Search Results (62)

Species-specific husbandry guidelines remain limited for blue-tongued skinks (Tiliqua scincoides), especially in relation to ultraviolet B (UVB) lighting and vitamin D requirements. This study aimed to determine whether UVB exposure is necessary for these skinks and how long 25-hydroxyvitamin D (25-OHD) concentrations persist after UVB withdrawal. Eleven adult skinks who had been fed with wet cat food were exposed to 12 or 2 h of UVB per day for four weeks. Plasma 25-OHD concentrations were very low at the baseline, and significantly increased post-UVB in both groups (p < 0.01), with the 12-hour group increasing from baseline concentrations of 18.5 [12.8–20.5] nmol/L to 820 [730–1251.3] nmol/L and the 2-hour group increasing from baseline concentrations of 22 [15.5–22] nmol/L to 635 [401–892.5] nmol/L. Following the discontinuation of UVB exposure, 25-OHD gradually declined and was not significantly different from baseline concentrations at 7 and 4 months for the 12-hour and 2-hour groups, respectively. Dietary vitamin D₃ (2.5 IU/g as dry matter basis), provided through wet cat food alone, appeared insufficient to support sustained plasma 25-OHD concentrations. These findings strongly suggest that blue-tongued skinks rely on UVB exposure to increase their 25-OHD concentrations. Moreover, the shorter 2-hour exposure provided a significant rise in 25-OHD concentrations and remained above baseline for 4 months, suggesting the shorter exposure can benefit these animals, while potentially reducing secondary risks associated with UVB exposure. Full article

Background: Immunomodulatory treatments targeting excessive host immune responses favorably shifting the course of COVID-19. High doses of calcifediol may reduce the mortality of this infection. Objective: To evaluate how a high dose of calcifediol modifies the risk of death in patients hospitalized with COVID-19 during the first outbreaks. Design: A retrospective, observational study to evaluate the relationship between treatment with calcifediol and the risk of death in patients hospitalized with COVID-19 at the “Complejo Hospitalario Universitario de Albacete” (CHUA), Spain, during the months of January to March 2021. Patients were treated with corticosteroids, and some patients also received baricitinib and/or high doses of calcifediol, according to CHUA’s therapeutic protocol 2021 for COVID-19. The primary outcome measure was mortality according to calcifediol treatment. Results: A total of 230 patients were included. 25(OH)D levels were measured on admission in 148 patients, showing a high prevalence of vitamin D deficiency [median 25(OH)D: 17.5 ng/mL]. Thirty-four (23%) had severe deficiency (25(OH)D ≤ 10 ng/mL). In the 119 patients (51.7%) who received in-hospital treatment with a high dose of calcifediol, the mortality rate was 12.6% (15 cases, 95% confidence interval [CI], 7.8–19.8%), while in 111 patients who did not receive treatment with calcifediol, the death rate was 23.4% (26 cases, 95% CI: 16.5–32.1%; p = 0.039). The odds ratio (OR) in treated vs. untreated patients was 0.47 (95% CI: 0.23–0.95). Among the patients admitted with severe deficiency, 16 received treatment with calcifediol, with a mortality rate of 0.0% (0 cases, 95% CI: 0.0–19.4%), while in the 18 not treated with calcifediol, a death rate of 38.9% was observed (7 cases, 95% CI: 20.3–61.4%; p = 0.008). The mortality rate was lower in patients treated with the combination of calcifediol and corticosteroids vs. those treated with corticosteroids alone (p = 0.038) and vs. those treated with corticosteroids and baricitinib (p = 0.033). Conclusions: In the ALBACOVIDIOL study, calcifediol treatment was associated with a lower observed mortality rate in hospitalized patients with COVID-19 treated with corticosteroids (with or without baricitinib), especially in those with severe vitamin D deficiency. Causality cannot be inferred due to the retrospective study design. (Public database: ClinicalTrials.gov, NCT05819918). Full article

