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perjantai 6. maaliskuuta 2020

Vitamin C Saves Wuhan Family from COVID-19





FOR IMMEDIATE RELEASE
Orthomolecular Medicine News Service, Mar 5, 2020 


Vitamin C Saves Wuhan Family from COVID-19

by Richard Cheng, M.D., Ph.D.



Vitamin C can help in healing from Coronaviruses 
Dr. Richard Cheng M.D., Ph. D

(OMNS Mar 5, 2020) Ms. N lives in Wuhan, China. She takes special care about the well-being of her entire family including her chronically-ill mother, aged 71. Ms. N has always been interested in nutrition and she recently learned about vitamin C's antiviral effects.

 

I am an American physician currently residing in Shanghai. I interviewed Ms. N by telephone after I received a forwarded story that she posted on Chinese social media, WeChat.

I made an effort to connect with Ms. N to verify the story and below is what she told me.
Ms. N lives with her child in the epicenter of COVID-19 pandemic.  

She is close to her parents and her brother and his wife. The six of them visit each other on a regular basis. Her mother has diabetes and heart disease with stents placed, in addition to several other chronic illnesses including reflux esophagitis.

Right before the Chinese New Year, around January 21st, her mother developed flu-like symptoms, with a low grade fever of 38C. Based on her knowledge. Ms. N advised all members of the family to take oral vitamin C.
She herself has been taking about 20,000 mg daily in divided-up doses. Her mother reluctantly took a smaller dose, probably half or less of what her daughter's been taking.


Her mother's condition was stable for 9-10 days.
But on January 30th, without deteriorating, her mother decided to go to Wuhan Union Hospital, Tongji College of Medicine, The Science and Technology University of Central China, a hospital prominent not only in Wuhan, but in all of China.


She wanted to check out if she was infected with the Wuhan pneumonia virus. She got her presumption confirmed. At the hospital, she was diagnosed of what became known now as Covid-19 pneumonia.
The second day upon admission, her fever started going up, as high as 39.6C. In about 10 days on February 10th she was admitted to the Intensive Care Unit and went on the heart-lung machine as a final attempt to save her life.


At this time Ms. N learned of the clinical trials with vitamin C, administered by infusion (IVC; intravenous vitamin C).

Immediately she requested the person in charge on the ICU to use large dose IVC on her mother. The attending physician agreed but would go only to around 10,000 mg
So it happened. 

After 20 days in ICU, her mother improved and was discharged to a regular ward a few days ago, continuing the IVC treatment, as insisted by Ms. N.
While in hospital, Miss N, her brother and sister-in-law took turns to visit and take care of her mother. They were wearing very simple protection: gloves and masks. Also noted is that while her mother got sick at home, none of the five other family members was wearing any mask for several days. But all of them went on oral vitamin C tablets. None of them developed COVID-19 infection.
So far this is the story of Ms. N. We wish her mother a full and rapid recovery.

In the context of the vast amount of research, clinical studies, case reports and my own decades of experience on vitamin C's use on viral infections, I summarize the story below with a few take-home messages:
  • 1. Vitamin C tablets at high doses daily may be the reason why the family didn't catch the infection.
  • 2. Given her age, history of chronic disease, and the high mortality of COVID-19 on seniors, IVC may have played a large role in her mother's improvement.
  • 3. The news of official IVC clinical trials has definitely had a positive impact in this case, as the attending physician was emboldened to use IVC.
  • 4. A well-functioning immune system is of the utmost importance to keep away the viral infection. And, vitamin C may support the defense against the COVID-19 virus, most importantly in chronically ill patients with a weakened immune system.

(Note from Andrew W. Saul, OMNS Editor-in-Chief: Dr. Richard Cheng is still in China now. He continues to work overtime with expert Chinese doctors and hospitals to facilitate providing intravenous vitamin C for the most seriously ill COVID-19 victims. 

