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Nathan Goodyear

The Role of Vitamin C in Human Immunity and Its Treatment Potential Against COVID-19: A... - 0 views

www.ncbi.nlm.nih.gov/...PMC9925039

COVID-19 SARS-CoV-2 COVID WBC ascorbic acid vitamin C

shared by Nathan Goodyear on 01 Sep 23 - No Cached
  • vitamins A, B, C, E, B6, B12, folate, zinc, iron, copper, and selenium
  • White blood cells, including neutrophils and monocytes, accumulate concentrations of vitamin C up to 100 times greater than that of plasma
  • Vitamin C is a crucial component of both the innate (nonspecific) and adaptive (specific) portions of the immune system
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  • play a role during the initial chemotactic response of neutrophils shortly after infection
  • following vitamin C supplementation, a 20% increase in neutrophil chemotactic activity was observed
  • also contributes to the phagocytosis and killing of microbes by neutrophils
  • low levels of vitamin C occurring in high-stress situations
  • maturation, proliferation, and viability of T cells have all been shown to be upregulated by the presence of normal physiologic concentrations of vitamin C
  • Vitamin C has been shown to directly affect the number of Igs released from B cells
  • vitamin C among healthy young adult males showed a significant increase in serum levels of IgA, IgG, and IgM
  • effects of high-dose vitamin C on cytokine levels in cancer patients, finding decreased amounts of the cytokines Interleukin-1 alpha (IL-1 alpha), IL-2, IL-8, and tumor necrosis factor-alpha (TNF-alpha) after high-dose vitamin C infusion
  • when vitamin C was supplemented with vitamin E in healthy adults, it increased the production of cytokines IL-1 beta and TNF-alpha
  • vitamin C acts to modulate the levels of cytokines to prevent them from fluctuating in either direction
  • vitamin C also acts as an important antioxidant to the cells of the immune system.
  • human leukocytes, neutrophils, in particular, possess the ability to transport the oxidized form of vitamin C across its membrane to use as a defense mechanism against ROS produced during an immune response
  • Vitamin C also can recover other endogenous antioxidants in the body such as vitamin E and glutathione, returning them to their active state
  • vitamin C can decrease the activation of NF-kB
  • can reduce harmful nitrogen-based compounds such as N-nitrosamines and nitrosamides, both of which are carcinogenic 
  • subjects taking oral vitamin C supplementation saw a 60% to 90% reduction in oxidative stress compared to a placebo control
  • subjects infused with vitamin C alone had a 516% increase in glutathione levels compared to subjects not provided the 500 mg daily supplementation
  • hydroxylating proline and lysine
  • mature and stabilize the tissue of a healing wound
  • healing
  • oral surgery
  • improved soft tissue regeneration
  • vitamin C increases the mRNA levels of type I and type III collagen in the human dermis
  • Studies have demonstrated that those with low levels of vitamin C are at a significantly higher risk of respiratory infection compared to those with normal levels
  • viral cold duration was reduced by about 8% in adults and 13.5% in children using prophylactic daily doses of 200 mg of oral vitamin C
  • prophylactically supplementing vitamin C decreases the risk of infection with respiratory viruses such as the common cold
  • combined with probiotics, oral vitamin C supplementation showed a 33% decrease in the incidence of respiratory tract infections in preschool-age children [
  • high-dose oral supplementation of vitamin C managed to prevent or reduce symptoms if taken before or just after the onset of cold- or flu-like symptoms
  • improvements in oxygen saturation and decreased IL-6 levels (a marker of inflammation) in the treatment group compared to the control group
  • 8 g doses of oral vitamin C
  • there is a negative correlation between age and serum levels of vitamin C
  • Patients with COVID-19 will likely also experience depletion in serum levels of vitamin C as a direct result of the upregulation of the immune system to combat the infection
  • Colunga et al. suggested that oral vitamin C can be combined with oral Quercetin, an antiviral flavonoid, to improve Quercetin’s ability to block viral membrane fusion of SARS-CoV-2
  • high doses of 1-2 g/day of oral vitamin C could prevent other upper respiratory infections
  • It appears vitamin C supplementation by itself does not provide a striking benefit in preventing COVID-19 infection for those without a deficiency
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Flawed statement. What is normal? Vitamin D. Many variables effect levels and dose, including the two compartment kinetics and absorption.
  • Hiedra et al. were able to show decreases in inflammatory biomarkers, such as D-dimer and ferritin
  • some evidence to support that prophylactic use of vitamin C helps reduce the severity of respiratory infection symptoms once a subject has already been infected
  • oral vitamin C in combination with zinc provided the largest amount of antibody titers 42 days
  • linear relationship between days of vitamin C therapy and survival duration
  • other studies were unable to find any definitive improvement concerning therapy with vitamin C
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Either these studies are designed to fail or the authors are lacking some basic understanding of pharmacokinetics and pharmacodynamics with vitamin C.
  • Fowler et al. aimed to see if a high-dose vitamin C infusion would benefit patients affected by ARDS, but they were unable to conclude that vitamin C infusion, compared to a placebo, could decrease vascular inflammation and damage in ARDS
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      At what dose, duration, frequency???
  • in a sample of 67 COVID-19-positive ICU patients, 82% of them displayed plasma vitamin C levels below 0.4 mg/dL
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      They are kind of make the point from my earlier note.
  • continuous vitamin C infusion at a rate of 60 mg/kg/day for four days decreased the need for mechanical ventilation and vasopressor use but had no significant effect on overall mortality
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Again, designed to fail or ignorance designed the study which failed
  • Carr et al. suggested that high-dose IV vitamin C is most effective when treating sepsis as septic patients receiving the normal daily recommendations through diet still showed decreased vitamin C levels
  • High-dose IV vitamin C treatment has also been shown by Kakodkar et al. to decrease syndecan-1, an endothelial glycocalyx that contributes to mortality in septic patients
  • combined with hydrocortisone and thiamine, septic patients treated with 1.5 g of IV vitamin C every six hours showed a distinct decrease in their SOFA scores and none of the patients treated developed organ failure
  • combined with hydrocortisone and thiamine, septic patients treated with 1.5 g of IV vitamin C every six hours showed a distinct decrease in their SOFA scores and none of the patients treated developed organ failure
  • reduced overall mortality
  • reduced overall mortality
  • propose the use for high-dose vitamin C to aid in the treatment of septic shock-induced hypotension
  • treatment of severe sepsis using a high dose (up to 200 mg/kg/day) of IV vitamin C was explored in phase I, a double-blind, randomized, placebo-controlled trial by Fowler et al. [75]. Their findings included a reduction in SOFA scores and decreased vascular injury compared to a placebo control group, all while showing minimal adverse side effects
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      High dose here is laughable. Again, duration and frequency also.
  • Maintaining a daily intake of 75 and 100 mg for men and women, respectively, as recommended by the U.S. Institute of Medicine
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      This recommendation is FRANK IGNORANCE
Nathan Goodyear

