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Patients with blood malignancies are often deficient in vitamin C, which is essential for the conversion of TET-induced 5-methyl cytosine (5mC) to 5-hydroxymeduclein (5hmC), the first step in the de-methylation of active DNA.
here, we look at whether oral vitamin C supplements can correct vitamin C deficiency and affect 5hmC/5mC ratios in patients with bone marrow cancer treated with DNA methyl transferase inhibitors (DNMTis).
we conducted a randomized, double-blind, placebo-controlled trial (NCT02877277) in Danish bone marrow cancer patients over 3 cycles of DNMTi treatment (5-nitrogen hematin, 10 0mg/m2/d, 5 days, 28 days cycle) and orally take 500mg of vitamin C (n=10) or placebo (n=10) supplements daily for the last 2 cycles.
results showed that 14 patients (70%) had insufficient plasma vitamin C, and 4 of the remaining 6 patients were taking vitamin supplements at the time of inclusion.
significantly higher overall DNA methylation in patients with severe vitamin C deficiency (-lt;11.4μM; vs. deoxygenation, 4.997 vs. 4.656% 5mC, 95% CI (0.126,0.556), P s 0.004).
oral supplements restored plasma vitamin C levels to the normal range for all patients in the vitamin C group (an average increase of 34.85±7.94μM, P s 0.0004).
For the first time, we showed a significant increase in overall 5hmC/5mC levels in monocyte bone marrow cells in patients receiving oral vitamin C compared to placebo (0.037% vs - 0.029%, 95% CI (-0.129, -0.003) and P .041).
, the results suggest that the biological effects of DNMTis may be enhanced by normalizing plasma vitamin C levels through oral vitamin C supplementation compared to patients in the placebo group, resulting in an increase in the 5hmC/5mC ratio.
clinical efficacy of oral vitamin C supplementation DNMTis should be further studied in large randomized, placebo-controlled clinical trials.
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