scholarly journals Oral vitamin C supplementation to patients with myeloid cancer on azacitidine treatment: Normalization of plasma vitamin C induces epigenetic changes

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Linn Gillberg ◽  
Andreas D. Ørskov ◽  
Ammar Nasif ◽  
Hitoshi Ohtani ◽  
Zachary Madaj ◽  
...  
Keyword(s):  
Vitamin C ◽  
Biological Effects ◽  
Pilot Trial ◽  
Dna Demethylation ◽  
Controlled Clinical Trial ◽  
Plasma Vitamin ◽  
Oral Vitamin ◽  
Oral Supplementation ◽  
Vitamin C Deficiency ◽  
Vitamin C Supplementation

Abstract Background Patients with haematological malignancies are often vitamin C deficient, and vitamin C is essential for the TET-induced conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), the first step in active DNA demethylation. Here, we investigate whether oral vitamin C supplementation can correct vitamin C deficiency and affect the 5hmC/5mC ratio in patients with myeloid cancers treated with DNA methyltransferase inhibitors (DNMTis). Results We conducted a randomized, double-blinded, placebo-controlled pilot trial (NCT02877277) in Danish patients with myeloid cancers performed during 3 cycles of DNMTi-treatment (5-azacytidine, 100 mg/m2/d for 5 days in 28-day cycles) supplemented by oral dose of 500 mg vitamin C (n = 10) or placebo (n = 10) daily during the last 2 cycles. Fourteen patients (70%) were deficient in plasma vitamin C (< 23 μM) and four of the remaining six patients were taking vitamin supplements at inclusion. Global DNA methylation was significantly higher in patients with severe vitamin C deficiency (< 11.4 μM; 4.997 vs 4.656% 5mC relative to deoxyguanosine, 95% CI [0.126, 0.556], P = 0.004). Oral supplementation restored plasma vitamin C levels to the normal range in all patients in the vitamin C arm (mean increase 34.85 ± 7.94 μM, P = 0.0004). We show for the first time that global 5hmC/5mC levels were significantly increased in mononuclear myeloid cells from patients receiving oral vitamin C compared to placebo (0.037% vs − 0.029%, 95% CI [− 0.129, − 0.003], P = 0.041). Conclusions Normalization of plasma vitamin C by oral supplementation leads to an increase in the 5hmC/5mC ratio compared to placebo-treated patients and may enhance the biological effects of DNMTis. The clinical efficacy of oral vitamin C supplementation to DNMTis should be investigated in a large randomized, placebo-controlled clinical trial. Trial registration ClinicalTrials.gov, NCT02877277. Registered on 9 August 2016, retrospectively registered.

scholarly journals Oral Vitamin C Supplementation to Azacitidine in Patients with Myeloid Cancer: Normalization of Plasma Vitamin C Induces Epigenetic Changes

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3079-3079
Author(s):  
Linn Gillberg ◽  
Andreas Due Ørskov ◽  
Ammar Nasif ◽  
Hitoshi Otani ◽  
Zachary Madaj ◽  
...  
Keyword(s):  
Vitamin C ◽  
Board Of Directors ◽  
Treatment Cycle ◽  
Dna Demethylation ◽  
Plasma Vitamin ◽  
Oral Vitamin ◽  
Advisory Committees ◽  
Oral Supplementation ◽  
Active Dna Demethylation ◽  
Vitamin C Supplementation

