Clinical Research at the Riordan Clinic: Continuous Intravenous Vitamin C in the Treatment of Cancer

Author: Nina Mikirova, PhD

The below summary is from a research article by Dr. Nina Mikirova, Director of Research at the Riordan Clinic. This article explains an innovative therapy being developed at the Riordan Clinic for patients who have cancer utilizing continuous infusion of intravenous vitamin C. Research is an important tool utilized at the Riordan Clinic for developing cutting edge clinical therapies.

Intravenous vitamin C (IVC) therapy is widely used in naturopathic and integrative oncology. Preclinical studies of large doses of ascorbic acid (vitamin C) have been reported to show significant anti-cancer effects in animal models and tissue culture investigations.

Studies on understanding the biological activities of ascorbate have led to a number of hypotheses for mechanisms of anti-cancer activity, such as the generation of significant quantities of hydrogen peroxide by the autoxidation of pharmacological concentrations of ascorbate, changes in the metabolic activity, and stimulation of the enzymes that have a cofactor requirement for ascorbate. In addition, high dose ascorbic acid may improve the anti-cancer action of chemotherapeutic agents, boost immune cell functioning, and inhibit angiogenesis.

Many case studies demonstrated the effectiveness of intravenous vitamin C, with varying degrees of success. Clinically published IVC case studies report efficacy against a variety of cancers in humans, including pancreatic cancer, bone metastases accompanying breast cancer, non-Hodgkin’s lymphoma, liver carcinoma, colon carcinoma, and ovarian cancer.

Several Phase I and Phase II clinical trials have been conducted in the last ten years to test safety and efficacy when IVC is used as an adjuvant with chemotherapy. The results of these trials confirm that IVC can be administered safely.

Most practitioners administer IV ascorbate to cancer patients by bolus infusions 2-3 times per week.

There have been two clinical trials that used continuous IVC infusions. Cameron and Pauling performed a clinical trial in 100 terminal cancer patients. The protocol included an initial 10 day course of IV ascorbate, at a relatively low daily dose of 10 g/day given by continuous infusions, followed by daily oral intakes of 10-30 g/day, in divided doses. Their results showed increased survival time and improved the quality of life of the patients, compared with patients who had not received IVC.

The ideas of Linus Pauling were extended in the model developed by Dr. Hickey.  He described “The dynamic flow model” that proposes restoring human physiology by administering excess ascorbate, over and above the amount normally absorbed, spread throughout the day, so a consistent supply is achieved.

The second trial of the treatment of cancer patients by continuous infusions was conducted by Dr. Riordan. In this Phase I clinical trial, patients were administered continuous infusions using an infusion pump. In the Riordan Clinic trial, patients were treated by continuous infusion, which was administered over much longer periods of time than bolus intermittent treatments. For most patients the duration of the continuous infusion was at least 20 hours, as the duration of bolus infusion is from one hour to three hours, depending on the dosage.

The trial lasted eight weeks and involved terminal patients with poor prognosis. 24 subjects were given continuous IVC at doses between 150 and 710 mg/kg/day (10-50 grams per day). Most of the patients had colon cancer with liver and lung metastasis and three patients had pancreatic or liver cancer. All patients had several chemotherapy/radiation treatments before entering the study.  79% of the patients had a metastatic tumor.

In our recent publication, we analyzed previously unpublished parameters from this clinical study, including blood chemistry and blood count parameters that are reportedly related to patient prognosis and degree of inflammation. This included: absolute neutrophil and lymphocyte counts and the neutrophil-to-lymphocyte ratio; lactate dehydrogenase, an enzyme involved in tumor initiation, metastasis, and recurrence; creatinine, the depletion of which is associated with cachexia; and glucose, as hyperglycemia is common in cancer patients.

The most obvious effect of IVC therapy was to increase patient vitamin C levels. Consistent with other reports, the plasma ascorbate measurements conducted in this trial showed that vitamin C depletion in cancer patients is common. In fact, ten out of twenty-four subjects entered the trial with plasma ascorbate concentrations undetectable by the colorimetric ascorbate assay used at that time, with another four having ascorbate concentrations below the normal range. IVC infusion increased plasma levels to 1 mM. This likely replenished depleted tissue ascorbate stores as well.

As lymphocytes and neutrophils have important roles in tumorigenesis and carcinogenesis, we analyzed the effect of the treatment on these parameters. As the result of chemotherapy, neutrophil and lymphocyte counts typically decrease in cancer patients, with the effect being more severe for lymphocytes.

Analysis of white blood cell counts for patients in this trial indicated the potential for IVC to increase lymphocyte and neutrophil counts for patients in whom these numbers are below normal, while reducing neutrophil counts in patients for whom neutrophil counts are elevated.

It was particularly important for lymphocyte counts. Lymphopenia commonly occurs in cancer patients who had chemotherapy and high levels of oxidative stress induced by treatment, predicting a poor prognosis.

