Researchers to study vitamin C as treatment for septic lung injury

[Emily]

http://www.cctr.vcu.edu/news/feature/fowler.html

Researchers to study vitamin C as treatment for septic lung injury

Researchers from Virginia Commonwealth University will lead a multicenter $3.2 million National Institutes of Health grant to study whether high doses of vitamin C can effectively treat septic lung injury resulting from infection. The VCU team will collaborate with colleagues from Wake Forest, University of Virginia and Emory to begin phase 2 clinical trials.
Sepsis is caused by the immune system’s response to a serious infection and is characterized by systemic inflammation, organ dysfunction and organ failure. Four out of 10 septic patients develop lung injury. Despite modern advances in critical care, one-third to half of all severely septic patients die, resulting in millions of deaths globally each year.
“When patients are septic, their bodies lose the ability to control blood pressure. We wanted to see if vitamin C could help to control the pressure,” said Alpha (Berry) Fowler III, M.D., chair of the Division of Pulmonary Disease and Critical Care Medicine and professor of internal medicine in the VCU School of Medicine. “We found that in preclinical studies, vitamin C prevented the inflammatory response in sepsis. We continued our work with a small clinical trial to study the safety of giving high doses of vitamin C to septic patients. We did not see any side effects from the vitamin C.”...
...
?We are looking to test vitamin C as an intervention for early lung injury due to sepsis. Our goal is to enroll about 170 patients among the four research sites in the next two to three years,? Fowler said. ?This research is important because the current standard of care doesn?t work and it is expensive. We?re hopeful that vitamin C might be an effective intervention that will save lives.?...

 

[Emily]

[h=1]Vitamin C revisited[/h] Heleen M Oudemans-van Straaten[SUP]*[/SUP], Angelique ME Spoelstra-de Man and Monique C de Waard

• * Corresponding author: Heleen M Oudemans-van Straaten hmoudemans@gmail.com

Author Affiliations
Department of Intensive Care, VU University Medical Centre, De Boelelaan 1117, Amsterdam 1081 HZ, the Netherlands

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Critical Care 2014, 18:460 doi:10.1186/s13054-014-0460-x
The electronic version of this article is the complete one and can be found online at: http://ccforum.com/content/18/4/460
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[TD]6 August 2014[/TD]
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? 2014 Oudemans-van Straaten et al., licensee BioMed Central Ltd.
The licensee has exclusive rights to distribute this article, in any medium, for 12 months following its publication. After this time, the article is available under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0) applies to the data made available in this article, unless otherwise stated.


[h=3]Abstract[/h] This narrative review summarizes the role of vitamin C in mitigating oxidative injury-induced microcirculatory impairment and associated organ failure in ischemia/reperfusion or sepsis. Preclinical studies show that high-dose vitamin C can prevent or restore microcirculatory flow impairment by inhibiting activation of nicotinamide adenine dinucleotide phosphate-oxidase and inducible nitric oxide synthase, augmenting tetrahydrobiopterin, preventing uncoupling of oxidative phosphorylation, and decreasing the formation of superoxide and peroxynitrite, and by directly scavenging superoxide. Vitamin C can additionally restore vascular responsiveness to vasoconstrictors, preserve endothelial barrier by maintaining cyclic guanylate phosphatase and occludin phosphorylation and preventing apoptosis. Finally, high-dose vitamin C can augment antibacterial defense. These protective effects against overwhelming oxidative stress due to ischemia/reperfusion, sepsis or burn seems to mitigate organ injury and dysfunction, and promote recovery after cardiac revascularization and in critically ill patients, in the latter partially in combination with other antioxidants. Of note, several questions remain to be solved, including optimal dose, timing and combination of vitamin C with other antioxidants. The combination obviously offers a synergistic effect and seems reasonable during sustained critical illness. High-dose vitamin C, however, provides a cheap, strong and multifaceted antioxidant, especially robust for resuscitation of the circulation. Vitamin C given as early as possible after the injurious event, or before if feasible, seems most effective. The latter could be considered at the start of cardiac surgery, organ transplant or major gastrointestinal surgery. Preoperative supplementation should consider the inhibiting effect of vitamin C on ischemic preconditioning. In critically ill patients, future research should focus on the use of short-term high-dose intravenous vitamin C as a resuscitation drug, to intervene as early as possible in the oxidant cascade in order to optimize macrocirculation and microcirculation and limit cellular injury...

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