Intravenous Vitamin Research Articles

Intravenous vitamin C therapy in adult patients with sepsis: A rapid practice guideline.

This Rapid Practice Guideline provides an evidence-based recommendation to address the question: in adults with sepsis or septic shock, should we recommend using or not using intravenous vitamin C therapy? The panel included 21 experts from 16 countries and used a strict policy for potential financial and intellectual conflicts of interest. Methodological support was provided by the Guidelines in Intensive Care, Development, and Evaluation (GUIDE) group. Based on an updated systematic review, and the grading of recommendations, assessment, development, and evaluation approach, we evaluated the certainty of evidence and developed recommendations using the evidence-to-decision framework. We conducted an electronic vote, requiring >80% agreement among the panel for a recommendation to be adopted. At longest follow-up, 90 days, intravenous vitamin C probably does not substantially impact (relative risk 1.05, 95% confidence interval [CI] 0.94 to 1.17; absolute risk difference 1.8%, 95% CI -2.2 to 6.2; 6 trials, n = 2148, moderate certainty). Effects of vitamin C on mortality at earlier timepoints was of low or very low certainty due to risk of bias of the included studies and significant heterogeneity between study results. Few adverse events were reported with the use of vitamin C. The panel did not identify any major differences in other outcomes, including duration of mechanical ventilation, ventilator free days, hospital or intensive care unit length of stay, acute kidney injury, need for renal replacement therapy. Vitamin C may result in a slight reduction in duration of vasopressor support (MD -18.9 h, 95% CI -26.5 to -11.4; 21 trials, n = 2661, low certainty); but may not reduce sequential organ failure assessment scores (MD -0.69, 95% CI -1.55 to 0.71; 24 trials, n = 4002, low certainty). The panel judged the undesirable consequences of using IV vitamin C to probably outweigh the desirable consequences, and therefore issued a conditional recommendation against using IV vitamin C therapy in sepsis. The panel suggests against use of intravenous vitamin C in adult patients with sepsis, beyond that of standard nutritional supplementation. Small and single center trials on this topic should be discouraged.

Adjunctive intravenous then oral vitamin C for moderate and severe community-acquired pneumonia in hospitalized adults: feasibility of randomized controlled trial

Patients hospitalised with community acquired pneumonia (CAP) have low peripheral blood vitamin C concentrations and limited antioxidant capacity. The feasibility of a trial of vitamin C supplementation to improve patient outcomes was assessed. Participants with moderate and severe CAP (CURB-65 ≥ 2) on intravenous antimicrobial treatment were randomised to either intravenous vitamin C (2.5 g 8 hourly) or placebo before switching to oral intervention (1 g tds) for 7 days when they were prescribed oral antimicrobial therapy. Of 344 patients screened 75 (22%) were randomised and analysed. The median age was 76 years, and 43 (57%) were male. In each group, one serious adverse event that was potentially intervention related occurred, and one subject discontinued treatment. Vitamin C concentrations were 226 µmol/L in the vitamin C group and 19 µmol/L in the placebo group (p < 0.001) after 3 intravneous doses. There were no signficant differences between the vitamin C and placebo groups for death within 28 days (0 vs. 2; p = 0.49), median length of stay (69 vs. 121 h; p = 0.07), time to clinical stability (22 vs. 49 h; p = 0.08), or readmission within 30 days (1 vs. 4; p = 0.22). The vitamin C doses given were safe, well tolerated and saturating. A randomised controlled trial to assess the efficacy of vitamin C in patients with CAP would require 932 participants (CURB-65 ≥ 2) to observe a difference in mortality and 200 participants to observe a difference with a composite endpoint such as mortality plus discharge after 7 days in hospital. These studies are feasible in a multicentre setting.

Intravenous vitamin C for vasoplegia: A double-blinded randomised clinical trial (VALENCIA trial)

PurposeTo determine whether intravenous vitamin C compared with placebo, reduces vasopressor requirements in patients with vasoplegic shock. MethodsDouble-blinded, randomised clinical trial (RCT) conducted in two intensive care units in Perth, Australia. Vasopressor requirements at enrolment needed to be >10 μg/min noradrenaline after hypovolaemia was clinically excluded. Patients received either intravenous 1.5 g sodium ascorbate in 100 ml normal saline every 6 h for 5 days, or placebo (100 ml normal saline). The primary outcome was duration of vasopressor usage in hours. Secondary outcomes were ICU and hospital length of stay, and 28-day, ICU and hospital mortality. ResultsOf the 71 patients randomised (35 vitamin C, 36 placebo group), the median vasopressor duration was 44 h [95% CI, 37–54 h] and 55 h [95% CI, 33–66 h]) in the vitamin C and placebo groups (p = 0.057). ICU and hospital length of stay, mortality outcomes were similar between groups. ConclusionsIn this RCT of patients with vasoplegic shock of at least moderate severity, the use of IV vitamin C compared with placebo did not significantly reduce the duration of vasopressors. Trial registrationProspective registration – trial number ACTRN12617001392358.