In our study population, about half of the patients who started intervention had lymphocyte counts lower than normal range. For patients with severe lymphopenia, who completed treatment, the median improvement in the lymphocyte count was 69%, and for all patients with lymphocyte levels lower than normal range the median improvement was 22%. These data proved that continuous IVC can improve immune function of cancer patients by increasing the level of lymphocytes, especially in patients with low lymphocyte count.   Our data also indicated that lower doses are more favorable for the improvement of lymphocyte count.

As absolute neutrophil counts and neutrophil-to-lymphocyte (NLR) ratios are useful prognostic factors in a variety of cancers, with higher values of NLR indicating lower survival times, the effect of continuous infusion on these parameters was analyzed. For cancer patients in general, increased neutrophil counts are consistent with systemic inflammation, and a neutrophilic response is associated with poor prognosis, as it can inhibit the immune system by suppressing the cytotoxic activity of T cells.  For most of the patients, the tendency during treatment was for normalization of the neutrophil counts, i.e. improvement of neutrophil counts at the low level of this parameter and a decrease for the higher values.

The present analysis of neutrophil-to-lymphocyte ratios (NLR) also demonstrated the regulatory effect of IVC. NLR has been used to assess inflammatory response and has been suggested as a prognostic factor in a variety of cancers. In particular, cut-off values ranging between 2.0 and 4.0 were associated with a significant increase in all-cause mortality. As NLR may reflect the balance between the activation of the inflammatory pathway and the anti-tumor immune function, elevated NLR due to neutrophilia is linked to accelerated tumor development.

In the present study, most of the patients entered the trial with NLRs well above this cut-off. Continuous IVC therapy tended to decrease the rate of growth of NLR. Moreover, we were able to confirm the predictive potential of NLR. Our data demonstrated the relationship between the survival of patients and the rate of growth of NLR, as NLR increases correlated with lower survival times of the patients.

We examined the rate of change in this ratio (ΔNLR) for each patient before and after therapy. The comparison of the trend in the change of NLR measured for periods one week before treatment and during treatment demonstrated that the rate of change was decreased. This suggests that IVC may reduce NLR levels, thus improving prognosis. Since the rate of increase in NLR for patients with initially elevated values decreased during IVC therapy, ascorbate may be decreasing inflammation in these subjects.

As activation of glycolytic metabolism is a significant characteristic of tumor cells, and since lactate dehydrogenase (LDH) is an important coenzyme in glycolysis, elevated levels of serum lactate dehydrogenase may be useful prognostic biomarkers. Lactate dehydrogenase is elevated in many types of cancers; it has been linked to tumor growth, maintenance, and invasion.

The rate of increase of LDH was calculated before and after treatment. The value of this parameter (LDH rate of growth) was decreased in 38% of the patients, increased in 28.6%, and was not changed in 33.4% of patients. The result that LDH decreased in 38% of the subjects is remarkable, considering their illness.

The median survival time for the all participants with initial LDH higher than the normal range  (LDH>245 U/L) was 95 days. In contrast, the median survival time for all subjects with normal initial LDH values was 173 days.

Hyperglycemia is another prognostic factor in cancer patients. It is common in cancer patients and represents a challenge during therapy. For example, about 70% of pancreatic cancer patients have impaired glucose tolerance. Moreover, there is a link between the lowering of blood glucose concentration and remission of malignancy. In one study, patients under insulin coma therapy for six months (for psychosis) were reported to become free of large tumor burdens considered incurable by their oncologists.

Hyperglycemia was common in our cancer patients. Two-thirds of the patients in our study had above-normal blood glucose concentrations. There were changes in blood glucose during IVC therapy. Blood glucose levels were decreased for patients with the concentrations higher than normal range during IVC therapy.

Several clinical trials have established that IVC can be administered safely. In the continuous IVC infusion trial, from which data for the present analysis were obtained, side effects were mostly minor, and the criterion for stopping the clinical trial (two or more Grade 3 or higher adverse events at a given dose at least possibly related to the treatment) was never reached. Briefly, blood chemistry parameters that serve as indicators of renal function (BUN, creatinine, and uric acid) remained relatively stable, or, in the case of uric acid, decreased during therapy. Only four subjects experienced BUN increases during therapy.

The most common side effects were nausea (11 subjects), injector port occlusion (10 subjects), dry skin or mouth (7 subjects), edema (7 subjects) and fatigue (6 subjects). These were generally minor (Grade 1). Most of the Grade 3 events involved hypokalemia, which is considered possibly related to the ascorbate therapy.

In summary, the present analysis demonstrated the regulatory and normalizing effect of continuous IVC infusions on lymphopenia, neutrophil-to-lymphocyte ratios, and absolute neutrophil counts. Despite the very poor health status of patients, continuous IVC treatment had positive effects on the important parameter that characterized tumor metabolism (lactate dehydrogenase) and blood glucose concentration.



Nina Mikirova, Joseph Casciari, Ronald Hunninghake. Continuous intravenous vitamin C in the cancer treatment: reevaluation of a Phase I clinical study. Functional Foods in Health and Disease 2019; 9(3): 180-204.