Treatment of pancreatic cancer with intravenous vitamin C: a case report.

Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis and is often discovered at an advanced stage with few therapeutic options. Current conventional regimens for PDA are associated with significant morbidity, decreased quality of life, and a considerable financial burden. As a result, some patients turn to integrative medicine therapies as an alternate option after a diagnosis of PDA. Intravenous pharmacologic ascorbic acid (PAA) is one such treatment. The use of PAA has been passionately debated for many years, but more recent rigorous scientific research has shown that there are significant blood concentration differences when ascorbic acid is given parenterally when compared to oral dosing. This pharmacologic difference appears to be critical for its role in oncology. Here, we report the use of PAA in a patient with poorly differentiated stage IV PDA as an exclusive chemotherapeutic regimen. The patient survived nearly 4 years after diagnosis, with PAA as his sole treatment, and he achieved objective regression of his disease. He died from sepsis and organ failure from a bowel perforation event. This case illustrates the possibility of PAA to effectively control tumor progression and serve as an adjunct to standard of care PDA chemotherapy regimens. Our patient's experience with PAA should be taken into consideration, along with previous research in cell, animal, and clinical experiments to design future treatment trials.

A convenient method for measuring blood ascorbate concentrations in patients receiving high-dose intravenous ascorbate.

OBJECTIVE: A simple method of using fingerstick blood glucose (FSBG) monitors to estimate blood ascorbate values after high-dose intravenous (IV) ascorbate infusion is evaluated as a substitution for high-performance liquid chromatography (HPLC) measurement. METHODS: In 33 participants, readings from FSBG monitors were taken before and after IV ascorbate infusions at various time points, with the postinfusion FSBG readings subtracted from the baseline glucose readings. The results of the subtractions (AAFSBG) were correlated with ascorbate concentrations detected by HPLC (AAHPLC). RESULTS: A linear regression was found between ascorbate concentrations detected by the fingerstick method (AAFSBG) and by HPLC (AAHPLC). The linear correlations were identical in healthy subjects, diabetic subjects, and cancer patients. Analysis of variance obtained an AAFSBG/AAHPLC ratio of 0.90, with a 90% confidence interval of (0.69, 1.20). The corrections of AAFSBG improved similarity to AAHPLC but did not significantly differ from the uncorrected values. CONCLUSION: The FSBG method can be used as an approximate estimation of high blood ascorbate concentration after IV ascorbate (>50 mg/dL, or 2.8 mM) without correction. However, this measurement is not accurate in detecting lower or baseline blood ascorbate. It is also important to highlight that in regard to glucose monitoring, FSBG readings will be erroneously elevated following IV ascorbate use and insulin should not be administered to patients based on these readings.

Design of the Trial to Assess Chelation Therapy (TACT).

TACT is an National Institutes of Health-sponsored, randomized, double-blind, placebo-controlled, 2 × 2 factorial clinical trial testing the benefits and risks of 40 infusions of a multicomponent disodium EDTA chelation solution compared with placebo and of an oral, high-dose multivitamin and mineral supplement. TACT has randomized and will follow up 1,708 patients for an average of approximately 4 years. The primary end point is a composite of all-cause mortality, myocardial infarction, stroke, coronary revascularization, and hospitalization for angina. A 900-patient substudy will examine quality-of-life outcomes. The trial is designed to have >85% power to detect a 25% relative reduction in the primary end point for each treatment factor. Enrollment began in September 2003 and was completed in October 2010.

High Dose Intravenous Vitamin C as Adjunctive Therapy for COVID-19 Patients with Cancer: Two Cases.

