Dietary Intake of Ascorbic Acid Attenuates Lipopolysaccharide-Induced Sepsis and Septic Inflammation in ODS Rats

Kawade, Noe; Tokuda, Yomei; Tsujino, Shogo; Aoyama, Hiroaki; Kobayashi, Misato; Murai, Atsushi; Horio, Fumihiko

doi:10.3177/jnsv.64.404

Cited by 11 publications

(13 citation statements)

References 22 publications

(28 reference statements)

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“…When our findings and mentioned literature data are evaluated together, AA might have anti-inflammatory properties that are prominent in the presence of increased inflammatory activity such as that caused by sepsis. 20 As expected, a significant decrease in CMAP amplitude and a significant increase in CMAP latency were detected in models of CIP. With AA treatment, a significant increase in CMAP amplitude and a significant decrease in CMAP latency were detected, indicating that this treatment was effective in countering the effects of CIP.…”

Section: Discussionsupporting

confidence: 75%

The Ameliorative Effects of Ascorbic Acid on Critical Illness Polyneuropathy in Rodent Sepsis Model

Silistre¹,

Erbaş

2020

J Pediatr Intensive Care

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Although the exact pathophysiology of critical illness polyneuropathy (CIP) is still unknown, there are several hypotheses, some of which are increased inflammation and oxidative stress. We used rodent sepsis model in which we induced sepsis through cecal ligation followed by cecal puncture. We then administered ascorbic acid (AA) and evaluated outcomes. The levels of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), interleukins (IL)-6 in the plasma, and heat shock protein-70 (HSP-70) levels in the sciatic nerve were measured, and also electromyography analyses were performed. While plasma MDA, TNF-α, and IL-6 levels were decreased significantly with AA treatment, sciatic nerve levels of HSP-70 were significantly elevated in the AA group. A significant increase in compound muscle action potential (CMAP) amplitude and a significant decrease in CMAP latency were detected in the AA group. We observed healing effects of AA on a rat model of CIP and these effects seem to be related to its anti-inflammatory and antioxidant properties.

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Section: Discussionsupporting

confidence: 75%

The Ameliorative Effects of Ascorbic Acid on Critical Illness Polyneuropathy in Rodent Sepsis Model

Silistre¹,

Erbaş

2020

J Pediatr Intensive Care

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“…This leads to more than 10 million deaths every year representing the cause of nearly 20% of all global deaths [1]. A cornerstone of its pathophysiology is based on reactive oxygen species (ROS)-driven modification of proteins affecting cellular signaling, gene expression, and other essential cellular processes which are initiated by enzymes such as nicotinamide adenine dinucleotide phosphate oxidase, uncoupling of mitochondrial oxidative phosphorylation, and endothelial nitric oxide synthase [2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Mortality in septic patients treated with vitamin C: a systematic meta-analysis

et al. 2021

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Background Supplementation of vitamin C in septic patients remains controversial despite eight large clinical trials published only in 2020. We aimed to evaluate the evidence on potential effects of vitamin C treatment on mortality in adult septic patients. Methods Data search included PubMed, Web of Science, and the Cochrane Library. A meta-analysis of eligible peer-reviewed studies was performed in accordance with the PRISMA statement. Only studies with valid classifications of sepsis and intravenous vitamin C treatment (alone or combined with hydrocortisone/thiamine) were included. Results A total of 17 studies including 3133 patients fulfilled the predefined criteria and were analyzed. Pooled analysis indicated no mortality reduction in patients treated with vitamin C when compared to reference (risk difference − 0.05 [95% CI − 0.11 to − 0.01]; p = 0.08; p for Cochran Q = 0.002; I2 = 56%). Notably, subgroup analyses revealed an improved survival, if vitamin C treatment was applied for 3–4 days (risk difference, − 0.10 [95% CI − 0.19 to − 0.02]; p = 0.02) when compared to patients treated for 1–2 or > 5 days. Also, timing of the pooled mortality assessment indicated a reduction concerning short-term mortality (< 30 days; risk difference, − 0.08 [95% CI − 0.15 to − 0.01]; p = 0.02; p for Cochran Q = 0.02; I2 = 63%). Presence of statistical heterogeneity was noted with no sign of significant publication bias. Conclusion Although vitamin C administration did not reduce pooled mortality, patients may profit if vitamin C is administered over 3 to 4 days. Consequently, further research is needed to identify patient subgroups that might benefit from intravenous supplementation of vitamin C.

