High-dose Vitamin Research Articles

Repeated High-Dose Vitamin A Supplements, Standard of Care for Treating Xerophthalmia, Leads to Hypervitaminosis A in Piglets

Repeated High-Dose Vitamin A Supplements, Standard of Care for Treating Xerophthalmia, Leads to Hypervitaminosis A in Piglets

Myelodysplastic Syndrome and Hemoglobin Improved by Intravenous Nutrient Therapy: A Case Report

Myelodysplastic syndromes (MDSs) are variations of bone marrow failure disorders that lead to insufficient production of healthy blood cells culminating in some combination of low red blood cells, low white cells, or both. This case report presents a case of increased hemoglobin levels following intravenous (IV) nutrient therapy. J.B. is a 74-year-old male who presented with a chief concern of MDS. He was experiencing extreme fatigue and exhaustion, episodes of shortness of breath and a decline in hemoglobin levels. He was being followed by a hematologist who monitored his complete blood count (CBC) at regular intervals, with primary focus on blood hemoglobin. His hemoglobin levels were significantly lower than the normal range, but never met the threshold for a blood transfusion (< 75 g/dL), his only treatment option. Beginning in November 2021, weekly to biweekly IV nutrient therapy treatments were initiated. In all, 39 IV treatments were given until August 2023. Intravenous nutrient formulas included Myer’s Cocktail, high-dose vitamin C (25 g), Hydrating Myer’s Cocktail and Hydrating Myer’s Cocktail + glutathione. As IV treatments were administered, a trend was observed showing a consistent improvement of hemoglobin levels over time, with the greatest degree of improvement observed after the series of Hydrating Myer’s Cocktails. The patient also reported decreased overall fatigue and reduced recovery time from activity. Delivering a series of IV infusions may have resulted in an improvement of hemoglobin levels in this patient. Further investigation is warranted to understand the potential effects IV nutrient therapy could have on MDS patients with a similar prognosis.

Fattening Pigs with Tannin-Rich Source (Ceratonia siliqua L.) and High Doses of Vitamin E: Effects on Growth Performance, Economics, Digestibility, Physiology, and Behaviour.

This study aimed to assess the impact on growth, economic results, apparent nutrient digestibility (CTTAD), physiological variables, and animal behaviour when 214 fattening pigs (78 ± 8.5 kg of initial body weight and 130 ± 4.5 days of age) of both sexes (gilts and boars) were fed two levels of carob pulp (Cp, 0 vs. 20%) and two doses of vitamin E (Vit E, 30 vs. 300 IU/kg) for 40 days. No interaction effects between factors studied (Cp, Vit E, and sex) were observed on the variables. Most productive traits were unaffected by Cp or Vit E inclusion. However, the Cp increased the feed conversion ratio during the first 20 days. The Cp group showed a higher CTTAD of ether extract and hemicellulose but lower CTTAD of crude protein. Pigs fed Cp had a lower plasmatic urea content than the control group. The high Vit E doses increased the CTTAD of every nutrient and the plasmatic α-tocopherol content. The pigs fed Cp tended to spend more time eating in the early morning, likely to mitigate tannins' astringent effects. Dietary inclusion of 20% Cp in finishing high-conformation pigs is possible without affecting overall performance though it reduces nutrient CTTAD and increases feeding cost. Supra-nutritional doses of Vit E do not affect pig performance but increase the α-tocopherol deposition with potential antioxidant effects.

