calcifediol / Generic mfg. - LARVOL DELTA

Increase in testosterone and cortisol one week after repeated exercise in a cold environment. (PubMed, Front Physiol) - "Circulating levels of testosterone, cortisol, androstenedione, dehydroepiandrosterone sulphate, 17-hydroxyprogesterone, calcifediol, interleukin-6, C-reactive protein, and erythrocyte superoxide dismutase activity were analysed...No significant changes were observed in Interleukin-6, C-reactive protein, or superoxide dismutase levels. A 5-day period of daily exercise in a cold environment showed no immediate effects, but a potential to elicit adaptive changes delayed for up to 7 days, leading to a significant increase in steroid hormones, without changing the testosterone/cortisol ratio."

Journal • CRP • IL6

Synergistic Tuning of Conformational Dynamics, Electron Tunneling, and Substrate Positioning Enhances Electron Transfer in a P450 Chimera for Calcifediol Biosynthesis. (PubMed, Adv Sci (Weinh)) - "In a semi-preparative-scale biotransformation, L21-M5 achieved 3.26 g/L production of calcifediol with 82 % conversion, underscoring its strong industrial potential. These results highlight the efficacy of the proposed ET-optimization strategy and provide a transferable workflow for engineering multi-domain redox biocatalysts."

Journal

An open-label interventional study on efficacy and safety of 25 µg of daily calcifediol capsule versus 100 µg of cholecalciferol sachets in apparently healthy volunteers. (PubMed, J Nutr Sci) - "However, hypercalciuria (spot urine calcium creatinine > 0.2 mg/mg) was noted in 8/46 individuals in the calcifediol group and 5/37 individuals in the cholecalciferol group at final visit with no significant difference between two groups. This study establishes the efficacy and safety of correcting vitamin D deficiency with daily 25 µg calcifediol capsules as an alternative to 4000 IU (100 µg) cholecalciferol sachets."

Clinical • Journal • Renal Calculi

Investigation of the causal effect and molecular signatures of serum hydroxyvitamin D on atherosclerosis: a Mendelian randomization and transcriptomic approach. (PubMed, Korean J Physiol Pharmacol) - "This multi-omics study establishes a causal relationship between serum hydroxyvitamin D levels and atherosclerosis while uncovering potential biomarkers and pathogenic mechanisms through analyses of gene expression, immune infiltration, and signaling pathways. These findings provide valuable insights into atherosclerosis research and may help guide future therapeutic strategies."

Journal • Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Coronary Artery Disease

Calcifediol high-strength formulation for vitamin D deficiency. (PubMed, Aust Prescr) - No abstract available

Journal • Review

Cholecalciferol vs. calcifediol supplementation on visceral adiposity in people with obesity: a real-world retrospective study. (PubMed, Front Nutr) - "Calcifediol supplementation, combined with a MHD, is more effective than cholecalciferol in improving vitamin D status and reducing visceral adiposity in subjects with obesity. These findings support the recommended use of calcifediol supplementation in obesity-related vitamin D deficiency management."

Journal • Real-world evidence • Retrospective data • Genetic Disorders • Obesity

Micronutrient bioavailability: concepts, influencing factors, and strategies for improvement. (PubMed, Front Nutr) - "Certain dietary factors increase the bioavailability of micronutrients: bioavailability can be enhanced by different vitamin forms (e.g., calcifediol is more bioavailable than cholecalciferol; methylfolate is more bioavailable than folic acid), and by the food matrix and nutrient interactions (e.g., fat increases absorption of fat-soluble vitamins; multiple vitamins support iron absorption and metabolism). These include permeation enhancers, lipid-based formulations, nutrient compounding/encapsulation, and phytase to increase bioavailability of minerals trapped by phytic acid. Solutions such as these will help supply highly absorbable and utilizable vitamins and minerals, help close widespread nutritional gaps, and support adequate nutritional status and optimal health across diverse populations worldwide."

Journal • Review • Cardiovascular • Hematological Disorders • Infectious Disease • Ophthalmology • Osteoporosis • Rheumatology

Is vitamin D deficiency a risk factor for obesity-related morbidity, prediabetes, and type 2 diabetes - a literature review and proposals from the experts of the Polish Society of Endocrinology. (PubMed, Endokrynol Pol) - "In the absence of the expected effects, the authors suggest that the dose of VD (usually vitamin D3) be increased or the treatment be switched to calcifediol or alfacalcidol, or calcitriol in special cases such as impaired kidney or liver function. It is important to emphasize the need to individualize the management and monitor blood calcium and creatinine levels during chronic VD therapy, including high-dose therapy."

