Long-term effects of oral vitamin C supplementation on the endothelial dysfunction in the iris microvessels of diabetic rats

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.

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Effects of Oral Vitamin C Supplementation on Anxiety in Students: A Double-Blind, Randomized, Placebo-Controlled Trial

Pakistan Journal of Biological Sciences ◽

10.3923/pjbs.2015.11.18 ◽

2014 ◽

Vol 18 (1) ◽

pp. 11-18 ◽

Cited By ~ 22

Author(s):

Ivaldo Jesus Lima de Oliveira ◽

Victor Vasconcelos de Souza ◽

Vitor Motta ◽

Sergio Leme Da-Silva

Keyword(s):

Vitamin C ◽

Controlled Trial ◽

Oral Vitamin ◽

Double Blind ◽

Vitamin C Supplementation

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Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women

Thrombosis and Haemostasis ◽

10.1160/th14-08-0675 ◽

2015 ◽

Vol 113 (05) ◽

pp. 1135-1144 ◽

Cited By ~ 89

Author(s):

Marjo H. J. Knapen ◽

Lavienja A. J. L. M. Braam ◽

Nadja E. Drummen ◽

Otto Bekers ◽

Arnold P. G. Hoeks ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Arterial Stiffness ◽

Postmenopausal Women ◽

Acute Phase ◽

Controlled Trial ◽

Advanced Glycation Endproducts ◽

Matrix Gla Protein ◽

Stiffness Index ◽

Long Term Effects

SummaryObservational data suggest a link between menaquinone (MK, vitamin K2) intake and cardiovascular (CV) health. However, MK intervention trials with vascular endpoints are lacking. We investigated long-term effects of MK-7 (180 μg MenaQ7/day) supplementation on arterial stiffness in a double-blind, placebo-controlled trial. Healthy postmenopausal women (n=244) received either placebo (n=124) or MK-7 (n=120) for three years. Indices of local carotid stiffness (intimamedia thickness IMT, Diameter end-diastole and Distension) were measured by echotracking. Regional aortic stiffness (carotid-femoral and carotid-radial Pulse Wave Velocity, cfPWV and crPWV, respectively) was measured using mechanotransducers. Circulating desphospho-uncarboxylated matrix Gla-protein (dp-ucMGP) as well as acute phase markers Interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP), tumour necrosis factor-α (TNF-α) and markers for endothelial dysfunction Vascular Cell Adhesion Molecule (VCAM), E-selectin, and Advanced Glycation Endproducts (AGEs) were measured. At baseline dp-ucMGP was associated with IMT, Diameter, cfPWV and with the mean z-scores of acute phase markers (APMscore) and of markers for endothelial dysfunction (EDFscore). After three year MK-7 supplementation cfPWV and the Stiffness Index β significantly decreased in the total group, whereas distension, compliance, distensibility, Young’s Modulus, and the local carotid PWV (cPWV) improved in women having a baseline Stiffness Index β above the median of 10.8. MK-7 decreased dp-ucMGP by 50 % compared to placebo, but did not influence the markers for acute phase and endothelial dysfunction. In conclusion, long-term use of MK-7 supplements improves arterial stiffness in healthy postmenopausal women, especially in women having a high arterial stiffness.

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

Blood ◽

10.1182/blood.v112.11.1858.1858 ◽

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<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 (<36μmol/l or 2SD from the mean, r=0.51, p<0.01) than replete patients (>36μmol/l) (r=0.88, p<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.

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