Indikace a možný benefit z podání vitamínu E

AEVD

• Vitamin E supplements in amounts well over 1000 mg/d have been prescribed for children with vitamin E deficiency
• Alpha-Tocopherol supplements are recommended
• Prevent the further progression of the neurologic abnormalities
• In some cases reverse them [7]
• High-dose vitamin E (800-1,200 mg/day) is used to prevent neurologic deterioration in AVED subjects [10]

Abetalipoproteinemia

• vit. E suppl. 1000mg/d
• Prevented neurologic symptoms and stopped the progression of myopathy in individuals with [7]
• Larger doses of alpha-tocopherol given by injection are required to treat neuropathy during its early stages or to overcome the defect of absorption and transport [9]

Nonalcoholic fatty liver disease

• Major cause of liver dysfunction
• Is increasing in children due to the increasing prevalence of obesity and type 2 diabetes
• Severe negative effects associated with nonalcoholic fatty liver disease include
• Progression to nonalcoholic steatohepatitis (NASH)
• Liver cirrhosis
• Liver cancer
• Vitamin E supplementation decreases histologic evidence of NASH [7]
• Supplementation has been tried in children with promising results

• D'Adamo et al. reported in obese children that 600 mg ?-tocopherol daily
• Doubled plasma concentrations from a mean (±SD) of 32.7 ± 1.5 µmol/L to 63 ± 14 µmol/L
• Did not provide lipid-corrected values
• Serum total cholesterol was, on average, 180 mg/dL (4.65 µmol/L)
• TGs were 83 mg/dL (0.94 µmol/L)
• After 6 mo of vitamin E treatment decreased:
• Serum alanine aminotransferase
• Urinary prostaglandin F2-alpha
• insulin,
• Fasting glucose concentrations
• Lipid profiles
• High-sensitivity C-reactive protein
• It is unclear how many of these changes are due to the diet and behavior intervention rather than to vitamin E supplementation [7]

• Sanyal et al. reported, “Vitamin E therapy, as compared with placebo, was associated with
• Significantly higher rate of improvement in nonalcoholic steatohepatitis (43% vs. 19%, P = 0.001) [7]

• Multicenter PIVENS
• PIoglitazone versus Vitamin E versus placebo for the treatment of Nonalcoholic Steatohepatitis) trial
• 247 nondiabetic subjects with NASH
• Randomized to receive
• 30 mg/day of pioglitazone (an insulin-sensitizing drug)
• 800 IU/day (536 mg/day) of RRR-alpha-tocopherol
• Placebo for 96 weeks [10]
• Only vitamin E supplementation significantly increased the overall rate of improvement in histological abnormalities that characterize NASH on liver biopsies
• Hepatocellular ballooning,
• Steatosis,
• Lobular inflammation [10]
• Both active treatments improved some markers of liver function
• Alanine aminotransferase
• Aspartate aminotransferase [10]

• Two-year, randomized controlled trial — called TONIC for Treatment Of Nonalcoholic fatty liver disease In Children
• 173 children (ages, 8-17 years) with NAFLD
• Failed to observe any significant reduction in blood concentrations of
• Alanine and aspartate aminotransferases
• Either with supplemental vitamin E (536 mg/day of RRR-alpha-tocopherol)
• Or with metformin (an anti-diabetic drug; 1,000 mg/day)
• Compared to placebo [10]
• vitamin E supplementation significantly improved the overall disease activity score
• Used to quantify the severity of the disease [10]

• Meta-analysis of another six trials
• vitamin E significantly lowered circulating aminotransferase concentrations in NAFLD and NASH patients [10]

• Small nonrandomized, unblinded, controlled study in 42 obese children (mean age, 8 years) with NAFLD
• Lifestyle recommendations combined with 600 mg/day of supplemental RRR-alpha-tocopheryl acetate for 6 months reduced
• Markers of oxidative stress
• Liver dysfunction
• insulin resistance
• lipids in the blood, when compared to baseline [10]
• No such changes in markers of oxidative stress, liver function, and glucose utilization were reported in the lifestyle intervention only group [10]

Type 2 diabetes mellitus

• Oxidative stress contributes to the progression of type 2 diabetes mellitus
• Auses damage to many organs and tissues, including the pancreas, brain, eyes, peripheral nerves, and kidneys [10]

