The Role of Vitamin E in Immunity
<p>The structures of tocopherol and tocotrienols.</p> "> Figure 2
<p>Immunomodulatory effects of vitamin E on immune cells. Abbreviations: PGE<sub>2</sub>, prostaglandin E<sub>2</sub>; COX2, Cyclooxygenase 2; NO, Nitric oxide; CD, Clusters of Differentiation; DCs, Dendritic cells; IL-12, Interleukin-12; Ab, antibody; NK, Natural killer.</p> ">
Abstract
:1. Vitamin E: Definition, Structure, Sources, and Functions
1.1. Definition and Structure
1.2. Sources
1.3. Functions
2. Modulation of Immune Responses and Infectious Diseases by Vitamin E Supplementation
2.1. Immune Responses in Animals
2.2. Immune Responses in Humans
2.3. Infectious Diseases in Animals
2.4. Infectious Diseases in Humans
3. Vitamin E and Immune Cells
3.1. Macrophages
3.2. Natural Killer Cells
3.3. Dendritic Cells
3.4. T Cells
3.5. B Cells
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Species | Dosage and Duration | Form of Vitamin E Used | Results | References |
---|---|---|---|---|
Chicks, female broiler (n = 6/group, 6 replicate) | 100 mg/kg diet for 21 days | dl-α-tocopheryl acetate | ↑Plasma IgM levels at day 21 | Dalia et al. 2018 [8] |
↔Splenic expressions of TNF-α, IFN-γ, IL-2, IL-10 | ||||
Pregnant cows (n = 24/group) | 250 IU/day from day 107 of gestation to day 21 of lactation | NA | ↑IgG and IgA concentration in sow plasma | Wang et al. 2017 [9] |
Domestic cats (39 castrated male and 33 intact female) (n = 8/group) | 225, 450 mg/kg diet for 28 days | α-tocopherol | ↑Lymphocyte proliferation (ConA, PHA) | O’ Brien et al. 2015 [10] |
Young and old mice (n = 11–13/group) | 500 mg/kg diet for 6 weeks | dl-α-tocotrienol | ↑Lymphocyte proliferation in old (ConA, PHA) | Ren et al. 2010 [11] |
↑IL-1β production in young | ||||
Young rats (n = 6/group) | 50, 200 mg/kg diet for 8–10 weeks | ↑Lymphocyte proliferation (ConA, LPS) | Bendich et al. 1986 [12] | |
Old mice (n = 10/group) | 500 mg/kg diet for 6 weeks | dl-α-tocopheryl acetate | ↑Lymphocyte proliferation (ConA, LPS) | Meydani et al. 1986 [13] |
↑DTH response | ||||
↑IL-2 production | ||||
↓PGE2 production | ||||
Young and old mice (n = 5/group) | 500 IU (500 mg) for 9 weeks | dl-α-tocopherol acetate | ↑Lymphocyte proliferation (ConA) in young | Wakikawa et al. 1999 [14] |
↔Lymphocyte proliferation (ConA) in old | ||||
↑IFN-γ in young under restraint stress | ||||
Young rats (n = 10/group) | 50, 100, 250, 500, 2500 mg/kg diet for 7 days | dl-α-tocopheryl acetate | ↑Lymphocyte proliferation (>100 mg/kg diet, ConA) (>250 mg/kg diet, LPS) | Moriguchi et al. 1990 [15] |
↑NK activity (>250 mg/kg diet) | ||||
Old rats (n = 5/group) | 585 mg/kg diet for 12 months | dl-α-tocopheryl nicotinate | ↑Lymphocyte proliferation (ConA, PHA) | Sakai S & Moriguchi 1997 [16] |
↑IL-2 production | ||||
Young calves (n = 8/group) | 125, 250, 500 IU (125, 250, 500 mg)/day for 24 weeks | dl-α-tocopheryl acetate | ↑Lymphocyte proliferation (PHA, ConA, pokeweed mitogen) | Reddy et al. 1987 [17] |
↑Antibovine herpesvirus Ab titer to booster in 125 IU/day group | ||||
Young mice (n = 8/group) | 200 mg/kg diet for 6–12 weeks | α-tocopheryl acetate | ↑Ab response | Tanake et al. 1979 [18] |
↑Helper T cell activity | ||||
Mice (n = 10/group) | 500 mg/kg diet for 6 months | α-tocopherol acetate (Tekland, Madison, WI) | ↓IL-6 and PGEs (unstimulated) production by macrophages | Beharka et al. 2000 [19] |
↓Nitric oxide production (LPS) by macrophages |
Subjects | Age | Amount and Duration of Supplementation | Form of Vitamin E Used | Effects on Immune Function | References |
---|---|---|---|---|---|
Young (n = 5) and senior athletes (n = 5) | 18–25, 35–57 | 4.6 ± 0.3 mg/100 mL of vitamin E-enriched beverage 5 days/week for 5 weeks | α-tocopherol acetate | ↑15LOX2, TNF-α expression | Capo et al. 2016 [20] |
