Vitamin C Dosing for Treating Cancer

Vitamin C Dosing for Treating Cancer

Vitamin C: low dose, high dose…how about the right dose.

What is the proper dosing strategy of intravenous vitamin C? What is an actual high dose of intravenous vitamin C? What is a low dose of intravenous vitamin C? An even better question would be what is the right dose of intravenous vitamin C? I propose that the right dose is the required dose dictated to achieve the desired effect from vitamin C. A caveat for some perspective, I am the Medical Director at An Oasis of Healing. We are a cancer healing center in the valley of the sun in Arizona. We treat patients with cancer and the vast majority of our patients have advanced cancer. It is through this prism and in this context that I use intravenous vitamin C discussed previously and below.

I have previously highlighted the evidence-based, broad, anti-cancer effects of vitamin C. A brief list of the anti-cancer effects of vitamin C include:

• Cytotoxic (direct cancer killing)
• Anti-proliferative (anti-growth)
• Anti-inflammatory
• Anti-oxidant
• Pro-oxidant
• Immunomodulator
• Anti-lymphangiogenic
• Anti-metastatic
• Alters genetic expression (epigenetics)
• Anti-viral
• Preservation of mitochondrial potential

The specifics of how vitamin C yields these anti-cancer effects is beyond the scope of the blogpost; this post is long enough as is.

Beyond the intended vitamin C desired effect, body weight, initial vitamin C deficiencies, level of inflammation, and tumor burden also play significant roles in the vitamin C dose required. Holistic therapies are not a a one-size-fits-all approach. Many, including physicians, look at holistic therapies through this view. One might think that holistic therapies are analogous to throwing something on the wall and hoping it sticks, or a politician throwing a finger in the air in an attempt to determine the political winds. Nothing could be further from reality. In addition, the misuse or misunderstanding of vitamin C amounts to a one-size-fits-all approach to vitamin that is nothing more than a holistic treatment entrapped in conventional medicine thinking; or worse, profit center driven over purpose driven—this applies to both the dose and duration of intravenous vitamin C.

Whatever the adjective that is given to describe vitamin C, the dose is important. In addition to the right dose, the duration of the delivered dose is also key to achieve effect. It is about both the dose and duration. Whether the dose be an actual low intravenous dose of vitamin C like the 2019 study highlighted below or whether it is a true high dose of intravenous vitamin C with doses up to 300 grams IV given over 24 hours by the historical fathers of high dose vitamin C, I propose that the right dose is the correct dose dependent on the desired effect. The pioneers, Dr. Frederick Klenner and Dr. Robert Cathcart, should be considered the dual father figure-heads of high-dose intravenous vitamin C (HDIVC). They used high-dose intravenous vitamin C in the treatment of tens of thousands of patients with viral infections, pneumonia, encephalitis, bacterial infections, autoimmune disease, and terminal cancer. They recognized that the dose of vitamin C that provides the intended and desired effect is the required dose to achieve the goal—the right dose. The desired effect of intravenous vitamin C (discussed here) is the target. The vitamin C dose is the means to get there. Too low a dose will lead to treatment failure and too high a dose could lead to the potential for increase side effects, though side effects with HDIVC are quite limited with proper awareness and follow up.

This brings me to a March 2019 study, Continuous intravenous vitamin C in the cancer treatment: re-evaluation of a Phase I clinical study, published in Functional Foods in Health and Disease ^[1] . This study followed 24 patients with advanced cancer treated with continuous intravenous vitamin C infusions. The study looked at varying doses of vitamin C: 150 mg/kg/day, 290 mg/kg/day, 430 mg/kg/day, 510 mg/kg/day, and 710 mg/kg/day given over 20-22 hours. Some context here is required to provide clarity. A 150 lb individual at 150 mg/kg/day and 710 mg/kg/day is equivalent to 10 grams and 50 grams respectively. In contrast, a 200 lb individual at the same weight-based daily dosing is 14 grams and 65 grams respectively. These numbers are rounded to the nearest whole number for simplification. This study found that plasma vitamin C leveled off at 1 mM (0.8 – 1.7 mM) with this continuous dosing vitamin C strategy. The ultimate outcome of this continuous vitamin C dosing study was the progression of disease—cancer progression. The authors pointed to several potential reasons for this cancer progression outcome, including increased renal excretion, which resulted in a short vitamin C half-life in the body. This conclusion is wrong.

