Table 1 Summary of randomized controlled trials on the effects of vitamin E supplementation on glycemic indices and insulin resistance in patients with diabetes mellitus
Author, year | Design | Participants, n | Diabetes Type | Age, yeara | Intervention | Duration (week) | Outcomes (changes)b | Adjust/matching3 | ||
|---|---|---|---|---|---|---|---|---|---|---|
Treatment group | Control group | Treatment group | Control group | |||||||
Koay et al. 2021 [14] | RA/PC/DB / PA | M/F: 59: Int: 31, Con: 28 | Diabetic nephropathy | Int: 66 ± 13, Con:70 ± 13 | 400 mg/d tocotrienol-Rich Vitamin E | Placebo: NR | 52 | HbA1c: 0.16 ± 0.86% | HbA1c: 0.42 ± 0.74% | Gender, duration of diabetes, baseline HbA1c |
Tat-Ng et al. 2020 | RA/PC/DB / PA | M/F: 80: Int: 39, Con: 41 | Diabetic neuropathy | Int: 63 ± 12, Con:64 ± 15 | 400 mg/d tocotrienol-Rich Vitamin E | Placebo: NR | 8 | HbA1c: 0.23 ± 1.05% | HbA1c: 0.41 ± 1.12% |  |
Dalan et al. 2020 [24] | RA/PC/DB / PA | M/F: 166: Int: 84, Con: 82 | T2DM | Int: 55 ± 10, Con: 57 ± 10 | 266 mg/d α-tocopherol | Placebo: NR | 24 | HbA1c: -0.08 ± 0.73% | HbA1c: -0.03 ± 0.82% | Baseline alpha-tocopherol, haptoglobin genotype |
Jie-Tan et al. 2019 | RA/PC/DB / PA | M/F: 54: Int: 27, Con: 27 | Diabetic nephropathy | Int: 59 ± 10, Con:62 ± 11 | 400 mg/d tocotrienol-Rich Vitamin E | Placebo: NR | 12 | HbA1c: -0.6 ± 0.95% | HbA1c: -0.38 ± 0.89% | Gender, duration of diabetes, baseline HbA1c |
Bril et al. 2019 [23] | RA/PC/DB / PA | M/F: 68: Int: 36, Con: 32 | T2DM | Int: 60 ± 9, Con:57 ± 11 | 720 mg/d vitamin E | Placebo: NR | 77 | Insulin: -3.0 ± 6.0 µIU/mL FBG: -3.0 ± 39.0 mg/dL HbA1c: -0.3 ± 1.2% | Insulin: 3.0 ± 12.0 µIU/mL FBG: 6.0 ± 53.0 mg/dL HbA1c: 0.3 ± 1.6% |  |
El-Aal et al. 2018 [26] | RA/PC/SB/ PA | M: 20: Int: 10, Con: 10 | T2DM | Int: 51, Con: 51 | 400 mg/d α-tocopherol + metformin | Placebo: metformin | 12 | Insulin: -3.8 ± 3.4 µIU/mL FBG: -23.1 ± 13.6 mg/dL HbA1c: -0.9 ± 1.2% HOMA: -4.7 ± 1.1 | Insulin: 1.7 ± 5.0 µIU/mL FBG: 14.2 ± 23.6 mg/dL HbA1c: 0.06 ± 0.8% HOMA: 1.5 ± 2.7 |  |
|  |  | M: 20: Int: 10, Con: 10 | T2DM | Int: 51, Con: 51 | 400 mg/d α-tocopherol + metformin + vitamin C | Placebo: metformin + vitamin C | 12 | Insulin: -5.0 ± 5.3 µIU/mL FBG: -29.2 ± 33.0 mg/dL HbA1c: -1.0 ± 0.8% HOMA: -4.5 ± 1.2 | Insulin: -4.3 ± 2.9 µIU/mL FBG: -24.5 ± 23.1 mg/dL HbA1c: -0.7 ± 0.6% HOMA: -2.3 ± 1.2 |  |