For background information on the plausibility of treating coronavirus with high-dose vitamin C: http://orthomolecular.org/resources/omns/v16n09.shtml
Dr. Cheng's personal presentation of the case above is posted at YouTube: https://youtu.be/6-elCYFhqJs 
An additional video from China by Dr. Cheng is at https://www.youtube.com/watch?v=TC0SO9KDG7U )

 Wuhan



Wuhan


To learn more about COVID-19 and vitamin C:
Mar 3, 2020Shanghai Government Officially Recommends Vitamin C for COVID-19
Mar 1, 2020News Media Attacks Vitamin C Treatment of COVID-19 Coronavirus
Feb 28, 2020Vitamin C and COVID-19 Coronavirus
Feb 23, 2020TONS OF VITAMIN C TO WUHAN: China Using Vitamin C against COVID
Feb 21, 2020Three Intravenous Vitamin C Research Studies Approved for Treating COVID-19
Feb 16, 2020Early Large Dose Intravenous Vitamin C is the Treatment of Choice for 2019-nCov Pneumonia
Feb 13, 2020Coronavirus Patients in China to be Treated with High-Dose Vitamin C
Feb 10, 2020VITAMIN C AND ITS APPLICATION TO THE TREATMENT OF nCoV CORONAVIRUS: How Vitamin C Reduces Severity and Deaths from Serious Viral Respiratory Diseases
Feb 2, 2020Hospital-based Intravenous Vitamin C Treatment for Coronavirus and Related Illnesses
Jan 30, 2020Nutritional Treatment of Coronavirus
Jan 26, 2020Vitamin C Protects Against Coronavirus


Nutritional Medicine is Orthomolecular Medicine

Orthomolecular medicine uses safe, effective nutritional therapy to fight illness. For more information: http://www.orthomolecular.org


Find a Doctor

To locate an orthomolecular physician near you: http://orthomolecular.org/resources/omns/v06n09.shtml


The peer-reviewed Orthomolecular Medicine News Service is a non-profit and non-commercial informational resource.


Editorial Review Board:

Ilyès Baghli, M.D. (Algeria)
Ian Brighthope, MBBS, FACNEM (Australia)
Prof. Gilbert Henri Crussol (Spain)
Carolyn Dean, M.D., N.D. (USA)
Damien Downing, M.D. (United Kingdom)
Michael Ellis, M.D. (Australia)
Martin P. Gallagher, M.D., D.C. (USA)
Michael J. Gonzalez, N.M.D., D.Sc., Ph.D. (Puerto Rico)
William B. Grant, Ph.D. (USA)
Tonya S. Heyman, M.D. (USA)
Suzanne Humphries, M.D. (USA)
Ron Hunninghake, M.D. (USA)
Robert E. Jenkins, D.C. (USA)
Bo H. Jonsson, M.D., Ph.D. (Sweden)
Jeffrey J. Kotulski, D.O. (USA)
Peter H. Lauda, M.D. (Austria)
Thomas Levy, M.D., J.D. (USA)
Homer Lim, M.D. (Philippines)
Stuart Lindsey, Pharm.D. (USA)
Victor A. Marcial-Vega, M.D. (Puerto Rico)
Charles C. Mary, Jr., M.D. (USA)
Mignonne Mary, M.D. (USA)
Jun Matsuyama, M.D., Ph.D. (Japan)
Joseph Mercola, D.O. (USA)
Jorge R. Miranda-Massari, Pharm.D. (Puerto Rico)
Karin Munsterhjelm-Ahumada, M.D. (Finland)
Tahar Naili, M.D. (Algeria)
W. Todd Penberthy, Ph.D. (USA)
Dag Viljen Poleszynski, Ph.D. (Norway)
Selvam Rengasamy, MBBS, FRCOG (Malaysia)
Jeffrey A. Ruterbusch, D.O. (USA)
Gert E. Schuitemaker, Ph.D. (Netherlands)
Hyoungjoo Shin, M.D. (South Korea)
Thomas L. Taxman, M.D. (USA)
Jagan Nathan Vamanan, M.D. (India)
Garry Vickar, MD (USA)
Ken Walker, M.D. (Canada)
Anne Zauderer, D.C. (USA)