Healthy women (n = 108) | 18–25 | 400 mg TRF/day for 56 days | d-α-tocotrienol | ↑IL-4 (TT vaccine), IFN-γ (ConA) | Mahalingam et al. 2011 [21] |
d-γ-tocotrienol | |||||
d-δ-tocotrienol | ↓IL-6 (LPS) | ||||
d-α-tocopherol | |||||
Healthy men and women (n = 19, 34) | 20–50 | 200 mg/day for 56 days | α-tocopherol | ↔IL-4, IFN-γ production (ConA) | Radhakrishnan et al. 2009 [22] |
Adult males and young boys (n = 18) | 25–30, 13–18 | 300 mg/day for 3 weeks | dl-α-tocopheryl acetate | ↓Lymphocyte proliferation (PHA) | Prasad 1980 [23] |
↔DTH | |||||
↓Bactericidal activity | |||||
Institutionalized adult males and females (n = 103) | 24–104 | 200, 400 mg/day for 6 months | α-tocopherol acetate | ↔Ab development to influenza virus | Harman and Miller 1986 [24] |
Healthy elderly males and females (n = 32) | ≥60 | 800 mg/day for 30 days | dl-α-tocopheryl acetate | ↑Lymphocyte proliferation (ConA) | Meydani et al. 1990 [25] |
↑DTH | |||||
↑IL-2 production (ConA) | |||||
↓PGE2 production (PHA) | |||||
Eldery males and females (n = 74) | ≥65 | 100 mg/day for 3 months | dl-α-tocopheryl acetate | ↔Lymphocyte proliferation (ConA, PHA) | De Waart et al. 1997 [26] |
↔IgG, IgA levels | |||||
Healthy elderly males and females (n = 88) | ≥65 | 60, 200, 800 mg/day for 235 days | dl-α-tocopherol | ↑DTH and antibody titer to hepatitis B with 200, 800 mg | Meydani et al. 1997 [27] |
Healthy elderly males and females (n = 161) | 65–80 | 50, 100 mg/day for 6 months | dl-α-tocopheryl acetate | ↑No. of positive DTH reaction with 100 mg | Pallast et al. 1999 [28] |
↑dDiameter of induration of DTH reaction in a subgroup supplemented with 100 mg | |||||
↔IL-2 production | |||||
↓IFN-γ production | |||||
Healthy young adults (n = 31) and premature infants (n = 10) | 24–31 | 600 mg/day for 3 months40 mg/kg body weight for 8–14 days | ↓Chemiluminescence | Okano et al. 1990 [29] | |
Cigarette smoker (n = 60) | 33 ± 4 | 900 IU/day for 6 weeks | ↓Chemiluminescence | Richards et al. 1990 [30] | |
Healthy males (n = 40) | 24–57 | 200 mg/day for 4 months | all-rac-α-tocopherol | Prevented fish-oil-induced suppression of ConA mitogenesis | Kramer et al. 1991 [31] |
Healthy elderly (n = 40) | >65 | 100, 200, or 400 mg/day for 3 months | dl-α-tocopherol | ↑DTH (maximal diameter) in 100, 200, 400 mg groups | Wu et al. 2006 [32] |
↑Lymphocyte proliferation (ConA) in 200 mg group | |||||
Sedentary young and elderly males (n = 21) | 22–29, 55–74 | 800 IU (727 mg)/day for 48 days | dl-α-tocopherol | ↓IL-6 secretion | Cannon et al. 1991 [33] |
↓Exercise-enhanced IL-1β secretion |
Subjects | Age | Dose and Duration of Supplementation | Form of Vitamin E Used | Infection Organism and Route of Infection | Results: Effects of Vitamin E Supplementation | References |
---|---|---|---|---|---|---|
Mice BALB/c (n = 3–6/group) | 6 months | 100 mg/kg for 8 days before MRSA-challenge | δ-, γ-Tocotrienol | MRSA, inoculated onto superficial surgical wounds | Higher NK cytotoxicity | Pierpaoli et al. 2017 [34] |
Higher IL-24 mRNA expression levels | ||||||
Young and aged male mice C57BL/6 (n = 6/group) | 2, 22–26 months | 500 mg/kg for 4 weeks prior to infection | d-α-tocopheryl acetate | Streptococcus pneumoniae, intra-tracheally injected | 1000-fold fewer bacteria in their lung | Bou Ghanem et al. 2015 [35] |
Age-associated higher production of proinflammatory cytokines (TNF-, IL-6) were reduced | ||||||
3-fold reduction in the number of PMNs | ||||||
Worm-free lambs (n =10/group) | 28–32 weeks | 5.3 IU (3.56 mg)/kg BW for 12 weeks | d-α-tocopherol | H. contortus L3 larvae, route NA | No difference in serum IgG or peripheral mRNA expression of IL-4 or IFN-γ | De Wolf et al. 2014 [36] |
Lower PCV, FEC, and worm burden | ||||||