EFFECTS OF MEGA DOSE VITAMIN C IN CRITICALLY ILL COVID-19 PATIENTS: A RANDOMIZED CONTROL TRIAL

Severe acute respiratory coronavirus 2 (SARS-CoV-2), COVID-19, caused a pandemic that took millions of lives worldwide. The main reason is a lack of preparedness and knowledge about the treatment options. With the advancement in the understanding of the SARS-CoV-2 virus, many treatment options have been analyzed that helped effectively to decrease the mortality caused by this virus. Vitamin C is known to boost immunity and slow down the progression of viral infection. The current study was designed to assess the effectiveness of a high dose of intravenous (IV) vitamin C in COVID-19 infection. The clinical trial registered on 23/12/2020 at ClinicalTrials.gov (NCT04682574) was conducted in Bahria Town International Hospital, Lahore (BTIHL), Fatima Memorial Hospital, Lahore (FMH), and Evercare Hospital Lahore from 28/12/2020 to 10/4/2022. Two hundred seventy-eight critically ill patients with COVID-19 were categorized into two groups. One hundred thirty-nine patients were randomized in group VC (vitamin C), which was given a high dose (30 grams) of intravenous (IV) vitamin C for four days, whereas distilled water as a placebo was given to the control group (n=139) along with standard treatment protocols. All the patients were analyzed for primary outcomes in partial pressure of arterial oxygen (PaO2) to Fraction inspired oxygen (P/F) ratio and survival analysis. At the same time, levels of inflammatory and biochemical markers needed for intubation and length of hospital stay in both groups were compared as the study's secondary endpoint. Among the two groups, we did not find any differences in 28-day mortality (Log Rank P= 0.11). Similarly, no difference in the P/F ratio on the fourth day after the start of IV vitamin C treatment was noted (p=0.24). The median values of biochemical and inflammatory variables improved significantly in group VC on day 4. However, only hemoglobin levels remained non-significant between the groups. Mean days of hospital stay were slightly longer in group C. However, no statistical significance (p=0.941) was found. Although Group VC needed fewer intubations than Group C, results remained statistically insignificant (p= 0.273). This trial did not find any mortality benefit or improvement of the P/F ratio in critically ill patients. However, the VC group showed improvement in biochemical variables of prognostic importance, which seems to lower the chance of intubation and LOS in group VC. A further clinical trial with a large sample size is needed to reach the final conclusion.

Vitamin C in critical illness: end of the story or still a place?

Critical illness is associated with decreased micronutrient levels, including vitamin C, an essential antioxidant for systemic inflammation. This review discusses the most recent evidence of high-dose vitamin C monotherapy in critically ill adults. Three randomized-controlled trials (RCTs) were published in 2022. A pilot study including 40 patients with septic shock could not detect significant differences in outcome parameters after administering vitamin C. A multicenter study with 124 septic patients showed no significant difference in 28-day mortality, while vitamin C was associated with an increased risk of acute kidney dysfunction. The LOVIT trial, an international prospective RCT in 872 septic patients, revealed an increased risk of the composite endpoint persistent organ dysfunction plus death at day 28 in the high-dose vitamin C group. Six systematic reviews and meta-analyses (SRMA), including up to 4740 patients published before and 2 SRMA publications including these RCTs showed divergent results on clinical endpoints including mortality. The use of high-dose intravenous vitamin C cannot be recommended for the septic critically ill in clinical practice since the LOVIT trial. Further research is needed to evaluate its potential role in other critically ill patients.

