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Neil Riordan IVC

A comprehensive collection on IVC Literature and Therapies

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Vitamin C and Coffee added to your colon prep is more delicious

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J Gastrointestin Liver Dis. 2016 Mar;25(1):63-9. doi: 10.15403/jgld.2014.1121.251.cff.

Effect of Coffee Added to a Polyethylene glycol plus Ascorbic acid Solution for Bowel Preparation prior to Colonoscopy.

Jung SW1, Moh IH2, Yoo H2, Jang SI2, Shin SR2, Kim JB2, Park SH2, Lee MS2.

Abstract

BACKGROUND AND AIMS:

Conventional bowel cleansers for colonoscopy have an unpleasant taste and a large volume of solution must be ingested. Coffee increases bowel motility and has an intense flavor. The addition of coffee to a polyethylene glycol+ascorbic acid solution reduces the volume of the solution to be consumed without reducing efficacy, improves the taste of the solution and enhances patient comfort.

METHODS:

Outpatients with clinical indication or people who wanted screening for cancer were considered eligible. Control group (PEGAS group) consumed a 1-L solution of polyethylene glycol+ascorbic acid twice. Study group (COF group) consumed 750 mL of coffee+polyethylene glycol+ascorbic acid twice. Bowel cleansing was rated using the Aronchick, Ottawa scale, polyp detection rate and colonoscopic insertion time. Tolerability, acceptability, preference, and adverse events were investigated by questionnaires.

RESULTS:

The COF group had non-inferiority in efficacy (non-inferiority margin, -15 %; lower limit of 95 % confidence interval for difference between success rates, – 4.7 % and -8.4 % from both scales, respectively). Polyp detection rates were 0.48 and 0.60, respectively (P=0.067). Colonoscopic insertion times were 323.6+/-166.8 s and 330.7+/-243.6 s, respectively (P=0.831). Significant improvement was observed with respect to ease of drinking (P=0.012), taste (P=0.026) and preference (P=0.046) in the COF group. Adverse events occurred in 52.4 % and 60.4 % in the two groups, respectively (P = 0.251).

CONCLUSION:

The addition of coffee to polyethylene glycol+ascorbic acid solution reduces the required volume for bowel preparation without reduced efficacy and enhances patient comfort in coffee-drinkers.

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High doses of Vitamin C selectively kill KRAS and BRAF cancer cells in mice

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High doses of vitamin C in mice impaired tumor growth by eliminating cells with mutations in the KRAS or BRAF genes – these are linked to certain kinds of colorectal cancers.

Science. 2015 Dec 11;350(6266):1391-6. doi: 10.1126/science.aaa5004.

Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH.

Yun J, Mullarky E, Lu C, Bosch KN, Kavalier A, Rivera K, Roper J, Chio II, Giannopoulou EG, Rago C, Muley A, Asara JM, Paik J, Elemento O,Chen Z, Pappin DJ, Dow LE, Papadopoulos N, Gross SS, Cantley LC.

Abstract

More than half of human colorectal cancers (CRCs) carry either KRAS or BRAF mutations and are often refractory to approved targeted therapies. We found that cultured human CRC cells harboring KRAS or BRAF mutations are selectively killed when exposed to high levels of vitamin C. This effect is due to increased uptake of the oxidized form of vitamin C, dehydroascorbate (DHA), via the GLUT1 glucose transporter. Increased DHA uptake causes oxidative stress as intracellular DHA is reduced to vitamin C, depleting glutathione. Thus, reactive oxygen species accumulate and inactivate glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Inhibition of GAPDH in highly glycolytic KRAS or BRAF mutant cells leads to an energetic crisis and cell death not seen in KRAS and BRAF wild-type cells. High-dose vitamin C impairs tumor growth in Apc/Kras(G12D) mutant mice. These results provide a mechanistic rationale for exploring the therapeutic use of vitamin C for CRCs with KRAS or BRAF mutations.

Copyright © 2015, American Association for the Advancement of Science.

 

PMID: 26541605

 

 

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High doses of Vitamin C enhance lipoprotein metabolism

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In this 2015 article, consuming high doses (1250 mg/day) of Vitamin C for 8 days was found to enhance lipoprotein (HDL) metabolism – usually associated with aging-related diseases (chronic inflammatory response, cardiovascular disease and diabetes…).