• Animal studies suggests
• vitamin E supplementation could mitigate the role of oxidative damage in the occurrence of diabetes complications [10]

• Alpha-Tocopherol Beta-Carotene cancer prevention (ATBC) trial in male smokers
• Supplementation with 50 mg/day of synthetic alpha-tocopherol (25 mg/day of RRR-alpha-tocopherol)
• Had no effect on
• Risk of incident type 2 diabetes mellitus during the 19-year post-intervention follow-up
• Made no difference on the incidence of macrovascular complications or mortality in participants with type 2 diabetes [10]

• Meta-analysis of 14 heterogeneous randomized controlled trials
• Including 714 type 2 diabetic individuals
• Supplementation with vitamin E (200-1,800 IU/day for 6-27 weeks)
• Had no effect on markers of glycemic control
• Glycated hemoglobin A1c (HbA1c) level
• Measures of fasting glucose
• Fasting insulin concentrations [10]
• Subgroup analyses indicated that higher doses of vitamin E (nad 400 IU/day) supplemented for longer periods (nad 12 weeks)
• Significantly reduced HbA1c level and fasting insulin concentration [10]
• Suggesting that vitamin E could possibly enhance insulin action and glucose disposal in type 2 diabetic individuals [10]

• Meta-analysis of randomized controlled trials
• Endothelial function in normal-weight and overweight — but not obese — patients with type 2 diabetes
• Was significantly improved by supplementation with vitamin E and/or vitamin C [10]

• May have utility in the management of type 2 diabetes
• Evidence for benefit from large, well-controlled clinical trials is still lacking [10]

Indi-kace/-kátory k suplementaci vit. E

PUFA intake

• Requirement for alpha-tocopherol related to the amount and degree of unsaturation of dietary PUFAs (Horwitt, 1960; Harris and Embree, 1963; Witting and Horwitt, 1964) [2]

Markers of alpha-tocopherol intake/status/function

• Plasma/serum alpha-tocopherol concentration
• Hydrogen peroxide-induced haemolysis
• Urinary alpha-CEHC excretion
• Adipose tissue alpha-tocopherol concentration
• Markers of oxidative damage
• Other biomarkers of function [2]

• At present, insufficient data on biomarkers to derive alpha-tocopherol requirement.
• Available data on alpha-tocopherol kinetics and body pools cannot be used to derive alpha-tocopherol requirement. [2]

IOM (2000) considered

• Long-term depletion–repletion study in men by Horwitt et al.
• Set DRVs for alpha-tocopherol
• Plasma alpha-tocopherol concentration of 12 micromol/L was associated with in vitro hydrogen peroxide-induced haemolysis
• Median excretion remained at a plateau of about 1.39 micromol/g creatinine until an intake of about 9 mg alpha-tocopherol/day, then the slope of the curve increased (Section 2.4.3).
• Estimation of daily losses of alpha-tocopherol of about 4–5 mg/day in healthy adults (with mean plasma alpha-tocopherol concentrations of about 20–23 micromol/L) from two kinetic studies (Bruno et al., 2006b; Novotny et al., 2012)
• Average alpha-tocopherol absorption from a usual diet of about 75 %
• About 6 mg alpha-tocopherol/day would need to be consumed to provide an amount of absorbed alpha-tocopherol to compensate these total daily losses. [2]

• EFSA concludes that a combination of these biomarkers/criteria cannot be used to derive DRVs for alpha-tocopherol also for Infants and children [2]
• Pregnant or lactating women [2]

KV onemocnění

• Individuals who consumed more than 7 mg/day of dietary alpha-tocopherol
• Were 35% less likely to die from heart disease
• Than those who consumed less than 3-5 mg/day of alpha-tocopherol [10]

• Two other large studies observed a significantly reduced risk of heart disease
• Only in women and men who consumed at least 100 IU (67 mg)/day of supplemental RRR-alpha-tocopherol [10]

• A randomized, placebo-controlled, intervention trial in 39,876 women (aged nad 45 years) in Women's Health Study (WHS)
• Supplementation with 600 IU (400 mg) of RRR-alpha-tocopherol every other day for 10 years
• 34% reduction in nonfatal myocardial infarction
• 49% reduction in cardiovascular-related deaths
• But only in women aged at least 65 years at baseline (10% of study participants) [10]

