Table 1.
In vivo studies to investigate the role of vitamins in stone disease
| Vitamin | Organism | Study group | Main findings | Ref. |
|---|---|---|---|---|
| Vitamin A | Animal models | Healthy male Wistar rats (young and old) | Vitamin A deficiency resulted in reduced urinary citrate and reduced pH | 51 |
| Healthy female Sprague–Dawley rats | Vitamin A deficiency led to increased renal calculi formation | 52 | ||
| Male Wistar rats with induced hyperoxaluria (oral 0.5% ethylene glycol) | Rats receiving oral supplementation with retinol had increased urinary pH and citrate but no change in renal accumulation of calcium and oxalate) compared with unsupplemented lithogenic rats | 53a | ||
| Human participants | Adult calcium oxalate stone formers and healthy individuals (male and female) | Plasma levels of retinol were not different between sex-matched stone formers and healthy individuals | 51 | |
| Male paediatric patients with vitamin A deficiency (Bitot’s spots) and healthy individuals | Paediatric patients with vitamin A deficiency had increased urinary calcium and oxalate, reduced citrate and increased presence of crystalluria. In these children, oral treatment with 24,000 IU vitamin A palmitate for 10 days reduced urinary oxalate and calcium to the level of healthy children and increased citrate (but not the level of healthy children) | 55 | ||
| Adult stone formers and healthy individuals (male and female) | Stone formers had lower plasma vitamin A than healthy individuals (case–control study) | 56 | ||
| Vitamin B6 | Animal models | Healthy male rats | Rats fed pyridoxine HCl had lower urinary oxalate than untreated rats | 89 |
| Healthy male Wistar rats | Vitamin B6-deficient rats developed calcium oxalate and calcium phosphate crystals in the renal tract | 90 | ||
| Human participants | Health care workers (adult male and female participants) | Meta-analysis of observational data suggests that vitamin B6 intake is not associated with the risk of kidney stones in both males and females (follow-up study) | 86 | |
| Health care workers (adult male participants) | Vitamin B6 intake is not associated with the risk of kidney stones (prospective study) | 87 | ||
| Health care workers (adult female participants) | High doses of vitamin B6 are associated with a reduced risk of kidney stones (prospective study) | 88 | ||
| Adults with a history of recurrent renal calculi (male participants) | Oral pyridoxine (250–500 mg/day) for up to 18 months reduced urinary oxalate | 93 | ||
| Adult recurrent calcium oxalate stone formers (male and female participants) | Oral magnesium oxide (300 mg/day) with pyridoxine-HCl (10 mg/day) for up to 120 days reduced urinary oxalate | 94 | ||
| Adult patients from a urology stone clinic (male and female participants) | Retrospective dietary intervention and oral pyridoxine (50–100 mg/day) for up to 1 year reduced urinary oxalate and calcium oxalate supersaturation | 95 | ||
| Adult patients with idiopathic calcium oxalate calculi (unknown gender) | Oral pyridoxine for up to 6 weeks reduced urinary oxalate and glycolate | 96 | ||
| Adult calcium oxalate stone formers (male and female participants) | Oral pyridoxine (60 mg/day) for 28 days did not change urinary oxalate levels | 97 | ||
| Adult patients with recurrent idiopathic hypocitraturia (male and female participants) | Oral UriKind-KM6 (1,100 mg potassium citrate, 375 mg magnesium citrate, and 20 mg pyridoxine-HCl) taken every 8 h for 24 h did not change urinary oxalate levels | 98 | ||
| Adult patients with recurrent idiopathic calcium stone formation and healthy individuals (male participants) | Stone formers had less serum vitamin B6 than healthy individuals. Oral pyridoxine (300 mg/day) for 7 days did not change urinary oxalate levels in either group | 99 | ||
| Adult patients with genetically confirmed primary hyperoxaluria type I (male and female participants) | Oral pyridoxine-HCl (5–20 mg/kg/day) for 24 weeks reduced urinary oxalate | 100 | ||
| Vitamin C | Animal models | Male Wistar rats with induced hyperoxaluria (oral 12% ethylene glycol) | Rats treated with oral vitamin C (100 mg/day) for 2 weeks had no change in renal crystals compared with untreated rats | 145 |
| Male Sprague–Dawley rats with induced hyperoxaluria (oral 2% hydroxyl L-proline) | Rats treated with intravenous vitamin C (500 mg/kg) alone for up to 20 days had reduced calcium oxalate dihydrate crystals in urine, but the formation of other crystal types was unchanged compared with unsupplemented rats | 146 | ||
