Pharmacological evaluation of vitamin D in COVID-19 and long COVID-19: recent studies confirm clinical validation and highlight metformin to improve VDR sensitivity and efficacy.

Nearly four years after its first appearance, and having gone from pandemic to endemic, the SARS-CoV-2 remains out of control globally. The purpose of this study was to evaluate the clinical efficacy of vitamin D (VD) in COVID-19 and long COVID-19, explain the discrepancy in clinical outcomes and highlight the potential impact of metformin on VD efficacy in recent articles. Articles from January 2022 to August 2023 were selected for this review. The objective of this study was achieved by reviewing, analyzing, and discussing articles demonstrating (1) the mechanism of action of VD (2) observational or randomized clinical trials (RCTs) that support or not the beneficial clinical effects of VD in COVID-19 or long COVID. (3) genetic and non-genetic reasons for the variation in the effects of VD. Articles were collected from electronic databases such as PubMed, Scopus, MEDLINE, Google Scholar, Egyptian Knowledge Bank, Science Direct, and Cochrane Database of Systematic Reviews. Twenty three studies conducted in vitro or in animal models indicated that VD may act in COVID-19 through protecting the respiratory system by antimicrobial peptide cathelicidins, reducing lung inflammation, regulating innate and adaptive immune functions and up regulation of autophagy gene activity. Our review identified 58 clinical studies that met the criteria. The number of publications supporting a beneficial clinical activity of VD in treating COVID-19 was 49 (86%), including 12 meta-analyses. Although the total patients included in all articles was 14,071,273, patients included in publications supporting a beneficial role of VD in COVID-19 were 14,029,411 (99.7%). Collectively, extensive observational studies indicated a decisive relationship between low VD levels and the severity of COVID-19 and mortality outcomes. Importantly, evidence from intervention studies has demonstrated the effectiveness of VD supplements in treating COVID-19. Furthermore, the results of 4 observational studies supported the beneficial role of VD in alleviating symptoms of long COVID-19 disease. However, eight RCTs and one meta-analysis of RCTs may contain low-grade evidence against a beneficial role of VD in COVID-19. Twenty-five articles have addressed the association between VDR and DBP genetic polymorphisms and treatment failure of VD in COVID-19. Impaired VDR signaling may underlie the variability of VD effects as non-genetic mechanisms. Interestingly, in recent studies, metformin has a beneficial therapeutic role in COVID-19 and long COVID-19, possibly by improving AMPK signaling of the VDR and enhancing the efficacy of the VD. In conclusion, evidence has been significantly strengthened over the past 18 months, with several meta-analyses and RCTs reporting conclusive beneficial effects of VD supplementation against COVID-19 and highlighting metformin to improve VDR sensitivity and efficacy in treating COVID-19 and long COVID-19.

Potential therapeutic effects of boswellic acids/Boswellia serrata extract in the prevention and therapy of type 2 diabetes and Alzheimer's disease.

The link between diabetes and cognitive dysfunction has been reported in many recent articles. There is currently no disease-modifying treatment available for cognitive impairment. Boswellia serrata (B. serrata) is used traditionally to treat chronic inflammatory diseases such as type 2 diabetes (T2D), insulin resistance (IR), and Alzheimer's disease (AD). This review aims to highlight current research on the potential use of boswellic acids (BAs)/B. serrata extract in T2D and AD. We reviewed the published information through June 2021. Studies have been collected through a search on online electronic databases (Academic libraries as PubMed, Scopus, Web of Science, and Egyptian Knowledge Bank). Accumulating evidence in preclinical and small human clinical studies has indicated that BAs/B. serrata extract has potential therapeutic effect in T2D and AD. According to most of the authors, the potential therapeutic effects of BAs/B. serrata extract in T2D and AD can be attributed to immunomodulatory, anti-inflammatory, antioxidant activity, and elimination of the senescent cells. BAs/B. serrata extract may act by inhibiting the IκB kinase/nuclear transcription factor-κB (IKK/NF-κB) signaling pathway and increasing the formation of selective anti-inflammatory LOX-isoform modulators. In conclusion, BAs/B. serrata extract may have positive therapeutic effects in prevention and therapy of T2D and AD. However, more randomized controlled trials with effective, large populations are needed to show a definitive conclusion about therapeutic efficacy of BAs/B. serrata extract in T2D and AD.

A Pilot Study of a Topical Intervention for Treatment of Female Sexual Dysfunction.

PURPOSE/BACKGROUND: Many investigators reported that pharmacological treatment of female sexual dysfunction (FSD) has been a promising field yet to be explored. The purpose of this pilot study was to investigate the efficacy and safety of a topical cream containing small concentrations of three vasodilators with different mechanisms of action in treating FSD. METHODS: In this randomized, controlled pilot trial, premenopausal (n = 30) and postmenopausal (n = 30) cases of 21- to 62-year age range with FSD were allocated randomly into 15 given placebo or 15 given active cream in each group. The women included had FSD for more than a 6-month duration and a total score of Female Sexual Distress Scale-Revised of at least 15. Assessing sexual function by measuring female sexual function index (FSFI) during five clinic visits, one at the end of baseline week and at the end of each week of the 4-week treatment period. The primary end point was changed from baseline FSFI total scores to week 4 treatment. Secondary end point included the changes from baseline arousal, desire, orgasm, and satisfaction scores to week 4 treatment. FINDINGS/RESULTS: The sexual problem reported by patients was orgasmic or/and arousal disorders. In premenopausal cases, active cream led to a high significant increase in mean change FSFI total score from the baseline to week 4 compared with placebo (1.7 ± 1.886 vs 13.35 ± 4.646, respectively; P < 0.0001). Greater improvement of mean change of orgasm and arousal domain score was also observed (0.3 ± 0.45 and 0.35 ± 0.39 vs. 2.66 ± 0.63 and 1.87 ± 0.168, respectively; P < 0.0001). In postmenopausal cases, there were significantly greater improvements with active cream in all sexual functions compared with placebo cream (P < 0.0001). In triple cream, mean change of FSFI total score, orgasm domain score, and arousal score domain were 14.85 ± 6.33, 1.87 ± 0.168 and 2.66 ± 1.182, whereas in the placebo cream, they were 1.54 ± 2.1,0.7 ± 0.76 and 0.22 ± 0.44, respectively. Meanwhile, orgasm scores increased significantly after the use of placebo cream. No serious adverse effects were reported during treatment. IMPLICATIONS/CONCLUSIONS: The results of the pilot trial suggest that topical cream containing small concentrations of three vasodilators may act synergistically, and was effective in improving arousal, orgasmic, and satisfaction disorder with a safer profile for premenopausal and postmenopausal women with FSD. Further studies are recommended to be conducted using a large number of nondepressive and depressive patients.