Dr. Weeks’ Comment: Vitamin C as an adjunctive treatment for cancer – don’t be confused; no real controversy remains. Dis-information persists, but when one carefully and responsibly reads to determine if the refuting studies actually replicated the study it was trying to refute, you see the intellectual dishonesty. The Proceedings of National Academy Science is a scientific publication which accepts no drug company money. What other agent can you name which “selectively kills cancer cells” and is published in the Proceedings of National Academy Science? “Selective killing of cancer cells”… interested?
Proc Natl Acad Sci U S A. 1978 Sep;75(9):4538-42.
Supplemental ascorbate in the supportive treatment of cancer: reevaluation of prolongation of survival times in terminal human cancer.
Abstract
A study has been made of the survival times of 100 terminal cancer patients who were given supplemental ascorbate, usually 10 g/day, as part of their routine management and 1000 matched controls, similar patients who had received the same treatment except for the ascorbate. The two sets of patients were in part the same as those used in our earlier study [Cameron, E. & Pauling, L. (1976) Proc. Natl. Acad. Sci. USA 73, 3685-3689]. Tests confirm that the ascorbate-treated patients and the matched controls are representative subpopulations of the same population of “untreatable” patients. Survival times were measured not only from the date of “untreatability” but also from the precisely known date of first hospital attendance for the cancer that eventually reached the terminal stage. The ascorbate-treated patients were found to have a mean survival time about 300 days greater than that of the controls. Survival times greater than 1 yr after the date of untreatability were observed for 22% of the ascorbate-treated patients and for 0.4% of the controls. The mean survival time of these 22 ascorbate-treated patients is 2.4 yr after reaching the apparently terminal stage; 8 of the ascorbate-treated patients are still alive, with a mean survival time after untreatability of 3.5 yr.
http://www.ncbi.nlm.nih.gov/pubmed/279931
Here what follows is the article intending to refute Dr. Pauling’s work.
N Engl J Med. 1985 Jan 17;312(3):137-41.
High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison.
Abstract
It has been claimed that high-dose vitamin C is beneficial in the treatment of patients with advanced cancer, especially patients who have had no prior chemotherapy. In a double-blind study 100 patients with advanced colorectal cancer were randomly assigned to treatment with either high-dose vitamin C (10 g daily) or placebo. Overall, these patients were in very good general condition, with minimal symptoms. 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. On the basis of this and our previous randomized study, it can be concluded that high-dose vitamin C therapy is not effective against advanced malignant disease regardless of whether the patient has had any prior chemotherapy.
REFUTATION: Linus Pauling’s study, which claimed to cure cancer, included both oral AND INTRAVENOUS vitamin C. This study used only oral vitamin C so it did not replicate the original study so, scientifically speaking, this study could not refuse Pauling’s study.
Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13604-9. Epub 2005 Sep 12.
Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues.
Source
Molecular and Clinical Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract
Human pharmacokinetics data indicate that i.v. ascorbic acid (ascorbate) in pharmacologic concentrations could have an unanticipated role in cancer treatment. Our goals here were to test whether ascorbate killed cancer cells selectively, and if so, to determine mechanisms, using clinically relevant conditions. Cell death in 10 cancer and 4 normal cell types was measured by using 1-h exposures. Normal cells were unaffected by 20 mM ascorbate, whereas 5 cancer lines had EC(50) values of <4 mM, a concentration easily achievable i.v. Human lymphoma cells were studied in detail because of their sensitivity to ascorbate (EC(50) of 0.5 mM) and suitability for addressing mechanisms. Extracellular but not intracellular ascorbate mediated cell death, which occurred by apoptosis and pyknosis/necrosis. Cell death was independent of metal chelators and absolutely dependent on H(2)O(2) formation. Cell death from H(2)O(2) added to cells was identical to that found when H(2)O(2) was generated by ascorbate treatment. H(2)O(2) generation was dependent on ascorbate concentration, incubation time, and the presence of 0.5-10% serum, and displayed a linear relationship with ascorbate radical formation. Although ascorbate addition to medium generated H(2)O(2), ascorbate addition to blood generated no detectable H(2)O(2) and only trace detectable ascorbate radical. Taken together, these data indicate that ascorbate at concentrations achieved only by i.v. administration may be a pro-drug for formation of H(2)O(2), and that blood can be a delivery system of the pro-drug to tissues. These findings give plausibility to i.v. ascorbic acid in cancer treatment, and have unexpected implications for treatment of infections where H(2)O(2) may be beneficial.
Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13604-9. Epub 2005 Sep 12.
Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues.
Source
Molecular and Clinical Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract
Human pharmacokinetics data indicate that i.v. ascorbic acid (ascorbate) in pharmacologic concentrations could have an unanticipated role in cancer treatment. Our goals here were to test whether ascorbate killed cancer cells selectively, and if so, to determine mechanisms, using clinically relevant conditions. Cell death in 10 cancer and 4 normal cell types was measured by using 1-h exposures. Normal cells were unaffected by 20 mM ascorbate, whereas 5 cancer lines had EC(50) values of <4 mM, a concentration easily achievable i.v. Human lymphoma cells were studied in detail because of their sensitivity to ascorbate (EC(50) of 0.5 mM) and suitability for addressing mechanisms. Extracellular but not intracellular ascorbate mediated cell death, which occurred by apoptosis and pyknosis/necrosis. Cell death was independent of metal chelators and absolutely dependent on H(2)O(2) formation. Cell death from H(2)O(2) added to cells was identical to that found when H(2)O(2) was generated by ascorbate treatment. H(2)O(2) generation was dependent on ascorbate concentration, incubation time, and the presence of 0.5-10% serum, and displayed a linear relationship with ascorbate radical formation. Although ascorbate addition to medium generated H(2)O(2), ascorbate addition to blood generated no detectable H(2)O(2) and only trace detectable ascorbate radical. Taken together, these data indicate that ascorbate at concentrations achieved only by i.v. administration may be a pro-drug for formation of H(2)O(2), and that blood can be a delivery system of the pro-drug to tissues. These findings give plausibility to i.v. ascorbic acid in cancer treatment, and have unexpected implications for treatment of infections where H(2)O(2) may be beneficial.
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Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11105-9. Epub 2008 Aug 4.
Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice.
Source
Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, and Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
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.
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Eur J Obstet Gynecol Reprod Biol. 2004 Nov 10;117(1):70-5.
Efficacy and safety of vitamin C vaginal tablets in the treatment of non-specific vaginitis. A randomised, double blind, placebo-controlled study.
Source
Section of Gynaecological Infectiology, Gynaecological University Clinic, Hugstetter Strasse 55, Freiburg D-79106, Germany.
Abstract
This was a randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of Vitamin C vaginal tablets (250 mg) given once a day in patients suffering from non-specific vaginitis. The total length of the study was 20 days, including a treatment phase of 6 days. The primary end-point was the presence in the two groups of non-specific vaginitis 1 and 2 weeks after the end of treatment, as assessed by at least 3 out of the 4 characteristic symptoms: discharge, fishy odour, vaginal pH >/= 4.7, and presence of clue cells. Secondary end-points were the individual symptoms and signs, above reported, and pruritus, fever, superinfections, microscopic findings on vaginal smear, and colposcopy.
PATIENTS:
One hundred female patients aged 18 years or older and suffering from non-specific vaginitis were included in the study after giving their informed consent. Fifty were randomised to the active treatment and 50 to placebo. Seven patients, three in the Vitamin C group and four in the placebo group, were lost to follow-up and did not complete the treatment period. Two patients in the active group showed protocol deviations (age under 18 years and HIV-positive, respectively). The two groups resulted comparable for demographics, history and baseline clinical picture.
RESULTS:
A cluster analysis of the four main symptoms showed a statistically significant difference between the active group and the placebo group; significantly more patients were still affected by non-specific vaginitis after placebo (35.7%) compared to patients treated with Vitamin C tablets (14.0%). The meaningful secondary variable, referring to the microscopic examination of vaginal smear, supported the trend for efficacy in the Vitamin C treated group. The clue cells disappeared in 79% of patients treated with the drug and in 53% of patients on placebo. Similarly, bacteria disappeared in 77 and 54%, respectively, while lactobacilli reappeared in 79.1 and 53.3%, respectively. Vaginal pH values decreased significantly in both groups, but the frequency rate of subjects with pH >/= 4.7, as measured 1 week after the drug discontinuation, was significantly lesser in the Vitamin C group (16.3%) than in the placebo group (38.6%). Adverse events occurred in four patients, two on placebo (pruritus, cystitis) and two on Vitamin C (two candidiasis).
Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo.
