A pilot clinical study of continuous intravenous ascorbate in terminal cancer patients

Case studies suggest that vitamin C, given intravenously at doses of 10-100 grams/day can improve patient well being and in some cases, reduce tumor size. While ascorbate is generally considered safe, clinical data on high intravenous doses is limited. Twenty-four late stage terminal cancer patients were given continuous infusions of 150 to 710 mg/kg/day for up to eight weeks. Blood chemistry and blood count profiles were obtained at roughly one-week intervals while patient health, adverse events and tumor progression were monitored. The majority of patients were vitamin C deficient prior to treatment. Intravenous infusions increased plasma ascorbate concentrations to a mean of 1.1 mM. The most common adverse events reported were nausea, edema, and dry mouth or skin; and these were generally minor. Two Grade 3 adverse events 'possibly related' to the agent were reported: one patient with a history of renal calculi developed a kidney stone after thirteen days of treatment and another patient experienced hypokalemia after six weeks of treatment. White blood cell counts were stable while hemoglobin and hematocrit levels dropped slightly during treatment, consistent with trends observed prior to therapy. Blood creatinine, BUN, glucose, and uric acid concentrations decreased or remained stable during therapy, suggesting that ascorbate infusions did not adversely affect renal function. One patient had stable disease and continued the treatment for forty-eight weeks. These data suggest that intravenous vitamin C therapy for cancer is relatively safe, provided the patient does not have a history of kidney stone formation.

Effects of high dose ascorbate administration on L-10 tumor growth in guinea pigs

Sodium ascorbate is preferentially toxic to tumor cells at high concentrations. It has not been established, however, whether sufficient intra-tumor ascorbate concentrations are safely achievable in vivo. We administered sodium ascorbate subcutaneously or orally for eighteen days to Sewall-Wright strain-2 guinea pigs bearing intradermal L-10 hepatocarcinoma tumors. Tumor masses and intra-tumor ascorbate concentrations were determined at necropsy. L-10 cells formed tumors that metastasized to the lymph nodes, with tumor burdens reaching nearly 50 grams in untreated animals. Subcutaneous injections of ascorbate (500 mg/kg/day) inhibited tumor growth by as much as sixty-five percent, with oral supplementation reducing it by roughly fifty percent. Tumor growth correlated inversely with intra-tumor ascorbate concentration, the latter exceeding 2 mM in some cases. Ascorbate concentrations sufficient to kill tumor cells can be safely achieved in solid tumors in vivo, suggesting a possible role for high dose intravenous ascorbate in treating cancer.

Intravenous ascorbic acid as a treatment for severe jellyfish stings

We report a case of jellyfish envenomation in a 39 year old male. He was stung extensively on both lower limbs by an unidentified jellyfish. This occurred in shallow waters of a beach in the vicinity of Labuan Island, Malaysia. The patient received ambulatory treatment with parenteral and oral ascorbate with remarkable recovery

Intravenous vitamin C as a chemotherapy agent: a report on clinical cases

A series of seven cases are presented in which intravenous vitamin C has been used as antineoplastic agent in the treatment of different types of cancers. The cancers cases reviewed are the following: Renal cell carcinoma (2), Colorectal cancer (1), Pancreatic cancer (1), Non-Hodgkin's lymphoma (2) and breast cancer (1). Toxic reactions were not observed at these high doses of intravenous Vitamin C. All patients were prescreened for Glucose 6--phosphate dehydrogenase deficiency before administering intravenous Vitamin C in order to prevent hemolysis

Erythrocyte membrane fatty acid composition in cancer patients

Essential fatty acids (EFA) have an important role in complex metabolic reactions. The metabolism of essential polyunsaturated fatty acids (PUFA) appears to be one of the critical targets in the complex metabolic stages that lead to, or are associated with cancer. The goal of our research was to analyze the erythrocyte specific types of membrane fatty acid content, level and distribution in cancer patients as compared to non-cancer patients. Changes in fatty acid composition may affect different aspects of cell structure and function, including proliferation. Analyses of RBCs membrane fatty acids were performed for 255 patients with different types of cancer (breast, prostate, liver, pancreas, colon, and lung), 2,800 non-cancer patients and 34 healthy volunteers. Our research study demonstrated a lower level of stearic acid and an increased content of oleic acid in RBC of cancer patients in comparison with control and non-cancer patients. According to the results of this investigation, the ratio of Eicosa pentaenoic acid (EPA) and Decosa hexaenoic acid (DHA) to Alpha-linolenic acid (ALA) may be useful to estimate PUFA imbalances in cancer patients. EPA and DHA acid may be recommended as supplementation and in addition to current therapy during cancer treatment

