The data appear to establish
the association of NaF with acceleration of the growth of tumor
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Favorable Outcome After Physiologic Dose of Sodium-d,l-3-Hydroxybutyrate in Severe MADD... - 0 views
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Combined oral sodium butyrate and mesalazine treatment compared to oral mesalazine alon... - 0 views
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shared by Nathan Goodyear on 16 Oct 13
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Effects of sodium ascorbate (vitamin ... [Anticancer Res. 1993 Jan-Feb] - PubMed - NCBI - 0 views
www.ncbi.nlm.nih.gov/...8476199
IV vitamin C IV vitamin K vitamin K3 C IV vitamin K3 cancer vitamin C vitamin K
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Effect of sodium fluoride on tumor growth - 0 views
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Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the... - 0 views
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Artificial colours or a sodium benzoate preservative (or both) in the diet result in increased hyperactivity in 3-year-old and 8/9-year-old children in the general population
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shared by Nathan Goodyear on 27 Jan 15
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Hypertonic (3%) sodium chloride for emergent treatment of exercise-... - PubMed - NCBI - 0 views
www.ncbi.nlm.nih.gov/...17465635
endurance athletes exercise induced hyponatremia hyponatremia marathon runners athletes SIADH
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Exercise-Associated Muscle Cramps - 0 views
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athletes who develop EAMC often ingest similar amounts of fluid during exercise as do their noncramping counterparts
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Oral fluid ingestion may be ineffective, and intravenous fluid may provide a faster delivery for athletes suffering from acute EAMC
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National Athletic Trainers’ Association recommends that athletes prone to muscle cramping add 0.3 to 0.7 g/L of salt to their drinks to stave off muscle cramps
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Others have recommended adding higher amounts of sodium (about 3.0 to 6.0 g/L) to sports drinks based on the frequency of EAMC
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intravenous infusion of fluids removes this delay, and it has been used to aid athletes who develop acute EAMC
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maintaining hydration and adequate electrolyte levels is a good prevention strategy for individuals susceptible to EAMC
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Fluid volumes of 1.8 L per hour have been well tolerated by tennis athletes who are susceptible to EAMC
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Monitoring an athlete’s body weight is an easy method of ensuring adequate fluid replacement and individualizes each athlete’s fluid needs
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the National Athletic Trainers’ Association and the American College of Sports Medicine recommend a volume of fluid that allows for less than a 2% body weight reduction
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Endurance training may also serve as an effective means of preventing EAMC by expanding plasma volume and the extracellular fluid compartment15 and delaying neuromuscular fatigue
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Current Concepts in Concussion: Evaluation and Management - American Family Physician - 0 views
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Shear forces disrupt neural membranes, allowing potassium efflux into extracellular space. Resultant increases of calcium and excitatory amino acids are followed by further potassium efflux, leading to suppression of neuron activity.8–10,12,20 As sodium-potassium pumps restore balance, there is increased energy requirement, yet a paradoxical decrease in cerebral blood flow.
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Long-term stabilization of stage 4 colon cancer using sodium dichloroacetate therapy - 1 views
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inhibition of aerobic glycolysis (the Warburg effect) and activation of mitochondrial potassium ion channels
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alteration of pH regulators V-ATPase and MCT1, and other cell survival regulators such as PUMA, GLUT1, Bcl2 and p53
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A protocol of natural medications was developed to address the dose-limiting neurologic toxicity, in collaboration with a naturopathic physician (Andrews). The oral DCA regimen that was developed included three natural medications acetyl L-carnitine[29-31], R-alpha lipoic acid[32-34] and benfotiamine[35-37], for the primary purpose of neuropathy prevention
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Sodium dichloroacetate selectively targets cells with defects in the mitochondrial ETC ... - 0 views
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Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a p... - 0 views
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Ascorbate is transported into cells as such by sodium-dependent transporters, whereas dehydroascorbic acid is transported into cells by glucose transporters and then immediately reduced internally to ascorbate
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Expression and/or activity of the SVCT2 ascorbate transporter may be decreased in many ... - 0 views
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shared by Nathan Goodyear on 09 Feb 11
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Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a p... - 0 views
www.pnas.org/...13604.full
IV vitamin C cancer ascorbic acid vitamin C H2O2 GPX glutathione Perioxidase
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Taken together, these data indicate that ascorbate at concentrations achieved only by i.v. administration may be a pro-drug for formation of H2O2, and that blood can be a delivery system of the pro-drug to tissues.