Usefulness of Vitamin C in critically ill patients: A systematic review

Abstract Background: Vitamin C, also known as ascorbic acid, is an essential micronutrient that plays a key role in fighting systemic inflammation in critically ill patients. Low levels of this vitamin are common in critically ill individuals due to increased oxidative stress. The objective of this study is to investigate and evaluate the use of vitamin C in critically ill patients admitted to intensive care units, with the purpose of identifying its advantages and limitations, and determining its effectiveness in reducing mortality in this group of patients. Material and methods: The present study is a systematic review; previously published articles were searched in the PubMed database. The research was carried out at the university level. 14 results were obtained. Results: Results from clinical and observational studies have been controversial, but some reports suggest improvements in organ function, shorter ICU stays, and reduced mortality in certain patient groups. Other studies did not show a significant change in mortality to justify the use of vitamin C therapy. Conclusion: Controversy regarding clinical results persists; monotherapy with high doses of vitamin C presents a biologically acceptable justification. While we wait for more results, it is important to ensure that critically ill patients receive the recommended dose of vitamin C to keep their immune and metabolic function optimized and ensure daily intake for healthy people.

Hemolysis attributed to high dose vitamin C: Two case reports

BACKGROUND High-dose vitamin C treatment (HVCT) can reduce the adverse effect of chemotherapy and enhance the effect of antitumor therapy, which has been considered one of the safest alternative treatments. However, the severity of its adverse effects may have been underestimated. The most serious adverse effect is hemolysis, which may result in acute kidney injury or death. Although glucose-6-phosphate dehydrogenase (G6PD) deficiency is considered to be the main cause, the probability and pathological mechanism are not completely understood, leading to a lack of effective and standardized treatment methods. CASE SUMMARY Two patients with colorectal cancer developed hemolytic anemia after using 1 g/kg HVCT. In contrast to previous cases, the lowest hemoglobin level in the two cases was < 50 g/L, which was lower than previously reported. This may be because Case 1 had chronic hepatitis B for many years, which caused abnormal liver reserve function, and Case 2 had grade II bone marrow suppression. Both patients improved and were discharged after blood replacement therapy. Our cases had the most severe degree of hemolysis but the best prognosis, suggesting that our treatment may be helpful for rescue of drug-induced hemolysis. This is the first review of the literature on hemolysis caused by HVCT, and we found that all patients with G6PD deficiency developed hemolysis after HVCT. CONCLUSION G6PD deficiency should be considered as a contraindication to HVCT, and it is not recommended for patients with bone marrow suppression, moderate-to-severe anemia, hematopoietic abnormalities, or abnormal liver and kidney function. Early blood purification and steroid therapy may avoid acute kidney injury or death caused by HVCT-related hemolytic anemia.

Use of Theoretical Women and Model-Based Compartmental Analysis to Evaluate the Impact of Vitamin A Intake with or without a Daily Vitamin A Supplement on Vitamin A Total Body Stores and Balance During Lactation

BackgroundInadequate vitamin A (VA) intake is common among lactating women in many communities worldwide, but high-dose VA supplementation for postpartum women is not recommended by the World Health Organization as an effective intervention. ObjectivesTo simulate the impact of VA intake via diet and daily VA supplements on VA total body stores (TBS) and balance in theoretical lactating women with low/moderate TBS. MethodsWe studied 6 theoretical subjects with assigned values for TBS from 219–624 μmol. Using Simulation, Analysis, and Modeling software and a previously published compartmental model for whole-body VA metabolism, we simulated TBS over 6 mo of established lactation for each subject under 4 conditions: 1) prelactation VA intake was increased to maintain VA balance (LSS); 2) prelactation VA intake was maintained (NLSS); 3) VA intake was the same as 2) but a daily VA supplement (2.8 μmol/d) was added (NLSS+S); and 4) VA intake was as 1) and the daily VA supplement was included (LSS+S). ResultsTo compensate for the loss of VA via milk while VA balance was maintained (LSS) over 6 mo of lactation, VA intake had to increase by 0.8–1.87 μmol/d (n = 6) compared with NLSS. Over 6 mo of NLSS treatment, VA balance was negative (geometric mean, −0.77 μmol/d) compared with LSS, whereas balance was positive under NLSS+S and LSS+S conditions (0.75 and 1.5 μmol/d, respectively). For LSS, the proportion of total VA disposal was 37% via breastmilk, 32% from VA stores, and 32% from nonstorage tissues. ConclusionsAdding a daily VA supplement (2.8 μmol/d) to the diet of lactating women with suboptimal VA intake may effectively counterbalance the negative VA balance resulting from the output of VA via breastmilk and thus benefit both mother and infant by maintaining or increasing VA stores and breastmilk VA concentration.

