The use of vitamin C in cancer prevention and treatment is another one of those controversial topics in oncology that I feel compelled to write about. I hope to shed some light on what we know and what we don’t know. Unless you are already using vitamin C for yourself or your patients, I think you might be surprised on what you’ll read.
What is Vitamin C?
Vitamin C, also known as ascorbic acid, is an essential water-soluble vitamin. Since our bodies can’t make it, we have to get it from food.
Why Do We Need It?
- Vitamin C is required by our body in the synthesis of collagen, which is an important component of our blood vessels, tendons, ligaments, and bone.
- Vitamin C is used in the synthesis of norepinephrine, a neurotransmitter which affects our brain function and mood.
- Vitamin C is used in the synthesis of carnitine, a protein that is required in the transport of fat into our mitochondria, where the fat is used as an energy source.
- Vitamin C is a potent antioxidant, which helps to protect against free radical damage to our proteins, fats, carbohydrates, DNA and RNA.
- Vitamin C MAY boost immune system function. Although there are numerous preclinical studies showing stimulatory effects on immune function, human studies have been conflicting.
- Does vitamin C supplementation help you fight off the common cold? If you are like me, you know lots of folks who go nuts and take tons of vitamin C at the first signs of a cold to try to prevent it. Unfortunately, most studies have shown that vitamin C can’t protect you from getting that cold.
How Much Vitamin C Do We Need For Disease Prevention?
To prevent a vitamin deficiency disease (such as scurvy), the U.S. Institutes of Medicine (IOM) recommends: Recommended daily allowance (RDA) 90 mg/day for adult men and 75 mg/day for adult women (add 35 mg/day more for smokers, because smoking “increases oxidative stress and metabolic turnover of vitamin C”.) The IOM report indicates that most of us in the U.S. consume adequate amounts of vitamin C in our daily diet (102 mg/day). The IOM set the upper intake level for adults at 2 g/day (as, higher levels can cause diarrhea and gastrointestinal cramping.)
What is the role of vitamin C in cardiovascular disease, and why might it matter in terms of cancer prevention?
Through studies on cardiovascular disease (CVD) prevention, investigators have reported that the estimated intake of vitamin C in most study participants are not much different than the RDA levels. Vitamin C advocates believe that the RDA levels are far too low to see benefits in chronic disease prevention. Some researchers insist that to see health benefits from vitamin C, levels need to be at least 400 mg/day (oral intake.)
Most people consuming a typical Western diet need to take a supplemental form of vitamin C to reach these levels. Oral intake levels below 400 mg/day will give you a plasma concentration of vitamin C well below the saturation threshold (see the figure to the right)
- as you go above the dose of 400 mg/day, there is very little benefit you gain in terms of reaching a higher plasma concentration; 500 mg of oral vitamin C daily will achieve about 90% of serum levels possible by oral intake, and 1000 mg will give 94-96% of possible serum levels. It is difficult for oral doses higher than that to raise levels any higher.
- as you go below doses of 400 mg/day, the plasma concentration curve drops sharply.
If you are in the camp of believing that vitamin C levels need to be higher to achieve health benefits, you will not be surprised by the studies that show no effect of vitamin C in reducing CVD when the subjects had intakes of vitamin C far below 400 mg/day.
- As you can see from the figure, as vitamin C intake (dietary+/-supplemental) increases, the risk of cardiovascular disease decreases (RR or “risk reduction.”) This was based on analysis of women in the Nurses’ Health Study, which found that those who took vitamin C supplements had a significantly lower risk (28% risk reduction) of incident coronary heart disease (CHD) than women who did not take vitamin C supplements.
So, does vitamin C protect us from getting cancer?
Preclinical studies seem to support the role of vitamin C in cancer prevention:
Human studies on the consumption of foods rich in antioxidant nutrients (fresh fruits and vegetables) have shown a reduced risk of developing most cancers.
- Based on those studies, the U.S. Centers for Disease Control and Prevention recommends that we consume a certain number of servings of a variety of fruits and vegetables each day to obtain this lower risk of cancer. You can calculate your servings here.
But, wait…none of this definitively tells us whether consuming vitamin C actually prevents cancer in humans. The only way to know for sure about the role an individual antioxidant nutrient in modulating cancer risk is to lock the subjects 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 follow them to determine the cancer outcomes…so far, we don’t have any of those studies.
