OBJECTIVE: Nutraceutical products are widely used for their claimed therapeutic benefits. However, falsified or adulterated nutraceuticals present a major health threat to consumers. This study investigates the pharmaceutical quality, safety and anti-inflammatory effects of six male enhancement nutraceuticals that claim to be 100% natural. METHODS: Three batches of six male enhancement products were tested to detect the presence and levels of adulterants via high-performance liquid chromatography (HPLC). The pharmaceutical quality of the selected nutraceuticals was tested with near infrared spectroscopy (NIR) and SeDeM. The cytotoxic effects of these products on HepG2 cells were determined through cell proliferation (XTT) and lactate dehydrogenase (LDH) cytotoxicity assays. Lastly, the in vitro inflammatory effects of these products were investigated using murine J774 macrophages through cytokine release analysis. RESULTS: HPLC analysis detected the presence of sildenafil citrate, a vasodilator, and the active ingredient in Viagra and Revatio, in all batches of the products we analyzed. Amount of sildenafil citrate ranged from 0.45 mg to 51.85 mg among different batches. NIR assessment showed inter- and intra-batch heterogeneity in product composition. Results of the XTT and LDH assays showed significant cytotoxic effects of the analyzed products. XTT analysis revealed that the viability of HepG2 treated with tested products varied from 27.57% to 41.43%. Interestingly, the male enhancement products also showed anti-inflammatory effects. CONCLUSION Despite their labeling as 100% natural, all products tested in this study contained levels of sildenafil citrate, which was not reported on the packaging. There was a lack of pharmaceutical uniformity among products of the same batch and across different batches. Additionally, the products we tested had cytotoxic effects. These study findings highlight the adulteration, poor quality and hazard of these nutraceuticals. Therefore, strict regulation of these products and standardization of the definition of nutraceuticals are urgently needed. Further, these falsely advertised products should be withdrawn from the market due to potential adverse effects on the health of their consumers.

Background: and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.