Tan et al. 2018 | RA/PC/DB / PA | M/F: 45: Int: 22, Con: 23 | T2DM | Int: 59 ± 10, Con:63 ± 10 | 400 mg/d tocotrienol-rich vitamin E | Placebo: NR | 8 | HbA1c: -0.55 ± 1.8% | HbA1c: -0.09 ± 1.3% | Age, baseline values |
Dass et al. 2018 [25] | RA/PA | M/F: 60: Int: 31, Con: 29 | T2DM | Int: 51 ± 9, Con:51 ± 7 | 400 mg/d vitamin E | Placebo: NR | 12 | FBG: -16.8 ± 18.3 mg/dL HbA1c: -0.19 ± 0.40% | FBG: -11.5 ± .19.2 mg/dL HbA1c: -0.31 ± 0.49% |  |
Rafraf et al. 2016 [28] | RA/PC/DB / PA | M/F: 83: Int: 42, Con: 41 | T2DM | Int: 53 ± 6, Con:53 ± 8 | 360 mg/d α-tocopherol | Placebo: NR | 8 | Insulin: -1.3 ± 2.4 µIU/mL FBG: -9.1 ± 20.8 mg/dL HbA1c: -0.31 ± 0.67% HOMA: -0.66 ± 0.85 | Insulin: -0.91 ± 2.90 µIU/mL FBG: 4.5 ± 19.1 mg/dL HbA1c: -0.19 ± 0.77% HOMA: -0.19 ± 1.13 | Gender, Age, BMI, medication,FBS level |
Stonehouse et al. 2016 [18] | RA/PC/DB / PA | M/F: 57: Int: 28, Con: 29 | T2DM | Int: 60 ± 6, Con:61 ± 5 | 1020 mg/d α-tocopherol | Placebo: Palm olein | 8 | Insulin: -1.6 ± 0.7 µIU/mL FBG: -5.4 ± 13.8 mg/dL HbA1c: 0.02 ± 0.35% HOMA: -0.21 ± 0.57 | Insulin: -0.78 ± 0.99 µIU/mL FBG: -1.9 ± 13.6 mg/dL HbA1c: 0.04 ± 0.34% HOMA: -0.11 ± 0.54 |  |
Keihan et al. 2016 [44] | RA/PC/DB / PA | M/F: 68: Int: 32, Con: 36 | DM | Int: 57 ± 6, Con:61 ± 6 | 150 mg/d α-tocopherol | Placebo: NR | 12 | FBG: -7.1 ± 12.3 mg/dL HbA1c: 0.54 ± 0.25% | FBG: -21.0 ± .7.1 mg/dL HbA1c: 0.4 ± 0.18% |  |
Khatami et al. 2016 [17] | RA/PC/DB / PA | M/F: 60: Int: 30, Con: 30 | Diabetic nephropathy | Int: 61 ± 10, Con:62 ± 13 | 804 mg/d vitamin E | Placebo: NR | 12 | Insulin: -0.50 ± 2.19 µIU/mL FBG: 11.7 ± 31.2 mg/dL HOMA: 0.10 ± 1.64 | Insulin: 0.70 ± 2.19 µIU/mL FBG: 1.7 ± 31.2 mg/dL HOMA: 0.30 ± 1.64 | Gender, Age, medications, duration of diabetes, baseline BMI |
Hejazi et al. 2015 [27] | RA/PC/SB / PA | M/F: 27: Int: 14, Con: 13 | T2DM | Int: 48 ± 6, Con:46 ± 7 | 360 mg/d vitamin E | Placebo: NR | 6 | Insulin: 0.2 ± 3.3 µIU/mL FBG: -8.5 ± 42.5 mg/dL HOMA: 0.01 ± 1.22 | Insulin: 2.7 ± 4.6 µIU/mL FBG: -16.0 ± 26.7 mg/dL HOMA: 0.06 ± 1.69 |  |
Hashemi et al. 2014 [21] | RA/PC/DB / PA | M/F: 66: Int: 32, Con: 36 | T2DM | Int: 44 ± 4, Con:45 ± 4 | 360 mg/d α-tocopherol acetate | Placebo: NR | 12 | Insulin: 0.3 ± 2.5 µIU/mL FBG: 36.1 ± 39.6 mg/dL HbA1c: 0.20 ± 0.85% HOMA: 0.50 ± 1.02 | Insulin: 1.5 ± 2.8 µIU/mL FBG: 4.7 ± 35.1 mg/dL HbA1c: 0.2 ± 1.11% HOMA: 0.70 ± 1.15 |  |