The outcome of this study is not acceptable! I believe the design of this study destined it to failure. It missed the mark on three very important points:

1. Dose
2. Plasma vitamin C target
3. Half-life

Dose and plasma vitamin C target are intimately intertwined. Previous studies have shown that optimal plasma vitamin C levels that are cytotoxic to cancer cells is 20 – 30 mM (350-450 mg/dl). First, this study only reached an average of 1 mM, far from the 20 mM threshold required to reach the direct anti-cancer killing effects of vitamin C. Hmmm. This is discussed more below. Second, and the cause of the low plasma level, is the dose given. The total daily doses (150 mg/kg/day to 710 mg/kg/day) given at the hourly infusion rates (10 ml/hour to 20 ml/hour) in this study did not achieve therapeutic levels. That is not my interpretation, it is their published data—1 mM. Duration is not enough, just as dose is not enough.

The study missed the dose target. In contrast, you could say that they did get the duration correct. As the authors here highlighted, most physicians that give intravenous vitamin C miss the duration target due to rapid infusion. The IV chair should not be viewed as a profit center, but a position for patient healing. Proper vitamin C dosing requires patience, of which medicine and many are short of these days. This lack of patience results in rapid infusions, which helps to miss the vitamin C therapeutic mark and contributes to the vast majority of side effects associated with intravenous vitamin C. No critique of this study can say the study was short on patience—20-22 hour infusions. However, the dose of vitamin C required to achieved therapeutic plasma levels for advance cancer in this study was far from adequate. As a result, the ultimate finding of disease progression is not surprising. In fact, it could have been predicted. It is important to remember, high tumor burden in advanced cancer requires higher dosing to achieve therapeutic vitamin C levels. In addition, the authors targeted renal excretion (contributor to shorter systemic half-life) as the reasons for the plasma plateau of 1 mM with this dosing regimen; a conclusion that I also believe misses the mark.

What about the half-life of vitamin C? It is an oversimplification to lay the short vitamin C half-life argument at the feet of the kidneys. Just as we are a product of our environment, the half-life of vitamin C is dictated by its environment. Cancer cells selectively increase uptake of vitamin C, compared to healthy cells, due to the presence and activity of glucose transporters (GLUTs) and sodium-dependent vitamin C transporters (SVCTs). More, research points to a different half-life of vitamin C in the different environments, i.e., healthy cells versus cancer cells, in the body. Let me restate this point to be very clear—vitamin C is preferentially absorbed by cancer cells into the tumor microenvironment over healthy cells, it has significantly longer staying power in the cancer cells and tumor microenvironment than non-cancer cells. Yes, you did read that right. The typically documented half-life of vitamin C in the plasma is well established to be a mere 1-2 hours ^[2]. In fact, elimination starts at 17 minutes. In addition, vitamin C in the plasma and normal liver returned to normal in 16 hours ^[3]. In contrast, vitamin C levels remained significantly elevated for up to 48 hours in the tumor microenvironment, indicating an increase in the half-life of vitamin C in cancer cells compared to non-cancer cells ³. Not only does cancer preferentially take up vitamin C, but it also has longer staying power. That is a win, win!

Based on the prior paragraph dealing with the 1/2 life of vitamin C, I believe that this study was on the right track. They recognized the flawed rapid infusion approach used by most physicians (mostly flawed duration). However, they achieved the same non-therapeutic outcome, just due to a different reason—a flawed dose. The study presents the kidneys and vitamin C half-life as some impassible mountain. Work the problem. Sure, the kidneys eliminate excess vitamin C. However, improper dosing results in inadequate plasma vitamin C levels, and a lack of awareness of vitamin C metabolism in healthy cells versus cancer cells all affect vitamin C’s half-life before the kidneys even get involved. In reality, the kidney excretion of vitamin C is minimal in effect; definitely not an insurmountable problem as presented.

I applaud the authors here for working to think outside the box of routine, typical vitamin C administration; but it is about dose, duration, and the context of the cellular environment of the delivered dose that requires a different perspective. Research like this study helps to advance the therapeutic use of vitamin C in cancer, so kudos to the authors for their work.

