High-Dose Vitamin C in G6PDA and Pyruvate Kinase Deficiency: A Safety Study
Summary
This study is testing whether high-dose Vitamin C is safe and well-tolerated in patients with two inherited red blood cell disorders - Pyruvate Kinase Deficiency (PKD) and Class A Glucose-6-Phosphate Dehydrogenase Deficiency (G6PDA). Both conditions cause red blood cells to break down too quickly, leading to anemia and related complications. Our earlier research showed that a single oral dose of Vitamin C (250 mg, 500 mg, or 750 mg) reduced red blood cell breakdown by approximately 50% within one hour. This study builds on those findings by testing different doses and frequencies of Vitamin C to find the safest and most effective dosing schedule. Participants will take Vitamin C once, twice, or three times daily over a 3-week period, with careful monitoring of blood counts, red blood cell survival, iron levels, and any side effects. The study will first enroll 3 adult patients with PKD at Huntsman Cancer Institute. If the results are safe and promising, the study will be extended to patients with G6PDA deficiency, and eventually to children ages 4 and older at Primary Children's Hospital in Salt Lake City. The goal is to establish a foundation for Vitamin C as a novel therapy to reduce anemia and red blood cell destruction in these rare inherited disorders.
Timeline
- Start
- 2026-07-15
- Primary completion
- 2027-07-15
- Completion
- 2027-12-15
Publications
- Background Gammal RS, Pirmohamed M, Somogyi AA, Morris SA, Formea CM, Elchynski AL, Oshikoya KA, McLeod HL, Haidar CE, Whirl-Carrillo M, Klein TE, Caudle KE, Relling MV. Expanded Clinical Pharmacogenetics Implementation Consortium Guideline for Medication Use in the Context of G6PD Genotype. Clin Pharmacol Ther. 2023 May;113(5):973-985. doi: 10.1002/cpt.2735. Epub 2022 Sep 24.
- Background Mohammed BM, Fisher BJ, Kraskauskas D, Ward S, Wayne JS, Brophy DF, Fowler AA 3rd, Yager DR, Natarajan R. Vitamin C promotes wound healing through novel pleiotropic mechanisms. Int Wound J. 2016 Aug;13(4):572-84. doi: 10.1111/iwj.12484. Epub 2015 Aug 20.
- Background Bechara N, Flood VM, Gunton JE. A Systematic Review on the Role of Vitamin C in Tissue Healing. Antioxidants (Basel). 2022 Aug 19;11(8):1605. doi: 10.3390/antiox11081605.
- Background Coffey R, Jung G, Olivera JD, Karin G, Pereira RC, Nemeth E, Ganz T. Erythroid overproduction of erythroferrone causes iron overload and developmental abnormalities in mice. Blood. 2022 Jan 20;139(3):439-451. doi: 10.1182/blood.2021014054.
- Background Grootendorst S, de Wilde J, van Dooijeweert B, van Vuren A, van Solinge W, Schutgens R, van Wijk R, Bartels M. The Interplay between Drivers of Erythropoiesis and Iron Homeostasis in Rare Hereditary Anemias: Tipping the Balance. Int J Mol Sci. 2021 Feb 23;22(4):2204. doi: 10.3390/ijms22042204.
- Background Lal A, Patterson L, Goldrich A, Marsh A. Point-of-care end-tidal carbon monoxide reflects severity of hemolysis in sickle cell anemia. Pediatr Blood Cancer. 2015 May;62(5):912-4. doi: 10.1002/pbc.25447. Epub 2015 Feb 14.
- Background Quinn J, Gerber B, Fouche R, Kenyon K, Blom Z, Muthukanagaraj P. Effect of High-Dose Vitamin C Infusion in a Glucose-6-Phosphate Dehydrogenase-Deficient Patient. Case Rep Med. 2017;2017:5202606. doi: 10.1155/2017/5202606. Epub 2017 Nov 26.
- Background Mehta JB, Singhal SB, Mehta BC. Ascorbic-acid-induced haemolysis in G-6-PD deficiency. Lancet. 1990 Oct 13;336(8720):944. doi: 10.1016/0140-6736(90)92317-b. No abstract available.
- Background McLennan JD, Sparshu S. Returning to Stimulants in Children with Treatment Resistant ADHD: A Case Series. J Can Acad Child Adolesc Psychiatry. 2018 Jan;27(1):50-56. Epub 2018 Jan 1.
- Background Padayatty SJ, Katz A, Wang Y, Eck P, Kwon O, Lee JH, Chen S, Corpe C, Dutta A, Dutta SK, Levine M. Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr. 2003 Feb;22(1):18-35. doi: 10.1080/07315724.2003.10719272.
- Background Carr AC, Maggini S. Vitamin C and Immune Function. Nutrients. 2017 Nov 3;9(11):1211. doi: 10.3390/nu9111211.
- Background Juneja D, Jain R, Nasa P. Vitamin C-induced Hemolysis: Meta-summary and Review of Literature. Indian J Crit Care Med. 2022 Feb;26(2):224-227. doi: 10.5005/jp-journals-10071-24111.
- Background Gayet RV, Ilia K, Razavi S, Tippens ND, Lalwani MA, Zhang K, Chen JX, Chen JC, Vargas-Asencio J, Collins JJ. Autocatalytic base editing for RNA-responsive translational control. Nat Commun. 2023 Mar 11;14(1):1339. doi: 10.1038/s41467-023-36851-z.
- Background Rubinstein MP, Lind NA, Purton JF, Filippou P, Best JA, McGhee PA, Surh CD, Goldrath AW. IL-7 and IL-15 differentially regulate CD8+ T-cell subsets during contraction of the immune response. Blood. 2008 Nov 1;112(9):3704-12. doi: 10.1182/blood-2008-06-160945. Epub 2008 Aug 8.
- Background Bahr TM, Agarwal AM, Meznarich JA, Prince WL, Wait TWP, Prchal JT, Christensen RD. Thirty-five males with severe (Class 1) G6PD deficiency (c.637G>T) in a North American family of European ancestry. Blood Cells Mol Dis. 2021 Dec;92:102625. doi: 10.1016/j.bcmd.2021.102625. Epub 2021 Nov 4.
- Background Sarangi P, Senthilkumar MB, Kumar N, Senguttuvan S, Vasudevan M, Jayandharan GR. Potential role of long non-coding RNA H19 and Neat1 in haemophilic arthropathy. J Cell Mol Med. 2023 Jun;27(12):1745-1749. doi: 10.1111/jcmm.17770. Epub 2023 May 14. No abstract available.
- Background Zhang J, Cao L, Wang H, Cheng X, Wang L, Zhu L, Yan T, Xie Y, Wu Y, Zhao M, Ma S, Wu M, Wang G, Hao H. Ginsenosides Regulate PXR/NF-kappaB Signaling and Attenuate Dextran Sulfate Sodium-Induced Colitis. Drug Metab Dispos. 2015 Aug;43(8):1181-9. doi: 10.1124/dmd.115.063800. Epub 2015 May 18.