Protocols and Literature for Vitamin C Therapy

Protocols and Literature

This page provides protocols and the scientific literature for taking vitamin C. It is aimed at health practitioners considering vitamin C therapy, particularly intravenous vitamin C therapy, for their patients. The page also allows patients to provide their doctors with protocols and the scientific literature.

Treating Cancer with Intravenous Vitamin C

General

The treatment of cancer by intravenously administering vitamin C has a long history dating back to the mid-1970s.

A detailed protocol for the treatment of cancer by intravenously administering vitamin C has been published by the Riordan Clinic. A review of intravenous vitamin C for cancer therapy and gaps in our knowledge was published in 2018. A systematic review of intravenous ascorbate in cancer clinical trials was published in 2018.

Clinical studies have so far been limited primarily to Phase I safety and pharmacokinetic trials.

However, a randomized clinical trial showed a trend toward overall survival, a significant 8.5-week increase in progression-free survival, and fewer adverse events for ovarian cancer patients treated with intravenous vitamin C.

There are also case reports of patients with advanced cancers who had remarkably long survival times following administration of high-dose intravenous vitamin C.

Scientific Basis

The basis for treating cancer with vitamin C is three-fold.

First, pharmacologic concentrations (0.3–20 mM) of vitamin C are selectively cytotoxic against cancer cells but not normal cells in the laboratory. This concentration of vitamin C can be achieved in blood plasma through the intravenous administration of vitamin C, but not through oral administration. The intestinal uptake of oral vitamin C is regulated via the sodium-dependent vitamin C transporter-1 (SVCT1), which is bypassed with intravenous administration. Plasma levels seen with intravenous administration are 100 to 500 times higher than levels seen with oral ingestion. (Peak plasma concentrations from oral ingestion rarely exceed 200 µmol/L while intravenous administration can result in peak plasma concentrations of 20 mmol/L.) The high level of plasma vitamin C has a half-life of about 2 h as the vitamin C is rapidly cleared by the kidneys. The vitamin C breaks down easily, generating hydrogen peroxide, which is a reactive oxygen species that damages tissue and DNA.

Specifically, tumor cells are much less capable of removing the damaging hydrogen peroxide than normal cells. This explains how extremely high levels of vitamin C do not affect normal tissue but can damage tumor tissue. Normal cells have several ways to remove hydrogen peroxide. The enzymes catalase and glutathione peroxidase are central to the removal of hydrogen peroxide generated by decomposing vitamin C. Cancers with low levels of these enzymes are therefore likely to be the most responsive to high-dose vitamin C therapy.

Additionally, there are possible tumor growth inhibition mechanisms relating to enzyme co-factor activity at lower plasma levels of vitamin C, and the anti-inflammatory and anti-oxidant activities of vitamin C. The reader is again referred to a review of intravenous vitamin C for cancer therapy.

The intravenous administration of vitamin C to guinea pigs and mice has been shown to reduce cancer growth in the cases of pancreatic cancer, colon cancer, sarcoma, leukemia, prostate cancer, and mesothelioma [1].

Second, cancer patients typically present with low blood plasma levels of vitamin C compared with healthy controls, with a large proportion of cancer patients presenting with hypovitaminosis C (<23 µmol/L) and vitamin C deficiency (<11 µmol/L). Plasma levels of vitamin C have been shown to decrease with increasing severity of lymphoma, breast, cervical, colorectal, and endometrial cancers. This compromised vitamin C status is likely due to enhanced metabolic turnover resulting from oxidative and inflammatory aspects of the cancer.

Furthermore, epidemiological studies showed a decreased incidence of cancer and improved survival in patients with higher dietary intakes of vitamin C or higher plasma levels of the vitamin. Inverse associations have been found between dietary vitamin C intake and cancers of the lung, breast, colon or rectum, stomach, oral cavity, larynx or pharynx, and esophagus.

These observations suggest that the body uses vitamin C in fighting cancer and the patient will benefit from vitamin C supplementation during treatment. At the very least, cancer patients need vitamin C supplementation for use in the body more generally.

Furthermore, there is evidence that adjunctive cancer therapies impact negatively on vitamin C levels (e.g., see the section on chemotherapy below).