Vitamin C for Offspring Pulmonary Protection from Maternal Smoking

Rigorously designed randomized controlled trials (RCTs) and meta-analysis of RCTs have failed to show a consistent efficacy for vitamin C supplementation in the intervention of common human diseases, including cardiovascular disorders, sepsis, diabetes, and cancer. It, however, has been becoming increasingly evident that vitamin C supplementation for pregnant smokers may be an effective modality for improving offspring airway function and pulmonary health. This Cutting-Edge Research Highlights article summarizes the latest clinical research development regarding vitamin C-mediated offspring pulmonary protection from maternal smoking. (First online: June 4, 2023) REFERENCES Sauberlich HE. Pharmacology of vitamin C. Annu Rev Nutr 1994; 14:371–91. doi: https://dx.doi.org/10.1146/annurev.nu.14.070194.002103 Young JI, Zuchner S, Wang G. Regulation of the epigenome by vitamin C. Annu Rev Nutr 2015; 35:545–64. doi: https://dx.doi.org/10.1146/annurev-nutr-071714-034228 An P, Wan S, Luo Y, Luo J, Zhang X, Zhou S, et al. Micronutrient supplementation to reduce cardiovascular risk. J Am Coll Cardiol 2022; 80(24):2269–85. doi: https://dx.doi.org/10.1016/j.jacc.2022.09.048 Sesso HD, Buring JE, Christen WG, Kurth T, Belanger C, MacFadyen J, et al. Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. JAMA 2008; 300(18):2123–33. doi: https://dx.doi.org/10.1001/jama.2008.600 Lamontagne F, Masse MH, Menard J, Sprague S, Pinto R, Heyland DK, et al. Intravenous vitamin C in adults with sepsis in the intensive care unit. N Engl J Med 2022; 386(25):2387–98. doi: https://dx.doi.org/10.1056/NEJMoa2200644 Mason SA, Keske MA, Wadley GD. Effects of vitamin C supplementation on glycemic control and cardiovascular risk factors in people with type 2 diabetes: a GRADE-assessed systematic review and meta-analysis of randomized controlled trials. Diabetes Care 2021; 44(2):618–30. doi: https://dx.doi.org/10.2337/dc20-1893 Zheng JS, Luan J, Sofianopoulou E, Imamura F, Stewart ID, Day FR, et al. Plasma vitamin C and type 2 diabetes: genome-wide association study and mendelian randomization analysis in european populations. Diabetes Care 2021; 44(1):98–106. doi: https://dx.doi.org/10.2337/dc20-1328 Creagan ET, Moertel CG, O'Fallon JR, Schutt AJ, O'Connell MJ, Rubin J, et al. Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer: a controlled trial. N Engl J Med 1979; 301(13):687–90. doi: https://dx.doi.org/10.1056/NEJM197909273011303 Moertel CG, Fleming TR, Creagan ET, Rubin J, O'Connell MJ, Ames MM. High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy: a randomized double-blind comparison. N Engl J Med 1985; 312(3):137–41. doi: https://dx.doi.org/10.1056/NEJM198501173120301 Lin J, Cook NR, Albert C, Zaharris E, Gaziano JM, Van Denburgh M, et al. Vitamins C and E and beta carotene supplementation and cancer risk: a randomized controlled trial. J Natl Cancer Inst 2009; 101(1):14–23. doi: https://dx.doi.org/10.1093/jnci/djn438 Tsuchiya M, Asada A, Kasahara E, Sato EF, Shindo M, Inoue M. Smoking a single cigarette rapidly reduces combined concentrations of nitrate and nitrite and concentrations of antioxidants in plasma. Circulation 2002; 105(10):1155–7. doi: https://dx.doi.org/10.1161/hc1002.105935 McEvoy CT, Schilling D, Clay N, Jackson K, Go MD, Spitale P, et al. Vitamin C supplementation for pregnant smoking women and pulmonary function in their newborn infants: a randomized clinical trial. JAMA 2014; 311(20):2074–82. doi: https://dx.doi.org/10.1001/jama.2014.5217 McEvoy CT, Shorey-Kendrick LE, Milner K, Schilling D, Tiller C, Vuylsteke B, et al. Oral vitamin C (500 mg/d) to pregnant smokers improves infant airway function at 3 months (VCSIP): a randomized trial. Am J Respir Crit Care Med 2019; 199(9):1139–47. doi: https://dx.doi.org/10.1164/rccm.201805-1011OC McEvoy CT, Shorey-Kendrick LE, Milner K, Schilling D, Tiller C, Vuylsteke B, et al. Vitamin C to pregnant smokers persistently improves infant airway function to 12 months of age: a randomised trial. Eur Respir J 2020. doi: https://dx.doi.org/10.1183/13993003.02208-2019 McEvoy CT, Shorey-Kendrick LE, Milner K, Harris J, Vuylsteke B, Cunningham M, et al. Effect of vitamin C supplementation for pregnant smokers on offspring airway function and wheeze at age 5 years: follow-up of a randomized clinical trial. JAMA Pediatr 2023; 177(1):16–24. doi: https://dx.doi.org/10.1001/jamapediatrics.2022.4401 Moshammer H, Hoek G, Luttmann-Gibson H, Neuberger MA, Antova T, Gehring U, et al. Parental smoking and lung function in children: an international study. Am J Respir Crit Care Med 2006; 173(11):1255–63. doi: https://dx.doi.org/10.1164/rccm.200510-1552OC Toppila-Salmi S, Luukkainen AT, Xu B, Lampi J, Auvinen J, Dhaygude K, et al. Maternal smoking during pregnancy affects adult onset of asthma in offspring: a follow up from birth to age 46 years. Eur Respir J 2020; 55(6). doi: https://dx.doi.org/10.1183/13993003.01857-2019