Vitamins are crucial micro-nutrients for overall well-being, making continuous monitoring essential. There are demands to provide an alternative detection, especially using a portable detection or a point-of-care-testing (POCT) device. One promising approach is employing an in situ electro-polymerised MIP (eMIP), which offers a straightforward polymerisation technique on screen-printed electrodes (SPEs). Here, we report a review based on three databases (PubMed, Scopus, and Web of Science) from 2014 to 2024 using medical subject heading (MeSH) terms “electrochemical polymerisation” OR “electropolymerisation” crossed with the terms “molecularly imprinted polymer” AND “vitamin A” OR “vitamin D” OR “vitamin E” OR “vitamin K” OR “fat soluble vitamin” OR “vitamin B” OR “vitamin C” OR “water soluble vitamin”. The resulting 12 articles covered the detection of vitamins in ascorbic acid, riboflavin, cholecalciferol, calcifediol, and menadione using monomers of catechol (CAT), 3,4-ethylenedioxythiophene (EDOT), o-aminophenol (oAP), o-phenylenediamine (oPD), pyrrole, p-aminophenol (pAP), p-phenylenediamine (pPD), or resorcinol (RES), using common bare electrodes including graphite rod electrode (GRE), glassy carbon electrode (GCE), gold electrode (GE), and screen-printed carbon electrode (SPCE). The most common electrochemical detections were differential pulse voltammetry (DPV) and linear sweep voltammetry (LSV). The imprinting factor (IF) of the eMIP-modified electrodes were from 1.6 to 21.0, whereas the cross-reactivity was from 0.0% to 29.9%. Several types of food and biological samples were tested, such as supplement tablets, poultry and pharmaceutical drugs, soft drinks, beverages, milk, infant formula, human and calf serum, and human plasma. However, more discoveries and development of detection methods needs to be performed, especially for the vitamins that have not been studied yet. This will allow the improvement in the application of eMIPs on portable-based detection and POCT devices. Full article

Background/Objectives: Adequate vitamin D levels are critical for overall health, yet vitamin D deficiency remains prevalent. This study aims to evaluate the efficacy and safety of a standardized weekly supplementation regimen of 100 μg calcifediol for patients with varying degrees of vitamin D deficiency. Methods: A post hoc pool analysis was conducted from a randomized, double-blind, placebo-controlled, multicenter, two-cohort trial. Cohort 1 included vitamin D mild deficiency patients (25(OH)D levels > 10 < 20 ng/mL) and Cohort 2 severe deficiency patients (25(OH)D levels ≤ 10 ng/mL). As both had placebo and weekly calcifediol 100 μg arms (ratio 1:2), a pooled analysis of safety and efficacy was conducted. The primary outcome was the percentage of subjects achieving 25(OH)D levels ≥ 20 ng/mL and/or ≥30 ng/mL at various time points. Results: A total of 401 participants across both cohorts were included in the analysis, 130 who received a placebo and 271 calcifediol 100 µg weekly. By week 52, 94.5% of individuals in the calcifediol group achieved 25(OH)D levels ≥ 20 ng/mL, compared to 25.3% in the placebo group (p < 0.0001). At this same week, 80.5% of subjects in the calcifediol group, but none in the placebo group (p < 0.0001), had 25(OH)D levels ≥ 30 ng/mL. The mean 25(OH)D level plateaued around 40.7 ng/mL from weeks 16 to 52. The frequency of treatment-emergent adverse events was similar in both groups, placebo and calcifediol. Conclusions: Weekly supplementation of 100 μg calcifediol effectively restores vitamin D levels in individuals with both mild and severe deficiencies, demonstrating a favourable safety profile. Full article