A review trip through the historical use of intravenous vitamin C will help to provide some insight into the dosing used by true vitamin C pioneers, that include the likes of Nobel prize winners (Linus Pauling) to NASA flight surgeons (Robert Davis), in the medicinal use of intravenous vitamin C for advanced cancer and other illnesses. These pioneers have not been given enough credit for their ground breaking work. I hope this post helps to take a step in the right direction.

The many physicians highlighted below include true vitamin C pioneers, their treatment targets, and dosing used: Dr. Frederick Klenner ^{[4] [5] [6] [7]}, Dr Ewan Cameron ^{[8] [9] [10]}, Dr. Linus Pauling ^{[11] [12]}, Dr’s A. Murata/F. Morishige/H. Yamaguchi ^[13],  Dr. Abram Hoffer ^[14], Dr. Hugh Riordan ^{[15] [16] [17]}, Dr. Robert Cathcart ^{[18] [19] [20]}, and Dr. Richard Davis. Beyond this list, there are many other significant contributors to the use of vitamin C in the treatment of a wide-variety of illnesses. I am sure that history will record many, many more in the years to come.

Physican(s)	Target	IV Dose
Dr. Frederick Klenner	Advanced cancer, wide variety of virus illnesses, pneumonia, autoimmune disease, encephalitis…	Up to 300 grams
Dr. Ewan Cameron/Dr. Linus Pauling	Terminal cancer	10 grams
Dr. Abram Hoffer	Cancer	10 grams
Murata A, Morishige F, Yamaguchi H	Terminal cancer	5-29 grams
Dr. Hugh Riordan	Advanced cancer	50-75 grams
Dr. Robert Cathcart	Advanced cancer, wide variety of virus illnesses, autoimmune disease…	Up to 300 grams
Dr. Richard Davis	Cancer	Up to 300 grams

WHAT IS AN INADEQUATE DOSE?

This is a great question and one that needs to be answered. It is important to realize that inadequate dose is not equal to low dose.  An inadequate dose of vitamin C is any dose or dose delivery that dose not follow known bioavailability or pharmacokinetics. Simply, how does vitamin C get into the body, how does vitamin C travel through the body, and how does vitamin C work. As a result, I believe that any oral vitamin C dosing should be deemed as inadequate dose. In the treatment of cancer and other significant illnesses, any oral dose should be deemed inadequate beyond its use to supplement a primary intravenous vitamin C treatment program. Oral vitamin C can provide a short-lived spike through stomach absorption ^[21], but this falls far short of the minimum levels required (discussed below) to destroy cancer cells. All is not loss with oral vitamin C, the addition of oral vitamin C to an intravenous vitamin C program can help provide an early increase in plasma vitamin C before the big punch with IV vitamin C begins. But, as a whole and individual therapy, oral vitamin C is inadequate.

WHAT IS LOW DOSE?

Any dose that does not achieve a therapeutic level of ascorbic acid (350 mg/dl—450 mg/dl or 20–30 mM) should be considered low-dose. In this context, low-dose includes both the oral or intravenous delivery routes. The 350–450 mg/dl is the optimal therapeutic plasma vitamin C target window described by Dr. Hugh Riordan. Oral dosing of vitamin C NEVER achieves the therapeutic window of 350—450 mg/dl of plasma ascorbic acid. This is in part due to the pharmacokinetics, the reduced bioavailability of oral vitamin C and the down regulation of the vitamin C transporters (SVCT and GLUT) in the gut lining with the higher oral doses. Oral doses typically only reach plasma levels of 70-80 µM ^[22], compared to the > 20,000 µM (20 mM) ^[23] achieved through the intravenous vitamin C delivery. That is a full 50-70 fold increase concentration of vitamin C with intravenous compared to the oral route. Research has shown that 30 grams ^[24] of intravenous vitamin C does not kill most cancer cells. Yet, for cancer, we know that plasma levels of 1000 µM (1 mM) ^[25] of vitamin C is toxic to cancer cells. Thus, 1 mM is the basement floor threshold of desired vitamin C plasma concentration required for minimally effective, anti-cancer treatment with vitamin C. However, 1 mM is no where near optimal. This can only be achieved through intravenous delivery. Even with the newer liposomal vitamin C products that are available to increase bioavailability, maximum levels of 500 µM (compared to 70-80 µM mentioned above) are best, but more reliably 200 µM ^[26] is achieved, which is still far below the desired minimum of 1000 µM and light-years away from the +20,000 µM (20 mM) optimal target range threshold. As stated in the conclusion of the article, Vitamin C pharmacokinetics: implications for oral and intravenous use ^[27], “Intravenous vitamin C may have a role in the treatment of cancer as a result of the plasma concentrations that can be achieved only by this route.”