Andrew W. Saul, Ph.D. (USA), Editor-In-Chief
Editor, Japanese Edition: Atsuo Yanagisawa, M.D., Ph.D. (Japan)
Editor, Chinese Edition: Richard Cheng, M.D., Ph.D. (USA)
Robert G. Smith, Ph.D. (USA), Associate Editor
Helen Saul Case, M.S. (USA), Assistant Editor
Michael S. Stewart, B.Sc.C.S. (USA), Technology Editor
Jason M. Saul, JD (USA), Legal Consultant
Comments and media contact: drsaul@doctoryourself.com OMNS welcomes but is unable to respond to individual reader emails. Reader comments become the property of OMNS and may or may not be used for publication.


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___

More:

The Ebola virus can be destroyed naturally – despite what you’ve been told



To date, not a single virus has been tested that is not inactivated (killed) by a large enough dose of vitamin C (ascorbic acid).

Many other antioxidants have similar virucidal effects, but vitamin C appears uniquely to be of greatest potency and clinical efficacy, as its simple chemical structure allows for it to be disseminated throughout the body with little restriction.
As such, it is able to effectively address viral populations present in both the intracellular and extracellular spaces.

Other antioxidants have been found to have higher ORAC (Oxygen Radical Absorbance Capacity) values – measurements which are used to quantify the antioxidant capacity of supplements (or foods). However, a virus can never be incapacitated by a potent antioxidant if the chemical structure of that antioxidant does not permit direct contact between the virus and the antioxidant. 


Why is vitamin C so effective in killing viruses?

A primary way in which vitamin C destroys viruses, or sets them up for destruction by the immune system, is by activating the ‘Fenton reaction. In a nutshell, this reaction can proceed inside the virus, inside cells in which viruses are replicating, and on the surfaces of the viruses themselves. The result of this reaction that is stimulated by the presence of vitamin C, one or more transition metal cations, and the local presence of peroxide is the immediate production of hydroxyl radicals. These radicals are the most reactive oxidizing agents ever identified.
As such, they radically upregulate oxidative stress and end up destroying whatever is in their immediate environment.

The effects of vitamin C in “mopping up” after it inflicts its viral damage are further supported by its potent and multifaceted support of the immune system. 


https://graviolateam.blogspot.com/2020/01/the-corona-virus-can-be-destroyed.html



___




Vitamin C Protects Against Coronavirus

"Some physicians would stand by and see their patient die rather than use ascorbic acid (Vitamin C) because in their finite minds it exists only as a vitamin."


VITAMIN C HAS BEEN KNOWN TO CURE OVER 30 MAJOR DISEASES FOR OVER 70 YEARS

- If so, why haven't you heard more about it?
- Why haven't more doctors used Vitamin C as medicine? 



Progress takes time, unfortunately. Fresh fruit was known to cure scurvy by 1753, yet governments ignored the fact for nearly 100 years. Countless thousands died in the meantime. The 19th century doctor who first advocated washing one's hands between patients died ignored and in disgrace with the medical profession. Toxic mercury was used as medicine into the twentieth century. And so it has been.  

The first physician to aggressively use vitamin C to cure diseases was Frederick R. Klenner, M.D. beginning back in the early 1940's.

Dr. Klenner consistently cured chicken pox, measles, mumps, tetanus and polio with huge doses of the vitamin. While vaccines are now available for these illnesses, please remember this was not the case in the 1940's. 




The following is a list of the conditions that Dr. Klenner successfully treated with aggressive vitamin C therapy: 

 
Pneumonia
Encephalitis
Herpes Zoster (shingles)


Herpes Simplex
Mononucleosis
Pancreatitis
Hepatitis
Rocky Mountain Spotted Fever
Bladder Infection
Alcoholism
Arthritis
Some Cancers
Leukemia
Atherosclerosis
Intervertebral Disc
High Cholesterol
Corneal Ulcer
Diabetes
Glaucoma
Schizophrenia
Burns and secondary infections
Heat Stroke
Radiation Burns