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

shared by Nathan Goodyear on 26 Aug 14 - No Cached
  • 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.
  • Our data also showed that cancer patients with metastasis tend to have lower post-IVC vitamin C levels than those without metastasis
  • 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.
  • Patients with metastatic tumors tend to achieve lower post infusion plasma ascorbate levels than those with localized tumors.
  • Meta-analyses of clinical studies involving cancer and vitamins also conclude that antioxidant supplementation does not interfere with the efficacy of chemotherapeutic regiments
  • Most of the prostate cancer patients studied, 75±19% (95% confidence), showed reductions in PSA levels during the course of their IVC therapy
  • Laboratory studies suggest that, at high concentrations, ascorbate does not interfere with chemotherapy or irradiation and may enhance efficacy in some situations
  • Cameron and Pauling observed fourfold survival times in terminal cancer patients treated with intravenous ascorbate infusions followed by oral supplementation
  • 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.
  • 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
  • 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
  • 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
  • Increased accumulation of ascorbic acid in the tumor site was supported by measurements of the level of ascorbic acid in tumors in animal experiments
  • patients with advanced malignancies may have lower level of ascorbic acid in tissue, creating a higher demand for the vitamin C
  • IVC therapy appears to reduce CRP levels in cancer patients.
  • CRP concentrations directly correlate with disease activity in many cases and can contribute to disease progression through a range of pro-inflammatory properties.
  • Being an exquisitely sensitive marker of systemic inflammation and tissue damage, CRP is very useful in screening for organic disease and monitoring treatment responses
  • ncreases in CRP concentrations have been associated with poorer prognosis of survival in cancer patients, particularly with advance disease independent of tumor stage
  • 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
  • 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
  • Inflammation is a marker of high cancer risk, and poor treatment outcome
  • 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
  • cancer patients may need higher doses to achieve a given plasma concentration.
  • patients with lower vitamin C levels may see more distribution of intravenously administered ascorbate into tissues and thus attain less in plasma.
  • 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.
  • 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
  • oral intake of vitamin C exceeded 200 mg administered once daily, it was difficult to increase plasma and tissue concentrations above roughly 200 μM.
  • Nathan Goodyear on 26 Aug 14
     
    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.
Nathan Goodyear

Oncotarget | NADH autofluorescence, a new metabolic biomarker for cancer stem cells: Id... - 0 views

www.oncotarget.com/index.php

vitamin C IV vitamin C cancer cancer stem cells milk thistle silymarin ascorbic acid bee propolis CAPE glycolytic inhibitor natural

