What happens to individuals with Glucose-6-phosphate dehydrogenase (G6PD) deficiency when taking vitamin C?

Vitamin C in G6PD Deficiency: Risk of Hemolysis

High-dose vitamin C can cause severe hemolysis, methemoglobinemia, and potentially life-threatening complications in individuals with G6PD deficiency, and should be avoided in these patients. 1, 2

Mechanism of Hemolysis in G6PD Deficiency

G6PD deficiency affects the hexose monophosphate shunt, which is the only source of NADPH in red blood cells. This leads to:

• Reduced ability to maintain glutathione in its reduced form
• Decreased protection against oxidative stress
• Increased vulnerability to hemolysis when exposed to oxidant drugs

When G6PD-deficient individuals are exposed to high-dose vitamin C (ascorbic acid), the following can occur:

• At supraphysiological doses, vitamin C acts as a pro-oxidant rather than an antioxidant
• Oxidative damage to red blood cells leads to hemolysis
• Methemoglobinemia may develop concurrently 2

Clinical Manifestations of Vitamin C-Induced Hemolysis

Symptoms typically develop within 3 days of vitamin C administration 1 and may include:

• Jaundice and scleral icterus
• Dark or tea-colored urine
• Fatigue and shortness of breath
• Back pain
• In severe cases: acute kidney injury, DIC, or methemoglobinemia 1

Dosage Considerations

The risk of hemolysis appears to be dose-dependent:

• Low physiological doses (less than 1g/day): Generally safe for most G6PD-deficient individuals
• Moderate doses (1-10g/day): May cause hemolysis in severely deficient individuals
• High doses (>10g/day): High risk of significant hemolysis 1, 2, 3

Interestingly, at physiological doses, vitamin C can actually be used as an alternative treatment for methemoglobinemia in G6PD-deficient patients when methylene blue is contraindicated 4, 5.

Recommendations for Clinical Practice

1. Screening for G6PD deficiency:

   • Screen patients before prescribing high-dose vitamin C, especially those from high-risk ethnic backgrounds (Mediterranean, African, Middle Eastern, Asian) 4
   • Consider family history of G6PD deficiency when emergency treatment is needed 4

2. Vitamin C administration in G6PD deficiency:

   • Avoid high-dose vitamin C supplementation (particularly IV formulations >1g) 1, 2, 3
   • For nutritional supplementation, use the lowest effective dose
   • Monitor for signs of hemolysis if vitamin C must be given

3. Treatment of methemoglobinemia in G6PD deficiency:

   • Methylene blue should be avoided as it may worsen hemolysis and methemoglobinemia 4, 5
   • Low-dose ascorbic acid is the treatment of choice for methemoglobinemia in G6PD-deficient patients 4
   • Dosing for methemoglobinemia treatment: 0.5-2g in adults, administered in divided doses 4
   • For severe cases, exchange transfusion may be necessary 4

Special Considerations

• Dapsone: Should be avoided in G6PD-deficient patients due to risk of hemolysis 4
• Monitoring: If vitamin C is administered, closely monitor hemoglobin, bilirubin, LDH, and haptoglobin levels
• Patient education: G6PD-deficient patients should be educated about avoiding high-dose vitamin C supplements and other oxidant drugs

Case Examples

Multiple case reports document hemolysis following vitamin C administration in G6PD-deficient patients:

• A 75-year-old woman developed methemoglobinemia and hemolytic anemia after receiving 30g IV vitamin C 2
• A 27-year-old man with known G6PD deficiency developed severe hemolytic jaundice after pharmacological doses of vitamin C 3
• Hemolysis has been reported even with doses as low as 1g/day in severely deficient individuals 1

While vitamin C at physiological doses is generally considered safe and even beneficial in G6PD deficiency, high-dose supplementation presents significant risks and should be avoided in this population.