Introduction:

Intravenous vitamin-C is often debated as a viable treatment option for adult cancer
patients, it is more widely accepted in alternative medicine than mainstream medicine. Some
experts believe it has implications for relieving cancer and cancer related symptoms, while others
disagree and deny its usefulness. So this raises the question does intravenous ascorbic acid have
an effect on cancer and cancer related symptoms in adults? It is an increasingly pertinent topic
with cancer on the rise throughout the world. Any assistance that could be achieved from the use
of intravenous vitamin-C is important to the future of cancer treatment.
Vitamin-C is an essential water soluble vitamin. It is needed for collagen, carnitine, and
neurotransmitter synthesis in the body1. It is also necessary to convert cholesterol into bile acids1
which is an important pathway for the removal of excess cholesterol from the body. Iron can be
difficult for some individuals to get enough of and with vitamin-C consumption with sources of
iron it can enhance the absorption of the iron1. Ascorbic assists in immune function by improving
T-cell in response to infections, and it is necessary for wound repair by stimulating collagen
synthesis1. It also plays a role atherosclerosis prevention by inhibiting the oxidation of LDL1.
These are all beneficial properties of vitamin-C in the body, but what are its uses in relation to
cancer?
One of the main physiologic properties of ascorbic acid are its oxido-reduction abilities1.
It is an important antioxidant, and this plays into its function in cancer prevention. The
antioxidant properties helps prevent oxidative damage to DNA, and macromolecules which are
implicated in chronic diseases1. It also has an active role in fighting cancer as it has properties
that cause cell death to some types of cancer cells through an oxidative mechanism1. Vitamin C

has the ability to produce H2O2 extracellular of the cancerous cells, and it is the H2O2 that has
the cytotoxic effects on cancer cells2. It has also been shown to have anti-proliferation effects on
tumor cells, due to its ability to interfere with the cell cycle3. To achieve cytotoxic effects of
ascorbic acid it must be administered in high doses that can only be achieved by intravenous
injection to bypass the plasma concentration limiting effect4.
Laboratory and Preclinical Trials with Pancreatic Cancer:
Intravenous vitamin-C at proper dosages has shown promising results in respect to
pancreatic cancer treatment. In a study done in mice implanted with pancreatic cancer
xenografts, high daily dosages of ascorbic acid were found to reduce tumor volume by 42%5.
Another study displayed a significant decrease in growth rates of pancreatic tumors in mice6.
When vitamin-C was added to multiple pancreatic cell lines for 1 hour in vitro it had reduced the
viability of all the cell lines and decreased the survival of their cloned cells7. However it had no
effect on the immortalized pancreatic ductal epithelial cell line7. The ascorbic acid performed
cell death by apoptosis in this study7. When the pancreatic cancer cells were delivered to the
mice in the experiment, treatment with intravenous vitamin-C decreased the growth of tumors
and contributed to a longer survival rate of the mice7. Gemcitabine is the main therapeutic
treatment for pancreatic cancer, and when combined with high doses of vitamin-C there were
surprising results. It was found that they worked well together and displayed a 50 % inhibition of
tumor growth, which was a much better result than when gemcitabine was used alone8. It is also
very important to note that this specific tumor type was non-responsive to solely gemcitabine,
which proves that the ascorbic acid enhanced its cytotoxic effects tremendously8.
Laboratory and Preclinical Trials with Ovarian and Breast Cancer:

Daily intravenous injections of ascorbic acid were shown to largely decline the growth
rates of ovarian tumors in mice6. Arsenic trioxide is one of the major treatments for ovarian
cancer9. When arsenic trioxide was used in conjunction with vitamin-C they worked
synergistically, and there was an enhanced cytotoxicity on the ovarian tumor cells in vitro9.
There was an increase in cell death by non-apoptotic means due to oxidative stress on the cancer
cells9. In another study that observed the role of intravenous vitamin-C in the treatment of breast
cancer, they discovered it was capable of inducing cell death on the cancer cells, but it was
completely dependent on the amount of sodium-dependent vitamin-C transporter (SVCT2)
present in the cells10. It was observed that the more dense in SVCT2 the breast cancer cells were,
the more effective ascorbic acids induced cell death10. Due to the intravenous vitamin-C
inhibition of the breast cancer tumors in the mice that were xenografted with the breast cancer
cells was concluded10.
Laboratory and Preclinical Trials with Various Types of Cancer:
Human lymphoma cancer cells are particularly sensitive to vitamin-C2. A study observed
the effect of ascorbic acid on lymphoma cell lines and normal cell types in vitro. The purpose
was to examine the cytotoxicity to the cancer cells and the effect on normal cells at the same
high dosages. It was concluded that although the ascorbic acid had cytotoxic effects on the
lymphoma cells, it had no negative effects on the normal cells2. Glioblastoma tumors in mice had
severely inhibited growth rates when intravenous vitamin-C was administered daily6.
Interestingly ascorbic acid was also shown to be useful in conjunction with radiation therapy on
glioblastoma multiforme; a type of cancer normally resistant to radiation treatment11. The

glioblastoma cells were made more radiosensitive by the addition of vitamin-C, and lead to cell
death11.
Human and Clinical Trials with Advanced Cancers:
Vitamin-C in high dosages has been observed to be very tolerable in many individuals
with various types of cancers. An early study done more than 40 years ago opened the doors to
ascorbic acid as a valid treatment for cancer and cancer related symptoms. With a roster of 50
advanced cancer patients they concluded that high dose vitamin-C had eased the symptoms of
theses terminal cancers and should be implicated as a supportive treatment12. Due to these
findings the scientists attempted to treat a patient with reticulum cell sarcoma who had not
responded to any treatment up to that point13. At the time the disease was widespread throughout
the patient and when the ascorbic acid was continuously administered the disease responded with
a severe decrease of its activity13. A few months after their successful treatment they reduced the
dosages and the cancer progressed13. In response they readjusted the dosages to the initial
amount and this induced a complete remission of the cancer for a second time13. In another
clinical trial that compared 100 terminal cancer patients treated with 1000 similar patients who
were not treated with intravenous vitamin-C14. It was calculated that 90% of deaths of the
ascorbic acid patients occurred at 1/3rd the rate of the control group, and the last 10% displayed
a much longer survival time14.
However with these promising results followed two randomized controlled trials around
the same time period that showed that the vitamin-C showed no therapeutic benefit in
relationship to survival time, symptoms, etc15,16. These were well designed studies and being
randomized controlled trials they provide very reliable data. But there was one common flaw in

the design of both of these studies, the 10g per day of ascorbic acid were not administered
intravenously15,16. To achieve cytotoxic effects on cancer cells the ascorbic acid must be present
in very high doses that can only be achieved intravenously. This bypasses the tight regulation of
plasma concentrations through the oral route17.
In modern day human trials the results are mixed since in these human trials the ascorbic
acid is often used in tandem with cancer therapy drugs, which can complicate the results.
Sometimes vitamin-C can work to sensitize the cancer cells to the the cytotoxic drugs and other
times it inhibits their function. One study reviewed three thoroughly documented cases of
advanced cancer patients that were receiving high dose intravenous vitamin-C18. These patents
were found to have unusually long survival times after receiving the treatment18. In a study
testing the use of ascorbic acid against advanced malignancy, they applied different dosage
ranges for various patients to determine what an optimal dose range should be19. Interestingly the
group receiving the lowest dose had a steep decline in physical function over the duration of the
study19. However the patients in the higher dosage ranges reported no such negative response19. It
was noted that in all dose ranges the intravenous ascorbic acid was well tolerated, but no positive
effects on cancer inhibition were observed in these advanced cases19.
Human and Clinical Trials in Combination with Cancer therapies:
Two separate studies were conducted to determine the effectiveness of ascorbic acid
combined with the traditional drug in order to determine its effectiveness on pancreatic cancer.
Both studies observed no increase in toxicity and the treatment was generally well tolerated by
the patients20,21. Seven out of the nine patients pancreatic cancer in one of the studies stabilized
with no regression or progression of their diseases, while two patients had experienced a