| Human participants | Health care workers (adult male participants) | Vitamin C intake is not associated with the risk of kidney stones (prospective study) | 87 | |
| Health care workers (adult female participants) | Vitamin C intake is not associated with the risk of kidney stones (prospective study) | 88 | ||
| Health care workers (adult male and female participants) | Total and supplemental vitamin C intake was associated with an increased risk of kidney stones in men but not in women (observational follow-up study) | 122 | ||
| Health care workers (adult male participants) | Men who consumed >1,000 mg/day of vitamin C were at a higher risk of stone formation than men who consumed 90 mg/day (observational follow-up study) | 123 | ||
| Individuals representative of the Swedish male population (adult male participants) | Men who took only vitamin C supplements were more likely to develop kidney stones than men who did not take the supplement (prospective study) | 125 | ||
| Healthy adults (male and female participants) | Oral treatment with 1 g/day of vitamin C did not change urinary oxalate levels, but 5 g/day and 10 g/day of vitamin C increased urinary oxalate | 128 | ||
| Adult calcium oxalate stone formers and healthy individuals (male and female participants) | Treatment with oral vitamin C (5 g/day) for 2 days significantly increased urinary oxalate in both groups compared with placebo (P < 0.01) | 129 | ||
| Adult calcium oxalate stone formers and healthy individuals (male and female participants) | Oral vitamin C (2 g/day) significantly increased oxalate absorption and urinary oxalate in stone formers but not in healthy individuals (P < 0.05) | 130 | ||
| Health care workers (adult male and female participants) | Participants who consumed >1 g/day total of vitamin C had excreted a significantly higher amount of urinary oxalate than participants consuming <1 g/day (trend P < 0.001) | 131 | ||
| Adult calcium stone-formers and healthy individuals (male and female participants) | Oral vitamin C (1 g/day and 2 g/day) for 3 days increased urinary oxalate | 132 | ||
| Adults with sensitivity to acidic foods (male and female participants) | Oral supplementation with vitamin C (500 mg/day) and vitamin C metabolites for 10 days resulted in a lower urinary oxalate than supplementation with vitamin C alone | 136 | ||
| Adult healthy individuals (male and female participants) | Parenteral vitamin C (100 mg/day and 200 mg/day) increased urinary oxalate in a dose-dependent manner | 138 | ||
| One adult woman admitted to the hospital with a complex medical history | Treatment with two doses of intravenous vitamin C (unknown concentration) at an alternative medicine clinic led to development of renal calculi (case report) | 139 | ||
| Two adult men admitted to hospital for SARS-CoV-2 | Patients receiving 50 mg/kg vitamin C four times per day developed renal calculi (case reports) | 140 | ||
| Two adults admitted to the hospital for thermal injuries (one man and one woman) | Patients treated with intravenous vitamin C (66 mg/kg/h) for 18 h and 20 h, respectively, showed calcium oxalate crystals in the kidney (case report) | 141 | ||
| Adult hospitalized patients receiving a high dose of intravenous vitamin C (male and female participants) | High-dose intravenous vitamin C did not cause renal calculi (prospective study) | 142 | ||
| Patients with various conditions receiving high-dose intravenous vitamin C | Scoping review of the harms of high-dose intravenous vitamin C. Renal calculi formation was observed in only one case study | 143 | ||
| Vitamin D | Human participants | Adult kidney stone formers and healthy individuals (male and female participants) | Calcium-containing stone formers had higher 1,25(OH)2D levels than healthy individuals, and hypercalciuria stone formers had higher 25(OH)D levels than normocalciuria stone formers and healthy individuals (meta-analysis) | 188 |
| Adult kidney stone formers and healthy individuals (male and female participants) | Long-term vitamin D supplementation resulted in increased risk of hypercalciuria but not increased risk of stone formation compared with placebo (meta-analysis) | 189 | ||
| Health care workers (adult male and female participants) | Vitamin D intake was not associated with kidney stone formation (meta-analysis) | 190 | ||
| Adult patients with a history of calcium kidney stones and individuals with no history of kidney stones from a urology clinic (male and female participants) | Calcium-containing stone formers had lower levels of circulating 25(OH)D than non-stone formers | 191 | ||
