Critically ill septic patients have elevated oxidative stress biomarkers: lack of attenuation by parenteral vitamin C

Spencer, Emma; Rosengrave, Patrice; Roberts, E. C.; Boden, Joseph M.; Shaw, Geoff; Carr, Anitra C.

doi:10.1016/j.nutres.2022.10.010

Cited by 4 publications

(7 citation statements)

References 35 publications

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“…At baseline, the total cohort had a median (Q1, Q3) plasma vitamin C status of 29 (15,41) µmol/L (Table 3). Of these, only 10% had adequate vitamin C concentrations (i.e., ≥50 µmol/L); 90% had inadequate concentrations (<50 µmol/L), 38% had hypovitaminosis C (≤23 µmol/L) and 19% had outright deficiency (≤11 µmol/L; Figure 2A).…”

Section: Participant Characteristicsmentioning

confidence: 99%

“…There was an inverse association between baseline vitamin C status and body weight (r = −0.229, p = 0.05) and a trend with BMI (r = −0.226, p = 0.06) (Figure 2B,C). At baseline, the total cohort had a median (Q1, Q3) plasma vitamin C status of 29 (15,41) µmol/L (Table 3). Of these, only 10% had adequate vitamin C concentrations (i.e., ≥50 µmol/L); 90% had inadequate concentrations (<50 µmol/L), 38% had hypovitaminosis C (≤23 µmol/L) and 19% had outright deficiency (≤11 µmol/L; Figure 2A).…”

Section: Participant Characteristicsmentioning

confidence: 99%

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A High Vitamin C Micronutrient Supplement Is Unable to Attenuate Inflammation in People with Metabolic Syndrome but May Improve Metabolic Health Indices: A Randomised Controlled Trial

Vlasiuk,

Zawari,

Whitehead

et al. 2024

Antioxidants

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Chronic low-grade inflammation is a characteristic of people with metabolic syndrome and is thought to contribute to the condition progressing to the more severe type 2 diabetes and cardiovascular disease (CVD). The aim was to carry out a double-blind randomised placebo-controlled trial in people with metabolic syndrome to determine if supplementation with a micronutrient formula containing 1000 mg/d vitamin C could attenuate inflammation in people with metabolic syndrome. We recruited 72 adults aged a median of 52 years with metabolic syndrome, defined as obesity (based on waist circumference or BMI), and at least two of hyperglycaemia, raised triglycerides, lowered HDL cholesterol, hypertension, or taking medications for these conditions. A further inclusion criteria comprised C-reactive protein (CRP) concentrations ≥ 3 mg/L, i.e., high risk of CVD. The participants were randomised to daily micronutrient formula (n = 37) or matched placebo control (n = 35) for 12 weeks. The primary outcome was change in CRP concentrations and secondary outcomes included changes in vitamin C concentrations, pro-inflammatory cytokines (IL-6, TNFα), oxidative stress marker (F2isoprostanes), glycaemic indices (glucose, insulin, HbA1c), lipid markers (triglycerides, LDL and HDL cholesterol), anthropometric parameters (weight, BMI), insulin resistance and insulin sensitivity, and metabolic severity score. The participants had a low median (Q1, Q3) vitamin C status of 29 (15, 41) µmol/L and a high proportion of hypovitaminosis C (38%) and outright deficiency (19%). Following 12 weeks of micronutrient supplementation, at least 70% of the participants reached adequate vitamin C status (≥50 µmol/L), however, there was no change in CRP concentrations relative to the placebo group (Δ−0.3 [95%CI −2.7, 2.1] mg/L, p = 0.8). Similar trends were observed for IL-6, TNFα and F2isoprostanes (p > 0.05). Instead, there were small improvements in BMI, fasting glucose and HbA1c concentrations, insulin sensitivity and metabolic severity score in the micronutrient group relative to placebo (p < 0.05). Overall, 12-week micronutrient supplementation was unable to mitigate systemic inflammation in people with metabolic syndrome but may improve several metabolic health indices.

