High Dose Intravenous Vitamin C (IVC)

Vitamin C is an essential part of a healthy immune system. As a cancer treatment, intravenous Vitamin C (IVC) has shown promise in treating some cancers. However, some contraindicationsCaution should be used when two drugs or procedures are used together. with chemotherapy exist – along with mild side effects – but overall, IVC therapy continues to be actively researched.

Introduction

Most likely, you probably don’t think about Vitamin C each day, but it is one of life’s fundamental nutritional components. As a cancer treatment, intravenous Vitamin C (IVC) has been shown to have promising results. However, results in human studies are varied.

Cut your finger (or worse)? Collagen – which is dependent upon Vitamin C ­– is part of the body’s connective tissue and plays a crucial role in wound healing. Amino acids are the building blocks of proteins. Guess what: Vitamin C is a fundamental part of L-carnitine, which is essential for fueling our bodies (including our cardiac muscles). Vitamin C also works in conjunction with Vitamin E to regenerate antioxidantsProtects cells from damage caused by free radicals (unstable molecules made by the process of oxidation during normal metabolism). Free radicals may play a part in cancer, heart disease, stroke, and other diseases of aging. Antioxidants include beta-carotene, lycopene, Vitamins A, C, and E, and other natural and manufactured substances. within the body to help avoid free radical damage to our cells.

That’s just a few examples of how Vitamin C works within our body. Vitamin C, also called L-ascorbic acid or ascorbate, is a nutrient found in citrus fruits and some vegetables. Vitamin C also is available in supplementA product, generally taken orally, that contains one or more ingredients (such as vitamins or amino acids) that are intended to supplement one's diet and are not considered food. form. [1] As for cancer, there is ongoing research examining whether Vitamin C may help prevent or delay the development of specific cancers, heart disease, and other illnesses.

Now, if you have insufficient Vitamin C intake, it can lead to scurvy. This condition may include aching limbs, fatigue, and general weakness. If left untreated, scurvy may evolve into more severe problems like anemia, gum disease, and skin hemorrhages.

Studies also have shown that cancer patients tend to have lower levels of Vitamin C than generally healthy people. [2-5] Cancer patients also have higher rates of insufficiency or deficiency of Vitamin C. Chemotherapy can negatively impact the Vitamin C status of oncology patients. Nonetheless, because of Vitamin C’s supportive functions in the body, increasing the Vitamin C status of cancer patients is likely to be of benefit.

History of IVC as a cancer treatment

While the nutritional value of Vitamin C is well known, did you know intravenous Vitamin C has been studied as a cancer treatment for almost 50 years? Nobel Prize-winning chemist Linus Pauling and Scottish physician Ewan Cameron studied the possible benefits of Vitamin C therapy in clinical trials in the late 1970s and early 1980s. Later, Pauling and Canadian physician Abram Hoffer collaborated on a micronutrient regime, which included high-dose Vitamin C as an adjunctiveAnother treatment used together with the primary treatment. Its purpose is to assist the primary treatment. cancer therapy.

The study by Pauling and Cameron suggested that Vitamin C, given by I.V., could extend the life of advanced cancer patients by as much as six times the estimated prognosis. [6] “Vitamin C is thought to act as a pro-oxidant inside the cell in high concentration, and some hydrogen peroxide is formed which is rapidly disposed of by catalase in a normal cell,” Dr. William Wassell said. “Since cancer cells have a deficiency or lack entirely of catalase, the peroxides kill the [cancer] cell.”

Riordan et al. (1995) demonstrated the likelihood that Vitamin C was an effective anti-tumor therapy as long as high enough concentrations of it could be achieved inside the tumor(s). These researchers also concluded that oral Vitamin C supplementation was unlikely to produce blood levels of Vitamin C high enough to have a direct killing effect on a given tumor.

Later, in studying a specific line of cancer cells and the ability of Vitamin C to kill those cancer cells, Casciari et al. (2001) demonstrated this point. They showed that the rapid intravenous infusion of Vitamin C as sodium ascorbate in combination with alpha-lipoic acid was effective in reaching Vitamin C levels that were toxic to cancer cells. They also showed that a fat-soluble analog of Vitamin C, phenyl-ascorbate, was able to kill cancer cells effectively at a dose roughly three times lower than seen with unaltered Vitamin C.

