A Randomized, Open-Label Study to Assess Efficacy of Weekly Assumption of Cholecalciferol versus Calcifediol in Older Patients with Hypovitaminosis D

Abstract

The aim of this single-center, open-label, randomized controlled study was to evaluate which formulation of vitamin D—between cholecalciferol and calcifediol—is most effective in the treatment of hypovitaminosis D in older adults. Demographic characteristics, clinical history, and comprehensive geriatric assessment were recorded at admission. Eligible patients were randomly assigned an equivalent vitamin D supplement, either with cholecalciferol or calcifediol, from the time of hospital admission to three months after discharge. Among the 140 older patients included (mean age 83 ± 6.6 years, 57.8% females), 69 received cholecalciferol and 71 received calcifediol. The mean plasma values of 25-hydroxyvitamin D3 (25OH-vitamin D3) found at the time of enrollment were 16.8 ± 9.9 ng/mL in patients receiving cholecalciferol and 18.8 ± 13.3 ng/mL in those treated with calcifediol (p = 0.31). At the three month follow-up, the mean concentration of 25OH-vitamin D3 was significantly higher in patients treated with calcifediol than in those receiving cholecalciferol (30.7 ± 8.4 vs. 45.4 ± 9.8 ng/mL, respectively; p < 0.001). Supplementation with either cholecalciferol or calcifediol effectively results in reaching the optimal circulating values of 25OH-vitamin D3 in older patients suffering from hypovitaminosis D. However, supplementation with calcifediol led to average circulating values of 25OH-vitamin D3 that were significantly higher (over 50%) than those obtained with cholecalciferol.

Vitamin D Endocrine System and COVID-19: Treatment with Calcifediol

“…The oral administration of 20 μg of calcifediol compared to 800 IU (20 μg) of cholecalcifeol was significantly more effective and faster in increasing serum 25OHD concentrations in postmenopausal women in the range above 30 ng/mL; furthermore, it produced significantly more pronounced suppression of eotaxin, IL-12, monocyte chemoattractant protein 1 MCP-1, and macrophage inflammatory protein 1 beta MIP-1β [96], which are markers implicated in the severity of COVID-19 [97]. Treatment with calcifediol prescribed for whatever health reason, such as osteoporosis, improves the 25OHD status [87,98], and thus may reduce the risk and impact of COVID-19 [53]. Indeed, in a retrospective cohort study in the Barcelona area (Spain) on a population of 4.6 million inhabitants collected in the public health system registries, from Calcifediol's ease of absorption and availability is especially relevant in patients with severe fat malabsorption [89].…”

“…Treatment with calcifediol prescribed for whatever health reason, such as osteoporosis, improves the 25OHD status [87,98], and thus may reduce the risk and impact of COVID-19 [53]. Indeed, in a retrospective cohort study in the Barcelona area (Spain) on a population of 4.6 million inhabitants collected in the public health system registries, from April 2019 to February 2020, the risk of COVID-19 infection during the first wave of the pandemic was assessed in patients who were prescribed cholecalciferol (n = 108,343) or calcifediol (n = 134,703) during the previous 4 months and were compared with propensity score-matched untreated controls [99].…”

Scientific opinion on the tolerable upper intake level for vitamin D, including the derivation of a conversion factor for calcidiol monohydrate