|  |  | M/F: 68: Int: 34, Con: 34 | T2DM | Int: 45 ± 4, Con:44 ± 5 | 360 mg/d α-tocopherol acetate + EPA | Placebo + EPA | 12 | Insulin: -1.6 ± 2.4 µIU/mL FBG: -10.1 ± 31.7 mg/dL HbA1c: -0.6 ± 0.85% HOMA: -0.7 ± 1.08 | Insulin: -0.6 ± 3.6 µIU/mL FBG: -19.5 ± 23.2 mg/dL HbA1c: -0.8 ± 0.79% HOMA: -0.6 ± 1.26 |  |
Shadman et al. 2013 [12] | RA/PC/DB / PA | M/F: 46: Int: 17, Con: 29 | Overweight T2DM | Int: 47 ± 4, Con:45 ± 6 | 90 mg/d vitamin E + CLA | Placebo: CLA | 8 | Insulin: -0.30 ± 4.15 µIU/mL FBG: -4.2 ± 10.7 mg/dL HbA1c: -0.50 ± 1.00% HOMA: -0.27 ± 1.94 | Insulin: 0.50 ± 2.09 µIU/mL FBG: 2.7 ± 12.5 mg/dL HbA1c: -1.01 ± 1.04% HOMA: -0.7 ± 1.70 | Body composition |
Rafraf et al. 2012 [11] | RA/PC/DB / PA | M/F: 83: Int: 42, Con: 41 | T2DM | Int: 35 ± 6, Con:35 ± 8 | 400 mg/d α-tocopherol acetate | Placebo: NR | 8 | FBG: -9.1 ± 21.3 mg/dL | FBG: 4.5 ± 19.4 mg/dL | Gender, Age, BMI, duration of diabetes, baseline values |
Udupa et al. 2012 [13] | RA/PC/DB / PA | M/F: 50: Int: 25, Con: 25 | T2DM | Int: 53 ± 2, Con:53 ± 2 | 400 mg/d vitamin E | Placebo: NR | 12 | FBG: -6.2 ± 14.4 mg/dL HbA1c: -1.54 ± 1.14% | FBG: 4.9 ± 14.6 mg/dL HbA1c: -0.41 ± 1.16% |  |
Vijayakumar et al. 2011 | RA/ PA | M/F: 74 Int: 38, Con: 36 | T2DM | Int: 54 ± 8, Con:56 ± 8 | 600 mg/d vitamin E | Placebo: NR | 13 | HbA1c: -1.16 ± 0.77% | HbA1c: -0.99 ± 0.77% |  |
Oliveira et al. 2011 [45] | RA/PC/DB / PA | M/F: 51 Int: 25, Con: 26 | T2DM | 30–79 | 800 mg/d α-tocopherol | Placebo: NR | 17 | Insulin: 0.80 ± 5.69 µIU/mL FBG: -1.0 ± 34.94 mg/dL HOMA: 0.40 ± 1.98 | Insulin: 0.00 ± 4.84 µIU/mL FBG: -0.30 ± 46.49 mg/dL HOMA: -0.20 ± 2.32 |  |
|  |  | M/F: 51 Int: 25, Con: 26 | T2DM | 30–79 | 800 mg/d α-tocopherol + lipoic acid | Placebo + lipoic acid | 17 | Insulin: 2.1 ± 4.7 µIU/mL FBG: -17.7 ± 42.5 mg/dL HOMA: 0.10 ± 1.26 | Insulin: -0.9 ± 6.69 µIU/mL FBG: -13.2 ± 57.9 mg/dL HOMA: -0.6 ± 3.51 |  |
Giannini et al. 2007 [46] | RA/PC/DB/ CO | M/F: 10 Int: 10, Con: 10 | T1DM | Int: 18 ± 3, Con: 18 ± 3 | 1200 mg/d α-tocopherol | Placebo: NR | 24 | HbA1c: -0.04 ± 0.37% | HbA1c: -0.02 ± 0.78% |  |
Winterbone et al. 2007 [47] | RA/PC/ PA | M/F: 19 Int: 10, Con: 9 | T2DM | Int: 62 ± 5, Con: 61 ± 5 | 1080 mg/d α-tocopherol | Placebo: NR | 4 | Insulin: 6.6 ± 19.2 µIU/mL FBG: -9.0 ± 32.6 mg/dL | Insulin: -1.0 ± 14.1 µIU/mL FBG: 1.8 ± 13.5 mg/dL |  |
