LONGECITY

Vitamin C Injections Slow Tumor Growth In Mice

High-dose injections of vitamin C, also known as ascorbate or ascorbic acid, reduced tumor weight and growth rate by about 50 percent in mouse models of brain, ovarian, and pancreatic cancers, researchers from the National Institutes of Health (NIH) report in the August 5, 2008, issue of the Proceedings of the National Academy of Sciences. The researchers traced ascorbate's anti-cancer effect to the formation of hydrogen peroxide in the extracellular fluid surrounding the tumors. Normal cells were unaffected.

Natural physiologic controls precisely regulate the amount of ascorbate absorbed by the body when it is taken orally. "When you eat foods containing more than 200 milligrams of vitamin C a day--for example, 2 oranges and a serving of broccoli--your body prevents blood levels of ascorbate from exceeding a narrow range," says Mark Levine, M.D., the study's lead author and chief of the Molecular and Clinical Nutrition Section of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the NIH. To bypass these normal controls, NIH scientists injected ascorbate into the veins or abdominal cavities of rodents with aggressive brain, ovarian, and pancreatic tumors. By doing so, they were able to deliver high doses of ascorbate, up to 4 grams per kilogram of body weight daily. "At these high injected doses, we hoped to see drug-like activity that might be useful in cancer treatment," said Levine.

Vitamin C plays a critical role in health, and a prolonged deficiency leads to scurvy and eventually to death. Some proteins known as enzymes, which have vital biochemical functions, require the vitamin to work properly. Vitamin C may also act as an antioxidant, protecting cells from the damaging effects of free radicals. The NIH researchers, however, tested the idea that ascorbate, when injected at high doses, may have prooxidant instead of antioxidant activity. Prooxidants would generate free radicals and the formation of hydrogen peroxide, which, the scientists hypothesized, might kill tumor cells. In their laboratory experiments on 43 cancer and 5 normal cell lines, the researchers discovered that high concentrations of ascorbate had anticancer effects in 75 percent of cancer cell lines tested, while sparing normal cells. In their paper, the researchers also showed that these high ascorbate concentrations could be achieved in people.

The team then tested ascorbate injections in immune-deficient mice with rapidly spreading ovarian, pancreatic, and glioblastoma (brain) tumors. The ascorbate injections reduced tumor growth and weight by 41 to 53 percent. In 30 percent of glioblastoma controls, the cancer had spread to other organs, but the ascorbate-treated animals had no signs of disseminated cancer. "These pre-clinical data provide the first firm basis for advancing pharmacologic ascorbate in cancer treatment in humans," the researchers conclude.

Interest in vitamin C as a potential cancer therapy peaked about 30 years ago when case series data showed a possible benefit. In 1979 and 1985, however, other researchers reported no benefit for cancer patients taking high oral doses of vitamin C in two double-blind, placebo-controlled clinical trials.

Several observations led the NIH researchers to revisit ascorbate as a cancer therapy. "Clinical and pharmacokinetic studies conducted in the past 12 years showed that oral ascorbate levels in plasma and tissue are tightly controlled. In the case series, ascorbate was given orally and intravenously, but in the trials ascorbate was just given orally. It was not realized at the time that only injected ascorbate might deliver the concentrations needed to see an anti-tumor effect," said Levine, who noted that new clinical trials of ascorbate as a cancer treatment are in the planning stages.

Data from Levine's earlier studies of the regulation and absorption of dietary vitamin C were used in the revision of the Institute of Medicine's Recommended Dietary Allowance for the vitamin in 2000. In the current study, Levine led a team of scientists from the NIDDK and the National Cancer Institute (NCI), both components of the NIH, as well as the University of Kansas. "NIH's unique translational environment, where researchers can pursue intellectual high-risk, out-of-the-box thinking with high potential payoff, enabled us to pursue this work," he said.

http://www.medicalne...cles/117252.php

The key statment is probably this:

The NIH researchers, however, tested the idea that ascorbate, when injected at high doses, may have prooxidant instead of antioxidant activity. Prooxidants would generate free radicals and the formation of hydrogen peroxide, which, the scientists hypothesized, might kill tumor cells. In their laboratory experiments on 43 cancer and 5 normal cell lines, the researchers discovered that high concentrations of ascorbate had anticancer effects in 75 percent of cancer cell lines tested, while sparing normal cells.

The vitamin c in high injected doses may be acting as a kind of chemotherapy, if it does indeed spare normal cells in vivo as it did in their in vitro tests then it may truly be promising, else it may be just another toxic chemotherapy choice perhaps with lower risk/reward perhaps not.

edit: People seem to think of vitamin c as benign because of the fact that you can take so much of it orally without it causing problems but in blood concentrations high enough (achieved only through IV therapy) to generate free radicals and hydrogen peroxide it looks like it becomes anything but benign.
Edited by edward, 05 August 2008 - 03:59 PM.