Nutritional and non-nutritional strategies in bodybuilding: Impact on kidney function

Bodybuilders routinely engage in many dietary and other practices purported to be harmful to kidney health. Thus, a structured narrative review of the literature was performed. The search strategy and parameters identifying areas of importance closely followed the PRISMA statement guidelines. This resulted in 13 relevant full-text articles consisting of 8 case reports and 5 case series, published since 2000. Kidney disease was described in 75 bodybuilders, with diagnoses ranging from acute kidney injury (AKI), acute tubular necrosis , focal segmental glomerular sclerosis (FSGS), nephrocalcinosis, acute interstitial nephritis , nephrosclerosis, chronic interstitial nephritis, an assortment of other glomerulonephritides. The development of AKI, FSGS and nephrocalcinosis may be particular risks. There is little evidence that high-protein diets and moderate creatine supplementation pose risks to individuals with normal kidney function though long-term high protein intake in those with underlying impairment of kidney function is inadvisable. The links between anabolic androgenic steroid use and FSGS are stronger, and there are undoubted dangers of nephrocalcinosis in those taking high doses of vitamins A, D and E. Dehydrating practices, including diuretic misuse, and NSAID use also carry potential risks. It is difficult to predict the effects of multiple practices carried out in concert. Investigations into subclinical kidney damage associated with these practices have rarely been undertaken. Future research is warranted to identify the clinical and subclinical harm associated with individual practices and combinations to enable appropriate and timely advice.

Vitamin D add on the standard treatment for myasthenia gravis symptoms following total gastrectomy: a case report

BackgroundMyasthenia gravis (MG) is a long-term autoimmune disorder that affects the neuromuscular junction, causing muscle weakness and fatigue as its primary clinical features. Vitamin D is crucial for both the autoimmune response and skeletal muscle function.Case presentationHere, we presented a case report documenting the substantial improvement in symptoms experienced by a patient who underwent subtotal gastrectomy for gastric cancer following high-dose Vitamin D supplementation. The patient developed generalized MG two months after the surgery and did not respond adequately to pyridostigmine therapy, experiencing a progressive deterioration of the condition. A significant reduction in vitamin D concentration was observed following subtotal gastrectomy. In response, high-dose vitamin D supplementation was administered to the patient. Within one week of treatment, swallowing symptoms improved, enabling the consumption of a small amount of liquid food. By the second week, substantial swallowing and neck function improvements were evident. After one month, the patient regained the ability to straighten the neck while walking and consumed a regular diet despite persistent difficulties chewing hard food.ConclusionsThis case underscores the therapeutic potential of vitamin D in alleviating MG symptoms, particularly in individuals with compromised vitamin D levels following gastrectomy. The observed improvements present a new perspective on the possible involvement of vitamin D supplementation in the management of postoperative MG cases.

Nutraceutical and dietary supplement use in the cancer population: The impact of evidence-based education.

