Pharmacokinetic Evaluation of Intravenous Vitamin C: A Classic Pharmacokinetic Study.

PURPOSE: Intravenous vitamin C (IVC) is used in a variety of disorders with limited supporting pharmacokinetic data. Herein we report a pharmacokinetic study in healthy volunteers and cancer participants with IVC doses in the range of 1-100 g. METHODS: A pharmacokinetic study was conducted in 21 healthy volunteers and 12 oncology participants. Healthy participants received IVC infusions of 1-100 g; oncology participants received IVC infusions of 25-100 g. Serial blood and complete urine samples were collected pre-infusion and for 24 h post-infusion. Pharmacokinetic parameters were computed using noncompartmental methods. Adverse events were monitored during the study. RESULTS: In both cohorts, IVC exhibited first-order kinetics at doses up to 75 g. At 100 g, maximum concentration (Cmax) plateaued in both groups, whereas area under the concentration-time curve (AUC) only plateaued in the healthy group. IVC was primarily excreted through urine. No saturation of clearance was observed; however, the mean 24-h total IVC excretion in urine for all doses was lower in oncology participants (89% of dose) than in healthy participants at 100 g (99%). No significant adverse events were observed; thus, maximum tolerated dose (MTD) was not reached. CONCLUSION: IVC followed first-order pharmacokinetics up to 75 g and at up to 100 g had complete renal clearance in 24 h. IVC up to 100 g elicited no adverse effects or significant physiological/biochemical changes and appears to be safe. These data can be used to rectify existing misinformation and to guide future clinical trials. REGISTRATION: ClinicalTrials.gov identifier number NCT01833351.

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.

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.

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.

The Next Generation of Dietitians: Implementing Dietetics Education and Practice in Integrative Medicine.

Integrative medicine is a quickly expanding field of health care that emphasizes nutrition as a key component. Dietitians and nutritionists have an opportunity to meet workforce demands by practicing dietetics and integrative medicine (DIM). The purpose of this article is to describe a DIM education program and practicum. We report the results of an interprofessional nutrition education and practicum program between the University of Kansas Medical Center (KUMC) Department of Dietetics and Nutrition and KU Integrative Medicine. This partnered program provides training that builds on the strong foundation of the Nutrition Care Process and adds graduate-level educational and practicum experiences in foundational integrative medicine knowledge, including nutritional approaches from a systems biology perspective, nutrigenomics, and biochemistry as the core knowledge to understand the root cause of a chronic disorder and to choose appropriate nutritional tools for interventions. This interprofessional KUMC program provides a dietetic internship, master's degree, and graduate certificate in DIM and fulfills a need for dietitians and nutritionists who seek careers practicing in an integrative medicine setting. The program fulfills expanding workforce needs to provide quality health care for patients with chronic illnesses.

Role of yoga as an adjunctive therapy in patients with neurocardiogenic syncope: a pilot study.

BACKGROUND: Neurocardiogenic syncope (NCS) is a common clinical condition characterized by abrupt cardiovascular autonomic changes resulting in syncope. This is a recurring condition with mixed results from current strategies of treatment. METHODS: Subjects with a diagnosis of NCS were screened and enrolled. All the participants were given a DVD containing yoga videos and were instructed to practice yoga therapy for 60 min, three times a week for 3 consecutive months. Syncope functional status questionnaire score (SFSQS) was administered at the beginning and the end of the study. The subjects were followed for 3 months and underwent repeat tilt table testing at the end of the study. RESULTS: Of the 60 patients screened, 44 subjects were enrolled, 21 in the intervention group and 23 in the control group. Most of the participants were females, and the mean age was 21 ± 3 years. In the intervention group, who finished the yoga regimen, there was a statistically significant improvement from control phase to the intervention phase, in number of episodes of syncope (4 ± 1 vs 1.3 ± 0.7, p < 0.001) and presyncope (4.7 ± 1.5 vs 1.5 ± 0.5, p < 0.001). The mean SFSQS also decreased from 67 ± 7.8 to 29.8 ± 4.6 (p < 0.001). All subjects had positive head up tilt table (HUTT) study at the time of enrollment compared to only six patients at the completion of intervention phase (10/100 vs 6/28 %, p < 0.0001). CONCLUSION: Yoga therapy can potentially improve the symptoms of presyncope and syncope in young female patients with NCS.

High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy.