Male mice BALB/c (n = 6–7/group) | At weaning | Deficient, Adequate (38.4 mg/kg diet), or Supplemented (384 mg/kg diet) for 4 weeks | dl-α-tocopheryl acetate | HSV-1, intranasally | Higher viral titre and ILβ, TNF-α, RANTES in the brain with E deficiency | Sheridan & Beck. 2008 [37] |
No difference in expressions of IL-6, TNFα, IL-1β, and IL-10 between adequate and supplemented | ||||||
Mice C57BL (n = 6–9/group) | 22 months | 500 mg/kg diet for 8 weeks | dl-α-tocopherol acetate | Influenza by nasal inoculation | Lower viral titer | Han et al. 2000 [6] |
Higher IL-2 and IFN-γ production | ||||||
Mice, C57BL/6 (n = 4–9) | 22 months | 500mg/kg diet for 6 weeks | dl-α-tocopherol acetate | Influenza A/PC/1/73 (H3N2) by nasal inoculation | Lower viral titre | Hayek et al. 1997 [7] |
Mice, C57BL/6 (n = 6) | 5 weeks | 160 IU/L liquid diet for 4, 8, 12, 16 weeks | all-rac-α-tocopheryl acetate | Murine LP-BM5 leukaemia retrovirus by IP injection | Restored IL-2 and IFN-γ production by splenocytes following infection | Wang et al. 1994 [38] |
Calves, Holstein (n = 7) | 1d | 1400 or 2800 mg orally once per week, 1400 mg injection once per week for 12 weeks | dl-α-tocopheryl acetate | Bovine rhinotracheitis virus, in vitro | Serum from vitamin E-supplemented calves inhibited the replication of bovine rhinotracheitis virus in vitro | Reddy et al. 1986 [39] |
Mice, Swiss Webster (n = 10) | 4 weeks | 180 mg/kg diet for 4 weeks | dl-α-tocopheryl acetate | Diplococcus pneumoniae type I by IP injection | Higher survival | Heinzerling et al. 1974a [5] |
Mice, BALB/C (n = 25) | NA | 25 or 250 mg/kg bw orally for 4 days, starting 2 days before burn injury | dl-α-tocopheryl acetate | Pseudomonas aeruginosa, subeschar injection to burned mice | Lower mortality rate | Fang et al. 1990 [40] |
Mice, BALB/C (NA) | 3 weeks | 4000mg/kg diet for 2, 4, or 14 weeks | Vitamin E injectable (aqueous) | Listeria monocytogenes by IP injection | No difference in resistance | Watson & Petro 1982 [41] |
Rats, Sprague-Dawley (n = 6) | 3 weeks | 180 mg/kg diet + 6000 IU vitamin A/kg diet for 6 weeks | dl-α-tocopheryl acetate | Mycoplasma pulmonis by aerosol | Higher resistance to infection | Tvedten et al. 1973 [42] |
Lambs (n = 10) | NA | 1000 IU orally, 300 mg/kg diet for 23 days | dl-α-tocopheryl acetate | Chlamydia by intratracheal inoculation | Faster recovery (higher food intake and weight gains) | Stephens et al. 1979 [43] |
Turkey, broadbreasted white poults (n = 6) | 1 day | 500 mg/kg diet for 14 days before infection and 18–21 days after infection | dl-α-tocopheryl acetate | Histomonas meleagridis, oral | No effect on mortality by vitamin E supplementation alone | Schildknecht & Squibb 1979 [44] |
Lower mortality and lesion score in combination with ipronidazole | ||||||
Pigs (n = 6) | NA | 200 mg/pig per day for 59 days before infection and 22 days after infection | dl-α-tocopheryl acetate | Treponema hyodysenteriae, oral | Improved weight gain and recovery rate | Teige et al. 1982 [45] |
No beneficial effect on appetite and diarrhoea | ||||||
Sheep (n = 12) | 3–6 months | 300 mg/kg diet starting 2 weeks before first vaccination | dl-α-tocopheryl acetate | Clostridium perfringens type D by IV injection after two IM vaccinations | Higher Ab titre | Tengerdy et al. 1983 [46] |
Fail to prove beneficial effect of vitamin E on protection (none of the vaccinated lambs died) | ||||||
Cows (n = 20) | NA | 740 mg/cow per day, duration NA | dl-α-tocopheryl acetate | Natural occurrence of clinical mastitis due to Streptococci, Coliform, Staphylococci, Clostridium bovis | Lower clinical cases of mastitis | Smith et al. 1984 [47] |
Chicks, broiler (n = 12–14) | 1day | 150 mg or 300mg/kg diet for 2 weeks before infection | dl-α-tocopheryl acetate | Escherichia coli, orally and post-thoracic air sac | Lower mortality | Heinzerling et al. 1974b [48] |
Higher Ab titre | ||||||
