INTRAVENOUS VITAMIN C

INTRAVENOUS VITAMIN C

June 29, 2021

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Vitamin C also referred to as ascorbic acid, is an essential nutrient that is not synthesized by the human body and must therefore be introduced through food or supplements. This vitamin is water-soluble and necessary for the body to synthesize collagen, which strengthens:

  • Bones

  • Cartilage

  • Muscles

  • Blood Vessels

It also is essential for the proper function of the immune system and promotes iron absorption.

There are lots of benefits from Vitamin C. It is known for its ability to act as an antioxidant agent, eliminating free radicals and minimizing the damage caused to the genome. The use of Vitamin C has also been adopted in the oncology field for the treatment of tumors. One of the most common forms of Vitamin C administration is intravenous.

WHAT IS INTRAVENOUS VITAMIN C?

This is a therapy based on the administration of ascorbic acid directly into the bloodstream. Depending on the case, Vitamin C can be given by injection or by intravenous infusion (what is commonly called a "drip"). Intravenous Vitamin C enters the bloodstream directly. As this pathway bypasses the stomach and intestines, it allows for very high levels of Vitamin C in the blood to be reached very quickly.

WHAT IS IT USED FOR?

In patients suffering from malnutrition or malabsorption, intravenously administered ascorbic acid can treat Vitamin C deficiency.

The use of intravenous Vitamin C has also been proposed as an alternative or complementary therapy in cancer treatment. However, current evidence on the effectiveness of these interventions is limited to observational studies, uncontrolled interventions, and case reports. Furthermore, intravenous administration of Vitamin C has recently gained popularity for its possible benefits in treating critically ill COVID-19 ICU patients.

ORAL VITAMIN C DIFFERENCES.

The quantities of Vitamin C circulating in the blood depend, in addition to the dietary intake, on three main factors:

‣ Intestinal Absorption

‣ Tissue Transport

‣ Renal Resorption

In healthy young adults, Vitamin C intake between 200 and 400 mg per day causes blood Vitamin C concentrations to reach a steady-state (between 60 and 80 μmol / l), albeit with some degree of individual variability.

Consequently, Vitamin C intakes above 400mg per day do not further increase plasma concentrations of ascorbic acid, as the kidney rapidly eliminates excess. Once the plasma concentrations of Vitamin C reach saturation, the additional Vitamin C taken by mouth is extensively excreted in the urine.

Again concerning oral intake, it is necessary to consider that the intestinal absorption capacity of Vitamin C is equal to 100% of the dose taken only up to doses of about 200 mg at a time. Higher doses (> 500 mg) result in fractionally less absorption of excess Vitamin C, decreasing with increasing dose.

Intravenous administration of Vitamin C bypasses the control of intestinal absorption, allowing very high concentrations of Vitamin C to be reached in plasma. Within a few hours, renal excretion will restore plasma concentrations to baseline even in case of intravenous administration. Compared to orally administered Vitamin C, intravenous Vitamin C can lead to 30 to 70 times higher plasma concentrations of ascorbic acid. 

HOW INTRAVENOUS VITAMIN C WORKS.

A Vitamin C solution is pumped into the bloodstream directly through a vein, usually in the arm. A doctor's prescription is required to get this therapy. They will first evaluate the absence of contraindications such as kidney disease, hemochromatosis, or hemolytic anemia.

It is important that intravenous administration of Vitamin C only takes place in a clinic or other medical setting, under the direct supervision of specialists.

THE MECHANISM OF ACTION.

The mechanism of action of intravenously administered ascorbic acid is still unclear. Vitamin C is a vital part of the immune system, but there is no reason to think that intravenous Vitamin C can strengthen the immune system beyond normal health. Vitamin C from foods or supplements is, in fact, more than enough to support healthy immunity.

A daily intake of 200-400 mg of Vitamin C can be easily satisfied through food, provided the diet includes at least a couple of servings of Vitamin C-rich fruits and vegetables (such as citrus fruits, kiwis, peppers) as part of the recommended daily intake of fruits and vegetables. To learn more, read: foods rich in Vitamin C.

