Retrospective studies showed a relationship between vitamin D status and COVID-19 severity and mortality, with an inverse relation between SARS-CoV-2 positivity and circulating calcifediol levels. The objective of this pilot study was to investigate the effect of vitamin D supplementation on the length of hospital stay and clinical improvement in patients with vitamin D deficiency hospitalized with COVID-19. The study was randomized, double blind and placebo controlled. A total of 50 subjects were enrolled and received, in addition to the best available COVID therapy, either vitamin D (25,000 IU per day over 4 consecutive days, followed by 25,000 IU per week up to 6 weeks) or placebo. The length of hospital stay decreased significantly in the vitamin D group compared to the placebo group (4 days vs. 8 days; p = 0.003). At Day 7, a significantly lower percentage of patients were still hospitalized in the vitamin D group compared to the placebo group (19% vs. 54%; p = 0.0161), and none of the patients treated with vitamin D were hospitalized after 21 days compared to 14% of the patients treated with placebo. Vitamin D significantly reduced the duration of supplemental oxygen among the patients who needed it (4 days vs. 7 days in the placebo group; p = 0.012) and significantly improved the clinical recovery of the patients, as assessed by the WHO scale (p = 0.0048). In conclusion, this study demonstrated that the clinical outcome of COVID-19 patients requiring hospitalization was improved by administration of vitamin D.

We aimed to determine whether a cumulative dose of vitamin D₃ produces the same effects on the serum concentration of 25(OH)D₃ if it is given daily or monthly. This is a monocentric, two-armed, randomized, interventional, open, and parallel study conducted from November 2016 to March 2017 in Belgium. We randomized 60 subjects with vitamin D deficiency to receive 2000 IU vitamin D₃ daily or 50,000 IU monthly. The same cumulative dose of vitamin D₃ was given to each treatment group (150,000 IU). The 25(OH)D₃ serum concentrations from baseline to day 75 were 14.3 ± 3.7 to 27.8 ± 3.9 ng/mL in the monthly group and 14.1 ± 3.4 to 28.8 ± 5.4 ng/mL in the daily group. The mean change versus the baseline level was significantly different between the groups at day 2, 4, 7, and 14 and no longer different from day 25. One day after the intake of vitamin D₃, as expected, serum 25(OH)D₃ and 1,25(OH)₂D₃ increased significantly in the monthly group, whereas they did not change significantly in the daily group. The median time to reach the 20 ng/mL target concentration was significantly different in the two groups, in favor of the monthly regimen (1 day versus 14 days; p = 0.02). In conclusion, a monthly administration of 50,000 IU vitamin D₃ provides an effective tool for a rapid normalization of 25(OH)D₃ in deficient subjects. A daily administration of the same cumulative dose is similarly effective but takes two weeks longer to reach the desirable level of 20 ng/mL.

Many people worldwide are vitamin D (VTD) deficient or insufficient, and there is still no consensus on the dose of VTD that should be administered to achieve a 25(OH)D concentration of 20 or 30 ng/mL. In this study, we aimed to determine an adapted supplementation of VTD able to quickly and safely increase the vitamin D status of healthy adults with low 25(OH)D. One hundred and fifty (150) subjects were randomized into three groups, each to receive, orally, a loading dose of 50,000, 100,000 or 200,000 IU of VTD3 at Week 0, followed by 25,000, 50,000 or 100,000 IU at Week 4 and Week 8. Whereas 25(OH)D baseline values were not different between groups (p = 0.42), a significant increase was observed at Week 12 (p < 0.0001) with a mean change from baseline of 7.72 ± 5.08, 13.3 ± 5.88 and 20.12 ± 7.79 ng/mL. A plateau was reached after eight weeks. No related adverse event was recorded. This study demonstrated a linear dose-response relationship with an increase in 25(OH)D levels proportional to the dose administered. In conclusion, a loading dose of 200,000 IU VTD3 followed by a monthly dose of 100,000 IU is the best dosing schedule to quickly and safely correct the VTD status.

Vitamin D₃ is known to be liposoluble and its release could be a factor limiting the rate of absorption. It was presumed that the presence of fat could favor absorption of vitamin D₃. However, as bioavailability is related not only to the active molecules but also to the formulations and excipients used, the optimization of the pharmaceutical form of vitamin D₃ is also important. The objective of this study was to evaluate if there is a food effect on absorption when a high dose of vitamin D₃ is completely solubilized in an oily solution. In the present cross-over study, 88 subjects were randomized and received a single dose of 50,000 IU of vitamin D₃ in fasting state or with a standardized high-fat breakfast. Assessment of serum concentrations of 25 hydroxyvitamin D₃ (25(OH)D₃) was performed three, five, seven, 14, 30 and 60 days after supplementation. In fed and fast conditions, the 25(OH)D₃ serum concentrations were significantly higher than the baseline value three days after administration and remained significantly higher during the first month. No significant difference between fasting vs. fed conditions was observed. It is therefore concluded that the vitamin D₃ absorption from an oily solution was not influenced by the presence or absence of a meal.