 

Food Funct. 2015 Nov;6(11):3604-12. doi: 10.1039/c5fo00738k.

Consumption of high-dose vitamin C (1250 mg per day) enhances functional and structural properties of serum lipoprotein to improve anti-oxidant, anti-atherosclerotic, and anti-aging effects via regulation of anti-inflammatory microRNA.

Kim SM1, Lim SM, Yoo JA, Woo MJ, Cho KH.

1School of Biotechnology, Yeungnam University, Gyeongsan, 712-749, Republic of Korea. chok@yu.ac.kr.

Abstract

Background Although the health effects of vitamin C are well known, its physiological effect on serum lipoproteins and microRNA still remain to be investigated, especially daily consumption of a high dosage.

Objectives To investigate the physiological effect of vitamin C on serum lipoprotein metabolism in terms of its anti-oxidant and anti-glycation activities, and gene expression via microRNA regulation.

Methods We analyzed blood parameters and lipoprotein parameters in young subjects (n = 46, 22 ± 2 years old) including smokers who consumed a high dose of vitamin C (1250 mg) daily for 8 weeks.

Results Antioxidant activity of serum was enhanced with the elevation of Vit C content in plasma during 8 weeks consumption. In the LDL fraction, the apo-B48 band disappeared at 8 weeks post-consumption in all subjects. In the HDL fraction, apoA-I expression was enhanced by 20% at 8 weeks, especially in male smokers. In the lipoprotein fraction, all subjects showed significantly reduced contents of advanced glycated end products and reactive oxygen species (ROS). Triglyceride (TG) contents in each LDL and HDL fraction were significantly reduced in all groups following the Vit C consumption, suggesting that the lipoprotein was changed to be more anti-inflammatory and atherogenic properties. Phagocytosis of LDL, which was purified from each individual, into macrophages was significantly reduced at 8-weeks post-consumption of vitamin C. Anti-inflammatory and anti-senescence effects of HDL from all subjects were enhanced after the 8-weeks consumption. The expression level of microRNA 155 in HDL3 was reduced by 49% and 75% in non-smokers and smokers, respectively.

Conclusion The daily consumption of a high dose of vitamin C for 8 weeks resulted in enhanced anti-senescence and anti-atherosclerotic effects via an improvement of lipoprotein parameters and microRNA expression through anti-oxidation and anti-glycation, especially in smokers.

 

PMID: 26333284

 

 

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General aspects of vitamin C biology in human health

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A very recent (January 2016) review of general aspects of vitamin C in human health, including:

  • Vitamin C interactions with the metabolism, physiology, enzymology and others;
  • Mechanisms of transport and absorption;
  • Experimental findings, current knowledge, current unknowns;

and many other features of Vitamin C.

 

Oral Dis. 2016 Jan 25. doi: 10.1111/odi.12446.

Vitamin C: the known, the unknown, and Goldilocks.

Padayatty SJ1, Levine M1.

1Molecular and Clinical Nutrition Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, 20892-1372, USA.

Abstract

Vitamin C (Ascorbic acid, abbreviated as AA; the terms vitamin C and ascorbic acid are used interchangeably) is synthesized by all plants and most animals (Smirnoff et al., 2001). It is a vitamin for humans because the gene for gulonolactone oxidase, the terminal enzyme in the AA synthesis pathway has undergone mutations that make it non-functional (Linster & Van Schaftingen, 2007). Animals that have lost the ability to synthesize ascorbic acid do not have a phylogenetic relationship with each other. These animals include non-human primates, guinea pigs, capybara and some birds and fish (Chaudhuri & Chatterjee, 1969, Chatterjee, 1973, Cueto et al., 2000). Deficiency of ascorbic acid produces the fatal disease scurvy, which can be cured only by the administration of vitamin C.

This article is protected by copyright. All rights reserved.

 

PMID: 26808119

 

 

 

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Review of mechanisms for transport and flow of Vitamin C in the cells

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A review by Italian researchers on current knowledge about how Vitamin C enters cells.
Arch Biochem Biophys. 2010 Aug 15;500(2):107-15. doi:10.1016/j.abb.2010.05.014.