10611 Background: The nutraceutical market is a multi-billion dollar industry. Studies show many cancer patients turn to vitamins and nutraceutical supplements, seeking health improvements post-diagnosis. Despite their popularity, the efficacy & safety of most substances remains unverified through clinical trials. Additionally, interaction with cancer treatments could potentially increase toxicities or diminish chemotherapy effects. In response, our Cancer Center initiated a comprehensive program aimed at enhancing informed decision-making. This involved conducting surveys to understand patient’s attitudes, knowledge, and perceptions about supplement use, alongside evaluating the impact of an educational intervention designed to encourage the discontinuation of self-prescribed vitamins and supplements during cancer treatment. Methods: We utilized a structured survey with open-closed-ended questions to assess dietary supplement use among cancer patients. The survey featured multiple-choice and 1-5 Likert scale questions covering supplement types (e.g., vitamins, minerals, herbs), reasons for use, duration, and timing of use, and beliefs about safety & efficacy. Clinicians also reviewed disclosed non-prescription supplements, advising on their continuation or cessation. Our goal was to understand patient perspectives on supplement use pre & post-educational intervention, among new patients undergoing oral or systemic cancer treatment. We analyzed changes in supplement use with McNemar’s Exact Tests for paired proportions. Results: Following the educational intervention with 144 cancer patients, the proportion not using any supplements rose from 44.4% to 50.0%, hinting at a trend towards discontinuing supplement use. Yet, McNemar’s tests for various supplement categories revealed no statistically significant changes (p>0.05). Of the 73 patients taking supplements and evaluated post-education by a physician, 53.4% were permitted to continue (primarily vitamins), 26% agreed to stop, and 20.5% reaffirmed they would not discontinue use. Of the resistant patients choosing to continue despite medical advice, 93.3% were taking high-dose vitamins, 20% minerals, and 13% herbs/botanical compounds. Conclusions: Supplements are heavily marketed as promoting various anticancer benefits. Our study shows the challenging nature of modifying cancer patients' perceptions. Despite a modest uptick in stopping, a significant portion persisted supplement use post-education, highlighting entrenched beliefs & attitudes. This emphasizes the importance of ongoing, tailored discussions within oncology care to reduce the risks associated with unsupervised supplement use. Our results advocate for incorporating longer-term educational strategies about supplements, underscoring the critical need for evidence-based guidance in managing their use among cancer patients.

Repeated High-Dose Vitamin A Supplements, Standard of Care for Treating Xerophthalmia, Leads to Hypervitaminosis A in Piglets

BackgroundVitamin A (VA) deficiency and excess negatively affect development, growth, and bone health. The World Health Organization’s standard of care for xerophthalmia due to VA deficiency, is 3 high-dose VA supplements of 50,000–200,000 IU, based on age, which may cause hypervitaminosis A in some individuals. ObjectivesThis study measured VA status following 3 VA doses in 2 piglet studies. MethodsIn Study 1, 5 groups of piglets (n = 10/group) were weaned 10 d postbirth to VA-free feed and orally administered 0; 25,000; 50,000; 100,000; or 200,000 IU VA ester on days 0, 1, and 7. On days 14 and 15, the piglets underwent the modified relative dose–response (MRDR) test for VA deficiency, and were killed. Tissues were collected for high-pressure liquid chromatography analysis. Study 2 used the same design in 3 groups (n = 13/group) weaned at 16 d and administered 0; 25,000; and 200,000 IU doses. ResultsIn Study 1 (final weight: 3.6 ± 0.7 kg), liver VA concentration was hypervitaminotic in 40%, 90%, and 100% of 50,000; 100,000; and 200,000 IU groups, respectively. The 25,000 IU group was 100% adequate, and the placebo group was 40% deficient. In Study 2 (final weight: 8.7 ± 0.8 kg), where 200,000 IU could be prescribed to infants with a similar body weight, 31% of the piglets were hypervitaminotic, the 25,000 IU group was 100% VA adequate, and the placebo group was 100% deficient. The MRDR test measured deficiency in 50% and 70% of the placebo group in each study but had 3 false positives among hypervitaminotic piglets in Study 1. ConclusionsRepeated high-dose VA may cause hypervitaminosis, indicating dose sizes may need reduction. The MRDR resulted in false positives in a hypervitaminotic state during malnutrition and should be paired with serum retinyl ester evaluation to enhance VA status assessment in populations with overlapping interventions.

Vitamin C for all?