Ascorbate (vitamin C) was an early, unorthodox therapy for cancer, with an outstanding safety profile and anecdotal clinical benefit. Because oral ascorbate was ineffective in two cancer clinical trials, ascorbate was abandoned by conventional oncology but continued to be used in complementary and alternative medicine. Recent studies provide rationale for reexamining ascorbate treatment. Because of marked pharmacokinetic differences, intravenous, but not oral, ascorbate produces millimolar concentrations both in blood and in tissues, killing cancer cells without harming normal tissues. In the interstitial fluid surrounding tumor cells, millimolar concentrations of ascorbate exert local pro-oxidant effects by mediating hydrogen peroxide (H(2)O(2)) formation, which kills cancer cells. We investigated downstream mechanisms of ascorbate-induced cell death. Data show that millimolar ascorbate, acting as a pro-oxidant, induced DNA damage and depleted cellular adenosine triphosphate (ATP), activated the ataxia telangiectasia mutated (ATM)/adenosine monophosphate-activated protein kinase (AMPK) pathway, and resulted in mammalian target of rapamycin (mTOR) inhibition and death in ovarian cancer cells. The combination of parenteral ascorbate with the conventional chemotherapeutic agents carboplatin and paclitaxel synergistically inhibited ovarian cancer in mouse models and reduced chemotherapy-associated toxicity in patients with ovarian cancer. On the basis of its potential benefit and minimal toxicity, examination of intravenous ascorbate in combination with standard chemotherapy is justified in larger clinical 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.

Inhibition of pancreatic cancer and potentiation of gemcitabine effects by the extract of Pao Pereira.

Lack of effective therapy is a major problem in the treatment of pancreatic cancer. In the present study, we investigated a natural product, the extract of Pao Pereira (Pao), for its anti-pancreatic cancer effect in vitro and in vivo, either alone or in combination with the first-line chemotherapeutic drug gemcitabine (Gem). Pao induced dose-dependent apoptosis to all five tested pancreatic cancer cell lines. The combination of Pao and Gem had a synergistic effect in the inhibition of cell growth, with combination indices (CIs) <1 by Chou-Talalay's median effect analysis based on the isobologram principle. Adding Pao to Gem treatment reduced the concentration of Gem to produce an equitoxic effect on pancreatic cancer cells. In an orthotopic pancreatic xenograft mouse model, mice bearing PACN-1 tumors were treated with Pao and Gem, either alone or in combination. The progression of tumors was monitored longitudinally by imaging of live animals. While Gem did not provide significant inhibition, Pao treatment significantly suppressed tumor growth by 70-72%. Combined Pao and Gem treatment further enhanced the tumor inhibitory effect compared to Gem alone, and markedly reduced metastatic lesions in the peritoneum. Collectively, these data suggest that the extract of Pao possesses anti-pancreatic cancer activity and can enhance the effects of Gem in vitro and in vivo.

Antitumor Activities of Rauwolfia vomitoria Extract and Potentiation of Carboplatin Effects Against Ovarian Cancer.

BACKGROUND: Tumor resistance to platinum-based drugs has been an obstacle to the treatment of ovarian cancer. Extract of the plant Rauwolfia vomitoria has long been used by cancer patients. However, there have not been systematic studies of its anticancer activity. OBJECTIVE: In an effort to enhance the effectiveness of platinum-based drugs, we investigated the anticancer effect of a Rauwolfia vomitoria extract (Rau), both alone and in combination with carboplatin (Cp). METHODS: In vitro cytotoxicity and colony formation were evaluated in several ovarian cancer cell lines. In vivo effects were evaluated in an intraperitoneal ovarian cancer mouse model. The combination of Rau and Cp was assessed using Chou-Talalay's constant ratio design and median effect analysis based on the isobologram principle to determine the combination index values. RESULTS: Rau decreased cell growth in all 3 tested ovarian cancer cell lines dose dependently and completely inhibited formation of colonies in soft agar. Apoptosis was induced in a time- and dose-dependent manner and was the predominant form of Rau-induced cell death. Synergy of Rau with Cp was detected, with combination index values <1 and dose reduction index values for Cp ranging from 1.7- to 7-fold. Tumor growth in mice was significantly suppressed by 36% or 66% with Rau treatment alone at a low (20 mg/kg) or a high dose (50 mg/kg), respectively, an effect comparable to that of Cp alone. The volume of ascitic fluid and the number of nonblood cells in ascites were also significantly decreased. Combining Rau with Cp remarkably enhanced the effect of Cp and reduced tumor burden by 87% to 90% and ascites volume by 89% to 97%. CONCLUSIONS: Rau has potent antitumor activity and in combination significantly enhances the effect of Cp against ovarian cancer.

Pharmacological ascorbate induces cytotoxicity in prostate cancer cells through ATP depletion and induction of autophagy.