BACKGROUND: Related to the SARS-CoV-2 pandemic leading to COVID-19 illness, patients with cancer comorbidity are known to have a higher risk of developing severe viral-related events, including death. To date, there are few treatments with proven efficacy for COVID-19. Vitamin C administered intravenously (IVC) has been extensively investigated in cancer treatment with a known safety profile and has been proposed to play a role in managing COVID-19. IVC was used to treat COVID-19 patients in hospitals in China, USA, and Europe with reported benefits. We report here unexpected beneficial results from the use of IVC in two severely ill oncology patients with documented COVID-19 lung disease. CASE REPORT: two oncology patients were diagnosed with SARS-CoV-2 infection. Prior to receiving IVC, lung infiltrates and systemic inflammation in both patients were progressing despite multiple anti-viral, antibiotic, and anti-inflammatory treatments with intensive supportive care. Both patients subsequently received 12 g of IVC delivered intravenously over 30 min, given 2 times daily for 7 days. Serial SARS-CoV-2 nucleic acid tests showed that the viral load was negative only after the 7-day IVC treatment. In both patients after receiving IVC infusions, imaging by chest CT or X-ray showed improving lung infiltrates. There were reductions in systematic inflammation by high-sensitivity C-reactive protein (hsCRP), and Interleukin-6 (IL-6) testing. No adverse events were observed related to IVC treatment. CONCLUSION: the use of high-dose IVC demonstrated unexpected clinical benefits in treating COVID-19 in two cancer patients presenting with complicated severe comorbidities where an unfavorable prognosis was anticipated.

Pharmacological ascorbate induces 'BRCAness' and enhances the effects of Poly(ADP-Ribose) polymerase inhibitors against BRCA1/2 wild-type ovarian cancer.

The promise of poly(ADP-ribose) polymerase inhibitors (PARPis) in the management of epithelial ovarian cancer (EOC) is hampered by the limited clinical activity against BRCA wild-type or homologous recombination-proficient EOC. In order to decrease the resistance and increase the efficacy of PARPis, combination treatments of pharmacological ascorbate and PARPis in preclinical BRCA wild-type EOC models were investigated. The cytotoxicity of pharmacological ascorbate, olaparib and veliparib in a panel of BRCA1/2 wild-type EOC cell lines were measured using MTT assays. Poly(ADP-ribose) levels were quantified using chemiluminescent ELISA. The expression of proteins involved in DNA damage and DNA double-strand breaks (DSBs) repair pathways were assessed by western blotting. The in vivo efficacy of pharmacological ascorbate, olaparib and their combination was evaluated in an intraperitoneal xenograft mouse model of BRCA1/2 wild-type EOC. Pharmacological ascorbate induced H2O2-dependent cytotoxicity in BRCA1/2 wild-type EOC cells. SHIN3 and OVCAR5 cells were resistant to olaparib and veliparib treatment; however, the combination of ascorbate with olaparib or veliparib significantly enhanced cell death. Pharmacological ascorbate enhanced the effects olaparib or veliparib by downregulating the expression of BRCA1, BRCA2 and RAD51. Consequently, the combination of pharmacological ascorbate and olaparib potently enhanced DNA DSBs and significantly decreased tumor burden, ascites volume and the number of tumor cells in ascites in mice bearing BRCA1/2 wild-type ovarian cancer xenografts. The combination of pharmacological ascorbate and PARPis may be a promising therapeutic approach worth clinical investigation in patients with BRCA wild-type or PARPi-resistant EOC.

High Dose Parenteral Ascorbate Inhibited Pancreatic Cancer Growth and Metastasis: Mechanisms and a Phase I/IIa study.

Pancreatic cancer is among the most lethal cancers with poorly tolerated treatments. There is increasing interest in using high-dose intravenous ascorbate (IVC) in treating this disease partially because of its low toxicity. IVC bypasses bioavailability barriers of oral ingestion, provides pharmacological concentrations in tissues, and exhibits selective cytotoxic effects in cancer cells through peroxide formation. Here, we further revealed its anti-pancreatic cancer mechanisms and conducted a phase I/IIa study to investigate pharmacokinetic interaction between IVC and gemcitabine. Pharmacological ascorbate induced cell death in pancreatic cancer cells with diverse mutational backgrounds. Pharmacological ascorbate depleted cellular NAD+ preferentially in cancer cells versus normal cells, leading to depletion of ATP and robustly increased α-tubulin acetylation in cancer cells. While ATP depletion led to cell death, over-acetylated tubulin led to inhibition of motility and mitosis. Collagen was increased, and cancer cell epithelial-mesenchymal transition (EMT) was inhibited, accompanied with inhibition in metastasis. IVC was safe in patients and showed the possibility to prolong patient survival. There was no interference to gemcitabine pharmacokinetics by IVC administration. Taken together, these data revealed a multi-targeting mechanism of pharmacological ascorbate's anti-cancer action, with minimal toxicity, and provided guidance to design larger definitive trials testing efficacy of IVC in treating advanced pancreatic cancer.

