Table 1.
Summary of clinical trials on the effects of vitamin E supplementation on inflammatory biomarkers in adults aged ≥ 20 years.
| Author, year | Design | Participants, n | Health condition | Age, yeara | Intervention | Duration (week) | Outcomes (changes)b | Adjust/matchingc | ||
|---|---|---|---|---|---|---|---|---|---|---|
| Treatment group | Control group | Treatment group | Control group | |||||||
| Upritchard et al. 2000 | RA/parallel | M/F: 25 Int: 12, Con: 13 | DM | Int: 56 ± 14, Con: 60 ± 6 | 800 IU/day α-tocopherol | 4 | CRP: − 2.70 ± 3.70 | CRP: 0.20 ± 1.75 | 4 | |
| Keith et al. 2001 | RA/DB/parallel | M/F: 56 Int: 30, Con: 26 | CVD | Int: 70, Con: 64 | 1000 IU/day α-tocopherol | 12 | TNF-α: 0.40 ± 2.22 | TNF-α: 0.99 ± 2.65 | ||
| Murphy et al. 2004 | RA/DB/parallel | M/F: 110 Int: 55, Con: 55 | CVD | Int: 65 ± 9, Con: 66 ± 13 | 400 IU/day α-tocopherol acetate | 26 | CRP: − 10.47 ± 10.48 | CRP: − 14.19 ± 33.09 | ||
| Lopez et al. 2004 | RA/DB/parallel | M/F: 40 Int: 20, Con: 20 | Healthy | Int: 33 ± 7, Con: 33 ± 10 | 800 IU/day all-rec α-tocopherol | 12 | CRP: 0.10 ± 4.75 | CRP: 0. ± 1.61 | ||
| M/F: 40 Int: 20, Con: 20 | Int: 29 ± 6, Con: 30 ± 9 | 800 IU/day all-rec α-tocopherol + 1.5 g n-3 PUFA | CRP: 0.40 ± 4.79 | CRP: 1.10 ± 6.28 | ||||||
| Hodkova et al. 2006 | RA/parallel | M/F: 29 Int: 15, Con: 14 | HD | Int: 63 ± 6, Con: 60 ± 8 | 400 mg/day α-tocopherol | 5 | CRP: − 0.72 ± 2.56 | CRP: 1.13 ± 3.28 | 1 | |
| Singh et al. 2007 | RA/DB/parallel | M/F: 26 Int: 14, Con: 12 | Healthy | Int: 20–40, Con: 20–40 | 100 mg/day γ-tocopherol | 5 | CRP: 0.50 ± 2.76 | CRP: − 0.30 ± 2.10 | 2,4 | |
| M/F: 25 Int: 13, Con: 12 | 200 mg/day γ-tocopherol | CRP: − 0.40 ± 1.45 | CRP: − 0.30 ± 2.10 | |||||||
| Wu et al. 2007 | RA/DB/parallel | M/F: 36 Int: 18, Con: 18 | DM | Int: 64 ± 30, Con: 62 ± 30 | 500 mg/day α-tocopherol | 6 |
CRP: 0.02 ± 1.34 TNF-α: 0.03 ± 0.15 IL-6: − 0.33 ± 0.65 |
CRP: − 0.20 ± 1.46 TNF-α: 0.03 ± 0.19 IL-6: 0.15 ± 0.71 |
4 | |
| M/F: 37 Int: 19, Con: 18 | Int: 58 ± 17, Con: 62 ± 30 | 500 mg/day mixed tocopherols |
CRP: − 0.21 ± 0.79 TNF-α: 0.02 ± 0.13 IL-6: 0.05 ± 0.45 |
CRP: − 0.20 ± 1.46 TNF-α: 0.03 ± 0.19 IL-6: 0.15 ± 0.71 |
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| Aryaeian et al. 2008 | RA/DB/parallel | M/F: 43 Int: 21, Con: 22 | rheumatoid arthritis | Int: 49 ± 12, Con: 48 ± 11 | 400 mg/day α-tocopherol | 12 | CRP: − 4.99 ± 11.00 | CRP: − 0.96 ± 4.77 | 4,9 | |
| M/F: 44 Int: 22, Con: 22 | Int: 44 ± 13, Con: 46 ± 3 | 400 mg/day α-tocopherol + CLA | CLA | CRP: − 2.06 ± 4.04 | CRP: − 1.72 ± 6.60 | |||||