Vitamin C was first suggested as a tool for cancer treatment in the 1950s. Its role in collagen production and protection led scientists to hypothesize that Vitamin C replenishment would protect healthy tissue from tumor invasiveness and metastasisThe spread of cancer cells from the place where they first formed to another part of the body. In metastasis, cancer cells break away from the original (primary) tumor, travel through the blood or lymph system, and form a new tumor in other organs or tissues of the body. The new, metastatic tumor is the same type of cancer as the primary tumor. For example, if breast cancer spreads to the lung, the cancer cells in the lung are breast cancer cells, not lung cancer cells. (McCormick, 1959; Cameron et al., 1979). Also, since cancer patients often experience a depletion of Vitamin C (Hoffman, 1985; Riordan et al., 2005), Vitamin C supplementation may improve immune system function and enhance patient health and well-being (Henson et al., 1991).

Cameron and Pauling observed survival rates four times as long as terminal cancer patients treated with intravenous ascorbate infusions, followed by oral supplementation (Cameron & Pauling, 1976). However, two randomized clinical trials reviewing 150 patients with advanced cancer using oral ascorbate alone conducted by the Mayo clinic showed no benefit. [7] As a result, intravenous ascorbate became the focus of further research. The rationales for using intravenous ascorbate infusions (IVC) to treat cancer include:

• Plasma ascorbate concentrations in the millimolar range can be safely achieved with IVC infusions.
• At molar concentrations, vitamin c is preferentially toxic to cancer cells in vitroThis means "outside the body" – or in the laboratory. and can inhibit angiogenesis in vitro and in vivoThis means "in the body.". 
• Vitamin C can accumulate in tumors, with significant tumor growth inhibition seen (in guinea pigs) at intra-tumor concentrations of 1 mM or higher.
• Published case studies report anti-cancer efficacy, improved patient well-being, and decreased markers of inflammation and tumor growth.
• Phase I clinical studies indicate that IVC can be administered safely with relatively few adverse effects.

If large amounts of Vitamin C present to cancer cells, it is suggested that large quantities will be absorbed. In these unusually large concentrations, the antioxidant Vitamin C will start behaving as a pro-oxidant as it interacts with intracellular copper and iron. This chemical interaction produces small amounts of hydrogen peroxide.

In theory, because the cancer cells are relatively low in the intracellular antioxidant enzymeA protein that speeds up chemical reactions in the body. catalase, the high dose Vitamin C induction of peroxide will continue to build up until it eventually breaks down the cancer cell from the inside out. This process may effectively make high-dose IVC a chemotherapeutic agent that can be given in conjunction with conventional cancer treatments. Based on the work of several Vitamin C pioneers before him, Dr. Riordan was able to show that Vitamin C was selectively toxic to cancer cells if given intravenously. This research was reproduced and published by Dr. Mark Levine at the National Institutes of Health.

However, only markedly higher doses of Vitamin C will selectively build up as peroxide in the cancer cells to the point of acting like chemotherapy. These tumor-toxic dosages can only be obtained by intravenous administration. While it is suggested that IVC is selectively toxic to cancer cells, no matter how high the concentration, Vitamin C does not harm healthy cells.

High-Dose Vitamin C as a cancer treatment

IV Administration for Vitamin C 

The IV administration of Vitamin C can achieve much higher plasma concentrations of Vitamin C. This is because the body regulates intestinal uptake of oral Vitamin C. It is believed that higher levels are required for some of the potential anti-cancer mechanisms of Vitamin C. IVC also has been known to enter solid tumors.

