The link between COVID-19 and VItamin D (VIVID): A systematic review and meta-analysis.

BACKGROUND: Disease severity and mortality rates due to COVID-19 infection are greater in the elderly and chronically ill patients, populations at high risk for vitamin D deficiency. Vitamin D plays an important role in immune function and inflammation. This systematic review and meta-analysis assesses the impact of vitamin D status and supplementation on COVID-19 related mortality and health outcomes. METHODS: We searched four databases until December 18th 2020, and trial registries until January 20th 2021. Two reviewers screened the studies, collected data, assessed the risk of bias, and graded the evidence for each outcome across studies, independently and in duplicate. Pre-specified outcomes of interest were mortality, ICU admission, invasive and non-invasive ventilation, hospitalization, time of hospital stay, disease severity and SARS-CoV-2 positivity. We only included data from peer-reviewed articles in our primary analyses. RESULTS: We identified 31 peer-reviewed observational studies. In our primary analysis, there was a positive trend between serum 25(OH)D level <20 ng/ml and an increased risk of mortality, ICU admission, invasive ventilation, non-invasive ventilation or SARS-CoV-2 positivity. However, these associations were not statistically significant. Mean 25(OH)D levels was 5.9 ng/ml (95% CI [-9.5, -2.3]) significantly lower in COVID-19 positive, compared to negative patients. The certainty of the evidence was very low. We identified 32 clinical trial protocols, but only three have published results to-date. The trials administer vitamin D doses of 357 to 60,000 IU/day, from one week to 12 months. Eight megatrials investigate the efficacy of vitamin D in outpatient populations. A pilot trial revealed a significant decrease in ICU admission with calcifediol, compared to placebo (OR = 0.003), but the certainty of the evidence was unclear. Another small trial showed that supplementation with cholecalciferol, 60,000 IU/day, decreased fibrinogen levels, but did not have an effect on D-dimer, procalcitonin and CRP levels, compared to placebo. The third trial did not find any effect of vitamin D supplementation on COVID-19 related health outcomes. CONCLUSION: While the available evidence to-date, from largely poor-quality observational studies, may be viewed as showing a trend for an association between low serum 25(OH)D levels and COVID-19 related health outcomes, this relationship was not found to be statistically significant. Calcifediol supplementation may have a protective effect on COVID-19 related ICU admissions. The current use of high doses of vitamin D in COVID-19 patients is not based on solid evidence. It awaits results from ongoing trials to determine the efficacy, desirable doses, and safety, of vitamin D supplementation to prevent and treat COVID-19 related health outcomes.

Anti-hyperglycemic effect of the aqueous extract of banana infructescence stalks in streptozotocin-induced diabetic rats.

Water extract of banana (Musa sapientum) infructescence stalks has been used in folk medicine in the treatment of diabetes mellitus. This work aims at verifying the claimed effect and elucidating its possible mode of action. The extract was given in replacement of drinking water to diabetic rats, and its mechanism of action was studied by investigating its involvement in glucose transport in Caco-2 monolayers, and in rat jejuna using an in situ perfusion technique. Its effect on the Na(+)/K(+) ATPase was studied by measuring the amount of inorganic phosphate liberated. The extract reduced significantly blood glucose levels in diabetic rats and glucose transport across rat jejuna and Caco-2 monolayers, and induced a 50 % decrease in their Na(+)/K(+) ATPase activity. The extract did not induce any further decrease in jejunal glucose uptake in the simultaneous presence of phloridzin and phloretin, respective inhibitors of SGLT1 and GLUT2 transporters nor did it induce a change in the protein expression of SGLT1 and GLUT2. It was concluded that the extract acts by reducing the Na(+)/K(+) ATPase activity of enterocytes and consequently the sodium gradient required for sugar transport by SGLT1, which leads to down-regulation of GLUT2 and contributes to the observed anti-hyperglycemic effect.

Pine bark extract inhibits glucose transport in enterocytes via mitogen-activated kinase and phosphoinositol 3-kinase.

OBJECTIVE: Pine bark extract (PBE) has been reported to have hypoglycemic effects but its mode of action is still unclear. This work studied the effect of PBE on glucose uptake by Caco-2 cells in isolation of its effect on insulin, which may appear if ingested by the animal. METHODS: Caco-2 cells were incubated in the presence of PBE and [(14)C] 3-O-methyl-D-glucose as a tracer and the change in radioactivity of the incubation medium was taken as a measurement of glucose uptake. To determine the mechanism of action of the extract and type of transporters involved, Na(+)-coupled glucose transporter-1 (SGLT1) and glucose transporter-2 (GLUT2) and different signaling mediators known to be involved in glucose transport were inactivated by specific inhibitors. Changes in the protein expression of glucose transporters were studied by western blotting. RESULTS: The extract significantly decreased glucose transport but did not affect the activity or expression of Na(+)/K(+) adenosine triphosphatase. It was concluded that PBE affects the number of glucose transporters in the brush-border membrane. This conclusion was confirmed by western blot analysis. The results showed that the extract acts by activating p38 mitogen-activated kinase, which in turn activates SGLT1 transporters and two different pathways that target GLUT2: an inhibitory pathway involving phosphoinositol 3-kinase and a stimulatory pathway involving mitogen activated protein kinase/extracellular signal-regulated kinase kinase. The activity of the two pathways is orchestrated by SGLT1. CONCLUSION: Pine bark extract inhibits glucose absorption by p38 mitogen-activated kinase and constitutes a potential complementary therapeutic or prophylactic agent for diabetes and its complications.