The Pharmacokinetics of Vitamin C

Lykkesfeldt, Jens; Tveden‐Nyborg, Pernille

doi:10.3390/nu11102412

Cited by 236 publications

(326 citation statements)

References 120 publications

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“…The pharmacokinetic properties of ascorbate in the vertebrate host are well studied [75][76][77][78][79] . Murine investigations on absorption, tissue distribution and retention of ascorbate [76][77][78] revealed that maximum ascorbate concentrations could be measured in liver and kidneys (alike in the urine of humans 75 ) approximately three hours following peroral single dose application 76 . Whereas in the lungs, adrenal glands, skin, white fat and pancreas peak levels were detectable as early as 6 hours, in the spleen increasing ascorbate concentrations could still be assessed until 24 hours following application 76 .…”

Section: Discussionmentioning

confidence: 99%

Vitamin C alleviates acute enterocolitis in Campylobacter jejuni infected mice

Mousavi

Escher

Thunhorst

et al. 2020

Sci Rep

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Human foodborne infections with the zoonotic pathogen Campylobacter jejuni are on the rise and constitute a significant socioeconomic burden worldwide. The health-beneficial, particularly antiinflammatory effects of vitamin C (ascorbate) are well known. In our preclinical intervention study, we assessed potential anti-pathogenic and immunomodulatory effects of ascorbate in C. jejuni-infected secondary abiotic IL-10 −/− mice developing acute campylobacteriosis similar to humans. Starting 4 days prior peroral C. jejuni-infection, mice received synthetic ascorbate via the drinking water until the end of the experiment. At day 6 post-infection, ascorbate-treated mice harbored slightly lower colonic pathogen loads and suffered from less severe C. jejuni-induced enterocolitis as compared to placebo control animals. Ascorbate treatment did not only alleviate macroscopic sequelae of infection, but also dampened apoptotic and inflammatory immune cell responses in the intestines that were accompanied by less pronounced pro-inflammatory cytokine secretion. Remarkably, the anti-inflammatory effects of ascorbate pretreatment in C. jejuni-infected mice were not restricted to the intestinal tract but could also be observed in extra-intestinal compartments including liver, kidneys and lungs. In conclusion, due to the potent anti-inflammatory effects observed in the clinical murine C. jejuniinfection model, ascorbate constitutes a promising novel option for prophylaxis and treatment of acute campylobacteriosis. Campylobacter jejuni are the most common cause of food-borne gastroenteritis with increasing prevalence worldwide 1,2. In fact, human campylobacteriosis represents a socioeconomic burden given estimated disease-associated costs of approximately 2.4 billion Euro 3. Most commonly, C. jejuni transfer via consumption of contaminated raw or undercooked meat and milk or the ingestion of contaminated surface water to humans 4-8. The intestinal colonization of C. jejuni induces a strong inflammatory response of the innate immune system affecting both, absorptive and secretory functions of the gastrointestinal tract 1. In fact, campylobacteriosis constitutes a classical sodium malabsorption syndrome 9 , which depending on the bacterial strain and the host immune status, results in illness of varying degree 10. Whereas some patients remain asymptomatic or display mild symptoms, others develop fever, abdominal pain and watery diarrhea, or suffer from acute campylobacteriosis characterized by severe enterocolitis with inflammatory, bloody diarrhea 1,11. In the majority of events, the disease is self-limited and treated symptomatically, whereas patients with immunosuppressive comorbidities require antibiotic treatment 11,12. However, in few instances, post-infectious sequelae including Guillain-Barré syndrome, Miller Fisher syndrome, reactive arthritis and chronic inflammatory conditions of the intestinal tract might develop with a latent period of weeks or longer 1,13. Even though human campylobacteriosis is becoming increasingly impo...

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Section: Discussionmentioning

confidence: 99%

Vitamin C alleviates acute enterocolitis in Campylobacter jejuni infected mice

Mousavi

Escher

Thunhorst

et al. 2020

Sci Rep

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“…However, Hy-line Brown layer has the ability of VC synthesis, which is much higher in kidney than in liver [8,28]. VC absorption, transportation and distribution are regulated primarily by SVCTs [15].…”

Section: Discussionmentioning

confidence: 99%

“…Whether VC was taken orally or intravenously, the plasma VC content could be quickly returned stability by metabolism and excretion [31]. Especially, it was di cult to achieve a high dose of plasma VC content through dietary VC supplementation [15,31]. The follicle maturation process is accompanied by the deposition of lipids [35], which is not bene t for VC deposition, and it only takes 1.5 h to complete albumen formation in magnum [13], which leads a very short window time provided for VC deposition.…”

Section: Discussionmentioning

confidence: 99%

“…So, if VC could be deposited in yolk and albumen of produced eggs, it would be inseparable from the transportation and secretion function in hen's ovary and magnum. The source of hen's VC pool is mainly from intestinal absorption by sodium-dependent VC transporter 1 and 2 (SVCT1 and SVCT2) and liver's and kidney's synthesis by GLO [15,16,17,18,19]. Although dehydroascorbic acid, the oxidized form of VC, can be transported by glucose transporters, plasma dehydroascorbic acid content was estimated as <1-2% of that of VC [20].…”

