A combination of omega-3 and low-dose acetylsalicylic acid (ASA) performed about as well as antibiotics in a yearlong study of people with severe periodontitis, raising the possibility of an alternative treatment for some patients.
The research was conducted by scientists affiliated with Albert Einstein Israelite Hospital, Guarulhos University (UNG), the University of Taubaté (UNITAU), and the Ribeirão Preto School of Dentistry at USP (FORP-USP) in Brazil, along with Harvard University in the United States. The findings were published in the Journal of Periodontology.
Researchers say the results could eventually help reduce antibiotic use in selected patients, an important consideration as bacterial resistance becomes an increasingly serious global health problem.
Severe Periodontitis Can Damage Bone and Teeth
Supported by FAPESP (projects 20/05874-2 and 20/05875-9), the clinical study included 109 people with advanced periodontitis who were followed for one year.
Periodontitis is a chronic inflammatory disease that develops when bacteria accumulate below the gumline and damage the tissues that hold teeth in place. In advanced cases, the disease can destroy supporting bone, loosen teeth, and eventually cause tooth loss.
“Patients with severe disease have very deep pockets, which act as reservoirs for bacteria associated with the disease. It’s a very challenging condition to treat,” says dental surgeon Nídia Cristina Castro dos Santos, the first author of the study and a professor and researcher at Einstein.
Researchers Compared Four Treatment Strategies
The participants were randomly divided into four groups. Everyone received subgingival instrumentation, popularly known as scaling, which is a standard treatment for periodontitis. The procedure removes bacterial deposits and other material from below the gums.
What differed among the groups was the additional treatment they received.
Participants in the control group were given placebo versions of the antibiotics, omega-3, and ASA, packaged in capsules that looked like the active treatments.
A second group received the antibiotics metronidazole and amoxicillin. This combination has some of the strongest scientific evidence supporting its use in severe periodontitis. Patients took the antibiotics three times per day for 14 days.
A third group received three grams of omega-3 each day along with a daily dose of aspirin for six months.
The fourth group received both approaches, taking antibiotics for two weeks while also following the omega-3 and ASA regimen for six months.
Researchers assessed the participants again after three, six, and twelve months.
Omega-3 and Aspirin Nearly Matched Antibiotics
After one year, about 58% of patients treated with antibiotics had reached the clinical target established by the researchers. That goal was defined as having no more than four remaining deep periodontal pockets.
The omega-3 and ASA group achieved a nearly identical result, with 57.7% of participants reaching the same target.
The difference compared with standard treatment alone was substantial. Among patients who received scaling plus placebo, only 23.1% met the clinical goal.
Surprisingly, using antibiotics together with omega-3 and ASA did not produce any additional benefit over either strategy alone.
“The use of antibiotics isn’t considered the gold standard of treatment. Although metronidazole and amoxicillin yield good results in the most severe cases, their use should be evaluated on a case-by-case basis due to risks related to bacterial resistance and possible adverse effects,” says Castro dos Santos.
Earlier Research Pointed to Omega-3’s Potential
The findings build on previous work examining omega-3 and inflammation in periodontal disease.
In an earlier FAPESP-supported study published in Scientific Reports, researchers found that omega-3 supplementation reduced inflammation and bone loss associated with periodontal disease in rats. The effect was particularly noticeable when supplementation was combined with physical exercise.
Because that research used an animal model, it could not establish whether the same effects would occur in people. However, it provided evidence that omega-3 might influence inflammatory processes involved in oral disease.
Helping the Body Resolve Inflammation
According to Castro, omega-3 works differently from conventional anti-inflammatory medications.
Rather than simply blocking particular inflammatory pathways, omega-3 can contribute to the production of molecules that help the body naturally bring inflammation to an end and promote tissue repair.
Low-dose ASA was included because it can enhance the production of these inflammation-resolving molecules. Researchers therefore suspected that combining omega-3 with ASA might help the body gain better control over the persistent inflammation associated with periodontitis.
“We imagined that the combination of antibiotics and omega-3 would be most effective in controlling periodontitis in these patients. We also believed that the results for the group that used omega-3 with ASA would be slightly lower than those for the antibiotic group. The result was surprising because the two therapies performed very similarly, paving the way for it to become a treatment option for these patients,” says Castro.
Benefits Continued After Treatment Ended
The researchers were also struck by how long the apparent benefits lasted.
Participants who had taken omega-3 and ASA continued to show results similar to those seen at the end of treatment even six months after supplementation had stopped.
According to Castro, the persistence of the effect raises the possibility that changing the way the body responds to inflammation could produce longer-lasting benefits. Researchers are still investigating exactly how this might happen.
For dental surgeon Magda Feres, the lead author of the study and a full professor at the Harvard School of Dental Medicine and the Graduate Program in Dentistry at UNG, the results suggest that targeting the inflammatory response could provide another option for certain patients.
“The combination of omega-3 and low-dose aspirin achieved clinical benefits comparable to those of the metronidazole and amoxicillin protocol, opening up a real alternative for those who can’t take antibiotics, especially patients with allergies or intolerance to these medications,” she says.
A Possible Way to Reduce Antibiotic Use
The potential to treat some cases without antibiotics is particularly relevant because antibiotic resistance is considered one of the major threats to global public health.
When bacteria are repeatedly exposed to antibiotics, strains that can survive the drugs may spread, making infections more difficult to treat. Reducing unnecessary antibiotic use is therefore an important public health goal.
“Demonstrating that it’s possible to treat severe periodontitis by modulating the body’s own response is new and relevant information that helps preserve antibiotics for when they are truly indispensable,” says Feres.
More Evidence Is Needed
Despite the promising results, the researchers stress that omega-3 and aspirin should not yet be viewed as a routine replacement for antibiotics in severe periodontitis.
The clinical trial included patients who did not have significant systemic or oral diseases. Additional studies will be needed to determine whether the findings hold true in broader and more diverse populations, and to establish which patients are most likely to benefit from each treatment strategy.
Researchers are also conducting microbiological analyses to understand what happens to bacteria inside periodontal pockets during treatment.
Preliminary findings suggest that the therapies may reduce bacterial species associated with periodontal disease while increasing microorganisms linked to healthier gums.
“It’s an important step forward, but not the end of the story. Therefore, the message is one of cautious optimism: we have a promising, scientifically plausible alternative to antibiotics in select cases. Routine replacement will require more evidence,” she concludes.