Heavy Metal Poisoning (Mercury, Lead), Venomous Bites (insects, snakes), Multiple Sclerosis, Chronic Fatigue, Complications of Surgery


This seems like an impossible list of vitamin C cures. At this point, you can either dismiss the subject or investigate further. Dr. Klenner chose to investigate.
https://graviolateam.blogspot.com/2020/02/vitamin-c-protects-against-coronavirus.html

___




 Orthomolecular Medicine News Service, Feb 21, 2020

Three Intravenous Vitamin C Research Studies Approved for Treating COVID-19

by Andrew W. Saul, Editor

(OMNS February 21, 2020) Intravenous vitamin C is already being employed in China against COVID-19 coronavirus. I am receiving regular updates because I am part of the Medical and Scientific Advisory Board to the International Intravenous Vitamin C China Epidemic Medical Support Team.

Its director is Richard Z. Cheng, MD, PhD; associate director is Hong Zhang, PhD. Among other team members are Qi Chen, PhD (Associate Professor, Kansas University Medical School); Jeanne Drisko, MD (Professor, University of Kansas Medical School); Thomas E. Levy, MD, JD; and Atsuo Yanagisawa, MD, PhD. (Professor, Kyorin University, Tokyo).

To read the treatment protocol information in English:
http://orthomolecular.org/resources/omns/v16n07.shtml
Protocol in Chinese at 
http://www.doctoryourself.com/Coronavirus_Chinese_IV_C_Protocol.pdf


Direct report from China

OMNS Chinese edition editor Dr. Richard Cheng is reporting from China about the first approved study of 12,000 to 24,000 mg/day of vitamin C by IV. The doctor also specifically calls for immediate use of vitamin C for prevention of coronavirus (COVID-19).

A second clinical trial of intravenous vitamin C was announced in China on Feb. 13th. In this second study, says Dr. Cheng, "They plan to give 6,000 mg/day and 12,000 mg/day per day for moderate and severe cases. We are also communicating with other hospitals about starting more intravenous vitamin C clinical studies. We would like to see oral vitamin C included in these studies, as the oral forms can be applied to more patients and at home."  
https://graviolateam.blogspot.com/2020/03/three-intravenous-vitamin-c-research.html


___




THE FENTON REACTION: pro-oxydant role of vitamin C

  • THE DOUBLE FACED CHARACTER OF VITAMIN C
  • THE FENTON REACTION
  • ASCORBIC ACID AND THE FENTON REACTION
  • VITAMIN C PRO-OXYDANT ACTIVITY DAMAGE
  • ASCORBIC ACID AND ITS PRO OXIDANT ACTIVITY AS A THERAPY


THE FENTON REACTION:
pro-oxydant role of vitamin C


ROS (Reactive Oxygen Species)

cristina ghia 04/06/2014
Valeria Ceolin
Cristina Ghia

INTRODUCTION



More than eighty years since its discovery, the understanding of the functions of ascorbic acid has evolved from the prevention of scurvy to its potential use as a therapeutic drug for cancer treatment.

Ascorbate maintains Fe2+ of collagen hydroxylases in an active state; therefore it plays a pivotal role in collagen synthesis; parallel reactions with a variety of dioxygenases affect the expression of a wide array of genes, for example via the 
HIF system, and possibly the epigenetic landscape of cells and tissues.
The ability to donate one  or two electrons makes ascorbate an excellent reducing agent and antioxidant.
However, in the presence of catalytic metals, ascorbate also has pro-oxidant effects, where the redox-active metal is reduced by ascorbate and then in turn reacts with oxygen, producing superoxide that subsequently dismutes to produce 
H2O2.


THE DOUBLE FACED CHARACTER OF VITAMIN C



Ascorbic acid or Vitamin C is a potent dietary antioxidant with a double faced character, in that it exhibits a pro-oxidant activity arising from its routine antioxidant property that generates reactive free radicals.