Background/Objectives: Cholecalciferol and Calcifediol are commonly used for oral supplementation in patients with vitamin D deficiency. Several studies have compared these two molecules; however, the studied population has only included healthy postmenopausal women so far. This retrospective observational study aims to evaluate which molecule is more effective and faster in achieving serum 25(oh)D levels within the normal range in post-stroke patients during the subacute phase. Secondary aims include assessing potential differences in functional outcomes and investigating the possible correlation between the degree of hypovitaminosis D and stroke severity. Methods: We observed 85 in-patients who received either Cholecalciferol or Calcifediol during intensive rehabilitation. All subjects underwent functional evaluations, blood tests, and a bone densitometry (DEXA) scan. Results: Four months after starting supplementation, subjects receiving calcifediol achieved significantly higher 25(oh)D levels (p < 0.001) compared to those receiving cholecalciferol. No significant between-group differences were observed in secondary outcomes. Another key finding is that no statistically significant correlation was found between serum of 25(oh)D levels and stroke severity. Conclusions: These results highlight the importance of further investigating bone metabolism in post-stroke patients, though findings should be confirmed in larger studies. Full article

Background/Objectives: Given the crucial health benefits of vitamin D, addressing severe deficiencies is a pressing medical concern. This study aimed to evaluate the effectiveness and safety of two new weekly doses of calcifediol (100 µg and 125 µg) for long-term management in patients with severe vitamin D deficiency, defined as plasma 25(OH)D levels ≤10 ng/mL. Methods: This study was a randomized, two-cohort, controlled, double-blind, multicentre phase II–III trial. Subjects were randomized 2:2:1 to weekly calcifediol 100 µg, 125 µg or a placebo. The primary endpoint was the proportion of patients achieving plasma 25(OH)D levels of ≥20 ng/mL and/or ≥30 ng/mL by week 16. Results: A total of 276 patients (mean age: 55.2 years, SD 15.42) were randomized. By week 16, 92.3% and 91.8% of patients in the calcifediol 100 µg and 125 µg groups, respectively, reached ≥20 ng/mL, compared to 7.3% in the placebo group. Levels of ≥30 ng/mL were achieved by 49% (100 µg) and 76.4% (125 µg) of participants, with none in the placebo group. Calcifediol demonstrated superior efficacy at all response levels and time points (p < 0.0001). Plasma 25(OH)D concentrations increased by week 24 and remained stable. The incidence of adverse events was comparable across groups. Conclusions: A weekly calcifediol dose of 100 µg demonstrates the best profile of efficacy and tolerability, providing a reliable solution for achieving and maintaining adequate vitamin D levels in patients with severe deficiency. Full article

Clinical trials consistently demonstrate an inverse correlation between serum 25-hydroxyvitamin D [25(OH)D; calcifediol] levels and the risk of symptomatic SARS-CoV-2 disease, complications, and mortality. This systematic review (SR), guided by Bradford Hill’s causality criteria, analyzed 294 peer-reviewed manuscripts published between December 2019 and November 2024, focusing on plausibility, consistency, and biological gradient. Evidence confirms that cholecalciferol (D₃) and calcifediol significantly reduce symptomatic disease, complications, hospitalizations, and mortality, with optimal effects above 50 ng/mL. While vitamin D requires 3–4 days to act, calcifediol shows effects within 24 h. Among 329 trials, only 11 (3%) showed no benefit due to flawed designs. At USD 2/patient, D₃ supplementation is far cheaper than hospitalization costs and more effective than standard interventions. This SR establishes a strong inverse relationship between 25(OH)D levels and SARS-CoV-2 vulnerability, meeting Hill’s criteria. Vitamin D₃ and calcifediol reduce infections, complications, hospitalizations, and deaths by ~50%, outperforming all patented, FDA-approved COVID-19 therapies. With over 300 trials confirming these findings, waiting for further studies is unnecessary before incorporating them into clinical protocols. Health agencies and scientific societies must recognize the significance of these results and incorporate D₃ and calcifediol for prophylaxis and early treatment protocols of SARS-CoV-2 and similar viral infections. Promoting safe sun exposure and adequate vitamin D₃ supplementation within communities to maintain 25(OH)D levels above 40 ng/mL (therapeutic range: 40–80 ng/mL) strengthens immune systems, reduces hospitalizations and deaths, and significantly lowers healthcare costs. When serum 25(OH)D levels exceed 70 ng/mL, taking vitamin K₂ (100 µg/day or 800 µg/week) alongside vitamin D helps direct any excess calcium to bones. The recommended vitamin D dosage (approximately 70 IU/kg of body weight for a non-obese adult) to maintain 25(OH)D levels between 50–100 ng/mL is safe and cost-effective for disease prevention, ensuring optimal health outcomes. Full article

