High-Dose Intravenous Vitamin C

Cameron, Pauling and the 1970s cancer claims

The National Cancer Institute's summary on intravenous vitamin C places the first use of oral and intravenous vitamin C for cancer in the 1970s, with the Scottish surgeon Ewan Cameron and a colleague, and says this work led to a collaboration with the Nobel Prize-winning chemist Linus Pauling. In 1976 Cameron and Pauling reported 100 terminal cancer patients given supplemental ascorbate alongside 1,000 patients described as similar, and concluded that survival was longer in the ascorbate group.

The NCI summary describes these as case series that used matched controls from the same hospital, and notes that the authors of the earlier 50-patient series acknowledged that the lack of controls prevented definite attribution of any response to the treatment.

The Mayo Clinic randomized trials

Two placebo-controlled Mayo Clinic trials tried to reproduce the claims. The 1979 trial randomized 150 people with advanced cancer and found no appreciable difference in symptoms, performance status, appetite or weight; median survival was about seven weeks and the survival curves essentially overlapped. The 1985 trial randomized 100 people with advanced colorectal cancer who had no previous chemotherapy and found no advantage over placebo in time to progression or survival, and no objective improvement among those with measurable disease. The NCI summary points out that both trials used oral vitamin C and gave no intravenous vitamin C.

Route of administration and later pharmacokinetic work

A 1996 depletion-repletion study in healthy volunteers found that plasma vitamin C concentrations level off as oral intake rises, with absorption falling at larger single oral amounts. A 2004 study by Levine's group of 17 healthy hospitalized volunteers found higher peak plasma concentrations after intravenous than oral dosing, with the gap widening as the amount rose. Modeling predicted peak plasma levels of about 220 micromol per liter for the maximum tolerated oral regimen against about 13,400 micromol per liter for a large intravenous amount. The authors noted that no patient data confirmed the modeling and argued that oral-only trials could not judge intravenous treatment.

In 2006 the same group described three patients with advanced cancer and long survival after intravenous vitamin C, reviewed under NCI Best Case Series guidelines, and called for the role of the treatment to be reassessed. The NCI summary adds that these patients also used other treatments such as vitamins, minerals and botanicals.

Use among complementary practitioners

A survey of attendees at complementary medicine conferences in 2006 and 2008 received 199 responses from 550 people. Of these, 172 practitioners had given intravenous vitamin C, to an estimated 11,233 patients in 2006 and 8,876 in 2008, most often for infection, cancer and fatigue. The authors said total patient numbers in the United States could not be estimated from the survey. The sources reviewed do not describe the Riordan protocols by name, so this page does not cover them.

Names used in the sources

The NCI summary titles its page intravenous vitamin C and notes that the substance is also known as ascorbate or L-ascorbic acid. The sources reviewed also use the terms high-dose intravenous vitamin C, pharmacological ascorbate and pharmacologic IV vitamin C. No source reviewed sets a single dose threshold for the word high, and this page does not state doses.

Distinctions that matter when reading the research

Oral vitamin C and intravenous vitamin C are treated as different exposures by the NCI summary, which says the early Mayo Clinic trials tested the oral form. Intravenous vitamin C alone is also distinct from the combination of vitamin C, thiamine and hydrocortisone tested in the VICTAS sepsis trial, so results for one cannot be assumed for the other. Studies in cancer, sepsis and COVID-19 enrolled different populations and are reported separately below.

What the infusion is

High-dose intravenous vitamin C is the delivery of ascorbic acid directly into a vein, which bypasses the limits on absorption and blood levels that apply to oral intake. The NCI summary states that intravenous administration produces much higher blood concentrations than oral administration of the same amount, and that plasma levels after infusion are maintained for more than four hours in the studies it cites. This page gives no doses, infusion rates or schedules.

Who delivers it and how it is overseen

The sources describe two settings. In trials, infusions were given to hospitalized adults, for example in intensive care units for sepsis and COVID-19, and in oncology research settings. Outside research, a survey found that complementary medicine practitioners give it, mainly for infection, cancer and fatigue. The NCI summary reports that trials screened out people with risk factors such as G6PD deficiency, kidney disease or kidney stones.

The sources reviewed do not describe a professional body register, training standard or code of practice specific to intravenous vitamin C. The 2023 sepsis guideline was written by a 21-member expert panel using a conflict-of-interest policy, which is a guideline group rather than a registry of practitioners. NCCIH advises people with cancer to discuss supplement use with their health care providers.

Related Machipedia pages

This practice is a member of the Machipedia family page IV Therapy, which covers infusion-based approaches generally. Readers comparing other infused preparations can consult the pages on Myers' Cocktail, Intravenous Glutathione and Chelation Therapy. Nutritional Therapy and Naturopathy cover the wider settings in which complementary practitioners work, including the practitioners surveyed in the 2010 study.

Uses described by practitioners and researchers

Practitioners surveyed in 2006 and 2008 reported giving intravenous vitamin C most often for infection, cancer and fatigue. A 2015 review noted that many people with cancer take vitamin C in the belief that it strengthens the anticancer effect of chemotherapy and reduces its toxicity. In sepsis, the CITRIS-ALI authors cited experimental data suggesting that vitamin C may attenuate inflammation and vascular injury.

