Intravenous Ascorbic Acid (also known as vitamin C or L-ascorbic acid), is a process that delivers soluble ascorbic acid directly into the bloodstream. It is not approved for use to treat any medical condition. The use of intravenous ascorbic acid as a proposed cancer treatment or co-treatment has been a controversial topic since the emergence of misleading data in the 1970s.

Contraindications

High doses of ascorbic acid administered by intravenous infusion have been shown to increase the absorption of

iron Iron () is a chemical element with Symbol (chemistry), symbol Fe (from la, Wikt:ferrum, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 element, group 8 of the periodic table. It is, Abundanc ...

. In individuals with

hemochromatosis Iron overload or hemochromatosis (also spelled ''haemochromatosis'' in British English) indicates increased total accumulation of iron in the body from any cause and resulting organ damage. The most important causes are hereditary haemochromatos ...

(a genetic disorder where the body takes up and stores too much iron), intravenous ascorbic acid is contraindicated as high dosages of ascorbic acid may result in iron overloading and therefore, lead to life-threatening complications such as heart disease, diabetes, or tissue damage. High dosages of ascorbic acid (such as those used in intravenous therapy) have been reported to cause some intestinal discomfort, diarrhoea, as well as increased gas and urination.

Alternative medicine and unproven applications

Sepsis

The "Marik protocol", or "HAT" protocol, as devised by Paul E. Marik, proposed a combination of intravenous

vitamin C Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) ...

hydrocortisone Hydrocortisone is the name for the hormone cortisol when supplied as a medication. Uses include conditions such as adrenocortical insufficiency, adrenogenital syndrome, high blood calcium, thyroiditis, rheumatoid arthritis, dermatitis, asthm ...

, and

thiamine Thiamine, also known as thiamin and vitamin B1, is a vitamin, an essential micronutrient, that cannot be made in the body. It is found in food and commercially synthesized to be a dietary supplement or medication. Phosphorylated forms of thi ...

as a treatment for preventing

sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...

for people in

intensive care Intensive care medicine, also called critical care medicine, is a medical specialty that deals with seriously or critically ill patients who have, are at risk of, or are recovering from conditions that may be life-threatening. It includes pro ...

. Marik's own initial research, published in 2017, showed a dramatic evidence of benefit, leading to the protocol becoming popular among intensive care physicians, especially after the protocol received attention on social media and

National Public Radio National Public Radio (NPR, stylized in all lowercase) is an American privately and state funded nonprofit media organization headquartered in Washington, D.C., with its NPR West headquarters in Culver City, California. It differs from other ...

, drawing criticism of

science by press conference Science by press conference or science by press release is the practice by which scientists put an unusual focus on publicizing results of research in the media, in the form of press conference events or press release statements. The term is usual ...

from the wider medical community. Subsequent independent research failed to replicate Marik's positive results, indicating the possibility that they had been compromised by bias. A systematic review of trials in 2021 found that the claimed benefits of the protocol could not be confirmed.

Pharmacology

Mechanism of action

Ascorbic acid operates as an anti-oxidant and essential enzyme cofactor in the human body. In ''

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...

'' studies, the primary mechanism of high dosage intravenous ascorbic acid can be related to ascorbic acid's

pro-oxidant Pro-oxidants are chemicals that induce oxidative stress, either by generating reactive oxygen species or by inhibiting antioxidant systems. The oxidative stress produced by these chemicals can damage cells and tissues, for example an overdose of t ...

activity, whereby hydrogen peroxide is formed. In the extracellular fluid of cells, ascorbic acid dissociates into an ascorbate radical upon the reduction of transition metal ions, such as ferric or cupric cations. These transition metal ions will then reduce dissolved oxygen into a superoxide radical – this will then react with hydrogen to form hydrogen peroxide. Furthermore, according to

Fenton chemistry Fenton's reagent is a solution of hydrogen peroxide (H2O2) with ferrous iron (typically iron(II) sulfate, FeSO4) as a catalyst that is used to oxidize contaminants or waste waters as part of an advanced oxidation process. Fenton's reagent can be us ...

, these transition metal ions can be further oxidised by hydrogen peroxide to generate a highly reactive hydroxyl radical. The formation of hydrogen peroxide and hydroxyl radicals is believed to induce cytotoxicity and apoptosis of cancer cells. Although many ''in vitro'' studies have studied hydrogen peroxide generation by ascorbic acid, the pharmacological mechanism of intravenous ascorbic acid ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

'' is still unclear.