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These findings give plausibility to i.v. ascorbic acid in cancer treatment, and have unexpected implications for treatment of infections where H2O2 may be beneficial
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pharmacologic concentrations of ascorbate killed cancer but not normal cells, that cell death was dependent only on extracellular but not intracellular ascorbate, and that killing was dependent on extracellular hydrogen peroxide (H2O2) formation with ascorbate radical as an intermediate
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Our data show that ascorbic acid selectively killed cancer but not normal cells, using concentrations that could only be achieved by i.v. administration
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Ascorbate-mediated cell death was due to protein-dependent extracellular H2O2 generation, via ascorbate radical formation from ascorbate as the electron donor. Like glucose, when ascorbate is infused i.v., the resulting pharmacologic concentrations should distribute rapidly in the extracellular water space (42). We showed that such pharmacologic ascorbate concentrations in media, as a surrogate for extracellular fluid, generated ascorbate radical and H2O2. In contrast, the same pharmacologic ascorbate concentrations in whole blood generated little detectable ascorbate radical and no detectable H2O2. These findings can be accounted for by efficient and redundant H2O2 catabolic pathways in whole blood (e.g., catalase and glutathione peroxidase) relative to those in media or extracellular fluid
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ascorbic acid administered i.v. in pharmacologic concentrations may serve as a pro-drug for H2O2 delivery to the extracellular milieu
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H2O2 generated in blood is normally removed by catalase and glutathione peroxidase within red blood cells, with internal glutathione providing reducing equivalents
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The electron source for glutathione is NADPH from the pentose shunt, via glucose-6-phosphate dehydrogenase. If activity of this enzyme is diminished, the predicted outcome is impaired H2O2 removal causing intravascular hemolysis, the observed clinical finding.
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Only recently has it been understood that the discordant clinical findings can be explained by previously unrecognized fundamental pharmacokinetics properties of ascorbate
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Intracellular transport of ascorbate is tightly controlled in relation to extracellular concentration
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Intravenous ascorbate infusion is expected to drastically change extracellular but not intracellular concentrations
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For i.v. ascorbate to be clinically useful in killing cancer cells, pharmacologic but not physiologic extracellular concentrations should be effective, independent of intracellular ascorbate concentrations.
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There was no correlation with ascorbate-induced cell death and glutathione, catalase activity, or glutathione peroxidase activity.
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H2O2, as the product of pharmacologic ascorbate concentrations, has potential therapeutic uses in addition to cancer treatment, especially in infections
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Use of ascorbate as an H2O2-delivery system against sensitive pathogens, viral or bacterial, has substantial clinical implications that deserve rapid exploration.
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Recent pharmacokinetics studies in men and women show that 10 g of ascorbate given i.v. is expected to produce plasma concentrations of nearly 6 mM, which are >25-fold higher than those concentrations from the same oral dose
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As much as a 70-fold difference in plasma concentrations is expected between oral and i.v. administration,
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Complementary and alternative medicine practitioners worldwide currently use ascorbate i.v. in some patients, in part because there is no apparent harm
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We first investigated whether ascorbate in pharmacologic concentrations selectively affected the survival of cancer cells by studying nine cancer cell lines
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Clinical pharmacokinetics analyses show that pharmacologic concentrations of plasma ascorbate, from 0.3 to 15 mM, are achievable only from i.v. administration
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plasma ascorbate concentrations from maximum possible oral doses cannot exceed 0.22 mM because of limited intestinal absorption
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For five of the nine cancer cell lines, ascorbate concentrations causing a 50% decrease in cell survival (EC50 values) were less than 5 mM, a concentration easily achievable from i.v. infusion
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All tested normal cells were insensitive to 20 mM ascorbate.