Recent studies have revealed the scientific basis for the use of intravenous (i.v.) vitamin C or ascorbic acid (ascorbate) in treating cancers, and raised the possibility of using i.v. ascorbate as a prooxidant anticancer therapy. Through the production of H2O2, pharmacologic ascorbate can induce some cancer cell death in vitro and inhibit a number of types of tumor growth in animal models. However, the mechanism of cell death triggered by ascorbate is not well understood. In this study, we investigated the cytotoxicity of pharmacological concentrations of ascorbate to human prostate cancer cells and the mechanisms involved. The results showed that ascorbate in the millimolar range induced cytotoxicity in five of the six tested prostate cancer cell lines. The IC50 values in the sensitive prostate cancer cells ranged from 1.9 to 3.5 mmol/l, concentrations clinically achievable with i.v. ascorbate use. All tested androgen-independent cells were sensitive to ascorbate treatment. The ascorbate-insensitive cell line LaPC4 is hormonally dependent. Whereas the reasons for sensitivity/resistance to ascorbate treatment need to be investigated further, cell death in sensitive cells was dependent on H2O2. Ascorbate treatment depleted ATP and induced autophagy in sensitive prostate cancer cells, resulting in cell death. Taken together with previous studies, high-dose ascorbate has the potential to be a novel treatment option to hormone-refractory prostate cancer.

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.

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.

Pharmacologic ascorbate synergizes with gemcitabine in preclinical models of pancreatic cancer.

Conventional treatment approaches have had little impact on the course of pancreatic cancer, which has the highest fatality rate among cancers. Gemcitabine, the primary therapeutic agent for pancreatic carcinoma, produces minimal survival benefit as a single agent. Therefore, numerous efforts have focused on gemcitabine combination treatments. Using a ratio design, this study established that combining pharmacologically achievable concentrations of ascorbate with gemcitabine resulted in a synergistic cytotoxic response in eight pancreatic tumor cell lines. Sensitization was evident regardless of inherent gemcitabine resistance and epithelial-mesenchymal phenotype. Our analysis suggested that the promiscuous oxidative actions of H(2)O(2) derived from pharmacologic ascorbate can culminate in synergism independent of the cancer cell's underlying phenotype and resistance to gemcitabine monotherapy. Gemcitabine-ascorbate combinations administered to mice bearing pancreatic tumor xenografts consistently enhanced inhibition of growth compared to gemcitabine alone, produced 50% growth inhibition in a tumor type not responsive to gemcitabine, and demonstrated a gemcitabine dose-sparing effect. These data support the testing of pharmacologic ascorbate in adjunctive treatments for cancers prone to high failure rates with conventional therapeutic regimens, such as pancreatic cancer.

Vitamin C: intravenous use by complementary and alternative medicine practitioners and adverse effects.

BACKGROUND: Anecdotal information and case reports suggest that intravenously administered vitamin C is used by Complementary and Alternate Medicine (CAM) practitioners. The scale of such use in the U.S. and associated side effects are unknown. METHODS AND FINDINGS: We surveyed attendees at annual CAM Conferences in 2006 and 2008, and determined sales of intravenous vitamin C by major U.S. manufacturers/distributors. We also queried practitioners for side effects, compiled published cases, and analyzed FDA's Adverse Events Database. Of 199 survey respondents (out of 550), 172 practitioners administered IV vitamin C to 11,233 patients in 2006 and 8876 patients in 2008. Average dose was 28 grams every 4 days, with 22 total treatments per patient. Estimated yearly doses used (as 25 g/50 ml vials) were 318,539 in 2006 and 354,647 in 2008. Manufacturers' yearly sales were 750,000 and 855,000 vials, respectively. Common reasons for treatment included infection, cancer, and fatigue. Of 9,328 patients for whom data is available, 101 had side effects, mostly minor, including lethargy/fatigue in 59 patients, change in mental status in 21 patients and vein irritation/phlebitis in 6 patients. Publications documented serious adverse events, including 2 deaths in patients known to be at risk for IV vitamin C. Due to confounding causes, the FDA Adverse Events Database was uninformative. Total numbers of patients treated in the US with high dose vitamin C cannot be accurately estimated from this study. CONCLUSIONS: High dose IV vitamin C is in unexpectedly wide use by CAM practitioners. Other than the known complications of IV vitamin C in those with renal impairment or glucose 6 phosphate dehydrogenase deficiency, high dose intravenous vitamin C appears to be remarkably safe. Physicians should inquire about IV vitamin C use in patients with cancer, chronic, untreatable, or intractable conditions and be observant of unexpected harm, drug interactions, or benefit.

Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice.

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.

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.

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 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.