Chicks, broiler (n = 10) | 1 day | 300 mg/kg diet for 6 weeks, starting 3 weeks before first infection | dl-α-tocopheryl acetate | E. coli, post-thoracic air sac | Lower mortality | Tengerdy & Nockels 1975 [49] |
Chicks, Leghorn (n = 22) | 1 day | 300 mg/kg diet for 4 weeks before infection | dl-α-tocopheryl acetate | E. coli by IV injection | Lower mortality | Likoff et al. 1981 [50] |
Pigs (n = 10) | 6–8 weeks | 100, 000 mg/t diet for 10 weeks, starting 2 weeks before infection | Vitamin E; Tompson-Hayward, Minneapolis, MN, USA | E. coli by IM injection | Higher serum Ab titre | Ellis & Vorhies 1976 [51] |
Subjects | Age | Dose and Duration of Supplementation | Form of Vitamin E Used | Infection Organism and Route of Infection | Results: Effects of Vitamin E Supplementation | References |
---|---|---|---|---|---|---|
Male smoker | 50–69 | 50 mg/d for median of 6 years | dl-α-tocopheryl acetate | Natural incidence of pneumonia | 69% Lower incidence of pneumonia among subgroups including participants who smoked 5–19 cigarettes per day at baseline and exercised at leisure time | Hemila et al. 2016 [52] |
14% Lower incidence of pneumonia among subgroups including participants who smoked ≥20 cigarettes per day at baseline and did not exercise | ||||||
HIV-infected pregnant Tanzanian women | 25.4 | 30 mg during pregnancy (multivitamin form with 20 mg vitamins B1, 20 mg B2, 25 mg B6, 100 mg niacin, 50 μg B12, 500 mg C, and 800 μg folic acid) | NA | Natural incidence of malaria after having received malaria prophylaxis during pregnancy | Lower incidence of presumptive clinical malaria, but higher risk of any malaria parasitemia | Olofin et al. 2014 [53] |
Patients with HCV-related cirrhosis | 54–75 | 900 IU (604.03 mg for d- or 818.18 mg for dl-)/day for 6 months | α-tocopherol | Natural incidence of cirrhosis | Reduced glutathione (GSH) and glutathione peroxidase, which are significantly lower in cirrhotic patients (p < 0.05), were comparably improved by vitamin E regimens | Marotta et al. 2007 [54] |
Patients with chronic HCV | 18–75 | 945 IU (634.23 mg)/day for 6 months with 500 mg ascorbic acid and 200 μg of selenium | d-α-tocopherol | Natural incidence of HCV | No difference in median log plasma HCV-RNA | Groenbak et al. 2006 [55] |
Nursing home residents | >65 | 200 IU/day for 1 year | dl-α-tocopherol | Natural incidence of respiratory infections | Fewer numbers of subjects with all and upper respiratory infections | Meydani et al. 2004 [56] |
Lower incidence of common cold | ||||||
No effect on lower respiratory infection | ||||||
Male smokers | 50–69 | 50 mg/day during 4-year follow-up | α-tocopherol | Natural incidence of common cold episodes | Lower incidence of common cold | Hemila et al. 2002 [57] |
Reduction was greatest among older city dwellers who smoked fewer than 15 cigarettes per day | ||||||
Male smokers | 50–69 years | 50 mg/day for median of 6.1 years | dl-α-tocopheryl acetate | Natural incidence of pneumonia | No overall effect on the incidence of pneumonia. | Hemila et al. 2004 [58] |
Lower incidence of pneumonia among the subjects who had initiated smoking at a later age (>21) | ||||||
Non-institutionalized individuals | >60 years | 200 mg/day for median of 441 days | α-tocopherol acetate | Natural incidence and severity of self-reported acute respiratory tract infections | No effect on incidence and severity of acute respiratory tract infections | Graat et al. 2002 [59] |
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Lee, G.Y.; Han, S.N. The Role of Vitamin E in Immunity. Nutrients 2018, 10, 1614. https://doi.org/10.3390/nu10111614
Lee GY, Han SN. The Role of Vitamin E in Immunity. Nutrients. 2018; 10(11):1614. https://doi.org/10.3390/nu10111614
Chicago/Turabian StyleLee, Ga Young, and Sung Nim Han. 2018. "The Role of Vitamin E in Immunity" Nutrients 10, no. 11: 1614. https://doi.org/10.3390/nu10111614