## 2 Materials and Methods
### Intervention  
The spring water of the spa centre \"El Raposo\" emerges at 16.5 \({}^{\circ}\)C and forms a stream where the mud is collected. In order for it to mature naturally, it is placed outdoors in a tank containing the mineral-medicinal water, and it is left for 5 to 8 months, when it acquires optimal biological, chemical, and thermophysical properties for application. However, artificially matured mud is a solid/liquid content mixture at controlled proportions, in order to obtain a final product with the same basic properties as the natural mud, which has clear industrial interest to enhance the consistency of their production and composition throughout the year, also improving their organoleptic properties. \"El Raposo peloid\" is composed of a mixture of bicarbonate mineral-medicinal water, a clayey-silt solid phase, implemented with a microalga and, potentially, with rosmarinic acid. Biological content (microalgae, _Monoraphidium pusillum_, identified by Spanish Bank of Algae) is obtained from the natural spring and cultivated separately using photobioreactors and later added to the mixture also at controlled proportions (1%). In this way, controlled mud takes at least two months to complete maturation. Finally, after maturation of peloid, 0.5% of rosmarinic acid (Sigma-Aldrich, Burlington, MA, USA, CAS number 20283 92-5), as bioactive compound, was added.  
The water of \"El Raposo\" spa is hypothermia, very hard, of medium mineralisation, and contains bicarbonate (396.5 mg/L) and calcium (130.2 mg/L) as predominant ions. The mineral-medicinal water fraction represents a 32% approximately of the mud. The muds' solid content (65% approximately) consists of a mixture of silt, clay and sand. They are basically composed of phyllosilicates (smectite and illite), quartz and calcite. The major chemical elements of the muds are SiO\({}_{2}\), CaO, Al\({}_{2}\)O\({}_{3}\) and Fe\({}_{2}\)O\({}_{3}\)[28; 29].  
Patients of both groups participated in daily mud therapy sessions for 10 consecutive days, in line with the therapeutic protocol prescribed by their healthcare professionals. The intervention was identical for both groups with the only difference being the type of mud, and it was always conducted in the morning by the same physiotherapists. The sessions consisted in the whole-body application of mud at 40-42 \({}^{\circ}\)C by brush, followed by a drying period of 45-60 min in a solarium. Subsequently, patients received a mud bath (consisting  
\begin{table}
\begin{tabular}{c c c c} \hline \hline  & \multicolumn{2}{c}{**Controlled Mud Therapy (CMT)**} & \multicolumn{2}{c}{**Controlled Mud with Rosmarinic Acid Therapy (CMRT)**} \\ \hline
**N** & **19** & **23** \\ \hline
**Sex (\%)** & Women (63\%) & Women (60\%) \\
**Ethnic group (\%)** & Caucasian (100\%) & Caucasian (100\%) \\
**Age (years)** & 71.7 \(\pm\) 2.51 & 70.2 \(\pm\) 1.61 \\
**Basal** & **Post-treatment** & **Basal** & **Post-treatment** \\
**BMI (kg/m\({}^{2}\))** & 30.1 \(\pm\) 0.9 & 30.2 \(\pm\) 0.8 & 29.4 \(\pm\) 0.8 & 29.1 \(\pm\) 0.8 \\ \hline \hline \end{tabular}
\end{table}
Table 1: Anthropometric data in OA patients participating in the study.  
of mineral-medicinal water and mud) at 38-40 \({}^{\circ}\)C for 15 min. Finally, mud remnants were removed with a thermal water jet (38-40 \({}^{\circ}\)C) for 2 min. It is noteworthy to mention that whole-body mud application by brush is a particularly characteristic technique carried out in this spa centre. There were no adverse events.