Vitamin C has antioxidant activity when it reduces oxidizing substances such as hydrogen peroxide, however, it can also reduce metal ions which leads to the generation of free radicals.
The metal ion in this reaction can be reduced, oxidized, and then re-reduced, in a process called redox cycling that can generate reactive oxygen species.

https://graviolat.blogspot.com/2020/02/the-fenton-reaction-pro-oxydant-role-of.html


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keskiviikko 5. helmikuuta 2020

THE FENTON REACTION: pro-oxydant role of vitamin C

  • THE DOUBLE FACED CHARACTER OF VITAMIN C
  • THE FENTON REACTION
  • ASCORBIC ACID AND THE FENTON REACTION
  • VITAMIN C PRO-OXYDANT ACTIVITY DAMAGE
  • ASCORBIC ACID AND ITS PRO OXIDANT ACTIVITY AS A THERAPY


THE FENTON REACTION:
pro-oxydant role of vitamin C


ROS (Reactive Oxygen Species)

cristina ghia 04/06/2014
Valeria Ceolin
Cristina Ghia

INTRODUCTION



More than eighty years since its discovery, the understanding of the functions of ascorbic acid has evolved from the prevention of scurvy to its potential use as a therapeutic drug for cancer treatment.

Ascorbate maintains Fe2+ of collagen hydroxylases in an active state; therefore it plays a pivotal role in collagen synthesis; parallel reactions with a variety of dioxygenases affect the expression of a wide array of genes, for example via the 
HIF system, and possibly the epigenetic landscape of cells and tissues.
The ability to donate one  or two electrons makes ascorbate an excellent reducing agent and antioxidant.
However, in the presence of catalytic metals, ascorbate also has pro-oxidant effects, where the redox-active metal is reduced by ascorbate and then in turn reacts with oxygen, producing superoxide that subsequently dismutes to produce 
H2O2.


THE DOUBLE FACED CHARACTER OF VITAMIN C



Ascorbic acid or Vitamin C is a potent dietary antioxidant with a double faced character, in that it exhibits a pro-oxidant activity arising from its routine antioxidant property that generates reactive free radicals.

Vitamin C has antioxidant activity when it reduces oxidizing substances such as hydrogen peroxide, however, it can also reduce metal ions which leads to the generation of free radicals.
The metal ion in this reaction can be reduced, oxidized, and then re-reduced, in a process called redox cycling that can generate reactive oxygen species.


Pro-oxydant - Wikipedia ]

So, although ascorbic acid has reported anti-oxidant properties, it plays a particular role in redox cycling metal ions and thus activates these ions to exacerbate oxidative stress.
Ascorbic acid has a number of known interactions with metal ions. These interactions involve redox reactions including the reduction reactions of Fe(III) to Fe(II), through the Fenton reaction.



THE FENTON REACTION

The oxidation of organic substrates by iron(II) and hydrogen peroxide is called the "Fenton chemistry" as it was first described by H.J.H. Fenton who first observed the oxidation of tartaric acid by H2O2 in the presence of ferrous iron ions. Alternatively, the name of “Fenton reaction” or “Fenton reagent” is often used, although Fenton never actually wrote it.
We know that the Fenton reagent defined as a mixture of hydrogen peroxide and ferrous iron is currently accepted as one of the most effective methods for the oxidation of organic pollutants.
More than 110 years after the Fenton reaction was discovered we know that this oxidation system is based on the formation of reactive oxidizing.


FENTON REACTION CONTROVERSY CONCERNING THE CHEMISTRY. 2009 ]

Iron(II) is oxidized by hydrogen peroxide to iron(III), forming a hydroxyl radical and a hydroxide ion in the process.
Iron(III) is then reduced back to iron(II) by another molecule of hydrogen peroxide, forming a peroxide radical and a proton.
The net effect is a disproportionation of hydrogen peroxide to create two different oxygen-radical species, with water (H+ + OH–) as a byproduct.



  1. Fe2+ + H2O2 → Fe3+ + HO• + OH–
  2. Fe3+ + H2O2 → Fe2+ + HOO• + H+




Because of that the toxicity of iron, similarly as for other transition metals, may stem from Fenton reaction.


