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

https://link.springer.com/content/pdf/10.1186%2Fs13054-014-0460-x.pdf

Vitamin C revisited

Ascorbic acid (AA), also known as vitamin C, was initially identified as the factor preventing the scurvy disease, and became very popular for its antioxidant properties. It is an important co-substrate of a large class of enzymes, and regulates gene expression by interacting with important transcription factors. AA is important in all stressful conditions that are linked to inflammatory processes and involve immunity. It has been known for decades that the persistence of an inflammatory stimulus is responsible for the onset of many diseases. AA is essential to stimulate the immune system by increasing the strength and protection of the organism. Therefore, its immunostimulant, antinflammatory, antiviral and antibacterial roles are well known, we have summarized its main functions in different types of diseases related to the immune system and chronic inflammation. We can conclude that AA, due to its effects and diversity of regulated pathways, is suitable for use in various fields of medicine including immunology, toxicology, radiobiology and others. AA is not preferable to be used as an isolated mode of treatment, but it can be co-applied as an adjuvant to regulate immunity, gene expression and other important physiological processes. However, we propose that future studies will take into consideration the research of new combinations of antioxidant natural substances and drugs.

Ascorbic Acid: Its Role in Immune System and Chronic Inflammation Diseases

Humans have lost their vitamin C-synthesizing capacities during evolution. Therefore, the uptake of this essential compound from external sources is mandatory in order to prevent vitamin C-deficient conditions resulting in severe morbidities such as scurvy. The potent antioxidant, immunomodulatory, and antiinfectious effects of vitamin C are known since the 1930s. We here (i) review the impact of vitamin C on innate and adaptive immune functions, (ii) provide an overview of its antimicrobial, antibacterial, antiviral, antiparasitic, and antifungal properties, and finally, (iii) discuss vitamin C as an adjunct treatment option for the combat of human infections by bacteria, particularly by emerging multidrug-resistant species.

Immunomodulatory and Antimicrobial Effects of Vitamin C.

Purpose of reviewVitamin C is not only an essential nutrient involved in many anabolic pathways, but also an important player of the endogenous antioxidant defense. Low plasma levels are very common in critical care patients and may reflect severe deficiency states.Recent findingsVitamin C scavenges

Vitamin C supplementation in the critically ill patient.

Endothelium derived relaxing factor

The history of ascorbic acid (AA) and cancer has been marked with controversy. Clinical studies evaluating AA in cancer outcome continue to the present day. However, the wealth of data suggesting that AA may be highly beneficial in addressing cancer-associated inflammation, particularly progression to systemic inflammatory response syndrome (SIRS) and multi organ failure (MOF), has been largely overlooked. Patients with advanced cancer are generally deficient in AA. Once these patients develop septic symptoms, a further decrease in ascorbic acid levels occurs. Given the known role of ascorbate in: a) maintaining endothelial and suppression of inflammatory markers; b) protection from sepsis in animal models; and c) direct antineoplastic effects, we propose the use of ascorbate as an adjuvant to existing modalities in the treatment and prevention of cancer-associated sepsis.

/pdf/intravenous-ascorbic-acid-to-prevent-and-treat-cancer-53flftekzf.pdf

Intravenous ascorbic acid to prevent and treat cancer-associated sepsis?

Interleukin-2 (IL-2) therapy has been demonstrated to induce responses in 10-20% of advanced melanoma and renal cell carcinoma patients, which translates into durable remissions in up to half of the responsers. Unfortunately the use of IL-2 has been associated with severe toxicity and death. It has been previously observed and reported that IL-2 therapy causes a major drop in circulating levels of ascorbic acid (AA). The IL-2 induced toxicity shares many features with sepsis such as capillary leakage, systemic complement activation, and a relatively non-specific rise in inflammatory mediators such as TNF-alpha, C-reactive protein, and in advanced cases organ failure. Animal models and clinical studies have shown rapid depletion of AA in conditions of sepsis and amelioration associated with administration of AA (JTM 9:1-7, 2011). In contrast to other approaches to dealing with IL-2 toxicity, which may also interfere with therapeutic effects, AA possesses the added advantage of having direct antitumor activity through cytotoxic mechanisms and suppression of angiogenesis. Here we present a scientific rationale to support the assessment of intravenous AA as an adjuvant to decrease IL-2 mediated toxicity and possibly increase treatment efficacy.

/pdf/intravenous-ascorbic-acid-as-an-adjuvant-to-interleukin-2-47ttyn2ijg.pdf

Intravenous ascorbic acid as an adjuvant to interleukin-2 immunotherapy

The present invention discloses methods of stimulating an immune response to cancer tissue and biological effectors used by tumors to defeat the host, through the immunization of a mammal using placental tissue, cells, molecules, and combinations thereof. In one embodiment, the invention provides the utilization of syngeneic, allogeneic, xenogeneic, and combinations thereof as immunizing sources.

Boris Markosian

Papers

Intravenous ascorbic acid to prevent and treat cancer-associated sepsis?

Intravenous ascorbic acid as an adjuvant to interleukin-2 immunotherapy

Placental vaccination therapy for cancer