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Neil Riordan IVC

A comprehensive collection on IVC Literature and Therapies

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Rationale for IV vitamin C for cancer and sepsis

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These two papers published in 2018 review the existing literature and make a strong case for the use of intravenous vitamin C in cancer and sepsis patients. Both articles highlight the fact that IV vitamin C has been shown to be a safe intervention leading to improvement of symptoms.

Curr Oncol. 2018 Apr;25(2):139-148. doi: 10.3747/co.25.3790

Intravenous vitamin C in the supportive care of cancer patients: a review and rational approach.

Klimant E, Wright H, Rubin D, Seely D, Markman M.

Abstract

This article reviews intravenous vitamin C (IV C) in cancer care and offers a rational approach to enable medical oncologists and integrative practitioners to safely provide IV C combined with oral vitamin C to patients. The use of IV C is a safe supportive intervention to decrease inflammation in the patient and to improve symptoms related to antioxidant deficiency, disease processes, and side effects of standard cancer treatments. A proposed rationale, together with relevant clinical safety considerations for the application of IV C in oncologic supportive care, is provided.

PMID: 29719430 PMCID: PMC5927785

 

 

Pharmacol Ther. 2018 Apr 21. pii: S0163-7258(18)30070-6. doi: DOI: 10.1016/j.pharmthera.2018.04.007

Vitamin C for the treatment of sepsis: The scientific rationale.

Marik PE.

Abstract

Most vertebrates can synthesize vitamin C with synthesis increasing during stress. Humans, however, have lost the ability to synthesize vitamin C. Vitamin C is an important anti-oxidant and an enzyme cofactor for many important biological reactions. Sepsis results in the overwhelming production of reactive oxygen species with widespread endothelial, cellular and mitochondrial injury leading to progressive organ failure. Sepsis is associated with an acute deficiency of vitamin C. In experimental sepsis models, intravenous vitamin C reduces organ injury and improves survival. In addition, emerging evidence suggests that the combination of vitamin C, corticosteroids and thiamine may act synergistically to reverse sepsis induced organ dysfunction. These findings are supported by a recent observational study. Randomized controlled trials are underway to investigate this novel approach to the treatment of sepsis.

PMID: 29684467

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Vitamin C after hemorrhagic shock decreases renal pathological score

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The kidneys are especially vulnerable following severe blood loss, as renal failure may occur. This study used a rat model to show that after a hemorrhage, treatment with intravenous vitamin C decreased the score measuring damage to the kidney.

 

Biochem Biophys Res Commun. 2018 Jun 22;501(2):358-364. DOI: 10.1016/j.bbrc.2018.04.111

Intravenous Vitamin C attenuates hemorrhagic shock-related renal injury through the induction of SIRT1 in rats.

Qi MZ, Yao Y, Xie RL, Sun SL, Sun WW, Wang JL, Chen Y, Zhao B, Chen EZ, Mao EQ.