Nutritional and Metabolic Biomarkers in Autism Spectrum Disorders: An Exploratory Study.

CONTEXT: Autism spectrum disorder (ASD) is currently on the rise, now affecting approximately 1 in 68 children in the United States according to a 2010 surveillance summary from the Centers for Disease Control and Prevention (CDC). This figure is an estimated increase of 78% from the figure in 2002. The CDC suggests that more investigation is needed to understand this astounding increase in autism in such a short period. OBJECTIVE: The aim of this pilot study was to determine whether a group of children with ASD exhibited similar variations in a broad array of potential correlates, including medical histories, symptoms, genetics, and multiple nutritional and metabolic biomarkers. DESIGN: This study was a retrospective, descriptive chart review. SETTING: The study took place at the University of Kansas Medical Center (KUMC). PARTICIPANTS: Participants were 7 children with ASD who had sought treatment at the Integrative Medicine Clinic at the medical center. RESULTS: A majority of the children exhibited an elevated copper:zinc ratio and abnormal vitamin D levels. Children also demonstrated abnormal levels of the essential fatty acids: (1) α-linolenic acid (ALA)- C13:3W3, and (2) linoleic acid (LA)-C18:2W6; high levels of docosahexaenoic acid (DHA); and an elevated ω-6:ω-3 ratio. Three of 7 children demonstrated abnormal manganese levels. Children did not demonstrate elevated urine pyruvate or lactate but did have abnormal detoxification markers. Three of 7 patients demonstrated abnormalities in citric acid metabolites, bacterial metabolism, and fatty acid oxidation markers. A majority demonstrated elevated serum immunoglobulin G (IgG) antibodies to casein, egg whites, egg yolks, and peanuts. A majority had absent glutathione S-transferase (GSTM) at the 1p13.3 location, and 3 of 7 children were heterozygous for the glutathione S-transferase I105V (GSTP1). A majority also exhibited genetic polymorphism of the mitochondrial gene superoxide dismutase A16V (SOD2). CONCLUSIONS: The findings from this small group of children with ASD points to the existence of nutritional, metabolic, and genetic correlates of ASD. These factors appear to be important potential abnormalities that warrant a case control study to evaluate their reliability and validity as markers of ASD.

Probiotics in health maintenance and disease prevention.

Probiotic microflora display numerous health benefits beyond providing basic nutritional value. They cooperatively maintain a delicate balance between the gastrointestinal tract and immune system. When this balance is disrupted, disease and inflammation result. Inflammation and over stimulation of the immune system by pathogenic bacteria are competitively inhibited by mucosal adherence of normal beneficial microflora. A healthy gastrointestinal tract with adequate mucus production and appropriate bacterial colonization prevents the overgrowth of pathogenic bacteria, modulates disease processes, and prevents widespread inflammatory disorders. The understanding of the function of probiotics in the maintenance of health and their importance in preventing disease serves to enhance the overall health of patients. With increasing understanding that beneficial microbes are required for health maintenance and disease prevention, probiotics may be commonly used as a therapeutic tool by health care practitioners in the not-too-distant future. This review presents a review of probiotics in health maintenance and disease prevention.

Pediatric Integrative Medicine Approaches to Attention Deficit Hyperactivity Disorder (ADHD).

