Vitamin C, Ascorbic Acid vs Sodiumascorbate

[linusbert]

i did a short ai session aout which form is better for me because i somehow have the feeling ascorbic acid sends my immunesystem into battle mode, making things worse, while the ascorbate seams to be better:​

Optimized Vitamin C Dosing and Form Selection under Oxidative Stress​

1. Optimal Absorption​

• The human body absorbs nearly 100% of oral vitamin C doses up to 200 mg at a time.
• To maximize absorption and minimize renal excretion, a split-dose protocol is recommended:
  • 200 mg per dose, 5 times daily (e.g. every 3–4 hours)
  • Total: 1 000 mg/day, almost fully absorbed.

2. Reduced Oxalate Risk​

• High single doses of vitamin C (≥1 000 mg) can result in the formation of oxalate, a metabolic byproduct that may burden the kidneys or contribute to kidney stones.
• With the 5 × 200 mg/day regimen, plasma levels stay below the renal threshold, and oxalate formation is negligible.
• This regimen is considered safe even for individuals with oxalate sensitivity.

3. Distribution After Absorption​

• After absorption in the small intestine, vitamin C enters the bloodstream and is transported to key tissues:
  • High-priority organs include the adrenal glands, brain, immune cells (especially leukocytes), liver, and eyes.
  • Intracellular uptake is mediated by active transporters (SVCT2), which concentrate vitamin C in these tissues well above plasma levels.

4. Ascorbic Acid vs. Ascorbate (e.g. Sodium Ascorbate)​

• Ascorbic acid (unbuffered, acidic form) may transiently stimulate certain immune responses more than ascorbate, likely due to local pH effects or redox-sensitive signaling pathways.
• However, ascorbate (e.g. sodium ascorbate) is:
  • pH-neutral and better tolerated (especially at high or prolonged doses),
  • more stable under physiological conditions,
  • less irritating to the GI tract, and
  • equally effective as an antioxidant, since both forms ultimately act via the ascorbate anion.

5. Recommendation under Oxidative Stress​

For individuals with high oxidative load (e.g., in chronic inflammation, mitochondrial dysfunction, toxic exposure, CFS/ME), the preferred form and protocol is:

• Buffered ascorbate (e.g. sodium ascorbate)
• Split dosing: 200 mg every 3–4 hours
• Ensures stable plasma levels, maximal cellular uptake, minimal kidney load, and low risk of oxalate accumulation

 

[linusbert]

i also read that citrates are binding with free calcium and thus prevent oxalate formation in kidneys. so if people go really high dose they might have benefits with magnesiumcitrate.
if someone has concerns about oxalate with high dose vitamin c.

 

[bad1080]

• Ascorbic acid (unbuffered, acidic form) may transiently stimulate certain immune responses more than ascorbate, likely due to local pH effects or redox-sensitive signaling pathways.

i had a day with notably enhanced cell respiration after a high dose of ascorbic acid but i could never replicate it. i don't understand how "pH effects" could possibly be the explanation as you constantly digest your own stomach acid (which for me is at pH1).

 

[pamojja]

The human body absorbs nearly 100% of oral vitamin C doses up to 200 mg at a time.

In the 1996 NIH absorption study only up to 3000mg was tested, and extrapolated to higher doses;

https://www.wholefoodsmagazine.com/...earch-on-optimizing-blood-and-cellular-levels In a recent column, I discussed Dr. Hickey’s point that there is a widely quoted dogma from a 1996 NIH study which claimed that the blood can become “saturated” with vitamin C at a single dose of 200 milligrams (4). Dr. Hickey had pointed out that this 1996 NIH study’s own data even showed this is not so (5). The figure that I included in the March 2018 column is shown again as Figure 1 here. It is based on page 82 of reference 6.

This paper 30 years later is still misinterpreted. 200 mg doses every few hours create a plasma concentration of about 60-70 µM/L at 100% absorption. 3 g spaced out will give plasma concentration of above 200-250 µM/L. 3-5 times higher plasma levels! (but relative to intake at much less percentage absorption).

The only study to my knowledge, which actually tested higher ascorbic acid intake of up to 20 g/d had interesting outcomes:

Journal of the New Zealand Medical Association, 23-August-2002, Vol 115 No 1160

Glycohaemoglobin and ascorbic acid

Copplestone et al1 (http://www.nzma.org.nz/journal/115-1157/25/) identified misleading glycohaemoglobin (GHb) results due to a haemoglobin variant (Hb D Punjab) and listed a number of other possible causes for such false results (ie, haemolytic anaemia, uraemia, lead poisoning, alcoholism, high-dose salicylates and hereditary persistence of foetal haemoglobin).