Abstract Introduction Hematological cancer patients are often vitamin C deficient, and vitamin C is essential for the TET induced conversion of 5-methylcytosine (5mC) to 5-hydroxymethylsytosine (5hmC); the first step in active DNA demethylation. In tissue culture, we have shown that restoration of vitamin C to normal concentrations can potentiate the effect of DNA methyltransferase inhibitors (DNMTis) by activation of DNA demethylation and induction of genes in the viral defense pathway, so called 'viral mimicry' (Liu et al. PNAS 2016). Here, we investigated whether oral vitamin C supplementation can correct vitamin C deficiency, enhance the efficacy of active DNA demethylation and induce upregulation of genes in the viral defense pathway in patients with myeloid cancers treated with the DNMTi 5-azacytidine. Study Design and Methods A randomized, placebo-controlled clinical trial of myelodysplastic syndrome (MDS; n=9), chronic myelomonocytic leukemia (CMML; n=4) and acute myeloid leukemia (AML; n=7) patients was performed during 3 cycles/12 weeks of DNMTi treatment (5-azacytidine, 100mg/m2 day 1 to 5 in a 4-week cycle) supplemented by oral dose of 500mg vitamin C (n=10) or placebo (n=10) daily during the last 8 weeks (Figure 1). Blood samples were drawn on day 1 and 5 of each treatment cycle before 5-azacytidine was administered and on day 28 of the third treatment cycle. Total plasma vitamin C was measured by HPLC in samples that had been acidified by 10% meta-phosphoric acid immediately after blood drawn. Mutational status of the 20 most commonly mutated genes in MDS were conducted by targeted next-generation sequencing. Global levels of 5mC and 5hmC were measured with LC-MS/MS in DNA extracted from MACS-sorted malignant cells and quoted relative to total levels of deoxyguanine. Total RNA-seq was performed on 20 RNA samples from 6 patients; cDNA libraries were prepared using KAPA RNA HyperPrep Kits and sequencing on a NextSeq 500 instrument (Illumina). Results Fourteen patients were deficient in plasma vitamin C (<23 µM) and 4 of the remaining 6 patients took vitamin supplement at inclusion. Global DNA methylation was significantly higher in patients with severe vitamin C deficiency (<11.4 µM; P=0.004) and borderline significantly higher in DNMTi naïve (n=11) compared to non-naïve patients (P=0.095). At baseline, global 5hmC/5mC levels were lower in the 7 patients with TET2 mutations (n=7; P= 0.013). Oral supplementation restored plasma vitamin C levels to the normal range in all patients in the vitamin C arm (P<0.0005). We show for the first time that active DNA demethylation, estimated as the change in global 5hmC/5mC levels, was significantly increased in patients receiving vitamin C compared to placebo (P=0.041). Preliminary RNA sequencing data show increased upregulation of genes involved in the viral defense pathway, including IRF7 and IFIT1, in vitamin C supplemented patients that were DNMTi naïve at study inclusion. Conclusions The increase in active DNA demethylation, indicated by the elevation of 5hmC/5mC levels in myeloid cells from vitamin C supplemented patients compared to placebos, plus the increased expression of viral defense genes in vitamin C treated DNMTi naïve patients, suggest that the efficacy of 5-azacytidine might be increased by oral supplementation of vitamin C. We suggest that normalization of plasma vitamin C by oral supplementation may enhance the biological effects of DNMTis in patients and prompts the investigation of the clinical relevance of vitamin C supplementation to DNMTis in a large randomized placebo controlled trial. Figure 1. Study design. Days 1, 5, and 28: before vitamin C/placebo exposure. Day 32: after short-term vitamin C/placebo exposure. Days 56, 60, and 84: after longer-term vitamin C/placebo exposure. C = cycle, D = day in cycle. Figure 1. Figure 1. Disclosures Jones: ZYMO Corporation: Consultancy. Grønbæk:Celgene: Membership on an entity's Board of Directors or advisory committees; Otsuka Pharma: Membership on an entity's Board of Directors or advisory committees; Janssen Pharma: Membership on an entity's Board of Directors or advisory committees.

Vitamin C Deficiency in Patients on Long-Term Deferasirox without Supplementation.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1858-1858
Author(s):  
Konstantinos Sarantos ◽  
Patricia Evans ◽  
Maciej Garbowski ◽  
Bernard Davis ◽  
John B Porter
Keyword(s):  
Vitamin C ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Plasma Levels ◽  
Plasma Vitamin ◽  
Liver Iron ◽  
Vitamin C Deficiency ◽  
Vitamin C Supplementation ◽  
Iron Excretion