Abstract

To investigate the effect of intravenous Vitamin C (VC) on hemorrhagic shock (HS)-associated rat renal injury and the involved mechanism. Thirty SD rats were randomly assigned to the sham surgery (sham), hemorrhagic shock (HS), HS+100 mg/kg VC (H + VL), HS+500 mg/kg VC (H + VH) and HS+100 mg/kg VC + EX527 (H + VL + E) groups. Tissue and blood samples were collected 6 h after surgery. Kidney pathological changes were scored. Creatinine (CRE), blood urea nitrogen (BUN), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) levels in serum and Vitamin C levels and superoxide dismutase (SOD) activity and the ability to suppress hydroxyl radical (RAFHR) in plasma were measured. The expression of Sirtuin1 (SIRT1), Acetyl-NF-κB (Ace-NF-κB), heme oxygenase-1 (HO-1), TNF-α, and IL-1β in tissues was analyzed by ELISA or western-blot. In the HS group, the kidney pathological score and CRE, BUN, TNF-α, and IL-1β levels in serum were significantly higher than in the Sham group (P < 0.05), while SOD and RAFHR were significantly decreased in the plasma (P < 0.05). SOD activity and SIRT1 expression were remarkably lower in the kidney in the HS group than in the Sham group (P < 0.05), while MDA, TNF-α, and IL-1β concentrations and Acetyl-NF-κB andHO-1 expression in the kidney showed a noteworthy increase compared to the Sham group (P < 0.05). Compared to the HS group, VC treatment led to a remarkable reduction in the kidney pathological score and CRE,BUN,TNF-α, and IL-1β levels (P < 0.05), and a significant increase in Vitamin C, SOD, and RAFHR levels in the plasma (P < 0.05). Additionally, MDA, TNF-α, IL-1β and Acetyl-NF-κB expression levels were decreased in the kidney (P < 0.05), while SOD, SIRT1 and HO-1 levels were notably enhanced. There were no differences between the H + VL and H + VH groups aside from plasma Vitamin C levels. The effect of Vitamin C was decreased after the addition of EX527, which inhibits SIRT1. Intravenous Vitamin C might attenuate HS-related renal injury via the SIRT1 pathway, and it appears that there were no differences in the effects between the high and low doses.

PMID: 29673592

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Vitamin C for vasoplegia after cardiac surgery

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Cardiac vasoplegia is a common complication after cardiac surgery. In this study, 3 patients received high-dose intravenous vitamin C after a bypass and saw a reduction in their need for vasopressors (drugs to contract their blood vessels) – 2 of them were taken off norepinephrine in 24 hours.

 

A A Pract. 2018 Feb 27. doi: 10.1213/XAA.0000000000000752

Vitamin C for Vasoplegia After Cardiopulmonary Bypass: A Case Series.

Wieruszewski PM, Nei SD, Maltais S, Schaff HV, Wittwer ED.

Abstract

Cardiac vasoplegia remains a significant contributor of morbidity and mortality in cardiac surgery patients after cardiopulmonary bypass. Effective therapeutic options for vasopressor-refractory vasoplegia are limited. We report 3 patients in whom we administered high-dose intravenous ascorbic acid (vitamin C), a cofactor for endogenous catecholamine synthesis, to treat vasoplegia refractory to epinephrine, vasopressin, and norepinephrine after surgery requiring cardiopulmonary bypass. Reductions in vasopressor requirements were observed in all 3 patients, and, in 2 patients, norepinephrine was completely discontinued within 24 hours. Ascorbic acid is a novel potential therapeutic option for cardiac vasoplegia that warrants rigorous prospective studies.

PMID: 29634537
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More studies needed to establish the benefits of vitamin C for sepsis

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The authors of this review examined 21 papers about the use of intravenous vitamin C in the case of sepsis, and found 3 relevant studies. While these studies report very positive outcomes, they have a small sample size. The authors recommend larger, multicenter, randomized trials to establish the potential benefits of intravenous vitamin C for sepsis.

 

Emerg Med J. 2018 Apr;35(4):272-274. doi: 10.1136/emermed-2018-207608.3.

Bet 2: Does intravenous vitamin C improve mortality in patients with severe sepsis?

Sheikh M, Horner D.

Abstract

A shortcut review was carried out to establish whether the use of intravenous vitamin C can reduce mortality or morbidity in patients diagnosed in the early phases of severe sepsis. Three directly relevant papers were found using the reported search strategy. The author, date and country of publication; patient group studied; study type; relevant outcomes; results and study weaknesses of the best papers are tabulated. It is concluded that there is insufficient high-quality research to justify the routine use of vitamin C in severe sepsis. Further multicentre, double-blinded randomised controlled trials are required in order to establish the role of vitamin C in sepsis.

PMID: 29559543

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High-dose intravenous vitamin C proposed after cardiac arrest

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This is a review article from the Annual Update in Intensive Care and Emergency Medicine 2018, where they argue that high-dose intravenous vitamin C is no longer alternative medicine, and they recommend the use of after cardiac arrest to prevent damage by ischemia.

