Effects of vitamin C supplementation in human volunteers with a range of cholesterol levels on biomarkers of oxygen radical-generated damage

2000 ◽  
Vol 72 (6) ◽  
pp. 973-983 ◽  
Author(s):  
D. Anderson ◽  
B. J. Phillips ◽  
Tian-Wei Yu ◽  
A. J. Edwards ◽  
R. Ayesh ◽  
...  

Twenty-four men and 24 women, all nonsmoking, and maintaining normal dietary habits were assigned to 3 groups of 16. Each group comprising 4 males with "low" cholesterol levels (<6 mmol/L) matched for age and build with 4 males with "high" cholesterol levels (>6 mmol/L) and 8 similarly matched females. A three-treatment, three-treatment period, cross-over design was adopted. The three treatments were placebo, 60 mg vitamin C/day (the recommended daily allowance) and 6 g vitamin C/day for 14 days with 6 weeks between treatments. Blood samples were taken at the end of each treatment period. Vitamin C supplementation significantly increased plasma vitamin C concentrations and total antioxidant capacity, but did not affect cholesterol status or plasma ras p21 protein levels. There was a nonsignificant dose-related decrease in plasma lipid peroxidation breakdown products. DNA damage, measured in lymphocytes by the Comet assay and chromosome aberration test, was not increased after vitamin C supplementation. Sensitivity to hydrogen peroxide (in the Comet assay) was also unaffected, but sensitivity to chromosome aberration induced by bleomycin was increased by supplementation. A significant gender difference was found in plasma vitamin C levels, antioxidant capacity, and number of chromosome aberrations. Results were independent of low and high cholesterol status.

2020 ◽  
Vol 16 (7) ◽  
pp. 1072-1082
Author(s):  
Tuba C. Dördü ◽  
Rüştü Hatipoğlu ◽  
Mehmet Topaktaş ◽  
Erman S. İstifli

Background: Ellagic Acid (EA) is a polyphenolic compound that is classified in the natural antioxidants group. Polyphenolic compounds that exert antioxidant activity possess particular importance for scientists, food producers and consumers due to their positive effects on human health. However, despite considerable evidence that EA shows antigenotoxic activity by binding to DNA, there is no systematic genotoxicity study of this substance, which can covalently bind to DNA. This study aims to reveal the possible genotoxic activity of EA using widely accepted assays for the assessment of DNA clastogenic activity: sister chromatid exchange, chromosome aberration, micronucleus and comet assays as well as to predict the interactions among EA and DNA through molecular docking. Methods: Different assays were carried out to identify the clastogenic activity of EA on human lymphocyte DNA using Sister Chromatid Exchange (SCE), Chromosome Aberration (CA), Micronucleus (MN) and single-cell gel electrophoresis (SCGE/comet) assays. For this aim, human peripheral blood lymphocytes were treated with EA (60, 80 and 100 μg/ml) for 24 and 48 hrs in the SCE, CA and MN assays and for 1 hr in the comet assay. Furthermore, molecular docking experiments were also performed to calculate the binding energy of EA on human B-DNA structure (B-DNA dodecamer) as well as to predict noncovalent interactions among these macromolecules. Results: At the concentrations and treatment times (24- or 48-hr) tested, EA did not induce either SCE or Chromosome Aberrations (CAs) as compared to the negative and solvent controls. Although EA slightly increased the percentage of Micronucleated Binuclear (%MNBN) cells as well as the percentage of Micronucleus (%MN) in 24 or 48-hr treatment periods at all concentrations, this increase was not statistically significant as compared to both controls. The effect of EA on DNA replication (nuclear division) was determined by the Proliferation Index (PI), the Nuclear Division Index (NDI) and the Mitotic Index (MI). No statistically significant differences were observed in the PI or NDI in 24- or 48-hr treatment periods in human lymphocyte cultures treated with EA at various concentrations. EA generally had no significant effect on the MI, as observed with the PI and NDI. Discussion: Although the concentrations of 60 and 80 μg/mL at a 24-hr treatment period and the concentrations of 60 μg/mL and 100 μg/mL at 48-hr treatment period generally decreased the MI, those decreases were not statistically significant when compared to negative and solvent controls. Moreover, none of the concentrations of EA tested in this study were able to increase DNA damage determined by the tail DNA length, %DNA in tail and tail moment parameters in the comet assay. Although the amount of DNA damage in the comet assay decreased with increasing concentrations of EA, this decrease was not statistically significant as compared to both controls. However, molecular docking experiments interestingly showed that the binding free energy of EA with B-DNA was -7.84 kcal/mol-1, indicating a strong interaction between the two molecules. Conclusion : Although the findings of our study show that EA does not have genotoxic potential in human chromosomes, molecular docking experiments revealed strong hydrogen bonding between EA and B-DNA molecules. Therefore, it has been proposed that the prevailing information suggesting that the molecules that bind to DNA cause genotoxic effects should be reconsidered from a wider perspective.


Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2330
Author(s):  
Bianca J. Collins ◽  
Mitali S. Mukherjee ◽  
Michelle D. Miller ◽  
Christopher L. Delaney

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.


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

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Linn Gillberg ◽  
Andreas D. Ørskov ◽  
Ammar Nasif ◽  
Hitoshi Ohtani ◽  
Zachary Madaj ◽  
...  

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.


1997 ◽  
Vol 77 (1) ◽  
pp. 59-72 ◽  
Author(s):  
Harri Hemilä

Although the role of vitamin C in common cold incidence had been studied extensively, the level of vitamin C intake has not been unequivocally shown to affect the incidence of colds. In the present study the six largest vitamin C supplementation (≥ 1 g/d) studies, including over 5000 episodes in all, have been analysed, and it is shown that common cold incidence is not reduced in the vitamin C-supplemented groups compared with the placebo groups (pooled rate ratio (RR) 0·99; 95% CI 0·93, 1·04). Consequently these six major studies give no evidence that high-dose vitamin C supplementation decreases common cold incidence in ordinary people. Nevertheless, the analysis was continued with the hypothesis that vitamin C intake may affect common cold susceptibility in specific groups of people. It was assumed that the potential effect of supplementation might be most conspicuous in subjects with low dietary vitamin C intake. The average vitamin C intake has been rather low in the UK and plasma vitamin C concentrations are in general lower in males than in females. In four studies with British females vitamin C supplementation had no marked effect on common cold incidence (pooled RR 0·95; 95% CI 0·86, 1·04). However, in four studies with British male schoolchildren and students a statistically highly significant reduction in common cold incidence was found in groups supplemented with vitamin C (pooled RR 0·70; 95% CI 0·60, 0·81). Thus, these studies with British males indicate that vitamin C intake has physiological effects on susceptibility to common cold infections, although the effect seems quantitatively meaningful only in limited groups of people and is not very large.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1858-1858
Author(s):  
Konstantinos Sarantos ◽  
Patricia Evans ◽  
Maciej Garbowski ◽  
Bernard Davis ◽  
John B Porter

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.


Author(s):  
Amanda K. Schlueter ◽  
Carol S. Johnston

Vitamin C functions in enzyme activation, oxidative stress reduction, and immune function. There is considerable evidence that vitamin C protects against respiratory tract infections and reduces risk for cardiovascular disease and some cancers. Current trials are examining the efficacy of intravenous vitamin C as cancer therapy. Many experts believe that the recommended intakes for vitamin C (45 to 90 mg daily) are several orders of magnitude too low to support optimal vitamin C functionality. Also, there is a misperception that vitamin C deficiency disease (scurvy) is largely historical and rarely observed in developed nations. Physical symptoms of scurvy include swelling of the lower extremities, bleeding gums, fatigue, and hemorrhaging, as well as psychological problems, including depression, hysteria, and social introversion. The long-term safety of vitamin C supplementation seems evident as large investigations have noted reduced risk of mortality in vitamin C supplementing populations and in those with elevated plasma vitamin C concentrations.


2001 ◽  
Vol 101 (9) ◽  
pp. A-61
Author(s):  
K. Silliman ◽  
J.W. Parry ◽  
L.L. Kirk ◽  
R.L. Prior

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