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Nathan Goodyear

Massive Doses of Vitamin C and the Virus Diseases - 0 views

www.seanet.com/...med_surg-1951-v103-n4-p101.htm

IV therapy IV C virus viral illness nutrition nutritional therapy

shared by Nathan Goodyear on 23 Jan 13 - No Cached
  • Nathan Goodyear on 23 Jan 13
     
    High dose IV vitamin C beneficial in viral illnesses.  This is a case study article, but it discusses how viral illnesses are associated with low vitamin C levels and how high dose vitamin C therapy benefits the immune activity against viral invaders.
Nathan Goodyear

Toxicity of the spike protein of COVID-19 is a redox shift phenomenon: A novel therapeu... - 0 views

www.sciencedirect.com/...S0891584923005014

COVID19 COVID-19 cancer inflammation SARS-CoV-2 spike proteins COVID spikeopathy

shared by Nathan Goodyear on 01 Sep 23 - No Cached
  • Redox shift is due to Warburg effect and mitochondrial impairment.
  • Redox shift is due to Warburg effect and mitochondrial impairment.
  • Redox shift is due to Warburg effect and mitochondrial impairment.
  • ...88 more annotations...
  • The cytokine storm is a consequence of mitochondrial dysfunction
  • The cytokine storm is a consequence of mitochondrial dysfunction
  • The cytokine storm is a consequence of mitochondrial dysfunction
  • The cytokine storm is a consequence of mitochondrial dysfunction
  • Lipoic acid, Methylene Blue and Chlorine dioxide relieve COVID-19 spike protein toxicity
  • Lipoic acid, Methylene Blue and Chlorine dioxide relieve COVID-19 spike protein toxicity
  • Lipoic acid, Methylene Blue and Chlorine dioxide relieve COVID-19 spike protein toxicity
  • Lipoic acid, Methylene Blue and Chlorine dioxide relieve COVID-19 spike protein toxicity
  • most diseases display a form of anabolism due to mitochondrial impairment
  • most diseases display a form of anabolism due to mitochondrial impairment
  • most diseases display a form of anabolism due to mitochondrial impairment
  • infection by Covid-19 follows a similar pattern
  • chronic inflammation
  • Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction
  • Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction
  • Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction
  • Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction
  • infection by Covid-19 follows a similar pattern
  • unrelenting anabolism leads to the cytokine storm,
  • unrelenting anabolism leads to the cytokine storm,
  • unrelenting anabolism leads to the cytokine storm,
  • chronic inflammation
  • chronic inflammation
  • infection by Covid-19 follows a similar pattern
  • Lipoic acid and Methylene Blue have been shown to enhance the mitochondrial activity, relieve the Warburg effect and increase catabolism
  • Lipoic acid and Methylene Blue have been shown to enhance the mitochondrial activity, relieve the Warburg effect and increase catabolism
  • Lipoic acid and Methylene Blue have been shown to enhance the mitochondrial activity, relieve the Warburg effect and increase catabolism
  • Methylene Blue, Chlorine dioxide and Lipoic acid may help reduce long-term Covid-19 effects by stimulating the catabolism
  • Methylene Blue, Chlorine dioxide and Lipoic acid may help reduce long-term Covid-19 effects by stimulating the catabolism
  • Methylene Blue, Chlorine dioxide and Lipoic acid may help reduce long-term Covid-19 effects by stimulating the catabolism
  • direct consequence of redox iMeBalance, itself a consequence of decreased energy yield by the mitochondria
  • direct consequence of redox iMeBalance, itself a consequence of decreased energy yield by the mitochondria
  • mitochondrial dysfunction and increased levels of lactate, which are important characteristics of metabolic shift and Warburg effect in many diseases
  • mitochondrial dysfunction and increased levels of lactate, which are important characteristics of metabolic shift and Warburg effect in many diseases
  • increased lactate dehydrogenase activity (LDH) was observed in COVID-19 patients
  • increased lactate dehydrogenase activity (LDH) was observed in COVID-19 patients
  • almost every disease presents an increased anabolism
  • almost every disease presents an increased anabolism
  • cell division is the most sophisticated way to release entropy
  • cell division is the most sophisticated way to release entropy
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Wow
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Wow
  • transition from catabolism to anabolism is driven by a redox shift
  • transition from catabolism to anabolism is driven by a redox shift
  • viral spike protein binds to ACE2 receptor of the host cell [22,23].
  • redox signaling plays an important role in regulating immune function and inflammation, and disruptions in this signaling can lead to excessive cytokine production and immune system activation
  • Aging is associated with a poor control of the redox balance