shared by Nathan Goodyear on 08 Dec 17 - No Cached
  • Vitamin C was ~10 times more potent than 2-DG for the targeting of CSCs
  • Cancer stem-like cells (CSCs) are thought to be the root cause of chemotherapy-resistance and radio-resistance
  • ultimately leading to treatment failure in patients with advanced disease [1-3]. They have been directly implicated mechanistically in tumor recurrence and metastasis, resulting in poor patient survival
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  • mitochondrial biogenesis may be a key driver of the CSC phenotype
  • Our results indicate that increased mitochondrial oxidative stress and high NADH levels are both key characteristics of the CSC metabolic phenotype
  • high levels of NAD(P)H auto-fluorescence are known to be a surrogate marker for mitochondrial “power”, high OXPHOS capacity and increased ATP production
  • CSCs may be strictly dependent on NAD(P)H to maintain their enhanced mitochondrial function
  • an intact NAD+ salvage pathway is strictly required for mammosphere formation, supporting our results using NAD(P)H auto-fluorescence, which enriched CSC activity by more than 5-fold.
  • Since glycolysis is especially critical for maintaining the TCA cycle, OXPHOS and overall mitochondrial function, we next assessed the effects of known glycolytic inhibitors
  • we show that two other natural products that function as effective glycolysis inhibitors, also inhibited mammosphere formation. More specifically, vitamin C (ascorbic acid), which induces oxidative stress and inhibits the activity of GAPDH (a key glycolytic enzyme) [17], also inhibited mammosphere formation, with an IC-50 of 1 mM (Figure 7B). Therefore, vitamin C was ~10 times more potent than 2-DG at targeting CSC propagation
  • silibinin (the major active constituent of silymarin, an extract of milk thistle seeds) [18], which specifically functions as an inhibitor of glucose uptake, blocked mammosphere formation, with an IC-50 between 200 and 400 µM
  • caffeic acid phenyl ester (CAPE), a key component of honey-bee propolis, has potent anti-cancer properties
  • Propolis has a strong history of medicinal use, dating back more than 2,000 years
  • Because of it aromatic ring structure (Figure 8), we speculated that CAPE might function as a potent inhibitor of oxidative mitochondrial metabolism
  • CAPE quantitatively inhibits the mitochondrial oxygen consumption rate (OCR) and, in turn, induces the onset of aerobic glycolysis (ECAR)
  • CAPE shows a clear selectivity for targeting CSCs and adherent cancer cells, relative to normal fibroblasts.
  • CAPE functions as a “natural” mitochondrial OXPHOS inhibitor, that preferentially targets the CSC sub-population. This could explain CAPE’s known anti-cancer properties
  • Our data directly shows that a small fraction of the total cell population, characterized by increased PGC1α activity, high mitochondrial ROS/H2O2 and high NADH levels, has the ability to survive and grow under anchorage-independent conditions, driving mammosphere formation
  • We highlight the utility of certain natural products, such as Silibinin, Vitamin C and CAPE, that could be used to therapeutically target CSCs. Silibinin is the major active component of silymarin, which is an extract prepared from milk thistle seeds.
  • high NADH is a property that is conserved between normal and cancerous stem cells
  • Previous studies have also shown that when non-CSCs and CSCs are both fed mitochondrial fuels (such as L-lactate or ketone bodies), that CSCs quantitatively produce more NADH in response to this stimulus
  • CSCs may be strictly dependent on NADH to maintain their enhanced mitochondrial function
  • The Noble Prize winner, Linus Pauling, was among the first to describe and clinically test the efficacy of Vitamin C, as a relatively non-toxic anti-cancer agent
  • Vitamin C has two mechanisms of action. First, it is a potent pro-oxidant, that actively depletes the reduced glutathione pool, leading to cellular oxidative stress and apoptosis in cancer cells. Moreover, it also behaves as an inhibitor of glycolysis, by targeting the activity of GAPDH, a key glycolytic enzyme.
  • Here, we show that Vitamin C can also be used to target the CSC population, as it is an inhibitor of energy metabolism that feeds into the mitochondrial TCA cycle and OXPHOS
  • Vitamin C may prove to be promising agent for new clinical trials, aimed at testing its ability to reduce CSC activity in cancer patients, as an add-on to more conventional therapies, to prevent tumor recurrence, further disease progression and metastasis
  • Interestingly, a breast cancer based clinical study has already shown that the use of Vitamin C, concurrent with or within 6 months of chemotherapy, significantly reduces both tumor recurrence and patient mortality
  • CAPE quantitatively reduces mitochondrial oxygen consumption (OCR), while inducing a reactive increase in glycolysis (ECAR). As such, it potently inhibits mammosphere formation with an IC-50 of ~2.5 µM. Similarly, it also significantly inhibits cell migration
  • we also demonstrate that 7 different inhibitors of key energetic pathways can be used to effectively block CSC propagation, including three natural products (silibinin, ascorbic acid and CAPE). Future studies will be necessary to test their potential for clinical benefit in cancer patients.
  • Nathan Goodyear on 08 Dec 17
     
    The future of cancer therapy is cancer stem cells.  Study finds that Vitamin C, silymarin, and bee propolis blocks mitochondrial energy pathways in cancer stem cells.  Vitamin C is a known glycolytic inhbitor. Vitamin C was found to inhibit glycolysis via GAPDH targeting to inhibit the energy pathways of the mitochondria in CSCs.  The authors propse that Vitamin C can be used as add on therapies for conventional therapies to specifically attack the CSCs and their contribution to recrurence, treatment resistance, and metastasis potential all in addition to the ability of vitamin C to reduce the side effects of chemotherapy.
Nathan Goodyear

Oncotarget | Vitamin C and Doxycycline: A synthetic lethal combination therapy targetin... - 0 views