We have observed a significant "false" lowering of GHb in animals and humans supplementing ascorbic acid (AA) at multigram levels. Mice receiving ~7.5 mg/d (equivalent to > 10 g/day in a 70 kg human) exhibited no decrease in plasma glucose, but a 23% reduction in GHb.2 In humans, supplementation of AA for several months did not lower fasting plasma glucose.3,4 We studied 139 consecutive consenting non-diabetic patients in an oncology clinic. The patients had been encouraged as part of their treatment to supplement AA. Self-reported daily intake varied from 0 to 20 g/day. The plasma AA levels ranged from 11.4 to 517 µmol/L and correlated well with the reported intake. Regression analysis of their GHb and plasma AA values showed a statistically significant inverse association (eg, each 30 µmol/L increase in plasma AA concentration resulted in a decrease of 0.1 in GHb).

A 1 g oral dose of AA can raise plasma AA to 130 µmol/L within an hour and such doses at intervals of about two hours throughout the day can maintain ~230 µmol AA/L.5 Similar levels could also be achieved by use of sustained-release AA tablets. This AA concentration would induce an approximate 0.7 depression in GHb. The GHb assay used in our study, affinity chromatography, is not affected by the presence of AA.3 Thus, unlike the case with Hb D Punjab, our results were not caused by analytical method artifact. More likely, the decreased GHb associated with AA supplementation appears related to an in vivo inhibition of glycation by the elevated plasma AA levels, and not a decrease in average plasma glucose.3 If this is true, the effect has implications not only for interpretation of GHb but also for human ageing, in which glycation of proteins plays a prominent role in age-related degenerative changes.

A misleading GHb lowering of the magnitude we observed can be clinically significant. Current recommendations for diabetics suggest that GHb be maintained at 7, a level that is associated with acceptable control and decreased risk of complications; when GHb exceeds 8, re-evaluation of treatment is necessary.6 Moreover, relatively small increases in average blood sugar (ie, GHb) can accompany adverse reproductive effects. A difference in mean maternal GHb of 0.8 was found for women giving birth to infants without or with congenital malformations.7 In either of these circumstances, an underestimation of GHb could obscure the need for more aggressive intervention.

Vitamin usage is common in New Zealand and after multivitamins, AA is the most often consumed supplement.8 Moreover, diabetics are encouraged to supplement antioxidants, including AA. Thus, it seems prudent for primary care health providers to inquire regarding the AA intake of patients, especially diabetics, when using GHb for diagnosis or treatment monitoring.

Cheryl A Krone
Senior Research Scientist
John TA Ely
Director
Applied Research Institute
PO Box 1925
Palmerston North

References:

1. Copplestone S, Mackay R, Brennan S. Normal glycated haemoglobin in a patient with poorly controlled diabetes mellitus and haemoglobin D Punjab: implications for assessment of control. NZ Med J 2002;115(1157). URL: http://www.nzma.org.nz/journal/115-1157/25/
2. Krone CA, Ely JTA. Vitamin C and glycohemoglobin revisited. Clin Chem 2001;47(1):148.
3. Davie SJ, Gould BJ, Yudkin JS. Effect of vitamin C on glycosylation of proteins. Diabetes 1992;41(2):167–73.
4. Paolisso G, Balbi V, Bolpe C, et al. Metabolic benefits deriving from chronic vitamin C supplementation in aged non-insulin dependent diabetics. J Am Coll Nutr 1995; 14(4):387–392.
5. Lewin S. Vitamin C: Its Molecular Biology and Medical Potential. New York: Academic Press; 1976.
6. Kenealey T, Braatvedt G, Scragg R. Screening for type 2 diabetes in non-pregnant adults in New Zealand: practice recommendations. NZ Med J 2002;115(1152):194–6.
7. Rosenn B, Miodovnik M, Dignan PS, et al. Minor congenital malformation in infants of insulin-dependent diabetic women: association with poor glycemic control. Obstet Gynecol 1990;76:745–9.
8. Allen T, Thomson WM, Emmerton LM, Poulton R. Nutritional supplement use among 26-year-olds. N Z Med J 2000;113(1113):274–7

(Emphasis added by me)

Therefore, with 5 daily doses of 200 mg (total 1 g(d), a steady plasma level of 60-70 µM/L is maintained.
With 5 daily doses of 3000 mg (total 15 g/d), a steady plasma level of 200-250 µM/L is maintained.
And 5 daily doses of 4000 mg (total 20 g/d), a steady plasma level of 400-500 µM/L seems feasible (thereby reducing HbA1C as potent as anti-diabetic drugs) according to the NewZealand study.

