•The vitamin D endocrine system have a variety of actions on cells and tissues involved in COVID-19 progression.•Early calcifediol (25-hydroxyvitamin D) treatment to hospitalized COVID-19 patients ...significantly reduced intensive care unit admissions-Calcifediol seems to be able to reduce severity of the COVID-19.•Calcifediol seems to be able to reduce severity of the disease.
The vitamin D endocrine system may have a variety of actions on cells and tissues involved in COVID-19 progression especially by decreasing the Acute Respiratory Distress Syndrome. Calcifediol can rapidly increase serum 25OHD concentration. We therefore evaluated the effect of calcifediol treatment, on Intensive Care Unit Admission and Mortality rate among Spanish patients hospitalized for COVID-19.
Parallel pilot randomized open label, double-masked clinical trial.
University hospital setting (Reina Sofia University Hospital, Córdoba Spain.)
76 consecutive patients hospitalized with COVID-19 infection, clinical picture of acute respiratory infection, confirmed by a radiographic pattern of viral pneumonia and by a positive SARS-CoV-2 PCR with CURB65 severity scale (recommending hospital admission in case of total score > 1).
All hospitalized patients received as best available therapy the same standard care, (per hospital protocol), of a combination of hydroxychloroquine (400 mg every 12 h on the first day, and 200 mg every 12 h for the following 5 days), azithromycin (500 mg orally for 5 days. Eligible patients were allocated at a 2 calcifediol:1 no calcifediol ratio through electronic randomization on the day of admission to take oral calcifediol (0.532 mg), or not. Patients in the calcifediol treatment group continued with oral calcifediol (0.266 mg) on day 3 and 7, and then weekly until discharge or ICU admission. Outcomes of effectiveness included rate of ICU admission and deaths.
Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50 %) p value X2 Fischer test p < 0.001. Univariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment versus without Calcifediol treatment: 0.02 (95 %CI 0.002−0.17). Multivariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment vs Without Calcifediol treatment ICU (adjusting by Hypertension and T2DM): 0.03 (95 %CI: 0.003-0.25). Of the patients treated with calcifediol, none died, and all were discharged, without complications. The 13 patients not treated with calcifediol, who were not admitted to the ICU, were discharged. Of the 13 patients admitted to the ICU, two died and the remaining 11 were discharged.
Our pilot study demonstrated that administration of a high dose of Calcifediol or 25-hydroxyvitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalization due to proven COVID-19. Calcifediol seems to be able to reduce severity of the disease, but larger trials with groups properly matched will be required to show a definitive answer.
Intestinal microbiota changes are associated with the development of obesity. However, studies in humans have generated conflicting results due to high inter-individual heterogeneity in terms of ...diet, age, and hormonal factors, and the largely unexplored influence of gender. In this work, we aimed to identify differential gut microbiota signatures associated with obesity, as a function of gender and changes in body mass index (BMI). Differences in the bacterial community structure were analyzed by 16S sequencing in 39 men and 36 post-menopausal women, who had similar dietary background, matched by age and stratified according to the BMI. We observed that the abundance of the Bacteroides genus was lower in men than in women (P<0.001, Q = 0.002) when BMI was > 33. In fact, the abundance of this genus decreased in men with an increase in BMI (P<0.001, Q<0.001). However, in women, it remained unchanged within the different ranges of BMI. We observed a higher presence of Veillonella (84.6% vs. 47.2%; X2 test P = 0.001, Q = 0.019) and Methanobrevibacter genera (84.6% vs. 47.2%; X2 test P = 0.002, Q = 0.026) in fecal samples in men compared to women. We also observed that the abundance of Bilophila was lower in men compared to women regardless of BMI (P = 0.002, Q = 0.041). Additionally, after correcting for age and sex, 66 bacterial taxa at the genus level were found to be associated with BMI and plasma lipids. Microbiota explained at P = 0.001, 31.17% variation in BMI, 29.04% in triglycerides, 33.70% in high-density lipoproteins, 46.86% in low-density lipoproteins, and 28.55% in total cholesterol. Our results suggest that gut microbiota may differ between men and women, and that these differences may be influenced by the grade of obesity. The divergence in gut microbiota observed between men and women might have a dominant role in the definition of gender differences in the prevalence of metabolic and intestinal inflammatory diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The COVID-19 pandemic is the greatest challenge facing modern medicine and public health systems. The viral evolution of SARS-CoV-2, with the emergence of new variants with in-creased infectious ...potential, is a cause for concern. In addition, vaccination coverage remains in-sufficient worldwide. Therefore, there is a need to develop new therapeutic options, and/or to optimize the repositioning of drugs approved for other indications for COVID-19. This may include the use of calcifediol, the prohormone of the vitamin D endocrine system (VDES) as it may have potential useful effects for the treatment of COVID-19. We review the aspects associating COVID-19 with VDES and the potential use of calcifediol in COVID-19. VDES/VDR stimulation may enhance innate antiviral effector mechanisms, facilitating the induction of antimicrobial peptides/autophagy, with a critical modulatory role in the subsequent host reactive hyperinflammatory phase during COVID-19: By decreasing the cytokine/chemokine storm, regulating the renin–angiotensin–bradykinin system (RAAS), modulating neutrophil activity and maintaining the integrity of the pulmonary epithelial barrier, stimulating epithelial repair, and directly and indirectly decreasing the increased coagulability and prothrombotic tendency associated with severe COVID-19 and its complications. Available evidence suggests that VDES/VDR stimulation, while maintaining optimal serum 25OHD status, in patients with SARS-CoV-2 infection may significantly reduce the risk of acute respiratory distress syndrome (ARDS) and severe COVID-19, with possible beneficial effects on the need for mechanical ventilation and/or intensive care unit (ICU) admission, as well as deaths in the course of the disease. The pharmacokinetic and functional characteristics of calcifediol give it superiority in rapidly optimizing 25OHD levels in COVID-19. A pilot study and several observational intervention studies using high doses of calcifediol (0.532 mg on day 1 and 0.266 mg on days 3, 7, 14, 21, and 28) dramatically decreased the need for ICU admission and the mortality rate. We, therefore, propose to use calcifediol at the doses described for the rapid correction of 25OHD deficiency in all patients in the early stages of COVID-19, in association, if necessary, with the new oral antiviral agents.
A growing interest has emerged in the beneficial effects of plant-based diets for the prevention of cardiovascular disease, diabetes and obesity. The Mediterranean diet, one of the most widely ...evaluated dietary patterns in scientific literature, includes in its nutrients two fluid foods: olive oil, as the main source of fats, and a low-to-moderate consumption of wine, mainly red, particularly during meals. Current mechanisms underlying the beneficial effects of the Mediterranean diet include a reduction in inflammatory and oxidative stress markers, improvement in lipid profile, insulin sensitivity and endothelial function, as well as antithrombotic properties. Most of these effects are attributable to bioactive ingredients including polyphenols, mono- and poly-unsaturated fatty acids. Polyphenols are a heterogeneous group of phytochemicals containing phenol rings. The principal classes of red wine polyphenols include flavonols (quercetin and myricetin), flavanols (catechin and epicatechin), anthocyanin and stilbenes (resveratrol). Olive oil has at least 30 phenolic compounds. Among them, the main are simple phenols (tyrosol and hydroxytyrosol), secoroids and lignans. The present narrative review focuses on phenols, part of red wine and virgin olive oil, discussing the evidence of their effects on lipids, blood pressure, atheromatous plaque and glucose metabolism.
Scope
The consumption of two healthy diets (Mediterranean (MED) and low‐fat (LF) diets) may restore the gut microbiome dysbiosis in obese patients depending on the degree of metabolic dysfunction.
...Methods and results
The differences in bacterial community at baseline and after 2 years of dietary intervention of 106 subjects from the CORDIOPREV study were analyzed, 33 of whom were obese patients with severe metabolic disease (5 criteria for metabolic syndrome) (MetS‐OB), 32 obese patients without metabolic dysfunction (2 or less criteria for metabolic syndrome) (NonMetS‐OB) and 41 non‐obese subjects (NonMetS‐NonOB). Our study showed a marked dysbiosis in people with severe metabolic disease (Met‐OB), compared with obese people without MetS (NonMetS‐OB) and non‐obese people (NonMetS‐NonOB). This disbiotic pattern was reversed by consumption of both MED (35% of calories as fat (22% MUFA fat, 6% PUFA fat and <10% saturated fat) or LF (<30% total fat (<10% saturated fat, 12%–14% MUFA fat and 6–8% PUFA fat) diets, whereas no significant microbiota changes were observed in NonMetS‐NonOB and NonMetS‐OB groups.