www.impactjournals.com/...index.php

cancer doxycycline IV vitamin C vitamin C

shared by Nathan Goodyear on 14 Jun 17 - No Cached
  • These eight distinct cancer types included: DCIS, breast (ER(+) and ER(-)), ovarian, prostate, lung, and pancreatic carcinomas, as well as melanoma and glioblastoma. Doxycycline was also effective in halting the propagation of primary cultures of CSCs from breast cancer patients, with advanced metastatic disease (isolated from ascites fluid and/or pleural effusions)
  • Doxycycline behaves as a strong radio-sensitizer, successfully overcoming radio-resistance in breast CSCs
  • cancer cells can indeed escape the effects of Doxycycline, by reverting to a purely glycolytic phenotype. Fortunately, the metabolic inflexibility conferred by this escape mechanism allows Doxycycline-resistant (DoxyR) CSCs to be more effectively targeted with many other metabolic inhibitors, including Vitamin C, which functionally blocks aerobic glycolysis
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  • Vitamin C inhibits GAPDH (a glycolytic enzyme) and depletes the cellular pool of glutathione, resulting in high ROS production and oxidative stress
  • DoxyR CSCs are between 4- to 10-fold more susceptible to the effects of Vitamin C
  • Doxycycline and Vitamin C may represent a new synthetic lethal drug combination for eradicating CSCs, by ultimately targeting both mitochondrial and glycolytic metabolism
  • inhibiting their propagation in the range of 100 to 250 µM
  • metabolic flexibility in cancer cells allows them to escape therapeutic eradication, leading to chemo- and radio-resistance
  • used doxycycline to pharmacologically induce metabolic inflexibility in CSCs, by chronically inhibiting mitochondrial biogenesis
  • This treatment resulted in a purely glycolytic population of surviving cancer cells
  • DoxyR cells are mainly glycolytic
  • MCF7 cells survive and develop Doxycycline-resistance, by adopting a purely glycolytic phenotype
  • Cancer stem cells (CSCs) are thought to be the “root cause” of tumor recurrence, distant metastasis and therapy-resistance
  • the conserved evolutionary similarities between aerobic bacteria and mitochondria, certain classes of antibiotics inhibit mitochondrial protein translation, as an off-target side-effect
  • Vitamin C was more potent than 2-DG; it inhibited DoxyR CSC propagation by > 90% at 250 µM and 100% at 500 µM
  • IC-50
  • DoxyR CSCs are between 4- to 10-fold more sensitive to Vitamin C than control MCF7 CSCs
  • Berberine, which is a naturally occurring antibiotic that also behaves as an OXPHOS inhibitor
  • treatment with Berberine effectively inhibited the propagation of the DoxyR CSCs by > 50% at 1 µM and > 80% at 10 µM.
  • Doxycycline, a clinically approved antibiotic, induces metabolic stress in cancer cells. This allows the remaining cancer cells to be synchronized towards a purely glycolytic phenotype, driving a form of metabolic inflexibility
  • Doxycycline-driven aerobic glycolysis
  • new synthetic lethal strategy for eradicating CSCs, by employing i) Doxycycline (to target mitochondria) and ii) Vitamin C (to target glycolysis)
  • Doxycycline inhibits mitochondrial biogenesis and OXPHOS,
  • hibits glycolytic metabolism by targeting and inhibiting the enzyme GAPDH
  • CSCs act as the main promoter of tumor recurrence and patient relapse
  • a metabolic shift from oxidative to glycolytic metabolism represents an escape mechanism for breast cancer cells chronically-treated with a mitochondrial stressor like Doxycycline, as mitochondrial dys-function leads to a stronger dependence on glucose
  • Vitamin C has been demonstrated to selectively kill cancer cells in vitro and to inhibit tumor growth in experimental mouse models
  • many of these actions have been attributed to the ability of Vitamin C to act as a glycolysis inhibitor, by targeting GAPDH and depleting the NAD pool
  • here we show that DoxyR CSCs are more vulnerable to the inhibitory effects of Vitamin C, at 4- to 10-fold lower concentrations, between 100 to 250 μM
  • concurrent use of Vitamin C, with standard chemotherapy, reduces tumor recurrence and patient mortality
  • after oral administration, Vitamin C plasma levels reach concentrations of ~70-220 μM
  • intravenous administration results in 30- to 70- fold higher plasma concentrations of Vitamin C
  • pro-oxidant activity results from Vitamin C’s action on metal ions, which generates free radicals and hydrogen peroxide, and is associated with cell toxicity
  • it has been shown that high-dose Vitamin C is more cytotoxic to cancer cells than to normal cells
  • This selectivity appears to be due to the higher catalase content observed in normal cells (~10-100 fold greater), as compared to tumor cells. Hence, Vitamin C may be regarded as a safe agent that selectively targets cancer cells
  • the concurrent use of Doxycycline and Vitamin C, in the context of this infectious disease, appeared to be highly synergistic in patients
  • Goc et al., 2016, showed that Doxycycline is synergistic in vitro with certain phytochemicals and micronutrients, including Vitamin C, in the in vitro killing of the vegetative spirochete form of Borrelia spp., the causative agent underlying Lyme disease
  • Doxycycline, an FDA-approved antibiotic, behaves as an inhibitor of mitochondrial protein translation
  • CSCs successfully escape from the anti-mitochondrial effects of Doxycycline, by assuming a purely glycolytic phenotype. Therefore, DoxyR CSCs are then more susceptible to other metabolic perturbations, because of their metabolic inflexibility
  • Nathan Goodyear on 14 Jun 17
     
    Not especially new, but IV vitamin C + daily doxycycline found to kill cancer stem cells.
Nathan Goodyear