| Castilla et al. 2008 | RA/parallel | M/F: 16 Int: 8, Con: 8 | HD | 33–79 | 800 IU/day α-tocopherol | Nothing | 2 | CRP: 3.50 ± 8.44 | CRP: 0.69 ± 6.36 | 4 |
| M/F: 16 Int: 8, Con: 8 | 800 IU/day α-tocopherol plus red grape juice | Red grape juice | CRP: − 1.10 ± 6.46 | CRP: 2.40 ± 10.78 | ||||||
| Devaraj et al. 2008 | RA/DB/parallel | M/F: 40 Int: 20, Con: 20 | MetS | Int: 51 ± 11, Con: 56 ± 11 | 800 mg/day α-tocopherol | 6 |
CRP: − 0.86 ± 3.15 TNF-α: − 0.04 ± 0.21 IL-6: 0.20 ± 1.46 |
CRP: − 0.38 ± 3.29 TNF-α: 0.08 ± 0.29 IL-6: 0.50 ± 1.64 |
1,3 | |
| M/F: 40 Int: 20, Con: 20 | Int: 50 ± 9, Con: 56 ± 11 | 800 mg/day γ-tocopherol |
CRP: − 1.49 ± 2.80 TNF-α: − 0.02 ± 0.27 IL-6: − 0.30 ± 1.02 |
CRP: − 0.38 ± 3.29 TNF-α: 0.08 ± 0.29 IL-6: 0.50 ± 1.64 |
||||||
| M/F: 40 Int: 20, Con: 20 | Int: 57 ± 14, Con: 56 ± 11 | 800 mg/day mixed tocopherols |
CRP: − 2.20 ± 3.05 TNF-α: − 0.14 ± 0.30 IL-6: 0.30 ± 1.26 |
CRP: − 0.38 ± 3.29 TNF-α: 0.08 ± 0.29 IL-6: 0.50 ± 1.64 |
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| Balmer et al. 2009 | RA/DB/parallel | M/F: 28 Int: 14, Con: 14 | NASH | Int: 47 ± 14, Con: 47 ± 12 | 800 IU/day α-tocopherol | 104 |
TNFα: − 0.75 ± 0.66 IL-6: − 0.47 ± 2.44 |
TNFα: − 1.65 ± 0.85 IL-6: 0.69 ± 1.88 |
1 | |
| Dalgard et al. 2009 | RA/DB/crossover | M/F: 48 Int: 24, Con: 24 | CVD | Int: 63 ± 7, Con: 57 ± 6 | 15 mg/day α-tocopherol + fruits juice | Fruits juice | 4 |
CRP: − 0.20 ± 0.74 IL-6: 0.10 ± 0.81 |
CRP: − 0.10 ± 2.00 IL-6: − 0.10 ± 0.96 |
|
| Ghiasvand et al. 2009 | RA/DB/parallel | M: 17 Int: 9, Con: 8 | Healthy | Int: 24 ± 2, Con: 21 ± 2 | 400 IU/day α-tocopherol | 6 | IL-6: − 0.10 ± 1.27 | IL-6: 0.16 ± 1.43 | 1,2 | |
| M: 17 Int: 9, Con: 8 | Int: 27 ± 5, Con: 24 ± 3 | 400 IU/day α-tocopherol + EPA | EPA | IL-6: − 2.83 ± 1.49 | IL-6: − 3.81 ± 0.94 | |||||
| Ghiasvand et al. 2010 | RA/DB/parallel | M: 17 Int: 9, Con: 8 | Healthy | Int: 23 ± 2, Con: 21 ± 2 | 400 IU/day α-tocopherol | 6 | TNF-α: 1.44 ± 3.60 | TNF-α: 0.37 ± 3.62 | 1,2 | |
| M: 17 Int: 9, Con: 8 | Int: 27 ± 5, Con: 24 ± 3 | 400 IU/day α-tocopherol + EPA | EPA | TNF-α: 3.50 ± 2.40 | TNF-α: 0.88 ± 4.45 | |||||
| Rafraf et al. 2012 | RA/DB/parallel | M/F: 83 Int: 42, Con: 41 | DM | Int: 35 ± 7, Con: 35 ± 8 | 400 mg/day α-tocopheryl acetate | 8 | CRP: − 0.03 ± 0.59 | CRP: 0.07 ± 0.79 | 1,2,3,4,6,8 | |
| Ahmadi et al. 2013 | RA/parallel | M/F: 41 Int: 17, Con: 24 | HD | Int: 45 ± 13, Con: 49 ± 12 | 400 IU/day α-tocopherol | 8 |
CRP: − 2.00 ± 5.17 IL-6: − 10.00 ± 20.26 |
CRP: 0.19 ± 3.92 IL-6: 10.9 ± 25.50 |
- | |
| M/F: 44 Int: 24, Con: 20 | Int: 53 ± 10, Con: 49 ± 11 | 400 IU/day α-tocopherol + lipoic acid | lipoic acid |
