Monday, January 28, 2019

Cancer Is A Metabolic Disease

Cancer Is A Metabolic Disease

Cancer is a metabolic disease, there is little doubt to that statement.

Cancer is rarely a genetic disease, though often discussed as such.  What genetic changes that do exist in cancer are likely the result of the metabolic dysfunction and poor adaptation for survival that results from a hypoxic environment.

This is the fourth article of a seven-part series by Nathan Goodyear, MD at An Oasis of Healing on the evidence and research on Vitamin C therapy for Cancer. If you missed the first three articles, you can go here for article number one and here for the second article and visit here for the third article to get caught up and read them in full.

Dr. Lodi does not like the word disease, so let’s look at that word and see why.  Disease is an early 14th-Century word that was more descriptive than diagnostic.

According to the Etymology dictionary, the original meaning of the word disease meant discomfort, inconvenient, distress…  The actual 2 root words are ‘dis’ (without) and ‘aise’ (ease) which gives the actual root meaning of disease as ‘without ease’.

Interestingly, in the late 15th Century the meaning of the word disease evolved to mean ‘to make ill’.  Since conventional medicine treatments are the 3rd leading cause of death, how can medicine not be called a means to make ill, a means to create dis “aise”, a disease itself.

The scientific literature really leaves little evidence for any other conclusion, but that cancer is the result of poor adaptation to metabolic distress.  In fact, cancer is the body’s attempt to adapt, though be it a poor attempt, to the presence of a low oxygen environment, oxidative stress, and poor energy production.

In the short-term, this adaptation pays dividends for survival, but in the long-term, this adaptation leads to the survival of very dysfunctional cells and what we know as cancer.  The genetic defects often found in cancer are more often the result of massive metabolic dysfunction, than a foundational genetic defect. In many ways, the genetic defects found in cancer are the effect of the extreme metabolic dysfunction in cancer rather than the cause of cancer.

I have had the pleasure of speaking at numerous conferences including the same conference as Dr. Thomas N. Seyfried, the author of Cancer is a Metabolic Disease.  Dr. Seyfried is extremely well published on the mechanisms of the dysfunctional metabolism of cancer.

His 2015 article entitled Cancer as a mitochondrial metabolic disease, published in the Journal Frontiers In Cell and Developmental Biology, is a heavy, but very good read on the metabolic mechanisms behind cancer.  In addition, Dr. Dominic P. D’Agostino at the University of South Florida spoke at the same conference on the use of the ketogenic diet in the management of metastatic cancer.

Now, I have the opportunity to work with my good friend, Dr. Thomas Lodi, a pioneer in Integrative Oncology.  These and other pillars in the cancer research community have helped to decipher the mechanisms behind the actions of IV vitamin C in cancer and apply them to clinical practice.  The combination of the knowledge of cancer metabolism and the mechanism and use of IV vitamin C in cancer metabolism provide a targeted, lethal combination in the fight against cancer.

Cancer as a Mitochondrial Metabolic Disease

To describe the mechanism of action of IV vitamin C in cancer, I need to get a little technical so please bear with me.  Put on your thinking caps.  Humans are one of several species that have lost the ability to make vitamin C, hence what vitamin C we have in our body comes through our diet and/or supplementation alone.

In addition, the human body has very limited capacity to store vitamin C.  This lack of productive capacity and lack of storage leaves most people with cancer with massive vitamin C deficiency in what I like to call metabolic scurvy.

One of the benefits of vitamin C in the battle against cancer is that vitamin C looks just like glucose—sugar.  Vitamin C is actually made from glucose by the enzyme gulonolactone oxidase. Humans lack this enzyme, which requires regular, continuous vitamin C from our diet.

As concerning as this enzymatic deficiency can be, this deficiency provides a silver lining in the fight against cancer.  Cancer thrives in the typical glucose-rich environment of the western American diet. The elimination of simple sugars, excessive carbohydrates, and high process foods from the diet will starve the cancer of its primary fuel source—glucose.

In the low glucose state induced by targeted nutrition plans, vitamin C is readily taken up by the energy-starved cancer cells via the receptors SVCT1 and SVCT2 because of vitamin C’s resemblance to glucose.  In this case, vitamin C is a stealthy, metabolic time bomb for cancer cells.  This is why nutrition is as much a part of treatment at an Oasis of Healing as the IV therapies are.