Source
Molecular and Clinical Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract
Ascorbate (ascorbic acid, vitamin C), in pharmacologic concentrations easily achieved in humans by i.v. administration, selectively kills some cancer cells but not normal cells. We proposed that pharmacologic ascorbate is a prodrug for preferential steady-state formation of ascorbate radical (Asc(*-)) and H(2)O(2) in the extracellular space compared with blood. Here we test this hypothesis in vivo. Rats were administered parenteral (i.v. or i.p.) or oral ascorbate in typical human pharmacologic doses ( approximately 0.25-0.5 mg per gram of body weight). After i.v. injection, ascorbate baseline concentrations of 50-100 microM in blood and extracellular fluid increased to peaks of >8 mM. After i.p. injection, peaks approached 3 mM in both fluids. By gavage, the same doses produced ascorbate concentrations of <150 microM in both fluids. In blood, Asc(*-) concentrations measured by EPR were undetectable with oral administration and always <50 nM with parenteral administration, even when corresponding ascorbate concentrations were >8 mM. After parenteral dosing, Asc(*-) concentrations in extracellular fluid were 4- to 12-fold higher than those in blood, were as high as 250 nM, and were a function of ascorbate concentrations. By using the synthesized probe peroxyxanthone, H(2)O(2) in extracellular fluid was detected only after parenteral administration of ascorbate and when Asc(*-) concentrations in extracellular fluid exceeded 100 nM. The data show that pharmacologic ascorbate is a prodrug for preferential steady-state formation of Asc(*-) and H(2)O(2) in the extracellular space but not blood. These data provide a foundation for pursuing pharmacologic ascorbate as a prooxidant therapeutic agent in cancer and infections.
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Vitamin C: a concentration-function approach yields pharmacology and therapeutic discoveries.
Source
Molecular and Clinical Nutrition Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1372, USA. MarkL@mail.nih.gov.
Abstract
A concentration-function approach to vitamin C (ascorbate) has yielded new physiology and pharmacology discoveries. To determine the range of vitamin C concentrations possible in humans, pharmacokinetics studies were conducted. They showed that when vitamin C is ingested by mouth, plasma and tissue concentrations are tightly controlled by at least 3 mechanisms in healthy humans: absorption, tissue accumulation, and renal reabsorption. A 4th mechanism, rate of utilization, may be important in disease. With ingested amounts found in foods, vitamin C plasma concentrations do not exceed 100 μmol/L. Even with supplementation approaching maximally tolerated doses, ascorbate plasma concentrations are always <250 μmol/L and frequently <150 μmol/L. By contrast, when ascorbate is i.v. injected, tight control is bypassed until excess ascorbate is eliminated by glomerular filtration and renal excretion. With i.v. infusion, pharmacologic ascorbate concentrations of 25-30 mmol/L are safely achieved. Pharmacologic ascorbate can act as a pro-drug for hydrogen peroxide (H(2)O(2)) formation, which can lead to extracellular fluid at concentrations as high as 200 μmol/L. Pharmacologic ascorbate can elicit cytotoxicity toward cancer cells and slow the growth of tumors in experimental murine models. The effects of pharmacologic ascorbate should be further studied in diseases, such as cancer and infections, which may respond to generation of reactive oxygen species via H(2)O(2).
N Engl J Med. 1985 Jan 17;312(3):137-41.
High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison.
Abstract
It has been claimed that high-dose vitamin C is beneficial in the treatment of patients with advanced cancer, especially patients who have had no prior chemotherapy. In a double-blind study 100 patients with advanced colorectal cancer were randomly assigned to treatment with either high-dose vitamin C (10 g daily) or placebo. Overall, these patients were in very good general condition, with minimal symptoms. 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. On the basis of this and our previous randomized study, it can be concluded that high-dose vitamin C therapy is not effective against advanced malignant disease regardless of whether the patient has had any prior chemotherapy.
REFUTATION: Linus Pauling’s study, which claimed to cure cancer, included both oral AND INTRAVENOUS vitamin C. This study used only oral vitamin C so it did not replicate the original study so, scientifically speaking, this study could not refuse Pauling’s study.
Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial.
Abstract
One hundred and fifty patients with advanced cancer participated in a controlled double-blind study to evaluate the effects of high-dose vitamin C on symptoms and survival. Patients were divided randomly into a group that received vitamin C (10 g per day) and one that received a comparably flavored lactose placebo. Sixty evaluable patients received vitamin C and 63 received a placebo. Both groups were similar in age, sex, site of primary tumor, performance score, tumor grade and previous chemotherapy. The two groups showed no appreciable difference in changes in symptoms, performance status, appetite or weight. The median survival for all patients was about seven weeks, and the survival curves essentially overlapped. In this selected group of patients, we were unable to show a therapeutic benefit of high-dose vitamin C treatment.