CRP: − 1.60 ± 4.08 IL-6: − 11.00 ± 20.13 |
CRP: − 2.50 ± 4.71 IL-6: − 7.50 ± 17.15 |
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| Daud et al. 2013 | RA/DB/parallel | M/F: 81 Int: 41, Con: 40 | HD | Int: 59 ± 12, Con: 58 ± 13 | 220 mg/day tocotrienol-rich fraction, all types | 16 |
CRP: 1.30 ± 16.90 IL-6: 1.00 ± 2.12 |
CRP: 1.30 ± 23.86 IL-6: 0.60 ± 4.40 |
||
| El-sisi et al. 2013 | RA/DB/parallel | M: 40 Int: 20, Con: 20 | Erectile dysfunction | 40–60 | 400 IU/day α-tocopherol | 6 |
CRP: 0.66 ± 2.55 IL-6: − 3.17 ± 2.32 |
CRP: 0.17 ± 1.74 IL-6: 0.79 ± 2.67 |
||
| Mah et al. 2013 | RA/DB/parallel | M/F: 30 Int: 16, Con: 14 | Healthy smokers | Int: 21 ± 4, Con: 22 ± 4 | 500 mg/day γ-tocopherol | 1 |
CRP: − 1.73 ± 5.28 TNF-α: − 0.29 ± 0.40 IL-6: − 0.02 ± 0.48 |
CRP: − 0.96 ± 2.31 TNF-α: − 0.05 ± 0.2 IL-6: − 0.38 ± 0.80 |
||
| Manning et al. 2013 | RA/DB/parallel | M/F: 76 Int: 36, Con: 40 | MetS | Int: 57 ± 10, Con: 57 ± 9 | 100 IU/day α-tocopherol | 52 |
CRP: 0.50 ± 2.42 TNFα: − 0.09 ± 0.44 IL-6: − 0.30 ± 0.44 |
CRP: 0.00 ± 2.01 TNFα: 0.00 ± 0.32 IL-6: 0.10 ± 0.79 |
2 | |
| M/F: 75 Int: 41, Con: 34 | Int: 54 ± 13, Con: 55 ± 10 | 100 IU/day α-tocopherol + lipoic acid | Lipoic acid |
CRP: − 0.20 ± 2.75 TNFα: 0.30 ± 0.40 IL-6: 0.40 ± 1.07 |
CRP: 0.30 ± 1.68 TNFα: 0.00 ± 0.44 IL-6: 0.99 ± 0.93 |
|||||
| Shadman et al. 2013 | RA/DB/parallel | M/F: 36 Int: 17, Con: 19 | Overweight DM | Int: 48 ± 4, Con: 45 ± 6 | 100 IU/day α-tocopherol | 8 |
CRP: − 0.98 ± 2.71 TNFα: − 2.80 ± 1.83 IL-6: − 0.60 ± 1.83 |
CRP: − 0.55 ± 1.58 TNFα: − 3:00 ± 1.50 IL-6: − 0.89 ± 0.98 |
1,2,3 | |
| Aryaeian et al. 2014 | RA/DB/parallel | M/F: 43 Int: 21, Con: 22 | rheumatoid arthritis | Int: 49 ± 12, Con: 48 ± 11 | 400 mg/day α-tocopherol | 12 | TNFα: − 1.17 ± 2.88 | TNFα: − 1.13 ± 2.74 | 1,2,10 | |
| M/F: 44 Int: 22, Con: 22 | Int: 44 ± 13, Con: 46 ± 13 | 400 mg/day α-tocopherol + CLA | TNFα: − 2.41 ± 2.59 | TNFα: − 2.36 ± 3.63 | ||||||
| Gopalan et al. 2014 | RA/DB/parallel | M/F: 88 Int: 46, Con: 42 | CVD | Int: 52 ± 9, Con: 52 ± 8 | 400 mg/day mixed tocotrienols | 104 | CRP: − 0.57 ± 4.27 | CRP: 2.12 ± 10.76 | ||
| Hejazi et al. 2015 | RA/SB/parallel | M/F: 27 Int: 14, Con: 13 | DM | Int: 48 ± 62, Con: 47 ± 8 | 400 IU/day α-tocopherol | 6 |
CRP: 1.30 ± 8.17 IL-6: 15.40 ± 8.96 |
CRP: − 0.70 ± 4.69 IL-6: 5.60 ± 3.83 |
||
| Modi et al. 2015 | RA/parallel | M/F: 72 Int: 36, Con: 36 | Renal calculi | Int: 39 ± 5, Con: 40 ± 4 | 800 mg/day α-tocopherol | 1 | CRP: 0.09 ± 1.40 | CRP: 2.99 ± 4.28 | ||