  • thiol/disulfide homeostasis
  • reduced extracellular environment in the elderly and the increased susceptibility to Covid-19 infection
  • reduced extracellular environment in the elderly and the increased susceptibility to Covid-19 infection
  • Redox signaling tightly modulates the inflammatory response and oxidative stress has been reported in acute Covid-19
  • People at high risk are the elderly, patients suffering from metabolic syndrome such as obesity, or those suffering from chronic diseases such as cancer or inflammation
  • COVID-19 patients with severe disease have higher levels of oxidative stress markers and lower antioxidant levels
  • oxidative stress can activate the NLRP3 inflammasome, which is a protein complex that plays a key role in the cytokine storm
  • inflammation leads to the formation of ROS and RNS, while redox iMeBalance results in cellular damage, which in turn triggers an inflammatory response
  • persistently elevated mtROS triggers endothelial dysfunction and inflammation, which results in a vicious loop involving ROS, inflammation, and mitochondrial dysfunction
  • Damaged mitochondria releasing ROS induce inflammation via the NLRP3 inflammasome
  • Damaged mitochondria releasing ROS induce inflammation via the NLRP3 inflammasome
  • reduced environment during the cytokine storm
  • IL-2 is highly up-regulated in Covid-19 patients [37], and IL-2 is known to significantly stimulate the generation of NO in patients
  • Nitric acid is also the key mediator of IL-2-induced hypotension and vascular leak syndrome
  • mitochondrial dysfunction has been linked to the pathogenesis of Covid-19
  • mitochondrial dysfunction triggered by SARS-CoV-2 leads to damage to the mitochondria
  • mitochondrial dysfunction triggered by SARS-CoV-2 leads to damage to the mitochondria
  • As catabolism is decreased, entropy is released through anabolism
  • Elevated levels of lactate, a characteristic of the Warburg effect, were also reported in the high-risk Covid-19
  • elevated levels of ventricular lactic acid consistent with oxidative stress
  • A decrease of ΔΨm is implicated in several inflammation-related diseases
  • decrease in ΔΨm in leucocytes from Covid-19 patients
  • vaccinated with RNA or DNA vaccines triggering the synthesis of the viral spike protein in human cells
  • viral reactivation in varicella-zoster virus [55] or hepatitis [56], coagulopathy and resulting stroke and myocarditis following both DNA-based vaccines [57] and RNA-based vaccines
  • Covid-19, mitochondrial impairment
  • characteristic of the Warburg effect is present in almost every disease and appears to be a central feature in most of the hallmarks of cancer
  • inflammation, mitochondrial dysfunction and increased lactate concentrations in the extracellular fluid
  • In Covid-19, like any inflammation, there is a metabolic rewiring where cells rely on glycolysis
  • As the mitochondria are impaired, the infected cell cannot catabolize efficiently. It will release lactic acid in the blood stream
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Mitochondrial impairment
  • Striking similarities are seen between cancer, Alzheimer's disease and Covid-19, all related to the Warburg effect
  • Cancer, inflammation, Alzheimer's, and Parkinson's diseases share a common peculiarity, the inability of the cell to export entropy outside the body in the harmless form of heat
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Entropy: lack of order or predictability; gradual decline into disorder.
  • MEB relieves the Warburg effect [87], improves memory [77], is active in the treatment of depressive episodes [79,80] and reduces the importance of ischemic strokes
  • MEB relieves the Warburg effect [87], improves memory [77], is active in the treatment of depressive episodes [79,80] and reduces the importance of ischemic strokes
  • MEB has been shown to inhibit SARS-Cov-2 replication in vitro
  • MEB has been shown to inhibit SARS-Cov-2 replication in vitro
  • It has been shown that Covid-19-patients treated with MEB, have a significant reduction in hospital stay duration and mortality
  • MeB is an acceptor-donor molecule
  • MeB + can take a pair of electrons (of H atoms) and MeBH can release this pair easily, so that MeB is partially recycled like a catalyst
  • MeB acts as an electron bridge between a donor (FADH2, FMNH, NADH) and an acceptor (complex IV of ETC or oxygen itself)
  • As a coenzyme of pyruvate dehydrogenase (PDH), alpha-lipoic acid (ALA) initiates the formation of acetyl-CoA to feed the TCA cycle
  • ALA enhances the catabolism of carbon. cycle and therefore may reduce the Warburg effect and consequently, lactate production
  • Methylene Blue plays a similar role after the TCA cycle, by carrying electrons to complex IV of the electron transport chain
  • Drugs such as lipoic acid and MeB, which target the metabolism, decrease the redox shift by increasing catabolism
Nathan Goodyear