What about intravenous vitamin C dose? Is there an intravenous vitamin C dose that would be considered low dose? Absolutely! It is important to realize that the intravenous administration of vitamin C does not de facto equal therapeutic dose. Any intravenous dose at 25 grams or less, I would consider being low dose. This fits with the research highlighted above where 30 grams of intravenous vitamin C does not kill most cancer cells ^[28]. For some patients, this low-dose could be as high as 50 grams. From this study, it is clear that 30 grams of vitamin C will fall far short of the optimal 350-450 mg/dl plasma therapeutic window. In addition, I propose that the 2019 article reviewed above was an example of low dose intravenous vitamin C because of their documented low 1 mM plasma levels.

WHAT IS HIGH DOSE?

Even with the historical journey above, it is hard to provide an accurate definition of what high dose intravenous vitamin C is. After all, it was media headlines that said intravenous 1.5 grams vitamin C given three to four times daily was “massive”. Based on our experience at An Oasis of Healing in the treatment of advanced cancer and the historical studies of intravenous vitamin C in the treatment of cancer, viral illnesses, pneumonia, encephalitis highlighted above, the best definition of high dose intravenous vitamin C is a dose that achieves and sustains the most time in the therapeutic plasma window of 350-450 mg/dl (20–30 mM). Research has shown that sick people are depleted of vitamin C ^[29] and simply require higher doses of vitamin C compared to healthy individuals ^[30]. Previous research by Dr. Riordan has shown that doses of 50-75 grams intravenously can achieve this therapeutic target of 350-450 mg/dl critical to the direct cancer cytotoxic effects of vitamin C. It is important to not oversimplify and underestimate the anti-cancer vitamin C effects to just the cytotoxic effects however.

What about the lower doses of intravenous vitamin C used by Dr. Cameron and Dr. Pauling highlighted in the chart above? That is a very good question. I consider their dose and research of vitamin C was low-dose. The lower intravenous vitamin C doses of 10 grams used in Dr. Cameron and Dr. Pauling’s research doesn’t reach the mark of 30 grams highlighted above; also, plasma levels were not evaluated in their research. If 30 grams is documented to not reach optimal plasma levels, it is safe to say that 10 grams is also not going to achieve optimal therapeutic levels either. However, it is likely going to achieve plasma concentrations that are similar to 1000 µM (1 mM), which is far above that obtained with historical oral dosing (70-80 µM) and still above that achieved through the newer liposomal formulations (200-500 µM). To be fair, the probability of achieving optimal plasma vitamin C therapeutic target range with 300 gram IV vitamin C, as performed by Dr. Klenner and Dr. Cathcart, is also unknown. Why? The same lack of published research of plasma levels. BUT, logically, if 50-75 grams is shown to achieve therapeutic levels, then 300 grams will as well. The 300 grams provides more therapeutic time in the target range compared to the lower 50-75 grams, but both are still high-dose. The question then become more of duration to maximize the time in the vitamin C therapeutic window. Dose and duration are both important here.  Beyond the lack of testing to determine the exact vitamin C plasma concentration in older research, many other variables can affect the dose and the ability of intravenous vitamin C to achieve the targeted range, which will be highlighted below.

THE BETTER QUESTION

The better question is, what is the right dose of IV vitamin C? The right dose is, the dose that maximizes the direct and indirect cancer-killing effects, the dose that blocks the inflammation of autoimmune disease or the out of control inflammatory response of the cytokine burst found in COVID19 pneumonia, sepsis, and septic shock, or the dose that aids detoxification…The right dose is simply the dose that provides the appropriate plasma vitamin C levels to achieve the desired effect. There is no way to expect this dose to be the same for each individual or for every condition. Just look at people, no two persons are alike, no two cancers are alike, and no two inflammatory conditions are alike. I think you get the picture. We are beautifully and wonderfully created unique. The one-size-fits-all approach is a fallacy that, unfortunately continues to exist in medicine today. These individual differences are the sources of the potential variables that effect intravenous vitamin C dose and the ability to achieve the therapeutic window. These variables include:

• The health of the individual
• The presence and extent of disease
• The status of vitamin C levels in the body before treatment
• Smoking status
• Amount of cancer in the body (called tumor burden)
• Level of inflammation
• Microenvironments

The healthier the individual, the higher the vitamin C levels in the body will be and the lower the dose required to achieve the higher plasma levels mentioned above. In contrast, cancer is a vitamin C deficient state ^{[31] [32]}. The presence of cancer, increased tumor burden in advanced cancer, and high inflammation in the body results in significantly lower vitamin C levels which requires significantly higher doses of intravenous vitamin C to reach the targeted range of 350-450 mg/dl. One cannot simply throw vitamin C at all the people of the world with all their different levels of health or dis-aise and expect similar results. Yet, that is surprisingly what is done.

A one-size-fits-all approach never works. This logic also applies to the use of intravenous vitamin C. High dose, low dose, massive dose, whatever dose, need not apply. Only, the right dose for each individual that will achieve the intended anti-cancer effects, the anti-inflammatory effects, the anti-viral effects (including COVID19) is the right dose, whether low, high, or “massive”. However, this must include an awareness of dose, duration, and the environment in to which the vitamin C is given.

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^[1] Mikirova, Nina & Casciari, Joseph & Hunninghake, Ronald. Continuous intravenous vitamin C in the cancer treatment: re- evaluation of a Phase I clinical study. Functional Foods in Health and Disease. 2019;9:180-204. 10.31989/ffhd.v9i3.590.

^[2] Padayatty SJ, Sun H, Wang Y, Riordan HD, Hewitt SM, Katz A, Wesley RA, Levine M. Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann Intern Med. Apr 2004;140(7):533-7. doi: 10.7326/0003-4819-140-7-200404060-00010.

^[3] Campbell EJ, Vissers MCM, Wohlrab C, Hicks KO, Strother RM, Bozonet SM, Robinson BA, Dachs GU. Pharmacokinetic and anti-cancer properties of high dose ascorbate in solid tumours of ascorbate-dependent mice. Free Radic Biol Med. Oct 2016;99:451-462. doi: 10.1016/j.freeradbiomed.2016.08.027.

^[4] Klenner FR. The role of ascorbic acid in therapeutics. (Letter) Tri-State Medical J. Nov 1955; 34.

^[5] Klenner FR. Massive Doses of Vitamin C and the Virus Diseases. South Med J. Ap 1951;113(4):101-7. PMID: 14855098.

^[6] Klenner FR. The Treatment of Poliomyelitis and Other Virus Diseases with Vitamin C. South Med J. July 1949; 3(7):209-214.

^[7] Klenner FR. Observations on the dose and administration of ascorbic acid when employed beyond the range of a vitamin in human pathology. J Applied Nutrition. 1971; 23:3-4.

^[8] Cameron, E., Pauling, L. & Leibovitz, B. Ascorbic acid and cancer, a review. Cancer Res. 1979;(39):663–81.

^[9] Cameron E, Rotman D. Ascorbic acid, cell proliferation, and cancer. Lancet. 1972;1:542.

^[10] Cameron E, Campbell A. The orthomolecular treatment of cancer, II: clinical trial of high-dose ascorbic acid supplements in advanced human cancer. Chem Biol Interact. 1974;9:285–315.

^[11] Cameron, E. & Pauling, L. Supplemental ascorbate in the supportive  treatment  of  cancer:  Prolongation  of  survival  times  in terminal human cancer. PNAS USA. 1976; (73):3685–9.

^[12] Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: reevaluation of prolongation of survival times in terminal human cancer. Proc Natl Acad Sci U S A. 1978;75(9):4538–4542. doi:10.1073/pnas.75.9.4538

^[13] Murata A, Morishige F, Yamaguchi H. Prolongation of survival times of terminal cancer patients by administration of large doses of ascorbate. Int J Vitam Nutr Res Suppl. 1982;23:103-13.

^[14] Hoffer A & Pauling L. Hardin Jones biostatistical analysis of mortality data for a second set of cohorts of cancer patients with a large fraction surviving at the termination of the study and a comparison of survival times of cancer patients receiving large regular oral doses of vitamin C and other nutrients with similar patients not receiving these doses. J of Orthomolecular Medicine. 1993;8:1547-167.