We now know that excessive consumption of isolated antioxidants can bring about toxic effects and even promote, instead of preventing, oxidative damage in a phenomenon called the "antioxidant paradox." Vitamin C is no exception, although this effect - demonstrated in vitro - does not appear to occur in vivo. 

According to this theory, the very high levels of ascorbic acid in the blood, achieved by intravenous administration, can create free radicals that destroy cancer cells, viruses, and bacteria. In particular, the production of high levels of hydrogen peroxide could be selectively toxic to cancer cells. On the contrary, the healthy cells of the body would be able to survive thanks to the best antioxidant defenses.

The high plasma Vitamin C concentration could also induce the deactivation of hypoxia-induced transcription factors (a transcription factor protecting the cancer cells from various kinds of stress). Intravenous Vitamin C also plays a valuable role in maintaining genetic data integrity and protecting against cell transformation by regulating histone demethylating enzymes and DNA. 

The high plasma concentrations of Vitamin C achieved through intravenous administration are comparable to those toxic to tumor cells in culture. However, it is not yet clear what the exact mechanism of action is in vivo.

EFFICACY AGAINST CANCER.

The use of intravenous ascorbic acid as a treatment or co-treatment of cancer is a controversial topic. 

Studies conducted in the 70s and 80s by Ewan Cameron, Linus Pauling, and colleagues show that large Vitamin C doses (10 g/day infused intravenously for 10 days, followed by at least 10 g/day orally timed indefinite) could increase the survival and quality of life of terminally ill cancer patients (Cameron & Pauling, 1976). 

However, some subsequent studies, including a randomized, double-blind, placebo-controlled clinical trial by Moertel and colleagues at the Mayo Clinic, did not support these results (Moertel et al., 1985). 

The authors of a 2003 review evaluating the effects of Vitamin C in patients with advanced cancer concluded that Vitamin C confers no significant benefit on mortality (Shekelle et al., 2003). 

You should note that most intervention studies, including those conducted by Moertel and colleagues, investigated the effects of oral Vitamin C administration. At the same time, Cameron and Pauling used intravenous (IV) and oral ascorbic acid.

Research in mice suggests that pharmacological doses of intravenous Vitamin C could promise to treat tumors that are otherwise difficult to treat (Chen et al., 2008). 

Observational studies in cancer patients undergoing chemotherapy and radiotherapy reported that complementary treatment with intravenous vitamin C was associated with reducing treatment-associated side effects and improved quality of life (Carr et al., 2014). 

The latest evidence of intravenous Vitamin C effectiveness in cancer patients remains limited to case reports, observational studies, and uncontrolled interventions (Fritz et al., 2014).

Larger and longer-term Phase II clinical trials testing the efficacy of intravenous Vitamin C in disease progression and overall survival are needed. 

In 2010, an academic review detailing 33 years of ascorbic acid and cancer research stated: "We do not yet know whether Vitamin C has clinically significant anticancer activity. Nor do we know which histological types of cancer, if any, are sensitive to this agent. Finally, we do not know what the recommended dose of Vitamin C is, if it exists, helpful in producing an antitumor response (Cabanillas, 2010).

EFFICACY AGAINST COVID-19

Vitamin C has made headlines in the fight against COVID-19, generating speculation and confusion in the population. Some preliminary reports say intravenous Vitamin C could help people suffering from this disease.

For example, intravenous Vitamin C appears in some COVID-19 critical care guidelines at Eastern Virginia Medical School.

Regarding the possible mechanisms of action, the hypotheses would concern:

‣ The ability to compensate for the severe deficiencies of vitamin C induced by the hypermetabolic response driven by the systemic inflammatory reaction;

‣ The ability to protect the vascular endothelium from oxidative damage;

‣ Anti-inflammatory action;

‣ Increased expression of alpha interferon

Clinical data from ongoing intravenous Vitamin C studies will not be available for several months. At the moment, we cannot say whether and how effective intravenous Vitamin C is or how it might work. 

However, there is some scientific evidence that intravenous Vitamin C may be useful in treating patients with sepsis (generalized infection in the blood) and septic shock (Fowler et al., 2014).

SAFETY AND SIDE EFFECTS.

The latest evidence from regulated clinical trials shows that intravenous ascorbic is well-tolerated in cancer patients and generally safe. 

