Table 1.

Summary of the key studies discussed

Study	Study type	Population	Study arms	Relevant outcomes
Vitamin C and respiratory illness/COVID-19
Hemila [4]	SRMA	Participants in controlled studies on VCS and the common cold	VCS ≥0.2 mg/d vs placebo	VCS had no effect on the risk of developing a cold in the general community, although there was a lower risk of developing a cold for marathon runners, skiers, and soldiers VCS reduced the duration of colds in both adults and children
Fowler [1]	Double-blind placebo-controlled study	Adult ICU patients with sepsis and acute respiratory distress syndrome	50 mg/kg IVVC every 6 h for 96 h vs placebo	Lower mortality rate in the IVVC group vs placebo Shorter ICU stay in the IVVC group vs placebo Shorter hospital stay in the IVVC group vs placebo
Vitamin D and respiratory illness/COVID-19
Illie [2]	Observational study	Europeans	European nation of residence	There was a significant negative correlation between mean national vitamin D levels and the number of national COVID-19 cases
Martineau [3]	SRMA	Participants in controlled studies on VDS and acute respiratory infections	VDS vs placebo	VDS was associated with a lower risk of acute respiratory tract infection The association was more pronounced for those with vitamin D deficiency The effect was dose-independent when VDS was administered in nonbolus forms
Vitamin C and hyperoxaluria/nephrolithiasis
Baxman [6]	Prospective partially randomized interventional study	A cohort of adults with a history of calcium stones and a cohort of NSFs	Stone-formers randomized to VCS of 500 mg BID for 3 d vs stone-formers randomized to VCS of 1000 mg BID for 3 d vs NSFs receiving VCS of 1000 mg BID for 3 d	24-hr urinary oxalate and the Tiselius index increased in all three groups after receiving VCS
Levine [7]	In-hospital depletion-repletion study	Healthy adult men aged 20–26 yr	Patients were admitted to hospital and started a very low vitamin C diet (<5 mg/d). They were then given increasing VCS doses starting at 30 mg/d progressively increasing to 2500 mg/d. The total study duration was 4–6 mo	Urinary oxalate was significantly higher at VCS of 1000 mg/d vs ≤200 mg/d Urinary oxalate was greater for 400 mg/d vs 200 mg/d and less vs 1000 mg/d, although the differences did not reach statistical significance
Ferraro [8]	Prospective large cohort study via surveys	Female nurses aged 22–55 yr and male health care workers aged 40–75 yr	Patients who developed incident kidney stones vs those who did not	VCS >1000 mg was associated with a higher risk of kidney stones for men VCS was not associated with a higher risk of kidney stones for women
Vitamin D and hypercalciuria/nephrolithiasis
Bjelakovic [10]	SRMA	Adults enrolled in trials comparing VDS to placebo or no intervention	VDS vs placebo or no intervention	Combined VDS and CCS increased the risk of developing kidney stones In the majority of studies included, CCS was not standardized in the experimental and control groups, making it unclear if the effect was secondary to VDS or calcium
Malihi [11]	SRMA	Adults enrolled in randomized controlled trials of ≥24 wk of VDS in which CCS was consistent between the control and experimental arms	VDS vs placebo	Patients receiving ≥24 wk of VDS had a higher risk of hypercalciuria, but not of kidney stones
Malihi [12]	SRMA	Adults enrolled in randomized controlled trials of ≥1 yr of high-dose (≥2800 IU/day) VDS in which CCS was consistent between the control and experimental arms	VDS vs placebo	Patients receiving high-dose VDS for >1 yr were not at higher risk of kidney stones, but were at borderline higher risk of developing hypercalciuria

BID = twice daily; CCS = calcium co-supplementation; ICU = intensive care unit; IVVC = intravenous vitamin C; NSFs = non–stone-formers; SRMA = systematic review and meta-analysis; VCS = vitamin C supplementation; VDS = vitamin D supplementation.