Stuck at the bench: Potential natural neuroprotective compounds for concussion - 0 views

www.ncbi.nlm.nih.gov/...PMC3205506

concussions concussion natural therapies brain curcumin omega 3 resveratrol green tea EGCG EPA DHA vitamin E vitamin c vitamin D

shared by Nathan Goodyear on 20 Feb 16 - No Cached
  • Long-chain polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are highly enriched in neuronal synaptosomal plasma membranes and vesicles
  • The predominant CNS polyunsaturated fatty acid is DHA
  • effective supplementation and/or increased ingestion of dietary sources rich in EPA and DHA, such as cold-water fish species and fish oil, may help improve a multitude of neuronal functions, including long-term potentiation and cognition.
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  • multiple preclinical studies have suggested that DHA and/or EPA supplementation may have potential benefit through a multitude of diverse, but complementary mechanisms
  • pre-injury dietary supplementation with fish oil effectively reduces post-traumatic elevations in protein oxidation
  • The benefits of pre-traumatic DHA supplementation have not only been independently confirmed,[150] but DHA supplementation has been shown to significantly reduce the number of swollen, disconnected and injured axons when administered following traumatic brain injury.
  • DHA has provided neuroprotection in experimental models of both focal and diffuse traumatic brain injury
  • potential mechanisms of neuroprotection, in addition to DHA and EPA's well-established anti-oxidant and anti-inflammatory properties
  • Despite abundant laboratory evidence supporting its neuroprotective effects in experimental models, the role of dietary DHA and/or EPA supplementation in human neurological diseases remains uncertain
  • Several population-based, observational studies have suggested that increased dietary fish and/or omega-3 polyunsaturated fatty acid consumption may reduce risk for ischemic stroke in several populations
  • Randomized control trials have also demonstrated significant reductions in ischemic stroke recurrence,[217] relative risk for ischemic stroke,[2] and reduced incidence of both symptomatic vasospasm and mortality following subarachnoid hemorrhage
  • Clinical trials in Alzheimer's disease have also been largely ineffective
  • The clinical evidence thus far appears equivocal
  • curcumin has gained much attention from Western researchers for its potential therapeutic benefits in large part due to its potent anti-oxidant[128,194,236] and anti-inflammatory properties
  • Curcumin is highly lipophilic and crosses the blood-brain barrier enabling it to exert a multitude of different established neuroprotective effects
  • in the context of TBI, a series of preclinical studies have suggested that pre-traumatic and post-traumatic curcumin supplementation may bolster the brain's resilience to injury and serve as a valuable therapeutic option
  • Curcumin may confer significant neuroprotection because of its ability to act on multiple deleterious post-traumatic, molecular cascades
  • studies demonstrated that both pre- and post-traumatic curcumin administration resulted in a significant reduction of neuroinflammation via inhibition of the pro-inflammatory molecules interleukin 1β and nuclear factor kappa B (NFκB)
  • no human studies have been conducted with respect to the effects of curcumin administration on the treatment of TBI, subarachnoid or intracranial hemorrhage, epilepsy or stroke
  • studies have demonstrated that resveratrol treatment reduces brain edema and lesion volume, as well as improves neurobehavioral functional performance following TBI
  • green tea consumption or supplementation with its derivatives may bolster cognitive function acutely and may slow cognitive decline
  • At least one population based study, though, did demonstrate that increased green tea consumption was associated with a reduced risk for Parkinson's disease independent of total caffeine intake
  • a randomized, placebo-controlled trial demonstrated that administration of green tea extract and L-theanine, over 16 weeks of treatment, improved indices of memory and brain theta wave activity on electroencephalography, suggesting greater cognitive alertness
  • Other animal studies have also demonstrated that theanine, another important component of green tea extract, exerts a multitude of neuroprotective benefits in experimental models of ischemic stroke,[63,97] Alzheimer's disease,[109] and Parkinson's disease
  • Theanine, like EGCG, contains multiple mechanisms of neuroprotective action including protection from excitotoxic injury[97] and inhibition of inflammation
  • potent anti-oxidant EGCG which is capable of crossing the blood-nerve and blood-brain barrier,
  • Epigallocatechin-3-gallate also displays neuroprotective properties
  • More recent research has suggested that vitamin D supplementation and the prevention of vitamin D deficiency may serve valuable roles in the treatment of TBI and may represents an important and necessary neuroprotective adjuvant for post-TBI progesterone therapy
  • Progesterone is one of the few agents to demonstrate significant reductions in mortality following TBI in human patients in preliminary trials
  • in vitro and in vivo studies have suggested that vitamin D supplementation with progesterone administration may significantly enhance neuroprotection
  • Vitamin D deficiency may increase inflammatory damage and behavioral impairment following experimental injury and attenuate the protective effects of post-traumatic progesterone treatment.[37]
  • emerging evidence has suggested that daily intravenous administration of vitamin E following TBI significantly decreases mortality and improves patient outcomes
  • high dose vitamin C administration following injury stabilized or reduced peri-lesional edema and infarction in the majority of patients receiving post-injury treatment
  • it has been speculated that combined vitamin C and E therapy may potentiate CNS anti-oxidation and act synergistically with regards to neuroprotection
  • one prospective human study has found that combined intake of vitamin C and E displays significant treatment interaction and reduces the risk of stroke
  • Pycnogenol has demonstrated the ability to slow or reduce the pathological processes associated with Alzheimer's disease
  • Pcynogenol administration, in a clinical study of elderly patients, led to improved cognition and reductions in markers of lipid peroxidase
  • One other point of consideration is that in neurodegenerative disease states like Alzheimer's disease and Parkinson's disease, where there are high levels of reactive oxygen species generation, vitamin E can tend to become oxidized itself. For maximal effectiveness and to maintain its anti-oxidant capacity, vitamin E must be given in conjunction with other anti-oxidants like vitamin C or flavonoids
  • These various factors might account for the null effects of alpha-tocopherol supplementation in patients with MCI and Alzheimer's disease
  • preliminary results obtained in a pediatric population have suggested that post-traumatic oral creatine administration (0.4 g/kg) given within four hours of traumatic brain injury and then daily thereafter, may improve both acute and long-term outcomes
  • Acutely, post-traumatic creatine administration seemed to reduce duration of post-traumatic amnesia, length of time spent in the intensive care unit, and duration of intubation
  • At three and six months post-injury, subjects in the creatine treatment group demonstrated improvement on indices of self care, communication abilities, locomotion, sociability, personality or behavior and cognitive function when compared to untreated controls
  • patients in the creatine-treatment group were less likely to experience headaches, dizziness and fatigue over six months of follow-up
  • CNS creatine is derived from both its local biosynthesis from the essential amino acids methionine, glycine and arginine
  • Studies of patients with CNS creatine deficiency and/or murine models with genetic ablation of creatine kinase have consistently demonstrated significant neurological impairment in the absence of proper creatine, phosphocreatine, or creatine kinase function; thus highlighting its functional importance
  • chronic dosing may partially reverse neurological impairments in human CNS creatine deficiency syndromes
  • Several studies have suggested that creatine supplementation may also reduce oxidative DNA damage and brain glutamate levels in Huntington disease patients
  • Another study highlighted that creatine supplementation marginally improved indices of mood and reduced the need for increased dopaminergic therapy in patients with Parkinson's disease
  • Nathan Goodyear on 20 Feb 16
     
