Combination of omega-3 and aspirin helps treat periodontitis in diabetics

Study conducted at São Paulo State University demonstrates for first time that simple and inexpensive strategy yields better results than conventional treatment and avoids indiscriminate use of antibiotics.

By Chloé Pinheiro  |  Agência FAPESP – Periodontitis, or chronic inflammation of the gums, occurs frequently in diabetics and significantly impairs the quality of life for these patients. Both periodontal disease and blood sugar levels improve markedly when omega-3 and aspirin are administered in association with the conventional treatment, according to a study supported by FAPESP and published in the Journal of Periodontology. 

The investigation was conducted during the PhD research of Nidia Cristina Castro dos Santos at São Paulo State University’s Institute of Science and Technology (ICT-UNESP) in São José dos Campos, Brazil.

“Periodontitis and diabetes are highly prevalent diseases and often occur together, so it’s important to find a relatively inexpensive treatment with few side-effects that can combat both problems at the same time,” said Castro dos Santos, first author of the published paper.

The placebo-controlled, double-blind, randomized clinical trial involved 75 volunteers with moderate to severe periodontitis and type 2 diabetes diagnosed at least five years previously. Many had decompensated diabetes. 

The participants were divided into three groups. A control group submitted only to debridement (mechanical removal of the bacterial biofilm from tooth surfaces and gums) was given placebo. A second group took 3 grams of fish oil, a source of omega-3, and 100 milligrams of aspirin for two months after debridement. A third group took the same doses of the substances for two months before debridement.

“The results were better than control, i.e. debridement only, in both groups submitted to the combined approach,” Castro dos Santos said. Post-debridement supplementation was best of all, with a success rate of 40% compared to 16% for control.

In addition, the volunteers submitted to this protocol showed a reduction in levels of interferon-gamma (IFN-γ), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), all of which are involved in inflammatory processes. Glycated hemoglobin levels fell, suggesting better control of blood sugar and diabetes.

Link between periodontitis and diabetes

Severe periodontitis, in which inflammation is exacerbated to the point of making chewing difficult, causing pain and potentially leading to tooth loss, is estimated to affect 11% of all adults worldwide. Among diabetics, its prevalence is about 32%. 

The relationship is two-way. “Diabetes increases the severity and frequency of periodontal disease, and periodontitis hinders control of blood sugar levels,” said Mauro Pedrine Santamaria, a professor in UNESP’s São José dos Campos Dental School and principal investigator for the project.

Inflammation is the link. Chronically high blood sugar, an effect of diabetes, leads to systemic inflammation, which facilitates the development of periodontitis. “Inflammation of the gums releases inflammatory mediators into the bloodstream, hindering the proper action of insulin and glucose metabolism,” Santamaria explained.

Omega-3, on the other hand, plays a well-established role in the resolution of inflammation. Previous work by a group of researchers at Harvard University’s Forsyth Institute in the US showed that the substance helps control gum disease in people without diabetes.

“It’s a substrate for production of lipids such as resolvins and maresins, which coordinate the immune response,” said Castro dos Santos, who thought of testing the strategy as a treatment for diabetics while on an internship at Forsyth Institute. 

Aspirin appears to enhance the synthesis of these lipids and heighten their action. For example, aspirin-triggered resolvin is known to prevent chronic inflammation.

Advantages of the treatment

The approach is considered affordable and cost-effective, as fish oil and aspirin are relatively cheap and easy to find in pharmacies. “This research opens doors to a more efficient protocol for patients who urgently need treatment,” Santamaria said. “It could even be used by the public healthcare system.”

Conventional treatment, involving debridement and scaling, is effective but often has to be supplemented with antibiotics. “Even so the periodontal disease can return, and indiscriminate use of antibiotics over a period of years produces drug resistance, reducing the beneficial effect of the medication,” Santamaria said.

Modulating inflammation in the host is an innovative strategy. “Hitherto most research has focused on bacteria,” Castro dos Santos said. It is also important that neither omega-3 nor aspirin has noteworthy side-effects. Aspirin is associated with a documented risk of gastrointestinal bleeding, but only in patients who take it for long periods.

Quality of life improves significantly for patients when their periodontitis is attenuated, and they tend to take less medication to control the diabetes (as other studies have shown). Self-esteem and diet are both adversely affected by advanced diabetes.

Santamaria, Castro dos Santos and colleagues are collaborating with researchers at Guarulhos University (UNG), also in the state of São Paulo, to complete a study that focuses specifically on this point. “The responses to our quality-of-life questionnaire show that diabetics are more likely to report problems of this kind than normoglycemic individuals,” Castro dos Santos said.

Another research line pursued by ICT-UNESP’s Periodontics Division entails an assessment, supported by FAPESP, of the same protocol for young patients with aggressive periodontitis.

The article “Omega-3 PUFA and aspirin as adjuncts to periodontal debridement in patients with periodontitis and type 2 diabetes mellitus: a randomized clinical trial” can be retrieved from: aap.onlinelibrary.wiley.com/doi/10.1002/JPER.19-0613.