Can Vitamin C Cause Hemolysis? Understanding the Risks

October 20, 2025 •

3 min read

According to a meta-summary of case reports, hemolysis was precipitated after high-dose vitamin C administration, particularly in individuals with Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency. This reveals a critical but often overlooked risk associated with what is widely considered a safe vitamin, raising the question: can vitamin C cause hemolysis?

Quick Summary

This article explores the specific circumstances under which vitamin C can cause the breakdown of red blood cells, focusing on the link with G6PD deficiency and the role of high dosages. It details the mechanisms involved, identifies at-risk populations, and provides guidance for safe supplementation.

Key Points

Risk Primarily Affects G6PD-Deficient Individuals: High-dose vitamin C can trigger hemolysis, or the destruction of red blood cells, in people with Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency.
High Dosages Cause Pro-Oxidant Effects: At very high concentrations, typically from intravenous administration, vitamin C acts as a pro-oxidant, generating reactive oxygen species that overwhelm the limited cellular defenses of G6PD-deficient red blood cells.
Normal Dosages Are Safe for Most: Standard oral intake of vitamin C is not a risk factor for hemolysis in healthy individuals, and excess is normally cleared by the kidneys.
Symptoms Include Jaundice and Dark Urine: Signs of vitamin C-induced hemolysis often appear within 72 hours and can include jaundice, dark-colored urine, unusual fatigue, and shortness of breath.
Screening is Recommended Before High-Dose Therapy: Screening for G6PD deficiency is advised before administering high-dose vitamin C, particularly to people from high-risk ethnic backgrounds.
Not Recommended for Some Conditions: High-dose vitamin C is contraindicated for G6PD-deficient patients and should be used with caution in those with kidney dysfunction, a history of kidney stones, or certain other health issues.

The Surprising Link Between Vitamin C and Hemolysis

While widely known as a powerful antioxidant, vitamin C (ascorbic acid) can act as a pro-oxidant at very high concentrations, potentially causing hemolysis or red blood cell destruction. Healthy individuals are generally protected by their bodies' antioxidant systems, but those with certain genetic conditions are vulnerable.

The Critical Role of G6PD Deficiency

The primary group at risk are those with Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency. This common inherited enzyme deficiency, prevalent in people of African, Asian, and Mediterranean descent, affects the red blood cells' ability to produce NADPH, which is vital for maintaining glutathione. Glutathione is a key antioxidant that protects red blood cells from damage.

When G6PD-deficient individuals are exposed to oxidative stressors like high-dose vitamin C, their red blood cells can't neutralize the resulting reactive oxygen species, leading to severe damage and acute hemolytic anemia.

How High-Dose Vitamin C Triggers Oxidative Stress

At very high doses, particularly intravenous ones, vitamin C generates reactive oxygen species through autoxidation. This overwhelms the limited antioxidant defenses in G6PD-deficient red blood cells.

High vitamin C concentrations lead to the production of hydrogen peroxide.
G6PD-deficient cells cannot replenish glutathione stores adequately.
Oxidative damage to the cell membrane and hemoglobin causes the red blood cell to break apart.
This results in hemolytic anemia and potentially complications like acute kidney injury.

Symptoms and Recognition

Symptoms of acute hemolysis from high-dose vitamin C usually appear within 72 hours and require immediate medical attention. These include:

Jaundice: Yellowing of skin and eyes due to bilirubin buildup.
Dark-Colored Urine: Often tea or cola-colored from released hemoglobin.
Fatigue and Weakness: Due to reduced oxygen-carrying capacity.
Shortness of Breath: Related to anemia.
Back Pain: May occur as cellular debris is processed.

High-Dose Vitamin C: A Comparison of Risk

The risk of vitamin C causing hemolysis depends on individual factors and dosage.


Feature	Healthy Individual (No G6PD Deficiency)	Individual with G6PD Deficiency
Effect of High-Dose Vitamin C	Generally safe; excess excreted. Potential GI upset or kidney stone risk above 2g/day.	High doses can trigger oxidative damage and hemolysis.
Recommended Dosage	RDA: 75-90 mg; UL: 2,000 mg.	Standard dietary intake is safe; High doses are contraindicated.
Administration Method	Mostly oral; IV rare outside clinical settings.	Oral and IV high doses can trigger hemolysis. IV is riskier due to rapid high concentrations.
Mechanism	Antioxidant properties usually dominate; Robust cellular defenses.	Impaired G6PD reduces protection against oxidative stress, making cells vulnerable to vitamin C's pro-oxidant effect at high doses.
Symptom Onset	Typically mild GI issues with excessive oral intake.	Rapid onset of severe symptoms within 72 hours.

Safe Supplementation and Clinical Best Practices

Precautions are necessary, especially when considering high-dose intravenous vitamin C. Identifying and monitoring at-risk patients is crucial.

Recommendations for Clinicians and Patients

G6PD Screening: Screening for G6PD deficiency is recommended before high-dose vitamin C, especially for those of African, Asian, or Mediterranean descent.
Patient Education: Individuals with G6PD deficiency should be informed about the risks of high-dose vitamin C supplements and other oxidants and advised to avoid them unless directed by a doctor.
Appropriate Dosages: Standard, low nutritional doses are generally safe. The risk is associated with megadoses.
Monitoring During Therapy: If high-dose vitamin C is necessary, closely monitor for signs of hemolysis, particularly within the first three days.

Conclusion

While standard oral vitamin C is safe for most, high doses can cause hemolysis in individuals with G6PD deficiency. This genetic condition compromises red blood cell defenses against oxidative damage. Awareness of this risk is essential for patients and healthcare providers to prevent life-threatening complications.

References

Juneja D, Jain R, Nasa P. Vitamin C-induced Hemolysis: Meta-summary and Review of Literature. Indian J Crit Care Med 2022;26(2):224–227. [https://pmc.ncbi.nlm.nih.gov/articles/PMC8857720/]

Frequently Asked Questions

No, it is highly unlikely. Standard oral dosages do not reach the high plasma concentrations needed to cause hemolysis, which is a risk primarily associated with very high-dose intravenous vitamin C in people with a pre-existing genetic condition called G6PD deficiency.

G6PD deficiency is a genetic condition where the body lacks an enzyme that protects red blood cells from oxidative damage. In these individuals, high doses of vitamin C can act as a pro-oxidant, overwhelming the weakened cellular defenses and causing the red blood cells to break down.

Symptoms typically appear within 72 hours and can include jaundice (yellowing skin/eyes), dark or tea-colored urine, unusual fatigue, and shortness of breath.

The primary risk group includes individuals with G6PD deficiency. The risk is significantly higher with high-dose, especially intravenous, vitamin C.

Most multivitamins contain standard, low doses of vitamin C and are generally considered safe for individuals with G6PD deficiency. However, high-dose supplements should be avoided.

If you experience symptoms like jaundice or very dark urine after taking high-dose vitamin C, seek immediate medical attention. Inform your doctor about your supplement use to help with diagnosis and treatment.

While there is no single consensus, high doses that can trigger hemolysis in susceptible individuals are often defined as exceeding 10 grams per day, particularly when administered intravenously.