    great review of natural therapies in the treatment of concussions
Nathan Goodyear

Frontiers | Management of Glioblastoma Multiforme in a Patient Treated With Ketogenic M... - 0 views

www.frontiersin.org/...full

press-pulse therapy hyperbaric ketogenic metabolic therapy cancer ketogenic diet Glioblastoma glioblastoma multiforme HBOT nutrition

shared by Nathan Goodyear on 01 Apr 18 - No Cached
  • The SOC for GBM was modified in this patient to initiate KMT prior to surgical resection, to eliminate steroid medication, and to include HBOT as part of the therapy
  • the greatest therapeutic benefit for patients (near 1.0)
  • The observed reduction in blood glucose in our patient would reduce lactic acid fermentation in the tumor cells, while the elevation of ketone bodies would fuel normal cells thus protecting them from hypoglycemia and oxidative stress
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  • Previous studies showed that GBM survival and tumor growth was correlated with blood glucose levels
  • Evidence indicates that glioma cells cannot effectively use ketone bodies for energy due to defects in the number, structure, and function of their mitochondria
  • The accuracy of the GKI as a predictor for therapeutic efficacy, however, is better when ketone bodies are measured from the blood than when measured from the urine
  • A reduction of glucose-driven lactic acid fermentation would not only increase tumor cell apoptosis, but would also reduce inflammation and edema in the tumor microenvironment thus reducing tumor cell angiogenesis and invasion
  • Besides serving as a metabolic fuel for GBM, glutamine is also an essential metabolite for normal immune cells
  • therapies that inhibit glutamine availability and utilization must be strategically employed to avoid inadvertent impairment of immune cell functions
  • we used the non-toxic green tea extract, EGCG, and chloroquine in an attempt to limit glutamine availability to the tumor cells
  • EGCG is thought to target the glutamate dehydrogenase activity that facilitates glutamine metabolism in GBM cells
  • Chloroquine, on the other hand, will inhibit lysosomal digestion thus restricting fermentable amino acids and carbohydrates from phagocytosed materials in the tumor microenvironment
  • HBOT to increase oxidative stress in the tumor cells
  • As glucose and glutamine fermentation protect tumor cells from oxidative stress, reduced availability of these metabolites under ketosis could enhance the therapeutic action of HBOT, as we recently described
  • Prior to subtotal tumor resection and standard of care (SOC), the patient conducted a 72-h water-only fast
  • Following the fast, the patient initiated a vitamin/mineral-supplemented ketogenic diet (KD) for 21 days that delivered 900 kcal/day
  • KD (increased to 1,500 kcal/day at day 22
  • the patient received metformin (1,000 mg/day), methylfolate (1,000 mg/day), chloroquine phosphate (150 mg/day), epigallocatechin gallate (400 mg/day), and hyperbaric oxygen therapy (HBOT) (60 min/session, 5 sessions/week at 2.5 ATA)
  • Biomarkers showed reduced blood glucose and elevated levels of urinary ketones with evidence of reduced metabolic activity (choline/N-acetylaspartate ratio) and normalized levels of insulin, triglycerides, and vitamin D
  • This is the first report of confirmed GBM treated with a modified SOC together with KMT and HBOT, and other targeted metabolic therapies
  • Glioblastoma multiforme (GBM) is the most common and malignant of the primary adult brain cancers
  • less than 20% of younger adults generally survive beyond 24 months
  • glucose and glutamine are the primary fuels that drive the rapid growth of most tumors including GBM
  • Glucose drives tumor growth through aerobic fermentation (Warburg effect), while glutamine drives tumor growth through glutaminolysis
  • The fermentation waste products of these molecules, i.e., lactic acid and succinic acid, respectively, acidify the tumor microenvironment thus contributing further to tumor progression
  • Glucose and glutamine metabolism is also responsible for the high antioxidant capacity of the tumor cells thus making them resistant to chemo- and radiotherapies
  • The reliance on glucose and glutamine for tumor cell malignancy comes largely from the documented defects in the number, structure, and function of mitochondria and mitochondrial-associated membranes
  • These abnormalities cause the neoplastic GBM cells to rely more heavily on substrate level phosphorylation than on oxidative phosphorylation for energy
  • dexamethasone not only increases blood glucose levels but also increases glutamine levels through its induction of glutamine synthetase activity
    • Nathan Goodyear
      Nathan Goodyear on 21 May 18
       
