Several studies have demonstrated that polyphenol-enriched diets may have beneficial effects against the development of degenerative diseases, including atherosclerosis and disorders affecting the central nervous system. This activity has been associated not only with antioxidant and anti-inflammatory properties, but also with additional mechanisms, such as the modulation of lipid metabolism and gut microbiota function. However, long-term studies on humans provided controversial results, making the prediction of polyphenol impact on health uncertain. The aim of this review is to provide an overview and critical analysis of the literature related to the effects of the principal dietary polyphenols on cardiovascular and neurodegenerative disorders. We critically considered and meta-analyzed randomized controlled clinical trials involving subjects taking polyphenol-based supplements. Although some polyphenols might improve specific markers of cardiovascular risk and cognitive status, many inconsistent data are present in literature. Therefore, definitive recommendations for the use of these compounds in the prevention of cardiovascular disease and cognitive decline are currently not applicable. Once pivotal aspects for the definition of polyphenol bioactivity, such as the characterization of pharmacokinetics and safety, are addressed, it will be possible to have a clear picture of the realistic potential of polyphenols for disease prevention.

Background: Human reproduction is regulated by the combined action of the follicle-stimulating hormone (FSH) and the luteinizing hormone (LH) on the gonads. Although FSH is largely used in female reproduction, in particular in women attending assisted reproductive techniques to stimulate multi-follicular growth, its efficacy in men with idiopathic infertility is not clearly demonstrated. Indeed, whether FSH administration improves fertility in patients with hypogonadotropic hypogonadism, the therapeutic benefit in men presenting alterations in sperm production despite normal FSH serum levels is still unclear. In the present review, we evaluate the potential pharmacological benefits of FSH administration in clinical practice. Methods: This is a narrative review, describing the FSH physiological role in spermatogenesis and its potential therapeutic action in men. Results: The FSH role on male fertility is reviewed starting from the physiological control of spermatogenesis, throughout its mechanism of action in Sertoli cells, the genetic regulation of its action on spermatogenesis, until the therapeutic options available to improve sperm production. Conclusion: FSH administration in infertile men has potential benefits, although its action should be considered by evaluating its synergic action with testosterone, and well-controlled, powerful trials are required. Prospective studies and new compounds could be developed in the near future.

Purpose: The relationship between probiotics and levothyroxine (LT₄) requirement has not yet been investigated. The aim of this study was to assess whether a mixture of highly charged Lactobacilli and Bifidobacteria (VSL#3^®) is able to influence LT₄ metabolism acting on the gut microbiota. Methods: A prospective, randomized, single-blind, controlled, investigator-started clinical trial was carried out. Patients with primary hypothyroidism were randomly assigned to the study (VSL#3^® + LT₄) and the control group (LT₄). A 2-month treatment phase was followed by 2 months of follow-up. Clinical examination, blood tests for thyroid function and for peripheral tissue markers of thyroid hormones (PTM) were performed monthly. LT₄ dose adjustments were performed when necessary. Results: Thirty-nine patients were enrolled in the study group and 41 in the control group. No difference in thyroid function [thyroid-stimulating hormone (TSH), free triiodothyronine (fT₃), and free thyroxine (fT₄)] and PTM was found between groups and among visits. FT₃/fT₄ ratio was directly correlated to TSH at each visit in both groups, with the exception of the first evaluation of probiotics-treated subjects (rho = 0.287, p = 0.076). LT₄ daily dose adjustments occurred more frequently in the control than in the study group (p = 0.007), despite no differences in the mean LT₄ daily dose. In particular, LT₄ doses were increased six times in the control group and decreased four times in the study group. Conclusion: VSL#3^® does not directly alter thyroid functional compensation. A probiotics-mediated influence on thyroid hormones homeostasis is suggested since probiotics supplementation could be able to prevent serum hormonal fluctuations. ClinicalTrials.gov ID: Registration number NCT03095963.