Cell membrane fatty acid composition differs between normal and malignant cell lines

Twenty-eight fatty acids (C8:0 to C24:l n-9) were measured by gas chromatography in four normal cell lines (C3H / 10T1 / 2, CCD-18Co, CCD-25SK and CCD-37Lu) and seven cancer cell lines (C-41, Caov-3, LS-180, PC-3, SK-MEL-28, SK-MES-1 and U-87 MG). Results show differences in the content and proportions of fatty acids when comparing cancer cell lines with their normal counterparts. Cancer cell lines showed lower C20: 4 n-6, C24:1 n-9, polyunsaturated fatty acids (PUFA's) and ratios of C20:4 n-6 to C20:5 n-3 and C16:0 to C18:1 n-9 and stearic to oleic (SA/OA) than their normal counterparts. All cancer cell lines had SA/OA ratios lower than 7.0 while normal cell lines had ratios greater than 0.7 (p<0.05). In addition, the ratios of total saturated fatty acids (SFA) to PUFA'S and the concentration of C18:1 n-9, C18:2 n-6, C20:5 n-3 were higher in cancer cell lines as compared to normal cell lines. A positive correlation was detected between C16:0 and longer SFA'S (r = +0.511, p<0.05) in normal cell lines whereas a negative correlation (r=0.608, p<0.05) was obtained for malignant cell lines. Moreover, cancerous cell lines exhibited a particular desaturation defect and an abnormal incorporation of C18:2 n-6 and C20-4 n-6 fatty acids

Intravenous ascorbic acid: protocol for its application and use

High dose intravenous(i.v.) ascorbic acid (AA) has been used as therapy for infectious disease from bacterial and viral origin and adjuvant therapy for cancer. In this publication we describe a clinical protocol that has been developed over the past twenty years utilizing high dose i.v. AA as therapy for cancer. This includes principles of treatment, rationale, baseline workup, infusion protocol, precautions and side effects.

Effects of a high molecular mass Convolvulus arvensis extract on tumor growth and angiogenesis

BACKGROUND: Plant materials represent promising sources of anti-cancer agents. We developed and tested a novel extract from the ubiquitous plant Convolvulus arvensis. MATERIALS AND METHODS: Convolvulus arvensis components were extracted in boiling water, and small molecules were removed by high-pressure filtration. The extract's biological activity was assessed by measuring its effects on S-180 fibrosarcoma growth in Kun Ming mice and on heparin-induced angiogenesis in chick embryos. We also examined the extract's effects on lymphocytes ex vivo and tumor cell growth in vitro. RESULTS: The extract (primarily proteins and polysaccharides) inhibited tumor growth in a dose-dependent fashion when administered orally. At the highest dose tested, 200 mg/kg/day, tumor growth was inhibited by roughly seventy percent. Subcutaneous or intraperitoneal administration at 50 mg/kg/day also inhibited tumor growth by over seventy percent. The extract's acute LD50 in Kun Ming mice was 500 mg/kg/day when injected, indicating that tumor growth inhibition occurred at non-toxic doses. It inhibited angiogenesis in chick embryos, improved lymphocyte survival ex vivo, and enhanced yeast phagocytosis, but did not kill tumor cells in culture. CONCLUSION: High molecular mass extract deserves further study as an anti-cancer agent.

Cytotoxicity of ascorbate, lipoic acid, and other antioxidants in hollow fibre in vitro tumours.

