Harm of IV High-Dose Vitamin C Therapy in Adult Patients: A Scoping Review.
Level 1 - systematic review of randomized trials
Systematic scoping review synthesizing evidence including 9 double-blind randomized controlled trials.
PubMed 32404636 · doi:10.1097/CCM.0000000000004396
What was done
Investigators conducted a scoping review searching MEDLINE, EMBASE, Cochrane Library, and trial registries for studies reporting harms of IV high-dose vitamin C in adults (defined as ≥6 g/d, ≥75 mg/kg/d, or ≥3 g/m²/d). Two independent investigators screened records and extracted adverse event data across all study designs.
What was found
From 8,149 records, 74 studies were included, covering 2,801 participants receiving high-dose IV vitamin C (median dose 22.5 g/d, 455 mg/kg/d, or 70 g/m²/d) with ≥932 adverse events reported. Across nine double-blind RCTs (2,310 patients), six reported no adverse events in either group. In the remaining three RCTs, adverse event rates per patient for vitamin C versus placebo were identical in one study (0.1 [1/10] vs 0.1 [1/10]), numerically lower in one (0.80 [672/839] vs 0.82 [709/869]), and numerically higher in one (0.33 [24/73] vs 0.23 [17/74]). Specific reported complications across all included studies were 5 cases of oxalate nephropathy, 5 cases of hypernatremia, 3 cases of hemolysis in glucose-6-phosphate dehydrogenase deficiency patients, 2 glucometer errors, and 1 case of kidney stones.
Why it matters
High-dose IV vitamin C is widely investigated in critical care, yet safety data had not been systematically aggregated. This review demonstrates no consistent increase in overall adverse events versus placebo in double-blind trials, while highlighting specific clinical risks requiring targeted monitoring.
Limits
The included literature is highly heterogeneous in design, dosing regimens, and patient populations. Adverse event reporting was inconsistent across trials, and the true incidence of rare, severe toxicities cannot be reliably established from case reports and small cohorts.
Cited by
- supports Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at risk of hemolysis when given intravenous vitamin C at doses of 40 grams or higher.