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)
- Meta-analysis of randomized controlled trials
- 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
- 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
- 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
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]