      use mannitol instead
  • Calorie restriction and restricted KD are anti-angiogenic, anti-inflammatory, anti-invasive, and also kill tumor cells through a proapoptotic mechanism
  • Evidence also shows that therapeutic ketosis can act synergistically with several drugs and procedures to enhance cancer management improving both progression free and overall survival
  • hyperbaric oxygen therapy (HBOT) increases oxidative stress on tumor cells especially when used alongside therapies that reduce blood glucose and raise blood ketones
  • The glutamine dehydrogenase inhibitor, epigallocatechin gallate (EGCG) is also proposed to target glutamine metabolism
  • Nathan Goodyear on 01 Apr 18
     
    Case study of Glioblastoma treated with ketogenic metabolic therapy as an adjuct to modified standard therapy.
Nathan Goodyear

High-dose Vitamin C (Ascorbic Acid) Therapy in the Treatment of Patients with Advanced ... - 0 views

ar.iiarjournals.org/...809.short

IV vitamin C cancer therapy treatment

shared by Nathan Goodyear on 14 Nov 11 - No Cached
  • Nathan Goodyear on 14 Nov 11
     
    vitamin C therapy has been shown to benefit cancer patients in much of the literature, though some research has been published to the contrary. High dose vitamin C IV therapy needs to be re-evaluated as potential therapy in cancer patients
Nathan Goodyear

The role of vitamin C in the treatment of pain: new insights - 0 views

www.ncbi.nlm.nih.gov/...PMC5391567

vitamin C pain arthritis

shared by Nathan Goodyear on 18 Sep 17 - No Cached
  • recommended that during illness one should be careful about the intake of vitamin C, keeping in mind that acute illness rapidly depletes stores of ascorbic acid
  • it is possible that other hospital-associated pain may be partly due to vitamin C deficiency, which is relatively prevalent in hospital settings
  • Vitamin C deficiency (defined as plasma vitamin C concentrations <11 µmol/L
  • ...5 more annotations...
  • Vitamin C is cost effective and appears to be a safe and effective adjunctive therapy for specific pain relief
  • it decreases the requirement for opioid analgesics, particularly post surgically and for bone metastasis
  • recent research has indicated a positive impact of high dose vitamin C on cancer- and chemotherapy-related quality of life, including pain
  • Cameron and Campbell [81] reported a number of cases of dramatic to complete amelioration of bone pain in patients with severe cancer-related pain given both high dose oral and intravenous vitamin C
  • hypovitaminosis C (defined as plasma vitamin C concentrations <23 µmol/L
  • Nathan Goodyear on 18 Sep 17
     
    vitamin C reduces pain; mechanism of action likely anti-inflammatory antioxidant, but yet inconclusive.
Nathan Goodyear

High-dose Vitamin C (Ascorbic Acid) Therapy in the Treatment of Patients with Advanced ... - 1 views

ar.iiarjournals.org/...809.long

IV vitamin C IV vitamin C therapy antioxidant antioxidants cancer

shared by Nathan Goodyear on 25 Sep 13 - No Cached
  • Nathan Goodyear on 25 Sep 13
     
    IV vitamin C dosing shown to be safe and effective.  The levels achieved by IV therapy supercedes that able to achieve by oral therapy by several factors.  This review of the data in this study is of high dose IV vitamin C--safety is reassured.
Nathan Goodyear

Intravenously administered vitamin C as cancer therapy: three cases - 0 views

www.ncbi.nlm.nih.gov/...PMC1405876

IV vitamin C vitamin C cancer

shared by Nathan Goodyear on 24 Apr 17 - No Cached
  • peak plasma concentrations obtained intravenously are estimated to reach 14 000 μmol/L, and concentrations above 2000 μmol/L may persist for several hours
  • Emerging in vitro data show that extracellular ascorbic acid selectively kills some cancer but no normal cells by generating hydrogen peroxide
  • Death is mediated exclusively by extracellular ascorbate, at pharmacologic concentrations that can be achieved only by intravenous administration
  • ...6 more annotations...
  • Vitamin C may serve as a pro-drug for hydrogen peroxide delivery to extravascular tissues, but without the presence of hydrogen peroxide in blood
  • not all cancer cells were killed by ascorbic acid in vitro
  • Intravascular hemolysis was reported after massive vitamin C administration in people with glucose-6-phosphate dehydrogenase deficiency
  • Administration of high-dose vitamin C to patients with systemic iron overload may increase iron absorption and represents a contraindication
  • Ascorbic acid is metabolized to oxalate, and 2 cases of acute oxalate nephropathy were reported in patients with pre-existing renal insufficiency given massive intravenous doses of vitamin C
  • Rare cases of acute tumour hemorrhage and necrosis were reported in patients with advanced cancer within a few days of starting high-dose intravenous vitamin C therapy, although this was not independently verified by pathologic review
  • Nathan Goodyear on 24 Apr 17
     
    IV vitamin C associated with prolonged survival in 3 patients with different cancers.  Peak serum levels reached 14,000 micromol/L, which levels above the 1,000 micro mol/L (cancer cell cytotoxic threshold) were maintained for hours
Nathan Goodyear