Ward et al. 2007 [19] | RA/PC/DB / PA | M/F: 36 Int: 18, Con: 18 | T2DM | Int: 64 ± 29, Con: 62 ± 29 | 500 mg/d α-tocopherol | Placebo: NR | 6 | Insulin: 1.1 ± 3.3 µIU/mL FBG: -3.6 ± 26.0 mg/dL | Insulin: -1.3 ± 6.2 µIU/mL FBG: -1.7 ± 28.1 mg/dL | Blood pressure |
M/F: 37 Int: 19, Con: 18 | Int: 58 ± 17, Con: 62 ± 29 | 500 mg/d mixed tocopherols | Placebo: NR | Insulin: -0.10 ± 4.56 µIU/mL FBG: 7.2 ± 33.2 mg/dL | Insulin: -1.30 ± 6.20 µIU/mL FBG: -1.7 ± 28.1 mg/dL | |||||
Baliarsingh et al. 2005 [48] | RA/PC/DB/ CO | M/F: 19 Int: 19, Con: 19 | T2DM | Int: 48 ± 6, Con: 52 ± 6 | 180 mg/d α-tocopherol | Placebo: NR | 8 | FBG: 1.4 ± 10.1 mg/dL HbA1c: 0.00 ± 0.25% | FBG: 5.9 ± 13.0 mg/dL HbA1c: 0.00 ± 0.25% |  |
Boshtam et al. 2005 [49] | RA/PC/TB / PA | M/F: 100 Int: 50, Con: 50 | T2DM | Int: 52 ± 9, Con: 54 ± 7 | 134 mg/d α-tocopherol | Placebo: NR | 27 | Insulin: 2.5 ± 6.9 µIU/mL FBG: -8.5 ± 36.9 mg/dL HbA1c: -0.40 ± 0.96% | Insulin: 2.1 ± 5.5 µIU/mL FBG: -27.0 ± 59.3 mg/dL HbA1c: 0.10 ± 1.01% | Gender, age, education, occupation |
Ble-Castillo et al. 2005 [20] | RA/PC/PA | F: 34:: Int: 13, Con: 21 | T2DM | Int: 51 ± 14, Con: 55 ± 11 | 800 mg/d α-tocopherol | Placebo: NR | 6 | FBG: 17.1 ± 14.5 mg/dL | FBG: -32.9 ± 53.8 mg/dL |  |
Economides et al. 2005 [50] | RA/PC/ DB/ PA | M/F: 66: Int: 34, Con: 32 | T2DM | Int: 53 ± 14, Con: 53 ± 14 | 1080 mg/d vitamin E | Placebo: NR | 52 | HbA1c: 0.00 ± 0.74% | HbA1c: 0.00 ± 0.66% |  |
Manzella et al. 2001 [51] | RA/PC/DB / PA | M/F: 50: Int: 25, Con: 25 | T2DM | Int: 63 ± 5, Con: 65 ± 4 | 600 mg/d α-tocopherol | Placebo: NR | 17 | Insulin: -11.1 ± 0.1 µIU/mL FBG: -1.8 ± 3.1 mg/dL HbA1c: -0.70 ± 0.18% HOMA: -0.53 ± 0.23 | Insulin: -0.4 ± 0.1 µIU/mL FBG: -1.8 ± 2.4 mg/dL HbA1c: -0.10 ± 0.36% HOMA: -0.01 ± 0.13 |  |
Park et al. 2001 | RA/PC/PA | M/F: 98 Int: 58, Con: 40 | T2DM | Int: 49 ± 9, Con: 49 ± 10 | 200 mg/d α-tocopherol + CSII | Placebo: CSII | 8 | Insulin: 6.1 ± 3.5 µIU/mL FBG: -91.8 ± 80.1 mg/dL HbA1c: -3.5 ± 1.3% | Insulin: 7.9 ± 1.3 µIU/mL FBG: -88.2 ± .65.3 mg/dL HbA1c: -3.3 ± 1.3% |  |
Feng et al. 2000 [52] | RA/PC/DB/ CO | M/F: 20 Int: 20, Con: 20 | T2DM | Int: 32 ± 8, Con: 32 ± 8 | 1620 mg/d vitamin E | Placebo: NR | 17 | HbA1c: 0.33 ± 0.80% | HbA1c: 0.18 ± 0.87% |  |
Bursell et al. 1999 [53] | RA/PC/DB/ CO | M/F: 36 Int: 36, Con: 36 | DM1 | Int: 31 ± 7, Con: 31 ± 7 | 1206 mg/d vitamin E | Placebo: NR | 36 | FBG: -17.2 ± 65.1 mg/dL HbA1c: 0.20 ± 1.02% | FBG: -31.7 ± 62.3 mg/dL HbA1c: 0.20 ± 1.27% |  |