“…The group was ignored as supplementation pattern was less frequent than weekly. Background vitamin D intake: NR Background calcium intake: NR Compliance NR Serum 25(OH)D: measured by HPLC and ultraviolet detection method time of blood collection after last dosage: NR Serum PTH: measured by ECLIA (Roche Diagnostic) Data extracted: unclear Serum 25(OH)D at 6mo (nmol/L) G1: 80.0 ± 2.0 G2: 161 ± 21.7 G3: 213.5 ± 80.0 Serum 25(OH)D at 12 mo (nmol/L) G1: 86.2 ± 23.7 G2: 188.0 ± 24.0 G3: 233.0 ± 81.2 Serum 25(OH)D, change over 12 mo (nmol/L) G1: 45.7 ± 19.5 G2: 150.8 ± 22.3 G3: 195 ± 79.3 Serum PTH at 6 mo (ng/L) G1: 46.5 ± 11.2 G2: 38.7 ± 10.7 G3: 35.4 ± 8.4 Serum iPTH at 12 mo (ng/L) G1: 41.6 ± 10.5 G2: 32.5 ± 8.8 G3: 29.0 ± 5.9 3 Okoye et al. (2022) Italy Latitude [assumed] 43.7° N From hospital admission to 3 mo after discharge. Unclear funding [stated no external funding received] RCT (parallel) Inclusion criteria: Geriatric patients consecutively hospitalized in the Geriatric Unit of the University Hospital of Pisa for acute illness, with 25(OH)D 3 levels <30 ng/mL [<75 nmol/L]. Exclusion criteria: Having received vitamin D supplementation during the past 6 mo; stage V renal insufficiency; liver failure (defined as a Child–Pugh classification of a B or C); hyperparathyroidism; malabsorption syndromes or the long‐term prescription of drugs reducing vitamin D absorption (i.e., antiepileptic drugs, long‐term corticosteroids, or bisphosphonates); neoplastic disease under treatment; patients being unable to give informed consent. N participants randomised/completed/analysed G1: 89/69/69 G2: 89/70/71 Sex (% females) G1: 56.5 G2: 59.1 Age (y): G1: 84.9 ± 6.4 G2: 82.7 ± 6.7 Plasma 25(OH)D 3 (ng/mL) G1: 16.8 ± 9.9 ng/mL [42.0 ± 24.75 nmol/L] G2: 18.8 ± 13.3 ng/mL [47.0 ± 33.25 nmol/L] PTH (ng/dL) G1: 48.1 ± 39.6 G2: 60.7 ± 36.9 BMI (kg/m 2 ) G1: 23.7 (7.2) G2: 25.0 (5.6) Ethnicity [assumed]: Majority Caucasian Smoking status: NR Alcohol use: NR Health status (%) Arterial hypertension: G1: 69.6 G2: 70.4 Coronary heart disease: G1 11.6 G2: 9.9 Atrial fibrillation: G1: 17.4 G2: 19.7 Heart failure: G1: 42.0 G2: 39.4 Diabetes: G1: 20.3 G2: 21.1 Chronic kidney disease: G1: 23.2 G2: 22.5 Chronic obstructive pulmonary disease: G1: 8.6 G2: 9.8 Season: May to Sept 2020 Doses G1: vitamin D 3 437.5 μg/wk [=62.5 μg/d] G2: calcidiol 140 μg/wk [=20 μg/d] Background vitamin D intake: NR Background calcium intake: NR Compliance Pill count method: Complete adherence stated. Plasma 25(OH)D 3 : measured by HPLC–MS/MS time of blood collection after last dosage: NR PTH: method of measurement NR Data extracted: unclear Plasma 25(OH)D 3 at 3 mo (ng/mL) G1: 30.7 ± 8.4 ng/mL [76.75 ± 21.0 nmol/L] G2: 45.4 ± 9.8 ng/mL [113.5 ± 24.5 nmol/L] PTH at 3 mo (ng/dL): NR 3 Ruggiero et al. (2019) Italy Latitude [assumed] 43.1° N From hospital admission to 7 mo after discharge. Unclear funding [stated no external funding received] RCT, pragmatic (parallel) Inclusion criteria: Community‐dwelling women and men, oldest‐old patients, aged >75 years, consecutively admitted to geriatric acute care ward. Exclusion criteria: On treatment with vitamin D, multivitamins, calcium supplements, anti‐fracture drugs or steroids; suffered from fragility fractures within 6 mo, cancer within 5 y, hyperparathyroidism, hypercalcaemia, hypercalciuria, hypoph...…”

“…No studies were identified as being influential based on leave out analysis. Excluding the three studies in RoB Tier 3 (Catalano et al, 2015;Navarro-Valverde et al, 2016;Okoye et al, 2022) had little impact on the results: ROM (95% CI) was 2.36 (1.82, 3.10) and heterogeneity remained high (Figure 3c). Since the dose-response curve between the intake of vitamin D 3 and serum 25(OH)D concentration tends to level-off gradually at high intakes, a sensitivity analysis was conducted excluding the two RCTs that used ∼ 60 μg/day vitamin D 3 as the reference dose (Figure 3d).…”

“…Nine RCTs were conducted in Europe (Bischoff‐Ferrari et al., 2012 ; Cashman et al., 2012 ; Catalano et al., 2015 ; Navarro‐Valverde et al., 2016 ; Vaes et al., 2018a , b ; Graeff‐Armas et al., 2020 ; Corrado et al., 2021 ; Okoye et al., 2022 ), and thus in Caucasian or assumed Caucasian populations, and one in the USA (Shieh et al., 2017 ) in a population of mixed ethnic origin (Appendix C.1 ). Except for the study run in the USA (age ≥ 18 years; sex not specified), RCTs were in adults of both sexes (n = 5) or females only (n = 4) 50 years of age and older.…”