Cholecalciferol

BackgroundTwo previous meta-analyses showed smaller differences between vitamin D3 and vitamin D2 in raising serum 25-hydroxyvitamin D [25(OH)D] and a consistently high heterogeneity when only including daily dosing studies.ObjectiveThis study aimed to compare more frequently dosed vitamin D2 and vitamin D3 in improving total 25(OH)D and determine the concomitant effect of response modifiers on heterogeneity, and secondly, to compare the vitamin D2-associated change in 25(OH)D2 with the vitamin D3-associated change in 25(OH)D3.MethodsPubMed, EMBASE, Cochrane, and the Web of Science Core collection were searched for randomized controlled trials of vitamin D2 compared with vitamin D3, daily or once/twice weekly dosed. After screening for eligibility, relevant data were extracted for meta-analyses to determine the standardized mean difference when different methods of 25(OH)D analyses were used. Otherwise, the weighted mean difference (WMD) was determined.ResultsOverall, the results based on 20 comparative studies showed vitamin D3 to be superior to vitamin D2 in raising total 25(OH)D concentrations, but vitamin D2 and vitamin D3 had a similar positive impact on their corresponding 25(OH)D hydroxylated forms. The WMD in change in total 25(OH)D based on 12 daily dosed vitamin D2-vitamin D3 comparisons, analyzed using liquid chromatography-tandem mass spectrometry, was 10.39 nmol/L (40%) lower for the vitamin D2 group compared with the vitamin D3 group (95% confidence interval: -14.62, -6.16; I2 = 64%; P 25 kg/m2 (P = 0.99). However, information on BMI was only available in 13/17 daily dosed comparisons.ConclusionsVitamin D3 leads to a greater increase of 25(OH)D than vitamin D2, even if limited to daily dose studies, but vitamin D2 and vitamin D3 had similar positive impacts on their corresponding 25(OH)D hydroxylated forms. Next to baseline 25(OH)D concentration, BMI should be considered when comparing the effect of daily vitamin D2 and vitamin D3 supplementation on total 25(OH)D concentration. This study was registered in PROSPERO as CRD42021272674.

Vitamin D3 replacement in older insufficient adults significantly improves their antigen-specific varicella zoster virus (VZV) cutaneous immunity. However, the mechanisms involved in this enhancement of cutaneous immunity are not known. Here, we show for the first time that vitamin D3 blocks the senescence-associated secretory phenotype (SASP) production by senescent fibroblasts by partially inhibiting the p38 MAPK pathway. Furthermore, transcriptomic analysis of skin biopsies from older subjects after vitamin D3 supplementation shows that vitamin D3 inhibits the same inflammatory pathways in response to saline as the specific p38 inhibitor, losmapimod, which also enhances immunity in the skin of older subjects. Vitamin D3 supplementation therefore may enhance immunity during ageing in part by blocking p38 MAPK signalling and in turn inhibit SASP production from senescent cells in vivo.

Alzheimer's disease (AD) is characterized by amyloid beta (Aβ) buildup and neuronal degeneration. An association between low serum vitamin D levels and an increased risk of AD has been reported in several epidemiological studies. Calcitriol (1,25-dihydroxycholecalciferol) is the active form of vitamin D, and is generated in the kidney and many other tissues/organs, including the brain. It is a steroid hormone that regulates important functions like calcium/phosphorous levels, bone mineralization, and immunomodulation, indicating its broader systemic significance. In addition, calcitriol confers neuroprotection by mitigating oxidative stress and neuroinflammation, promoting the clearance of Aβ, myelin formation, neurogenesis, neurotransmission, and autophagy. The receptors to which calcitriol binds (vitamin D receptors; VDRs) to exert its effects are distributed over many organs and tissues, representing other significant roles of calcitriol beyond sustaining bone health. The biological effects of calcitriol are manifested through genomic (classical) and non-genomic actions through different pathways. The first is a slow genomic effect involving nuclear VDR directly affecting gene transcription. The association of AD with VDR gene polymorphisms relies on the changes in vitamin D consumption, which lowers VDR expression, protein stability, and binding affinity. It leads to the altered expression of genes involved in the neuroprotective effects of calcitriol. This review summarizes the neuroprotective mechanism of calcitriol and the role of VDR polymorphisms in AD, and might help develop potential therapeutic strategies and markers for AD in the future.

Background: Vitamin D is involved in musculoskeletal function, but evidence that supplementation improves athletic performance remains inconsistent, particularly in athletes with sufficient baseline vitamin D status. Methods: In this double-blind randomized controlled trial, 18 professional female soccer players were randomized during the autumn preparatory period (August-September) to receive vitamin D3 (4000 IU/day; n = 9) or placebo (n = 9) for eight weeks. Outcomes included total serum 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations, hematological variables, RAST total sprint time, 5- and 30-m sprint performance, and countermovement-jump outcomes. Results: At baseline, after summer exposure, 25% of participants had insufficient or deficient 25(OH)D concentrations (≤30 ng/mL). The remaining cohort (75%) had sufficient 25(OH)D concentrations (>30 ng/mL). After eight weeks, no statistically significant between-group differences were observed in vitamin D metabolites, hematological variables, or performance outcomes (Δ25(OH)D: SG +12.4 ± 8.2 ng/mL vs. PG +3.1 ± 6.5 ng/mL; p = 0.12). RAST total sprint time (p = 0.001) and 30-m sprint performance (p = 0.005) improved over time. Conclusions: Vitamin D3 supplementation at 4000 IU/day for eight weeks was not associated with additional improvements in muscle strength, sprint performance, or countermovement-jump outcomes compared with placebo. Because most participants had sufficient baseline 25(OH)D concentrations, larger trials in female athletes with confirmed vitamin D insufficiency or deficiency are needed to determine whether individualized supplementation or longer intervention periods provide additional physiological or performance-related benefits. The trial was retrospectively registered at ClinicalTrials.gov (NCT07641075) on 8 June 2026.