Insights on Localized and Systemic Delivery of Redox-Based Therapeutics

Table 2

Preclinical and clinical studies using vitamin E.

Vitamin E
Route	Results	Reference
Preclinical studies
In vitro	α-Tocopherol activates Nrf2 in human retinal pigment epithelial cell line ARPE-19, thus inducing transcription of phase II enzymes	[32]
Oral	16 weeks of 1500 IU vitamin E daily is able to rescue Nrf2 function in alveolar macrophages from human atopic asthmatics	[33]
In vitro	α-Tocopheryl succinate activates Nrf2 in PC3 prostate cancer cell line which inhibits NF-κB nuclear translocation and neoplastic activity	[31]
Oral; I.M.	Vitamin E significantly reduced atherosclerotic plaque progression in rabbits fed a high-cholesterol diet	[26]
Oral	Vitamin E significantly reduced atherosclerotic plaque progression in ApoE^−/− mice	[27]
Oral	Vitamin E deficiency disrupts grass carp growth and physiology while vitamin E supplementation is able to reverse the negative effects	[34]
Clinical studies
400–800 IU; Oral	Daily vitamin E supplementation showed substantial reduction in nonfatal myocardial infarction in patients with angiographically proven coronary atherosclerosis, yet no significant benefit on risk of cardiovascular death was observed	[38]
400 IU; Oral	4–6 years of daily vitamin E supplementation showed no therapeutic benefit on cardiovascular events in high-risk patients 55 years of age or older	[39]
100–3200 IU; Oral	16 weeks of at least 800 IU/day of vitamin E required to reduce the plasma F2-isoprostane concentration	[40]
400 IU; Oral	Daily supplementation of vitamin E only therapeutic in type 2 diabetes with genotype for systemically elevated oxidative stress	[41]
400 IU; Oral	Hemodialysis patients experienced reduced rate of plasma MDA level increase following 2 months of vitamin E supplementation.	[44]
400 mg; Oral	Patients with Down syndrome had their abnormal superoxide dismutase and catalase activity as well as low levels of reduced glutathione returned to physiological levels following vitamin E supplementation	[45]
2000 IU; Oral	Daily high dose of vitamin E slowed the functional decline of Alzheimer’s disease patients	[46]
400 IU; Oral	Eight weeks of daily vitamin E supplementation increased paraoxonase-1 enzyme activity but did not lower serum malondialdehyde levels in type 2 diabetic patients	[43]
300 mg; Oral	Three months of daily vitamin E supplementation significantly reduced serum malondialdehyde levels in insulin-dependent type 2 diabetic patients	[42]
Ointment; S.C.	Patients undergoing colorectal cancer surgery exposed to vitamin E at the surgical site experienced a reduced rate of surgical site infection and lowered inflammatory response	[47]

I.M.: intramuscular; S.C.: subcutaneous.