It is commonly accepted that the oxidizing intermediates involved in Fenton reactions cause damage to biomolecules and play a major role in the aging process and a variety of diseases such as cancer. 


The Fenton reaction has been found to be the key reaction in the oxidation of membrane lipids, oxidation of amino acids and in the reactions where biological reduction agents are present, such as ascorbic acid. 

Its occurrence is also supposed in heart diseases, such as ischemia and reperfusion. Our knowledge of Fenton chemistry occurrence in biological systems is important also for its participation in pathological processes such as carcinogenesis, neurodegenerative diseases, atherosclerosis, etc. Finally, it could be said that the Fenton reaction has played an important role in biology for all of the time that life has existed on our planet, but its role in modern civilization diseases is new.


FENTON CHEMISTRY IN BIOLOGY AND MEDICINE. 2007 ]


ASCORBIC ACID AND THE FENTON REACTION

Ascorbic acid can recycle Fe(III) to Fe(II) facilitating further generation of reactive oxygen species by subsequent Fenton cycles.

  1. 2 Fe2+ + 2 H2O2 → 2 Fe3+ + 2 OH• + 2 OH−
  2. 2 Fe3+ + Ascorbate → 2 Fe2+ + Dehydroascorbate




It is speculated that in the presence of O2, complexation between Fe(II) and ascorbic acid results in the formation of an active oxygen species. 
The proposed mechanism shows the oxidation of ascorbic acid to dehydroascorbic acid, by electron transfer through Fe(II), and subsequent hydroxylation of an aromatic compound.


The Fenton reaction

iron added to sodium ascorbate and h2o2






From Wikipedia

Dehydroascorbic acid (DHA) is an oxidized form of ascorbic acid (vitamin C). It is actively imported into the endoplasmic reticulum of cells via glucose transporters.[1] It is trapped therein by reduction back to ascorbate by glutathione and other thiols.[2]

Although a sodium-dependent transporter for vitamin C exists, it is present mainly in specialized cells, whereas the glucose transporters, the most notable being GLUT1, transport Vitamin C (in its oxidized form, DHA)[3] in most cells, where recycling back to ascorbate generates the necessary enzyme cofactor and intracellular antioxidant.

Vitamin C accumulates in mitochondria, where most of the free radicals are produced, by entering as DHA through the glucose transporters, GLUT10. Ascorbic acid protects the mitochondrial genome and membrane.[3] 
 https://en.wikipedia.org/wiki/Dehydroascorbic_acid









Iron and ascorbic acid form a potentially toxic cocktail.
The chemical mechanisms given above have been established demonstrating the potential for these compounds to interact and oxidatively damage surrounding tissues.



VITAMIN C PRO-OXYDANT ACTIVITY DAMAGE

Ascorbic acid has been shown to exhibit both anti-oxidant and pro-oxidant effects in a dose related fashion.
So we can say that depending on concentrations, the effects of ascorbate can be pro- or antioxidant. There is considerable variability in the literature; this variability appears to be a result of the different concentrations and form of transition metal ions in the experiments. 


The pro-oxidant effects of ascorbate may be important in vivo depending on the availability of catalytic metal ions. In healthy individuals, iron is largely sequestered by iron binding proteins such as transferrin and ferritin. 

This iron is essentially redox inactive. Instead, in pathological situations, such as thalassemia or hemochromatosis, non-transferrin-bound iron is present. Thus, supplemental ascorbate without administration of an iron chelator can lead to deleterious effects. 
Tissue damage resulting from ischemia/reperfusion is another example of increased availability of catalytic metal occurring in vivo. Intravenous ascorbate prior to vascular surgery increased concentrations of ascorbate radical and lipid hydroperoxides suggesting that catalytic iron released into the circulation during the ischemic phase of the surgery with ascorbate may promote iron-induced lipid peroxidation. 