Bowel tolerance permitting (mine goes up to 50 g a day).

Ensures stable plasma levels, maximal cellular uptake, minimal kidney load, and low risk of oxalate accumulation

Misunderstood. Higher doses taken throughout the day - like 20 g total - also ensure stable plasma levels (except during sleep), about 7 times higher plasma uptake (about cellular one doesn't have to worry, brain tissue for example contains 15 times higher ascorbate than plasma levels), and only higher oxalate excretion was shown in studies. But until today, not one case without better explaining comorbidities, for kidney stones.

 

[linusbert]

i was missing you, recently wanted to talk about citric acid preventing oxalatcrystal formation. do you take magnesiumcitrate or similiar while you also take high dose vitamin c?
we had this discussion not long ago about oxalate and vitamin c.

how much vitamin c and what scheme would you recommend to someone with copper deficiency?

 

[linusbert]

i had a day with notably enhanced cell respiration after a high dose of ascorbic acid but i could never replicate it. i don't understand how "pH effects" could possibly be the explanation as you constantly digest your own stomach acid (which for me is at pH1).

thats interesting question. i also never understood how it makes sense. when i take ascorbic acid in small amounts i already get diarrhea. but when i do sodiumascorbate i can take like 5-10g and not get diarrhea.
i also noticed this for some other acidic stuff.
i mean, a weak acid meets a strong acid in the stomach.. how can this be of any relevance?
maybe the kind of acid plays a role. maybe HCL is fine, but other forms trigger some kind of immune or mcas stress. (and indeed, if i take betain HCL i do not get diarrhea!)

 

[pamojja]

do you take magnesiumcitrate or similiar while you also take high dose vitamin c?

I do get various amounts of citrate (from Potassium- and Mg-citrate mainly). Per year from none up to 3.9 g/d. In average 1.4 g/d in average for the last 16 years.

we had this discussion not long ago about oxalate and vitamin c.

From http://www.doctoryourself.com/titration.html - excerpts:

INTRODUCTION​

Over the past ten-year period I have treated over 9,000 patients with largedoses of vitamin C (Cathcart 1, 2, 3, 4, 5). The effects of this substancewhen used in adequate amounts markedly alters the course of many diseases.Stressful conditions of any kind greatly increase utilization of vitamin C. Ascorbate excreted in the urine drops markedly with stresses of any magnitude unless vitamin C is provided in large amounts. However, a more convenient and clinically useful measure of ascorbate need and presumably utilization is the BOWEL TOLERANCE.

COMPLICATIONS​

It is my experience that ascorbic acid probably prevents most kidney stones. I have had a few patients who had had kidney stones before starting boweltolerance doses who have subsequently had no more difficulty with them. Acute and chronic urinary tract infections are often eliminated; this factmay remove one of the causes of kidney stones. Six patients have had mildpain on urination; five of these patients were over fifty and none had stones.

Three out of thousands had a light rash which cleared with subsequent doses. It was difficult to evaluate the cause of this because of concomitant infections. Several patients had discoloration of the skin under jewelryof certain metals. A few patients complaining of small sores in the mouth with the taking of small doses of ascorbate had them clear with bowel tolerancedoses.

Patients with hidden peptic ulcers may have pain, but some are benefitted .Mineral ascorbates can be used for maintenance doses in these cases. Two patients who had mild epigastric discomfort with maintenance doses of ascorbic acid who after being given ascorbate by vein for several days were thenable to tolerate the acid orally.

It is my experience that high maintenance doses reduce the incidence of gouty arthritis. I have not seen difficulties with giving large amountsof ascorbic acid to patients with gout. Almost all my patients have been Caucasian, so I have no comment on the report that ascorbate can causecertain blood problems in certain non-white groups (30).

There has been no clinical evidence as Herbert and Jacob (31) suspectedthat ascorbic acid destroys vitamin B12.

If maintenance doses of ascorbic acid in solution are used over verylong periods of time I would rinse the teeth after each dose. I would notbrush my teeth with calcium ascorbate. ...

