## 4 Discussion
### Clinical Parameters  
Practically all studies reported statistically significant results on the effect of melatonin on periodontitis after NSPT. All six included studies that were considered the basic clinical parameters (PD and CAL). Some studies also considered GI, PI, and BOP. There was a positive overall result with different melatonin concentration levels and follow-up,thus improving the periodontal parameters for the control and melatonin groups, with statistically significant results for the test group. The systemic use of melatonin was used by [PERSON] et al. [35], [PERSON] et al. [32], [PERSON] et al. [34], [PERSON] et al. [33], and [PERSON] et al. [31]. According to [PERSON] et al. [38], the systemic administration of melatonin was more effective than topical (mouthwash or gel). This may be explained by the GCF (gingival crevicular fluid, periodontal defense fluid) presence, which is an exudate composed of plasma and transports molecules from the bloodstream. The clinical results obtained were better in these studies, supporting the use of melatonin capsules as an auxiliary in treating periodontitis. For all studies, PD levels statistically significantly decreased, and a considerable gain in CAL was also obtained. [PERSON] et al. [34] observed that the results were significant for the melatonin groups for 4-5 mm and >5 mm PD sites (\(p\) < 0.001). [PERSON] et al. [31] evaluated and correlated BOP and HbA1c. Plaque index (PI) and BOP decreased, after systemic administration of melatonin (patients received two melatonin tablets 250 mg that contained 3 mg of melatonin), showing significantly lower values. There was also a significant reduction in HbA1c during the studies, which was suggested to be matched to the NSPT. Still, a significant decrease was shown in the melatonin-treated group, compared to the control group. A couple of studies used patients with T2 DM and periodontal disease [31; 32; 33]. [PERSON] et al. [49], in addition to the HbA1c, also detected the value of serum insulin levels. The results on the effectiveness in glycemic control were also exposed in the study. Thereby, [PERSON] et al. [31] confirmed the veracity of the previous studies, showing that melatonin acted on periodontal parameters and had a relevant effect on glycemic control. Some divergent results from the studies can probably be attributed to the sample studied, follow-up, and the different dosages of melatonin. [PERSON] et al. [33] analyzed the effect of melatonin, in addition to NSPT in patients with T2 DM and periodontal disease. The intervention group consisted of 25 patients who received 2 tablets daily of 250 mg for 8 weeks. The results showed that melatonin intake significantly changed various clinical parameters. All the studies included supported that the use of melatonin helped the NSPT. In contrast, [PERSON] et al. 's study [51] instructed patients to use 20 mL of melatonin, 5 mg/mL solution, to rinse the oral cavity before sleep and after brushing their teeth for 14 days, without having been subjected to the NSPT. The patients were observed one year after the two-week melatonin treatment and showed no improvement. In fact, the scored parameters and oxidative stress markers did not change. The probable causes of the study failure may depend on various factors, such as the presence of refractory periodontitis that was not assessed, the type of administration (oral rinse), the duration of treatment, and the concentration of melatonin administered. Mouthwash administration is a topical treatment; consequently, its effect depends on the volume and speed of absorption of melatonin from the oral mucosa and the time the patients take to rinse their mouths. In that study, the better and correct way of using mouthwash was not reported to the patients. For the mouthwash acts, the duration of rinsing and the contact time with the oral mucosa must allow the melatonin to be adequately absorbed by the tissues and, thus, produce effects.