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Dark side of Antioxidants like "Vitamin" C, etc

The below data could hopefully give some hints why balancing nutrition over other "vitamins" (not just "A" but "C" too) may be useful for chronic sufferers, and particularly why Grant's diet(very low in "Vitamin" C) in some cases could be more close to ideal one than other low-A diets.

Antioxidant Supplementation Enhances Bacterial Peritonitis in Mice by Inhibiting Phagocytosis
https://www.researchgate.net/publication/259203252_Antioxidant_Supplementation_Enhances_Bacterial_Peritonitis_in_Mice_by_Inhibiting_Phagocytosis
Antioxidants are known to exhibit numerous health benefits including anti-aging, anti-apoptotic and immuno-stimulatory effects. However, we present the data showing counterproductive effects of therapeutically relevant antioxidants on bacterial clearance by immune system in murine peritonitic model. The antioxidants ascorbic acid (Asc), glutathione (GSH) and N-acetylcysteine (NAC) augmented morbidity and mortality in mice carrying E. coli induced acute bacterial peritonitis. Treatment of peritonitic mice with antioxidants significantly increased their bacterial load in the range of 0.3 to 2 log orders. Antioxidant administration to peritonitic mice resulted in decreased number of macrophages, B cells and dendritic cells at the primary site of infection and increased neutrophil infiltration.

The serum Tumor Necrosis Factor-α levels were also decreased in antioxidant treated peritonitic mice.

In vitro experiments showed that antioxidants reduced phagocytic efficacy of peritoneal macrophages by ≈60-75% and also decreased E. coli induced oxidative burst in macrophages cells.

Taken together our data indicate that the antioxidants increased severity of peritonitis via decreasing the phagocytic efficiency, oxidative burst, TNF- alpha production and increasing neutrophil infiltration.

Based on these results we propose that antioxidant supplementation during the course of bacterial infection is not recommended as it could be detrimental for the host. Besides, the present study underlines the importance of timing and context of antioxidants administration as opposed to indiscriminate usage to gain best possible therapeutic advantage of these redox compounds.

^
Survival, body weight and peritoneal bacterial load after antioxidant administration in peritonitic mice. (a) Survival of the mice given different treatments over a period of 30 days. The mice were challenged with ~3108 E. coli cells and 500 mg (kg body weight)”1 of one of the antioxidants (GSH/Asc[ascorbic acid]/NAC) through the i.p. route (n56 mice per group). (b) Changes in body weight of the mice during 30 days after injection of E. coli and one of the antioxidants (n56 mice per group). Each data point represents mean±SEM. (c) Changes in peritoneal bacterial load of mice subjected to different combinations of E. coli and antioxidant treatments (n54 mice per group). *P,0.05 compared with the control; #P,0.05 compared with the E. coli-treated group.

Effect of antioxidants on intracellular ROS levels in peritoneal macrophages in vitro

Upon exposure to bacteria, phagocytes produce high levels of ROS by a process called oxidative burst. The bacteria induced alterations in intracellular ROS levels of murine peritoneal macrophages were measured in the presence or absence of exogenously added antioxidants.
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The decrease in E. coli-induced ROS production was more prominent in macrophages co-incubated with antioxidants compared with those pre-incubated with antioxidants.
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The present study conceivably proposes that antioxidant administration in animals with bacterial infection could be harmful for the host physiology. This statement is supported by our data that antioxidant administration caused increased bacterial load in the peritonitic mice, ultimately leading to their decreased survival
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Thus, the antioxidant-mediated decrease in phagocytosis and oxidative burst would disarm the host immune response and thus contribute to the increased bacterial load, leading to higher host mortality. Our proposal is further supported by an independent recent report showing a curcumin-mediated compromised immunological response against invading pathogens in a murine typhoid model (Marathe et al., 2013).
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Similarly, increased progression of Chlamydia trachomatis infection in the presence of GSH and NAC has been reported previously (Lazarev et al., 2010). Moreover, the presence of supplementary antioxidants at the site of infection could also interfere with the antibody-mediated bacterial killing via the ozonolysis pathway, thereby inhibiting the formation of neutrophil extracellular traps, which facilitate the clearance of bacterial infection from the host’s body (Brinkmann et al., 2004). However, these propositions are yet to be validated experimentally.
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On the whole, the results of our present study reveal for the first time that antioxidant administration in animals having acute bacterial peritonitis leads to overall deterioration of host conditions. This is the fallout of antioxidant-mediated modulation of three important immunological parameters involved in antibacterial defence:

(i) phagocytic efficacy and oxidative burst;
(ii) neutrophil infiltration and Gr1 expression;
(iii) expression of CD11b, which is a component of complement receptor CR3.

This is an initial but significant step towards understanding the in vivo role of antioxidant supplementation during clearance of bacterial infection. Importantly, we previously established that antioxidants eliminate antibiotic-induced bacterial killing (Goswami et al., 2006, 2007), and our current study indicates that they can also promote bacterial infection by decreasing the capacity of immune cells. Therefore, the knowledge obtained from our previous and present studies strengthens the hypothesis that antioxidants may interfere with the overall clearance of bacterial infections in vivo.