| Ramezani et al. 2015 | RA/DB/parallel | M/F: 42 Int: 20, Con: 22 | CVD | Int: 56 ± 2, Con: 55 ± 1 | 400 IU/day α-tocopherol | 8 | CRP: − 1.57 ± 2.41 | CRP: − 1.29 ± 1.99 | ||
| Khatami et al. 2016 | RA/DB/parallel | M/F: 60 Int: 30, Con: 30 | DM | Int: 61 ± 10, Con: 62 ± 14 | 1200 IU/day α-tocopherol | 12 | TNF-α: − 32.8 ± 24.90 | TNF-α: 3.0 ± 24.09 | 1,2,3,4,6,7 | |
| Sohrabi et al. 2016 | RA/parallel | M/F: 46 Int: 23, Con: 23 | HD | Int: 56 ± 9, Con: 57 ± 10 | 1800 IU/week all-rec α-tocopherol + whey protein | 8 |
CRP: − 0.98 ± 0.23 IL-6: − 1.18 ± 2.70 |
CRP: − 0.34 ± 0.87 IL-6: − 3.96 ± 14.25 |
4 | |
| M/F: 46 Int: 23, Con: 23 | Int: 58 ± 8, Con: 55 ± 6 | 1800 IU/week all-rec α-tocopherol | Nothing |
CRP: 0.002 ± 0.90 IL-6: − 5.10 ± 17.90 |
CRP: 0.06 ± 0.34 IL-6: 2.77 ± 4.80 |
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| Stonehouse et al. 2016 | RA/DB/parallel | M/F: 57 Int: 28, Con: 29 | DM | Int: 60 ± 7, Con: 61 ± 6 | 552 mg/day tocotrienol, all types | 8 |
CRP: 0.38 ± 1.68 TNF-α: − 0.09 ± 1.32 IL-6: 0.37 ± 5.77 |
CRP: − 0.07 ± 1.52 TNF-α: − 0.4 ± 1.29 IL-6: − 2.13 ± 5.67 |
1,2,3,5,6 | |
| Ekhlasi et al. 2017 | RA/DB/parallel | M/F: 30 Int: 15, Con: 15 | NAFLD | 25–64 | 400 IU/day α-tocopherol | 8 | TNF-α: − 11.66 ± 10.4 | TNF-α: 2.57 ± 10.1 | 1,3,4 | |
| 400 IU/day α-tocopherol + probiotic strain | Probiotic strain | TNF-α: − 15.01 ± 10.0 | TNF-α: − 9.1 ± 10.1 | |||||||
| Pervez et al. 2018 | RA/DB/parallel | M/F: 64 Int: 31, Con: 33 | NAFLD | Int: 45 ± 9, Con: 44 ± 10 | 600 mg/day δ-tocotrienol (90%) and γ-tocotrienol (10%) | 12 | CRP: − 0.74 ± 0.29 | CRP: − 0.26 ± 0.30 | 4 | |
| Devaraj et al. 2007 | RA/DB/parallel | M/F: 90 Int: 44, Con: 46 | CVD | Int: 59 ± 7, Con: 62 ± 6 | 1200 IU/day α-tocopherol | 104 | CRP: − 1.69 ± 1.69 | CRP: 0.61 ± 1.76 | ||
| Rachelle et al. 2011 | RA/DB/parallel | M/F: 50 Int: 25, Con: 25 | HD | Int: , Con: | 400 IU/day α-tocopherol | 8 | CRP: − 5.80 ± 13.29 | CRP: 6.40 ± 11.48 | 4 | |
CRP C-reactive protein, IL-6 interleukin 6, TNF-α tumour necrosis factor-α, DM diabetes mellitus, CVD cardiovascular disease, NASH nonalcoholic steatohepatitis, NAFLD non-alcoholic fatty liver disease, HD hemodialysis, MetS metabolic syndrome, RA randomized, DB double-blinded, M male, F female, Int intervention, Con control.
aValues are mean ± SD or range (for age).
bChanges in cytokine concentrations are presented by common units for CRP (mg/L), IL-6 (pg/mL) and TNF-α (pg/mL).
cAdjustment or matching: age (1), sex (2), BMI (3), baseline values of cytokines (4), DM (5), duration of DM (6), use of medication or supplements (7), dietary intake of vitamin E (8), changes in other variables (9), disease duration (10).