Section: Introductionmentioning

confidence: 99%

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Dynamic Alterations on Synthesis and Transportation of Vitamin C and Deposition Status in Produced Eggs Induced by Dietary Vitamin C Supplementation in Hy-Line Brown Layer Model

Zhu

Zhao

Guo

et al. 2020

Preprint

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Abstract Background: Some previous studies have indicated that in ovo feeding (IOF) of vitamin C (VC) had positive effects on the performance in poultry. In order to realize embryonic VC supplementation, an idea about hen’s dietary VC supplementation to achieve VC enrichment in produced eggs was proposed. And this study was executed to investigate the effects of dietary VC supplementation on synthesis and transportation of VC in layers and VC deposition status in produced eggs.Results: Compared with Arbor Acres breeder eggs, egg VC content was lower in Isa Brown breeder eggs and Hy-Line Brown layer eggs (P < 0.05). Sodium-dependent vitamin C transporter 1 (SVCT1) and SVCT2 expression was higher in ileum than in duodenum and jejunum (P < 0.05). SVCT1 expression was extremely higher in magnum than in ovary, while SVCT2 expression was lower (P < 0.05). L-gulonolactone oxidase (GLO) expression was extremely higher and SVCT1 expression was higher in kidney than in liver, while SVCT2 was lower (P < 0.05). 400 mg/kg VC supplementation increased SVCT1 expression in duodenum, ovary and magnum, while decreased GLO and SVCT1 expression in liver (P < 0.05). 200 and 400 mg/kg VC supplementation increased SVCT2 expression in duodenum, while decreased GLO and SVCT1 expression in kidney and SVCT2 expression in liver (P < 0.05).Conclusions: Hy-Line Brown layer was a useful model for investigating effects of dietary VC supplementation on VC deposition in produced eggs. Dietary VC supplementation promoted VC absorption in duodenum and jejunum, but reduced endogenous VC synthesis in liver and kidney. Although dietary VC supplementation enhanced VC transportation in ovary and magnum, it finally failed to increase VC deposition in produced eggs.

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“…Pharmacokinetic and modelling data have demonstrated that tight regulation of ascorbate uptake and excretion means that plasma concentrations do not readily exceed 100 µM following oral intake (4,5). In contrast, intravenous ascorbate administration bypasses uptake regulation in the gastrointestinal tract and results in dose-dependent increases in plasma levels, even in excess of 20 mM (4,(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Vitamin C administration by intravenous infusion increases tumour ascorbate content in patients with colon cancer: a clinical intervention study

Dachs

Gandhi²,

Wohlrab

et al. 2020

Preprint

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Background: The use of high dose ascorbate infusions in cancer patients is widespread, but without evidence of efficacy. Several mechanisms whereby ascorbate could affect tumour progression have been proposed, including (i) the localised generation of cytotoxic quantities of H2O2, (ii) ascorbate-dependent activation of the 2-oxoglutarate-dependent dioxygenases that control the hypoxia-inducible factors (HIFs) and that are responsible for the demethylation of DNA and histones and (iii) increased oxidative stress induced by dehydroascorbic acid. We hypothesise that the dysfunctional vasculature of solid tumours results in compromised delivery of ascorbate to poorly perfused regions of the tumour and that this ascorbate deficit acts as an additional driver of the hypoxic response via upregulation of HIFs. Using a randomised ‘therapeutic window of opportunity’ clinical study we aimed to determine whether ascorbate infusions affected tumour ascorbate content and tumour biology.Methods: Patients with colon cancer were randomised to receive infusions of up to 1 g/kg ascorbate for four days before surgical resection (n=9) or to not receive infusions (n=6). Ascorbate was measured in plasma, erythrocytes, tumour and histologically normal mucosa at diagnostic colonoscopy and at surgery. Protein markers of tumour hypoxia or DNA damage were monitored in resected tissue.Results: Plasma ascorbate reached millimolar levels following infusion and returned to micromolar levels over 24 h. Pre-infusion plasma ascorbate increased from 38 ± 10 mM to 241 ± 33 mM (p<0.0001) over four days and erythrocyte ascorbate from 14 ± 15 mM to 2004 ± 814 mM (p<0.005). Tumour ascorbate increased from 15 ± 6 to 28 ± 6 mg/100g tissue (p<0.0001) and normal tissue from 14 ± 6 to 21 ± 4 mg/100g (p<0.001). A gradient of lower ascorbate was evident towards the tumour centre in both control and infusion samples. Lower expression of hypoxia-associated proteins was seen in post-infusion tumours compared with controls. There were no significant adverse events and quality of life was unaffected by ascorbate infusion.Conclusions: This is the first clinical study to demonstrate that tumour ascorbate levels increase following infusion, even in regions of poor diffusion, and that this could modify tumour biology. Trial registration: ANZCTR Trail ID ACTRN12615001277538

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The Pharmacokinetics of Vitamin C

Cited by 236 publications

References 120 publications

Vitamin C alleviates acute enterocolitis in Campylobacter jejuni infected mice

Vitamin C alleviates acute enterocolitis in Campylobacter jejuni infected mice

Dynamic Alterations on Synthesis and Transportation of Vitamin C and Deposition Status in Produced Eggs Induced by Dietary Vitamin C Supplementation in Hy-Line Brown Layer Model

Vitamin C administration by intravenous infusion increases tumour ascorbate content in patients with colon cancer: a clinical intervention study

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