IVC side effects and safety 

IVC is generally considered well-tolerated and quite safe. In one clinical trial of 14 patients, it caused minor temporary side effects, including a possible increase in urinary flow, thirst, nausea, and vomiting, and chills, some of which may have been prevented. [8] 

There are some cautions that patients who are considering IVC should be aware of. Patients with reduced kidney function may have problems clearing high doses of IVC from circulation. [9] Patients with G6PD deficiency may struggle to detoxify oxidative stress generated by IVC. IVC also may interfere with glucoseA type of sugar; the chief source of energy for living organisms. monitors. IVC can assist the body in iron absorption and is not recommended for patients who have hemochromatosis. [10]

IVC contraindications

Preclinical studies have suggested that high doses of Vitamin C can have unfavorable interactions with some anticancer agents. [11] A 2013 Phase I clinical study evaluated the safety of combining high-dose IV ascorbate with the chemo drug gemcitabine in Stage IV pancreatic cancer patients, and the results showed the combination was well tolerated by patients, and they reported no significant adverse events. [12]

The NIH’s High-Dose Vitamin C (PDQ) reports,

“In vitro and in vivo animal studies have suggested that combining oral Vitamin C with bortezomib interferes with the drug’s ability to act as a proteasome inhibitor and blocks bortezomib-initiated apoptosisA type of cell death in which a series of molecular steps in a cell lead to its death. This is one method the body uses to get rid of unneeded or abnormal cells. The process of apoptosis may be blocked in cancer cells. Also called programmed cell death..[15-17] This interference occurred even with the oral administration of Vitamin C (40 mg/kg/day) to animals. Studies in cell culture and performed by adding blood plasma from healthy volunteers given oral Vitamin C (1 g/day) also showed a significant decrease in bortezomib’s growth inhibitory effect on multiple myeloma cells. Another study found similar results. Plasma from healthy volunteers who took 1 g of oral Vitamin C per day was shown to decrease bortezomib growth inhibition in multiple myeloma cells and to block its inhibitory effect on 20S proteasome activity. However, a study that utilized mice harboring human prostate cancer cell xenografts failed to find any significant effect of oral Vitamin C (40 mg/kg/day or 500 mg/kg/day) on the tumor growth inhibitory action of bortezomib.

“Several studies have been performed to assess the potential synergistic or inhibitory action of Vitamin C on certain chemotherapy drugs, with variable results. A series of studies in cell culture and in animals bearing tumors has shown that when given at high concentrations or dosages, dehydroascorbic acid (an oxidized form of Vitamin C) can interfere with the cytotoxic effects of several chemotherapy drugs. However, dehydroascorbic acid is generally present only at low concentrations in dietary supplements and fresh foods.” [13]

IVC and chemotherapy, radiation 

Clinical trials suggest that IVC does not negatively affect chemotherapy, and pre-clinical studies indicate that it may act in a cooperative manner in combination with different chemotherapeutic agents. [14] However, not all studies combining Vitamin C with chemotherapy have shown improved outcomes. [15-16]

Research is limited surrounding IVC and radiotherapy. Few studies have explored the use of IVC with radiation – and those that exist show conflicting results. There are several clinical trials currently being run exploring the interactions between IVC and standard anticancer regimens. 

IVC as an antioxidant/anti-inflammatory agent

Both pre-clinical and clinical studies suggest that IVC can lower the toxicity of chemotherapy, possibly due to its antioxidant and anti-inflammatory activities, without affecting the effectiveness of the chemotherapeutic agents. [17] The reduction in specific chemo-related side-effects results in an overall improvement in the health-related quality of life of oncology patients.

IVC anti-cancer mechanisms 

There are several suggestions relating to the anti-cancer mechanisms of IVC, including the generation of hydrogen peroxide, [18-21] enzyme cofactor activities, [22-23] along with it’s antioxidant and anti-inflammatory functions. [24] IVC likely affects different cancers in different ways. Still, more work should be focused on specific cancer types and underlying mechanisms of IVC that correlate to them.