Background/Objectives: Vitamin D is essential for bone health, immune function, and overall well-being. Numerous ecological, observational, and prospective studies, including randomized controlled clinical trials (RCTs), report an inverse association between higher serum 25-hydroxyvitamin D [25(OH)D; calcifediol] levels in various conditions, including cardiovascular disease, metabolic disorders such as diabetes and obesity, susceptibility to infection-related complications, autoimmune diseases, and all-cause mortality. Results: Vitamin D operates through two distinct systems. The endocrine system comprises the renal tubular cell-derived circulatory calcitriol, which primarily regulates calcium homeostasis and muscular functions. In contrast, intracellularly generated calcitriol in peripheral target cells is responsible for intracrine/paracrine system signaling and calcitriol–vitamin D receptor-mediated genomic effects. Government-appointed committees and health organizations have developed various clinical practice guidelines for vitamin D supplementation and management. However, these guidelines heavily relied on the 2011 Institute of Medicine (IoM) report, which focused solely on the skeletal effects of vitamin D, ignoring other body systems. Thus, they do not represent maintaining good overall health and aspects of disease prevention. Additionally, the IoM report was intended as a public health recommendation for the government and is not a clinical guideline. Discussion: New country- and regional-specific guidelines must focus on healthy nations through disease prevention and reducing healthcare costs. They should not be restricted to bone effect and must encompass all extra-skeletal benefits. Nevertheless, due to misunderstandings, medical societies and other governments have used faulty IoM report as a foundation for creating vitamin D guidelines. Consequently, they placed disproportionate emphasis on bone health while largely overlooking its benefits for other bodily systems, making current guidelines, including 2024, the Endocrine Society less applicable to the public. As a result, the utility of published guidelines has been significantly reduced for clinical practice and RCTs that designed on bone-centric are generate misleading information and remain suboptimal for public health and disease prevention. Conclusions: This review and its recommendations address the gaps in current vitamin D clinical practice guidelines and propose a framework for developing more effective, country and region-specific recommendations that capture the extra-skeletal benefits of vitamin D to prevent multiple diseases and enhance public health. Full article

Background/Objective: Optimal vitamin D levels are required for bone health and proper functionality of the nervous, musculoskeletal and immune systems. The objective of this study was to assess the efficacy and safety profiles of new weekly calcifediol formulations with the potential to improve adherence and outcome. Methods: A Phase II-III, double-blind, randomized, multicentre trial (EudraCT 2020-001099-14 and NCT04735926). Subjects were randomized 2:2:1 to calcifediol 75 µg, 100 µg and placebo. 25(OH)D levels were measured at 4, 16, 24, 32 and 52 weeks. The main outcome was the percentage of subjects who achieved a response defined as 25(OH)D levels ≥20 ng/mL and/or ≥30 ng/mL at week 16. Results: 398 subjects (51.1 ± 15.96 years, 74.2% females, 98.7% Caucasian) with plasma 25(OH)D levels between 10 and 20 ng/mL were randomized. A total of 376 subjects completed 16 weeks of treatment, and 355 subjects completed the study. Six patients withdrew due to an adverse event, all unrelated to treatment. At week 16, 93.6% and 74.4% of subjects receiving calcifediol 75 µg achieved response levels of ≥20 ng/mL and ≥30 ng/mL, respectively. The calcifediol 100 µg group showed 98.7% and 89.9% of responders for ≥20 ng/mL and ≥30 ng/mL, respectively. Both calcifediol groups showed superiority over placebo at each response level at all time points analyzed (p < 0.0001). Calcifediol treatments increased 25(OH)D levels from baseline to week 24 and remained stable thereafter. The frequency of treatment-emergent adverse events was balanced between groups. Conclusions: New weekly calcifediol 75 and 100 µg formulations showed an effective and sustained response with a good long-term safety profile. Full article

