Podání vit. E bez prokázaného benefitu

Age-related maculopathy

• Meta-analysis of two RCTs providing more than 50 mg/day of supplemental alpha-tocopherol
• Did not show a significant effect of supplementation on the risk of age-related maculopathy compared with placebo (I2 = 19 %) (Evans, 2008). [2]

Alzheimer’s disease

• Systematic review with meta-analysis of seven observational studies (Li et al., 2012)
• Significant inverse association between dietary intake of ‘vitamin E’ from food and the risk (pooled RR (95 % CI): 0.76 (0.67–0.84), I2 = 43.2 %, p = 0.103).
• No quantitative data can be derived from these meta-analyses in order to set DRVs for alpha-tocopherol [2]
• No convincing evidence that doses of up to 2000 units/day slow the progression of Alzheimer disease [9]
• No decrease the risk of prostate cancer [9]

Mild cognitive impairment (MCI) and those with AD

• Level of markers of oxidative damage to DNA, proteins, and lipids is increased
• Expression and activities of glutathione and antioxidant enzymes are reduced [10]

• Meta-analysis
• Circulating concentrations of vitamins, including vitamin A, vitamin C, and vitamin E
• Significantly lower in AD patients than in cognitively healthy individuals

• Other studies
• Low concentrations of vitamin E in cerebrospinal fluid of cognitively impaired patients [10]

• Reduction in oxidative stress may help maintain cognitive status
• And/or prevent deterioration

• Multicenter, randomized, placebo-controlled study in individuals with AD of moderate severity
• Supplementation with 2,000 IU/day of all-rac-alpha-tocopherol (equivalent to 900 mg/day of RRR-alpha-tocopherol) for 2 years
• Significantly delayed cognitive decline
• Slowed disease progression
• Increased median survival

• Placebo-controlled trial in 769 patients with MCI
• Same dosage of vitamin E
• Did not affect the probability of progression from MCI to AD over a 3-year period

• Double-blind, placebo-controlled trial
• Randomized to receive 800 IU/day of all-rac-alpha-tocopherol (360 mg/day of RRR-alpha-tocopherol) for 6 months
• Mini Mental State Examination (MMSE) scoring system improved
• Only when the treatment effectively reduced oxidative stress
• Assessed by the measure of total glutathione
• Markers of lipid peroxidation in the blood
• Failure to reduce oxidative stress resulted in supplemental vitamin E being more detrimental to the cognitive function of AD patients than placebo !!!

• Multicenter, randomized, double-blind, placebo-controlled study
• Supplemental vitamin E (2,000 IU/day; form of vitamin E not mentioned in the publication) for over 2 years
• Significantly delayed functional decline
• Determined by the (in)ability to perform basic activities of daily living
• Reduced the annual mortality rate
• In mild and moderate AD patients
• vitamin E failed to affect cognitive performance measured with MMSE scores and other cognitive ability tests [10]

• Little evidence to suggest that long-term supplementation of vitamin E provides any cognitive benefits in healthy older adults [10]

Katarakta

• Cross-sectional study
• vitamin E concentrations were found to be significantly lower in the lens and blood of subjects with
• Age-related nuclear, but not cortical, cataracts
• When compared with an age-matched control group [10]

• Earlier studies reported higher vitamin E concentrations in the lenses and blood of patients with cataracts [10]

• Results of several observational studies
• Examined the association between vitamin E consumption and the incidence or severity of cataracts
• Are also mixed
• Some reported that increased vitamin E intake protected against cataract development
• Others found no association [10]

• Meta-analysis of eight studies
• Including 15,021 participants
• Found a 17% reduction in the risk of age-related cataract in subjects
• In the highest versus lowest quantile of dietary vitamin E intake [10]

• Prospective cohort study of 31,120 Swedish men
• Followed for a mean of 8.4 years
• Observed a greater risk of developing cataract in occasional and regular users of high-dose (about 100 mg/day) vitamin E supplements only
• When compared with non-supplement users
• Use of supplemental high-dose vitamin E with additional supplements or the use of low-dose vitamin E-containing multivitamin supplements was not found to be associated with an elevated cataract risk [10]

• A meta-analysis based on data from over 350,000 participants in 10 studies
• Including the above-cited study by Zheng Selin et al.
• Found no association between supplemental vitamin E and risk of cataract [10]

• Supplementation of high-dose vitamin E — alone or in addition to other supplements
• Was found to be safe
• Benefits regarding cataract risk or progression were limited [10]

• Early intervention trial
• Daily supplement of 50 mg of synthetic alpha-tocopherol (equivalent to 25 mg of RRR-alpha-tocopherol)
• Did not alter the incidence of cataract surgery in male smokers [10]

• A randomized, placebo-controlled intervention trial in 4,629 men and women
• Daily supplement
• 500 mg of vitamin C
• 400 IU of all-rac-alpha-tocopheryl acetate (equivalent to 180 mg of RRR-alpha-tocopherol)
• 15 mg of beta-carotene [10]
• Did not affect development and progression of age-related cataracts over a seven-year period
• Did not limit the progression of cataract in a five-year intervention trial [10]

• Four-armed, randomized, placebo-controlled study of 11,267 men
• From the Selenium and Vitamin E Cancer prevention trial (SELECT)
• Failed to observe a reduction in cataract incidence
• With 400 IU/day of supplemental all-rac-alpha-tocopheryl acetate (180 mg/day of RRR-alpha-tocopherol)
• Alone or in combination with selenium (200 µg/day)
• During a mean 5.6 years of follow-up [10]

• Four-year randomized, placebo-controlled trial
• 500 IU/day (335 mg/day) of RRR-alpha-tocopherol
• Did not reduce the incidence or progression of cataract in older adults [10]