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As ascorbate concentration increased, the pattern of death changed from apoptosis to pyknosis/necrosis, a pattern suggestive of H2O2-mediated cell death
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Apoptosis occurred by 6 h after exposure, and cell death by pyknosis was ≈90% at 14 h after exposure
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In contrast to lymphoma cells, there was little or no killing of normal lymphocytes and monocytes by ascorbate
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Ascorbate is transported into cells as such by sodium-dependent transporters, whereas dehydroascorbic acid is transported into cells by glucose transporters and then immediately reduced internally to ascorbate
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Whether or not intracellular ascorbate was preloaded, extracellular ascorbate induced the same amount and type of death.
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extracellular ascorbate in pharmacologic concentrations mediates death of lymphoma cells by apoptosis and pyknosis/necrosis, independently of intracellular ascorbate.
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Because these data implicated H2O2 in cell killing, we added H2O2 to lymphoma cells and studied death patterns using nuclear staining (19, 28). The death patterns found with exogenous H2O2 exposure were similar to those found with ascorbate
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For both ascorbate and H2O2, death changed from apoptosis to pyknosis/necrosis as concentrations increased
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Sensitivity to direct exposure to H2O2 was greater in lymphoma cells compared with normal lymphocytes and normal monocytes
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There was no association between the EC50 for ascorbate-mediated cell death and intracellular glutathione concentrations, catalase activity, or glutathione peroxidase activity
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H2O2 generation was dependent on time, ascorbate concentration, and the presence of trace amounts of serum in media
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whatever H2O2 is generated should be removed by glutathione peroxidase and catalase within red blood cells, because H2O2 is membrane permeable
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The data are consistent with the hypothesis that ascorbate in pharmacologic concentrations is a pro-drug for H2O2 generation in the extracellular milieu but not in blood.
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In patients with glucose-6-phosphate dehydrogenase deficiency, i.v. ascorbate is contraindicated because it causes intravascular hemolysis
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ascorbate, an electron-donor in such reactions, ironically initiates pro-oxidant chemistry and H2O2 formation
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data here showed that ascorbate initiated H2O2 formation extracellularly, but H2O2 targets could be either intracellular or extracellular, because H2O2 is membrane permeant
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More than 100 patients have been described, presumably without glucose-6-phosphate dehydrogenase deficiency, who received 10 g or more of i.v. ascorbate with no reported adverse effects other than tumor lysis
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shared by Nathan Goodyear on 30 Jan 18
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Vitamin C preferentially kills cancer stem cells in hepatocellular carcinoma via SVCT-2... - 0 views
www.nature.com/...s41698-017-0044-8
cancer cancer stem cells liver cancer vitamin C IV vitamin C oncology
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Chen et al. have revealed that ascorbate at pharmacologic concentrations (0.3–20 mM) achieved only by intravenously (i.v.) administration selectively kills a variety of cancer cell lines in vitro, but has little cytotoxic effect on normal cells.
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Ascorbic acid (the reduced form of vitamin C) is specifically transported into cells by sodium-dependent vitamin C transporters (SVCTs)
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differential sensitivity to VC may result from variations in VC flow into cells, which is dependent on SVCT-2 expression.
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high-dose VC significantly impaired both the tumorspheres initiation (Fig. 4d, e) and the growth of established tumorspheres derived from HCC cells (Fig. 4f, g) in a time-dependent and dose-dependent manner.