Vaccines backfire: Veterinary vaccines found to combine into new infectious viruses - 0 views

www.sciencedaily.com/...120712144754.htm

vaccine vaccines vaccinations

shared by Nathan Goodyear on 30 Jul 12 - No Cached
  • Nathan Goodyear on 30 Jul 12
     
    scary result.  Vaccine used in the prevention of ILT in chickens resulted in a new viral strain.  Two different virus strains were used.  These combined and resulted in a brand new viral strain. Apply this to our multi-dose vaccine schedule i.e. MMR
Jadibuti jadibuti.net

Home Remedies for Cough - 0 views

jadibuti.net/home-remedies-cough

Cough

shared by Jadibuti jadibuti.net on 29 May 16 - No Cached
  • Jadibuti jadibuti.net on 29 May 16
     
    Coughing is common health problem and it may arise due to blockage or irritant in your throat or upper respiratory tract. Coughing can also be due to a viral infection, common cold, flu, and smoking or health problems such as asthma, ...
  • Jadibuti jadibuti.net on 29 May 16
     
    Coughing is common health problem and it may arise due to blockage or irritant in your throat or upper respiratory tract. Coughing can also be due to a viral infection, common cold, flu, and smoking or health problems such as asthma, ...
arunaraayala

Dragon caught on Camera in China - Locality News - 0 views

www.localitynews.com/agon-caught-on-camera-in-china

TRENDING NEWS dragon china

shared by arunaraayala on 25 Oct 16 - No Cached
  • arunaraayala on 25 Oct 16
     
    Dragon was spotted in the camera in China and this video is going viral in Social media.
Nathan Goodyear

S-adenosyl methionine improves early viral responses and interferon-stimulated gene ind... - 0 views

www.ncbi.nlm.nih.gov/...PMC3021477

SAMe Hepatitis C virus viral infection

shared by Nathan Goodyear on 27 Jun 12 - No Cached
  • Nathan Goodyear on 27 Jun 12
     
    SAMe shown to be beneficial as an early response treatment in Hepatitis C. Maybe as a treatment for flu?
Nathan Goodyear

ingentaconnect Adipose Tissue Macrophages, Low Grade Inflammation and Insulin Re... - 0 views

www.ingentaconnect.com/...art00009

ATMs obesity inflammation inflammatory reaction insulin resistance IR diabetes DM type II macrophages

shared by Nathan Goodyear on 10 Jan 12 - No Cached
  • “M1” or “classically activated” macrophages
  • PPAR-gamma agonists
  • “M2” or an “alternatively activated” anti-inflammatory phenotype
  • Nathan Goodyear on 10 Jan 12
     
    ATMs and obesity induced inflammation initiates insulin resistance and thus type II diabetes. The bodies reaction to a fat cell is no different than a bacterial, viral, or parasitic infection.  The body recognizes something (fat) that shouldn't be there and it attempts to destroy it and remove it.
Nathan Goodyear

Overview of antibacterial, antitoxin, anti... [Mol Nutr Food Res. 2007] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...17195249

green tea EGCG flavanoids polyphenols flu influenza anti-viral cold viral virus

shared by Nathan Goodyear on 22 Nov 11 - No Cached
  • Nathan Goodyear on 22 Nov 11
     
    green tea flavanoids shown to have antiviral properties
Nathan Goodyear

Plasma lipoproteins are important components of the immune system - Han - 2010 - Microb... - 0 views

onlinelibrary.wiley.com/...full

lipoproteins LPS inflammation innate immunity VLDL LDL Lp(a) HDL cholesterol microbiology immunology

shared by Nathan Goodyear on 26 Sep 12 - No Cached
  • Nathan Goodyear on 26 Sep 12
     
    Is all cholesterol bad?  Of course not.  We have got to get away from the linear thinking that plagues medicine.  This article proposes and supports  a protective claim of lipoproteins: VLDL, LDL, Lp(a), and HDL.  Even shown to protect against bacterial, viral, LPS, and parasitic infectious damage.
Nathan Goodyear

Systemic sclerosis: environmental factors. [J Rheumatol. 2009] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...19797508

scleroderma environmental toxin toxins autoimmune disease

shared by Nathan Goodyear on 22 Jan 14 - No Cached
  • Nathan Goodyear on 22 Jan 14
     