^[15] Riordan H. D., Riordan N. H., Jackson J. A., Casciari J. J., Hunninghake R., Gonzalez M. J., et al. Intravenous vitamin C as a chemotherapy agent: a report on clinical cases. PR Health Sci. J. 2004;23:115–118.

^[16] Riordan H. D., Casciari J. J., Gonzalez M. J., Riordan N. H., Miranda-Massari J. R., Taylor P., et al. A pilot clinical study of continuous intravenous ascorbate in terminal cancer patients. PR Health Sci. J. 2005;24:269–276.

^[17] Riordan, H. et al. Intravenous ascorbic acid: protocol for its application and use. PR Health Sci. J. 2003;(22):225–32.

^[18] Cathcart R. Vitamin C in the treatment of Acquired Immune Deficiency Syndrome (AIDS).

Medical Hypothesis. Aug 1984;14(4):423-433.

^[19] Cathcart R. A Unique Function for Ascorbate. Medical Hypothesis. May 1991;35:32-37.

^[20] Cathcart RF. Vitamin C, titrating to bowel tolerance, anascorbemia, and acute induced scurvy. Med Hypotheses. 1981;7:1359-76.

^[21] Fonorrow O, Hickey S. Unexpected early response in Oral Bioavailability of Ascorbic Acid. Townsend Letter. March 13, 2020.

^[22] Levine M, Conry-Cantilena C,  Wang  Y.  et al. Vitamin  C pharmacokinetics in healthy volunteers: Evidence for  a recommended dietary allowance. PNAS. 1996;93:3704–3709.

^[23] Duconge J1, Miranda-Massari JR, Gonzalez MJ, Jackson JA, Warnock W, Riordan NH. Pharmacokinetics of vitamin C: insights into the oral and intravenous administration of ascorbate. P R Health Sci J. Mar 2008;27(1):7-19.

^[24] Riordan NH, Riordan HD, Casciari JJ. Clinical and Experimental Experiences with Intravenous Vitamin C. J of Orthomolecular Medicine 2000;15(4):201-213.

^[25] Chen Q, Espey MG, Krishna MC, Mitchell JB, Corpe CP, Buettner GR, Shacter E, Levine M.  Ascorbic  acid at pharmacologic concentrations selectively kills cancer cells: ascorbic acid as a pro-drug for hydrogen peroxide delivery to tissues. Proc Natl  Acad  Sci USA 2005;102:13604-13609.

^[26] Davis, J.L.; Paris, H.L.; Beals, J.W.; Binns, S.E.; Giordano, G.R.; Scalzo, R.L.; Schweder, M.M.; Blair, E.; Bell, C. Liposomal-encapsulated Ascorbic Acid: Influence on Vitamin C Bioavailability and Capacity to Protect Against Ischemia-Reperfusion Injury. Nutr. Metab. Insights. 2016;9:25–30.

^[27] Padayatty SJ, Sun H, Wang Y, et al. Vitamin C Pharmacokinetics: Implications for Oral and Intravenous Use. Ann Intern Med. 2004;140:533–537. doi: https://doi.org/10.7326/0003-4819-140-7-200404060-00010

^[28] Riordan NH, Riordan HD, Casciari JJ. Clinical and Experimental Experiences with Intravenous Vitamin C. J of Orthomolecular Medicine 2000;15(4):201-213.

^[29] Grosso G, Bei R, Mistretta A, Marventano S, Calabrese G, Masuelli L, Giganti MG, Modesti A, Galvano F, Gazzolo D. Effects of vitamin C on health: a review of evidence. Front Biosci (Landmark Ed). Jun 2013;18:1017-29. doi: 10.2741/4160.

^[30] Carr, A.C.; Rosengrave, P.C.; Bayer, S.; Chambers, S.; Mehrtens, J.; Shaw, G.M. Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes. Crit. Care. 2017; 21;300.

^[31] Gillberg L, Ørskov AD, Liu M, Harsløf LBS, Jones PA, Grønbæk K. Vitamin C – A new player in regulation of the cancer epigenome. Semin Cancer Biol. Aug 2018;51:59-67. doi: 10.1016/j.semcancer.2017.11.001.

^[32] Carr AC, Frei B. Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans. Am J Clin Nutr 1999;69:1086-107.