Cellular pathways for transport and efflux of ascorbate and dehydroascorbate.

Corti A1, Casini AF, Pompella A.
1Dipartimento di Patologia Sperimentale, Università di Pisa, Italy

Abstract

The mechanisms allowing the cellular transport of ascorbic acid represent a primary aspect for the understanding of the roles played by this vitamin in pathophysiology. Considerable research effort has been spent in the field, on several animal models and different cell types. Several mechanisms have been described to date, mediating the movements of different redox forms of ascorbic acid across cell membranes. Vitamin C can enter cells both in its reduced and oxidized form, ascorbic acid (AA) and dehydroascorbate (DHA), utilizing respectively sodium-dependent transporters (SVCT) or glucose transporters (GLUT). Modulation of SVCT expression and function has been described by cytokines, steroids and post-translational protein modification. Cellular uptake of DHA is followed by its intracellular reduction to AA by several enzymatic and non-enzymatic systems. Efflux of vitamin C has been also described in a number of cell types and different pathophysiological functions were proposed for this phenomenon, in dependence of the cell model studied. Cellular efflux of AA is mediated through volume-sensitive (VSOAC) and Ca(2+)-dependent anion channels, gap-junction hemichannels, exocytosis of secretory vesicles and possibly through homo- and hetero-exchange systems at the plasma membrane level. Altogether, available data suggest that cellular efflux of ascorbic acid – besides its uptake – should be taken into account when evaluating the cellular homeostasis and functions of this important vitamin.

2010 Elsevier Inc. All rights reserved.

 

PMID: 20494648
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High-dose of vitamin C supplementation reduces amyloid plaque burden

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Cell Death Dis. 2014 Feb 27;5:e1083. doi: 10.1038/cddis.2014.26.

High-dose of vitamin C supplementation reduces amyloid plaque burden and ameliorates pathological changes in the brain of 5XFAD mice.

Abstract

Blood-brain barrier (BBB) breakdown and mitochondrial dysfunction have been implicated in the pathogenesis of Alzheimer’s disease (AD), a neurodegenerative disease characterized by cognitive deficits and neuronal loss. Besides vitamin C being as one of the important antioxidants, recently, it has also been reported as a modulator of BBB integrity and mitochondria morphology. Plasma levels of vitamin C are decreased in AD patients, which can affect disease progression. However, investigation using animal models on the role of vitamin C in the AD pathogenesis has been hampered because rodents produce with no dependence on external supply. Therefore, to identify the pathogenic importance of vitamin C in an AD mouse model, we cross-bred 5 familial Alzheimer’s disease mutation (5XFAD) mice (AD mouse model) with ι-gulono-γ-lactone oxidase (Gulo) knockout (KO) mice, which are unable to synthesize their own vitamin C, and produced Gulo KO mice with 5XFAD mice background (KO-Tg). These mice were maintained on either low (0.66 g/l) or high (3.3 g/l) supplementation of vitamin C. We found that the higher supplementation of vitamin Chad reduced amyloid plaque burden in the cortex and hippocampus in KO-Tg mice, resulting in amelioration of BBB disruption and mitochondrial alteration. These results suggest that intake of a larger amount of vitamin C could be protective against AD-like pathologies. 
PMID:

 