Attention deficit hyperactivity disorder (ADHD) is the most common neuropsychiatric disorder in children and is increasing in prevalence. There has also been a related increase in prescribing stimulant medication despite some controversy whether ADHD medication makes a lasting difference in school performance or achievement. Families who are apprehensive about side effects and with concerns for efficacy of medication pursue integrative medicine as an alternative or adjunct to pharmacologic and cognitive behavioral treatment approaches. Integrative medicine incorporates evidence-based medicine, both conventional and complementary and alternative therapies, to deliver personalized care to the patient, emphasizing diet, nutrients, gut health, and environmental influences as a means to decrease symptoms associated with chronic disorders. Pediatric integrative medicine practitioners are increasing in number throughout the United States because of improvement in patient health outcomes. However, limited funding and poor research design interfere with generalizable treatment approaches utilizing integrative medicine. The use of research designs originally intended for drugs and procedures are not suitable for many integrative medicine approaches. This article serves to highlight integrative medicine approaches in use today for children with ADHD, including dietary therapies, nutritional supplements, environmental hygiene, and neurofeedback.

Anti-cancer effect of pharmacologic ascorbate and its interaction with supplementary parenteral glutathione in preclinical cancer models.

Two popular complementary, alternative, and integrative medicine therapies, high-dose intravenous ascorbic acid (AA) and intravenous glutathione (GSH), are often coadministered to cancer patients with unclear efficacy and drug-drug interaction. In this study we provide the first survey evidence for clinical use of iv GSH with iv AA. To address questions of efficacy and drug-drug interaction, we tested 10 cancer cell lines with AA, GSH, and their combination. The results showed that pharmacologic AA induced cytotoxicity in all tested cancer cells, with IC(50) less than 4 mM, a concentration easily achievable in humans. GSH reduced cytotoxicity by 10-95% by attenuating AA-induced H(2)O(2) production. Treatment in mouse pancreatic cancer xenografts showed that intraperitoneal AA at 4 g/kg daily reduced tumor volume by 42%. Addition of intraperitoneal GSH inhibited the AA-induced tumor volume reduction. Although all treatments (AA, GSH, and AA+GSH) improved survival rate, AA+GSH inhibited the cytotoxic effect of AA alone and failed to provide further survival benefit. These data confirm the pro-oxidative anti-cancer mechanism of pharmacologic AA and suggest that AA and GSH administered together provide no additional benefit compared with AA alone. There is an antagonism between ascorbate and glutathione in treating cancer, and therefore iv AA and iv GSH should not be coadministered to cancer patients on the same day.

Prostate imaging modalities that can be used for complementary and alternative medicine clinical studies.

This article provides an overview of imaging modalities that aid in diagnosing, staging, and assessing therapeutic response in prostate cancer. Prostate cancer is the second most common type of cancer in American men and the second leading cause of cancer death among men. Prostate cancer is difficult to diagnose in early stages, and advanced disease often recurs after treatment. To localize sites of recurrence many imaging modalities have been used with varying success. This article presents case studies of PET scanning using carbon 11 acetate and discusses intravenously infused ascorbate, a complementary and alternative medicine therapy for prostate cancer.

The use of antioxidants in transmissible spongiform encephalopathies: a case report.

BACKGROUND: Transmissible spongiform encephalopathies (TSE), which include Creutzfeldt-Jakob disease and new variant Creutzfeldt-Jakob disease, are diseases characterized by progressive deterioration in the central nervous system with neuronal degeneration, vacuolatization of the neuropil, and gliosis. Little is known about the pathogenic mechanisms of infection, and controversy exits around the inciting infective agent. It has been shown that an important factor in pathogenesis is the immune system. CASE: The reported case points to beneficial effects when antioxidant therapies are used in transmissible spongiform encephalopathies. The case revealed an early reversal in cognitive decline and subsequent improvements in myoclonus, apnea and rigidity. Although death was the ultimate outcome, the patient succumbed to the illness over 22 months after the onset of symptoms when the early rapid decline predicted demise within a few months. CONCLUSION: It is possible that strategies blocking the effect of proinflammatory cytokines and the resulting oxidative damage may stem the progressive damage to the neuropil that occurs in spongiform encephalopathies. Further investigation into the use of antioxidants and other types of agents quelling inflammation needs to be undertaken. If antioxidants could be combined with treatments for the inciting infective agent, a new direction could be taken in the outcome of transmissible spongiform encephalopathies including CJD and vCJD.