    Environmental toxins such as slice and organic solvents have been associated with the development of scleroderma.  Other exposures include bacterial, viral, pesticides, prescription drugs...
wheelchairindia9

Cp Child Wheelchair - 0 views

www.wheelchairindia.com/...CP-Wheelchair

Wheelchair Offers New Vistas For Persons With Cerebral Palsy cerebellum and the cortex common causes of brain damage cause like chicken pox or measles neurological problems are properly managed

shared by wheelchairindia9 on 05 May 15 - No Cached
  • wheelchairindia9 on 05 May 15
     
    young children have a different set of needs than adults. Aesthetically, devices designed for kids are often sleek and colorful, and functionally, they are typically lightweight and adjustable. As any parent knows, young people don't stay the same size for long and since a wheelchair is a major purchase -- don't want a simple growth spurt to render it useless. Wheelchair category offers models that feature seat width and depth adjustability, elevating legrests, and other versatile features. As a weight-bearing activity is critical to proper physical and mental function-which is why children with cerebral palsy, who may sit for stretches in a wheelchair and typically are unable to stand on their own, can benefit greatly from pediatric standers as part of a comprehensive pediatric rehabilitation program. Pediatric standers are offered in passive, active and mobile formats: Passive standers stay in one place and feature a support surface, active standers allow reciprocal movement of the extremities while in a standing position, and mobile standers enable users to self-propel. Cerebral Palsy Wheelchair: Cerebral Palsy Wheelchair Description: The model designed for cerebral palsy child only. Ultra light weight aluminium alloy frame. Seat Width 38 cms (15"). Net Weight: 18.5 kgs. Epoxy powder coated frame. Detachable arm rest & foot rest provided. Elevated and swinging foot rest. Elevated foot rest provided to elevate leg angle. Height adjustable and detachable head rest. Hydraulic reclining high back for a comfortable posture. Hydraulic adjustable seat angle. Detachable back and seat pad. Extra cushion upholstery provided to under arm, head & calg Foldable. Lever and paddle brakes provided. Safety belt provided. Maintenance free rear solid wheels. Cloth look like water proof upholstery. Anti wheels for better safety and stability. Extra cushion upholstery provided to under arm, head & leg. Folding action. Lever and paddle brakes provide
wheelchairindia9

Chair For Cerebral Palsy Child - 0 views

www.wheelchairindia.com/...Cerebral-Palsy-Wheelchair

cerebellum and the cortex common causes of brain damage cause like chicken pox or measles neurological problems are properly managed

shared by wheelchairindia9 on 12 May 15 - No Cached
  • wheelchairindia9 on 12 May 15
     
    Cerebral palsy (CP) is a group of conditions caused by medical abnormalities in the development of a fetus or the early life of a child. These lead to damage or delayed development in the brain. The disorder is permanent and, though it does not worsen with age, the level of functionality of a person with cerebral palsy varies widely: in some cases, effects may be very minor, while in others, movement is impaired to the extent that a wheelchair is required. Common complications associated with CP vary by the type of CP disorder but can include vision problems, seizures, learning disabilities, and issues speaking, writing, and performing other tasks. Cerebral palsy causes problems with muscle tone, movement, balance and/or coordination. Symptoms and effects range from mild to severe. In some infants, problems are evident soon after birth. In others, diagnosis comes in later infancy or toddlerhood. Cerebral Palsy Wheelchair Description: The model designed for cerebral palsy child only. Ultra light weight aluminium alloy frame. Seat Width 38 cms (15"). Net Weight: 18.5 kgs. Epoxy powder coated frame. Detachable arm rest & foot rest provided. Elevated and swinging foot rest. Elevated foot rest provided to elevate leg angle. Height adjustable and detachable head rest. Hydraulic reclining high back for a comfortable posture. Hydraulic adjustable seat angle. Detachable back and seat pad. Extra cushion upholstery provided to under arm, head & calg Foldable. Lever and paddle brakes provided. Safety belt provided. Maintenance free rear solid wheels. Cloth look like water proof upholstery. Anti wheels for better safety and stability. Extra cushion upholstery provided to under arm, head & leg Folding action. Lever and paddle brakes provided. Safety belt provided. Maintenance free rear solid wheels. Cerebral Palsy Wheelchair Recline system: Recline system provides kids with the most comfortable resting environment. It also allows stretching abdomin
Nathan Goodyear

