## 2 Materials and Methods
### Outcome Parameters  
The following outcome parameters were evaluated at the beginning, after 6 weeks, and after 12 weeks: total amount and pH of saliva; the salivary markers calprotectin and interleukin-6  
\begin{table}
\begin{tabular}{c c c c c c c c} \hline \hline
**Treatment** & **Gender** & **Age** & **CSI** & **VAS** & **P1 max** & **G1 max** & **OHIP-G** \\ \hline HA & f & 71 & 2 & 4.8 & 2 & 2 & 71 \\ HA & m & 33 & 2 & 1.1 & 2 & 1 & 36 \\ HA & f & 48 & 2 & 5 & 1 & 1 & 53 \\ HA & m & 49 & 1 & 2.5 & 1 & 2 & 37 \\ HA & f & 18 & 3 & 2.5 & 1 & 2 & 30 \\ HA & f & 37 & 1 & 1.7 & 1 & 2 & 47 \\ HA & f & 47 & 2 & 0.5 & 2 & 2 & 30 \\ Placebo & f & 59 & 1 & 2.5 & 2 & 1 & 38 \\ Placebo & f & 71 & 4 & 2.5 & 2 & 1 & 30 \\ Placebo & f & 63 & 5 & 4 & 1 & 3 & 98 \\ Placebo & m & 48 & 1 & 0.5 & 1 & 1 & 9 \\ Placebo & m & 44 & 3 & 2.5 & 2 & 2 & 25 \\ Placebo & m & 71 & 1 & 0.5 & 3 & 2 & 0 \\ Placebo & m & 62 & 3 & 0.5 & 2 & 2 & 41 \\ \hline \hline \end{tabular}
\end{table}
Table 1: Patients included in the study at baseline clinical severity score (CSI), visual analogue scale (VAS), plaque index maximal value (P1 max), gingival index highest value (G1 max), Oral Health Impact Profile summary score German version (OHIP-G).  
measured by ELISA assays (S100 AB/A9, Buehlmann, Schoenenbuch, Switzerland for Calprotectin; Human IL-6 Quantikine HS ELISA Kit #HS600B, R&D Systems, Minneapolis, MN, USA for IL-6). Periodontopathic bacteria _Aggregatibacter actinomycetemcomitants, Porphromonas gingivalis, Tannerella forystthia, Treponema deticola, Prevotella intermedia, Parcinomas micra, Campylobacterbacter rectus, Eubacterium nodatum, Eikenella corrodens, Campocytophaga species, and Fusobacterium nucleatum_ were determined by 16S ribosomal RNA-based polymerase chain reaction (ParoCheck(r), Greiner Bio-One, Kremsmuenster, Austria) according to the protocol used in previous studies [34].  
For clinical parameters, the Clinical Severity Index (CSI) [35] for the differentiation of the area affected by OLP, a gingival index (GI) [36], and a plaque index (PI) [37] for the assessment of gingival inflammation and plaque deposits, respectively, were evaluated.  
Subjective outcome parameters were evaluated as follows:  
To analyze oral health-related quality of life, a standardized questionnaire validated in cross-sectional, as well as longitudinal, studies was used. The Oral Health Impact Profile questionnaire German version (OHIP-G) contains 53 questions concerning the previous four weeks [38]. Answers are given on a Likert-type five-point scale (0 = never; 1 = hardly ever; 2 = occasionally; 3 = fairly often; and 4 = very often). In this analysis, the total summary OHIP-G53 score was utilized, calculated by summing the score of the answers to each question. Higher scores indicate lower oral health-related quality of life. Four dimensions (psychosocial impact, orofacial pain, oral functions, and appearance) serve as principal components of oral health-related quality of life. The dimensions were calculated as described previously [2].  
For measuring pain intensity, a visual analogue scale (VAS), a 100 mm numeric rating scale, was used; patients can rate their pain on a scale between 0 and 10. Scores of 0 imply \"no pain\", while 10 means the \"worst pain imaginable\". A recommendation for interpretation of the ratings suggest 0 to 4 mm to be read as no pain, 5 to 44 mm as mild pain, 45 to 74 mm as moderate pain, and 75 to 100 mm as severe pain. With this subjective evaluation method, it is possible to compare pain levels at every visit, to see score changes over time [39].