What are safe oral vitamin C dose ranges for people with different G6PD variants?
Executive summary
A careful reading of case reports, reviews and guideline responses shows that routine oral vitamin C at physiological doses (tens to a few hundred milligrams per day) poses negligible documented risk for people with G6PD deficiency, but prolonged or “high‑dose” oral intake—particularly gram‑level daily doses—has been associated with hemolysis in some case reports and deserves caution; the risk rises with more severe G6PD variants and with very large intravenous regimens (grams to tens of grams) [1] [2] [3]. Clinical authors therefore advise testing or close monitoring before giving pharmacologic vitamin C to those with known or suspected G6PD deficiency and to avoid rapid high‑concentration infusions [4] [5].
1. Why the question matters: variant‑dependent risk and the evidence base
G6PD deficiency is genetically heterogeneous and the degree of enzyme deficiency correlates with susceptibility to oxidative hemolysis, so any summary of “safe” dosing must acknowledge that published risk differs by variant and clinical context; major clinical reviews and case meta‑analyses report hemolysis after exposure to high doses of vitamin C but also document cases where moderate doses were therapeutic, especially for methemoglobinemia when methylene blue is contraindicated [6] [1] [3].
2. What the literature actually shows about oral doses and harms
A meta‑summary of case reports identified vitamin C exposures ranging from 1 g/day to 200 g/day in patients who experienced hemolysis, and concluded that high‑dose IV use is most commonly implicated while prolonged large oral doses have also been reported to trigger hemolysis [1]. A single‑case review and other case reports describe hemolysis and methemoglobinemia after what authors call “high‑dose” regimens (for example an adult case linked to ~30 g total vitamin C) [2] [7]. Conversely, several reviews note that low‑to‑moderate parenteral doses (and by extension physiological oral dosing) can be beneficial or at least not clearly harmful in some settings [3] [5].
3. Practical dose ranges that appear safe, with caveats
Physiological and traditional supplementation ranges—milligram doses up to several hundred mg daily (for example 100–300 mg/day used to treat scurvy historically)—are not implicated in the case literature as causes of hemolysis in G6PD patients and are generally regarded as safe in the absence of other oxidative stressors [8] [1]. There is weaker evidence about single‑gram oral dosing: case reports include exposures at 1 g/day in cohorts with hemolysis, but these were mixed with much larger doses and confounders, so 1 g/day cannot be declared categorically unsafe; risk likely increases with sustained gram‑level daily dosing and with more severe variants [1] [6].
4. When vitamin C turns risky: high oral and IV doses
High‑dose regimens used in alternative or investigational settings—tens of grams per day or rapid high‑concentration IV infusions—are repeatedly associated with hemolysis or methemoglobinemia in G6PD‑deficient patients and have prompted authors to recommend caution or exclusion of known/suspected G6PD deficiency from trials testing 6 g/day IV or higher without strict monitoring [2] [4] [9]. Several experts suggest an upper parenteral ceiling of roughly 4–6 g IV with strict monitoring when no alternative exists, underscoring that higher IV doses (and very large oral regimens used by some clinics) have produced adverse events [4] [6].
5. Guidance for clinicians and implicit agendas in reporting
Clinical authors urge that vitamin C at pharmacologic doses be treated as a medication with monitoring—test for G6PD when feasible, avoid rapid infusions, and exclude known or suspected G6PD deficiency from high‑dose studies unless monitoring is guaranteed [5] [4]. Some case reports come from settings promoting high‑dose vitamin C therapies, which creates an implicit agenda to downplay risks; systematic reviews and guideline responses recommend prudence and emphasize that evidence is largely case‑based rather than randomized [9] [1].
6. Bottom line and research gaps
For most people with G6PD variants, standard oral supplementation at physiologic doses (tens to a few hundred mg/day) is supported by the literature as low risk, while sustained gram‑level oral dosing and any high‑concentration IV regimens carry documented risk of hemolysis in susceptible individuals and should prompt G6PD testing or close monitoring; the evidence lacks large controlled trials stratified by genotype, so precise “safe” gram‑level cutoffs across variants remain indeterminate [8] [1] [4].