Subjects. Three female treated subjects, in reality, did not comprehensive the study because of reported gastrointestinal problems, major us to hypothesize that the quantity of Serenoa repens present in the OFS represented an overdose. Additionally, in male OFS individuals, we observed a reduction in somatization, anxiousness and depression state in the finish of your study (soon after six weeks of OFS assumption). These outcomes appear to be in line using the outcomes obtained around the improvement of urinary symptoms in male subgroups. Gender variations have already been reported for polyphenols along with other bioactive compounds, related to their biotransformation, bioavailability, pharmacodynamics and pharmacokinetics. The metabolism of polyphenolic compounds takes place by means of gut microbiota and through endogenous enzymes for instance cytochrome P450 mono-oxygenases in a gender-dependent manner. The distinct targets of those bioactive compounds is usually differently expressed in the diverse genders. Their renal excretion, which can be the key excretion route, presents sex differences [704]. As a result, the gender is really a variable that should be meticulously deemed. From this point of view, and in accordance with the outcomes of this pilot study, the research will continue with all the experimentation of two unique OFSs, distinct for gender: the OFS (described above) for male patients in addition to a newly formulated OFS, avoiding the use of Serenoa repens extract, for female sufferers. 5. Conclusions The psychophysical distress induced by UTI recurrence, the feasible negative BRDT supplier effects related to repeated antibiotics therapy, plus the possibility of antibiotic-resistance, have led to interest in locating a natural OFS developed to counteract recurrent UTIs and increase the good quality of life of patients. The preliminary results of our pilot study demonstrate the probable therapeutic and preventive efficacy of a natural OFS based on polyphenols, particularly based on Sweet Chestnut tannins, in UTI recurrent sufferers. However, these results seem to be referable only to male individuals. The considerable unwanted effects related with all the poor capacity to reduce microbial flora in female patients raises the problem of getting a all-natural OFS capable to counteract UTIs in female subjects. To confirm the outcomes obtained for the parameters related to oxidative strain, inflammatory status and genderdependent antimicrobial activity, a future study should be planned on a larger sample of sufferers selected by gender, also such as a placebo group not treated with tannins. This study ought to take into account gender variations, formulating two OFS that differ with respect to the presence of Serenoa repens extract, that is not fully tolerated by the female population.Author Contributions: Conceptualization, A.N., N.D.D. along with a.R.; methodology, F.D.D., M.C., M.D.L., A.P.Z. and G.M.; investigation, M.D.L., A.P.Z. and G.M.; data curation, F.D.D. and M.C.; writing–original draft preparation, A.N. plus a.R.; writing–review and editing, N.D.D.; supervision, A.N. and a.R.; All authors have study and agreed to the published version on the manuscript. ALK7 Compound Funding: This investigation was funded by Tuscany Region, PSR 2014-2020–PS-GO project CAST-AMIBEN–Use, revolutionary transformation and enhancement of the Amiata Mount Chestnut PGI in the food, nutraceutical and wellness sectors. Project leader Gruppo Mauro Saviola srl. Institutional Review Board Statement: The study was performed according to the recommendations in the Helsinki declaration by the PTV Independent Ethics.