Back to the how of Vitamin C in cancer.  The first key step, as I have discussed previously, is the pharmacologic dosing of vitamin C and not the physiologic dosing.  Dosing vitamin C at levels that prevent scurvy will never achieve therapeutic anti-cancer effects.

Vitamin C must be dosed as a medicine.  This is a point that most physicians completely miss.  It goes back to the pharmacokinetics that I have discussed previously; but then again, most physicians don’t pay attention to pharmacokinetics.

The Evidence of the Effects of Vitamin C on Cancer Cells shows this therapy should be a part of every cancer patients treatment protocol

Cancer And Mitochondrial Dysfunction

Recent evidence points to the extracellular production of the Reactive Oxidative Species (ROS) superoxide anions O2- and then eventually H2O2 by pharmacologic dosing of vitamin C is what appears to precipitate the cascade of events that eventually results in cancer cell death.  It is the intracellular effects of H2O2, however, that leads to oxidative damage via the increase in hydroxyl free radicals and eventual death of the cancer cell via overwhelming oxidative stress.

An important point that needs to be made here: it is the altered energy cell metabolism of cancer cells i.e. aerobic glycolysis or “the Warburg effect” and the increased cell metabolic rate of the cancer cells that increases the baseline level of ROS species, which, in turn, increases the labile iron (Fe) pool (via an increase in the cellular uptake of Fe and a corresponding decrease in the elimination of Fe by the cancer cell), which provides the necessary environment and sensitizes the cancer cells for therapeutic vitamin C and resultant H2O2 to overwhelm the cancer cell with ROS.

The image directly above highlights the proposed pathway and effects of vitamin C as well as the different effects in normal cells vs cancer cells as published in the recent article published by Schoenfeld JD et al in Cancer Cell.  The exact mechanism of cell death has not been exactly determined and, in fact, is probably quite variable.

Despite the exact mechanism of action known, recent studies and review articles have shown that the intracellular H2O2 interacts with elevated iron pools and/or elevated copper levels to produce hydroxyl free radicals to directly damage the DNA of the cancer cells, damage DNA repair proteins of the cancer cells, inhibition of cell growth cycle, up-regulation of the tumor suppressor gene p53, compromised energy production via damage to the cancer cells (mitochondria) energy powerhouse, and even modification of genetic expression via what is known as epigenetics.    The pro-oxidant effect of H2O2 in cancer cells (discussed in another post) is the dagger in the heart of the cancer cell.

Cancer cells have limited catalase and glutathione peroxidase activity compared to healthy cells leaving cancer cells susceptible to the destructive oxidative effects of the Reactive Oxygen Species.  These key enzymes are used by the cell to handle the oxidative effects of H2O2.  These limited glutathione peroxidases and/or catalase levels and/or activity render the cancer cell vulnerable to the oxidative effects of H2O2 from pharmacologic vitamin C dosing.  That is the science.

Though the exact mechanism, down to every fine detail, of the effects of vitamin C on cancer cells, is not yet determined, the knowledge of the effects of vitamin C in cancer far exceeds that of many FDA approved drugs.  If you ever have insomnia, read the package insert for the drugs sometime and you will often find the words, “exact mechanism of action not known”.

Despite that statement, physicians prescribe and the public takes.  The word insanity comes to mind.  The history supports vitamin C, the volume of evidence supports vitamin C, the evidence supports the biochemistry effects of vitamin C, and finally, the thousands of patients with cancer that have benefited from vitamin C confirms the evidence.

The only thing stopping physicians from using more vitamin C is simple ignorance, whether intentional or not.  Now, you are informed.  Take control of your journey in the defeat of cancer and the restoration of health.

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High Dose Vitamin C Benefits And Cancer Cell Metabolism


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Wednesday, January 23, 2019

Is Vitamin C An Antioxidant Or A Pro-Oxidant?

Is Vitamin C An Antioxidant Or A Pro-Oxidant

Let’s answer the question, is Vitamin C an Antioxidant or a Pro-oxidant? 

