Study: Vitamin C Infusions in Combination with Decitabine Extend Lifespan in Leukemia

The prognosis of AML has steadily improved since the 1970s. However, the therapeutic advances primarily concern young patients. The prognosis for those over 70 to 75 years of age has remained unchanged and poor.

Pathophysiological background

In AML, pathological clones of proliferating myeloid cells overgrow the healthy bone marrow and lead to the displacement of healthy hematopoiesis.
A decisive cause for the development of AML are various mutations, including in genes for enzymes that are responsible for DNA methylation. These include enzymes of the TET group. Their function includes causing the demythylation of DNA and thereby inducing the formation of tumor suppressor factors. Mutations consequently lead to an insufficient formation of these tumor suppressor factors – tumor progression occurs. The crucial point: TET2 enzymes are hydroxylases that use vitamin C as a cofactor.

Study: clinical data in combination with experimental investigations on the mode of action

In the present publication (Zhao, Zhu et al. 2018), scientists investigated in cell cultures the influence of vitamin C in combination with decitabine on the proliferation and apoptosis of leukemia cells and on the formation and activity of TET2 enzymes.
In addition, the clinical course of the combination of vitamin C i.v. (50 – 80 mg/kg body weight) and decitabine in elderly AML patients was investigated in a randomized, controlled study.

Vitamin C increases TET2 enzyme activity and synergistically supports the effect of decitabine

The experimental investigations on leukemia cells showed that decitabine increases the formation and activity of TET2 and that vitamin C also improves the enzyme activity. Together, both substances show significant synergistic effects on the enzyme activity.

Vitamin C infusions significantly improve the response rate to chemotherapy

The study included 73 older (> 60 years) patients with newly diagnosed primary or secondary AML who were unsuitable for intensive chemotherapy or refused it. The patients were randomly assigned to 2 groups. They received either the combination of decitabine, granulocyte-colony-stimulating factor, cytarabine and aclarubicin, or this combination plus daily vitamin C infusion. Two therapy cycles were performed. Patients with complete or partial remission received 4 – 5 further therapy cycles.
The results are very promising:

• After the first therapy cycle, significantly more patients in the vitamin C group showed a complete remission (79.92% vs. 44.11%; P=0.004).
• The median overall survival time was prolonged in the vitamin C group (15.3 months vs. 9.3 months, P=0.039).
• Vitamin C was well tolerated and did not lead to an increase in toxicity.

Vitamin C deficiency states are common in patients with malignant hematological diseases (Huijskens, Wodzig et al. 2016). This explains the biological plausibility of the good efficacy of vitamin C infusions observed in the present study:
Through intravenous administration, vitamin C as a cofactor of the TET enzymes improved the activity and thus the formation of tumor suppressor factors.

The synergy of Vitamin C with decitabine activates TET2 in leukemic cells and significantly improves overall survival in elderly patients with acut… – PubMed – NCBI

Huijskens, M. J., W. K. Wodzig, M. Walczak, W. T. Germeraad and G. M. Bos (2016). “Ascorbic acid serum levels are reduced in patients with hematological malignancies.” Results Immunol 6: 8-10.
Zhao, H., H. Zhu, J. Huang, Y. Zhu, M. Hong, H. Zhu, J. Zhang, S. Li, L. Yang, Y. Lian, S. Wang, J. Mao, Y. Chen, J. Li and S. Qian (2018). “The synergy of Vitamin C with decitabine activates TET2 in leukemic cells and significantly improves overall survival in elderly patients with acute myeloid leukemia.” Leuk Res 66: 1-7.