The anti-cancer mechanism of action observed for high dose vitamin C is as a pro-oxidant (not an antioxidant). Ascorbate radical concentrations over a certain threshhold (~100 nanomolar) leads to the formation of hydrogen peroxide radical that is toxic to cancer cells.
However, mouse studies show these pro-oxidant levels of ascorbic acid (vitamin C) are possible with intravenous administration but not with any amount of oral administration. With oral administration, the ascorbate radical was actually undetectable in blood.
"Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo" https://www.ncbi.nlm.nih.gov/pubmed/17502596
Based on data like this, there is a trial underway of *intravenous* vitamin C for GBM. https://clinicaltrials.gov/ct2/show/NCT01752491
However I'd be hesitant about the use of either oral or intravenous vitamin C during radiation, because if pro-oxidant levels of ascorbate weren't succesfully achieved, antioxidant doses of vitamin C could potentially interfere with radiation therapy, as seen in mouse studies.
High-Dose Intravenous Vitamin C Combined with Cytotoxic Chemotherapy in Patients with Advanced Cancer: A Phase I-II Clinical Trial http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0120228
You may be right. My personal feeling is that there's not enough evidence to either completely dismiss it or to definitely say it has benefit. There are many therapies in that category. It might be useful for specific solid tumor subtypes that are particularly vulnerable to prooxidant therapy.
My daughter has done IV vitamin C along with a metronomic dose of chemotherapy for the last year when recurrence was inoperable and they had nothing left to offer (and she was put on palliative care). You have to start at 15-25g then build up from there since IVC can cause swelling and you don't want to do too much too fast.
Do you mind sharing how your daughter is doing? Is she still receiving both chemo and IVC? How do you find the Rothfeld Center to be as far as knowledge of this treatment? Also, how often is your daughter receiving the infusions and, if you don't mind, how much does each cost?
Low grade left thalamic glioma patient(inoperable,no biopsy done due to fear of functional damage and no conventional radiation and chemptherapy)being stable for 2 years with no growth has now started symptoms of blurred vision,headache and occassional vomitting.The NO advise a shunt.Is this necessary or could swelling be controlled by other alternate/off lable medicines?The tumour hasnt grown last 2 years and in fact altering signals in brain stem disappeared.The patient is on DCA,Ketone esters,benagene(oxaloacetate).Pls advise.
High doses of vitamin C to improve cancer treatment passes human safety trial https://www.sciencedaily.com/releases/2017/03/170330142341.htm
"This guarded optimism is based on the phase I trial data showing an increase in overall survival of 4-6 months in 11 glioblastoma multiforme patients (18-22 months) versus the 14-16 months survival typically seen with the standard treatment."
Excellent find Matjaz! I've uploaded the full scientific study (including all supplementary info) the article is based on into the Brain Tumor Library, in the following folder and subfolder:
The target ascorbate plasma concentration of at least 20 mM (millimolar) was achieved in all subjects at the dose level of 87.5 grams of ascorbate per intravenous infusion. In other words, very high doses were used, and these high doses were found to be safe.
Although the number of participating patients is small, the survival statistics are impressive, especially for the 8 GBM patients with unmethylated MGMT status. Median overall survival for this subgroup (MGMT unmethylated) is currently 23 months, with 3 patients still alive, two of them with at least 3 years of follow up (see figure 7).
All patients in this small trial received the ascorbate infusions (3 times per week) during the ~7 weeks of radiation, and during at least some of the monthly TMZ cycles. Ascorbate injections continued for the full period of monthly chemotherapy, except when therapy was stopped because of disease progression, and two patients stopped prematurely (prior to disease progression).
How to find a clinic that will administrate ascorbate infusions? I assume we will not get support from NO and we will have to pay for this kind of therapy ourselves?
I found places by googling "IV Vitamin C" and major cities near you. You may also want to google "integrative medicine". If you live in Massachusetts, I can refer you to the place we use and also share a few other places I found.
At the moment we are considering high-dose intravenous vitamin C. Can you tell us more about the G6PD test? Is it only necessary for men?
"Deficiency of the enzyme glucose-6-phosphate dehydrogenase, or G6PD, is a hereditary anomaly, and it is really widespread, which occurs in about ten percent of the male population of the planet."
