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.