Age-related macular degeneration

• Pooled analysis of four randomized controlled trials in 62,520 subjects
• Found that supplemental vitamin E or beta-carotene
• Did not reduce the risk of developing age-related macular degeneration (AMD) [10]

• Review of currently available data
• Supplements of antioxidants plus zinc
• May reduce the progression of AMD and vision loss in affected individuals [10]

• Age-Related Eye Disease Study (AREDS)
• Participants with borderline to advanced age-related macular degeneration (AMD)
• Randomized to receive
• (1) placebo;
• (2) 15 mg/day of beta-carotene, 500 mg/day of ascorbic acid, and 400 IU/day of all-rac-alpha-tocopheryl acetate
• (3) zinc (80 mg/day) and copper (2 mg/day)
• (4) both antioxidant vitamins and zinc and copper
• Five-year results indicated that the risk of developing advanced AMD was
• Significantly reduced in those taking zinc with or without antioxidant vitamins [10]
• Antioxidant vitamins alone failed to prevent the progression to advanced AMD
• Even in individuals at higher risk
• Combination of antioxidant vitamins and minerals may benefit people with intermediate AMD or advanced AMD in one eye [10]

Ca obecně

• Most clinical trials have failed to find any beneficial effects of vitamin E supplementation on the risk of various cancers

• Randomized, placebo-controlled trial (RCT) in 39,876 women
• Women's Health Study
• Supplementation with 600 IU (400 mg) of RRR-alpha-tocopherol every other day for 10 years
• Had no effect on overall cancer incidence or cancer-related deaths [10]

Cardiovascular disease-related outcomes

• ‘vitamin E’ or alpha-tocopherol through diet or supplementation (alone or in combination)
• Number of systematic reviews, RCTs, prospective cohort studies and case–control studies (Heinonen et al., 2012).
• Effect of aspirin or 300 mg/day of ‘synthetic alpha-tocopherol’ supplementation compared with a placebo = no conclusion [2]
• Alpha-tocopherol supplementation of at least 50 mg/day
• Did not have an effect on
• Intermittent claudication (Tornwall et al., 1997; Tornwall et al., 1999),
• Abdominal aortic aneurysm (Tornwall et al., 2001),
• Intima–media thickness (Hodis et al., 2002)
• Cardiovascular events (fatal and non-fatal) (Tornwall et al., 2004b) [2]
• Alpha-Tocopherol supplementation (50 mg/day, background alpha-tocopherol intake not reported)
• Did not have any significant effect on
• Primary stroke incidence [2]
• Mortality in normotensive male smokers (50–69 years at inclusion) during an RCT (median duration: six years) or post trial (Leppala et al., 2000b; Leppala et al., 2000a; Tornwall et al., 2004a). [2]
• Prospective cohort study in 34 492 post-menopausal women followed for 11 years
• No relationship between risk of death from stroke and quintiles of intake of ‘vitamin E’ from food and supplements, food only or supplements only [2]
• Prospective cohort study in 559 men (mean age: 72 years) free of chronic diseases in 1985
• Mean alpha-tocopherol intake (± SD), without dietary supplements, was 9.1 ± 4.6 mg/day at baseline (Buijsse et al., 2008) [2]
• After 15 years alpha-Tocopherol dietary intake at baseline was not associated with
• 15-year cardiovascular disease mortality after adjustments, in all the models tested. [2]

Cancer

• No relationship was observed between ‘vitamin E’ or alpha-tocopherol intake and
• Breast cancer (Yuan et al., 1995; Freudenheim et al., 1996; Do et al., 2003; Nissen et al., 2003; Frazier et al., 2004; Nagel et al., 2010),
• Bladder cancer (Riboli et al., 1991; Albanes et al., 1995; Jacobs et al., 2002; Brinkman et al., 2010),
• Cervical, endometrial and ovarian cancers (Fairfield et al., 2001; Xu et al., 2007; Ghosh et al., 2008; Kim et al., 2010),
• Renal cancer (Hu et al., 2009),
• Pancreatic cancer (Rautalahti et al., 1999),
• Stomach cancer (Alkhenizan and Hafez, 2007),
• Testicular cancer (Bonner et al., 2002),
• Skin carcinomas (Kirkpatrick et al., 1994; Fung et al., 2002)
• Lung cancer (1994; Albanes et al., 1995; Ocke et al., 1997; Alkhenizan and Hafez, 2007). [2]
• Inconsistent results
• Risk of colorectal carcinoma (Bostick et al., 1993; Ferraroni et al., 1994; Albanes et al., 1995; Slattery et al., 1998; Malila et al., 1999; Jacobs et al., 2001; Wu et al., 2002; Chiu et al., 2003; Satia-Abouta et al., 2003; Murtaugh et al., 2004; Kune and Watson, 2006; Arain and Abdul Qadeer, 2010).
• Risk of prostate cancer (Albanes et al., 1995; Rautalahti et al., 1999; Alkhenizan and Hafez, 2007; Wright et al., 2007; Bidoli et al., 2009; Gaziano et al., 2009; Lippman et al., 2009; Klein et al., 2011; Kristal et al., 2014; Wang et al., 2014). [2]

All-cause mortality

• Three meta-analyses of RCTs (Miller et al., 2005; Bjelakovic et al., 2007; Abner et al., 2011)
• ‘vitamin E’ supplementation, alone or in combination with other micronutrients, and all-cause mortality.
• Often performed in patients with chronic diseases, form of ‘vitamin E’ was often unknown, trials often used doses of the vitamin exceeding the UL [2]

Primary open-angle glaucoma

• Two large prospective cohort studies (one in men and the other in women)
• No significant association between ‘vitamin E’ intake (Kang et al., 2003). [2]

Tarditive diskinesia

• Whether supplements can protect against tardive dyskinesia is controversial [9]