"Fatal Hemolysis can occur if a patient has glucose-6-phosphate dehydrogenase deficiency. It is thus recommended that G6PD levels be assessed prior to the onset of therapy. The treatment is contra-indicated in situations where increased fluids, sodium, or chelating may cause serious problems. These situations include congestive heart failure, edema, ascites, chronic hemodialysis, unusual iron overload, and inadequate hydration or urine void volume (Rivers, 1987)."
"The gene [G6PD] is found on the X chromosome, males being more severely affected than females. Females may be variably affected by virtue of random inactivation of the X chromosome."
"Roughly 10% of black Americans were found to have the mildly defective A glucose-6-phosphate dehydrogenase variant, more severe B variants occurring around the Mediterranean and in South East Asia. It is the commonest enzymopathy affecting erythrocytes."
"G6PD deficiency is a hereditary X-linked recessive disorder with an estimated worldwide prevalence of at least 329 million people. Prevalence varies among different geographical regions and ethnicities. Because of the X-linked nature of this disorder and subsequent X-chromosomal inactivation of females, the clinical phenotype is relatively variable. As a result, most prevalence studies are estimated based on male subjects as the phenotypic presentation is more stable"
"When broken down by race, African Americans (10.2%) and Asians (3.6%) were more likely to have G6PD deficiency than Hispanics or Caucasians" https://www.hindawi.com/journals/crim/2017/5202606/
Is there any information on the interaction of high-dose vitamin C and other drugs often used in a cocktail? For example, we now have Avastin droppers, daily Chloroquine, Sirolimus, Metformin ...
Here is a list from drugs.com of drugs with "moderate" interaction with vitamin C. None of these drugs are common brain tumor cocktail drugs. High dose intravenous vitamin C might have a different list of interactions, but there isn't much information on that, not being a standard treatment for any disease.
I added this comment here https://www.cancertreatmentsresearch.com/high-dose-vitamin-c-cancer/#comment-8058 and also post it on this blog:
“Augmentation of intracellular iron using iron sucrose enhances the toxicity of pharmacological ascorbate in colon cancer cells”. 2018 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5591450/
“The tumor cell toxicity of pharmacological ascorbate is significantly increased with increasing levels of intracellular labile iron, which may be manipulated with Fe-sucrose to enhance cancer cell killing… Given our in vitro finding that extracellular Fe-sucrose can inhibit ascorbate toxicity, further pre-clinical in vivo research is needed to determine the optimal strategy and pharmacokinetics of iron sucrose administration, relative to administration of ascorbate. This could be important to maximizing the sensitization of cancer cells by increasing intracellular labile iron without significantly inhibiting ascorbate toxicity by increasing the extracellular labile iron.”
So, what could be the optimal strategy to increase intracellular labile iron, reduce extracellular labile iron, and administer intravenous vitamin C?
1. My mom has glioblastoma. We use vitamin C droppers at a dose of 97.5 grams per dropper 3 times a week on Mondays, Wednesdays and Fridays. On Saturday, we make Venofer 100mg dropper. https://www.drugs.com/venofer.html
2. We have abandoned a large dose of curcumin, as this study indicates that curcumin is an iron chelator and I fear that it may reduce the intracellular iron content in the tumor. https://www.ncbi.nlm.nih.gov/pubmed/25936466 http://sci-hub.tw/https://doi.org/10.1016/j.tem.2015.03.008
Due to the findings of this study, the role of antioxidants, many of which generate H2O2, is unclear. Should antioxidants be taken in combination with vitamin C droppers? Would this not be counterproductive?
High dose as in intravenous?
ReplyDeleteNo oral.
ReplyDeleteThe anti-cancer mechanism of action observed for high dose vitamin C is as a pro-oxidant (not an antioxidant). Ascorbate radical concentrations over a certain threshhold (~100 nanomolar) leads to the formation of hydrogen peroxide radical that is toxic to cancer cells.
ReplyDeleteHowever, mouse studies show these pro-oxidant levels of ascorbic acid (vitamin C) are possible with intravenous administration but not with any amount of oral administration. With oral administration, the ascorbate radical was actually undetectable in blood.
"Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo"
https://www.ncbi.nlm.nih.gov/pubmed/17502596
Based on data like this, there is a trial underway of *intravenous* vitamin C for GBM.
https://clinicaltrials.gov/ct2/show/NCT01752491
However I'd be hesitant about the use of either oral or intravenous vitamin C during radiation, because if pro-oxidant levels of ascorbate weren't succesfully achieved, antioxidant doses of vitamin C could potentially interfere with radiation therapy, as seen in mouse studies.
