decreased gingival crevicular fluid (GCF) interleukin‐1β and C‐reactive protein levels within 3 months in the group assigned to DHA + aspirin therapy 14 …”

Omega‐3 Polyunsaturated Fatty Acids as an Adjunct to Non‐Surgical Treatment of Periodontitis

“…[40] This antiinflammatory activity of acetylsalicylic acid has been used in the studies where periodontal patients received simultaneously omega-3 PUFAs and low-dose of aspirin, obtaining a synergistic interaction of both compounds in resolution of inflammation. In addition, this study revealed that the use of acetylsalicylic acid alone did not result in reduction of periodontal inflammation [41] (Figure 2). [39,40] Moreover, significant reduction of monocyte chemotactic protein-3 and IL-1β levels in the gingival crevicular fluid, [39] as well as higher reduction of IL-1β and an increase in IL-10 level in gingival cervicular fluid were obtained.…”

“…In addition, acetylation of the cyclooxygenase-2 enzyme contributes to the formation of 15-epilipoxins which have stronger anti-inflammatory properties than lipoxins produced in the absence of acetylsalicylic acid. [41] In the intervention group, a significant improvement in probing pocket depth was gained. Higher improvement in clinical parameters such as PD, CAL, and GI has been demonstrated in the patients receiving combined treatment compared to the control groups.…”

Low-grade Systemic Inflammation May Increase the Risk of Periodontitis

“…First, the magnitude of periodontal destruction associated with inflammation was similar to that reported in clinical trials evaluating anti-inflammatory medication and periodontal destruction. 7 Second, proinflammatory gene variants were positively associated with periodontal disease progression in a recent prospective study. 8 Third, the effect of inflammation was specific to periodontal destruction and was not related to carious or restored tooth surfaces, 2 reducing the possibility of confounding by unmeasured factors being an alternative explanation.…”