Abstract Background: Under conditions of iron overload, ascorbic acid is oxidised at an increased rate leading to a risk of vitamin C deficiency. With deferoxamine (DFO) standard therapy, vitamin C is usually given at a dose of 2–3mg/kg on the days of DFO infusion as this increases iron excretion by up to 30%. With deferarisox (DFX) chelation treatment, although supplementation is permitted, there is currently no information about the effects of vitamin C supplementation on iron excretion and it is often left to patients or their clinician’s discretion as to whether supplementation is given. With long-term treatment, in the absence of supplementation there is a potential risk that vitamin C deficiency will develop and this could influence response to treatment. Patients and Methods: We have measured fasting plasma vitamin C in 41 patients who have been on long term deferasirox treatment for transfusional iron overload for between 1.5 and 5 years. 32 of these patients had received no supplementation and 9 patients had received 2–3 mg/kg/ day of supplementation. We have examined whether trends in serum ferritin, myocardial T2* and liver iron, during the final year of observation, relate to plasma levels of vitamin C. Results: Fasting plasma Vitamin C was significantly lower in the 41 patients (mean=30.3μmol/l, SD=20.8) than healthy control patients (mean=60.29μmol/l SD=12.6) (P&lt;0.0001). Fasting vitamin C levels were significantly lower in patients without supplementation (mean=26.1μmol/l, n=32) (p=0.011) than in patients who received regular supplementation (mean=45.5μmol/l, n=9). In the 32 patients without supplementation 23 (72%) had plasma levels less than two standard deviations from the control mean. Fasting vitamin C levels after a minimum of 1 year treatment without vitamin C supplementation negatively correlated with liver iron concentration as estimated by T2* MRI. One patient, who was subsequently found to have the lowest fating vitamin c level (2.9μmol/l) developed clinical signs consistent with scurvy with severe gum disease requiring dental clearance. We found no difference in the change of ferritin trend, LIC decrease or cT2* trend in the patients receiving supplementation from those who did not. We found that the correlation between LIC and serum ferritin was less clear in deficient patients (&lt;36μmol/l or 2SD from the mean, r=0.51, p&lt;0.01) than replete patients (&gt;36μmol/l) (r=0.88, p&lt;0.0001). Conclusions: We conclude that with long-term deferasirox therapy without vitamin C supplementation, there is a significant risk of vitamin C deficiency with a potential for clinical scurvy. The risk of ascorbate deficiency is further increased at higher levels of body iron loading. These findings suggest that vitamin C supplementation (2–3mg/kg/day) should be recommended as standard for patients on long-term chelation therapy with deferasirox. It would also be of value to determine whether long term-response was improved by ascorbate supplementation.

scholarly journals Effect of Dietary or Supplemental Vitamin C Intake on Vitamin C Levels in Patients with and without Cardiovascular Disease: A Systematic Review

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2330
Author(s):  
Bianca J. Collins ◽  
Mitali S. Mukherjee ◽  
Michelle D. Miller ◽  
Christopher L. Delaney
Keyword(s):  
Systematic Review ◽  
Cardiovascular Disease ◽  
Vitamin C ◽  
Antioxidant Properties ◽  
Plasma Vitamin ◽  
Healthy Population ◽  
Post Intervention ◽  
Supplemental Vitamin ◽  
Vitamin C Supplementation ◽  
Elderly Cohort

Atherosclerosis is a pro-oxidative and pro-inflammatory disease state, which is the underlying cause of most cardiovascular events, estimated to affect 5.2% of the Australian population. Diet, and specifically vitamin C, through its antioxidant properties can play a role in impeding the development and progression of atherosclerosis. This systematic review conducted comprehensive searches in Medline, Emcare, Scopus, PubMed, and Cochrane using key search terms for vitamin C, plasma vitamin C, supplementation, and cardiovascular disease (CVD). The results demonstrated that vitamin C supplementation resulted in a significant increase in vitamin C levels in populations with or without CVD, except for one study on the CVD population. It was also seen that the healthy population baseline and post-intervention vitamin C levels were high compared to the CVD population. However, further research is indicated for CVD population groups with varying baseline vitamin C levels, such as low baseline vitamin C, within a more representative elderly cohort in order to formulate and update vitamin C repletion guidelines.

Faster plasma vitamin E disappearance in smokers is normalized by vitamin C supplementation

2006 ◽  
Vol 40 (4) ◽  
pp. 689-697 ◽  
Author(s):  
Richard S. Bruno ◽  
Scott W. Leonard ◽  
Jeffery Atkinson ◽  
Thomas J. Montine ◽  
Rajasekhar Ramakrishnan ◽  
...  
Keyword(s):  
Vitamin E ◽  
Vitamin C ◽  
Plasma Vitamin ◽  
Vitamin C Supplementation ◽  
Plasma Vitamin E

Effect of Oral Vitamin C Supplementation on High-Altitude Hyperuricemia in Young Men Initially Migrating to High Altitude: A Pilot Study