Forestalling Hungry Bone Syndrome after Parathyroidectomy in Patients with Primary and Renal Hyperparathyroidism.

overview HBS following PTx according to a dual perspective: pre- and post-operative outcome in PHPT and RHPT. This is a case- and study-based narrative review. key research words "hungry bone syndrome" and "parathyroidectomy"; PubMed access; in extenso articles; publication timeline from Inception to April 2023. non-PTx-related HBS; hypoparathyroidism following PTx. We identified 120 original studies covering different levels of statistical evidence. We are not aware of a larger analysis on published cases concerning HBS (N = 14,349). PHPT: 14 studies (N = 1545 patients, maximum 425 participants per study), and 36 case reports (N = 37), a total of 1582 adults, aged between 20 and 72. Pediatric PHPT: 3 studies (N = 232, maximum of 182 participants per study), and 15 case reports (N = 19), a total of 251 patients, aged between 6 and 18. RHPT: 27 studies (N = 12,468 individuals, the largest cohort of 7171) and 25 case reports/series (N = 48), a total of 12,516 persons, aged between 23 and 74. HBS involves an early post-operatory (emergency) phase (EP) followed by a recovery phase (RP). EP is due to severe hypocalcemia with various clinical elements (<8.4 mg/dL) with non-low PTH (to be differentiated from hypoparathyroidism), starting with day 3 (1 to 7) with a 3-day duration (up to 30) requiring prompt intravenous calcium (Ca) intervention and vitamin D (VD) (mostly calcitriol) replacement. Hypophosphatemia and hypomagnesiemia may be found. RP: mildly/asymptomatic hypocalcemia controlled under oral Ca+VD for maximum 12 months (protracted HBS is up to 42 months). RHPT associates a higher risk of developing HBS as compared to PHPT. HBS prevalence varied from 15% to 25% up to 75-92% in RHPT, while in PHPT, mostly one out of five adults, respectively, one out of three children and teenagers might be affected (if any, depending on study). In PHPT, there were four clusters of HBS indicators. The first (mostly important) is represented by pre-operatory biochemistry and hormonal panel, especially, increased PTH and alkaline phosphatase (additional indicators were elevated blood urea nitrogen, and a high serum calcium). The second category is the clinical presentation: an older age for adults (yet, not all authors agree); particular skeleton involvement (level of case reports) such as brown tumors and osteitis fibrosa cystica; insufficient evidence for the patients with osteoporosis or those admitted for a parathyroid crisis. The third category involves parathyroid tumor features (increased weight and diameter; giant, atypical, carcinomas, some ectopic adenomas). The fourth category relates to the intra-operatory and early post-surgery management, meaning an associated thyroid surgery and, maybe, a prolonged PTx time (but this is still an open issue) increases the risk, as opposite to prompt recognition of HBS based on calcium (and PTH) assays and rapid intervention (specific interventional protocols are rather used in RHPT than in PHPT). Two important aspects are not clarified yet: the use of pre-operatory bisphosphonates and the role of 25-hydroxyitamin D assay as pointer of HBS. In RHPT, we mentioned three types of evidence. Firstly, risk factors for HBS with a solid level of statistical evidence: younger age at PTx, pre-operatory elevated bone alkaline phosphatase, and PTH, respectively, normal/low serum calcium. The second group includes active interventional (hospital-based) protocols that either reduce the rate or improve the severity of HBS, in addition to an adequate use of dialysis following PTx. The third category involves data with inconsistent evidence that might be the objective of future studies to a better understanding; for instance, longer pre-surgery dialysis duration, obesity, an elevated pre-operatory calcitonin, prior use of cinalcet, the co-presence of brown tumors, and osteitis fibrosa cystica as seen in PHPT. HBS remains a rare complication following PTx, yet extremely severe and with a certain level of predictability; thus, the importance of being adequately identified and managed. The pre-operatory spectrum of assessments is based on biochemistry and hormonal panel in addition to a specific (mostly severe) clinical presentation while the parathyroid tumor itself might provide useful insights as potential risk factors. Particularly in RHPT, prompt interventional protocols of electrolytes surveillance and replacement, despite not being yet a matter of a unified, HBS-specific guideline, prevent symptomatic hypocalcemia, reduce the hospitalization stay, and the re-admission rates.

