Table 1. Summary of main characteristics and findings of the included studies.
| Study, year (ref) | Study population | Population characteristics | Intervention | Control | Vintage | Outcome(s) | Results | Notes |
|---|---|---|---|---|---|---|---|---|
| Klein et al. 1995 [13] | Normoalbuminuric IDDM patients with hyperfiltration | N = 24 - Male = 100% - Age = ~ 32.5 yrs - Diabetes vintage = ~7.5 yrs - GFR~141.5 ml min-1 1.73m2 |
Vitamin C (3 g twice a day) (n = 12) |
Placebo (n = 11) |
4 wks | UAE (μg min-1) | -No significant difference between intervention and control group (7.4±2.1 vs 7.4±2.8) | - Double-blind - One drop-out from placebo group for stomachache - No adverse events in the intervention group reported |
| GFR (ml min-1 1.73m2) | -No significant difference between intervention and control group (134±12 vs 137±16) | |||||||
| Sinclair et al 1997 [21] | NIDDM patients with microalbuminuria | N = 14 - Male = 57% - Age = 65 yrs |
Vitamin C (750 mg/day) Vitamin E (600 mg/day) Beta-carotene (18 mg/day) (n = 6) |
Placebo (n = 4) |
12 wks | UAE (μg min-1) | - Average change over active period (-201±0.23) and over placebo period (0.054±0.15) (p = 0.0054) | - Cross-over - Four drop-out - Six patients received treatment for 6 wks in each arm |
| McAuliffe et al 1998 [22] | IDDM and NIDDM patients with microalbuminuria | N = 20 -Male = 75% -Age = ~58 yrs - Diabetes vintage = ~12 yrs - NIDDM = 90% -UAE = ~60 μg min |
Vitamin C (500 mg twice a day) (n = 10) |
Placebo (n = 10) |
12 mo | UAE (μg min-1) | -Significant decrease in intervention group (p = 0.03) | - Double-blind -One drop-out from intervention group for bladder carcinoma |
| Gaede et al 2001 [14] | NIDDM patients with microalbuminuria | N = 29 -Male = 69% -Age = 58.7±7.3 -Diabetes vintage = 12.2±4.4 yrs |
Vitamin C (1250 mg/day) Vitamin E (680 IU) (n = 29) |
Placebo (n = 29) |
4 wks | UAE (mg/24 h) | -Significant decrease in intervention group (19%, 95% CI 6–34%; p = 0.04) | -Double-blind -Cross-over -No adverse events reported |
| Serum Cr (μmol/L) | -No difference between intervention (85±20) and placebo group (86±19; p = 0.55) | |||||||
| Yokoyama et al 2001 [23] | NIDDM patients with microalbuminuria | N = 54 Not specified |
Vitamin E (600 mg/day) (n = 29) |
No treatment (n = 25) | 6 mo | UAE (mg/day) | - No significant difference between intervention and placebo group | -Open label |
| Lonn et al 2002 [24] | IDDM and NIDDM patients | N = 3654 - Male = 63% - Age = ~65.4 - Diabetes vintage = ~11.45 yrs - NIDDM = ~97.75% - 31.6% with microalbuminuria |
Vitamin E (400 IU/day) (n = 1838) | Placebo (n = 1816) | Average 4.5 yrs | Dialysis (%) | - No significant difference between intervention (0.5) and placebo group (0.5) (p = 0.97) | - Double-blind - No adverse events reported |
| UAE (mg/g Cr) | - No significant difference between groups | |||||||
| Incidence of new-onset microalbuminuria (%) | - No significant difference between intervention (35.3) and placebo group (37.5) (p = 0.14) | |||||||
| Farvid et al 2005 [15] | NIDDM patients with microalbuminuria | N = 76 - Male = 47% - Age = 50.5 yrs - Diabetes vintage = ~8.5 yrs - UAE = ~31.5 mg/g cr |
-Group M (Zinc sulphate 15 mg + magnesium oxide 100 mg (n = 18) -Group V (Vitamin C 100 mg + Vitamin E 50 IU) (n = 20) -Group MV (Zinc sulphate 15 mg + magnesium oxide 100 mg + Vitamin C 100 mg + Vitamin E 50 IU) (n = 19) |
Placebo (n = 19) | 3 mo | UAE (mg/g Cr) | - Significant decrease in group MV (29.3 vs 10.8, p = 0.005) - Significant decrease in group V (35.6 vs 22.1, p = 0.034) |
- Double-blind - Two drop-out for side effects - Five excluded from statistical analysis because of protocol violation |
| Urinary protein (g/g cr) | - No within-group significant difference | |||||||
| Giannini et al 2007 [16] | IDDM patients with microalbuminuria | N = 10 - Male = 70% - Age = 18.9±2.9 yrs - Diabetes vintage = 12.6±3.4 yrs - UAE = 33.4±7.6 |