In vitro evaluation of the antiviral effects of the homeopathic preparation Gripp-Heel ... - 0 views

www.nrcresearchpress.com/...Y07-100

cold flu homeopathy homeopathic treatment natural health

shared by Nathan Goodyear on 27 Sep 11 - No Cached
  • Nathan Goodyear on 27 Sep 11
     
    Homeopathy shown to reduce infection rate of cold/flu viruses by 20-40%.  The control was acyclovir, ribavirin, and amantadine, all commonly prescribed anti-virals
Nathan Goodyear

Effect of high dose vitamin C on Epstein-Barr viral infection - 0 views

www.ncbi.nlm.nih.gov/...PMC4015650

IVC IV intravenous vitamin C IV vitamin C intravenous vitamin C vitamin C Epstein-Barr Epstein-Barr virus EBV viral infection

shared by Nathan Goodyear on 27 Aug 14 - No Cached
  • Nathan Goodyear on 27 Aug 14
     
    IV vitamin C shown to reduce EBV EA IgG and EBV VCA IgM using 7.5 grams to 50 gram infusions.  This protocol found that Magnesium reduced discomfort with the IVC therapy.
Nathan Goodyear

Antagonism of glycolysis and reductive carboxylation of glutamine potentiates activity ... - 0 views

cancerres.aacrjournals.org/...0008-5472.CAN-18-1326

Cancer oncolytic therapy glucos glycolysis

shared by Nathan Goodyear on 03 Dec 18 - No Cached
  • Nathan Goodyear on 03 Dec 18
     
    Nice article out of the UK finds low glucose environment and glycolysis inhibitors improve oncolytic viral therapies.
Nathan Goodyear

Oncolytic virotherapy promotes intratumoral T cell infiltration and improves Anti-PD-1... - 0 views

www.cell.com/...S0092-8674(17)30952-2

immunotherapy cancer RIGVIR oncolytic therapy PD-1 check point inhibitors

shared by Nathan Goodyear on 23 Oct 18 - No Cached
  • Nathan Goodyear on 23 Oct 18
     
    Study found that viral oncolytic therapy improved efficacy of PD-1 check point inhibitors by 62%. Increased CD8 expression, interferon-gamma...Interesting, starting CD8 levels played no role in predicting outcome.
Nathan Goodyear

XMRV is present in malignant prostatic epithelium and is associated with prostate cance... - 0 views

www.ncbi.nlm.nih.gov/...PMC2739868

prostate cancer virus cancer

shared by Nathan Goodyear on 03 Oct 18 - No Cached
  • Nathan Goodyear on 03 Oct 18
     
    Is prostate cancer, in part, a result of viral insult.  Study finds XMRV is highly associated with high-grade prostate cancer.
Nathan Goodyear

Human papillomavirus and Epstein Barr virus in prostate cancer: Koilocytes indicate pot... - 0 views

onlinelibrary.wiley.com/...pros.22562

cancer virus prostate cancer EBV HPV Epstein-Barr virus human papilloma virus

shared by Nathan Goodyear on 03 Oct 18 - No Cached
  • Nathan Goodyear on 03 Oct 18
     
    Is prostate cancer the result of viral infection.  Study suggests HPV and EBV play a role.
Nathan Goodyear

Human cytomegalovirus in high grade serous ovarian cancer possible implications for pat... - 0 views

www.ncbi.nlm.nih.gov/...PMC5794372

Cancer "ovarian cancer" CMV cytomegalovirus

shared by Nathan Goodyear on 14 Feb 19 - No Cached
  • Nathan Goodyear on 14 Feb 19
     
    CMV plays role in ovarian cancer. EBV, HPV have shown to play role in other cancers. The likely mechanism is via genetic incorporation of viral genome into the cancer genome.
Nathan Goodyear

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

shared by Nathan Goodyear on 09 Feb 11 - Cached
  • 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.
  • 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
  • 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
  • ...48 more annotations...
  • Our data show that ascorbic acid selectively killed cancer but not normal cells, using concentrations that could only be achieved by i.v. administration
  • 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
  • ascorbic acid administered i.v. in pharmacologic concentrations may serve as a pro-drug for H2O2 delivery to the extracellular milieu
  • H2O2 generated in blood is normally removed by catalase and glutathione peroxidase within red blood cells, with internal glutathione providing reducing equivalents
  • 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.
    • Nathan Goodyear
      Nathan Goodyear on 05 Mar 18
       