Randomized placebo-controlled trial of intravenous vitamin C plus docetaxel in metastatic prostate cancer.

e17050 Background: Some phase I/II trials showed that combining high dose IV vitamin C with chemotherapies decreased toxicities and improved QoL in advanced cancers, while others failed to show benefits. While grade ¾ AEs are not typically a co-primary endpoint, they are a measure of cumulative toxicity. We investigated whether high-dose IV vitamin C could improve prostate-specific antigen (PSA) response rate and mitigate docetaxel toxicities in patients with metastatic castrate-resistant prostate cancer (mCRPC) receiving docetaxel. Methods: Patients were randomized (2:1) to receive docetaxel (75mg/m2 IV every 3 weeks) plus IV vitamin C (1g/kg) or placebo twice a week. The primary endpoints were PSA50 response by24 weeks and adverse events (AEs) of fatigue, nausea, bone pain, and anorexia. Secondary endpoints included overall survival (OS) and QoL measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P). Results: 50 patients were randomized, 47 received therapy (treatment N = 32, control N = 15), 3 untreated (withdrawal, elevated creatine, low hemoglobin). The median age was 74 years (range 45-85) and ECOG 1. The median PSA was 108.3 ng/mL (range: 0.3, 2102.3). The median number of chemotherapy cycles was 6 (IQR 3-8). The study was suspended after the pre-specified interim analysis for primary endpoints showed futility. The PSA50 response was 41% for treatment and 33% for control (P = 0.44). Grade 1-2 and grade 3-4 prespecified AEs occurred in 69% and 6% of treatment group patients versus 60% and 0% of control group patients (one-sided Cochran Armitage test, P =0.90). Diarrhea (72% vs 19%) and anemia (47% vs 25%) and neutropenia (22% vs 19%) are more frequent in the Vit C group. Compared with the control group, treatment group patients showed a trend towards shorter median OS. FACT-P was not significantly different at any timepoints. Conclusions: Initial concurrent high-dose IV vitamin C with docetaxel did not improve PSA response, toxicity, or clinical outcomes. MCRPC patients receiving docetaxel should be advised against seeking concurrent high-dose IV vitamin C. Clinical trial information: NCT02516670 .

Effect of vitamin C on coagulation factors and endothelium function in patients with sepsis

Objective: Sepsis is one of the leading causes of mortality in intensive care unit. Despite advances in its management, its mortality rate remains high. Recently, high dose of vitamin C in sepsis treatment has attracted the attention of researchers. In the current study, the impacts of 25 mg/kg of vitamin C every 6 hours as a bolus for 3 days were assessed in septic patients in intensive care unit (ICU).&#x0D; Methods: This was a prospective cohort study that was performed on adult patients with diagnosis of sepsis. Patients were assigned to control group (administration of placebo) or intervention group, i.e., those receiving a 25 mg/kg dose of vitamin C every 6 hours as a bolus for 3 days. Clinical data were recorded before and after the experiment. Also, plasma levels of antithrombin III, syndecan-1, fibrin degradation product (FDP), D-dimer, and C-reactive protein (CRP) were measured at 0, 24, 48, and 72 hours.&#x0D; Results: In septic patients receiving vitamin C, a significant upregulation of antithrombin III and significant decreases in the levels of syndecan-1 (at 48 hours; P-value=0.046 and at 72 hours; P-value=0.007), D-dimer and CRP were observed compared to the control. Reductions in sequential organ failure assessment (SOFA) score, in-hospital mortality, and ICU length of stay were seen in septic patients receiving vitamin C.&#x0D; Conclusion: Prescribing high dose of intravenous vitamin C can reduce the mortality of sepsis patients and reduce the length of stay in the ICU.

High-dose intravenous versus low-dose oral vitamin C in burn care: potential protective effects in the severely burned: a retrospective cohort study.

The hospital burn database was used to obtain data on all patients with second-degree or deeper burns of 20% total-body-surface-area or greater. Fourteen patients were selected at random to receive a scheduled dose of 1250mg intravenous ascorbic acid every 6h for 72h. This was considered the high-dose group. During same period, 40 patients received scheduled 500mg oral ascorbic acid every 6h for 72h and this was considered the low-dose group. We gathered sociodemographic and clinical variables associated with ascorbic acid dosing. In our study, statistically significant variables were fluid requirements (p<0.001), hospital stay (p=0.011), length of time intubated on ventilator (p<0.001), colloids used (p=0.002), and total procedures required (p=0.014). Despite higher modified Baux predicted mortality in the high-dose group (10 patients vs. 24 patients, p=0.026) there was no noted significant association in days until the first infection and mortality rate (p=0.451 and 0.326, respectively). The calculated modified Baux predicted a higher mortality rate with the higher dosing group, yet this study did not find a mortality difference between the groups. We speculate that high-dose intravenous ascorbic acid may have protective effects in burn resuscitation. This finding may support some previous studies that found that high-dose ascorbic acid may improve clinical outcomes.