Trombózy

• Women in the vitamin E arm of Women's Health Study (WHS)
• Experienced a 21% reduction in risk of venous thromboembolism (VTE) compared to placebo
• 12% in women younger than 55 years old
• 26% in women aged 65 years and older
• 44% in women with a history of VTE [10]

• Large randomized controlled trial — the Physicians’ Health Study II (PHSII)
• Healthy middle-aged men
• No significant effect of 400 IU of synthetic alpha-tocopherol (180 mg of RRR-alpha-tocopherol) every other day for 8 years
• On major cardiovascular events in the entire cohort and in subgroup analyses
• Risk of harmful effect of high-dose vitamin E supplementation on the risk of hemorrhagic stroke in this cohort [10]

Secondary prevention in individuals with or at risk of cardiovascular disease

• Cigarette smoking, physical inactivity, hypertension, dyslipidemia, and being overweight or obese
• Oxidative stress and inflammation, 2 diabetes mellitus, chronic kidney disease
• Trials do not appear to support any cardiovascular benefit in healthy middle-aged and older subjects
• vitamin E supplementation might help improve cardiovascular health and/or lower the risk of CVD in specific, higher risk subjects [10]

• Observational studies of atherosclerotic plaques in arterial walls
• Cross-sectional Asymptomatic Carotid Atherosclerosis Disease In Manfredonia (ACADIM) study in 640 at-risk individuals
• Inverse association between carotid intima-media thickness (CIMT) — a marker of atherosclerosis — and circulating concentrations of antioxidants, including vitamin E
• Other observational studies found no association between plasma vitamin E concentrations and CIMT [10]

• Intervention studies: A small randomized controlled study assessing the effect of lipid-lowering drugs in men who had previously undergone a coronary artery bypass surgery
• Use of at least 100 IU/day (compared to less than 100 IU/day) of supplemental alpha-tocopherol (45 mg of RRR-alpha-tocopherol)
• Associated with reduced CIMT progression over a two-year period
• But only among participants in the placebo arm of the study - those who did not receive lipid-lowering drugs !!! [10]

• Recent meta-analysis of seven small placebo-controlled trials
• Little evidence that vitamin E supplementation may improve flow-mediated vascular dilation (FMD) of the brachial artery
• A marker of vascular endothelial health- adversely affected by CVD risk factors

• Cambridge Heart AntiOxidant Study (CHAOS), a randomized, placebo-controlled intervention trial in 2,002 patients with coronary heart disease
• Daily supplementation with either 400 IU or 800 IU of synthetic alpha-tocopherol (180 mg or 360 mg of RRR-alpha-tocopherol)
• For a median 18 months
• Dramatically reduced the occurrence of nonfatal myocardial infarctions by 77%
• vitamin E supplementation did not significantly reduce total or cardiovascular-related deaths [10]

• Small trial in patients with renal failure — the Secondary Prevention with Antioxidants of cardiovascular disease in End-stage renal disease (SPACE)
• Supplementation with 800 IU (536 mg)/day of RRR-alpha-tocopherol for an average of 1.4 years
• Significantly reduced the risk of myocardial infarction compared to placebo

• Randomized controlled study
• vitamin E supplementation may benefit a subgroup of patients with type 2 diabetes mellitus

• Multicenter study by Milman et al. in 1,434 type 2 diabetics (nad 55 years old)
• Carrying a specific variant of the haptoglobin protein (Hp), Hp2-2
• Has a lower efficacy to bind and remove pro-oxidant, free hemoglobin from plasma, compared to Hp1-1 and Hp1-2 variants
• Daily supplementation with 400 IU (268 mg) of RRR-alpha-tocopherol for 18 months
• Resulted in a lower risk of myocardial infarction compared to placebo [10]

Cognitive decline slower

• Or loss of functional abilities
• In cognitively impaired subjects in some, but not all, clinical studies [10]

If malabsorption causes clinically evident deficiency

• Alpha-tocopherol 15 - 25 mg/kg orally once a day should be given [9]
• Or mixed tocopherols 200 to 400 units can be given [9]