 

Effect of vitamin C on inflammation and metabolic markers in hypertensive and/or diabetic obese adults: a randomized controlled trial
https://www.dovepress.com/effect-of-vitamin-c-on-inflammation-and-metabolic-markers-in-hypertens-peer-reviewed-fulltext-article-DDDT

In the experimental group, vitamin C significantly reduced the levels of high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), fasting blood glucose (FBG), and triglyceride (TG) after 8 weeks of treatment (overall: P<0.001); no changes appeared in total cholesterol (TC). In the control group, there were significant reductions in FBG and TG (P=0.001 and P=0.026, respectively), and no changes in hs-CRP, IL-6, or TC. On comparing the changes in the experimental group with those in the control group at the endpoint, vitamin C was found to have achieved clinical significance in treating effectiveness for reducing hs-CRP, IL-6, and FBG levels (P=0.01, P=0.001, and P<0.001, respectively), but no significant changes in TC or TG were found.
Conclusion: Vitamin C (500 mg twice daily) has potential effects in alleviating inflammatory status by reducing hs-CRP, IL-6, and FBG in hypertensive and/or diabetic obese patients.

Effect of mega doses of vitamin C on bactericidal ativity of leukocytes
https://pubmed.ncbi.nlm.nih.gov/327791/
Effect of ingesting mega doses of ascorbic acid was studied on the leukocyte function in five normal human subjects. During the first 15 days the subjects received daily supplements of 200 mg of ascorbic acid, and during the next 2 weeks they were given 2 g of vitamin C per day. Supplementation of 200 mg as well as 2 g of ascorbic acid stimulated hexose monophosphate shunt activity of resting leukocytes indicating an increase in resting metabolism. Intakes of 200 mg of ascorbic acid per day did not affect bacterial killing by leukocytesOn the other hand, daily intakes of 2 g of ascorbic acid for 2 weeks significantly impaired bactericidal activity. Four weeks after withdrawal of the vitamin supplementation, bactericidal activity returned to normal.
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The mean ascorbic acid concentration in leukocytes at the beginning of the study was 9.3 ± 0.61 g/108 cells. At the end of 15 days supplementation with 200 mg of the vitamin per day and 2 g of ascorbic acid per day the levels increased significantly (P < 0.005) to 14.1 ± 0.39 g/10 cells and 16.1 ± 1 .02 g/10 cells, respectively.
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Daily intakes of 2 g of ascorbic acid have been found to result in increased concentrations of cyclic adenosine monophosphate in blood (18). Boume et al. (19) have shown that cyclic adenosine monophosphate inhibits the killing of ingested bacteria. Circulating levels of cyclic nucleotides were not measured in the subjects investigated here and it is not possible to comment on this possibility.

 

 

Ourania and Даниил have reacted to this post.
OuraniaДаниил

Thank you @rockarolla

rockarolla has reacted to this post.
rockarolla

@rockarolla Can you pls summarize that text for my monkey brain? Thx

Rachel has reacted to this post.
Rachel

Just don't supplement vitamin C. the study said 2 grams of vitamin C had a detrimental effect but 200 mg of vitamin C didn't. You can never get 2 grams of vitamin C without supplements. An apple only has 6,4 mg of vitamin C. One pound of boiled potatoes without the skin has 33,6 mg of vitamin C. 
The other anti-oxidants that people ingest are anthocyanidins which cause purple, blue or red colors in foods like red grapes, black beans, purple flesh potatoes, blueberries etc.
Coffee is also high in anti-oxidants. But anti-oxidants can also be helpful by inhibiting the production of the toxic retinoic acids. I personally don't avoid coffee, polyphenols, or vitamin C that occurs naturally in food. I eat coffee, black beans and purple flesh potatoes.

saraleah11, rockarolla and Armin have reacted to this post.
saraleah11rockarollaArmin
Quote from Jiří on February 10, 2021, 12:26 am

@rockarolla Can you pls summarize that text for my monkey brain? Thx

^^^

Quote from Vinero on February 10, 2021, 2:14 am

Just don't supplement vitamin C.

🙂

Arena has reacted to this post.
Arena

@vinero Hm I am not sure that it's so simple and this idea that we shouldn't do anything that is unnatural also makes no sense now. When we don't live in natural environment natural lives..For example in my case I am 100% sure I have copper toxicity and from time to time during "copper dump" my free copper in the blood goes sky high. Free copper ix crazy strong oxidant and destroys things like vit C on the contact. vit C is needed for DAO enzyme that breaks down histamine. That was the reason I had a lot of  histamine issues for so long.. I can't fix that with 100mg of natural C from potatoes.. I agree that high doses of vit C can be a problem. But if you know what are you doing(why are you taking vit C) and you don't go overboard with it like intravenous etc.. I don't see a problem. I love that idea not taking anything and just balance and heal my body with diet. But for most people it is impossible in the world we live in..

@jiri if you have chronic infections like chronic lung/brain/gut ones megadosing C = asking for troubles IMHO. 

@rockarolla that's why I asked what is in that article.. Btw "megadosing" to me is like 10 and more grams a day. I take maybe 1-2g a day..

1..2 grams day is way too much. It takes up to 2 weeks for the immune system to come back on track after 2g dose according to the above info - also there is a blood test for "Vit" C - maybe you are not deficient at all at the first place

@rockarolla So you will not tell me what vit C should do with immune system in your words?