The redox metabolome of humans receiving supraphysiological doses of intravenous vitamin C

The redox metabolome of humans receiving supraphysiological doses of intravenous vitamin C

Nitrous Oxide-Induced Subacute Combined Degeneration in a 38-Year-Old Pregnant Female After Recreational Use

Nitrous oxide (N2O) misuse creates a diagnostic dilemma due to its clinical presentation, difficulty in identification, and toxicity related to its chronic abuse, with resultant morbidity and mortality. Chronic abuse can lead to myeloneuropathy and subacute combined degeneration in otherwise healthy individuals. Health professionals should be aware of the commercial availability and abuse of N2O by the public, and N2O toxicity should be included in the differential diagnosis in patients presenting with myelopathy of unknown etiology. A case report was conducted on a 38-year-old female at approximately 30 weeks of gestation who presented to the emergency department with worsening bilateral lower extremity numbness, tingling, and weakness. The patient admitted to nitrous oxide inhalation during the two months prior to admission. She reported using four cans of whippets per week (approximately 8 g of N2O per whippet) up to 50 cans per day (400 g N2O) prior to the onset of symptoms. An MRI of the cervical spine was performed, showing T2 hyperintensity from C2 to C6 involving dorsal columns indicative of subacute combined degeneration. The patient was treated with intravenous vitamin B12 due to the clinical and radiographic evidence of nitrous oxide-induced myelopathy. The pathophysiology of N2O toxicity involves the oxidation of the cobalt atom of cobalamin (vitamin B12) from its reduced active 1+ valent state to its oxidized inactive 3+ valent state. This oxidation inactivates the enzyme methionine synthetase. B12 is an essential cofactor for downstream DNA synthesis. Consequently, excess N2O creates functional B12 deficiency leading to irreversible nerve damage if left undiagnosed and untreated.

Association of Oral or Intravenous Vitamin C Supplementation with Mortality: A Systematic Review and Meta-Analysis.

Mortality is the most clinically serious outcome, and its prevention remains a constant struggle. This study was to assess whether intravenous or oral vitamin C (Vit-C) therapy is related to reduced mortality in adults. Data from Medline, Embase, and the Cochrane Central Register databases were acquired from their inception to 26 October 2022. All randomized controlled trials (RCTs) involving intravenous or oral Vit-C against a placebo or no therapy for mortality were selected. The primary outcome was all-cause mortality. Secondary outcomes were sepsis, COVID-19, cardiac surgery, noncardiac surgery, cancer, and other mortalities. Forty-four trials with 26540 participants were selected. Although a substantial statistical difference was observed in all-cause mortality between the control and the Vit-C-supplemented groups (p = 0.009, RR 0.87, 95% CI 0.78 to 0.97, I2 = 36%), the result was not validated by sequential trial analysis. In the subgroup analysis, mortality was markedly reduced in Vit-C trials with the sepsis patients (p = 0.005, RR 0.74, 95% CI 0.59 to 0.91, I2 = 47%), and this result was confirmed by trial sequential analysis. In addition, a substantial statistical difference was revealed in COVID-19 patient mortality between the Vit-C monotherapy and the control groups (p = 0.03, RR 0.84, 95% CI 0.72 to 0.98, I2 = 0%). However, the trial sequential analysis suggested the need for more trials to confirm its efficacy. Overall, Vit-C monotherapy does decrease the risk of death by sepsis by 26%. To confirm Vit-C is associated with reduced COVID-19 mortality, additional clinical random control trials are required.

Abstract 2119: Intravenous vitamin C therapy for cisplatin ineligible bladder cancer patients (CI-MIBC): Early investigation into potential pharmacodynamic biomarkers