Pathological states marked by oxidative stress and systemic inflammation frequently compromise the functional capacity of muscular cells. This progressive decline in muscle mass and tone can significantly hamper the patient’s motor abilities, impeding even the most basic physical tasks. Muscle dysfunction can lead to metabolic disorders and severe muscle wasting, which, in turn, can potentially progress to sarcopenia. The functionality of skeletal muscle is profoundly influenced by factors such as environmental, nutritional, physical, and genetic components. A well-balanced diet, rich in proteins and vitamins, alongside an active lifestyle, plays a crucial role in fortifying tissues and mitigating general weakness and pathological conditions. Vitamin D, exerting antioxidant effects, is essential for skeletal muscle. Epidemiological evidence underscores a global prevalence of vitamin D deficiency, which induces oxidative harm, mitochondrial dysfunction, reduced adenosine triphosphate production, and impaired muscle function. This review explores the intricate molecular mechanisms through which vitamin D modulates oxidative stress and its consequent effects on muscle function. The aim is to evaluate if vitamin D supplementation in conditions involving oxidative stress and inflammation could prevent decline and promote or maintain muscle function effectively. Full article

Medical treatment of coronavirus 19 disease (COVID-19) is a therapeutic challenge. The available data strongly suggest that calcifediol treatment may reduce the severity of COVID-19, and corticosteroids are the treatment of choice worldwide for severe COVID-19. Both have a very similar action profile, and their combined use in patients may modify the contribution of each administered compound. Objective: To evaluate how treatment with calcifediol and/or corticosteroids in medical practice modified the need for ICU admission, death, or poor prognosis of patients hospitalized with COVID-19 during the first outbreaks. Design, patients and setting: A retrospective observational cohort study of patients admitted for COVID-19 to the Pneumology Unit of the Hospital Universitario Reina Sofía (Córdoba, Spain). Interventions: Patients were treated with calcifediol or/and corticosteroids with the best available therapy and standard care, according to clinical practice guidelines. Measurements: Admission to the intensive care unit (ICU) or death during hospitalization and poor prognosis. Results: Seven hundred and twenty-eight patients were included. According to the treatment received, they were included in four groups: calcifediol (n = 68), glucocorticoids (n = 112), both (n = 510), or neither (n = 38). Of the 578 patients treated with calcifediol, 88 were admitted to the ICU (15%), while of the 150 not treated with calcifediol, 39 required ICU admission (26%) (p < 0.01). Among the patients taking calcifediol without glucocorticoids, only 4 of 68 (5.8%) required ICU admission, compared to 84 of 510 (16.5%) treated with both (p = 0.022). Of the 595 patients who had a good prognosis, 568 (82.01%) had received treatment with calcifediol versus the 133 patients with a poor prognosis, of whom 90 (67.66%) had received calcifediol (p < 0.001). This difference was not found for corticosteroids. Interpretation: The treatment of choice for hospitalized patients with moderate or mild COVID-19 could be calcifediol, not administering corticosteroids, until the natural history of the disease reaches a stage of hyperinflammation. Full article

