PurposeThis study aimed to evaluate the impact of dietary supplementation with omega-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) combined with scaling and root planing (SRP) in untreated periodontitis stage III and IV.MethodsForty patients were randomly assigned to the test group receiving SRP plus omega-3 PUFAs (n= 20) or control group receiving SRP alone (n= 20). Clinical changes of pocket probing depths (PD), clinical attachment level (CAL), bleeding on probing (BOP) and rates of closed pockets (PPD ≤ 4 mm without BOP) were evaluated at baseline and after 3 and 6 months.Phorphyromonas gingivalis, Tanarella forsythia, Treponema denticola and Aggregatibacter actinomycetemcomitanscounts were analysed at baseline and at 6 months. Serum was subjected to lipid gas chromatography/mass spectrometry analysis at baseline and at 6 months.ResultsSignificant improvement of all clinical parameters at 3 and 6 months was observed in both groups. For the primary outcome “change of mean PD,” no significant difference was detected between the groups. Patients treated with omega-3 PUFAs demonstrated significantly lower rates of BOP, higher gain of CAL and higher number of closed pockets at 3 months in comparison to the control group. After 6 months, no clinical differences between the groups were found, with the exception of lower BOP rates. Moreover, in the test group, the number of key periodontal bacteria was significantly lower than in the control group at 6 months. Increased proportions of serum n-3 PUFAs and decreased proportions of n-6 PUFAs were detected at 6 months in the patients from the test group.ConclusionHigh-dose omega-3 PUFA intake during non-surgical treatment of periodontitis results in short-term clinical and microbiological benefits.The study protocol was approved by the ethical committee of Medical University of Lodz (reference number RNN/251/17/KE) and registered at clinicaltrials.gov (NCT04477395) on 20/07/2020.