2018 ◽  
Vol 19 (4) ◽  
pp. 373-381
Author(s):  
Hui Peng ◽  
Dongfang Feng ◽  
Yingkai Wang ◽  
Zixi Dong ◽  
Qing Chen ◽  
...  
Keyword(s):  
Pilot Study ◽  
Vitamin C ◽  
High Altitude ◽  
Young Men ◽  
Oral Vitamin ◽  
Vitamin C Supplementation

scholarly journals Vitamin C—An Adjunctive Therapy for Respiratory Infection, Sepsis and COVID-19

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3760 ◽  
Author(s):  
Patrick Holford ◽  
Anitra C. Carr ◽  
Thomas H. Jovic ◽  
Stephen R. Ali ◽  
Iain S. Whitaker ◽  
...  
Keyword(s):  
Vitamin C ◽  
Adjunctive Therapy ◽  
Respiratory Infections ◽  
Low Cost ◽  
Oral Vitamin ◽  
Vitamin C Deficiency ◽  
Favourable Safety ◽  
Favourable Safety Profile ◽  
Hospital Stays ◽  
Intravenous Vitamin

There are limited proven therapies for COVID-19. Vitamin C’s antioxidant, anti-inflammatory and immunomodulating effects make it a potential therapeutic candidate, both for the prevention and amelioration of COVID-19 infection, and as an adjunctive therapy in the critical care of COVID-19. This literature review focuses on vitamin C deficiency in respiratory infections, including COVID-19, and the mechanisms of action in infectious disease, including support of the stress response, its role in preventing and treating colds and pneumonia, and its role in treating sepsis and COVID-19. The evidence to date indicates that oral vitamin C (2–8 g/day) may reduce the incidence and duration of respiratory infections and intravenous vitamin C (6–24 g/day) has been shown to reduce mortality, intensive care unit (ICU) and hospital stays, and time on mechanical ventilation for severe respiratory infections. Further trials are urgently warranted. Given the favourable safety profile and low cost of vitamin C, and the frequency of vitamin C deficiency in respiratory infections, it may be worthwhile testing patients’ vitamin C status and treating them accordingly with intravenous administration within ICUs and oral administration in hospitalised persons with COVID-19.

scholarly journals Effects of oral vitamin C supplementation on oxidative stress and inflammation status in haemodialysis patients

2005 ◽  
Vol 20 (9) ◽  
pp. 1874-1879 ◽  
Author(s):  
Christine Fumeron ◽  
Thao Nguyen-Khoa ◽  
Claudine Saltiel ◽  
Messeret Kebede ◽  
Claude Buisson ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vitamin C ◽  
Oral Vitamin ◽  
Vitamin C Supplementation

scholarly journals Exercise Training and Vitamin C Supplementation Affects Ferritin mRNA in Leukocytes without Affecting Prooxidative/Antioxidative Balance in Elderly Women

2020 ◽  
Vol 21 (18) ◽  
pp. 6469
Author(s):  
Małgorzata Żychowska ◽  
Agata Grzybkowska ◽  
Monika Wiech ◽  
Robert Urbański ◽  
Wanda Pilch ◽  
...  
Keyword(s):  
Vitamin C ◽  
Iron Homeostasis ◽  
Elderly Women ◽  
Mrna Levels ◽  
Oral Supplementation ◽  
Ferritin Heavy Chain ◽  
Health Related ◽  
Vitamin C Supplementation ◽  
Group 2 ◽  
Group 1

Physical training and antioxidant supplementation may influence iron metabolism through reduced oxidative stress and subsequent lowering of mRNA levels of genes that are easily induced by this stress, including those responsible for iron homeostasis. Fifteen elderly women participated in our 12-week experiment, involving six weeks of training without supplementation and six weeks of training supported by oral supplementation of 1000 mg of vitamin C daily. The participants were divided into two groups (n = 7 in group 1 and n = 8 in group 2). In group 1, we applied vitamin C supplementation in the first six weeks of training, while in group 2 during the remaining six weeks of training. In both phases, the health-related training occurred three times per week. Training accompanied by vitamin C supplementation did not affect prooxidative/antioxidative balance but significantly decreased ferritin heavy chain (FTH) and ferritin light chain (FTL) mRNA in leukocytes (for FTH mRNA from 2^64.24 to 2^11.06, p = 0.03 in group 1 and from 2^60.54 to 2^16.03, p = 0.01 in group 2, for FTL mRNA from 2^20.22 to 2^4.53, p = 0.01 in group 2). We concluded that vitamin C supplementation might have caused a decrease in gene expression of two important antioxidative genes (FTH, FTL) and had no effect on plasma prooxidative/antioxidative balance.

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