Two clinical trials reported improved quality of life or mood with the intravenous administration of vitamin C in doses of 10 g or less. Animals that synthesize their own vitamin C produce greater amounts when under a tumor load. Intravenous vitamin C has been shown to reduce inflammation in cancer patients.

Third, studies have suggested that vitamin C inhibits tumor angiogenesis, which is the process of new blood vessel growth toward and into a tumor and considered critical to tumor growth and metastasis. The inhibition is possibly achieved through several mechanisms.

Dosing

An example dosing of ascorbate is 1 g/kg, at a minimum frequency of twice weekly. The infusion is performed at a rate of 0.5 g per minute. Plasma vitamin C levels are checked to ascertain if a therapeutic range of 350–400 mg/dL is achieved, and subsequent adjustments to the dose are made. Efficacy is assessed with a minimum of a two-month and preferably three-month trial period. However, further research is needed before well-defined clinical recommendations can be made. Therapy less than twice weekly, with dosing less than 1 g/kg, appears to be therapeutically ineffective, while dosing at 1 g/kg at least twice weekly has promise. Again, the reader is referred to the Riordan Clinic Protocol and Review of Intravenous Vitamin C for Cancer Therapy.

Safety

Vitamin C has been shown to be safe in nearly all patient populations, alone and in combination with chemotherapy.

In a survey of 9328 patients receiving intravenous vitamin C, only 1% reported minor side effects, which included lethargy, fatigue, change in mental status, and vein irritation. Recent Phase-1 safety trials of high-dose intravenous vitamin C indicated only minor side effects and no adverse events over and above what would be expected from the underlying cancer or chemotherapy side effects.

Precautions and Complications

Patients are typically screened for glucose-6-phosphate dehydrogenase (G6PD) deficiency because of the risk of hemolytic anemia. Patients with this deficiency can receive intravenous vitamin C but at lower doses.

The intravenous administration of vitamin C can interfere with point-of-care glucose meters used by diabetics. This does not apply to laboratory meters or the oral intake of vitamin C.

The intravenous administration of vitamin C typically begins at relatively low doses around 15 grams to reduce risks associated with tumor necrosis or tumor lysis syndrome, where the killing of a tumor releases toxins.

It has been speculated that the intravenous administration of vitamin C causes kidney stones for some patients having existing renal dysfunction. The idea is that a minor product of vitamin C metabolism is oxalate, which has the potential to form calcium oxalate crystals in individuals predisposed to renal stone formation. One study reported that a patient with a history of renal calculi developed a kidney stone following 2 weeks of continuous intravenous vitamin C infusion while another study reported acute oxalate nephropathy following high-dose intravenous vitamin C administration for some patients having existing renal dysfunction. Although this evidence is far from conclusive, some clinicians screen patients for existing renal dysfunction. A 2009 study found that less than 0.5% of a very large intravenous dose of vitamin C is recovered as urinary oxalic acid in people with normal renal function. The experience of one clinic having treated hundreds of cancer patients with intravenous vitamin C is that the incidence of kidney stones is negligible.

Vitamin C can increase iron absorption and thus elevate iron stores in patients with iron overload.

Interactions with Chemotherapy

There has been much discussion of the interaction of chemotherapy and vitamin C.

In terms of safety, the combination of intravenous vitamin C and chemotherapy is non-toxic and generally well tolerated.

In terms of the need for vitamin C supplementation when a patient receives chemotherapy, it is noted that chemotherapy increases oxidative stress and inflammation, and the administration of intravenous vitamin C leads to lower levels of circulating vitamin C in chemotherapy patients than in healthy controls. Some anticancer therapies, such as cisplatin, fluorouracil, nilotinib, and interleukin-2, are known to lower the vitamin C levels of cancer patients, sometimes resulting in scurvy-like symptoms.

In terms of the efficacy of combining chemotherapy and vitamin C, clinicians have often avoided concurrent administration of intravenous vitamin C and chemotherapy drugs owing to vitamin C being an antioxidant. However, only some drugs act via an oxidizing mechanism.

Further details on chemotherapy and radiative treatment to come.