So out of another 9000 patients, we don't know their citrate intake (from food, for example), the few patients who actually suffered from kidney stones, subsequently to extraordinary high ascorbic acid intake didn't.

As I already wrote, I suspect the increased excretion of oxalate, probably a very beneficial effect against oxalate kidney stones. Beside assisting in the reversal of my CKD stage 1.

how much vitamin c and what scheme would you recommend to someone with copper deficiency?

First read here, what I just posted: https://forums.phoenixrising.me/threads/high-dose-vitamin-c-mystery.93203/page-3#post-2477035

Again, due to biochemical individuality, there is no recommended dose in every case. What I did however repeatedly recommend:

An advise first: I made the experience that it is always more efficient and safe to start with the lowest possible dose of a new supplement, then increase gradually over months and years. And better start with one agent at a time.

• You could catch an always possible allergic reaction early on, and not as severe as at full dose. Which also could come from other ingredients in a supplement. And are able to rectify the offender right away.
• You will know at exactly which dose what effect to expect. There could be a marked U-curve response, and sometimes more is not better. If it still would be, you'll find the exact effective dose eventually. And don't waste your money.
• Increasing one nutrient to high dose will invariably increase the need for others involved with the same metabolic pathway. By increasing slowly you'll catch them early on, were they are still easier to correct.
• Supplementing with many chronic diseases and biochemical-individuality is a life-long project. You don't take the pills and you're done. You probably will adjust it for the rest of your life. Because specific deficiencies will have improved, and other worsened. So take your time to find the most effective protocol for your preconditions and situation.

While doing actual lab-tests to see critical nutrients stay in range, ie. serum 25(OH)D, ferritin, retinol and retinol binding protein, copper, selenium, electrolytes, .. additional to regular tests like CBC, kidney and liver functions, hormones, etc.

With copper deficiency, as with too high serum levels (as was and is still the case with me, and in average of 25 g/d of ascorbic acid for 16 years), do monitor copper levels. Mine didn't lower from excessive at all.

 

[pamojja]

i also never understood how it makes sense. when i take ascorbic acid in small amounts i already get diarrhea. but when i do sodiumascorbate i can take like 5-10g and not get diarrhea.

Also from http://www.doctoryourself.com/titration.html

It is important for the physician to understand the principles of treating this vast majority of tolerant persons. Patients frequently underdose themselves and need professional guidance to push the doses to effective levels. The small number of persons, especially elderly persons, intolerant to oral doses are in my experience able to take intravenous ascorbate without difficulties. Additionally, patients with severe problems may need to be treated intravenously if very high doses will have to be maintained for some time for adequatesuppression of symptoms.

Usually oral bowel tolerance doses will reverse hepatitis rapidly. Stoolsregularly return to normal color in 2 days. It generally takes about 6 days for the jaundice to clear, but the patient will feel almost well after4 to 5 days. Because of the diarrhea caused by the disease, intravenous ascorbate may need to be used in very severe cases. Often large doses of ascorbic acid, taken orally despite diarrhea, will cause a paradoxical cessation of the diarrhea.

Frequently I have the patient take oral doses of ascorbic acid at the same time he is taking intravenous sodium ascorbate. Bowel tolerance is actually increased by concomitant use of intravenous ascorbate. Care and experience is necessary with concomitant use because tolerance drops precipitously when the intravenous infusion is discontinued.

One reason for low oral tolerance of ascorbic acid is good health. Since I can't assume this in your case, instead I suspect very severe deficiency due to taxing conditions.

 

[linusbert]

yes, but i do tolerate high dose ascorbate. the problem is only with ascorbic acid.
a deficiency might indeed be severe. the first time i crashed and got into the clinic they did do vitamin C , and it was severe deficient. doubt this changed much.

as i do not tolerate ascorbic acid, and my sodiumascorbate provider did change to bad quality i do not tolerate either. i found now another vendor which seams fine. i want to get at it again. but i have this persistent copper deficiency and i do not want to aggravate it any more.
in my case, i am low in serum copper, urine copper, hair copper, coeruloplasmin... just everything low.
but when i take copper or iron i get really bad nausea and spinning issues. like after the worst alcohol hangover. i suspect it being oxidation due to lack of antioxidants and somehow a fenton reaction going on. because 6 years ago i could take iron without spinning issues. copper though also didnt work back then.

i did read chapter 10, but i do not understand how it helps me with the copper issue?

