Dr. Weeks’ Comment: Many, if not most, treatments for AML involve immune depleting treatments which leave the cancer patient without a robust immune system. Life is indeed scarier if your “physician within” is deprived of a healthy self-defense mechanism. High dose vitamin C has been well studied and found to selectively target AML cancer cells which is great news. Greater still is the fact that vitamin C at high doses has no significant side-effects. Search the terms “Vitamin C and Cancer” at www.weeksmd.com and also at https://pubmed.ncbi.nlm.nih.gov.
PEER REVIEWED SCIENTIFIC ARTICLES
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Jun;28(3):833-841. doi: 10.19746/j.cnki.issn.1009-2137.2020.03.019.
[Article in Chinese]
Xiao-Jing Lin 1 , ET AL
- PMID: 32552944 DOI: 10.19746/j.cnki.issn.1009-2137.2020.03.019
Results: The proliferation of HL-60 and U937 cells could be inhibited by high dose vitamin C, which showed a concentration-dependent manner (r=-0.9664; r=-0.9796). HL-60 and U937 cells were treated with different concentrations of vitamin C (8 and 20 mmol/L) for 24 hours, respectively, it was found that with the increasing of vitamin C concentration, cell apoptosis rate was significantly increased (r=0.9905; r=0.9971), and the expression of apoptosis related proteins including cleaved caspase 3, cleaved caspase-9 and cleaved PARP was aslo significantly increased with the increasing of concentration. In addition, it was found that with or without the mutation of TET2, high dose vitamin C could inhibit the proliferation (r=-0.9719; r=-0.9699) and promote the apoptosis (r=0.9998; r=0.9901) of primary CD34+leukemia cells in AML, which showed a dose-dependent manner, but it showed no effect on the proliferation (r=-0.2032) and apoptosis (r=0.1912) of normal CD34+cells.
Conclusion: High dose vitamin C can inhibit the proliferation and promote the apoptosis of acute myeloid leukemia cells, and selectively kill primary CD34+leukemia cells in AML.
Nutrients. 2013 Sep 9;5(9):3496-505. doi: 10.3390/nu5093496.
Free PMC article
The effect of high doses of vitamin C for the treatment of cancer has been controversial. Our previous studies, and studies by others, have reported that vitamin C at concentrations of 0.25-1.0 mM induced a dose- and time-dependent inhibition of proliferation in acute myeloid leukemia (AML) cell lines and in leukemic cells from peripheral blood specimens obtained from patients with AML. Treatment of cells with high doses of vitamin C resulted in an immediate increase in intracellular total glutathione content and glutathione-S transferase activity that was accompanied by the uptake of cysteine. These results suggest a new role for high concentrations of vitamin C in modulation of intracellular sulfur containing compounds, such as glutathione and cysteine. This review, discussing biochemical pharmacologic studies, including pharmacogenomic and pharmacoproteomic studies, presents the different pharmacological effects of vitamin C currently under investigation.
Antioxidants (Basel). 2018 Jul 16;7(7):92. doi: 10.3390/antiox7070092.
Mike N Foster 1 , ET AL
Free PMC article
A 52-year-old female presented to Integrated Health Options Clinic in October 2014 with a history of relapsed acute myeloid leukaemia (AML, diagnosed in 2009 and relapsed in 2014). Intravenous(IV) vitamin C therapy was initiated (in 2014) following completion of chemotherapy as an alternative to haematopoietic stem cell transplantation. IV vitamin C was administered twice weekly at a dose of 70 g/infusion. Within 4 weeks of initiation of IV vitamin C therapy, there was a dramatic improvement in the patient’s blood indices with platelet cell counts increasing from 25 × 10⁸/L to 196 × 10⁸/L and white blood cell counts increasing from 0.29 × 10⁸/L to 4.0 × 10⁸/L, with further improvements observed over the next 18 months. Furthermore, there was a clear and sustained improvement in the patient’s health-related quality of life scores assessed using a validated questionnaire. She has remained healthy and in complete remission until the present day. This case study highlights the benefits of IV vitamin C as a supportive therapy for previously relapsed AML.
Anticancer Agents Med Chem.2010 Jul;10(6):504-10. doi: 10.2174/1871520611009060504.