The best studies we have are those that prospectively follow very large groups of individuals, over years, and we ask them to recollect what they consumed over time using food diaries or questionnaires. I don’t know about you, but I often don’t remember the specific details of what I ate yesterday. A few of the better studies occasionally assessed nutrient blood levels at different time intervals. Nevertheless, all of these studies suffer from the multitude of uncontrolled variables that are inherent in not locking your study subjects up in a room and feeding them a controlled diet.
Based on the prospective studies, here’s what the data shows for vitamin C intake in humans:
- An analysis of 8 prospective studies concluded that dietary vitamin C did not modify the risk of developing lung cancer when the analysis was controlled for other dietary factors.
- Most large prospective studies observed no association between the risk of developing breast cancer and vitamin C intake.
- Although, two important studies do show a reduced risk of breast cancer with vitamin C intake:
- Nurses’ Health Study (premenopausal women with a family history of breast cancer): those who consumed an average of 205 mg/day of vitamin C from foods had a 63% lower risk of breast cancer than those who consumed an average of 70 mg/day.
- Swedish Mammography Screening Cohort: overweight women who consumed an average of 110 mg/day of vitamin C had a 39% lower risk of breast cancer compared to overweight women who consumed an average of 31 mg/day.
- Physicians’ Health Study (PHS) II: reported vitamin C supplementation (500 mg/day) for an average of eight years had no significant effect on total cancer or site-specific cancers, including colorectal, lung, and prostate cancer.
- Most cancers take decades to develop, so an 8 year intervention with supplemental vitamin C is likely not long enough to see effects on cancer incidence.
In conclusion: I’m not terribly impressed with these studies. They did their best to explore the potential benefits of vitamin C (and many other factors) in human health, but the results are inconclusive as they pertain to any specific benefit in reducing cancer risk (or cardiovascular disease.)
Some general comments on the prevention and health promotion role of antioxidants:
- It appears that the benefit of antioxidants for protection against CVD (and probably cancer) is best obtained by eating a variety of healthy foods, rather than by taking antioxidant supplements.
- Antioxidant supplements may reduce the risk of cancer, but they will need to be taken for many years (and we have no quality studies that demonstrate this outcome.)
Many preclinical studies have reported the anti-cancer effects of vitamin C of numerous cell types.
In the 1970’s and 1980’s, Linus Pauling and colleagues published results of their experience treating terminal cancer patients with intravenous (“high-dose”) vitamin C. Based on these case reports, they reported that intravenous (IV) vitamin C (10 grams/day for 10 days, followed by 10 g per day orally, indefinitely) demonstrated improved survival times and quality of life.
These favorable results seen with IV vitamin C were investigated in two randomized, double-blind, placebo-controlled trials in terminal cancer patients…but instead of using IV vitamin C, they used oral vitamin C (10 grams/day).
- A 2014 study demonstrates that IV vitamin C increased the effectiveness of chemotherapy against cancer in a mouse experiment. This anticancer effect was reportedly due to the finding that vitamin C gets converted into hydrogen peroxide, which preferentially kills cancer cells with no toxic effect on normal cells. An accompanying human study published in the same journal found that cancer patients who received IV vitamin C during their chemotherapy had less side effects from their chemotherapy (more energy and less nausea) than those who didn’t receive IV vitamin C.
- Study: 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: 100 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. Among patients with measurable disease, none had objective improvement.
Unfortunately, these studies essentially shut the door on hope of using vitamin C as a cancer therapy for conventional oncologists for years.
Linus Pauling and his colleagues knew that IV vitamin C acted as a completely different animal compared with orally administered vitamin C, so the fact that those two studies were conducted with oral vitamin C was a point he made quite loudly until his own death from prostate cancer in 1994.
Here’s the difference between IV versus oral vitamin C:
First of all, 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.)
- The University of Kansas clinicians who use IV vitamin C in cancer patients aim for a 400 millimolar level in the blood (levels much higher than achievable by oral intake.) In their experience, they state that “IV vitamin C, given together with chemotherapy, works better than either alone. A cheap way to check for adequate Vitamin C levels is to do an accucheck before and after IV Vitamin C infusion. This is because the IV Vitamin C ‘fools’ the glucometer and is read as glucose. Subtract the initial reading from the post infusion reading to get a rough estimate of serum levels.”
At the high blood levels achieved by IV administration, studies show that vitamin C does not act like an antioxidant…it acts like a pro-oxidant (through the production of hydrogen peroxide), meaning it can cause DNA damage (just like radiation therapy and chemotherapy) and it selectively does this in tumor cells.