Background: We assessed the long-term (24 months) efficacy and safety of monthly calcifediol (0.266 mg) in the correction and maintenance of total 25(OH)D levels in postmenopausal women with basal values <30 ng/mL. Methods: We initially enrolled 45 consecutive patients during the period September 2019–September 2020. After an initial visit, patients were instructed to return at 3, 6, 9, 12 and 24 months for measuring serum total 25(OH)D, ionised calcium, creatinine and isoenzyme of alkaline phosphatase (bALP). Here, we report only the per-protocol analysis, because the COVID-19 pandemic precluded adherence to the scheduled visits for some patients. Results: The patients’ mean age was 62.4 ± 9.0 years. Mean basal 25(OH)D levels were 20.5 ± 5.3 ng/mL. There was a continuous increase of mean 25(OH)D values (p for trend < 0.001). However, mean values at month 24 (36.7 ± 15.9) were not significantly different in respect to values at month 12 (41.2 ± 11.18). At 24 months, only 1 out 19 patients had a value <20 ng/mL. There was a significant decrease with time of mean values of bALP (p < 0.0216), with no significant changes between 12 and 24 months. No significant changes were observed as far as ionised calcium or creatinine were concerned. Conclusions: The long-term administration of calcifediol maintains stable and sustained 25(OH)D concentrations, with no safety concerns. Full article

Vitamin D is a crucial micronutrient, critical to human health, and influences many physiological processes. Oral and skin-derived vitamin D is hydroxylated to form calcifediol (25(OH)D) in the liver, then to 1,25(OH)₂D (calcitriol) in the kidney. Alongside the parathyroid hormone, calcitriol regulates neuro-musculoskeletal activities by tightly controlling blood-ionized calcium concentrations through intestinal calcium absorption, renal tubular reabsorption, and skeletal mineralization. Beyond its classical roles, evidence underscores the impact of vitamin D on the prevention and reduction of the severity of diverse conditions such as cardiovascular and metabolic diseases, autoimmune disorders, infection, and cancer. Peripheral target cells, like immune cells, obtain vitamin D and 25(OH)D through concentration-dependent diffusion from the circulation. Calcitriol is synthesized intracellularly in these cells from these precursors, which is crucial for their protective physiological actions. Its deficiency exacerbates inflammation, oxidative stress, and increased susceptibility to metabolic disorders and infections; deficiency also causes premature deaths. Thus, maintaining optimal serum levels above 40 ng/mL is vital for health and disease prevention. However, achieving it requires several times more than the government’s recommended vitamin D doses. Despite extensive published research, recommended daily intake and therapeutic serum 25(OH)D concentrations have lagged and are outdated, preventing people from benefiting. Evidence suggests that maintaining the 25(OH)D concentrations above 40 ng/mL with a range of 40–80 ng/mL in the population is optimal for disease prevention and reducing morbidities and mortality without adverse effects. The recommendation for individuals is to maintain serum 25(OH)D concentrations above 50 ng/mL (125 nmol/L) for optimal clinical outcomes. Insights from metabolomics, transcriptomics, and epigenetics offer promise for better clinical outcomes from vitamin D sufficiency. Given its broader positive impact on human health with minimal cost and little adverse effects, proactively integrating vitamin D assessment and supplementation into clinical practice promises significant benefits, including reduced healthcare costs. This review synthesized recent novel findings related to the physiology of vitamin D that have significant implications for disease prevention. Full article