The vitamin c in high injected doses may be acting as a kind of chemotherapy, if it does indeed spare normal cells in vivo as it did in their in vitro tests then it may truly be promising, else it may be just another toxic chemotherapy choice perhaps with lower risk/reward perhaps not.

The study showed that lab mice had a reduction in tumor growth of 50%. So there are some in vivo results, human results however remain to be seen. Well that is only partially true, I believe that there has been some effort to IV vitamin C as cancer treatment for patients, but I don't believe that there has been a medical study or very rigorous data collection on results.

Here is the actual study:
http://www.pnas.org/...226105.abstract

Ascorbic acid is an essential nutrient commonly regarded as an antioxidant. In this study, we showed that ascorbate at pharmacologic concentrations was a prooxidant, generating hydrogen-peroxide-dependent cytotoxicity toward a variety of cancer cells in vitro without adversely affecting normal cells. To test this action in vivo, normal oral tight control was bypassed by parenteral ascorbate administration. Real-time microdialysis sampling in mice bearing glioblastoma xenografts showed that a single pharmacologic dose of ascorbate produced sustained ascorbate radical and hydrogen peroxide formation selectively within interstitial fluids of tumors but not in blood. Moreover, a regimen of daily pharmacologic ascorbate treatment significantly decreased growth rates of ovarian (P < 0.005), pancreatic (P < 0.05), and glioblastoma (P < 0.001) tumors established in mice. Similar pharmacologic concentrations were readily achieved in humans given ascorbate intravenously. These data suggest that ascorbate as a prodrug may have benefits in cancers with poor prognosis and limited therapeutic options.

Edited by lucid, 05 August 2008 - 04:31 PM.

The study showed that lab mice had a reduction in tumor growth of 50%. So there are some in vivo results, human results however remain to be seen. Well that is only partially true, I believe that there has been some effort to IV vitamin C as cancer treatment for patients, but I don't believe that there has been a medical study or very rigorous data collection on results.

True, I was just pointing out that in their in vitro results they mention the vitamin c spared the normal cells (represented by their cell lines) from destruction, while it killed cancer cells presumably by a hydrogen peroxide free radical mechanism, bringing up the familiar risk/reward damage to healthy cells/damage to tumor cells dilema of standard chemotherapy options.

In the body however high concentrations of vitamin c free flowing in the blood stream forming hydrogen peroxide and free radicals may indeed do lots of damage that was not captured in the in vitro studies with the cell lines (perhaps these cells were not as sensitive or susceptible as some etc.). In the in vivo studies potential damage to other tissues may have not been apparent.

BUT....


Real-time microdialysis sampling in mice bearing glioblastoma xenografts showed that a single pharmacologic dose of ascorbate produced sustained ascorbate radical and hydrogen peroxide formation selectively within interstitial fluids of tumors but not in blood.

This statement looks very promising almost too good to be true, I wonder what the mechanism is that causes the acorbate radical and hydrogen peroxide formation ONLY within the tumor cells (which are simply normal cells gone amok with no programmed cell death)

...requesting full study in members resource sharing if someone has access to it...

edit: spelin 'n gramur
Edited by edward, 06 August 2008 - 04:45 AM.

btw

this thread should be merged with this one or vica versa

http://www.imminst.o...mp;#entry255315

Members can now go to the resource sharing page to view a PDF of the entire study. Very interesting, I will look at it in detail later
Edited by edward, 06 August 2008 - 03:39 PM.

The study and similar ones have been posted and discussed over at bb.com
Edited by kismet, 09 September 2008 - 08:21 PM.

I realize that its a weak acid but I wonder what it does to your blood pH and chemistry, esp. at the site of injection? It might really burn going in........

I realize that its a weak acid but I wonder what it does to your blood pH and chemistry, esp. at the site of injection? It might really burn going in........

It is injected as ascorbate, not ascorbic acid. Usually Sodium Ascorbate. Just like Ester-C, calcium Ascorbate, which has a neutral pH.

I realize that its a weak acid but I wonder what it does to your blood pH and chemistry, esp. at the site of injection? It might really burn going in........

It is injected as ascorbate, not ascorbic acid. Usually Sodium Ascorbate. Just like Ester-C, calcium Ascorbate, which has a neutral pH.

Sodium Ascorbate is actually weakly basic in solution. This is because some of the ascorbate anions grab a proton from water to form undissociated ascorbic acid. That leaves some hydroxide ions floating around. This is a general property of salts of weak acids.

edit: People seem to think of vitamin c as benign because of the fact that you can take so much of it orally without it causing problems but in blood concentrations high enough (achieved only through IV therapy) to generate free radicals and hydrogen peroxide it looks like it becomes anything but benign.

Sure but what are the harmful effects of free radicals and oxidants? The main ones that come to mind are cell death, aging effects and most significantly mutation. Since this is being evaluated as a cancer therapy it seems that increasing the risk of future malignancies in the course of obviating a current one is an acceptable trade off barring better alternatives. An exception would be for something like prostate cancer where it may be safer not to treat.