24577081
An external file that holds a picture, illustration, etc. Object name is cddis201426f1.jpg
Amyloid plaque burden is decreased in the cortex and hippocampus of the high-supplementation group of 5XFAD mice. (a) Coronal serial sections of brains from 6-month-old mice (n=4 for each of the groups) were stained with anti-Aβ antibody (green; 4G8) and imaged by confocal microscopy. There were no signals in the frontal cortex of KO-WT mice in either of the two treatment. 4G8-positive areas were decreased in the frontal cortex of KO-Tg on the high-dose vitamin C treatment. Scale bar=600 μm. The section shown is at the interaural level, 4.78 mm; Bregma, −0.98 mm (Fig. 23 in Franklin and Paxinos57). (b) Frontal cortex of KO-Tg mice of both treatment groups was magnified. (a and d) Somatosensory region; (b and c) motor region. Scale bar=100 μm. (c) Coronal serial sections of brains from 6-month-old mice (n=4 for each of the groups) were stained with anti-Aβ antibody (green; 4G8) and imaged by confocal microscopy. There were no signals in the hippocampus of KO-WT mice in either treatment groups. Plaques were particularly decreased in the hippocampus of KO-Tg on the high-dose vitamin C treatment. Scale bar=600 μm. The section shown is at the interaural level, 1.86 mm; Bregma, −1.94 mm (Fig. 47 in Franklin and Paxinos57). (d) Hippocampus of KO-Tg mice of both treatment groups was magnified. Nuclei were stained with 4′-6-diamidino-2-phenylindole. Scale bar=100 μm. (e) Compared with the low-dose supplemented KO-Tg mice, the high-dose supplementation KO-Tg mice exhibited significantly less plaque burden in the cortex and hippocampus. Both P values (***P<0.001 and *P<0.05) mean the high-dose versus the low-dose supplemented KO-Tg group
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Restoring physiological levels of vitamin C slows tumor growth

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Cancer Med. 2015 Feb;4(2):303-14. doi: 10.1002/cam4.349. Epub 2014 Oct 30.

Restoring physiological levels of ascorbate slows tumor growth and moderates HIF-1 pathway activity in Gulo(-/-) mice.

Campbell EJ1, Vissers MC, Bozonet S, Dyer A, Robinson BA, Dachs GU.

Author information

  • 1Mackenzie Cancer Research Group, Department of Pathology, University of Otago, Christchurch, New Zealand.

Abstract

Hypoxia-inducible factor-1 (HIF-1) governs cellular adaption to the hypoxic microenvironment and is associated with a proliferative, metastatic, and treatment-resistant tumor phenotype. HIF-1 levels and transcriptional activity are regulated by proline and asparagine hydroxylases, which require ascorbate as cofactor. Ascorbate supplementation reduced HIF-1 activation in vitro, but only limited data are available in relevant animal models. There is no information of the effect of physiological levels of ascorbate on HIF activity and tumor growth, which was measured in this study. C57BL/6 Gulo(-/-) mice (a model of the human ascorbate dependency condition) were supplemented with 3300 mg/L, 330 mg/L, or 33 mg/L of ascorbate in their drinking water before and during subcutaneous tumor growth of B16-F10 melanoma or Lewis lung carcinoma (LL/2). Ascorbate levels in tumors increased significantly with elevated ascorbate intake and restoration of wild-type ascorbate levels led to a reduction in growth of B16-F10 (log phase P < 0.001) and LL/2 tumors (lag growth P < 0.001, log phase P < 0.05). Levels of HIF-1α protein in tumors decreased as dietary ascorbate supplementation increased for both tumor models (P < 0.001). Similarly, tumor ascorbate was inversely correlated with levels of the HIF-1 target proteins CA-IX, GLUT-1, and VEGF in both B16-F10 and LL/2 tumors (P < 0.05). The extent of necrosis was similar between ascorbate groups but varied between models (30% for B16-F10 and 21% for LL/2), indicating that ascorbate did not affect tumor hypoxia. Our data support the hypothesis that restoration of optimal intracellular ascorbate levels reduces tumor growth via moderation of HIF-1 pathway activity.

© 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

KEYWORDS:

Gulonolactone oxidase; VEGF; hypoxia-inducible factor 1; vitamin C

PMID:
25354695
[PubMed – in process]
PMCID:
PMC4329013
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Vitamin C and Cancer–neither proved or disproved in Montreal?

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In this trial, the patients had a less than 33% likelihood of achieving a meaningful response from any treatment. In spite of that, three of the 14 patients had increased energy level, functional improvement, and transient stable disease.

PLoS One. 2015 Apr 7;10(4):e0120228. doi: 10.1371/journal.pone.0120228. eCollection 2015.

High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

Hoffer LJ1, Robitaille L2, Zakarian R3, Melnychuk D4, Kavan P5, Agulnik J6, Cohen V7, Small D6, Miller WH Jr8.