- PMID: 20812901 DOI: 10.2174/1871520611009060504
Arsenic trioxide (ATO) has shown great promise in the treatment of patients with relapsed or refractory acute promyelocytic leukemia (APL).However, the risk/benefit ratios of ATO in hematologic malignancies other than APL are still unclear. In this review, the author attempts to provide current experimental and clinical challenges to gain more knowledge of the effects of ATO by examining combination therapies with other agents, especially for non-APL hematologic malignancies, such as acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), chronic myeloid leukemia (CML), chronic lymphoid leukemia (CLL) and multiple myeloma (MM). The drugs combined with ATO can be roughly classified into (1) signaling inhibitors (imatinib, PD184352, LY294002, 17-Allylamino-17-demethoxygeldanamycin: 17-AAG), (2) oxidative stress pathway modulators (ascorbic acid, 2-methoxyestradiol: 2-ME, dl-buthionine-[S,R]-sulfoximine: BSO), (3) a chemotherapeutic drug (melphalan) and (4) others (bortezomib, ATRA). Some of these combination therapies have shown promising results in MM not only at the experimental level but also at the clinical level. However, studies are still ongoing for other non-APL hematologic malignancies. Since ATO is well tolerated and its toxicities are manageable and reversible, cell type-specific and efficient combination therapies with ATO are advantageous for non-APL hematological malignancies and should be developed in the near future.
Oncotarget. 2017 May 16;8(20):32550-32565. doi: 10.18632/oncotarget.15925.
Nélida I Noguera 1 et AL
The use of high-dose ascorbate (ASC) for the treatment of human cancer has been attempted several decades ago and has been recently revived by several in vitro and in vivo studies in solid tumors. We tested the cytotoxic effects of ASC, alone or in combination with arsenic trioxide (ATO) in acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL).Leukemic cell lines and primary blasts from AML and APL patients were treated with graded concentrations of ASC, alone or in association with standard concentration (1 μM) of ATO. The ASC/ATO combination killed myeloid blasts, including leukemic CD34+ cells, while sparing CD34+ progenitors obtained from normal cord blood and bone marrow. Actually, approximately one-third (11/36) of primary AML cases were highly sensitive to the ASC/ATO combination. The mechanism of cell killing appeared to be related to increased oxidative stress and overproduction of ROS in a non-quantitative fashion, which resulted in induction of apoptosis. These effects were reverted by the addition of the antioxidant N-Acetyl-Cysteine (NAC). In the APL NB4 model, ASC induced direct degradation of the PML and PML/RARA proteins via caspase activation, while the transcriptional repressor DAXX was recruited in re-constituted PML nuclear bodies. Our findings encourage the design of pilot studies to explore the potential clinical benefit of ASC alone or in combination with ATO in advanced AML and APL.
Int J Biochem Cell Biol. 2004 Nov;36(11):2180-95. doi: 10.1016/j.biocel.2004.04.005.
- PMID: 15313465 DOI: 10.1016/j.biocel.2004.04.005
L-Ascorbic acid (LAA) is being investigated clinically for the treatment of patients with acute myeloid leukemia (AML) based on the observed effects of LAA on AML progenitorcells in vitro. However, the mechanism for LAA-induced cytoreduction remains to be elucidated. LAA at concentrations of 0.25-1.0 mM induced a dose- and time-dependent inhibition of proliferation in three AML cell lines and also in leukemic cells from peripheral blood specimens obtained from three patients with AML. In contrast, ovarian cancer cell lines were only minimally affected. Flow cytometric analysis showed that LAA at concentrations of 0.25-1.0 mM could significantly induce apoptosis in the AML cell lines. LAA induced oxidation of glutathione to oxidized form (GSSG) and subsequent H(2)O(2) accumulation in a concentration-dependent manner, in parallel to induction of apoptosis. The direct role of H(2)O(2) in the induction of apoptosis in AML cells was clearly demonstrated by the finding that catalase could completely abrogate LAA-induced apoptosis. Induction of apoptosis in LAA-treated AML cells involved a dose-dependent increase of Bax protein, release of cytochrome C from mitochondria to cytosol, activation of caspase 9 and caspase 3, and cleavage of poly[ADP-ribose]polymerase. In conclusion, LAA can induce apoptosis in AML cells, and this is clearly due to H(2)O(2) which accumulates intracellularly as a result of oxidation of reduced glutathione by LAA.