It should be noted that - since the intravenous administration of 80g of Vitamin C precipitated hemolytic anemia in two subjects with glucose -6-phosphate dehydrogenase deficiency - patients who are candidates for therapy are systematically screened for this genetic disorder (Carr & Cook, 2018).

Four Phase I clinical trials in patients with advanced cancer found that intravenous administration of Vitamin C at doses up to 1.5 g / kg body weight (equivalent to approximately 100 g / day for a 70 kg person) and 70 to 80 g / m 2 was well tolerated and safe in patients undergoing preliminary screening (Stephenson et al., 2013).

Although intravenous administration of Vitamin C appears to be safe and well-tolerated, there is a non-negligible risk of oxalate nephropathy (a rare cause of renal failure) in these critically ill patients. 

In people with hemochromatosis (a specific genetic condition where the body absorbs and stores excess iron), intravenous Vitamin C is contraindicated; it can cause iron overload leading to life-threatening complications such as heart disease, diabetes, or tissue damage.


REFERENCES

  • Cabanillas, F. (2010). Vitamin C and cancer: What can we conclude--1,609 patients and 33 years later? Puerto Rico Health Sciences Journal, 29(3), 215–217.

  • Cameron, E., & Pauling, L. (1976). Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer. Proceedings of the National Academy of Sciences of the United States of America, 73(10), 3685–3689. https://doi.org/10.1073/pnas.73.10.3685

  • Carr, A. C., & Cook, J. (2018). Intravenous Vitamin C for Cancer Therapy—Identifying the Current Gaps in Our Knowledge. Frontiers in Physiology, 9, 1182. https://doi.org/10.3389/fphys.2018.01182

  • Carr, A. C., Vissers, M. C. M., & Cook, J. S. (2014). The effect of intravenous vitamin C on cancer- and chemotherapy-related fatigue and quality of life. Frontiers in Oncology, 4, 283. https://doi.org/10.3389/fonc.2014.00283

  • Chen, Q., Espey, M. G., Sun, A. Y., Pooput, C., Kirk, K. L., Krishna, M. C., Khosh, D. B., Drisko, J., & Levine, M. (2008). Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proceedings of the National Academy of Sciences of the United States of America, 105(32), 11105–11109. https://doi.org/10.1073/pnas.0804226105

  • Fowler, A. A., Syed, A. A., Knowlson, S., Sculthorpe, R., Farthing, D., DeWilde, C., Farthing, C. A., Larus, T. L., Martin, E., Brophy, D. F., Gupta, S., Medical Respiratory Intensive Care Unit Nursing, Fisher, B. J., & Natarajan, R. (2014). Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. Journal of Translational Medicine, 12, 32. https://doi.org/10.1186/1479-5876-12-32

  • Fritz, H., Flower, G., Weeks, L., Cooley, K., Callachan, M., McGowan, J., Skidmore, B., Kirchner, L., & Seely, D. (2014). Intravenous Vitamin C and Cancer: A Systematic Review. Integrative Cancer Therapies, 13(4), 280–300. https://doi.org/10.1177/1534735414534463

  • Moertel, C. G., Fleming, T. R., Creagan, E. T., Rubin, J., O’Connell, M. J., & Ames, M. M. (1985). High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison. The New England Journal of Medicine, 312(3), 137–141. https://doi.org/10.1056/NEJM198501173120301

  • Shekelle, P., Hardy, M. L., Coulter, I., Udani, J., Spar, M., Oda, K., Jungvig, L. K., Tu, W., Suttorp, M. J., Valentine, D., Ramirez, L., Shanman, R., & Newberry, S. J. (2003). Effect of the supplemental use of antioxidants vitamin C, vitamin E, and coenzyme Q10 for the prevention and treatment of cancer. Evidence Report/Technology Assessment (Summary), 75, 1–3.

  • Stephenson, C. M., Levin, R. D., Spector, T., & Lis, C. G. (2013). Phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics of high-dose intravenous ascorbic acid in patients with advanced cancer. Cancer Chemotherapy and Pharmacology, 72(1), 139–146. https://doi.org/10.1007/s00280-013-2179-9

Rebecca LaMarca