History

Pioneering research

Although the pharmacology of ascorbic acid had been studied since its discovery in the 1930s, the method of administration and its medicinal potential to human patients was not investigated until the 1940s. In 1949, American physician, Frederick Klenner, published his scientific report, “The Treatment of Poliomyelitis and Other Virus Diseases with ascorbic acid”, which detailed the use of intravenous ascorbic acid to treat

polio Poliomyelitis, commonly shortened to polio, is an infectious disease caused by the poliovirus. Approximately 70% of cases are asymptomatic; mild symptoms which can occur include sore throat and fever; in a proportion of cases more severe s ...

in children. Klenner's research pioneered future studies investigating the medicinal role of intravenous ascorbic acid. Klenner's work was recognised by Linus Pauling in the foreword to the ''Clinical Guide'': "Dr. Fred Klenner's early research reports provide much information on the use of high-dose ascorbic acid for the prevention and cure of many diseases, and these reports are still important."

Linus Pauling

Nobel Prize The Nobel Prizes ( ; sv, Nobelpriset ; no, Nobelprisen ) are five separate prizes that, according to Alfred Nobel's will of 1895, are awarded to "those who, during the preceding year, have conferred the greatest benefit to humankind." Alfr ...

winner and biochemist, Linus Pauling, was pivotal in the re-emergence of intravenous ascorbic acid research. Over the course of the 1970s, Pauling would begin a long-term collaboration with fellow physician, Ewan Cameron, on the medical potential of intravenous ascorbate acid as cancer therapy in

terminally ill Terminal illness or end-stage disease is a disease that cannot be cured or adequately treated and is expected to result in the death of the patient. This term is more commonly used for progressive diseases such as cancer, dementia or advanced h ...

patients. In 1976, Pauling and Cameron co-authored a study whereby a group of 100 terminal cancer patients underwent supplementary ascorbic acid therapy (10g/day by intravenous infusion and oral thereafter) and the control group of 1,000 patients did not. Their findings reported that the survival rate of the terminal cancer patients increased by four-fold, compared to the control group, stating that: "the treatment of ascorbate in amounts of 10g/day or more is of real value in extending the life of patients with advanced cancer." Subsequent studies by Pauling and Cameron hypothesised that ascorbic acid's role in enhanced collagen production would lead to the encapsulation of tumours and thus, protect normal tissue from

metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then ...

. Following these findings, Pauling became a strong advocate for vitamin megadosing and continued to investigate the medicinal potential of intravenous ascorbic acid across a range of illnesses, including:

HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...

transmission, the common cold,

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no s ...

, and

angina pectoris Angina, also known as angina pectoris, is chest pain or pressure, usually caused by insufficient blood flow to the heart muscle (myocardium). It is most commonly a symptom of coronary artery disease. Angina is typically the result of obstru ...

Medical controversy

The efficacy of intravenous ascorbic acid therapy came under scrutiny of the medical and science community, following the numerous high-profile studies authored by Linus Pauling in the 1970s. The experimental design of Pauling and Cameron's 1976 publication, "Supplemental ascorbate in the supportive treatment of cancer", had garnered considerable criticism as it was neither randomised nor placebo controlled. To test the validity of Pauling and Cameron's findings, the Mayo Clinic conducted three independent experiments in 1979, 1983 and 1985, whereby terminal cancer patients were given doses of oral ascorbic acid under randomised, double bind and placebo-controlled conditions. All studies concluded that high doses of oral ascorbic acid were not effective against cancer. The use of intravenous ascorbic acid in the treatment of cancer has been a contentious issue. There is no evidence to indicate that intravenous ascorbic acid therapy can cure cancer. According to the

U.S. Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA), high-dose vitamin C (such as intravenous ascorbic acid therapy) has not been approved as a treatment for cancer or any other medical condition. There many been multiple studies devoted to investigating the medicinal properties of ascorbic acid. The use of high-dosage intravenous ascorbic acid as a cancer treatment was first promoted by Linus Pauling and Ewan Cameron in the 1970s; however, these findings were not reproduced using oral administration by subsequent Mayo Clinic studies in the 1980s. In 2010, an academic review which detailed 33 years of ascorbic acid and cancer research stated: "we still do not know whether Vitamin C has any clinically significant anti-tumor activity. Nor do we know which histological types of cancers, if any, are susceptible to this agent. Finally, we don't know what the recommended dose of Vitamin C is, if there is indeed such a dose, that can produce an anti-tumor response".

Research

The turn of the 21st century saw a renewed interest in the medical potential of intravenous ascorbic acid therapy. In the early 2010s, ''in vitro'' preclinical and clinical trials were undertaken to investigate the pharmacological mechanism of action of intravenous ascorbic acid therapy. These findings demonstrated ascorbic acid's pro-oxidant capabilities to produce hydrogen peroxide and thus, proposed a possible pharmacological mechanism of action against cancer cells. Nonetheless, ascorbic acid's potential as an anti-tumour therapy is still dubious, as other pro-oxidant substances (such as

menadione Menadione is a natural organic compound with the formula C6H4(CO)2C2H(CH3). It is an analog of 1,4-naphthoquinone with a methyl group in the 2-position. It is sometimes called vitamin K3. Use is allowed as a nutritional supplement in animal feed ...

) have been unsuccessful in the treatment of cancer patients.

References

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