Table 1 Summary of clinical trials on the effects of vitamin E supplementation on inflammatory biomarkers in adults aged ≥ 20 years.

From: The effect of vitamin E supplementation on selected inflammatory biomarkers in adults: a systematic review and meta-analysis of randomized clinical trials

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

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

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

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

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

  1. 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.
  2. aValues are mean ± SD or range (for age).
  3. bChanges in cytokine concentrations are presented by common units for CRP (mg/L), IL-6 (pg/mL) and TNF-α (pg/mL).
  4. 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).