Vitamin C can be a potential adjunctive treatment option for critically ill individuals due to its pleiotropic effects as electron donor in many enzymatic reactions throughout the body. Recently, several important randomized controlled trials (RCTs) investigating vitamin C in critically ill patients have been published. Two recent large RCTs administering high-dose vitamin C to patients with sepsis and COVID-19 showed signs of harm. Though performed at high standard, these trials had several limitations. Recent studies in cardiac surgery and burns showed decreased cardiac enzymes and improved clinical outcomes after cardiac surgery, and decreased fluid requirements, reduced wound healing time and in-hospital mortality after burns. Vitamin C may hold benefit in the management of other ischemia/reperfusion injury populations, including postcardiac arrest patients and after solid organ transplantation. Currently, covering basal vitamin C requirements during critical illness is recommended, though the exact dose remains to be determined. Future work should address optimal vitamin C timing, since early versus late drug administration are likely distinct, and duration of therapy, where withdrawal-induced injury is possible. Additionally accurate assessment of body stores with determination of individual vitamin requirements is crucial to ascertain patient and subgroups most likely to benefit from vitamin C.

High-dose oral vitamin D: An emerging therapeutic for skin toxicities associated with cancer treatment

High-dose oral vitamin D: An emerging therapeutic for skin toxicities associated with cancer treatment

Network pharmacology and molecular docking technology for exploring the effect and mechanism of high-dose vitamin c on ferroptosis of tumor cells: A review.

To investigate the mechanism by which high-dose vitamin C (HVC) promotes ferroptosis in tumor cells via network pharmacology, vitamin C-related and ferroptosis-related targets were obtained from the PharmMapper and GeneCards databases, respectively, and their common targets were compared using the Venn diagram. Common targets were imported into the STRING database for protein-protein interaction analysis, and core targets were defined. Core targets were enriched for Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways using the R language packages. A map of the core target-based interaction network and a map of the mechanism by which HVC regulates ferroptosis were constructed. A total of 238 vitamin C-related and 721 ferroptosis-related targets were identified, of which 21 targets were common to both. Furthermore, ALDOA, AHCY, LDHB, HSPA8, LGALS3, and GSTP1 were identified as core targets. GO enrichment analysis suggested that the main biological processes included the extrinsic apoptotic signaling pathway and pyruvate metabolic process. KEGG enrichment analysis suggested that HVC regulates ferroptosis mainly through the amino acid and carbohydrate metabolic pathways. The targets were validated by molecular docking. In conclusion, HVC may promote ferroptosis in tumor cells by regulating metabolic pathways, and there is a synergistic effect between HVC and type I ferroptosis inducers. Glycolysis-dependent tumors may be beneficial for HVC therapy. Our study provides a reference for further clinical studies on HVC antitumor therapy.

Safety and efficacy of monthly high-dose vitamin D3 supplementation in children and adolescents with sickle cell disease

