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

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

E. Klimant, MD,* H. Wright, ND,†D. Rubin, ND,† D. Seely, ND MSc,‡ and M. Markman, MD§
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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.

 

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INTRODUCTION​

Historically, Cameron and Campbell1 and Cameron and Pauling2investigated oral and intravenous vitamin C (IV C) treatment in patients with advanced malignancy. Phase i trials in which IV C doses of 75–220 g (up to 1.5 g/kg or 110 mg/m2) were given to patients with advanced malignancies alone and in combination with chemotherapy demonstrated both safety and tolerability, providing some reduction in symptoms, but did not allow for conclusions to be drawn about tumour response or overall treatment efficacy3–8.

Extensive literature demonstrates that cancer patients experience vitamin C deficiency correlated with reduced oral intake, inflammation, infection, disease processes, and treatments such as radiation, chemotherapy, and surgery9–29. Studies report reductions in inflammatory markers and suggest some improvement in symptoms, with a possible benefit in quality of life (qol) when IV C alone or in combination with oral vitamin C is used in oncologic care30–34.

 

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We propose a pragmatic approach for the administration of IV and oral vitamin C as a supportive therapy, including recommendations to ensure safety before and after chemotherapy. In the post-adjuvant and advanced incurable settings, IV C with radiation treatment is not discussed.
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METHODS​

Using the ovid platform in medline, a scoping review was conducted current to October 2016 to address these questions:

• ■ What are the pharmacokinetics of IV C and how would administration affect cancer patients?
• ■ Do cancer patients, compared with healthy subjects, experience vitamin C deficiency?
• ■ Is it safe to administer IV C to cancer patients during and after chemotherapy? Does IV C have the potential to improve qol?

Overall, the literature to date has not supported the efficacy of IV C as monotherapy in anticancer treatment, and our research questions therefore did not address that topic. Instead, we set out to address the potential value of vitamin C in supportive care. To be included in the review, studies had to be conducted in humans, to be published in English, and to provide information about the safety of IV C in malignant conditions, about any reductions in side effects or cancer-related symptoms, or about the effect for qol. We included controlled, uncontrolled, and nonrandomized studies. We excluded studies assessing oral ascorbate only and included those that assessed IV C or IV C combined with oral vitamin C administration.

 

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CONCLUSIONS​

In doses up to 25 g, IV C can safely be used to treat presumptive ascorbate deficiency based on symptoms and could favourably affect clinical parameters such as inflammation, fatigue, and qol. Using a rational, evidence-based approach such as that presented in Table v, clinicians can safely provide IV C as supportive care to patients with cancer.

The potential synergy of IV C with chemotherapy or radiation treatment, and the effect on overall outcomes, including survival, of a combined treatment approach, warrant further study. Studies that have already explored the effects of IV C in supportive care have design flaws such as small sample sizes and lack of a control group; thus, future studies could add a placebo control in a parallel-arm or crossover design. Studies that include blood biomarkers are also needed. How long any potential effect of an individual IV C treatment lasts is unknown. Studies designed to test that factor could be useful in creating evidence-based guidelines for optimal or sustained improvement in qol. Studies measuring vitamin C status before and during standard-of-care treatment could elucidate whether ongoing or intermittent deficiencies exist and whether such deficiencies could be related to symptoms that affect qol. Additional research is needed to study the roles of IV C and oral ascorbate with respect to dose, metabolic clearance, and infusion time. The role of target vitamin C plasma levels in relation to objective treatment response in humans requires further investigation as well. Although caution is warranted with respect to the use of IV C with surgery, chemotherapy, and radiation in the curative setting, vitamin C is a low-cost, safe therapy for the supportive care setting that might be an effective tool for improved supportive care.