progression in their disease state20. The study concluded that a phase II study was warranted to
determine if patients would experience suppression of their disease with a longer span of
treatment20. The second study showed some success as well and concluded further studies were
needed21.
The ABC regimen is a combination of arsenic trioxide/bortezomib/and ascorbic acid.
This combination treatment was being tested to see its effects on multiple myeloma22. This
regimen showed some early signs of success and was tolerated well by the patients who received
it22. In another study a combination treatment of melphalan, arsenic trioxide, and ascorbic acid
(MAC) was used against multiple myeloma as well. This regimen was well tolerated by this
group who had undergone heavy pretreatment23. The results showed sufficient success, and was
concluded to be a new treatment option for patients with this disease23.
Success was not always observed in these combination treatment studies, and in fact two
studies in particular had to be discontinued due to severe negative reactions to the treatment24,25.
In a study testing the effectiveness of arsenic trioxide and intravenous vitamin-C on colorectal
carcinoma, all of the patients had moderate to severe side effects to the therapy24. The second
study used arsenic trioxide, ascorbic acid, and temozolomide in combination in patients with
advanced melanoma25. No responses were observed to the treatment and there were moderate
side effects, so this study was discontinued as well25.
Human and Clinical Trials Observing Quality of Life Enhancement:
Intravenous vitamin-C has been reported to have alleviating effects in terms of cancer
and cancer treatment related side effects in many studies. It has been shown to commonly reduce
nausea, improve appetite, and alleviate fatigue amongst these studies26,27,28,29. Two studies noted

reductions in sleep disorders26,29, and general improvements were observed in physical,

emotional, and cognitive function as well27,28,29. Significant reductions in depression, dizziness,
and haemorrhagic diathesis26 were reported in one of the studies. As well as a reduction in pain,
improved overall health, and social functioning29.
Conclusion of Laboratory and Preclinical Trials:
Laboratory and preclinical trials have had positive results, and well displayed the effects
of intravenous vitamin-C on various cancers. Ascorbic acid is particularly effective at decreasing
cell proliferation in pancreatic cancer5. Most of ascorbic acids cytotoxicity is attributed to its
ability to form hydrogen peroxide through a chemical reaction extracellularly2. While it acts as a
cytotoxic agent to cancerous cells it has been shown to be generally safe to normal tissues2. It
also can be concluded that vitamin-C can work synergistically with some cancer treatments,
while inhibiting others. In particular it has shown to work well with gemcitabine8, arsenic
trioxide9, and radiation therapy11.
Conclusion of Human and Clinical Trials:
High dose intravenous ascorbic acid is generally well tolerated and shows few adverse
effects, even in combination with certain cancer treatments20,21. The results were less promising
in the human and clinical trials than the laboratory and preclinical trials. Early studies show
increases in survival times14,18, while later studies do not show as many positive results in cancer
regression. Although it is important to note that modern studies are almost always combined with
cancer drugs and therapies which may complicate the results. It can be concluded that more
research is needed in human and clinical trials to determine ascorbic acids role in cancer
treatment.

Although the cytotoxic effects of ascorbic acid have been inconsistent in humans, there
seems to be one thing that remains consistent in most studies. Not only is intravenous vitamin-C
well tolerated but it also has beneficial effects on the negative side effects imposed by cancer and
cancer treatments26,27,28,29. More research is needed to solidify its role in improving the quality of
life of cancer patients.
Applications in the Field:
Intravenous vitamin-C should not be considered as a sole treatment option for cancer
patients. Studies prove that it is not cytotoxic enough to fight cancer alone, even in combination
with proven cytotoxic drugs they can still be ineffective. Until more research is done, ascorbic
acid should only be considered a supplemental treatment. It should be integrated with
chemotherapy and radiation therapy regimens. Vitamin-C should not be combined with just any
type of cancer treatment, it is important to refer to these studies to confirm that it has beneficial
effects on the properties of that treatment. As long as ascorbic acid has been shown to be safe
and synergistic with the cancer therapy, it should always be included. Mainly due to its proven
ability to remain safe and well tolerated, and its positive effects on the quality of life often
displayed in patients undergoing treatment.

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