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Elimination of Ascorbic Acid After High‐Dose Infusion in Prostate Cancer Pati... - 1 views

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    Small study finds that plasma AA levels increase with accumulating doses of weekly IV vitamin C only at 60 gram.
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The acute effect of high-dose intravenous vitamin C and other nutrients on blood pressu... - 0 views

  • the reduction in BP within the first 10–20 min may be primarily attributed to a direct vasodilatory physiological effect, described as venodilation
  • BP reduction observed after 70–90 min is likely attributable to pharmacokinetically plausible vitamin C absorption and vasodilation because of nitric oxide release
  • Pharmacokinetic studies of IVC administration observed peak plasma levels within the first 90 min, with plasma levels reaching 13350 μmol/l for 50 g of IVC
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  • Essential hypertension, associated with endothelial dysfunction because of an impaired nitric oxide/l-arginine pathway and impaired vasodilation can be restored by vitamin C
  • marked increase in BP response when IVB12 is administered
  • The mean BP increased significantly up to 12–16 mmHg systolic and diastolic independent of the dosage of vitamin B12
  • The production of norepinephrine, which can stimulate angiotensin-II production, which in turn influences BP, has been suggested as a possible mechanism for the increase in BP with IVB12
  • excess norephinephrine levels stimulate the sympathetic nervous system, leading to increased cortisol production, which has also been linked to increases in BP
  • Animal studies have found higher serum levels of norepinephrine (noradrenaline) in the adrenal medulla of rats receiving methylcobalamin (methyl-vitamin B12)
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    IV vitamin C in mostly normotensive patients (> 30 grams) reduced blood pressure.  Some of the patients were pre-hypertensive. Vitamin B12 increase the blood pressure.
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Effect of Ascorbate on the Activity of Hypoxia-inducible Factor in Cancer Cells | Cance... - 0 views

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    "Ascorbate at physiological concentrations (25 μm) strikingly suppressed HIF-1α protein levels and HIF transcriptional targets, particularly when the system was oncogenically activated in normoxic cells. Similar results were obtained with iron supplementation" Here, physiologic levels of plasma AA decrease HIF-1alpha activity.
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Vitamin C Administration by Intravenous Infusion Increases Tumor Ascorbate Content in P... - 0 views

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    Very interesting study. They gave IV vitamin C up to 75 grams to increase tumor delivery and found there was correlation between plasma and tumor levels post resection. This correlation was to a point-saturation curve. Also, there was a reduction in VEGF and hypoxia scores.
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Communication between genomic and non-genomic signaling events coordinate steroid hormo... - 0 views

