@Lucian Miles @Tolulope Olukayode Jaiyeola@Ojochenemi Nora Unuata@Jonathan Ibrahim@AtapiaMessiah@Ochonong Emmanuel Ogar

Nice question — Vitamin C has surprisingly low acute lethality but some real risks at very high doses or in vulnerable people. Below I summarize LD₅₀ data (animals), what we know about humans, common adverse effects of high doses, and key case/study evidence — with sources so you can follow up.

Short answer (TL;DR)

No ethical human LD₅₀ exists — humans haven’t been given lethal-dose experiments.

Animal oral LD₅₀ values are high (i.e., low acute toxicity): rats ≈ 11,900 mg/kg, mice ≈ 3,300–8,000 mg/kg (varies by source/route). (MilliporeSigma, dept.harpercollege.edu)

Human safety guidance: the established Tolerable Upper Intake Level (UL) for adults is 2,000 mg/day (2 g/day) to avoid gastrointestinal adverse effects; this is far below doses associated with serious toxicity. (NCBI, Office of Dietary Supplements)

Serious adverse events (acute kidney injury from oxalate nephropathy, hemolysis in G6PD deficiency, iron overload concerns) have been reported with megadoses or IV high-dose vitamin C (grams to tens/hundreds of grams). (PMC, PubMed)

LD₅₀ / acute toxicity (animal data)

Rat (oral): ~11,900 mg/kg (11.9 g/kg). Multiple safety data sheets and toxicology sources report this value. (MilliporeSigma, Cayman Chemical)

Mouse (oral): commonly reported values ~3,300 mg/kg (some sources report up to ~8,000 mg/kg depending on testing conditions and route). (dept.harpercollege.edu, enartis.com)

Rabbit: LD₅₀ values vary by source (examples ~7 g/kg reported in older datasets).

Note: LD₅₀ depends strongly on species and route (oral vs. intraperitoneal, etc.), so animal numbers are only approximate guides. PubChem/SDS documents are a good starting point for authoritative animal LD₅₀ listings. (PubChem, MilliporeSigma)

Humans — what the literature says

No controlled human LD₅₀. Ethically impossible, so estimates come from case reports, clinical IV studies, and extrapolation from animals.

High-dose IV studies (oncology, sepsis): phase I/early clinical work has used IV vitamin C doses up to tens or even ~100 g per infusion with careful monitoring; many studies report acceptable acute safety in patients with normal renal function when protocols are followed. However, these are supervised clinical settings, not daily unsupervised megadoses. (Frederick National Laboratory, PMC)

Dietary guidance: Institute of Medicine / NIH list a UL of 2 g/day for adults — the adverse effect that led to the UL was primarily osmotic diarrhea and GI upset. Chronic higher oral intake increases risk of other complications in susceptible people. (NCBI, Office of Dietary Supplements)

Documented adverse effects & who’s at risk

Gastrointestinal upset: nausea, abdominal cramps, osmotic diarrhea — common at oral doses >2 g/day. (basis for the UL). (NCBI)

Oxalate nephropathy / acute kidney injury (AKI): vitamin C is metabolized partly to oxalate; megadoses (oral or IV) have been linked to renal oxalate crystal deposition and AKI in case reports — especially in patients with preexisting CKD, renal impairment, or other risk factors (e.g., prior bowel surgery). Several biopsy-confirmed case reports and case series exist. (PMC)

Hemolysis / methemoglobinemia in G6PD deficiency: high IV doses have caused hemolytic anemia in people with G6PD deficiency in case reports and small series — caution or avoidance is recommended for that population when using high-dose IV vitamin C. (PMC)

Iron overload / enhanced iron absorption: vitamin C increases non-heme iron absorption; patients with hemochromatosis or iron overload disorders may risk worsening iron stores with high chronic intake. (Mechanistic and clinical concern; monitor iron indices if high supplementation is used.) (Linus Pauling Institute)

Other: metabolic/osmotic issues, interactions with some chemotherapies are discussed in oncology literature; always check drug-specific data before combining treatments. (PMC)

High-dose IV vitamin C — safer than “megadose supplements”?

In controlled clinical trials for cancer or sepsis, IV vitamin C at high doses (grams to tens of grams per infusion) has been administered safely under monitoring, but these trials screen out/monitor for renal dysfunction and G6PD deficiency. Serious adverse events have occurred when patients had unrecognized risk factors or when very large/unsupervised doses were used. (Frederick National Laboratory, PMC)

Practical takeaways

For the general, healthy adult: standard supplementation (≤ 1000–2000 mg/day) is unlikely to be dangerous; GI side effects are the usual limit. UL = 2 g/day. (NCBI)

Avoid unsupervised megadoses (grams daily or large IV infusions) if you have CKD/renal impairment, G6PD deficiency, or hemochromatosis — those groups have documented adverse outcomes. (PMC)

Clinical/high-dose IV use should only occur under medical supervision (screening for renal dysfunction and G6PD, monitoring renal function and urine oxalate if indicated). (Frederick National Laboratory, PMC)

If you want to dig deeper (I can fetch these for you)

Full SDS / toxicology sheets (Sigma, Cayman, PubChem) for animal LD₅₀s and experimental details. (MilliporeSigma, Cayman Chemical)

Key case reports/reviews on oxalate nephropathy and vitamin C (biopsy-proven cases). (PMC)

Reviews / meta-summaries covering hemolysis and G6PD interactions with high-dose vitamin C. (PMC, PubMed)

Clinical trial reports of high-dose IV vitamin C in cancer/sepsis (safety endpoints). (Frederick National Laboratory, PMC).

Thank you for to the significant contribution

"The median lethal dose (LD50) for Vitamin C is 11900 mg per 1 kg Value is measured via oral route in rat(s)." Source: AATBioquest www.aatbio.com