Little is known about the impact of vitamin D supplementation on hand grip strength (HGS) and health-related quality of life (HRQoL) in children and adolescents with sickle cell disease (SCD). We aimed to evaluate the safety and efficacy of monthly high-dose vitamin D3 supplementation and its implications on bone mineral density (BMD), HGS, and HRQoL in patients with SCD and healthy controls. The study included 42 children with SCD and 42 healthy matched controls. The study participants were supplemented with high-dose monthly oral vitamin D3. Changes in the serum level of 25(OH) vitamin D3, maximum HGS, and BMD from baseline to 6 months were assessed, and the HRQoL questionnaire and Childhood Health Assessment Questionnaire (CHAQ) were used to evaluate the functional capacity. At baseline, SCD subjects had poorer growth status indicated by negative Z scores. Suboptimal BMD was detected by significantly lower Z score, and lower HGS and worse HRQL parameters were found compared to the controls (P < 0.001). Median 25(OH) vitamin D3 was significantly lower in SCD patients compared to controls (16.5 vs. 28 ng/mL, respectively (P < 0.001)). After 6 months of vitamin D supplementation, there was significant improvement in the DEXA Z-score (P < 0.001), limitation of physical health (P = 0.02), pain scores (P < 0.001), and CHAQ grades (P = 0.01) in SCD patients. A significant improvement in HGS (P < 0.001 and P = 0.005) as well as the CHAQ score (P < 0.001 and P = 0.003) was detected in the SCD group and controls, respectively. There were no reported clinical adverse events (AEs) or new concomitant medications (CMs) during the study duration, and safe levels of Ca and 25 (OH) D3 were observed at 3 and 6 months for both groups. There was a significant positive correlation between HGS and total physical score (r = 0.831, P < 0.001) and a negative correlation with CHAQ score (r = − 0.685, P < 0.001). We also detected a significant positive correlation between vitamin D levels at 6 months and HGS (r = 0.584, P < 0.001), pain score (r = 0.446, P < 0.001), and a negative correlation with CHAQ score (r = − 0.399, P < 0.001). Conclusion: Monthly oral high-dose vitamin D supplementation was safe and effective in improving vitamin D levels, HGS, and HRQoL in SCD children and healthy subjects, and BMD scores in SCD patients. Further randomized controlled trials are warranted to assess an optimal dosing strategy and to investigate the impact on clinically significant outcomes in children and adolescents with SCD and their healthy counterparts. Trial registration: ClinicalTrials.gov, identifier NCT06274203, date of registration: 23/02/2024, retrospectively registered.What is known:• Several studies have reported a high prevalence of vitamin D deficiency and suboptimal bone mineral density (BMD) in sickle cell disease (SCD) patients.• Musculoskeletal dysfunction is reported in SCD patients with a negative impact on physical activity and health-related quality of life (HRQL).• Little is known regarding the impact of vitamin D3 supplementation in children and adolescents with SCD.What is new:• We found that monthly oral high-dose vitamin D3 supplementation was safe, tolerated, and effective in improving serum vitamin D levels, HGS, BMD scores, and HRQL in SCD patients.

Resolution of the national interdisciplinary council of experts "High-dose vitamin D (Devilam) in the practice of an obstetrician-gynecologist"

On March 28, 2024, the Council of Experts "High-dose vitamin D (Devilam) in the practice of obstetrician-gynecologist, gynecologist and endocrinologist" was held in Moscow with the participation of leading experts gynecologists, endocrinologists and obstetricians-gynecologists, during which new possibilities for the use of high-dose vitamin D in patients of various ages who need correction of existing vitamin D deficiency or insufficiency.

Treatment of severe radiation proctitis with high dosage of vitamin C in combination with cyclooxygenase-2 inhibitor

ObjectiveTo explore the new treatment strategies for radiation proctitis, which is the most common complication of pelvic tumor malignancies. MethodsFour cases of patients with severe radiation proctitis were treated with high-dosage vitamin C (VC, 12–24 ​g/d, iv) combined with cyclooxygenase-2 (cyclooxygenase-2, COX-2) inhibitors. ResultsFor these four cases, the diarrhea, hematochezia, tenesmus, pain, and other symptoms were significantly improved. The edema of the rectal wall is also significantly improved in the imaging review. ConclusionThe high-dosage VC combined with the treatment of severe radiation proctitis is safe and effective.

DESIGN, DEVELOPMENT AND IMPROVEMENT OF AN EMULGEL CONTAINING SILVER NANOPARTICLES AND VITAMIN D-3 FOR ITS POTENTIAL TO ACCELERATE THE HEALING OF WOUND