  • steroid hormones typically interact with their cognate receptor in the cytoplasm for AR, glucocorticoid receptor (GR) and PR, but may also bind receptor in the nucleus as appears to often be the case for ERα and ERβ
  • This ligand binding results in a conformational change in the cytoplasmic NRs that leads to the dissociation of HSPs, translocation of the ligand-bound receptor to the nucleus
  • In the nucleus, the ligand-bound receptor dimerizes and then binds to DNA at specific HREs to regulate gene transcription
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  • some steroid hormone-induced nuclear events can occur in minutes
  • the genomic effects of steroid hormones take longer, with changes in gene expression occurring on the timescale of hours
  • Classical steroid hormone signaling occurs when hormone binds nuclear receptors (NR) in the cytoplasm, setting off a chain of genomic events that results in, among other changes, dimerization and translocation to the nucleus where the ligand-bound receptor forms a complex with coregulators to modulate gene transcription through direct interactions with a hormone response element (HRE)
  • NRs have been found at the plasma membrane of cells, where they can propagate signal transduction often through kinase pathways
  • Membrane-localized ER, PR and AR have been reported to modulate the activity of MAPK/ERK, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), nitric oxide (NO), PKC, calcium flux and increase inositol triphosphate (IP3) levels to promote cell processes including autophagy, proliferation, apoptosis, survival, differentiation, and vasodilation
  • ERα36, a 36kDa truncated form of ERα that lacks the transcriptional activation domains of the full-length protein. Membrane-localized ERα36 can activate pathways including protein kinase C (PKC) and/or mitogen activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) to promote the progression of various cancers
  • G protein-coupled receptor 30 (GPR30), also referred to as G protein-coupled estrogen receptor (GPER), is a membrane-localized receptor that has been observed to respond to estrogen to activate rapid signaling
  • hormone-responsive G protein coupled receptor is Zip9, which androgens can activate
  • GPRC6A is another G protein-coupled membrane receptor that is responsive to androgen
  • androgen-mediated non-genomic signaling through this GPCR can modulate male fertility, hormone secretion and prostate cancer progression
  • non-NR proteins located at the cell surface can bind to steroid hormones and respond by eliciting rapid signaling events
  • Estrogens have been shown to induce rapid (i.e. seconds) calcium flux via membrane-localized ER (mER)
  • ER-calcium dynamics lead to activation of kinase pathways such as MAPK/ERK which can result in cellular effects like migration and proliferation
  • 17β-estradiol (E2) has been reported to promote angiogenesis through the activation of GPER
  • Membrane NRs may also mediate rapid signaling through crosstalk with growth factor receptors (GFR)
  • A similar crosstalk occurs between the receptor tyrosine kinase insulin-related growth factor-1 receptor (IGF-IR) and ERα. Not only does IGF-IR activate ERα, but inhibition of IGF-IR downregulates estrogen-mediated ERα activity, suggesting that IGF-IR is essential for maximal ERα signaling
    • Nathan Goodyear
       
      This is a bombshell that shatters the current right brain approach to ER. It completely shatters the concept of eat sugar, whatever you want, with cancer treatment in ER+ or hormonally responsive cancer!
  • Further, ER activates IGF-IR pathways including MAPK
  • GPER is involved in the transactivation of the EGFR independent of classical ER
  • tight interconnection between genomic and non-genomic effects of NRs.
  • non-genomic pathways can also lead to genomic effects
  • androgen-bound AR associates with the kinase Src at the plasma membrane, activating Src which then leads to a signaling cascade through MAPK/ERK
  • However, Src can also increase the expression of AR target genes by the ligand-independent transactivation of AR
  • extranuclear steroid hormone actions can potentially reprogram nuclear NR events
  • estrogen modulated the expression of several genes including endothelial nitric oxide synthase (eNOS) via rapid signaling pathways
  • epigenetic changes can then mediate genomic events in uterine tissue and breast cancer cells
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Pharmacokinetic modeling of ascorbate diffusion through normal and tumor tissue | Reque... - 0 views

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    Plasma levels of 100 microMolar to penetrate all hypoxic areas of tumor.
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Pharmacokinetic modeling of ascorbate diffusion through normal and tumor tissue - PubMed - 0 views

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    supraphysiological plasma ascorbate concentrations (>100 μM) are required to achieve effective delivery of ascorbate to poorly vascularized tumor tissue
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The Role of Vitamin C in Human Immunity and Its Treatment Potential Against COVID-19: A... - 0 views

  • 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
       
      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
       
      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
       
      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
       
      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
       
      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
       
      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
       
      This recommendation is FRANK IGNORANCE
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Effect of high-dose intravenous vitamin C on prognosis in patients with SARS-CoV-2 pneu... - 0 views

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    At 2 grams per day, this study was designed to fail…and they did not even evaluate plasma AA levels.
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ScienceDirect.com - Physiology & Behavior - Mitochondrial complex I inhibition depletes... - 0 views

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    Testosterone is known to provide anti-inflammatory signaling in men.  This study, inhibition of mitochondrial complex I (coQ dependent) resulted in lower testosterone in rat models.  One of the major side effects of statin therapy is poor memory and brain fog. Hmmm.
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Plasma lipoproteins: composition, structure and biochemistry - 0 views