Obezita a vit. E

• obese children do not have low plasma alpha-tocopherol concentrations
• Corrected for their circulating lipids
• Alpha-tocopherol:lipid ratios were significantly lower than those in the control group
• obese children had elevated circulating cholesterol and TG concentrations
• Vitamin E supplements in apparently adequately nourished obese children decrease oxidative stress markers
• V.s. protože: obese children routinely consume inadequate amounts of antioxidants to prevent oxidative stress
• Likely that increased oxidative stress is a consequence of chronic inflammation, which is seen secondary to obesity [7]

• Murer et al. reported
• Median urinary ?-CEHC excretion in obese and overweight children in the placebo group
• Median (range) for baseline
• 1.2 (0.01–2.9) µmol/g creatinine
• Median (range) for postintervention
• 1.2 (0.3–15.9) µmol/g creatinine [7]
• Median urinary ?-CEHC excretion in obese and overweight children in the antioxidant group
• Low before supplementation
• 1.8 (0.5–19.2) µmol/g creatinine
• Increased dramatically after antioxidant supplementation
• 16.3 (0.01–81.2) µmol/g creatinine [7]
• Despite apparently normal plasma alpha-tocopherol concentrations in the study
• Urinary alpha-CEHC excretion suggests inadequate vitamin E status
• vitamin E supplementation in these children also decreased
• F2-isoprostanes
• But not markers of inflammation [7]

Parkinson’s disease

• Case–control study in Japan (Miyake et al., 2011)
• ‘vitamin E’ intake from food only was assessed by a diet history questionnaire
• After adjustments, ‘vitamin E’ intake was significantly associated with a reduced risk of Parkinson’s disease
• Quartile 4, nad 9.8 mg/day
• Compared with quartile 1, pod 7.2 mg/day [2]
• Odds ratio (OR) (95 % CI): 0.45 (0.25–0.79), p for trend 0.009 [2]

• A systematic review with meta-analysis of observational studies considered seven studies (five case–control, one cohort and one cross-sectional) investigating the relationship between ‘vitamin E’ intake and the risk of Parkinson’s disease (Etminan et al., 2005)
• ORs or relative risks (RRs) were pooled by the authors by ‘moderate’ or ‘high’ intakes
• ‘moderate’ - second or third quartiles or second, third or fourth quintiles in each study
• ‘high’ was defined as intake in the last quartile or quintile [2]
• Only ‘moderate’ dietary intake of ‘vitamin E’ (value not given) was associated with a significantly reduced risk of Parkinson’s disease (RR: 0.81, 95 % CI: 0.67–0.98, p heterogeneity = 0.68) [2]

Treatment for AVED

• vitamin E supplements
• Will prevent AVED from developing if given before symptoms begin
• May reverse some neurological symptoms if begun after AVED develops [3]
• When treated early, some symptoms, such as ataxia and intellectual decline, can be reversed [3]
• In older patients, treatment may slow disease progression, but some symptoms remain [3]
• If vitamin E treatment is initiated in presymptomatic individuals with two mutations in the TTPA gene
• Younger sibs of an affected individual
• Symptoms of AVED will not develop [3]

Surveillance:

• Monitor plasma vitamin E concentration every six months, particularly in children. [4]

Agents/circumstances to avoid:

• Smoking; occupations requiring quick responses or good balance. [4]

Evaluation of relatives at risk:

• Evaluation for vitamin E deficiency, especially in younger sibs of a proband. [4]

Other: Before attempting to drive a car

• Assessment to determine if the affected individual can drive safely. [4]

Parents of an affected child

• Are obligate heterozygotes
• Carry one pathogenic variant
• Heterozygotes are asymptomatic [4]

Dědivost

• At conception, each sib of an affected individual has a
• 25% chance of being affected
• 50% chance of being an asymptomatic carrier
• 25% chance of being unaffected and not a carrier [4]

Věkem podmíněná makulární degenerace

• Tyčinky a pigmetnový epitel jsou citlivé na plasmatické hladiny vit. E
• Existuje více studií, které dokládají protektivní efekt alfa-tokoferolu ve vztahu k AMD než ke kataraktě
• BDES studie - signif. pokles rizika AMD velkých drůz při vysokém příjmu vit. E [1]