Crit Care. 2018 Mar 20;22(1):70. doi:10.1186/s13054-018-1996-y

Making sense of early high-dose intravenous vitamin C in ischemia/reperfusion injury.

Spoelstra-de Man AME, Elbers PWG, Oudemans-van Straaten HM.

Abstract (Conclusion)

An increasing number of preclinical and clinical studies show that high-dose i. v. vitamin C can mitigate systemic, cerebral and myocardial ischemia/reperfusion injury. Vitamin C administration has been associated with reduced oxidative stress, myocardial injury and arrhythmias and improved microcirculation, neurological outcome and survival, although not all studies showed benefit. Because of the common pathophysiological pathway of sepsis and ischemia/reperfusion injury, the potential role of vitamin C for ischemia/reperfusion injury is further supported by the results of preliminary sepsis studies, showing earlier recovery from organ failure and higher survival rates. Therefore, early, high-dose i. v. vitamin C is a promising therapeutic intervention after cardiac arrest to diminish the systemic ischemia/reperfusion injury due to overwhelming oxidative stress. The supportive evidence from preclinical and clinical studies is too large to continue considering early high-dose i. v. vitamin C as alternative medicine. An RCT is urgently required to provide definitive proof as to whether this cheap and safe therapy does indeed improve outcome.

PMID: 29558975 PMCID: PMC5861638

 

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Vitamin C derivative as anti-tumor alternative for renal failure patients

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Patients with renal (kidney) failure have difficulties processing vitamin C , and the excess ascorbate can accumulate in the body in harmful levels. This research team from Japan studied a molecule derived from vitamin C that can be absorbed more easily: it was found that it also has antitumor properties. This could be an interesting alternative to vitamin C cancer treatment for patients with renal failure.

 

Int J Mol Sci. 2018 Feb 10;19(2). pii: E535. doi: 10.3390/ijms19020535

Potential Antitumor Activity of 2-O-α-d-Glucopyranosyl-6-O-(2-Pentylheptanoyl)-l-Ascorbic Acid.

Miura K, Haraguchi M, Ito H, Tai A.

Abstract

Intravenous administration of high-dose ascorbic acid (AA) has been reported as a treatment for cancer patients. However, cancer patients with renal failure cannot receive this therapy because high-dose AA infusion can have side effects. To solve this problem, we evaluated the antitumor activity of a lipophilic stable AA derivative, 2-O-α-d-glucopyranosyl-6-O-(2-pentylheptanoyl)-l-ascorbic acid (6-bOcta-AA-2G). Intravenous administration of 6-bOcta-AA-2G suppressed tumor growth in colon-26 tumor-bearing mice more strongly than did AA, even at 1/10 of the molar amount of AA. Experiments on the biodistribution and clearance of 6-bOcta-AA-2G and its metabolites in tumor-bearing mice showed that 6-bOcta-AA-2G was hydrolyzed to 6-O-(2-propylpentanoyl)-l-ascorbic acid (6-bOcta-AA) slowly to yield AA, and the results suggested that this characteristic metabolic pattern is responsible for making the antitumor activity of 6-bOcta-AA-2G stronger than that of AA and that the active form of 6-bOcta-AA-2G showing antitumor activity is 6-bOcta-AA. In in vitro experiments, the oxidized form of 6-bOcta-AA as well as 6-bOcta-AA showed significant cytotoxicity, while the oxidized forms of ascorbic acid showed no cytotoxicity at all, suggesting that the antitumor activity mechanism of 6-bOcta-AA-2G is different from that of AA and that the antitumor activity is due to the reduced and oxidized form of 6-bOcta-AA. The findings suggest that 6-bOcta-AA-2G is a potent candidate as an alternative drug to intravenous high-dose AA.