Abstract Neoadjuvant cisplatin based chemotherapy is considered standard of care for patients with locally advanced bladder cancer (BCa). However, upwards of 50% of patients are ineligible due to poor performance status, underlying kidney disease, peripheral neuropathy, hearing loss and/or cardiac disease. There are currently no accepted alternative regimens with significant activity, and many cisplatin ineligible patients usually proceed directly to surgery. Prior research in other cancers has indicated intravenous vitamin C (IVC), or ascorbate, may serve as a beneficial adjuvant to less toxic therapeutic regimens. We initiated a single arm, Simon 2-stage, Window of Opportunity trial using high dose IVC with single cycle gemcitabine/carboplatin (GCa) (NCT04046094). The primary outcome was pathologic downstaging. Twelve patients with newly diagnosed CI-MIBC were enrolled. Patients received single cycle GCa and IVC titrated to 350-400 mg/dL for ~21 days followed by cystectomy after ~4-6 weeks. As reported, pathological downstaging (&amp;lt;ypT2N0Mx) was present in 4 (33%) of patients. Three of the four patients had a complete response (ypT0NoMx) including one patient with plasmacytoid variant histology. Treatment was well tolerated with no attributable AE/SAEs. Given the discrepancy in response levels, we began identifying potential markers of pharmacodynamic efficacy to inform future trials. Novel data evaluating Ki67+ cells by immunohistochemistry indicate widespread proliferation in non-responders to IVC/GCa, whereas responding patients had visibly fewer positive cells, suggesting a direct effect on cell death and proliferation. TUNEL staining was present in all samples, although often minimally, and thus TUNEL may not yield enough signal to reliably make determinations about treatment outcomes. Urinary cytokine values were assessed using multiplex ELISA and reported as pg/mL urine. Multiple cytokines including IL-1RA, CCL2, IL-8, CXCL10 were present at markedly high concentrations in patients with BCa. Cytokine levels generally increased between diagnostic resection and radical cystectomy indicating potential immune activation by the IVC/GCa treatment. Cytokine levels generally fell between radical cystectomy and follow-up samples suggesting resolution of inflammation after cystectomy. In conclusion, IVC/GCa may be a viable alternative neoadjuvant treatment strategy for patients with BCa that are ineligible for cisplatin-based chemotherapy. Identifying biomarkers of response remains a major area of interest to refine study designs and identify patients most likely to benefit from therapy. Citation Format: Benjamin L. Woolbright, Ganeshkumar Rajendran, Erika Abbott, Zeb Zacharias, Jon Houtman, Rahul Parikh, Qi Chen, Ameer Hamza, Elizabeth Wulff-Burchfield, Jeffrey M. Holzbeierlein, Jeanne Drisko, Michael D. Henry, John A. Taylor. Intravenous vitamin C therapy for cisplatin ineligible bladder cancer patients (CI-MIBC): Early investigation into potential pharmacodynamic biomarkers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2119.

Macronutrient and micronutrient requirements and therapeutic effects in critically ill patients with SARS‐CoV‐2: A narrative review

COVID-19 can lead to critical illness and induce hypermetabolism, protein catabolism, and inflammation. These pathological processes may alter energy and protein requirements, and certain micronutrients may attenuate the associated detriments. This narrative review summarizes the macronutrient and micronutrient requirements and therapeutic effects in critically ill patients with SARS-CoV-2. We searched four databases for randomized controlled trials (RCTs) and studies that measured macronutrient and micronutrient requirements, published from February 2020 to September 2022. Ten articles reported on energy and protein requirements, and five articles reported the therapeutic effects of ω-3 (n = 1), group B vitamins (n = 1), and vitamin C (n = 3). Patients' resting energy expenditure gradually increased with time, measuring approximately 20 kcal/kg body weight (BW), 25 kcal/kg BW, and 30 kcal/kg BW for the first, second, and third week onwards, respectively. Patients remained in negative nitrogen balances in the first week, and a protein intake of ≥1.5 g/kg BW may be necessary to achieve nitrogen equilibrium. Preliminary evidence suggests that ω-3 fatty acids may protect against renal and respiratory impairments. The therapeutic effects of group B vitamins and vitamin C cannot be ascertained, although intravenous vitamin C appears promising in reducing mortality and inflammation. There are no RCTs to guide the optimal dose of energy and protein in critically ill patients with SARS-CoV-2. Additional larger-scale, well-designed RCTs are needed to elucidate the therapeutic effects of ω-3, group B vitamins, and vitamin C.

Red Blood Cell Exchange for a Patient with Dapsone-Induced Methemoglobinemia, Severe Methylene Blue Allergy, and Refractoriness to Intravenous Vitamin C Therapy

Red Blood Cell Exchange for a Patient with Dapsone-Induced Methemoglobinemia, Severe Methylene Blue Allergy, and Refractoriness to Intravenous Vitamin C Therapy

How to Start an IV Drip Bar.

The practice of administering intravenous (IV) vitamin infusions is going to increase in the future and medspas are already meeting this demand. Many practices are striving to create an IV drip bar that complements their aesthetic practice. In this article, we provide a blueprint for starting an IV drip bar. We break down the process into several easy steps designed to make any aesthetic practice successful.

Multiple Bone Metastatic Invasion with Clinical Implications due to Ductal Mammary Carcinoma – Case report and Short Literature Review

Multidisciplinary approach of clinical cases in rehabilitations units can be very complex and divers. Method: We present a case of a woman 30 years old, whose oncological histo-ry begins 9 years ago, when the diagnosis of invasive ductal mammary infiltrating ca-nelular carcinoma grade I was made and treated by tumorectomy (lumpectomy). The pa-tient refused oncological treatment at that time and resorted to alternative medicine dur-ing a period of 7 years: diet without sugar and animal products; regular vitamin B17 treatments; almond kernel cure; high-dose intravenous vitamin C treatment for; intrave-nous ozone therapy; apitherapy with bee venom; oral administration of cannabis oil dur-ing the past four years until now; physical therapy. Results: The evolution is marked by the appearance of multiple bone metastatic lesions. The most worst clinical consequence was a hyperalgesic cervicobrachial neuralgia, due to multiple C6-T3 lytic lesions diag-nosed 2 years ago and C7 compression (close to spinal cord injury), situation which had as medical approach two surgeries interventions, radiotherapy and chemotherapy. Con-clusions: The rehabilitation program was adapted to every stage of clinical evolution and was marked by many complications. All the steps were made for functional improvement and for increase the quality of life.