IVC treatment dosing, frequency, and duration 

There is still no definitive agreement by the medical community as to dose amounts, frequency of dosing, and the duration of IVC to cancer patients. Pre-clinical studies indicate that more frequent dosing seems to show better efficacy. However, depending on the underlying mechanisms involved, there is potential for a patient to need long-term treatment over several years. This is far longer than the weeks or months of most clinical trials. [25-26]

A Phase 1 study in 2019 examined the maximum tolerated dose for safety, efficacy, and absorption and distribution in the body to set dosing limits for the Phase 2 portion of the study. [27] According to the NIH PDQ on IV Vitamin C, the study reported: [28]

“For the dose-escalation portion of the study, ascorbic acid doses ranged from 0.2 g/kg to 1.5 g/kg. To determine the optimal administration rate of ascorbic acid, patient cohorts received infusion rates set at 0.6 g/min, 0.8 g/min, or 1 g/min. The study showed no dose-limiting toxicity for all doses and dosing rates; thus, a maximum-tolerated dose was not reached, leading to a recommended phase II dose of 1.5 g/kg for ascorbic acid. Overall, no severe adverse reactions occurred, and the treatments were deemed safe and tolerable. A randomized Phase III trial (NCT02969681) is being conducted to determine the clinical efficacy of ascorbic acid with mFOLFOX6 with or without bevacizumab in patients with metastatic colorectal cancer.”

The Science of high-dose Vitamin C

IVC: in vitro and in vivo studies

In in vitro (laboratory) studies, the anticancer effects of certain substances are tested on tumor cells. In in vivo (animal) studies, the substance or procedure is tested for safety and efficacy. In vitro and in vivo studies are done before a substance is tested in people.

Laboratory studies suggest that high levels of Vitamin C may kill cancer cells. Studies have demonstrated the suppression of tumor growth after treatment with pharmacological ascorbate during in vitro models of pancreatic cancer, [29-31] liver cancer, [32] prostate cancer, [33] sarcoma, [34] mesothelioma, [35] and ovarian cancer. [36]

IVC and human studies

There have been several studies on high-dose Vitamin C given alone or in combination with other drugs in patients with cancer.

Human studies of IV Vitamin C alone

Two studies found that patients who received IV Vitamin C had a better quality of life and fewer side effects than those who did not. [37-38]

A case report in 1975 noted tumor regression in a patient with reticulum cell sarcoma. Once treated with ascorbic acid, the patient experienced improved well-being, along with the resolution of lung tumors. Interestingly, when the patient’s dose of ascorbic acid was reduced, he experienced some signs of disease regression, however, when returned to the higher dose of ascorbic acid, the patient, again, experienced remission. [39]

In a study of healthy volunteers as a control group, and cancer patients, Vitamin C was shown to be safe at doses up to 1.5 g/kg in patients who do not have kidney stones, other kidney diseases, or G6PD deficiency. [40-41] Studies have also shown that Vitamin C levels in the blood are higher when given by IV than when taken by mouth and last for more than 4 hours.

Human studies of IV Vitamin C combined with other drugs

Studies of IV Vitamin C combined with other drugs have shown mixed results. During a 2013 study of 14 patients with advanced pancreatic cancer, IV Vitamin C was given along with the chemotherapy agent gemcitabine, and the targeted therapy erlotinib. [42-43] Five patients did not complete the treatment because the tumor continued to grow during treatment. The nine patients who completed the treatment had stable disease, as shown by imaging studies. Patients had only a few side effects with the Vitamin C treatment.

In another small study of nine patients with advanced pancreatic cancer, patients were given IV Vitamin C twice a week for four weeks during each chemo cycle.[44] The results show no progression of the disease over an average of six months, and no severe side effects were reported.

A 2014 study of 27 patients with advanced ovarian cancer were given chemotherapy alone, or in the combination of chemo and IV Vitamin C. IV Vitamin C was administered during chemotherapy and for six months after chemo treatment ended. Patients who received the IVC had fewer side effects. [45]

Patients with non-small cell lung cancer or glioblastoma multiforme in two pilot trials were given standard therapy plus IV Vitamin C. Patients had better overall survival and fewer side effects compared to the control groups.[46]

More studies on combining IV high-dose Vitamin C with other drugs are being done. These include several clinical trials combining IV Vitamin C with arsenic trioxide (ATO), showing mixed results. ATO has been shown to promote cell death of malignant plasma cells by including inhibition of DNA binding by nuclear factor kappa-B, a key player in the development of chemoresistance in multiple myeloma (MM). [47]

Conclusion 

While IVC as a cancer treatment option has demonstrated encouraging results in some models, the overall results in human studies are mixed. The interactions with other cancer treatment modalities, as well as the mechanical details of IVC, have not been fully defined.