PMID: 29439410 PMCID: PMC5855757

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Metastatic pancreatic cancer survival up to 4 years with IV vitamin C

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Pancreatic cancer, and in particular pancreatic ductal adenocarcinoma (PDA), has a very poor prognosis – only 6% survive within 5 years of diagnosis. This case report presents a  PDA patient with metastasis, with an expected survival of 6 months. He was treated with intravenous vitamin C 2-3 times a week. At the 8-month follow-up, most masses had decreased in size and continued decreasing in subsequent follow-ups. The patient survived 4 years with this regimen, and died of causes indirectly related to PDA, but not associated with PDA progression.

 

Anticancer Drugs. 2018 Apr;29(4):373-379. doi: 10.1097/CAD.0000000000000603

Treatment of pancreatic cancer with intravenous vitamin C: a case report.

Drisko JA, Serrano OK, Spruce LR, Chen Q, Levine M.

Abstract

Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis and is often discovered at an advanced stage with few therapeutic options. Current conventional regimens for PDA are associated with significant morbidity, decreased quality of life, and a considerable financial burden. As a result, some patients turn to integrative medicine therapies as an alternate option after a diagnosis of PDA. Intravenous pharmacologic ascorbic acid (PAA) is one such treatment. The use of PAA has been passionately debated for many years, but more recent rigorous scientific research has shown that there are significant blood concentration differences when ascorbic acid is given parenterally when compared to oral dosing. This pharmacologic difference appears to be critical for its role in oncology. Here, we report the use of PAA in a patient with poorly differentiated stage IV PDA as an exclusive chemotherapeutic regimen. The patient survived nearly 4 years after diagnosis, with PAA as his sole treatment, and he achieved objective regression of his disease. He died from sepsis and organ failure from a bowel perforation event. This case illustrates the possibility of PAA to effectively control tumor progression and serve as an adjunct to standard of care PDA chemotherapy regimens. Our patient’s experience with PAA should be taken into consideration, along with previous research in cell, animal, and clinical experiments to design future treatment trials.

PMID: 29438178  PMCID: PMC5882293

 

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Low-dose intravenous vitamin C for ARDS in psoriasis

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The inflammation associated with psoriasis may affect the lungs and respiratory system. This case report presents a patient diagnosed with psoriasis-linked acute respiratory distress symptom (ARDS). After treatment with immunosuppressants, steroids and low-dose intravenous vitamin C and thiamine, she recovered in 24 hours and was discharged within days.

 

 

BMJ Case Rep. 2018 Feb 2;2018. pii: bcr-2017-223475. doi: 10.1136/bcr-2017-223475

ARDS complicating pustular psoriasis: treatment with low-dose corticosteroids, vitamin C and thiamine.

Marik PE, Long A.

Abstract

We report the case of a 45-year-old Caucasian woman with a history of psoriasis, admitted to our Medical intensive care unit following the acute onset of diffuse rash and progressive dyspnoea and hypoxaemia requiring escalating respiratory support (continuous positive airway pressure of 10 cm H2O). Her chest X-ray was consistent with findings of non-cardiogenic pulmonary oedema. Echocardiogram was normal. Dermatology considered her skin lesions to be consistent with psoriasis vulgaris with pustular flare. In the absence of an identifiable cause for her respiratory failure, she was diagnosed with acute respiratory distress syndrome due to her psoriatic flare. Treatment with cyclosporine was initiated together with low-dose systemic corticosteroids, intravenous vitamin C and thiamine. The patient made a dramatic recovery being weaned to nasal cannulae within 24 hours after the initiation of this treatment protocol and was discharged home a few days later.

PMID: 29420246

 

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Intravenous vitamin C and decitabine for better overall survival in acute myeloid leukemia

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Acute myeloid leukemia (AML) is a type of cancer that affects the bone marrow, and it may sometimes be treated with decitabine. In this study, AML patients received intravenous low-dose vitamin C and decitabine: they had significantly better overall survival (6 months longer) and a significantly higher remission rate than those who received decitabine alone.

 

Leuk Res. 2018 Mar;66:1-7. doi: 10.1016/j.leukres.2017.12.009

The synergy of Vitamin C with decitabine activates TET2 in leukemic cells and significantly improves overall survival in elderly patients with acute myeloid leukemia.