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The antioxidant, N-acetyl-L-cysteine (NAC), preventing VC-induced ROS production (a ROS scavenger), completely restored the viability and colony formation among VC-treated cells
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Interestingly, the combination of VC and cisplatin was even more effective in reducing tumor growth and weight
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Consistent with the in vitro results, stemness-related genes expressions in tumor xenograft were remarkably reduced after VC or VC+cisplatin treatment, whereas conventional cisplatin therapy alone led to the increase of CSCs
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Interestingly, at extracellular concentrations greater than 1 mM, VC induces strong cytotoxicity to cancer cells including liver cancer cells
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we hypothesized that intravenous VC might reduce the risk of recurrence in HCC patients after curative liver resection.
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Intriguingly, the 5-year disease-free survival (DFS) for patients who received intravenous VC was 24%, as opposed to 15% for no intravenous VC-treated patients
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In this study, based on the elevated expression of SVCT-2, which is responsible for VC uptake, in liver CSCs, we revealed that clinically achievable concentrations of VC preferentially eradicated liver CSCs in vitro and in vivo
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Additionally, we found that intravenous VC reduced the risk of post-surgical HCC progression in a retrospective cohort study.
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Three hundred thirty-nine participants (55.3%) received 2 g intravenous VC for 4 or more days after initial hepatectomy
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As the key protein responsible for VC uptake in the liver, SVCT-2 played crucial roles in regulating the sensitivity to ascorbate-induced cytotoxicity
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we also observed that SVCT-2 was highly expressed in human HCC samples and preferentially elevated in liver CSCs
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we revealed that VC treatment dramatically reduced the self-renewal ability, expression levels of CSC-associated genes, and percentages of CSCs in HCC, indicating that CSCs were more susceptible to VC-induced cell death
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as a drug for eradicating CSCs, VC may represent a promising strategy for treatment of HCC, alone or particularly in combination with chemotherapeutic drugs
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In HCC, we found that VC-generated ROS caused genotoxic stress (DNA damage) and metabolic stress (ATP depletion), which further activated the cyclin-dependent kinase inhibitor p21, leading to G2/M phase cell cycle arrest and caspase-dependent apoptosis in HCC cells
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we demonstrated a synergistic effect of VC and chemotherapeutic drug cisplatin on killing HCC both in vitro and in vivo
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Intravenous VC has also been reported to reduce chemotherapy-associated toxicity of carboplatin and paclitaxel in patients,38 but the specific mechanism needs further investigation
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Our retrospective cohort study also showed that intravenous VC use (2 g) was related to the improved DFS in HCC patients after initial hepatectomy
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several clinical trials of high-dose intravenous VC have been conducted in patients with advanced cancer and have revealed improved quality of life and prolonged OS
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high expression (grade 2+/3+) of SVCT-2 was in agreement with poorer overall survival (OS) of HCC patients (Fig. 1c) and more aggressive tumor behavior
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these data suggest that SVCT-2 is preferentially expressed in liver CSCs and is required for the maintenance of liver CSCs.
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pharmacologic concentrations of plasma VC higher than 0.3 mM are achievable only from i.v. administration
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The viabilities of HCC cells were dramatically decreased after exposure to VC in dose-dependent manner
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These results verify that VC inhibits tumor growth in HCC PDX models and SVCT-2 expression level is associated with VC response
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qPCR and IHC analysis demonstrated that expression levels of CSC-associated genes and percentages of CSCs in PDXs dramatically declined after VC treatment, confirming the inhibitory role of VC in liver CSCs
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shared by Nathan Goodyear on 26 Aug 14
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Clinical experience with intravenous administration of ascorbic acid: achievable levels... - 0 views
www.ncbi.nlm.nih.gov/...PMC3751545
IV vitamin C dosing ascorbic acid inflammation disease cancer IV vitamin C intravenous vitamin C IV intravenous vitamin C vitamin C CRP therapy treatment alternative
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Patients with higher tumor markers are likely to have higher tumor burden, higher oxidative stress and, therefore, are more likely to have lower post IVC plasma levels.
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Our data also showed that cancer patients with metastasis tend to have lower post-IVC vitamin C levels than those without metastasis
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Lower peak plasma concentrations are obtained in cancer patients than in healthy subjects. Cancer patients who are deficient in vitamin C prior to therapy tend to achieve lower plasma levels post infusion.