 The answer is yes and yes.  The environment dictates the effects of vitamin C.  In the right environment, vitamin C can be a pro-oxidant; equally, in the right environment, the same vitamin C can be an antioxidant.

This is the third article of a seven-part series by Nathan Goodyear, MD at An Oasis of Healing on the evidence and research on Vitamin C therapy for Cancer. If you missed the first two articles, you can go here for the first article and then here for the second to get caught up and read them in full.

 It comes down to the redox potential.  Redox is the balance of the ability to oxidize versus the ability to reduce.  Breakdown the word redox: red- is the ability to reduce and -ox is the ability to oxidize.  The reduction ability is equivalent to the anti-oxidant and the oxidation ability is equivalent to the pro-oxidant.

 What is a pro-oxidant?  A pro-oxidant is something that is simply pro oxidation  Rust is a good example of the oxidative process.  Picture your dream car.  Now picture that beautiful, shiny car just off the showroom floor in your driveway.  The sun just glistens off the polished, new paint on the body of the car.

The body of the car is smooth and in pristine condition without a scratch or blemish.  Put the key in the ignition and turn to hear the crisp, clear ignition and the gentle hum of the engine.   Push the gas pedal and feel the horsepower take over.  There is no delay.  There is no dysfunction.  That is the lack of the presence of oxidation.

Vitamin C as a Pro-oxidant

A pro-oxidant is synonymous with anything that is oxidative.  The oxidative process is the cause of stress to the cell, thus the term oxidative stress.   Oxidative stress is the result of Reactive Oxygen Species (ROS).

Reactive Oxygen species are oxidative species i.e. hydrogen peroxide (H2O2), hydroxyl free radicals (OH−), and superoxide anions (·O2−), that react with cell components to create stress to the cell and if unchecked—damage.  The end result can be oxidative damage.

Now, back to that car.  Let that car sit out in the elements for days, months, years on end with continuous exposure to the elements i.e. rain, heat, cold…  With time, what once was a beautiful, shiny car is now a disfigured, rusty image of its former self.

Open the door and hear the creep and crack of what once silence and smooth movement.  Insert the key and turn to hear the sputter, delayed turnover of what once was a crisp, clear ignition start.  What was once a gentle hum that calmed the soul, is now a loud, chaotic noise disrupts the soul.

Push the gas pedal to find a delayed, sub-optimal gas injection and movement where once a horse-power dream existed.  That is the effects of the oxidative process on a car.  The most visible evidence of this process is better known as rust.

What does rust have to do with cancer?  Rust is the interaction of the oxidative process (oxygen) with iron.  Iron exists in the imagery of the car above as it exists in the body.  In the imagery above, the oxidative process is with the car.

However, in cancer, the oxidative process is with the cancer cell.  Whether it is on the body of the car or in the body or cell of a person, the effects of oxidation are the same—damage, visibly evident as rust.

Watch Dr. Nathan Goodyear explain why Vitamin C is both an Antioxidant and a Pro-Oxidant

What is an antioxidant?  An antioxidant is simply something that is anti-oxidation.  An antioxidant is something that counters the potential destructive oxidative process.  An Antioxidant, whether on the body of the car or inside the body or cell of a person, is anti-rust.   Some common antioxidants are vitamin E, beta-carotene, Quercetin…  The most famous and powerful antioxidant is vitamin C.

How can vitamin C be both an antioxidant and a pro-oxidant?  This is a question and yet a true statement at the same time that confounds many cancer doctors today.  As I stated previously, the environment dictates the response

High Dose Vitamin C For Cancer

Vitamin C, especially at the higher dosages, that can be obtained only through IV vitamin C delivery, has been shown to be a potent pro-oxidant (not an antioxidant) in cancer cells.   The baseline level of ROS in the cancer cell is already elevated. The high metabolic requirement to meet the high growth present in cancer appears to be the primary cause of this increase in base-line ROS.

It is the pro-oxidant activity of vitamin C in cancer cells that generate the required increase in the levels of ROS, such as H2O2, OH−, ·O2−, to then kill cancer cells. The H2O2 works more like a messenger that ends in oxidation with OH− and ·O2−, rather than the end cause of oxidation.  In the presence of this high ROS, cancer cells carry a high labile iron pool due to an increase in iron transport into the cancer cell and a decrease in the transport of iron out of the cancer cell.