High-Dose Intravenous Vitamin C Combined
ReplyDeletewith Cytotoxic Chemotherapy in Patients
with Advanced Cancer: A Phase I-II Clinical
Trial
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0120228
To me, this is good data against use. There are lots of anecdotal stories but even the case studies are underwhelming.
DeleteYou may be right. My personal feeling is that there's not enough evidence to either completely dismiss it or to definitely say it has benefit. There are many therapies in that category. It might be useful for specific solid tumor subtypes that are particularly vulnerable to prooxidant therapy.
DeleteMy daughter has done IV vitamin C along with a metronomic dose of chemotherapy for the last year when recurrence was inoperable and they had nothing left to offer (and she was put on palliative care). You have to start at 15-25g then build up from there since IVC can cause swelling and you don't want to do too much too fast.
ReplyDeleteHi CaL,
DeleteDo you mind sharing how your daughter is doing? Is she still receiving both chemo and IVC? How do you find the Rothfeld Center to be as far as knowledge of this treatment? Also, how often is your daughter receiving the infusions and, if you don't mind, how much does each cost?
Thank you.
Low grade left thalamic glioma patient(inoperable,no biopsy done due to fear of functional damage and no conventional radiation and chemptherapy)being stable for 2 years with no growth has now started symptoms of blurred vision,headache and occassional vomitting.The NO advise a shunt.Is this necessary or could swelling be controlled by other alternate/off lable medicines?The tumour hasnt grown last 2 years and in fact altering signals in brain stem disappeared.The patient is on DCA,Ketone esters,benagene(oxaloacetate).Pls advise.
ReplyDeleteIt depends if the symptoms are caused by swelling (edema) or hydrocephalus. If it's the latter, then a shunt is probably necessary.
DeleteHigh doses of vitamin C to improve cancer treatment passes human safety trial
ReplyDeletehttps://www.sciencedaily.com/releases/2017/03/170330142341.htm
"This guarded optimism is based on the phase I trial data showing an increase in overall survival of 4-6 months in 11 glioblastoma multiforme patients (18-22 months) versus the 14-16 months survival typically seen with the standard treatment."
Excellent find Matjaz! I've uploaded the full scientific study (including all supplementary info) the article is based on into the Brain Tumor Library, in the following folder and subfolder:
Delete1. Therapies - Human Studies -> Ascorbate (vitamin C), intravenous ->
The target ascorbate plasma concentration of at least 20 mM (millimolar) was achieved in all subjects at the dose level of 87.5 grams of ascorbate per intravenous infusion. In other words, very high doses were used, and these high doses were found to be safe.
DeleteAlthough the number of participating patients is small, the survival statistics are impressive, especially for the 8 GBM patients with unmethylated MGMT status. Median overall survival for this subgroup (MGMT unmethylated) is currently 23 months, with 3 patients still alive, two of them with at least 3 years of follow up (see figure 7).
All patients in this small trial received the ascorbate infusions (3 times per week) during the ~7 weeks of radiation, and during at least some of the monthly TMZ cycles. Ascorbate injections continued for the full period of monthly chemotherapy, except when therapy was stopped because of disease progression, and two patients stopped prematurely (prior to disease progression).
How to find a clinic that will administrate ascorbate infusions? I assume we will not get support from NO and we will have to pay for this kind of therapy ourselves?
DeleteI found places by googling "IV Vitamin C" and major cities near you. You may also want to google "integrative medicine". If you live in Massachusetts, I can refer you to the place we use and also share a few other places I found.
DeleteThank you Chosen and Loved. We live in SF bay area. I can found a few clinics that administrate IV Vitamin C. How do you determine which one is good?
DeleteBe sure that they do a G6PD test and follow the Kansas University Medical Center's protocols (Jeanne Drisko, M.D.).
DeleteAt the moment we are considering high-dose intravenous vitamin C.
DeleteCan you tell us more about the G6PD test? Is it only necessary for men?
"Deficiency of the enzyme glucose-6-phosphate dehydrogenase, or G6PD, is a hereditary anomaly, and it is really widespread, which occurs in about ten percent of the male population of the planet."
Our doctor recommends us with intravenous vitamin C take omeprazole! he says that there will be an irritation of the gastric mucosa. It's strange.