Vitamin C (ascorbate) is toxic to tumour cells, and has been suggested as an adjuvant cancer treatment. Our goal was to determine if ascorbate, in combination with other antioxidants, could kill cells in the SW620 hollow fibre in vitro solid tumour model at clinically achievable concentrations. Ascorbate anti-cancer efficacy, alone or in combination with lipoic acid, vitamin K3, phenyl ascorbate, or doxorubicin, was assessed using annexin V staining and standard survival assays. 2-day treatments with 10 mM ascorbate increased the percentage of apoptotic cells in SW620 hollow fibre tumours. Lipoic acid synergistically enhanced ascorbate cytotoxicity, reducing the 2-day LC(50)in hollow fibre tumours from 34 mM to 4 mM. Lipoic acid, unlike ascorbate, was equally effective against proliferating and non-proliferating cells. Ascorbate levels in human blood plasma were measured during and after intravenous ascorbate infusions. Infusions of 60 g produced peak plasma concentrations exceeding 20 mM with an area under the curve (24 h) of 76 mM h. Thus, tumoricidal concentrations may be achievable in vivo. Ascorbate efficacy was enhanced in an additive fashion by phenyl ascorbate or vitamin K3. The effect of ascorbate on doxorubicin efficacy was concentration dependent; low doses were protective while high doses increased cell killing.

Integrative medicine: a paradigm shift in medical education and practice.

The use of alternative/complementary medicine has been increasing considerably. Conventional medicine must begin to address issues related to the use, safety, regulation, research and education of alternative/complementary medicine. Integrative medicine combines conventional medicine and alternative complementary practices. Integrative medicine is an innovative approach to medicine and medical education. It involves the understanding of the interaction of the mind, body and spirit and how to interpret this relationship in the dynamics of health and disease. Integrative medicine shifts the orientation of the medical practice from disease based approach to a healing based approach. It does not reject conventional medicine nor uncritically accepts unconventional practices. Integrative medicine is an effective, more fulfilling human approach to medicine based on the benefit of the patient by following good medicine practices in a scientific manner.

Intravenous ascorbate as a tumor cytotoxic chemotherapeutic agent.

Ascorbic acid and its salts (AA) are preferentially toxic to tumor cells in vitro and in vivo. Given in high enough doses to maintain plasma concentrations above levels that have been shown to be toxic to tumor cells in vitro, AA has the potential to selectively kill tumor cells in a manner similar to other tumor cytotoxic chemotherapeutic agents. Most studies of AA and cancer to date have not utilized high enough doses of AA to maintain tumor cytotoxic plasma concentrations of AA. Data are presented which demonstrate the ability to sustain plasma levels of AA in humans above levels which are toxic to tumor cells in vitro and suggests the feasibility of using AA as a cytotoxic chemotherapeutic agent.

Improved microplate fluorometer counting of viable tumor and normal cells.

An improved method has been developed to count cells in situ based on the measurement of esterase activity with carboxyfluorescein diacetate. This sensitive, semiautomated microplate fluorometer assay was able to estimate viable cell numbers over a range of 5 x 10(2) to 2.6 x 10(5) cells/well in a tumor cell line. Sensitivity to 10(3) was demonstrated in two other cell lines. Sub- and supranormal fluorescence events which can be responsible for unreliable readings when using a fluorescence assay for cell counting were quantified in a menadione (cytotoxic agent)/U-87 MG (cell line) model. There was a close correlation between the fluorometer method and Coulter counter method for two different tumor cell lines when this method was performed on cells after sub- and supranormal fluorescence events had ceased.

Differences in human serum copper and zinc levels in healthy and patient populations.

This report is designed to re-examine the use of our presently accepted normal laboratory levels for human serum zinc and copper and to suggest a technique, previously unreported in the literature, to more precisely understand the relationship of serum zinc and copper in health and disease. Data from a patient population of 95 and a healthy population of 115 who met certain criteria are compared.

Clinical correlations between serum glucose variance and reported symptoms in human subjects.

The evidence presented in this report suggests that, in both a healthy people and patient populations, there are clinical and biochemical (fasting serum glucose) gradations of health and sickness. What is particularly fascinating is the fact that, as one progressively develops a symptomless and signfree subset, the blood glucose levels become more homogeneous, meaning that glucose scores cluster to the mean. This enhances the diagnostic, therapeutic and predictive utility of blood glucose scores. While such clinico-biochemical parallelisms are clear, it is essential to mention the point that they do not necessarily prove cause-and-effect. But our interest has been sufficiently stimulated to study several other possible correlates between biochemical variances and the degree of reported symptomatology.