Laboratory rationale

The NCI summary reports that very high ascorbic acid concentrations decreased cell proliferation in several cancer cell lines, including prostate, pancreatic, colon and mesothelioma lines, and that this effect has been linked to a reaction that generates hydrogen peroxide. It also reports tumor growth inhibition in some animal models, and other laboratory and animal work in which vitamin C interfered with anticancer drugs. These findings come from cells and animals and do not establish an effect in people.

Cancer: systematic reviews

A 2015 systematic review of 34 studies (five randomized trials with 322 people, 12 phase I/II trials, six observational studies and 11 case reports) found no statistically significant improvement in overall or progression-free survival, or reduced toxicity, in any randomized trial, with evidence of antitumor effect limited to case reports and uncontrolled studies. A 2018 review of 23 phase I/II trials in 385 patients found only one randomized trial, in ovarian cancer, and its authors called for placebo-controlled trials. A 2021 review of 21 studies in 1,961 patients found heterogeneous data for intravenous use and no randomized trials with statistical group comparisons.

Cancer: recent trials and agency statements

The NCI summary, updated in May 2025, describes two randomized phase II trials published in 2024. In 47 men with metastatic castration-resistant prostate cancer, adding intravenous vitamin C to docetaxel did not improve PSA response, toxicity or other outcomes. In 34 people with stage IV pancreatic cancer, adding it to gemcitabine and nab-paclitaxel was reported to prolong overall and progression-free survival without added toxicity. The summary says early findings appear promising and are well tolerated but limited by weak trial design. NCCIH states that human research is limited and that evidence on tumor growth and survival is mixed.

Sepsis and septic shock trials

CITRIS-ALI randomized 167 adults with sepsis and ARDS and found no significant difference in the change in organ failure score or in inflammation and vascular injury markers. Of 46 secondary outcomes, 43 did not differ; exploratory 28-day mortality was 29.8 percent with vitamin C and 46.3 percent with placebo, which the authors said was not adjusted for multiple comparisons. VICTAS tested vitamin C with thiamine and hydrocortisone in 501 adults and found no significant difference in ventilator- and vasopressor-free days; it ended early for administrative reasons and may have been underpowered.

LOVIT randomized 872 adults with sepsis who were receiving vasopressors. Death or persistent organ dysfunction at 28 days occurred in 44.5 percent given vitamin C and 38.5 percent given placebo (risk ratio 1.21, 95% confidence interval 1.04 to 1.40); death alone was 35.4 percent against 31.6 percent (risk ratio 1.17, 0.98 to 1.40).

Syntheses and guideline in sepsis

A meta-analysis of 16 trials in 2,130 critically ill adults reported lower mortality (risk ratio 0.73) but rated the finding low certainty. The 2023 rapid practice guideline found that at 90 days vitamin C probably does not substantially affect mortality (moderate certainty, six trials, 2,148 patients), and made a conditional recommendation against using it in adult sepsis beyond standard nutritional supplementation.

COVID-19 trials

A 56-patient pilot trial in China found no difference in ventilator-free days or 28-day mortality, with higher oxygenation ratios and lower interleukin-6 at day seven that the authors called a possible signal. The harmonized LOVIT-COVID and REMAP-CAP trials stopped after statistical triggers for harm and futility were met; the adjusted odds ratio for the primary outcome was 0.88 in critically ill and 0.80 in not critically ill patients, and the authors concluded vitamin C had a low probability of improving outcomes.

Kidney effects

A case report describes a woman in her seventies with endometrial cancer who developed acute kidney injury after weekly intravenous vitamin C from an alternative provider; biopsy showed tubular injury with calcium oxalate crystals, and she needed permanent dialysis. The NCI summary reports renal failure after ascorbic acid in people with existing kidney disease, and trials screened out people with kidney disease or stones. NCCIH lists iron overload and kidney disease as conditions with higher risk of serious toxicity.

Blood and laboratory effects

A review of 14 case reports of vitamin C-induced hemolysis found that 71.4 percent of patients had G6PD deficiency; 57.1 percent received intravenous vitamin C, half developed complications including acute kidney injury, and one death was reported. Testing of three hospital glucose meters found false elevations on two of them as ascorbic acid concentration rose, and the third gave error messages, which the NCI summary also notes for strip-based meters.

Reported adverse events and fluid load

Among 9,328 patients with data in the practitioner survey, 101 had side effects, mostly minor: fatigue in 59, mental status change in 21 and vein irritation in six. Published serious events included two deaths in people known to be at risk. LOVIT reported one severe hypoglycemic episode and one serious anaphylaxis event in the vitamin C group. The NCI summary mentions one study with fluid overload, possibly related to the delivery method.

Interactions and care boundaries

The NCI summary says interactions with anticancer drugs have mainly been seen in preclinical work, including cell and animal studies of oral vitamin C with bortezomib, and that human data on intravenous vitamin C with bortezomib are lacking. Gemcitabine combinations were well tolerated in early trials. NCCIH advises discussing antioxidant supplements with health care providers during cancer treatment. Intravenous vitamin C should not delay or replace necessary medical care.