Elevated levels of catalytic metal ions have also been demonstrated in chronic inflammatory diseases. There is an increased deposition of iron proteins in the synovial membranes in rheumatoid arthritis. Ascorbate radical has been detected in synovial fluid from patients with synovitis disease indicating that catalytic iron is in part responsible for the decreased levels of ascorbate and increased levels of DHA. In addition, ascorbate concentrations were decreased while levels of catalytic iron increased in patients with sepsis, compared to healthy subjects.

VITAMIN C CONTRIBUTES TO INFLAMMATION VIA RADICAL GENERATING MECHANISMS: A CAUTIONARY NOTE. 2003 - full text available on Biblioteca Biomedica Integrata Università A.S.O. S. Luigi ]

A study demonstrated that ferritin released by neuroblastoma cells  enhanced pharmacologic ascorbate induced-cytotoxicity, indicating that ferritin with high iron-saturation could be a source of catalytic iron. Consistent with this, ascorbate has also been shown to be capable of releasing iron from cellular ferritin. Ferritin is only one candidate as a source of catalytic iron; extracellular iron chelates are present in tissue and seem to be increased under pathological conditions.

H(2)O(2)-MEDIATED CYTOTOXICITY OF PHARMACOLOGIC ASCORBATE CONCENTRATIONS TO NEUROBLASTOMA CELLSPOTENTIAL ROLE OF LACTATE AND FERRITIN. 2010 ]

Even in healthy subjects a positive or negative deviation from the optimal plasma ascorbic acid level results in oxidative damage.
A study published in Nature shows that vitamin C administered as a dietary supplement to healthy humans exhibits a pro-oxidant, as well as an antioxidant, effect in vivo.
Although the antioxidant nature in vivo of vitamin C has been questioned, it is nonetheless marketed as supplements in doses of 500 mg per day as an ‘antioxidant’. The discovery of an increase in a potentially mutagenic lesion following a typical vitamin C supplementation should therefore be of some concern, although at doses of less than 500 mg per day the antioxidant effect may predominate.


VITAMIN C EXHIBITS PRO-OXIDANT PROPERTIES. 1998 - full text available on Nature, vol. 392 ]


ASCORBIC ACID AND ITS PRO OXIDANT ACTIVITY AS A THERAPY

These many observations provide insights on the mechanism by which pharmacologic concentrations of ascorbate have potential in treating certain types of cancer. The inhibition effects of pharmacologic ascorbate on tumor growth have been confirmed in many laboratories.
It has been shown that ascorbate at pharmacologic concentrations was a pro-oxidant, generating hydrogen-peroxide-dependent cytotoxicity toward a variety of cancer cells in vitro without adversely affecting normal cells. 


In vitro, pharmacologic ascorbate concentrations mediated selective cancer cell toxicity via formation of Asc•− and H2O2 in cell culture media, with minimal Asc•− and no H2O2 detectable in blood . H2O2 in vitro were toxic to cancer cells.
Based on these data, many studies propose in vivo that pharmacologic ascorbate concentrations selectively generate Asc•− in extracellular fluid but not in blood. Pharmacokinetic data indicate that intravenous administration of ascorbate bypasses the tight control of the gut and renal excretion; thus, intravenous administration of ascorbate will produce highly elevated plasma levels; this ascorbate will autoxidize and the electron lost from ascorbate would reduce a protein-centered metal, resulting in a high flux of extracellular H2O2. 


This H2O2 will readily diffuse into cells challenging the intracellular peroxide-removal system, initiating oxidative cascades. 

These high fluxes of H2O2 appear to have little effect on normal cells but can be detrimental to certain tumor cells. In fact, in blood pharmacologic ascorbate concentrations would produce low Asc•− concentrations compared with extracellular fluid, whereas any H2O2 formed in blood would be immediately destroyed.

Knowledge and understanding of these mechanisms brings a rationale to the use of high-dose ascorbate to treat disease and thereby is reviving interest in the use of i.v. ascorbate in cancer treatment.


