The use of vitamin C in cancer prevention and treatment is a controversial topic in oncology. Unless you are already using vitamin C, you may be surprised on what you’ll read.
Vitamin C, also known as ascorbic acid, is a water-soluble vitamin. Since our bodies can’t make it, we must get it from the food we eat.
Vitamin C is needed by our body for the synthesis of collagen, an important component of blood vessels, tendons, ligaments and bone. It is used in the synthesis of norepinephrine, a neurotransmitter that affects our brain function and mood. It is also involved in the synthesis of carnitine, a protein that is required in the transport of fat into our cells, where the fat is used as an energy source. Vitamin C is a potent antioxidant that helps to protect our cells and the genetic material in them (DNA) against free radical damage. It may boost immune system function. Although there are numerous preclinical studies showing that vitamin C stimulates immune function, human studies have yielded conflicting results.
In a preclinical 🐭 study, published in 2020, IV vitamin C was used as part of an immunotherapy regimen.
—The researchers found that adding high doses of vitamin C without immunotherapy resulted in delayed tumor growth in test mice.
—When it was given as part of an immunotherapy regimen with the mice, they found it slowed or stopped growth of melanoma, colorectal, pancreatic and breast cancer tumors.
—Furthermore, they found that it did so by providing support to T cells.
—They also found that vitamin C boosted the effectiveness of PD-1 and CTLA-4 checkpoint antibodies.
—And they found that in some cases, adding vitamin C to the immunotherapy regimen resulted in some breast cancer tumors disappearing completely.
How Much Vitamin C Do We Need?
To prevent a vitamin deficiency disease (such as scurvy), the U.S. Institutes of Medicine (IOM) recommends an intake of 90 mg per day for men and 75 mg per day for women. Smokers should add 35 mg/day to this, because smoking increases oxidative stress and increases the body’s need for vitamin C. Most Americans consume adequate amounts of vitamin C in their diet (102 mg per day).
Defenders of vitamin C believe, however, that the recommended daily allowance (RDA) for vitamin C is far too low to produce benefits in disease prevention. The prestigious Linus Pauling Institute recommends that to see health benefits from vitamin C, intake needs to be at least 400 mg per day (REF). Thus, most people eating a typical Western diet would need to supplement with vitamin C to reach these levels.
This view appears to be supported by studies that show no effect of vitamin C in reducing cardiovascular disease when the subjects had intakes of vitamin C far below 400 mg per day. As vitamin C intake increases, the risk of cardiovascular disease decreases. In the Nurses’ Health Study, those who took vitamin C supplements had a 28% reduced risk of coronary heart disease than women who did not take vitamin C supplements.
Does Vitamin C Protect Us From Cancer?
Test tube and animal studies support the role of vitamin C in cancer prevention thanks to its antioxidant activity, its anti-inflammatory activity and because it can block tumor initiation and promotion.
Human studies show that people eating foods rich in antioxidant nutrients – notably fresh fruits and vegetables – have a reduced risk of developing most cancers (but of course the benefits of fruits and vegetables go way beyond their vitamin C content). Based on these studies, the U.S. Centers for Disease Control and Prevention recommends that we consume a certain number of servings of various fruits and vegetables each day to obtain this lower risk of cancer.
But none of this tells us whether consuming vitamin C can prevent cancer in humans. There is only way to know for sure about the role an individual antioxidant nutrient in modulating cancer risk: lock people in a room for decades (cancers take decades to develop), feed them a very controlled diet (making sure they don’t eat anything else that might mess up the study results), measure blood levels of the nutrient in question, and then follow them to determine the cancer outcomes. We don’t have any of those studies so far and won’t any time soon.
The best studies we do have are those that follow large groups of individuals over years and ask them to recollect what they consumed over time using food diaries or questionnaires. These types of studies are notoriously unreliable; we often don’t remember what we ate yesterday, let alone weeks or months earlier. Some higher-quality studies occasionally assess nutrient blood levels at different time intervals. Nevertheless, all these studies suffer from the multitude of uncontrolled variables that are inevitable when trying to follow humans living in the real word, rather than captive subjects in a controlled environment.
Based on these less-than-perfect studies, the data for vitamin C and cancer risk in humans is mixed.
- An analysis of eight prospective studies concluded that dietary vitamin C did not affect the risk of developing lung cancer when the analysis was controlled for other dietary factors.
- Most large studies observed no association between the risk of developing breast cancer and vitamin C intake.