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“…High-dose intravenous (IV) vitamin C has recently been explored as an adjunctive therapy in sepsis because of its anti-inflammatory and antioxidant properties. [5][6][7][8] A previous randomized trial of 24 patients showed that high-dose IV vitamin C attenuated organ failure associated with sepsis in a dose-dependent manner. 9 Thiamine deficiency has also been reported in 20% of critically ill patients with sepsis, 10 and thiamine supplementation has been shown to improve lactate clearance in patients with sepsis.…”

mentioning

confidence: 99%

Effect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on Time Alive and Free of Vasopressor Support Among Patients With Septic Shock

Fujii

Luethi

Young

et al. 2020

JAMA

390

512

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It is unclear whether vitamin C, hydrocortisone, and thiamine are more effective than hydrocortisone alone in expediting resolution of septic shock.OBJECTIVE To determine whether the combination of vitamin C, hydrocortisone, and thiamine, compared with hydrocortisone alone, improves the duration of time alive and free of vasopressor administration in patients with septic shock. DESIGN, SETTING, AND PARTICIPANTSMulticenter, open-label, randomized clinical trial conducted in 10 intensive care units in Australia, New Zealand, and Brazil that recruited 216 patients fulfilling the Sepsis-3 definition of septic shock. The first patient was enrolled on May 8, 2018, and the last on July 9, 2019. The final date of follow-up was October 6, 2019.INTERVENTIONS Patients were randomized to the intervention group (n = 109), consisting of intravenous vitamin C (1.5 g every 6 hours), hydrocortisone (50 mg every 6 hours), and thiamine (200 mg every 12 hours), or to the control group (n = 107), consisting of intravenous hydrocortisone (50 mg every 6 hours) alone until shock resolution or up to 10 days. MAIN OUTCOMES AND MEASURESThe primary trial outcome was duration of time alive and free of vasopressor administration up to day 7. Ten secondary outcomes were prespecified, including 90-day mortality.RESULTS Among 216 patients who were randomized, 211 provided consent and completed the primary outcome measurement (mean age, 61.7 years [SD, 15.0]; 133 men [63%]). Time alive and vasopressor free up to day 7 was 122.1 hours (interquartile range [IQR], in the intervention group and 124.6 hours (IQR, 82.1-147.0 hours) in the control group; the median of all paired differences was -0.6 hours (95% CI, -8.3 to 7.2 hours; P = .83). Of 10 prespecified secondary outcomes, 9 showed no statistically significant difference. Ninety-day mortality was 30/105 (28.6%) in the intervention group and 25/102 (24.5%) in the control group (hazard ratio, 1.18; 95% CI, 0.69-2.00). No serious adverse events were reported. CONCLUSIONS AND RELEVANCEIn patients with septic shock, treatment with intravenous vitamin C, hydrocortisone, and thiamine, compared with intravenous hydrocortisone alone, did not significantly improve the duration of time alive and free of vasopressor administration over 7 days. The finding suggests that treatment with intravenous vitamin C, hydrocortisone, and thiamine does not lead to a more rapid resolution of septic shock compared with intravenous hydrocortisone alone.

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Dietary Intake of Ascorbic Acid Attenuates Lipopolysaccharide-Induced Sepsis and Septic Inflammation in ODS Rats

Cited by 11 publications

References 22 publications

The Ameliorative Effects of Ascorbic Acid on Critical Illness Polyneuropathy in Rodent Sepsis Model

The Ameliorative Effects of Ascorbic Acid on Critical Illness Polyneuropathy in Rodent Sepsis Model

Mortality in septic patients treated with vitamin C: a systematic meta-analysis

Effect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on Time Alive and Free of Vasopressor Support Among Patients With Septic Shock

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