The use of antioxidant therapies during chemotherapy.

OBJECTIVE: At the present time, many cancer patients combine some form of complementary and alternative medicine therapies with their conventional therapies. The most common choice of these therapies is the use of antioxidants. RESULTS: A review of four common antioxidants is undertaken, which includes vitamin E (mixed tocopherols and tocotrienols), beta-carotene (natural mixed carotenoids), vitamin C (ascorbic acid), and vitamin A (retinoic acid). Antioxidants act as electron acceptors as well as therapeutic biologic response modifiers. Despite the fact that chemotherapy-induced formation of free radicals is well-demonstrated, chemotherapy-induced cytotoxicity in general does not seem to depend on formation of reactive oxygen species. CONCLUSIONS: Currently, evidence is growing that antioxidants may provide some benefit when combined with certain types of chemotherapy. Because of the potential for positive benefits, a randomized controlled trial evaluating the safety and efficacy of adding antioxidants to chemotherapy in newly diagnosed ovarian cancer is underway at the University of Kansas Medical Center.

The use of antioxidants with first-line chemotherapy in two cases of ovarian cancer.

OBJECTIVE: Because of poor overall survival in advanced ovarian malignancies, patients often turn to alternative therapies despite controversy surrounding their use. Currently, the majority of cancer patients combine some form of complementary and alternative medicine with conventional therapies. Of these therapies, antioxidants, added to chemotherapy, are a frequent choice. METHODS: For this preliminary report, two patients with advanced epithelial ovarian cancer were studied. One patient had Stage IIIC papillary serous adenocarcinoma, and the other had Stage IIIC mixed papillary serous and seromucinous adenocarcinoma. Both patients were optimally cytoreduced prior to first-line carboplatinum/paclitaxel chemotherapy. Patient 2 had a delay in initiation of chemotherapy secondary to co-morbid conditions and had evidence for progression of disease prior to institution of therapy. Patient 1 began oral high-dose antioxidant therapy during her first month of therapy. This consisted of oral vitamin C, vitamin E, beta-carotene, coenzyme Q-10 and a multivitamin/mineral complex. In addition to the oral antioxidant therapy, patient 1 added parenteral ascorbic acid at a total dose of 60 grams given twice weekly at the end of her chemotherapy and prior to consolidation paclitaxel chemotherapy. Patient 2 added oral antioxidants just prior to beginning chemotherapy, including vitamin C, beta-carotene, vitamin E, coenzyme Q-10 and a multivitamin/mineral complex. Patient 2 received six cycles of paclitaxel/carboplatinum chemotherapy and refused consolidation chemotherapy despite radiographic evidence of persistent disease. Instead, she elected to add intravenous ascorbic acid at 60 grams twice weekly. Both patients gave written consent for the use of their records in this report. RESULTS: Patient 1 had normalization of her CA-125 after the first cycle of chemotherapy and has remained normal, almost 3(1/2) years after diagnosis. CT scans of the abdomen and pelvis remain without evidence of recurrence. Patient 2 had normalization of her CA-125 after the first cycle of chemotherapy. After her first round of chemotherapy, the patient was noted to have residual disease in the pelvis. She declined further chemotherapy and added intravenous ascorbic acid. There is no evidence for recurrent disease by physical examination, and her CA-125 has remained normal three years after diagnosis. CONCLUSION: Antioxidants, when added adjunctively, to first-line chemotherapy, may improve the efficacy of chemotherapy and may prove to be safe. A review of four common antioxidants follows. Because of the positive results found in these two patients, a randomized controlled trial is now underway at the University of Kansas Medical Center evaluating safety and efficacy of antioxidants when added to chemotherapy in newly diagnosed ovarian cancer.