Zhao H, Zhu H, Huang J, Zhu Y, Hong M, Zhu H, Zhang J, Li S, Yang L, Lian Y, Wang S, Mao J, Chen Y, Li J, Qian S.

Abstract

BACKGROUND:

Decitabine is widely used in the treatment of acute myeloid leukemia (AML) in elderly patients. Low-dose Vitamin C has also been indicated to induce DNA demethylation at the cellular level. However, little is known whether low-dose Vitamin C has a synergistic effect with decitabine in clinic.

METHODS:

The effect of combined low-dose Vitamin C and decitabine on cell proliferation, the cell cycle, apoptosis and the expression level and activity of TET2 was investigated in HL60 and NB4 human leukemic cells. Additionally, we analyzed the clinical outcomes of 73 elderly AML patients who received A-DCAG (intravenous Vitamin C [IVC] plus DCAG [n = 39]) or DCAG (n = 34) treatment.

RESULTS:

We found that low-dose Vitamin C and decitabine has a synergistic efficacy on proliferation, apoptosis, TET2 expression and activity, compared to drug-alone treatment in HL60 and NB4 cell lines in vitro. In clinic, feasibility and safety evaluations revealed that patients who received A-DCAG regimen have a higher complete remission (CR) rate than those who received the DCAG regimen (79.92% vs. 44.11%; P = 0.004) after one cycle of chemotherapy. The median overall survival (OS) was better in the A-DCAG group compared with the DCAG group (15.3 months vs. 9.3 months, P = 0.039). Patients with adverse cytogenetics did benefit from CR. There was no clinically significant additional toxicity observed with the addition of IVC.

CONCLUSION:

On the basis of these results, the addition of IVC at low doses to DCAG appeared to improve CR and prolong OS, compared with DCAG, in elderly patients with AML.

PMID: 29331774

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Late stage metastasized cancer resolved after high-dose IV vitamin C regimen

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In this case report, a patient with renal cancer had his left kidney removed, but cancer metastasized to the left lung. With no conventional therapy options left, he was entered into  an intravenous high-dose vitamin C and alpha lipoic acid regimen. The tumor was resolved on PET/CT scan 19 months into the regimen and did not reappear. The patient was healthy as of September 2017, 6 years after the start of treatment.

 

 

Integr Cancer Ther. 2017 Dec 1:1534735417747984. doi: 10.1177/1534735417747984

The Long-Term Survival of a Patient With Stage IV Renal Cell Carcinoma Following an Integrative Treatment Approach Including the Intravenous α-Lipoic Acid/Low-Dose Naltrexone Protocol.

Berkson BM, Calvo Riera F.

Abstract

In this case report, we describe the treatment of a 64-year-old male patient diagnosed with metastatic renal cell carcinoma (RCC) in June of 2008. In spite of a left nephrectomy and the standard oncological protocols, the patient developed a solitary left lung metastasis that continued to grow. He was informed that given his diagnosis and poor response to conventional therapy, any further treatment would, at best, be palliative. The patient arrived at the Integrative Medical Center of New Mexico in August of 2010. He was in very poor health, weak, and cachectic. An integrative program-developed by one of the authors using intravenous (IV) α-lipoic acid, IV vitamin C, low-dose naltrexone, and hydroxycitrate, and a healthy life style program-was initiated. From August 2010 to August 2015, the patient’s RCC with left lung metastasis was followed closely using computed tomography and positron emission tomography/computed tomography imaging. His most recent positron emission tomography scan demonstrated no residual increased glucose uptake in his left lung. After only a few treatments of IV α-lipoic acid and IV vitamin C, his symptoms began to improve, and the patient regained his baseline weight. His energy and outlook improved, and he returned to work. The patient had stable disease with disappearance of the signs and symptoms of stage IV RCC, a full 9 years following diagnosis, with a gentle integrative program, which is essentially free of side effects. As of November 2017 the patient feels well and is working at his full-time job.

PMID: 29258346

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