The therapeutic vitamin C is converted to the oxidative H2O2 messenger outside the cancer cell and then transported inside the cancer cell to then interact with the high labile iron pool to create the oxidative stress, deplete the glutathione pool in the cancer cell and cause oxidative damage— again, think cellular rust.  This intra-cellular process of oxidative stress and oxidative damage begins the death spiral within the cancer cell which triggers cell death (apoptosis).

In addition, Reactive Nitrogen Species (RNS) via Nitric Oxide (NO), can also play a part in the oxidative process.   Where there is iron, whether on the body of the car or in the body of the person, oxygen will interact with it to create rust, oxidative stress, and potentially oxidative damage.

The key factor that separates cancer cells from healthy cells is that cancer cells lack the appropriate levels of certain enzymes, such as catalase and glutathione peroxidase, to counter these high ROS levels through the reduction of oxidative stress and a decrease in the oxidative damage potential.  This appears to be only true about cancer cells that lack stem activity.  We will discuss this at a later post: the difference in ROS in cancer cells without stem activity versus cancer stem cells.

Vitamin C challenges Cancer Cells at a Metabolic Level and Causes Cell Die-Off

Healthy cells, that is non-cancer cells, retain appropriate catalase and glutathione peroxidase activity and are thus perfectly capable of reducing the high ROS levels, prevent oxidative stress and the associated potential oxidative damage.  Vitamin C, thus, functions as an anti-oxidant in healthy cells but as a pro-oxidant in cancer cells, as dictated by the environment.

Vitamin C Fights Cancer

The story for vitamin C does not end there.  Vitamin C also behaves as an inhibitor of the glycolysis pathway (see image below).  Glycolysis is a key pathway in the cell cycle of energy production and the primary mechanism of energy production in cancer cells.

Vitamin C targets and blocks the activity of Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), a key enzyme in glycolysis.  This blockade of the GAPDH enzyme shuts down a cancer cells favorite way to make energy.  

 Is vitamin C an antioxidant or a pro-oxidant?  Yes.  Vitamin C can be a pro-oxidant in cancer cells and yet can be an anti-oxidant in healthy cells at the same time.  They are cells, yes!  But, the environment of these cells are different in every way.

They are different in their environment, different in cell metabolism, different in redox potential, different in detoxification potential, different in antioxidant and pro-oxidant potential…  In fact, you can say the same about cancer cells that lack stem activity in comparison to cancer stem cells, but that is for another time and in another post.

The functions highlighted above make vitamin C a potent anti-cancer therapy that leaves healthy cells unharmed.  A therapy that attacks cancer and heals the body at the same time—what a great combination and a novel concept!  Now you are informed.

Monday, January 7, 2019

What Are The Benefits Of IV Vitamin C In Cancer?

What are the Benefits of IV vitamin C in Cancer?The benefits of iv vitamin c in cancer are clearly stated in close to 3,000 published articles on PubMed.

The fact that a natural therapy has such a significant level of evidence to support its use is surprising to a lot of people—physicians included.  In fact, when you look at the evidence of the benefits of IV vitamin C in cancer, the volume actually dwarfs much of the research that pushes many prescriptions drugs to market today.

This is the second article of a seven-part series by Nathan Goodyear, MD at An Oasis of Healing on the evidence and research on Vitamin C therapy for Cancer. If you missed the first article, you can go here to read it in full.

Just compare and contrast the latest FDA approved anti-cancer drug Vitrakvi (larotrectinib).  This new anti-cancer drug was “approved under accelerated approval” based on 3 studies.  Contrast the 3 studies with the current 2,746 articles published on PubMed for vitamin C and cancer.

The published evidence for the benefit of IV vitamin C in the treatment of cancer includes:

  • Improved Quality of Life
  • Increased overall survival
  • Reduction in pain
  • Increased energy
  • Increased appetite
  • Decreased cancer-associated inflammation
  • Prevents cancer-associated sepsis
  • Combats infections (viral, bacterial, fungi)
  • Reduces side effects and toxicity of chemotherapy
  • Reduces side effects and toxicity of radiation
  • Augments the cancer kill rate of chemotherapy
  • Augments the cancer kill rate of radiation
  • Reduces cancer angiogenesis
  • Kills cancer cells
  • Allows a decrease in dose of chemotherapy, yet maintains the same cancer kill rate
  • Improves surgery recovery time
  • Reduces post-surgery pain
  • May even decrease post-surgery cancer recurrence
  • Kills Cancer Stem Cells (CSC)

All of these benefits of IV Vitamin C and it is non-toxic to healthy cells. 