Association of Vitamin C, Thiamine, and Hydrocortisone Infusion With Long-term Cognitive, Psychological, and Functional Outcomes in Sepsis Survivors

Sepsis is associated with long-term cognitive impairment and worse psychological and functional outcomes. Potential mechanisms include intracerebral oxidative stress and inflammation, yet little is known about the effects of early antioxidant and anti-inflammatory therapy on cognitive, psychological, and functional outcomes in sepsis survivors. To describe observed differences in long-term cognitive, psychological, and functional outcomes of vitamin C, thiamine, and hydrocortisone between the intervention and control groups in the Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) randomized clinical trial. This prespecified secondary analysis reports the 6-month outcomes of the multicenter, double-blind, placebo-controlled VICTAS randomized clinical trial, which was conducted between August 2018 and July 2019. Adult patients with sepsis-induced respiratory and/or cardiovascular dysfunction who survived to discharge or day 30 were recruited from 43 intensive care units in the US. Participants were randomized 1:1 to either the intervention or control group. Cognitive, psychological, and functional outcomes at 6 months after randomization were assessed via telephone through January 2020. Data analyses were conducted between February 2021 and December 2022. The intervention group received intravenous vitamin C (1.5 g), thiamine hydrochloride (100 mg), and hydrocortisone sodium succinate (50 mg) every 6 hours for 96 hours or until death or intensive care unit discharge. The control group received matching placebo. Cognitive performance, risk of posttraumatic stress disorder and depression, and functional status were assessed using a battery of standardized instruments that were administered during a 1-hour telephone call 6 months after randomization. After exclusions, withdrawals, and deaths, the final sample included 213 participants (median [IQR] age, 57 [47-67] years; 112 males [52.6%]) who underwent long-term outcomes assessment and had been randomized to either the intervention group (n = 108) or control group (n = 105). The intervention group had lower immediate memory scores (adjusted OR [aOR], 0.49; 95% CI, 0.26-0.89), higher odds of posttraumatic stress disorder (aOR, 3.51; 95% CI, 1.18-10.40), and lower odds of receiving mental health care (aOR, 0.38; 95% CI, 0.16-0.89). No other statistically significant differences in cognitive, psychological, and functional outcomes were found between the 2 groups. In survivors of sepsis, treatment with vitamin C, thiamine, and hydrocortisone did not improve or had worse cognitive, psychological, and functional outcomes at 6 months compared with patients who received placebo. These findings challenge the hypothesis that antioxidant and anti-inflammatory therapy during critical illness mitigates the development of long-term cognitive, psychological, and functional impairment in sepsis survivors. ClinicalTrials.gov Identifier: NCT03509350.

Evaluation of Response to High-Dose Intravenous Vitamin K Administration.

Essential to the coagulation pathway, vitamin K (phytonadione) is used to correct clotting factor deficiencies and for reversal of warfarin-induced bleeding. In practice, high-dose intravenous (IV) vitamin K is often used, despite limited evidence supporting repeated dosing. This study sought to characterize differences in responders and nonresponders to high-dose vitamin K to guide dosing strategies. This was a case-control study of hospitalized adults who received vitamin K 10 mg IV daily for 3 days. Cases were represented by patients who responded to the first dose of IV vitamin K and controls were nonresponders. The primary outcome was change in international normalized ratio (INR) over time with subsequent vitamin K doses. Secondary outcomes included factors associated with response to vitamin K and incidence of safety events. The Cleveland Clinic Institutional Review Board approved this study. There were 497 patients included, and 182 were responders. Most patients had underlying cirrhosis (91.5%). In responders, the INR decreased from 1.89 at baseline (95% CI = [1.74-2.04]) to 1.40 on day 3 (95% CI = [1.30-1.50]). In nonresponders, the INR decreased from 1.97 (95% CI = [1.83-2.13]) to 1.85 ([1.72-1.99]). Factors associated with response included lower body weight, absence of cirrhosis, and lower bilirubin. There was a low incidence of safety events observed. In this study of mainly patients with cirrhosis, the overall adjusted decrease in INR over 3 days was 0.3, which may have minimal clinical impact. Additional studies are needed to identify populations who may benefit from repeated daily doses of high-dose IV vitamin K.