Gazis et al. 1999 [54] | RA/PC/DB / PA | M/F: 48 Int: 23, Con: 25 | T2DM | Int: 56 ± 11, Con: 57 ± 11 | 1440 mg/d α-tocopherol | Placebo: NR | 8 | FBG: 2.3 ± 33.7 mg/dL HbA1c: 0.20 ± 0.98% | FBG: 5.4 ± 36.7 mg/dL HbA1c: 0.00 ± 0.67% |  |
Tutuncu et al. 1998 | RA/PC/DB / PA | M/F: 48 Int: 23, Con: 25 | T2DM | Int: 56 ± 11, Con: 57 ± 11 | 900 mg/d vitamin E | Placebo: NR | 24 | FBG: 9.0 ± 24.1 mg/dL HbA1c: -1.80 ± 1.07% | FBG: 7.2 ± 11.7 mg/dL HbA1c: 1.10 ± 2.02% | Age, duration of disease, metabolic control |
Colette et al. 1998 | RA/PC/DB/ CO | M/F: 9 Int: 9, Con: 9 | T1DM | Int: 51 ± 11, Con: 51 ± 11 | 1000 mg/d vitamin E | Placebo: NR | 5 | HbA1c: 0.00 ± 0.94% | HbA1c: 0.70 ± 1.36% | Age, gender, weight |
Duntas et al. 1996 [55] | RA/PC/PA | M/F: 24: Int: 12, Con: 12 | T1DM | Int: 41 ± 12, Con:39 ± 12 | 360 mg/d α-tocopherol | Placebo: NR | 26 | FBG: -1.8 ± 19.7 mg/dL HbA1c: -0.12 ± 0.51% | FBG: 0.0 ± 19.7 mg/dL HbA1c: 0.7 ± 0.80% | Duration of disease, weight, glycemic control, insulin dose |
M/F: 24: Int: 12, Con: 12 | 720 mg/d α-tocopherol | Placebo: NR | FBG: -3.6 ± 18.7 mg/dL HbA1c: -0.56 ± 0.46% | FBG: 0.0 ± 19.7 mg/dL HbA1c: 0.7 ± 0.80% | ||||||
Fuller et al. 1996 [56] | RA/PC/PA | M/F: 30 Int: 15, Con: 15 | T1DM | Int: 47 ± 14, Con: 47 ± 12 | 1080 mg/d α-tocopherol | Placebo: NR | 8 | FBG: 27.0 ± 68.0 mg/dL HbA1c: -0.30 ± 1.14% | FBG: 27.0 ± 46.5 mg/dL HbA1c: 0.40 ± 1.59% |  |
Reaven et al. 1995 [57] | RA/PC/DB / PA | M: 21: Int: 10, Con: 11 | T2DM | Int: 60 ± 6, Con:61 ± 8 | 1440 mg/d α-tocopherol | Placebo: NR | 10 | FBG: -0.72 ± 22.76 mg/dL HbA1c: 0.20 ± 0.67% | FBG: -2.1 ± 21.3 mg/dL HbA1c: 0.00 ± 0.66% |  |
Paolisso et al. 1993 [10] | RA/PC/DB/ CO | NR: 25: Int: 25, Con: 25 | T2DM | Int: 71, Con:71 | 900 mg/d d-a-tocopherol Ephynal | Placebo: NR | 12 | FBG: -12.6 ± 24.1 mg/dL HbA1c: -0.60 ± 1.58% | FBG: 1.8 ± 21.6 mg/dL HbA1c: 0.10 ± 1.58% |  |
Ceriello et al. 1991 [7] | RA/PC/PA | M/F: 20: Int: 10, Con: 10 | T2DM | Int: 41 ± 4, Con:40 ± 4 | 1200 mg/d vitamin E | Placebo: NR | 8 | FBG: 9.0 ± 43.1 mg/dL HbA1c: -4.3 ± 1.3% | FBG: -1.8 ± 41.9 mg/dL HbA1c: -0.10 ± 1.39% | Age, duration of disease, metabolic control |
T2DM | Int: 42 ± 3, Con:40 ± 4 | 600 mg/d vitamin E | Placebo: NR | FBG: 10.8 ± 45.3 mg/dL HbA1c: -2.9 ± 1.9% | FBG: -1.8 ± 41.99 mg/dL HbA1c: -0.10 ± 1.39% | |||||