Background and Purpose: The aim of the study was to provide valuable real‐world long‐term safety data of the fixed pravastatin 40 mg/fenofibrate 160 mg combination in comparison of monotherapy with statins of moderate intensity.Materials and Methods: POSE study was an observational, comparative study conducted in three European countries. Patients treated or planned to be treated with pravastatin 40 mg/fenofibrate 160 mg or with a moderate‐intensity statin in monotherapy were assessed over 3 years. The main safety endpoints included the incidence of renal or urinary disorder, musculoskeletal or connective tissue disorder, hepatobiliary disorder and cardiovascular events.Results: The study included 3075 patients treated for dyslipidaemia, with diabetes mellitus (47%), hypertension (56%) and/or established cardiovascular disease (61%). Over the 3 years of follow‐up, the difference in incidence rate of safety events between the pravastatin 40 mg/fenofibrate 160 mg group and the statin group was not statistically significant (RR = 1.366 [95% CI = 0.967–1.929]). The most frequently occurring events were musculoskeletal and connective tissue disorders (AR = 0.030 in the pravastatin 40 mg/fenofibrate 160 mg group and 0.024 in the statin group), renal and urinary disorders (AR = 0.019 vs. 0.016, respectively) and aggravated diabetes mellitus (0.021 vs. 0.014). Most events occurred during the first year, then incidence decreased over the 3‐year period. No statistically significant difference was observed between treatment groups regarding the cardiovascular events (RR = 1.209 [95% CI = 0.596–2.453]) and no new signal emerged from the long‐term follow‐up.Conclusions: This study demonstrates a reassuring long‐term safety profile of the fixed pravastatin 40 mg/fenofibrate 160 mg combination in routine clinical practice, with low and similar incidence of events over the 3 years follow‐up compared to a monotherapy with statins of moderate intensity.

Background: Given the increasing prevalence of dyslipidaemia and multimorbidity in the elderly population, the lack of safety data on combined statin–fenofibrate therapy in this age group represents a critical gap. The post hoc subgroup analysis of the Pose study addresses this issue. Materials and methods: The POSE study was a 3-year, real-world, observational, comparative, non-interventional study conducted in Europe. Patients with mixed dyslipidaemia treated either by a fixed-dose combination of pravastatin 40 mg/fenofibrate 160 mg or a moderate-intensity statin monotherapy were enrolled. Safety outcomes included the occurrence of renal or urinary disorders, musculoskeletal or connective tissue disorders, hepatobiliary disorders, cholelithiasis, thromboembolic events, pancreatitis, worsening diabetes mellitus, elevated blood homocysteine levels, interstitial pneumopathy, phototoxicity, and fatal or non-fatal cardiovascular events. Laboratory parameters related to lipid control and renal, muscular, and hepatic functions were additionally evaluated. The post hoc analysis focuses on the subgroup of patients aged 75 years and older. Results: A total of 458 patients were included in the analysis. The majority had hypertension (79.3%) and diabetes mellitus (55.0%). Over the 3-year study period, there was no difference in incidence rate of safety events between groups (RR = 2.18 [95% CI = 0.99–4.81]). Renal and urinary disorders were more frequent with the combination (5.5% vs 0.8%), whereas musculoskeletal disorders, aggravated diabetes mellitus, and cardiovascular events, showed no significant difference between groups, the 95% CI spanning 1. Globally, there were no significant differences regarding the evolution of hepatic, muscle and renal biological parameters. As expected, the pravastatin/fenofibrate combination achieved a more pronounced TG reduction and a modest increase in HDL-C, whereas the statin group showed more modest changes in these parameters. Conclusions: This real-life observational post hoc subgroup analysis suggests that in patients aged 75 years and older with mixed dyslipidaemia at high or very high CV risk, pravastatin 40 mg/fenofibrate 160 mg is well tolerated and can be used with acceptable long‑term safety. The combination offers additional TG lowering and HDL‑C improvement beyond moderate‑intensity statin monotherapy, without a significant increase in overall safety events over three years. The study confirms the positive benefit / risk balance of the fixed-dose combination of pravastatin 40 mg/fenofibrate 160 mg in this growing population of patients aged 75 years and older.