      The mechansism here is inadequate recycling of GSH due to lack of G6PD, build up of intracellular H2O2 and RBC lysis--hemolysis.
  • Only recently has it been understood that the discordant clinical findings can be explained by previously unrecognized fundamental pharmacokinetics properties of ascorbate
  • Intracellular transport of ascorbate is tightly controlled in relation to extracellular concentration
  • Intravenous ascorbate infusion is expected to drastically change extracellular but not intracellular concentrations
  • 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.
    • Nathan Goodyear
      Nathan Goodyear on 05 Mar 18
       
      accumulation of extracellular vitamin C is the effect.
  • It is unknown why ascorbate, via H2O2, killed some cancer cells but not normal cells.
  • There was no correlation with ascorbate-induced cell death and glutathione, catalase activity, or glutathione peroxidase activity.
  • H2O2, as the product of pharmacologic ascorbate concentrations, has potential therapeutic uses in addition to cancer treatment, especially in infections
  • Neutrophils generate H2O2 from superoxide,
  • i.v. ascorbate is effective in some viral infections
  • H2O2 is toxic to hepatitis C
  • Use of ascorbate as an H2O2-delivery system against sensitive pathogens, viral or bacterial, has substantial clinical implications that deserve rapid exploration.
  • 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
  • As much as a 70-fold difference in plasma concentrations is expected between oral and i.v. administration,
  • Complementary and alternative medicine practitioners worldwide currently use ascorbate i.v. in some patients, in part because there is no apparent harm
  • Human Burkitt's lymphoma cells
  • We first investigated whether ascorbate in pharmacologic concentrations selectively affected the survival of cancer cells by studying nine cancer cell lines
  • Clinical pharmacokinetics analyses show that pharmacologic concentrations of plasma ascorbate, from 0.3 to 15 mM, are achievable only from i.v. administration
  • plasma ascorbate concentrations from maximum possible oral doses cannot exceed 0.22 mM because of limited intestinal absorption
  • 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
  • All tested normal cells were insensitive to 20 mM ascorbate.
    • Nathan Goodyear
      Nathan Goodyear on 05 Mar 18
       
      meaning safe.
  • Lymphoma cells were selected because of their sensitivity to ascorbate
  • As ascorbate concentration increased, the pattern of death changed from apoptosis to pyknosis/necrosis, a pattern suggestive of H2O2-mediated cell death
  • Apoptosis occurred by 6 h after exposure, and cell death by pyknosis was ≈90% at 14 h after exposure
    • Nathan Goodyear
      Nathan Goodyear on 05 Mar 18
       
      work continued beyond the IVC therapy itself
  • In contrast to lymphoma cells, there was little or no killing of normal lymphocytes and monocytes by ascorbate
  • 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
  • Whether or not intracellular ascorbate was preloaded, extracellular ascorbate induced the same amount and type of death.
  • extracellular ascorbate in pharmacologic concentrations mediates death of lymphoma cells by apoptosis and pyknosis/necrosis, independently of intracellular ascorbate.
  • H2O2 as the effector species mediating pharmacologic ascorbate-induced cell death
  • Superoxide dismutase was not protective
  • 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
  • For both ascorbate and H2O2, death changed from apoptosis to pyknosis/necrosis as concentrations increased
  • Sensitivity to direct exposure to H2O2 was greater in lymphoma cells compared with normal lymphocytes and normal monocytes
  • There was no association between the EC50 for ascorbate-mediated cell death and intracellular glutathione concentrations, catalase activity, or glutathione peroxidase activity
  • H2O2 generation was dependent on time, ascorbate concentration, and the presence of trace amounts of serum in media
  • ascorbate radical is a surrogate marker for H2O2 formation.
  • whatever H2O2 is generated should be removed by glutathione peroxidase and catalase within red blood cells, because H2O2 is membrane permeable
  • 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.
  • The occurrence of one predicted complication, oxalate kidney stones, is controversial
  • In patients with glucose-6-phosphate dehydrogenase deficiency, i.v. ascorbate is contraindicated because it causes intravascular hemolysis
  • ascorbate at pharmacologic concentrations in blood is a pro-drug for H2O2 delivery to tissues.
  • ascorbate, an electron-donor in such reactions, ironically initiates pro-oxidant chemistry and H2O2 formation
  • data here showed that ascorbate initiated H2O2 formation extracellularly, but H2O2 targets could be either intracellular or extracellular, because H2O2 is membrane permeant
    • Nathan Goodyear
      Nathan Goodyear on 05 Mar 18
       
      the conversion of ascorbate to H2O2 occurs extracellular
  • 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
  • Nathan Goodyear on 09 Feb 11
     
    IV vitamin C benefits cancer patients
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