Safety and Tolerability of Supratherapeutic Vitamin C Supplementation in Class A Glucose-6-Phosphate Dehydrogenase (G6PD A) Deficiency and Pyruvate Kinase Deficiency (PKD)

Pyruvate kinase deficiency (PKD) and Class A Glucose-6-Phosphate Dehydrogenase deficiency (G6PDA) are inherited red blood cell enzyme disorders characterized by chronic hemolytic anemia. Current treatment options are limited and do not fully address the underlying mechanisms of red blood cell destruction, iron overload, and oxidative stress.

Our preliminary studies demonstrated that oral Vitamin C administration at doses of 250 mg, 500 mg, and 750 mg reduced the rate of hemolysis by approximately 50% within one hour of administration, as measured by end-tidal carbon monoxide corrected for ambient CO (ETCOc) - a validated marker of red blood cell breakdown. These findings provide a strong rationale for evaluating the safety and optimal dosing frequency of Vitamin C supplementation in these patient populations.

Study Design:

This is a Phase I, single-site, sequential within-patient dose escalation study. Three adult PKD patients will be enrolled in the initial cohort, each assigned to a different starting dose:

Patient 1: 250 mg daily → 250 mg twice daily → 250 mg three times daily Patient 2: 500 mg daily → 500 mg twice daily → 500 mg three times daily Patient 3: 750 mg daily → 750 mg twice daily → 750 mg twice daily + 500 mg once daily (to reach the NIH-recommended maximum daily dose of 2,000 mg/day)