If this premise is indeed true, oncologists might feel less concerned about administering IV vitamin C along with chemotherapy or radiation therapy. One of the hesitations of oncologists and basic science researchers is that there is a theoretical risk of any antioxidant (i.e. vitamin C) reducing the effectiveness of therapies that purposely causes free radical injury to cancer cells. Based on these studies of IV vitamin C acting instead as a pro-oxidant, the concern of reducing treatment efficacy may be unfounded at high dose levels of vitamin C.
Reassuringly, regardless of the antioxidant/pro-oxidant status of vitamin C, there have been no human studies that have yet shown that antioxidants reduce the effectiveness of chemotherapy or radiation therapy. In fact, even a very potent, synthetic antioxidant compound (Amifostine) has not been shown to reduce efficacy of chemotherapy or radiation therapy in clinical studies.
In fact, most of the preclinical studies demonstrate increased efficacy (or at least no reduced efficacy) when vitamin C is co-administered with cancer drugs. **It was actually a talk, “Intravenous Ascorbate and Standard Therapies in Oncology: The state of the science, application and practice of intravenous ascorbate with standard oncologic therapies” from the 2013 OncANP conference, by Paul Anderson, ND, that got me fired up to write this post. His talk was essentially a length list of mostly favorable interactions (synergistic) of vitamin C with cancer drugs.**
One notable exception from all of the favorable studies is this one:
In this study, investigators administered vitamin C along with a variety of cancer drugs (vincristine, doxorubicin, methotrexate, cisplatin, imatinib, actinonin) in the treatment of cancer cells and mouse tumors (intravenous vitamin C.) They noted a significant reduction in efficacy in all of the cancer drugs (see the figure to the right.) 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. Additionally, this study contradicts previously reported studies that have shown increased tumor killing effects when co-admininistered with vitamin C.
Currently, there are no results from clinical trials indicating that vitamin C adversely affects the survival of cancer patients.
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 only received the cancer treatments (no IV vitamin C.) To be safe, they did not administer IV vitamin C on the days of chemo- and radiotherapy (in the discussion section of their paper, the authors referenced my review article on the potential concern of interactions of antioxidants and cancer therapies as a reason for them ‘playing it safe.’)
- a significant reduction of side effects induced by the disease and chemo-/radiotherapy, in particular of 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.
Although this was not a randomized controlled trial, it is correlates with the reports from other institutions and clinics that routinely use IV vitamin C in their cancer patients while undergoing conventional cancer therapies.
Oxidative stress is believed to be one of the main factors involved in cancer treatment (chemotherapy, surgery and radiation therapy) related side effects. Cancer treatment, cancer metabolism, and systemic inflammation can all increase free radicals (producing oxidative stress.) Over time, this will deplete antioxidants in the body, leading to a deficit. Systemic oxidative stress (as a result of cancer treatment and reduced antioxidant intake) has been linked to worse side effects and quality of life outcomes (including treatment delays) in patients undergoing cancer treatment.
- In one study, low intakes of vitamin C, among children undergoing treatment for leukemia, was the most predictive of all the nutrient intakes studied with respect to the occurrence of side effects (importantly, only 7% of the patients were not consuming the RDA for vitamin C). The investigators therefore recommended that an increase in the requirement for vitamin C in these patients should be considered.
By reducing systemic oxidative stress with antioxidants, it is hypothesized that the intensity of many of these untoward symptoms could be mitigated.
One recent report demonstrated very few adverse events among thousands of IV vitamin C administrations.
The most common side effects are: lethargy or fatigue, vein irritation, and nausea and vomiting.
IV vitamin C is contraindicated among those 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.
- Vitamin C, through dietary intake, may reduce the risk of developing various cancers, but the absolute benefit it not known. Daily consumption of a variety fresh fruits and vegetables, rich in antioxidant compounds and numerous other anti-cancer molecules, is the best preventive approach.
As a component of cancer treatment:
- Oral intake or IV 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.
- If you want to achieve any significant level of vitamin C in your blood and tissues (without an IV infusion) you need to get it from the most highly absorbable form: Liposomal Vitamin C.
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 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 theoretical and potential risk before offering vitamin C therapy.
More High Quality Studies Need To Be Conducted:
This is an exciting time in vitamin C research, as there are multiple clinical trials currently evaluating the efficacy of vitamin C in cancer treatment. However, we’ll need more phase III (double-blind, randomized, placebo-controlled trials) to 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?
Here are 3 great videos on this subject by one of my favorite physician nutrition experts, Dr. Michael Gregor (NutritionFacts.org)