Objective: The aim of this research work was to prepare a topical emulgel based dosage form incorporated with vitamin D-3 and silver nanoparticles to reduce the wound healing time in any kind of wound. Methods: Central Composite Design (CCD) was applied for the optimization of emulgel by using Design expert software. Three responses (pH, viscosity, and in vitro drug release) and two factors (Carbopol concentration and stirring duration) were chosen, and Statistical Analysis of Variance (ANOVA) revealed that all the factors were significantly affecting the responses. Silver Nanoparticles (SNPs) was prepared with Green Tea Extract (GTE) and evaluated for particle size, Poly Dispersity Index (PDI), zeta potential and Fourier Transform Infra-red (FTIR) spectroscopy and revealed that SNPs of desired range and stability have been synthesized. Here excision wound model was used to evaluate the wound healing activity of formulation in vivo. Results: Maximum in vitro release 88.2±2.1 has shown by the optimized formulation F13, pH and viscosity were also found in optimum range i.e., 6.2±0.4 and 1672±33 respectively, followed by Korsmeyer and Peppas model. Total eight groups were designed for animal study and silver sulphadiazine was used as marketed formulation. F13 formulation was further evaluated for in vivo data, it was revealed that emulgel loaded with high dose of vitamin D-3 along with silver nanoparticles has shown 100.5±1.7% wound contraction, while marketed formulation has shown 103.7±1.1% wound contraction, which was much similar with test formulation. Cytotoxic cell study was done using assay on chicken egg, formulation has not shown any cytotoxic behaviour like haemolysis and cell damage on chick embryo’s blood vessels. Accelerated stability study of the optimized formulation was also performed to check whether the formulation was stable or not and it was revealed that optimized formulation was found stable for the period of six months. Conclusion: It was revealed that emulgel loaded with high dose of vitamin D-3 and SNPs found suitable to accelerate wound healing and showed almost similar response in wound contraction on comparison with marketed formulation. This emulgel promised to controlled the delivery of the drug for the longer duration.

Novel homozygous pathogenic variant in the Vitamin-D binding protein in a patient with undetectable Vitamin D levels despite treatment with high doses of vitamin D

Novel homozygous pathogenic variant in the Vitamin-D binding protein in a patient with undetectable Vitamin D levels despite treatment with high doses of vitamin D

Administration of high dose vitamin E in female rabbits with hypercholesterolemia increases acutely androgen levels: an animal model study

Administration of high dose vitamin E in female rabbits with hypercholesterolemia increases acutely androgen levels: an animal model study

Outcomes of High-Dose Versus Low-Dose Vitamin D on Prognosis of Sepsis Requiring Mechanical Ventilation: A Randomized Controlled Trial.

Background: Critically ill patients with sepsis have a high incidence of vitamin D deficiency. Vitamin D promotes the synthesis of human cathelicidin antimicrobial peptide, a precursor of LL-37, which is a part of the innate immune system. This study investigated the effectiveness and safety of the early administration of high-dose enteral vitamin D3 in comparison with low-dose vitamin D3 in patients with sepsis requiring mechanical ventilation (MV). Methods: Eighty adult patients with sepsis requiring MV with known vitamin D deficiency were randomly assigned to receive either an enteral 50 000 IU (Group I) or 5000 IU (Group II) vitamin D supplementation. Clinical and laboratory parameters were evaluated at baseline and on days 4 and 7 between the study groups. The change in serum procalcitonin (PCT) levels on day 7 was the primary outcome, while the change in serum LL-37 levels on day 7, changes in sequential organ failure assessment (SOFA) score, and clinical pulmonary infection score on day 7, MV duration, and hospital length of stay (LOS) were the secondary outcomes. Results: The (day 7-day 0) change in serum PCT and LL-37 levels and SOFA score were significantly different in Group I (P = .010, P < .001, and P < .001, respectively). The SOFA score was significantly different on days 4 and 7 in Group I (P < .001 and P < .001, respectively). The incidence of early ventilator-associated pneumonia was significantly different between both treatment groups (P = .025). The hospital LOS was shorter in Group I (P < .001). No 25-hydroxyvitamin-D toxicity was observed in either group. Conclusions: Early enteral administration of high-dose vitamin D3 in critically ill patients with sepsis requiring MV along with standard treatment for sepsis decreased serum procalcitonin levels, increased serum LL-37 levels, and ameliorated illness severity scores.