Compare and contrast vitamin C with many of the latest wonder drugs approved by the FDA only to be pulled from the market due to danger to the general public.  The graveyard of FDA approved drugs is long and includes the blockbuster drugs Zelnorm, Vioxx, Propulsid, and Rezulin to name a few.

These drugs were pulled secondary to side effects including heart arrhythmias, liver failure, heart attacks, sudden cardiac failures, and strokes.  In total, approximately 30,000 reported deaths were linked to these 4 drugs alone.

What about the unreported deaths?  In fact, prescription drugs are the 4th leading cause of death in the U.S. causing an estimated 128,000 deaths annually.  Combine the number of deaths reported from Europe by the European Commission and that number rises to over 300,000 deaths annually.

And what of Vitamin C?

Vitamin C will never be pulled from the market because of safety reasons. Intravenous vitamin C has repeatedly been shown to be safe at therapeutic dosing as high as 300 grams IV daily in patients with sepsis.

One death in 1979 was reported from tumor lysis syndrome after the initiation of high dose vitamin C.  Tumor lysis syndrome is secondary to massive cancer cell death that results in a massive inflammatory reaction.

Tumor Lysis Syndrome can be found in any therapy that kills cancer cells i.e. chemotherapy.  How does this compare to your average approved drug, chemotherapy, radiation, or surgical treatment for cancer?

Is vitamin C safe?  Check.  Is vitamin C effective?  Check.  Is there evidence to support the safe and effective use of IV vitamin C in the treatment of cancer?  Check times 2,746 articles and thousands upon thousands of patient cases.

The safety, the increased quality of life and the increased overall survival alone are all reasons for people battling cancer should receive IV vitamin C.  Though it should be primary, the anti-cancer effects of vitamin C are simply icing on the cake. Any therapy that is safe, improves outcome, reduces side effects, and kills cancer cells should be an absolute must!

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High Dose Vitamin C For Cancer


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Wednesday, January 2, 2019

IV Vitamin C For Cancer Treatment

IV Vitamin C For Cancer Treatment

Background on IV Vitamin C for Cancer Treatment

 This is the first of a seven-part series by Nathan Goodyear, MD at An Oasis of Healing on the evidence and research on the use of Vitamin C with Cancer. For years, Dr. Lodi and I have been strong advocates for IV Vitamin C for cancer treatment and the following clearly shows why we support this therapy.
The science on IVC is not new and, in fact, has been around for quite some time.  Linus Pauling and Ewan Cameron published their landmark study, Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer, on IV Vitamin C in cancer over 40 years ago in 1976.  In this early study, Cameron and Pauling found that IVC increased the survival time of those who received a very low dose of IVC (10 grams) in those with advanced cancer compared to those who did not.
Even though Linus Pauling won the Nobel Prize for his work on Vitamin C, it was WJ McCormick that was the first to propose the benefits of Vitamin C in the treatment of cancer even earlier in 1954. At the time of writing this blog, there were 2746 articles listed on PubMed alone on the topic of Vitamin C and cancer.
Despite the long history of the study of IV Vitamin C and cancer, the research on IV Vitamin C in the treatment of cancer continues.  The use of IV Vitamin C in cancer is currently being studied at numerous sites across the US, including the University of Iowa, Thomas Jefferson University, the University of Kansas Medical Center, and Johns Hopkins University, throughout Europe and the rest of the world.
Intravenous Vitamin C is a natural, yet very powerful tool to directly attack cancer and yes, kill cancer cells.  Recent evidence also highlights the cancer-killing effects of Vitamin C in cancer stem cells.
In general, patients with cancer have been shown to have significantly depleted levels of Vitamin C compared to individuals without cancer—a modern-day metabolic scurvy if you will. The scientific evidence for the use of IV Vitamin C as a treatment option and a treatment adjunct in cancer continues to grow.
In fact, it is my opinion that the evidence for the intravenous use of Vitamin C in cancer is so strong, it should be considered a mainstay in any and all treatment plans in the treatment of cancer.  I would even use the mainstream medicine words standard of care in reference to and for the support of IV Vitamin C in the treatment of cancer.
Not standard of care as defined by mainstream medicine, what everybody is doing, but instead use the standard of care that results from the overwhelming evidence that supports its efficacy and safety.  There are a lot of cancer treatments used on people every day that can’t meet the level of evidence available for IV Vitamin C.
Just look at some of the latest FDA approved drugs for the treatment of cancer.  These new drugs often are approved on the basis of 1 study, have limited long-term follow up, or are even approved under “expedited” means.  Compare and contrast that with that of vitamin C.