- Two important studies, however, do show a reduced risk of breast cancer with vitamin C intake: in the Nurses’ Health Study, those who consumed an average of 205 mg per day of vitamin C from foods had a 63% lower risk of breast cancer than those who consumed an average of 70 mg per day. In the Swedish Mammography Screening Cohort, overweight women who consumed an average of 110 mg per day of vitamin C had a 39% lower risk of breast cancer compared to overweight women who consumed an average of 31 mg per day.
- The Physicians’ Health Study (PHS) II reported that vitamin C supplementation (500 mg per day) for an average of eight years had no significant effect on total cancer or site-specific cancers, including colorectal, lung, and prostate cancer.
I am not terribly impressed with these studies. The researchers did their best to explore the potential benefits of vitamin C in human health, but regarding cancer risk, the results are inconclusive at best. It appears that the greatest benefit of antioxidants for protection against cancer is obtained by eating a variety of healthy foods, rather than by taking antioxidant supplements. Antioxidant supplements may reduce the risk of cancer, but they need to be taken for many years (and there are currently no reliable studies that demonstrate this outcome).
Does Vitamin C Improve Cancer Outcomes?
Many preclinical studies have reported anti-cancer effects of vitamin C of numerous cell types. In the 1970′s and 1980′s, two-times Nobel Prize winner Linus Pauling and colleagues published results of their experience treating terminal cancer patients with intravenous (“high-dose”) vitamin C. Based on these cases, they reported that intravenous (IV) vitamin Cimproved survival times and quality of life. In one study (REF), 100 terminal cancer patients were treated with ascorbate (10 g/day for 10 days IV, then orally) and compared with 1,000 matched controls from the same hospital. The mean survival time for ascorbate-treated patients was 300 days longer than that of the matched controls.
The favorable results obtained with IV vitamin C were tested in two randomized, double-blind, placebo-controlled trials in terminal cancer patients. Instead of using IV vitamin C, however, they used oral vitamin C (10 grams/day).
- Study 1: One hundred and fifty patients with advanced cancer were randomly assigned to receive vitamin C or a placebo. The two groups showed no appreciable difference in changes in symptoms, performance status, appetite or weight. The median survival for all patients was seven weeks (no differences between the groups).
- Study 2: One hundred patients with advanced colorectal cancer were randomly assigned to receive either vitamin C or a placebo. None had received any previous treatment with cytotoxic drugs. Vitamin C therapy showed no advantage over placebo therapy with regard to either the interval between the beginning of treatment and disease progression or patient survival.
These studies shut the door on using vitamin C as a cancer therapy for conventional oncologists for years. Linus Pauling and his colleagues knew, however, that intravenous vitamin C behaved completely differently than orally administered vitamin C.
For one, the levels of vitamin C achievable through oral intake are much lower than what can be achieved by IV administration. In one study, urine concentrations of vitamin C from IV administration were 140-times higher than those from maximum oral doses. At the high blood levels achieved by IV administration, studies show that vitamin C does not act like an antioxidant; rather, it acts like a pro-oxidant. Studies have found that at high-doses, vitamin C causes the production of hydrogen peroxide, which can cause cell death preferentially in cancer cells through oxidative DNA damage (REF). Other studies have reported that high-dose vitamin C can slow cancer progression by downregulation transcription factors and activating cancer cell autophagy (REF).
Proposed mechanism of antitumor effects of vitamin C. The administration of more than 10 g of ascorbate is proposed to achieve plasma concentrations of 1 to 5 mM. At this time, vitamin C at high plasma concentration may function as a pro-oxidant. This occurs in the presence of free transition metals, such as copper and iron, which are reduced by ascorbate and, in turn, react with hydrogen peroxide (H2O2), leading to the formation of highly reactive and damaging hydroxyl radicals. As normal tissue receives adequate blood flow and is rich in antioxidant enzymes (e.g. catalase, glutathione peroxidase; GP) in the blood, any H2O2 formed will be immediately destroyed. Meanwhile, tumor tissue is often associated with reduced blood flow and antioxidant enzymes, and consequently formed H2O2 remains active leading to cell damage and death (REF).
What is the Role of Vitamin C in Symptom Management or Quality of Life?
In one study of 125 patients with stage II-III breast cancer, investigators gave 53 of these patients IV vitamin C (7.5 grams) with their usual cancer treatments (chemotherapy and/or radiation therapy.) The remainder of the patients received the same cancer treatments, but no IV vitamin C. To be safe, they did not administer IV vitamin C on the days of chemo- and radiotherapy.