  • triacylglycerols
  • The most abundant lipid constituents are triacylglycerols, free cholesterol, cholesterol esters and phospholipids (phosphatidylcholine and sphingomyelin especially ), though fat-soluble vitamins and anti-oxidants are also transported in this way
  • the lipoprotein aggregates should be described in terms of the different protein components or apoproteins (or 'apolipoproteins'
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  • these classes can be further refined by improved separation procedures, and intermediate-density lipoproteins (IDL) and subdivisions of the HDL (e.g. HDL1, HDL2, HDL3 and so forth
  • Density is determined largely by the relative concentrations of triacylglycerols and proteins and by the diameters of the broadly spherical particles
  • Lipoproteins are spherical (VLDL, LDL, HDL) to discoidal (nascent HDL) in shape with a core of non-polar lipids, triacylglycerols and cholesterol esters, and a surface monolayer, ~20Å thick, consisting of apoproteins, phospholipids and non-esterified cholesterol, which serves to present a hydrophobic face to the aqueous phase
  • the various lipid components should not be considered as absolute, as they are in a state of constant flux
  • Apo A1 is the main protein component of HDL
  • Apo A2 is the second most important HDL apolipoprotein
  • the main groups are classified as chylomicrons (CM), very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL) and high-density lipoproteins (HDL), based on the relative densities of the aggregates on ultracentrifugation
  • The lipoproteins can be categorised simplistically according to their two main metabolic functions. The principal role of the chylomicrons and VLDL is to transport triacylglycerols ‘forward’ as a source of fatty acids from the intestines or liver to the peripheral tissues. In contrast, the HDL remove excess cholesterol from peripheral tissues and deliver it to the liver for excretion in bile in the form of bile acids (‘reverse cholesterol transport’). While these functions are considered separately here for convenience, it should be recognised that the processes are highly complex and inter-related, and they involve transfer of apoproteins, enzymes and lipid constituents among the heterogeneous mix of all the lipoprotein fractions.
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    Awesome review of apolipoproteins, their function, and their metabolism.
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Plasma vitamin C concentrations predict risk of incident stroke over 10 y in 20 649 par... - 0 views

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    IV vitamin C is the only delivery method shown to increase serum vitamin C levels.  Additionally, the stroke incidence is this study was found to be lowered by 42% with the elevation of serum vitamin C levels, which  can only be done by IV.
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Plasma concentration of gonadotrophins,... [Br J Obstet Gynaecol. 1975] - PubMed - NCBI - 0 views

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    Sex hormone imbalance plays a role in hypothyroidism.
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Preventing Chronic Disease | Plasma Vitamin D and Biomarkers of Cardiometabolic Disease... - 0 views

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    Higher vitamin D levels associated with lower cardio biomarkers: insulin, insulin resistance, triglycerides, TC, LDL and TC:HDL.  Not found to be associated: glucose, apoliporotein A1 and B, CRP, fibrinogen, and homocysteine.
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Metabolic Signatures of Exercise in Human Plasma - 0 views

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    Nice article that describes the biochemical benefits of exercise.
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Thyroid Hormones Decrease Plasma 1α,25-Dihydroxyvitamin D Levels Through Tran... - 0 views

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    T3 can suppress kidney production of 1 alpha,25-dihyddroxyvitamin D.
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Plasma vitamin C is lower in postherpetic neural... [Clin J Pain. 2009] - PubMed - NCBI - 0 views

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    IV vitamin C aids pain control in postherpetic neuralgia.
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Evaluation of Plasma, Salivary, and Urinary Cortisol Levels for Diagnosis of Cushing's ... - 0 views

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    Salivary cortisol shown to have "high sensitivity and specificity" in subclinical and overt Cushing's syndrome. Again, why the opposition to saliva??? Ignorance.
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Diet-hormone interactions: Protein/carbohydrate ratio alters reciprocally the plasma le... - 0 views

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    small study, but complex carbs found to increase Testosterone more than high protein diet.  That goes against most marketing.  In contrast, cortisol was the opposite.
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