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Section: Participant Characteristicsmentioning

confidence: 99%

Section: Participant Characteristicsmentioning

confidence: 99%

A High Vitamin C Micronutrient Supplement Is Unable to Attenuate Inflammation in People with Metabolic Syndrome but May Improve Metabolic Health Indices: A Randomised Controlled Trial

Vlasiuk,

Zawari,

Whitehead

et al. 2024

Antioxidants

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“…vitamin C can reduce organ failure in 270 postcardiac arrest patients [56] by neutralizing reactive oxygen species (ROS) generated during ischemia/reperfusion after a cardiac arrest. RCT tested the impact of ascorbic acid on F2-isoprostane in 40 septic shock patients and showed no significant effect on this marker [57].…”

Section: Ascorbic Acidmentioning

confidence: 99%

An update on essential micronutrients in critical illness

Berger

2023

Current Opinion in Critical Care

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Purpose of review Numerous micronutrients are involved in antioxidant and immune defence, while their blood concentrations are frequently low in critically ill patients: this has fuelled many supplementation trials. Numerous observational, randomized studies have been published, which are presented herein. Recent findings Micronutrient concentrations must be analysed considering the context of the inflammatory response in critical illness. Low levels do not always indicate a deficiency without objective micronutrients losses with biological fluids. Nevertheless, higher needs and deficiencies are frequent for some micronutrients, such as thiamine, vitamins C and D, selenium, zinc and iron, and have been acknowledged with identifying patients at risk, such as those requiring continuous renal replacement therapy (CRRT). The most important trials and progress in understanding have occurred with vitamin D (25(OH)D), iron and carnitine. Vitamin D blood levels less than 12 ng/ml are associated with poor clinical outcomes: supplementation in deficient ICU patients generates favourable metabolic changes and decreases mortality. Single high-dose 25(OH)D should not be delivered anymore, as boluses induce a negative feedback mechanism causing inhibition of this vitamin. Iron-deficient anaemia is frequent and can be treated safely with high-dose intravenous iron under the guidance of hepcidin to confirm deficiency diagnosis. Summary The needs in critical illness are higher than those of healthy individuals and must be covered to support immunity. Monitoring selected micronutrients is justified in patients requiring more prolonged ICU therapy. Actual results point towards combinations of essential micronutrients at doses below upper tolerable levels. Finally, the time of high-dose micronutrient monotherapy is probably over.

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“…Moreover, the largest study published to date suggested harm from vitamin C in the composite outcome of death or persistent organ dysfunction 11 . Recent studies suggested that vitamin C may not attenuate oxidative stress in sepsis, as increased concentrations of vitamin C did not lead to any changes in oxidative stress as measured by 8‐isoprostane F 2α concentrations (prostaglandin‐like biomarker of oxidative stress) 12 …”

Section: Introductionmentioning

confidence: 99%

“…11 Recent studies suggested that vitamin C may not attenuate oxidative stress in sepsis, as increased concentrations of vitamin C did not lead to any changes in oxidative stress as measured by 8-isoprostane F 2α concentrations (prostaglandin-like biomarker of oxidative stress). 12 For the clinician, the publication of heterogenous studies with conflicting results make it difficult to determine whether vitamin C should be given to patients with sepsis. This intensive care medicine rapid practice guideline (ICM-RPG) gives an overview of the evidence; makes recommendations for clinical practice in light of the conflicting results; and considers how future research could address the remaining uncertainties on this topic.…”

Section: Introductionmentioning

confidence: 99%

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

Blaser

Alhazzani

Belley‐Côté

et al. 2023

Acta Anaesthesiol Scand

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BackgroundThis 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?MethodsThe 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.ResultsAt 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.ConclusionsThe 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.

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Critically ill septic patients have elevated oxidative stress biomarkers: lack of attenuation by parenteral vitamin C

Cited by 4 publications

References 35 publications

A High Vitamin C Micronutrient Supplement Is Unable to Attenuate Inflammation in People with Metabolic Syndrome but May Improve Metabolic Health Indices: A Randomised Controlled Trial

A High Vitamin C Micronutrient Supplement Is Unable to Attenuate Inflammation in People with Metabolic Syndrome but May Improve Metabolic Health Indices: A Randomised Controlled Trial

An update on essential micronutrients in critical illness

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

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