Author information

  • 1Department of Medicine, Jewish General Hospital, Montreal, Canada.
  • 2Lady Davis Institute for Medical Research, Montreal, Canada.
  • 3Lady Davis Institute for Medical Research, Montreal, Canada; Clinical Research Unit, Segal Cancer Centre, Jewish General Hospital, Montreal, Canada.
  • 4Lady Davis Institute for Medical Research, Montreal, Canada; Department of Oncology, Segal Cancer Centre, Jewish General Hospital, Montreal, Canada.
  • 5Lady Davis Institute for Medical Research, Montreal, Canada; Departments of Oncology and Medicine, Segal Cancer Centre, Montreal, Canada.
  • 6Lady Davis Institute for Medical Research, Montreal, Canada; Departments of Medicine and Oncology, Peter Brojde Lung Cancer Centre, Jewish General Hospital, Montreal, Canada.
  • 7Lady Davis Institute for Medical Research, Montreal, Canada; Departments of Oncology and Medicine, Segal Cancer Centre, Montreal, Canada; Departments of Medicine and Oncology, Peter Brojde Lung Cancer Centre, Jewish General Hospital, Montreal, Canada.
  • 8Lady Davis Institute for Medical Research, Montreal, Canada; Clinical Research Unit, Segal Cancer Centre, Jewish General Hospital, Montreal, Canada; Departments of Oncology and Medicine, Segal Cancer Centre, Montreal, Canada.

Abstract

BACKGROUND:

Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC) could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail.

METHODS AND FINDINGS:

We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalicacid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement.

CONCLUSIONS:

Despite IVC’s biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC’s value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type, chemotherapy regimen and IVC in which exceptional responses occur frequently enough to justify appropriately focused clinical trials.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01050621.

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Chikungunya viral infection symptoms improved with IVC and peroxide.

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Bol Asoc Med P R. 2015 Jan-Mar;107(1):20-4.

Intravenous ascorbic acid and hydrogen peroxide in the management of patients with chikungunya.

Marcial-Vega V, Idxian Gonzalez-Terron G, Levy TE.

Abstract

Chikungunya is a viral illness characterized by severe joint pains, which may persist for months to years. There is no effective treatment for this disease. We treated 56 patients with moderate to severe persistent pains with a single infusion of ascorbic acid ranging from 25-50 grams and hydrogen peroxide (3 cc of a 3% solution) from July to October 2014. Patients were asked about their pain using the Verbal Numerical Rating Scale-11 immediately before and after treatment. The mean Pain Score before and after treatment was 8 and 2 respectively (60%) (p < 0.001); and 5 patients (9%) had a Pain Score of 0. The use of intravenous ascorbic acid and hydrogen peroxide resulted in a statistically significant reduction of pain in patients with moderate to severe pain from the Chikungunya virus immediately after treatment.

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Low vitamin C levels promote atherosclerosis

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Am J Cardiovasc Dis. 2015 Mar 20;5(1):53-62. eCollection 2015.  Hypoascorbemia induces atherosclerosis and vascular deposition of lipoprotein(a) in transgenic mice.
Dr. Rath Research Institute Santa Clara, CA, USA.

Abstract

Lipoprotein(a), a variant of LDL carrying the adhesive glycoprotein apo(a), is a leading risk factor for cardiovascular disease. Lipoprotein(a) (Lp(a)) is found in humans and subhuman primates but rarely in lower mammals. Better understanding of the evolutionary advantage of this molecule should elucidate its physiological role. We developed a new mouse model with two characteristics of human metabolism: the expression of Lp(a) and the lack of endogenous ascorbate (vitamin C) production. We show that dietary deficiency of ascorbate increases serum levels of Lp(a). Moreover, chronic hypoascorbemia and complete depletion of ascorbate (scurvy) leads to Lp(a) accumulation in the vascular wall and parallels atherosclerotic lesion development. The results suggest that dietary ascorbate deficiency is a risk factor for atherosclerosis independent of dietary lipids. We provide support for the concept that Lp(a) functions as a mobile repair molecule compensating for the structural impairment of the vascular wall, a morphological hallmark of hypoascorbemia and scurvy. 

KEYWORDS:

Gulo-/-; Lipoprotein(a); Lp(a); Lp(a) transgene; atherosclerosis; cvd risk factors; hypoascorbemia; vascular plaques; vitamin C
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