FAQ

IVC Clinical Trials

A list of currently active (as of 01/16/2020) clinical trials using ascorbic acid/Vitamin C for cancer for which you may be eligible.

High Dose Vitamin C Intravenous Infusion in Patients with Resectable or Metastatic Solid Tumor Malignancies

• Phase: I
• Status: Open as of 01/16/2020
• Location: Upper East Side – Manhattan
• Gender: men and women
• Age: 18 and over
• Disease Criteria: resectable or metastatic solid tumor malignancies
• View Trial Details

The Effectiveness of High-dose Intravenous Vitamin c With Very Low Carbohydrate Diet for Terminal Colon Cancer Patients

• Phase: Pilot Study
• Status: Not Yet Recruiting, as of 01/16/2020
• Location: Taiwan
• Gender: men and women
• Age: 20 and over
• Disease Criteria: stage IV colon cancer; with KRAS and BRAF mutation
• View Trial Details

High Doses of Vitamin C with Chemotherapy and Radiation Therapy in Treating Patients with Non-Small Cell Lung Cancer

• Phase: II
• Status: Recruiting, as of 01/16/2020
• Location: University of Iowa / Holden Comprehensive Cancer Center
• Gender: men and women
• Age: not listed
• Disease Criteria: non-small cell lung cancer
• View Trial Details

Gemcitabine and Nab-Paclitaxel with or without Pharmacological Ascorbate in Treating Patients with Metastatic Pancreatic Cancer

• Phase: II
• Status: Recruiting, as of 01/16/2020
• Location: University of Iowa / Holden Comprehensive Cancer Center
• Gender: men and women
• Age: 18 and over
• Disease Criteria: Pathologic diagnosis (cell samples, biopsy, brushing, surgical sample) of adenocarcinomaCancer that begins in glandular (secretory) cells. Most cancers of the breast, pancreas, lung, prostate, and colon are adenocarcinomas. of the pancreas. Cancer from the Ampullae of Vater is also eligible.
• View Trial Details

A Clinical Trial Evaluating the Effect of Pharmacological Ascorbate on Radiation Therapy for Pancreatic Cancer Patients (XACT-PANC-2)

• Phase: II
• Status: Not yet recruiting, as of 01/16/2020
• Location: University of Iowa / Holden Comprehensive Cancer Center
• Gender: men and women
• Age: 18 and over
• Disease Criteria: Histologic or cytologic diagnosis of pancreatic adenocarcinoma
• View Trial Details

High-Dose Ascorbic Acid, Temozolomide, and Radiation Therapy in Treating Patients with Glioblastoma

• Phase: II
• Status: Recruiting, as of 01/16/2020
• Location: University of Iowa / Holden Comprehensive Cancer Center
• Gender: men and women
• Age: 18 and over
• Disease Criteria: newly diagnosed (i.e., within 5 weeks), histologically or cytologically confirmed glioblastoma multiforme
• View Trial Details

High Dose Ascorbate and Radiation Therapy before Surgery in Treating Patients with Stage IIB-IV Soft Tissue Sarcomas of Extremity, Trunk, and Retroperitoneum

• Phase: 1b/2
• Status: Recruiting, as of 01/16/2020
• Location: University of Iowa / Holden Comprehensive Cancer Center
• Gender: Men and women
• Age: 18 and over
• Disease Criteria: Soft Tissue Sarcoma
• View Trial Details

For the most recent list of all clinical trials using IVC for cancers, see ClinicalTrials.gov Vitamin C + Cancer Results.

Questions to ask your health care provider about IVC

• What benefits can be expected from IVC?
• What are the possible side effects of IVC?
• Is IVC safe for someone in my circumstances?
• Will IVC affect chemotherapy or radiation?
• Is this therapy part of a clinical trial?
• If so, who is the sponsor of the trial?
• Is IVC covered by my health insurance?
• What can I expect during my appointment?