 

[lyran]

If you use ascorbic acid powder, you can put a bit of sodium bicarbonate into glass of water with it to turn it into sodium ascorbate.

 

[bad1080]

has anybody with me-cfs gotten better with high dose vit.c?

 

[pamojja]

as i do not tolerate ascorbic acid, and my sodiumascorbate provider did change to bad quality i do not tolerate either.

you can put a bit of sodium bicarbonate into glass of water with it to turn it into sodium ascorbate.

To be precise, Up to half the weight of ascorbic acid as sodium bicarbonate is mixed in a glass of water, to make it pH neutral sodium ascorbate out of both. Much cheaper too.

has anybody with me-cfs gotten better with high dose vit.c?

I have got better. PEMs ceased 7 years ago, with high dose ascorbic acid, along with comprehensive supplementation and life-style changes. Though vitamin C certainly wasn't responsible alone, if I look at my varying intakes during the last 16 years of all supplements - it had been highest then - and 3 years earlier during another remarkable remission from a walking disability from PAD. Again 3 years earlier with a remission from symptoms of COPD stage1.

Which proofs nothing, other than 3 improbable remissions correlating with the highest vitamin C intakes (clearly above my average 25 g/d intake during 16 years). No other supplement's highest intakes correlates with all 3 remissions. Vitamin B5 for example, does with 2 only.

All with the understanding of biochemical individuality, as pointed out in this post: https://forums.phoenixrising.me/threads/high-dose-vitamin-c-mystery.93203/page-3#post-2477035 - where after one might understand why for some it does wonders, and for others naught.

i did read chapter 10, but i do not understand how it helps me with the copper issue?

Its last words were:

It is likely that many of the low excretors of ascorbic acid shown in the illustration on page 114 have a genetic defect such that a low intake of vitamin C is more damaging to them than to other people. For them a larger intake of the vitamin may be essential if they are to avoid a short and miserable life. At the present time it is very difficult to determine the nutritional needs of an individual person except by trial of various intakes, but we may hope that reliable clinical tests that show the individual needs will be developed before long.

And therefore would regularly monitor copper lab tests. To assure vitamin C intake wouldn't make it worse. With tiny, with higher doses, or none too.

 

[bad1080]

I have got better. PEMs ceased 7 years ago, with high dose ascorbic acid, along with comprehensive supplementation and life-style changes. Though vitamin C certainly wasn't responsible alone, if I look at my varying intakes during the last 16 years of all supplements - it had been highest then - and 3 years earlier during another remarkable remission from a walking disability from PAD. Again 3 years earlier with a remission from symptoms of COPD stage1.

thanks for the reply! like i said i had one day of remission (or whatever you wanna call it) on maybe 2-3g but it was not to be replicated. and after a while of daily doses i couldn't stand the acidity any longer, so i switched to sodium ascorbate.

 

[pamojja]

i had one day of remission (or whatever you wanna call it)

I would call it temporary improvement. Don't think it makes much sense to speak of remission, if an improvement hasn't stayed for at least a year. Better still 5 years.

No other supplement's highest intakes correlates with all 3 remissions. Vitamin B5 for example, does with 2 only.

Actually didn't check carefully enough. If I add vitamin B5 in the form of pantethine, then it correlates with all 3 remissions too. However, many other nutrients didn't show such distinct intake peaks, due to being increased more gradually, and thereby less obvious correlated with the 3 remission over 9 years too.

Vitamin C and vitamin B5 are different, in that keeping such high intakes well above 25 g/d is difficult with the former - because it necessitates such a high water-intake (=frequent urination+disrupted sleep)- and the latter is simply too expensive, to always keep taking it above 2 g/d.

 

[pamojja]

After absorption in the small intestine, vitamin C enters the bloodstream and is transported to key tissues:

• High-priority organs include the adrenal glands, brain, immune cells (especially leukocytes), liver, and eyes.
• Intracellular uptake is mediated by active transporters (SVCT2), which concentrate vitamin C in these tissues well above plasma levels.