The researchers found a significant reduction of side effects induced by the disease and cancer treatments, in particular nausea, loss of appetite, fatigue, depression, sleep disorders, dizziness and bleeding problems. The overall intensity score of symptoms during adjuvant therapy and aftercare was nearly twice as high in the control group compared to the IV vitamin C group. There were no differences noted in tumor outcomes between the two groups after 6 or 12 months. These results tally with reports from clinics that routinely use IV vitamin C in their cancer patients while undergoing conventional cancer therapies.
How Might Vitamin C Improve Symptoms?
Cancer treatment, cancer metabolism, and systemic inflammation can all increase the production of free radicals, producing oxidative stress. Oxidative stress in turn is believed to be one of the main triggers of cancer treatment side-effects.
Over time, a high level of oxidative stress depletes antioxidants in the body, leading to a deficit. Systemic oxidative stress has been linked to worse side effects and quality of life outcomes in patients undergoing cancer treatment. By reducing systemic oxidative stress with the help of antioxidants like vitamin C, it is thought that the intensity of many unpleasant symptoms could be mitigated.
Is Vitamin C Safe?
One recent report demonstrated very few adverse events among thousands of IV vitamin C administrations. When there are side-effects, they most commonly include lethargy or fatigue, vein irritation, and nausea and vomiting. IV vitamin C is should not be used in people with pre-existing renal insufficiency/failure or glucose 6-phosphate dehydrogenase (G6PD) deficiency, as both of these conditions are known to predispose to vitamin C toxicity.
Combining vitamin C with conventional cancer treatments could theoretically reduce the effectiveness of chemotherapy or radiation therapy or impair the built-in protective anticancer mechanisms in cancer cells (i.e. apoptosis), leading to enhanced cancer cell survival.
Examples:
- Treating leukemia and lymphoma cells with a form of vitamin C that increases levels of intracellular ascorbic acid) reduced the cancer cell killing effectiveness of a variety of chemotherapy drugs (i.e. doxorubicin, methotrexate, and cisplatin) by 30-70% (REF) The form of vitamin C used in this study (dehydroascorbic acid) has been criticized by researchers who claim that it is not a relevant comparison to typical forms used in the real world and clinic.
- Treating multiple myelomacells with the cancer drug bortezomib was less effective in the presence of vitamin C (REF)
Commonly Recommended High-Dose IV Vitamin C Dose Regimen:
- 50-75 grams intravenous 3 x/week
- The Riordan Clinic IV vitamin C (IVC) protocol:“In our experience, the majority of cancer patients require 50 gram IVC infusions 2-3x/week to maintain therapeutic IVC plasma levels (350- 400 mg/dL). All patients reaching therapeutic range should still be monitored monthly with post IVC plasma levels to ensure that these levels are maintained long term. We advise patients to orally supplement with at least 4 grams of vitamin C daily, especially on the days when no infusions are given.”
Dr. Lawenda’s Bottomline On Vitamin C:
Oral intake or IV (preferred, due to the pro-oxidant effect) administration of vitamin C may reduce side effects associated with cancer therapy. By decreasing side effects, vitamin C may increase the tolerance to cancer treatments…more tolerance to cancer treatment (i.e. fewer, shorter treatment breaks, less treatment intensity reductions) should translate to improved cancer specific outcomes.
As noted above (preclinical study), there is a possibility that IV vitamin C might improve the effectiveness of immunotherapy drugs and one’s innate anticancer immunity.
No human studies have demonstrated an increased or decreased efficacy of cancer therapies when co-administered with oral or IV vitamin C (although many preclinical studies show synergistic effects.) Although no clinical studies have demonstrated a reduced efficacy of chemotherapy or radiation therapy with the co-administration of vitamin C, patients need to be made fully aware of this potential risk before starting vitamin C therapy.
High-dose IV vitamin C, the most promising anticancer form of ascorbic acid, appears to be tolerable and safe based on small, pilot clinical studies. Numerous pahse 1 and 2 clinical trials are currently enrolling patients to further explore the safety, tolerability, dosing and potential efficacy of vitamin C in cancer patients (REF). We will eventually need phase 3 (double-blind, randomized, placebo-controlled trials) to more definitively answer the big questions:
- What is vitamin C role in cancer treatment (and prevention)?
- Does it have anticancer activity in IV doses?
- Is IV vitamin C effective as a cancer drug by itself or in combination with our cancer therapies?
- Does it decrease or increase the efficacy of other cancer therapies?
- Does vitamin C improve quality of life outcomes?