Journal • Review • Endocrine Disorders • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Vitamins A and D and Their Combinations for Breast and Colorectal Cancers: Analysis of the Clinical, Epidemiological, Preclinical and Transcriptomic Data. (PubMed, Pharmaceuticals (Basel)) - "Preclinical and transcriptomics studies provide compelling evidence that vitamins A and D combinations may be more effective for the prevention and treatment of breast and colon cancers, due to their significant synergistic effects and the larger number of cancer-signaling pathways impacted. Vitamins A and D reduce breast and colorectal cancer incidence, risk and mortality through multiple mechanisms of action, and offer significant potential as therapeutic and chemopreventative agents."

Journal • Preclinical • Review • Breast Cancer • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

VITD: Cholecalciferol and Calcifediol Are Both Useful to Improve Vitamin D Serum Levels (clinicaltrials.gov) - P=N/A | N=90 | Recruiting | Sponsor: Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Nov 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date

Effect of Race, Gender and Age on Intrinsic Diurnal Variation of Serum Calcifediol. (PubMed, J Steroid Biochem Mol Biol) - "No significant differences in rhythmicity were observed between subgroups based on race, gender or age. These data showed that intrinsic diurnal variation of circulating calcifediol is low, suggesting that serum 25D concentrations are highly regulated and that stable circulating levels of 25D reduce the risk of toxicity."

Journal

Vitamin D Metabolome (VDM) Profiles After Single and Repeated Doses of Extended-Release Calcifediol (ERC) in Patients on Hemodialysis (HD) (KIDNEY WEEK 2025) - "DBP, Ca and P remained unchanged versus placebo. Conclusion ERC therapy produced dose-proportional increases in circulating concentrations of total and free calcifediol and 1,25D, decreases in 24,25D 3 ratios and no changes in DBP, Ca or P. Increases in 1,25D likely resulted from substrate-driven production by extra-renal CYP27B1."

Clinical • Late-breaking abstract

Extended-Release Calcifediol (ERC) for Secondary Hyperparathyroidism (SHPT) in Chinese Patients with Stages 3 and 4 CKD: A Phase 3 Trial (KIDNEY WEEK 2025) - "None experienced hypercalciuria (>0.2 Ca:Cr). Conclusion Oral ERC was effective and safe in treating SHPT in Chinese adults with stage 3 or 4 CKD and VDI."

Clinical • Late-breaking abstract • P3 data • Chronic Kidney Disease • Endocrine Disorders • Metabolic Disorders • Secondary Hyperparathyroidism

Vitamin D and chronic kidney disease: mechanisms, clinical implications, and future perspectives. (PubMed, Front Med (Lausanne)) - "A pragmatic approach is warranted: replete deficiency with nutritional vitamin D (prefer D₃; consider calcifediol when faster repletion or persistent SHPT is relevant), avoid mega-bolus dosing, and reserve active VDRAs for clear SHPT indications with careful calcium-phosphate-parathyroid hormone (PTH) monitoring-rather than positioning vitamin D as disease-modifying therapy for unselected CKD. Future trials should enrich truly deficient, higher-risk phenotypes, standardize regimens, and prioritize event-driven hard endpoints with embedded mechanistic markers to confirm on-target biology."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Endocrine Disorders • Fibrosis • Immunology • Inflammation • Metabolic Disorders • Musculoskeletal Diseases • Nephrology • Orthopedics • Renal Disease • Secondary Hyperparathyroidism • Transplantation

Measuring the Rise and Fall of Plasma 25-Hydroxyvitamin D Concentrations in Blue-Tongued Skinks (Tiliqua scincoides) Following Ultraviolet B Exposure and Withdrawal. (PubMed, Vet Sci) - "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."

Journal

Rapid and dose-dependent increase of 25(OH)D levels after calcifediol supplementation in a woman with obesity, chronic liver disease, and osteoporosis. (PubMed, Arch Endocrinol Metab) - "Current guidelines recommend considering calcifediol in cases of obesity, malabsorption syndromes, and chronic hepatic diseases, although optimal dosages remain uncertain. Based on the commercially available tablet in Brazil, we suggest initiating calcifediol at 10 mcg per day and adjusting the dose according to 25(OH)D levels."

Journal • Diabetes • Fibrosis • Gastrointestinal Disorder • Genetic Disorders • Hepatology • Immunology • Metabolic Disorders • Obesity • Osteoporosis • Rheumatology • Type 2 Diabetes Mellitus

Bone disease in kidney transplant: don't forget about osteomalacia: a case report and literature review. (PubMed, Int Urol Nephrol) - "Early recognition of osteomalacia after kidney transplantation and aggressive correction of vitamin D deficiency, phosphate wasting, and hyperparathyroidism can result in rapid symptomatic relief and partial reversal of bone loss. Routine monitoring of mineral metabolism and bone turnover markers should therefore be integrated into post-transplant care to prevent delayed diagnosis. Controlled studies are warranted to define optimal supplementation protocols and thresholds in this population."