Actually quite amazing, how many times more organ tissue than plasma is able to contain:

Table 9.312 Human tissue & fluid ascorbic acid concentrations

Organ/Tissue	Vitamin C Concentration*	Organ/Tissue	Vitamin C Concentration*
Pituitary Gland	40-50	Lungs	7
Adrenal Gland	30-40	Skeletal Muscle	3-4
Eye Lens	25-31	Testes	3
Liver	10-16	Thyroid	2
Brain	13-15	Cerebrospinal Fluid	3.8
Pancreas	10-15	Plasma	0.4-1
Spleen	10-15	Saliva	0.1-9.1
Kidneys	5-15

* mg/100 g wet tissue, mg/100 mL fluids

How does the body accumulate such high levels of vitamin C? There are 2 primary mechanisms:

1. Ascorbic Acid (Ascorbate) uptake using sodium-dependent vitamin C transporter (SVCT) 1 or 2
2. Ascorbic Acid (Ascorbate) Recycling

 

[linusbert]

this saturation table also gives a idea which organs will suffer most from a deficiency.


i had today a ai discussion about pro oxidative situation with vitamin c supplementation. fenton reactions with iron and copper which can set off a chain reaction under bad conditions. leading to more stress then if no VC was actually given.
interesting in cases of too much free iron/copper.

Spoiler

The pro-oxidant potential of ascorbate (vitamin C) arises under specific biochemical conditions, particularly in the presence of free transition metals like iron (Fe³⁺/Fe²⁺) and copper (Cu²⁺/Cu⁺). Although ascorbate is a well-known antioxidant, under certain conditions it can participate in redox cycling, producing reactive oxygen species (ROS).

---

1. Mechanism of Pro-oxidant Action​

Ascorbate acts as a reducing agent:

• Reduces Fe³⁺ → Fe²⁺ and Cu²⁺ → Cu⁺
• The reduced metal (Fe²⁺ or Cu⁺) then reacts with hydrogen peroxide (H₂O₂) in Fenton reactions, generating highly reactive hydroxyl radicals (•OH):

Fenton-type reaction (with iron or copper):​

Fe2++H2O2→Fe3++⋅OH+OH−\text{Fe}^{2+} + \text{H}_2\text{O}_2 \rightarrow \text{Fe}^{3+} + \cdot\text{OH} + \text{OH}^-Fe2++H2O2→Fe3++⋅OH+OH−Cu++H2O2→Cu2++⋅OH+OH−\text{Cu}^{+} + \text{H}_2\text{O}_2 \rightarrow \text{Cu}^{2+} + \cdot\text{OH} + \text{OH}^-Cu++H2O2→Cu2++⋅OH+OH−
These hydroxyl radicals are extremely reactive, causing lipid peroxidation, protein oxidation, and DNA damage.

---

2. Conditions Under Which This Occurs​

• High doses of ascorbate (>500–1000 mg/day), particularly intravenous doses
• Elevated free (unbound) iron or copper, as seen in:
  • Iron overload (e.g., hemochromatosis)
  • Wilson’s disease or disrupted copper metabolism
  • Localized tissue injury or hemorrhage
• Low levels of protective antioxidants (e.g., glutathione, catalase, superoxide dismutase), as may occur with SOD2 deficiency

---

3. Physiological vs. Pharmacological Contexts​

• Physiological context:
  • In normal nutrition, ascorbate acts almost exclusively as an antioxidant.
  • Free transition metals are minimal due to tight binding by proteins (transferrin, ceruloplasmin, ferritin).
• Pharmacological or pathological context:
  • In cancer therapy, high-dose IV ascorbate (10–100 g) exploits its pro-oxidant effect to selectively kill tumor cells through oxidative stress.
  • In disorders of iron or copper overload, oral ascorbate may enhance metal-catalyzed oxidative injury.

---

4. Experimental Evidence​

• In vitro: Ascorbate + free copper/iron → oxidative DNA and lipid damage
• In vivo (rodents): High-dose ascorbate + iron leads to tissue oxidative injury
• Clinical: Cancer trials using IV ascorbate observe pro-oxidant cytotoxicity in tumor tissue, sparing normal cells (due to differential metal availability and antioxidant defenses)

---

5. Implications​

• In copper-deficient or copper-impaired individuals with abnormal copper trafficking (e.g., unbound Cu²⁺), high ascorbate may catalyze ROS formation.
• With SOD2 polymorphism (as in your case), mitochondrial oxidative stress is already elevated, increasing susceptibility to ascorbate-induced ROS if free copper is present.