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Patients with higher inflammation or tumor burdens, as measured by CRP levels or tumor antigen levels, tend to show lower peak plasma ascorbate levels after IVC.
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Patients with metastatic tumors tend to achieve lower post infusion plasma ascorbate levels than those with localized tumors.
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Meta-analyses of clinical studies involving cancer and vitamins also conclude that antioxidant supplementation does not interfere with the efficacy of chemotherapeutic regiments
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Most of the prostate cancer patients studied, 75±19% (95% confidence), showed reductions in PSA levels during the course of their IVC therapy
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Laboratory studies suggest that, at high concentrations, ascorbate does not interfere with chemotherapy or irradiation and may enhance efficacy in some situations
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Cameron and Pauling observed fourfold survival times in terminal cancer patients treated with intravenous ascorbate infusions followed by oral supplementation
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The inflammatory microenvironment of cancer cells leads to increasing oxidative stress, which apparently depletes vitamin C, resulting in lower plasma ascorbate concentrations in blood samples post IVC infusion. Another explanation for this finding may be that cancers are themselves more metabolically active in their uptake of vitamin C, causing subjects to absorb more of the vitamin, and as a results show lower plasma ascorbate concentrations in blood post IVC infusion.
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patients with severely elevated CRP levels attain plasma ascorbate concentrations after IVC infusions that are only 65% of those attained for subjects with normal CRP levels
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The finding of decreased plasma ascorbate levels in cancer patients may relate to the molecular structure of ascorbic acid; in particular, the similarity of its oxidized form, dihydroascorbic acid, to glucose
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Since tumor have increased requirement for glucose [67], transport of dehydroascorbate into the cancer cells via glucose transport molecules and ascorbate through sodium-dependent transporter may be elevated
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Increased accumulation of ascorbic acid in the tumor site was supported by measurements of the level of ascorbic acid in tumors in animal experiments
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patients with advanced malignancies may have lower level of ascorbic acid in tissue, creating a higher demand for the vitamin C
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CRP concentrations directly correlate with disease activity in many cases and can contribute to disease progression through a range of pro-inflammatory properties.
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Being an exquisitely sensitive marker of systemic inflammation and tissue damage, CRP is very useful in screening for organic disease and monitoring treatment responses
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ncreases in CRP concentrations have been associated with poorer prognosis of survival in cancer patients, particularly with advance disease independent of tumor stage
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Regarding inflammation, 73±13% of subjects (95% confidence) showed a reduction in CRP levels during therapy. This was an even more dramatic 86±13% (95% confidence) in subjects who started therapy with CRP levels above 10 mg/L
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patients treated by IVC with follow-up several year showed that suppression of inflammation in cancer patients by high-dose IVC is feasible and potentially beneficial
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The subjects with highly elevated CRP concentrations have a three-fold elevation “all-cause” mortality risk and a twenty-eight fold increase in cancer mortality risk
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patients with lower vitamin C levels may see more distribution of intravenously administered ascorbate into tissues and thus attain less in plasma.
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When treating patients with IVC, the first treatment likely serves to replenish depleted tissue stores, if those subjects were vitamin C deficient at the beginning of the treatment. Then, in subsequent treatments, with increasing doses, higher plasma concentrations can be attained. On-going treatments serve to progressively reduce oxidative stress in cancer patients.
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large doses given intravenously may result in maximum plasma concentrations of roughly 30 mM, a level that has been shown to be sufficient for preferential cytotoxicity against cancer cells
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oral intake of vitamin C exceeded 200 mg administered once daily, it was difficult to increase plasma and tissue concentrations above roughly 200 μM.
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Great review on the use of IV vitamin C in cancer and to reduce inflammation. The article does a great job of discussing the mechanism of vitamin C therapy in cancer as well as the proposed reasons for low vitamin C in cancer patients. The study also highlights the obstacles to rise in vitamin C levels post IV vitamin C in cancer patients.
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