Oral Vitamin C versus Intravenous Vitamin C

Why not just use oral Vitamin C?  This gets technical, but an important question to answer.  The simple answer is pharmacokinetics.  Pharmacokinetics is the study of the body’s absorption, distribution, metabolism and the excretion of drugs, which also includes vitamins/supplements.
The perfect example of pharmacokinetics in action is the very powerful antibiotic Vancomycin.  Oral and IV Vancomycin have very different effects because of the different absorption, distribution, metabolism and excretion properties of the IV and oral delivery.
It is not that one delivery method alone is outright better than another, but that the body processes the treatment therapy, the Vancomycin drug in this example, which dictates and effects the therapy effectiveness.  Pharmacokinetics can also apply to vitamins and in this case Vitamin C.
Know this next bit of information and you will know more than most doctors and empower your healing.  Oral Vitamin C is limited by 3 significant factors.

Vitamin C Therapy and Cancer

First, high dose oral Vitamin C is associated with significant gastrointestinal side effects i.e. diarrhea, limiting the ability to achieve high dosing. Second, Vitamin C has a maximum gastrointestinal absorption rate of approximately 200 mg/hour.
Most Vitamin C supplements far exceed 1,000 mg, let alone 200 mg.  If one takes > 200 mg oral Vitamin C, the vast majority of it is flushed out of the body and not used by the body.
Vitamin C Therapy And CancerThird, and probably most important, oral Vitamin C has a very low peak plasma concentration, likely related to the second point.  Oral Vitamin C will not raise plasma concentration significantly higher than 200 microMolar. What level or range of Vitamin C in the blood has been shown to be toxic to cancer cells?
The lowest plasma concentration that has been shown to be toxic to cancer cells is 500 microMolar with the target maximum cancer kill rate in the 10 – 20 millimolar range (see diagram to left from the Riordan Clinic).  Oral Vitamin C has never been shown to achieve the therapeutic, cancer killing blood levels required.
In contrast, IV Vitamin C has been shown to reach peak plasma concentrations of 20-40 millimolar and higher.  That is at least a 20,000 x higher peak blood concentration with IV Vitamin C compared to oral Vitamin C.  That is the power of pharmacokinetics.
Pharmacokinetics is also the reason why two follow up studies (published in 1979 and 1985) to Pauling’s original 1976 research, found no benefit from oral Vitamin C, yet the research on IV Vitamin C that has followed, has repeatedly shown the benefit of IV Vitamin C. It has been 68 years since Vitamin C was first proposed to have benefit in the fight against cancer.  As of the writing of this blog post, 2746 articles on the topic of Vitamin C and cancer were listed on PubMed.
The anti-cancer target range of Vitamin C in the plasma is known and well described.  The anti-cancer target range of Vitamin C can only be achieved by the intravenous route. Pharmacokinetics explains the difference between the anti-cancer benefit of IV Vitamin C with the no anti-cancer benefit of oral Vitamin C.
The level of evidence for the use of IV Vitamin C in the fight against cancer is overwhelming.  The medical community’s ignorance of the issue of Vitamin C and cancer can no longer be accepted and must be rejected.
Patients suffer because of this ignorance. The level of evidence is too strong and too large to remain ignorant.  Ignorance is simply ignoring the evidence available.
Even if physicians and the medical community at large choose to remain ignorant, you are now no longer ignorant on the issue.  You are now informed, equipped and empowered to advocate for your best treatment with Vitamin C
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