---

Summary Table​

Context	Ascorbate Role	Risk of Pro-oxidant Effect
Normal diet	Antioxidant	Low
High-dose oral (>1 g/day)	Mixed (depends on metal status)	Moderate, if iron/copper unbound
IV high-dose (≥10 g)	Pro-oxidant (therapeutic)	High in cancer therapy
Iron/copper overload	Pro-oxidant	High
SOD2 impairment	Sensitive to ROS	Moderate–high

---

In conclusion, ascorbate becomes pro-oxidant primarily in the presence of free iron or copper and when antioxidant defenses are impaired. In SOD2 homozygotes with possible mismanaged copper, even moderate oxidative potential from high-dose ascorbate may be clinically relevant.

 

[pamojja]

I have too high free copper. And despite 25 g/d of ascorbic acid for 16 years experienced 3 improbable remissions. Only benefits in my case. I let perpexity.ai explain:

No published human study has conclusively shown that oral ascorbic acid at doses above 1 g/day, even in the presence of high unbound copper or iron, causes clinically significant pro-oxidant damage or adverse effects in humans. The concern about ascorbate's pro-oxidant potential in the presence of free transition metals is based primarily on in vitro experiments and animal studies, not on direct evidence from human trials.
Key findings from the literature:

• In vitro and animal studies:
  Ascorbic acid can act as a pro-oxidant in the presence of free copper or iron, leading to oxidative DNA damage and protein oxidation in cell cultures and in animal models12. For example, a 2023 mouse study showed that oral administration of ascorbic acid combined with copper induced systemic oxidative stress and some organ injury, but this was not observed with ascorbic acid alone2.
• Human studies:
  Reviews and studies specifically addressing high-dose oral ascorbic acid in humans with elevated unbound metals have generally not found increased oxidative damage. A review by Gerster (1999) concluded that, while ascorbic acid can act as a pro-oxidant in vitro, its major function in the living organism is antioxidant, and high intakes have not been found to increase oxidative damage in humans—even in those with high iron stores5. Similarly, a 2023 review states that the pro-oxidant effects of vitamin C are typically observed only at very high doses and are not a concern for most individuals6.
• Clinical experience:
  Your personal experience of significant health improvements (remission of PAD, COPD, and PEM) while taking 25 g/day of ascorbic acid for 16 years, despite high serum and whole blood copper, aligns with the general scientific consensus that high-dose vitamin C is not harmful in most cases and may even be beneficial, except in rare pathological contexts56.

Summary Table of Evidence

Context	Evidence of Harm in Humans?	Source Type
In vitro (cells)	Yes, with free metals	1
Animal (mice)	Yes, with added metals	2
Human (high-dose oral)	No clear evidence	56

Conclusion:
There is no human study demonstrating that oral ascorbic acid >1 g/day, even with high unbound metals, causes harm or pro-oxidant effects in humans. Most evidence for pro-oxidant risk comes from in vitro or animal research, not from clinical trials or epidemiological studies in humans56. Your positive experience is consistent with the available human data.

Citations:​

1. https://pubmed.ncbi.nlm.nih.gov/20213077/
2. https://pmc.ncbi.nlm.nih.gov/articles/PMC9856059/
3. https://www.sciencedirect.com/science/article/pii/S0021925818393785
4. https://ijomeh.eu/pdf-2262-2130?filename=2130.pdf
5. https://article.imrpress.com/journa....69.2.67/5ae33e861954836782204b696098724f.pdf
6. https://www.mdpi.com/2075-1729/15/2/238
7. https://www.sciencedirect.com/science/article/pii/S0022316622095438

---

Antwort von Perplexity: https://www.perplexity.ai/search/re...I8LBVn0xQaOzsqkQYjleLw?utm_source=copy_output

The problem with AI is lack of critical input. AI will find sources for any claim. But if one doesn't check even most improbable sources, as neglected by you above, it will give you the confirmation bias you seek.

 

[pamojja]

In the last column, my average lab results during the last 16 years (I've added lab's normal ranges, optimal range would be much narrower, for unbound copper 5 - 20% only):

Copper

µg / dl

65 - 165

126

unbound Copper

% Cu

30

(whole blood) Copper

mg / l

1.1 - 1.2

1,2

Ceruloplasmin - CP

mg / dl

15 - 30

27

;My average antioxidant enzymes results:

Superoxide dismutase (Cu, Zn) - SOD1

µg / ml

4 - 40

41

Glutathion peroxidase (Se) - GSH-Px

U / gHb

27.5 - 73.6

64

And the only oxidation marker reasonable available to me, averaged:

oxidated LDL - oxLDL

ug / l

20 - 170

83

As the saying goes: Test, don't guess!