Conclusion
Our results suggest that the chronic intake of two healthy dietary patterns partially restores the gut microbiome dysbiosis in obese patients with coronary heart disease, depending on the degree of metabolic dysfunction.
A dysbiotic pattern in gut microbiota is found in obese people with metabolic dysfunction whereas the gut microbiota of obese people without metabolic disease is only partially altered as compared with non‐obese people. This dysbiosis is reversed by the chronic consumption of both Mediterranean or low‐fat diets, shaping microbiota to the pattern found in metabolically healthy people. However, no relevant microbiota changes were observed after the dietary intervention in non‐obese and obese people without metabolic dysfunction.
Most of diurnal time is spent in a postprandial state due to successive meal intakes during the day. As long as the meals contain enough fat, a transient increase in triacylglycerolaemia and a change ...in lipoprotein pattern occurs. The extent and kinetics of such postprandial changes are highly variable and are modulated by numerous factors. This review focuses on factors affecting postprandial lipoprotein metabolism and genes, their variability and their relationship with intermediate phenotypes and risk of CHD. Postprandial lipoprotein metabolism is modulated by background dietary pattern as well as meal composition (fat amount and type, carbohydrate, protein, fibre, alcohol) and several lifestyle conditions (physical activity, tobacco use), physiological factors (age, gender, menopausal status) and pathological conditions (obesity, insulin resistance, diabetes mellitus). The roles of many genes have been explored in order to establish the possible implications of their variability in lipid metabolism and CHD risk. The postprandial lipid response has been shown to be modified by polymorphisms within the genes for apo A-I, A-IV, A-V, E, B, C-I and C-III, lipoprotein lipase, hepatic lipase, fatty acid binding and transport proteins, microsomal triglyceride transfer protein and scavenger receptor class B type I. Overall, the variability in postprandial response is important and complex, and the interactions between nutrients or dietary or meal compositions and gene variants need further investigation. The extent of present knowledge and needs for future studies are discussed in light of ongoing developments in nutrigenetics.
Context:
Gut microbiota, which acts collectively as a fully integrated organ in the host metabolism, can be shaped by long-term dietary interventions after a specific diet.
Objective:
The aim was to ...study the changes in microbiota after 1 year's consumption of a Mediterranean diet (Med diet) or a low-fat, high-complex carbohydrate diet (LFHCC diet) in an obese population.
Design:
Participants were randomized to receive the Med diet (35% fat, 22% monounsaturated) and the LFHCC diet (28% fat, 12% monounsaturated).
Setting and Participants:
The study was conducted in 20 obese patients (men) within the Coronary Diet Intervention With Olive Oil and Cardiovascular Prevention (CORDIOPREV) study, an ongoing prospective, randomized, opened, controlled trial in patients with coronary heart disease.
Main Outcome Measure:
We evaluated the bacterial composition and its relationship with the whole fecal and plasma metabolome.
Results:
The LFHCC diet increased the Prevotella and decreased the Roseburia genera, whereas the Med diet decreased the Prevotella and increased the Roseburia and Oscillospira genera (P = .028, .002, and .016, respectively). The abundance of Parabacteroides distasonis (P = .025) and Faecalibacterium prausnitzii (P = .020) increased after long-term consumption of the Med diet and the LFHCC diet, respectively. The changes in the abundance of 7 of 572 metabolites found in feces, including mainly amino acid, peptide, and sphingolipid metabolism, could be linked to the changes in the gut microbiota.
Conclusions:
Our results suggest that long-term consumption of the Med and LFHCC diets exerts a protective effect on the development of type 2 diabetes by different specific changes in the gut microbiota, increasing the abundance of the Roseburia genus and F. prausnitzii, respectively.
•Phenol enriched virgin olive oil (FVOO) improves human endothelial function.•Postprandial values of glucose and triglycerides were lower after FVOO versus VOO.•Postprandial values of PAI-I, and ...hsCRP were lower after FVOO versus VOO.•FVOO increases VOO healthy properties when consuming the same amount of fat.
