Table 3.

Effects of vitamin E supplementation on infectious diseases in animal models.

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]

Ab, antibody; FEC, fecal egg count; HSV, Herpes simplex virus; MRSA, IFN-γ, interferon-γ; IM, intramuscular; IV, intravenous; Methicillin-resistant Staphylococcus aureus; NK, natural killer; PCV, packed cell volume; PMN, polymorphonuclear leukocyte, RANTES, regulated on activation, normal T cell expressed and secreted; TNF-α, tumor necrosis factor-α.