ASCORBATE IN PHARMACOLOGIC CONCENTRATIONS SELECTIVELY GENERATES ASCORBATE RADICAL AND HYDROGEN PEROXIDE IN EXTRACELLULAR FLUID IN VIVO. 2007 ]

The beneficial effects of ascorbate in cancer treatment reflect the ability of ascorbate to inhibit cancer cell proliferation. Ascorbate, acting as a pro-oxidant, inhibited cancer cell growth through other  mechanisms, including induction of endoplasmic reticulum stress,  suppression of insulin-like growth factor production, and inhibition of angiogenic factor production. Ascorbate can also inhibit the immune escape of cancer cells through suppression of IL-18 expression. 

Thus, ascorbate may be a model antineoplastic agent, prolonging survival and improving the quality of life through selective inhibition of tumor growth.


THE PROSPECTS OF VITAMIN C IN CANCER THERAPY. 2009 ]

Real-time microdialysis sampling in mice bearing glioblastomaxenografts showed that a single pharmacologic dose of ascorbate produced sustained ascorbate radical and hydrogen peroxide formation selectively within interstitial fluids of tumors but not in blood.
Moreover, a regimen of daily pharmacologic ascorbate treatment significantly decreased growth rates of ovarian (P < 0.005), pancreatic (P < 0.05), and glioblastoma (P < 0.001) tumors established in mice. Similar pharmacologic concentrations were readily achieved in humans given ascorbate intravenously. These data suggest that ascorbate as a prodrug may have benefits in cancers with poor prognosis and limited therapeutic options.


PHARMACOLOGIC DOSES OF ASCORBATE ACT AS A PROOXIDANT AND DECREASE GROWTH OF AGGRESSIVE TUMOR XENOGRAFTS IN MICE. 2008 ]

A systematic review of the studies reported in literature that have studied the pro-oxidant activity of ascorbic acid as a therapeutic option for treatment of oral neoplasms and its effects on normal oral cells shows that the pro-oxidant activity of pharmacologic ascorbic acid is a part of its dose-dependent bimodal activity and is a result of the proposed Fenton mechanism. In vitro, animal and ex vivo studies of pharmacologic ascorbic acid (AA) have yielded meritorious results proving vitamin C as an effective cytotoxic agent against oral neoplastic cells with potentially no harming effects on normal cells. However, a shortage of clinical trials and in vivo human studies pertaining to evaluation of anti-tumour activity of vitamin C in tumours of oral cavity remains a lacuna in concluding ascorbic acid as a beneficial therapeutic option in treatment of oral neoplasms.

ASCORBIC ACID AND ITS PRO-OXIDANT ACTIVITY AS A THERAPY FOR TUMOURS OF ORAL CAVITY -- A SYSTEMATIC REVIEW. 2013 ]


Ascorbic acid just haven’t got a role in treating cancer: Mycobacterium tuberculosis is extraordinarily sensitive to killing by a vitamin C-induced Fenton reaction.


Vitamin C, driving the Fenton reaction, sterilizes cultures of drug-susceptible and drug-resistant Mycobacterium tuberculosis, the causative agent of tuberculosis.
The bactericidal activity of vitamin C against M. tuberculosis is dependent on high ferrous ion levels and reactive oxygen species production, and causes a pleiotropic effect affecting several biological processes.






Vitamin C, driving the Fenton reaction, sterilizes cultures of
drug-susceptible and drug-resistant Mycobacterium tuberculosis



MYCOBACTERIUM TUBERCULOSIS IS EXTRAORDINARILY SENSITIVE TO KILLING BY A VITAMIN C-INDUCED FENTON REACTION. 2013 ]


CONCLUSION

The biological role of ascorbate is to act as a reducing agent, donating electrons to various enzymatic and a few non-enzymatic reactions.
Ascorbic acid behaves not only as an antioxidant but also as a pro-oxidant. However, usually in the body, free transition elements are  unlikely to be present, while iron and copper are bound to diverse proteins and the use of a normal dose of vitamin C does not appear to increase pro-oxidant activity.
Instead, it has been studied the mechanistic basis for applying ascorbate as a pro-oxidant therapeutic agent, above all for cancer treatment.


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2014-06-25T13:49:27 - cristina ghia 

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the fenton reaction





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