Intravenous Vitamin C and Cancer: A Syste... [Integr Cancer Ther. 2014] - PubMed - NCBI - 1 views

www.ncbi.nlm.nih.gov/...24867961

IV vitamin C intravenous vitamin C vitamin C IV intravenous cancer IVC ascorbic acid

shared by Nathan Goodyear on 27 Aug 14 - No Cached
  • Nathan Goodyear on 27 Aug 14
     
    So help me out here:  If IV vitamin C has been shown to prolong time to cancer relapse, aid in reducing tumor size, improve survival with chemotherapy, improve quality of life, improve physical function, reduce chemo side effects, improve energy, reduce nausea, aid insomnia, reduce constipation, and improve depression in cancer patient--then why does the author say that IV vitamin C is contentious?  Add that IV vitamin C has not been implicated in any deaths in cancer therapy.  Contrast that with chemotherapy.  Why again is this contentious?  Whom is best served by this being contentious?
Nathan Goodyear

Arthritis Research & Therapy | Abstract | Restoration of regulatory and effector T cell... - 0 views

arthritis-research.com/...abstract

lupus SLE vitamin D D3 vitamin D Th1 Th17 inflammation autoimmune disease autoimmunity arthritis

shared by Nathan Goodyear on 28 Oct 12 - No Cached
  • Nathan Goodyear on 28 Oct 12
     
    Vitamin D supplementation in those individuals with SLE found to benefit these patients.   Vitamin D found to reduce TH1 and Th17 activity.  It also was found to decrease memory B cells and auto-antibodies.  Also of note is the level of vitamin D after therapy-only at 51.4 at 2 months and 41.5 at 6 months.
Nathan Goodyear

Intravenously administered vitamin C as cancer therapy: three cases - 0 views

www.cmaj.ca/...937.full

IV vitamin C intravenous therapy treatment cancer

shared by Nathan Goodyear on 14 Nov 11 - No Cached
  • Nathan Goodyear on 14 Nov 11
     
    high dose IV vitamin C therapy shown to benefit patients with cancer.  Three cases documented vitamin C therapy in patients with cancer
Nathan Goodyear

High-dose vitamin C therapy for inclusion body myositis. - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...11411094

vitamin C IV vitamin C myositis autoimmune disease intravenous vitamin C inflammation

shared by Nathan Goodyear on 17 Aug 17 - No Cached
  • Nathan Goodyear on 17 Aug 17
     
    study finds "high dose" IV vitamin C benefited 3 of 5 patients in short 4 week study.  The "high dose" was not high dose at all, so that fact that a low dose of IV vitamin C will benefit dermatomysotis in over 50% of the patients in this very small study points to the question, what if actually high dose vitamin C is used.
Nathan Goodyear

Effect of high dose intravenous ascorbic acid on the level of inflammation in patients ... - 0 views

www.riordanclinic.org/...MRI-v01n02-p26.pdf

RA rheumatoid arthritis rheumatoid arthritis IV vitamin C intravenous IV vitamin C ascorbic vitamin C inflammation autoimmune

shared by Nathan Goodyear on 10 Dec 12 - No Cached
  • Nathan Goodyear on 10 Dec 12
     
    This study, small pilot, showed that they were able to lower inflammation in those suffering from RA, through high dose vitamin C IV therapy. This study stopped at 25 gms. The vitamin C is a scavenger of ROS and ROS stimulates inflammation through NF-kappaB. This is how vitamin C can reduce inflammation.
Nathan Goodyear

Tolerance and safety of vitamin E: a toxicological position report. - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...1628854

vitamin E vitamins alternative medicine

shared by Nathan Goodyear on 13 Jun 16 - No Cached
  • Nathan Goodyear on 13 Jun 16
     
    Only abstract available here.  The quote that "the toxicity of vitamin E is very low" tells the story.  Always have levels evaluated to ensure need.  In this review of human studies, doses up to 3,200 IU daily "led to no consistent adverse effects".  Also consider the effects of vitamin K effects in those on vitamin E therapy.
Nathan Goodyear

Intravenous administration of vitamin C in the... [Med Sci Monit. 2010] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...20424557

IV IV therapy IV vitamin C nutritional therapy vitamin C herpetic neuralgia vitamins vitamin vitamin therapy

shared by Nathan Goodyear on 23 Jan 13 - No Cached
  • Nathan Goodyear on 23 Jan 13
     
    Two case studies that show IV vitamin C aided in the resolution of herpetic neuralgia.
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

The Beneficial Effects of Antioxidant Supplementation in Enteral Feeding in Critically ... - 0 views

www.anesthesia-analgesia.org/...857.long

IV intravenous vitamin C E critically ill sepsis antioxidant therapy treatment

shared by Nathan Goodyear on 29 Feb 12 - No Cached
  • Nathan Goodyear on 29 Feb 12
     
    IV vitamin C and vitamin E was found to lower the mortality rate in those with critical illness at the 28 day mark.  This study showed the safety and efficacy of IV vitamin C and vitamin E in those critically ill.
Nathan Goodyear

Vitamin C Pharmacokinetics: Implications for Oral and Intravenous Use - 0 views

www.annals.org/...533.short

IV intravenous vitamin C therapy treatment minerals vitamins

shared by Nathan Goodyear on 22 Nov 11 - No Cached
  • Nathan Goodyear on 22 Nov 11
     
    only high dose IV vitamin C shown to produce high plasma vitamin C concentrations compared to oral vitamin c.
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