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: 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.

Background: Given the increasing prevalence of dyslipidemia and multimorbidity in the older patient 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 dyslipidemia 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 focused on a 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, the incidence rate of composite safety events was numerically higher with the combination, though this did not reach statistical significance (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, as the 95% confidence interval included 1. Globally, there were no significant differences regarding evolution of the hepatic, muscle, and renal biological parameters. From baseline to Year 3, TG levels decreased by 44.3% with pravastatin/fenofibrate and by 10.7% with statin monotherapy, while HDL-C levels increased by 26.5% and 0.4%, respectively. Conclusions: This real-life observational post hoc subgroup analysis suggests that in patients aged 75 years and older with mixed dyslipidemia at high or very high CV risk, pravastatin 40 mg/fenofibrate 160 mg demonstrates an acceptable long-term safety profile. 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.