Vitamin E 1200 mg/day (n = 10) |
Placebo (n = 10) |
6 mo | UAE (μg min-1) | - No significant difference between intervention group (24.35±8.67) and placebo group (27.29±11.89) (p = 0.59) | - Double-blind - Cross-over - No adverse events reported |
| CrCl (μg min-1/1.73 m2) |
- No significant difference between intervention group (154.6±29.1) and placebo group (155.6±29.3) (p = 0.34) | |||||||
| Parham et al 2008 [17] | NIDDM patients with microalbuminuria | N = 50 - Male = 57% - Age = ~53 yrs - Diabetes vintage = ~11.2 yrs - UAE = ~88.5 mg/g cr |
Zinc (30 mg/day) (n = 21) |
Placebo (n = 21) |
3 mo | UAE (mg/g Cr) | - Significant decrease in intervention group (86±57 vs 75±71) (p = 0.05) - No significant difference in placebo group - Significant difference between intervention (75±71) and placebo group (90±60) (p<0.05) |
- Double-blind - Cross-over - Eight drop-out: Intervention group: four (one for epigastric pain, one for change of drugs, two for poor compliance) Control group: four (one for epigastric pain, one for change of drugs, two for starting insulin therapy) |
| GFR (ml/min) | - No significant difference within intervention (88±29) and placebo group (83±20) | |||||||
| Abarghouei et al 2012 [25] | NIDDM patients with macroalbuminuria | N = 60 Not specified |
Sylimarin (420 mg/day) (n = 30) |
Placebo (n = 30) | 3 mo | UAE (mg/day) | - Significant within-group decrease - Higher decrease in the intervention vs control group (p = 0.005) |
- Double-blind |
| Khan et al 2013 [18] | NIDDM patients with microalbuminuria | N = 54 - Age = ~56 yrs - Diabetes vintage = ~9 yrs - UAE = ~146 mg/day |
Zinc (50 mg/day) (n = 23) |
No treatment (n = 21) |
12 wks | UAE (mg/day) | - Significant decrease in intervention group (146.87±30.83 vs 80.70±33.99) (p<0.0001) - Significant increase in control group (145.05±45.97 vs 157.43±49.51) (p = 0.02) |
- 10 drop-out: 4 Intervention group: four (change of drug) 6 Control group: six (poor compliance) |
| Noori et al 2013 [19] | NIDDM patients with microalbuminuria | N = 34 - Male = 38% - Age = ~60.5 yrs - Diabetes vintage = ~13.5 yrs - UAE = ~208.5 mg/g cr |
Lipoic acid (800 mg) + pyridoxine (80 mg)/day (n = 17) |
Placebo (n = 17) |
12 wks | UAE (mg/g cr) | - Significant decrease in intervention group (236±75 vs 162±44) (p<0.05) - Significant difference between groups (p<0.05) |
- Double-blind, - No adverse events reported |
| Haghighat et al 2014 [20] | NIDDM patients with microalbuminuria | N = 50 - Male = 27% - Age = ~ 55 yrs - Diabetes vintage = ~4.7 yrs - UAE = ~ 20 nmol/dl |
Tocotrienol-enriched canola oil (15 ml/day) (n = 23) |
Placebo (n = 22) |
4 wks | UAE (nmol/dl) | - Significant difference between groups (intervention: Median 11 IR: 9–25, control: Median 22 IR: 15–39.75; p<0.001) | - Double-blind -Five drop-out: Intervention group: two (one for lost to follow-up, one for changing in treatment protocol); Control group: three (one for inability to walk to centre, one for unavailability of 24h urine collection, one for unwillingness) - No adverse events reported |
| Jadhav et al 2014 [26] | Patients with diabetic nephropathy | N = 216 Not specified |
- Vitamin C + Vitamin E - Reduced glutathione - Vitamin C + Vitamin E + Reduced glutathione |
No treatment | 4 mo | UAE (mg/g cr) | - Significant decrease in vitamins C + E group (33.2±2 vs 30.5±2; p<0.009) - Significant decrease in reduced glutathione group (31.4±2 vs 30.1±1; p<0.002) - Significant decrease in the vitamins plus glutathione group (33.3±2 vs 27.2±2; p<0.001) |
- Open label - Sample size and dose of treatments in each group not specified |
Cr: creatinine; CrCl: creatinine clearance; GFR: glomerular filtration rate; IDDM: insulin-dependent diabetes mellitus; IR: interquartile range; MO: months; NIDDM: non-insulin-dependent diabetes mellitus; UAE: urinary albumin excretion rate; wks: weeks; yrs: years;