Delete"Fatal Hemolysis can occur if a patient has glucose-6-phosphate dehydrogenase deficiency. It is thus recommended that G6PD levels be assessed prior to the onset of therapy. The treatment is contra-indicated in situations where increased fluids, sodium, or chelating may cause serious problems. These situations include congestive heart failure, edema, ascites, chronic hemodialysis, unusual iron overload, and inadequate hydration or urine void volume (Rivers, 1987)."
Delete"The gene [G6PD] is found on the X chromosome, males being more severely affected than females. Females may be variably affected by virtue of
Deleterandom inactivation of the X chromosome."
"Roughly 10% of black Americans were found to have the mildly
defective A glucose-6-phosphate dehydrogenase variant, more severe
B variants occurring around the Mediterranean and in South East Asia. It is the commonest enzymopathy affecting erythrocytes."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1677333/pdf/bmj00013-0043.pdf
"G6PD deficiency is a hereditary X-linked recessive disorder with an estimated worldwide prevalence of at least 329 million people. Prevalence varies among different geographical regions and ethnicities. Because of the X-linked nature of this disorder and subsequent X-chromosomal inactivation of females, the clinical phenotype is relatively variable. As a result, most prevalence studies are estimated based on male subjects as the phenotypic presentation is more stable"
"When broken down by race, African Americans (10.2%) and Asians (3.6%) were more likely to have G6PD deficiency than Hispanics or Caucasians"
https://www.hindawi.com/journals/crim/2017/5202606/
Is there any information on the interaction of high-dose vitamin C and other drugs often used in a cocktail?
ReplyDeleteFor example, we now have Avastin droppers, daily Chloroquine, Sirolimus, Metformin ...
Here is a list from drugs.com of drugs with "moderate" interaction with vitamin C. None of these drugs are common brain tumor cocktail drugs. High dose intravenous vitamin C might have a different list of interactions, but there isn't much information on that, not being a standard treatment for any disease.
Deletehttps://www.drugs.com/drug-interactions/ascorbic-acid,vitamin-c-index.html?filter=2&generic_only=
There's a study if doxycycline is taken with high dose vitamin c , it's 35× more effective
ReplyDeletehttp://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B0%5D=18428&path%5B1%5D=59195
ReplyDeleteI added this comment here https://www.cancertreatmentsresearch.com/high-dose-vitamin-c-cancer/#comment-8058
ReplyDeleteand also post it on this blog:
“Augmentation of intracellular iron using iron sucrose enhances the toxicity of pharmacological ascorbate in colon cancer cells”.
2018 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5591450/
“The tumor cell toxicity of pharmacological ascorbate is significantly increased with increasing levels of intracellular labile iron, which may be manipulated with Fe-sucrose to enhance cancer cell killing…
Given our in vitro finding that extracellular Fe-sucrose can inhibit ascorbate toxicity, further pre-clinical in vivo research is needed to determine the optimal strategy and pharmacokinetics of iron sucrose administration, relative to administration of ascorbate. This could be important to maximizing the sensitization of cancer cells by increasing intracellular labile iron without significantly inhibiting ascorbate toxicity by increasing the extracellular labile iron.”
So, what could be the optimal strategy to increase intracellular labile iron, reduce extracellular labile iron, and administer intravenous vitamin C?
1. My mom has glioblastoma. We use vitamin C droppers at a dose of 97.5 grams per dropper 3 times a week on Mondays, Wednesdays and Fridays. On Saturday, we make Venofer 100mg dropper.
https://www.drugs.com/venofer.html
2. We have abandoned a large dose of curcumin, as this study indicates that curcumin is an iron chelator and I fear that it may reduce the intracellular iron content in the tumor.
https://www.ncbi.nlm.nih.gov/pubmed/25936466
http://sci-hub.tw/https://doi.org/10.1016/j.tem.2015.03.008
Any comments?
I also found an interesting study on the synergy of vitamin C and auronofin on malignant lymphoma cells:
ReplyDelete2018 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302138/
It looks very intriguing - to combine auronofin, which has already been proposed for glioblastoma, and high-dose vitamin C dropper.
Your opinion?
Due to the findings of this study, the role of antioxidants, many of which generate H2O2, is unclear. Should antioxidants be taken in combination with vitamin C droppers? Would this not be counterproductive?
Delete