The additional health-promoting properties of functional virgin olive oil (FVOO) enriched with its own phenolic compounds (OOPC) versus the parental virgin olive oil (VOO) must be tested in appropriate human clinical trials. Our aim was to assess the effects of FVOO on endothelial function in hypertensive patients. Thirteen pre- and stage-1 hypertensive patients received a single dose of 30mL of FVOO (OOPC=961mg/kg) or VOO (OOPC=289mg/kg) in a postprandial randomised, double blind, crossover trial. Endothelial function, measured as ischemic reactive hyperemia (IRH) and related biomarkers, were followed for 5h after consumption. Compared with VOO, FVOO increased IRH (P<0.05) and plasma Cmax of hydroxytyrosol sulphate, a metabolite of OOPC 2h postprandial (P=0.05). After FVOO ingestion, oxidised LDL decreased (P=0.010) in an inverse relationship with IRH AUC values (P=0.01). FVOO provided more benefits on endothelial function than a standard natural virgin olive oil in pre- and hypertensive patients. Trial registration: isrctn.org. Identifier ISRCTN03450153.
Background and objectives
A Mediterranean lifestyle may prevent and mitigate cardiometabolic disorders. We explored whether adherence to a Mediterranean lifestyle was prospectively associated with ...the risk of metabolic syndrome (MetS) among coronary heart disease (CHD) patients.
Methods
The Coronary Diet Intervention with Olive Oil and Cardiovascular Prevention (CORDIOPREV) study was an interventional diet study to compare a Mediterranean diet with a low‐fat diet, in 1002 CHD patients. The Mediterranean lifestyle (MEDLIFE) index was used to assess adherence to a MEDLIFE at baseline, and after 5 years, in 851 participants from the CORDIOPREV study. Subjects were classified as having high (>13 points), moderate (12–13 points), and low (<12 points) adherence to the MEDLIFE. Multivariable logistic regression models were used to determine the association between MEDLIFE adherence and the risk of MetS development or reversal.
Results
During the 5‐year follow‐up, CORDIOPREV participants with high adherence to MEDLIFE had a lower risk of MetS development (odds ratio OR 0.37, 95% confidence interval CI 0.19–0.75, p < 0.01) and a higher likelihood of reversing preexisting MetS (OR 2.08 CI 95% 1.11–3.91, p = 0.02) compared with participants in the low MEDLIFE adherence group. Each additional one‐point increment in the MEDLIFE index was associated with a 24% lower risk of MetS development (OR 0.76, 95% CI 0.64–0.90, p < 0.01) and a 21% higher likelihood of reversing preexisting MetS (OR 1.21 CI 95% 1.04–1.41, p = 0.01).
Conclusions
Our results showed that greater adherence to a MEDLIFE reduced the risk of subsequent MetS development and increased the likelihood of reversing preexisting MetS among patients with CHD at baseline.
Abstract
Aims
Familial hypercholesterolaemia (FH) and elevated lipoprotein(a) Lp(a) are inherited disorders associated with premature atherosclerotic cardiovascular disease (ASCVD). Aortic valve ...stenosis (AVS) is the most prevalent valvular heart disease and low-density lipoprotein cholesterol (LDL-C) and Lp(a) may be involved in its pathobiology. We investigated the frequency and predictors of severe AVS requiring aortic valve replacement (AVR) in molecularly defined patients with FH.
Methods and results
SAFEHEART is a long-term prospective cohort study of a population with FH and non-affected relatives (NAR). We analysed the frequency and predictors of the need for AVR due to AVS in this cohort. Five thousand and twenty-two subjects were enrolled (3712 with FH; 1310 NAR). Fifty patients with FH (1.48%) and 3 NAR (0.27%) required AVR odds ratio 5.71; 95% confidence interval (CI): 1.78–18.4; P = 0.003 after a mean follow-up of 7.48 (3.75) years. The incidence of AVR was significantly higher in patients with FH (log-rank 5.93; P = 0.015). Cox regression analysis demonstrated an association between FH and AVR (hazard ratio: 3.89; 95% CI: 1.20–12.63; P = 0.024), with older age, previous ASCVD, hypertension, increased LDL-CLp(a)-years, and elevated Lp(a) being independently predictive of an event.
Conclusion
The need for AVR due to AVS is significantly increased in FH patients, particularly in those who are older and have previous ASCVD, hypertension, increased LDL-CLp(a)-years and elevated Lp(a). Reduction in LDL-C and Lp(a) together with control of hypertension could retard the progression of AVS in FH, but this needs testing in clinical trials.
ClinicalTrials.gov number NCT02693548.
Graphical abstract
PDF