Journal • Review • Chronic Kidney Disease • Endocrine Disorders • Immunology • Musculoskeletal Diseases • Musculoskeletal Pain • Nephrology • Orthopedics • Osteoporosis • Pain • Renal Disease • Secondary Hyperparathyroidism • Transplantation

Efficacy of two calcifediol supplementation regimens in older adults post-hip fracture surgery. A clinical trial. (PubMed, Eur Geriatr Med) - P4 | "Both daily and weekly calcifediol regimens effectively corrected vitamin D deficiency in older adults with hip fracture. Functional improvement at discharge was observed in both groups and was clinically relevant."

Clinical • Journal • Musculoskeletal Diseases • Orthopedics

Effects of Short-Term Calcifediol Supplementation on Leukocyte Cytokine Production in Healthy Dogs: A Randomized, Double-Blinded, Placebo-Controlled Crossover Trial. (PubMed, J Vet Intern Med) - "Calcifediol supplementation for 7 days was well-tolerated and decreased LPS-stimulated IL-6 concentrations. Oral calcifediol supplementation may have anti-inflammatory effects in dogs."

Clinical • Journal • Inflammation • Oncology • IL10 • IL6 • TNFA

Randomized trial of activated vitamin D for acute kidney injury prevention in critically ill patients. (PubMed, JCI Insight) - P2 | "Treatment with calcifediol or calcitriol in critically ill adults upregulated multiple genes and pathways involving immunomodulation, DNA repair, and heme metabolism, but did not attenuate AKI."

Clinical • Journal • Acute Kidney Injury • Endocrine Disorders • Immunology • Metabolic Disorders • Nephrology • Renal Disease • CD14 • IFNG

PORTRAY: RAYALDEE Non Interventional Study (NIS) on Effectiveness in ND-CKD SHPT Patients (clinicaltrials.gov) - P=N/A | N=110 | Completed | Sponsor: Vifor (International) Inc. | Active, not recruiting ➔ Completed | Trial completion date: Sep 2025 ➔ Jun 2025

Real-world evidence • Trial completion • Trial completion date • Chronic Kidney Disease • Endocrine Disorders • Nephrology • Renal Disease • Secondary Hyperparathyroidism

Microbial phytase and 25-hydroxy-vitamin D3 fed to growing pigs increase digestibility of calcium and phosphorus and influence plasma vitamin D metabolites and serum bone biomarkers, but effects are not always additive. (PubMed, J Anim Sci) - "The objective was to test the hypothesis that calcifediol [25(OH)D₃] and microbial phytase have additive effects on the standardized total tract digestibility (STTD) of Ca and P, serum bone biomarkers, and plasma vitamin D₃ metabolites when fed to growing pigs...Plasma 1,25(OH)₂D₃ was greater (P < 0.001) in pigs fed the diet with 75% of the required Ca and P and no phytase or 25(OH)D₃ than in pigs fed the PC diet, but microbial phytase decreased (P < 0.001) plasma 1,25(OH)₂D₃. In conclusion, microbial phytase and 25(OH)D₃ increased Ca and P digestibility and serum osteocalcin, and vitamin D₃ status was improved with addition of 25(OH)D₃ to the diet fed to growing pigs, but effects of 25(OH)D₃ and microbial phytase were not always additive."

Biomarker • Journal • FGF23

High-dose extended-release calcifediol successfully treated advanced secondary hyperparathyroidism in an end-stage kidney disease patient: a case report. (PubMed, BMC Nephrol) - "The observations from this case report are consistent with the conclusion from the full RCT with ERC in HD patients that serum 25D repletion can control elevated iPTH in advanced chronic kidney disease by supporting adequate extra-renal 1,25D production. They also indicate that serum 25D levels required for adequate extra-renal 1,25D production and effective iPTH control are much higher than commonly used repletion targets of 20 or 30 ng/mL, and published estimates of serum 25D toxicity thresholds are probably too low for ERC. These observations, however, require substantiation in further clinical trials with ERC in end-stage kidney disease patients."

Journal • Chronic Kidney Disease • Endocrine Disorders • Metabolic Disorders • Nephrology • Renal Disease • Secondary Hyperparathyroidism

Effect of calcifediol on chronic rhinosinusitis, a randomized clinical trial. (PubMed, Rhinology) - "Calcifediol in saline nasal lavage with budesonide results in clinically significant benefits beyond the benefits of saline with budesonide alone for patients with CRS."

Clinical • Journal • Otorhinolaryngology • Respiratory Diseases • Sinusitis

Preoperative serum vitamin D deficiency is associated with increased rotator cuff fatty degeneration but is unlikely to influence post repair outcomes: a systematic review and meta-analysis of correlation coefficients. (PubMed, JSES Rev Rep Tech) - "While higher vitamin D levels are associated with lower rates of rotator cuff FD and possible lower retear rates, it does not necessarily lead to better clinical outcomes post-repair. This study's findings do not justify routine testing and supplementation of vitamin D in patients undergoing RCR."

Journal • Retrospective data • Review • Orthopedics