The aim of this pilot study was to evaluate and compare bioavailability and safety of two Vitamin D₃ formulations (softgels) in healthy adults, at single daily doses of 1000 and 2500 IU, over a 60-day period. A total of 69 participants were initially screened for eligibility in a double-blind randomized study with a four-arm parallel design; 35 participants were randomized to treatment groups: (1) standard Vitamin D₃ 1000 IU (STD1000), (2) micellar Vitamin D₃ 1000 IU (LMD1000), (3) standard Vitamin D₃ 2500 IU (STD2500), and (4) micellar Vitamin D₃ 2500 IU (LMD2500). Serum Vitamin D concentrations were determined through calcifediol [25(OH)D] at baseline (=before treatment), at day 5, 10, and 15 (=during treatment), at day 30 (=end of treatment), and at day 45 and 60 (=during follow-up/post treatment). Safety markers and minerals were evaluated at baseline and at day 30 and day 60. The pharmacokinetic parameters with respect to iAUC were found to be significantly different between LMD1000 vs. STD1000: iAUC(5–60): 992 ± 260 vs. 177 ± 140 nmol day/L; p < 0.05, suggesting up to 6 times higher Vitamin D₃ absorption of LMD when measured incrementally. During follow-up, participants in the LMD1000 treatment group showed approx. 7 times higher Vitamin D₃ concentrations than the STD1000 group (iAUC(30–60): 680 ± 190 vs. 104 ± 91 nmol day/L; p < 0.05). However, no significant differences were found between the pharmacokinetics of the higher dosing groups STD2500 and LMD2500. No significant changes in serum 1,25(OH)₂D concentrations or other biochemical safety markers were detected at day 60; no excess risks of hypercalcemia (i.e., total serum calcium > 2.63 mmol/L) or other adverse events were identified. LMD, a micellar delivery vehicle for microencapsulating Vitamin D₃ (LipoMicel^®), proved to be safe and only showed superior bioavailability when compared to standard Vitamin D at the lower dose of 1000 IU. This study has clinical trial registration: NCT05209425. Full article

Background: Vitamin D plays a vital role in modulating both innate and adaptive immune systems. Therefore, vitamin D deficiency has been associated with higher levels of autoimmune response and increased susceptibility to infections. CYP27B1 encodes a member of the cytochrome P450 superfamily of enzymes. It is instrumental in the conversion of circulating vitamin D (calcifediol) to active vitamin D (calcitriol). This is a crucial step for macrophages to express Cathelicidin Anti-microbial Peptide (CAMP), an anti-bacterial factor released during the immune response. Our recent study indicated that a Crohn’s disease (CD)-associated pathogen known as Mycobacterium avium paratuberculosis (MAP) decreases vitamin D activation in macrophages, thereby impeding cathelicidin production and MAP infection clearance. The mechanism by which MAP infection exerts these effects on the vitamin D metabolic axis remains elusive. Methods: We used two cell culture models of THP-1 macrophages and Caco-2 monolayers to establish the effects of MAP infection on the vitamin D metabolic axis. We also tested the effects of Calcifediol, Calcitriol, and SB203580 treatments on the relative expression of the vitamin D metabolic genes, oxidative stress biomarkers, and inflammatory cytokines profile. Results: In this study, we found that MAP infection interferes with vitamin D activation inside THP-1 macrophages by reducing levels of CYP27B1 and vitamin D receptor (VDR) gene expression via interaction with the TLR2-dependent p38/MAPK pathway. MAP infection exerts its effects in a time-dependent manner, with the maximal inhibition observed at 24 h post-infection. We also demonstrated the necessity to have toll-like receptor 2 (TLR2) for MAP infection to influence CYP27B1 and CAMP expression, as TLR2 gene knockdown resulted in an average increase of 7.78 ± 0.88 and 13.90 ± 3.5 folds in their expression, respectively. MAP infection also clearly decreased the levels of p38 phosphorylation and showed dependency on the p38/MAPK pathway to influence the expression of CYP27B1, VDR, and CAMP which was evident by the average fold increase of 1.93 ± 0.28, 1.86 ± 0.27, and 6.34 ± 0.51 in their expression, respectively, following p38 antagonism. Finally, we showed that calcitriol treatment and p38/MAPK blockade reduce cellular oxidative stress and inflammatory markers in Caco-2 monolayers following macrophage-mediated MAP infection. Conclusions: This study characterized the primary mechanism by which MAP infection leads to diminished levels of active vitamin D and cathelicidin in CD patients, which may explain the exacerbated vitamin D deficiency state in these cases. Full article