| Adult patients with history of calcium kidney stones and individuals with no history of kidney stones (male and female participants) | Serum levels of 25(OH)D were higher in calcium-containing stone formers than in non-stone formers (retrospective study) | 192 | ||
| Adult kidney stone formers and healthy individuals (male and female participants) | Participants with urolithiasis had an increased prevalence of vitamin D deficiency compared with individuals without urolithiasis (prospective case–control study) | 193 | ||
| Vitamin E | Animal models | Male Sprague–Dawley rats with induced hyperoxaluria (oral 2% hydroxyl L-proline) | Rats treated with intraperitoneal vitamin E (200 mg/kg) alone or in combination with intravenous vitamin C (500 mg/kg) for up to 20 days had reduced calcium oxalate crystals in urine | 146 |
| Male Sprague–Dawley rats with induced hyperoxaluria (oral 150 mg/day ethylene glycol) | Rats treated with an excess (2,000 U/kg) of vitamin E had fewer renal calculi and reduced oxidative stress markers after receiving ethylene glycol than rats receiving adequate (100 U vitamin E/kg) amounts of vitamin E and vitamin E-deficient rats | 230 | ||
| Male Wistar rats with induced hyperoxaluria (oral 0.75% ethylene glycol) | Rats receiving two intraperitoneal injections per week of 200 mg/kg vitamin E for 6 weeks had a reduced Tiselius Risk index for stone oxidative stress markers than unsupplemented rats | 231 | ||
| Male Wistar rats receiving lithogenic diet (calculi-inducing diet) | Rats receiving 400 mg/kg of vitamin E had increased production of antioxidant enzymes and reduced markers of lipid peroxidation compared with control rats | 232 | ||
| Male Sprague–Dawley rats with induced hyperoxaluria (oral 2% hydroxyl L-proline) | Rats treated with intraperitoneal vitamin E (200 mg/kg) alone or in combination with intravenous vitamin C (500 mg/kg) for up to 20 days had reduced calcium oxalate crystals in urine | 146 | ||
| Human participants | Adult calcium oxalate stone formers and healthy individuals (male and female participants) | Plasma levels of tocopherol were higher in sex-matched stone formers than in healthy individuals | 51 | |
| Adult stone formers and healthy individuals (male and female participants) | Stone formers had lower plasma vitamin E than healthy individuals (case–control study) | 56 | ||
| Adult patients with lithiasis (male participants) | Stone formers had significantly (P < 0.05) lower levels of vitamin E than reference values observed in healthy individuals | 233 | ||
| Adult patients with fat malabsorption with or without kidney stones (male and female participants) | Vitamin E levels were lower and markers of oxidative damage were higher in stone formers than in non-stone formers | 234 | ||
| Adult calcium oxalate stone formers and healthy individuals (male and female participants) | Stone formers had lower vitamin E and increased markers of oxidative damage than healthy individuals | 235 | ||
| Adult stone formers and healthy individuals (male and female participants) | Stone formers receiving vitamin E (400 mg/day) for 9 months produced Tamm–Horsfall protein with an increased inhibitory activity against calcium oxalate crystals compared with stone formers who did not receive vitamin E | 238 | ||
| Vitamin K | Animal models | Male Sprague–Dawley rats with induced hyperoxaluria (oral 0.75% ethylene glycol) | Rats treated with vitamin K2 for 6 weeks showed reduced crystal deposition compared with untreated rats | 290 |
| Human participants | Paediatric patients with bladder stones (male participants) | Gla residues found in amino acids isolated from calcium oxalate and hydroxyapatite stones | 276 | |
| Adult patients with kidney stones | Gla residues found in amino acids isolated from calcium oxalate and hydroxyapatite stones | 277 | ||
| Adult patients with calcium oxalate kidney stones and non-stone formers | Reduced number of Gla residues and lower crystal affinity of a human glycoprotein (nephrocalcin) in stone formers than in non-stone formers | 280 | ||
| Adults from Flemish population (male and female participants) | Increased levels of plasma dp-ucMGP were associated with an increased risk of stone formation (Mendelian randomization study) | 291 | ||
| Adult first-time stone formers and healthy individuals (male and female participants) | No change in serum levels of dp-ucMGP in stone formers compared with healthy individuals (prospective study) | 292 |
HCl, hydrochloric acid; Dp-ucMGP, dephosphorylated-uncarboxylated Matrix Gla protein; Gla, γ-carboxyglutamate. aNo statistics performed in the study.