Patofyzilogie a význam vitamínu E
BUD13
- Variation in the blood carriage capacity - BUD13 [5]
Cluster of the differentiation (CD36)
- Gene variants in SEC14L2, CYP3A, CETP, and CD36 did not reach genome-wide significance
Cytochrome p450, family 3, subfamily A (CYP3A)
CYP4F2
Rs2108622 in CYP4F2
- Reported to be associated with
- Altered fatty acid metabolism
- But not with TG (P values ranging from 0.39 to 0.97) in meta-analyses
- Supporting a potential nonlipid transport function for CYP4F2 in vitamin E metabolism
- I.e., by catalyzing tocopherol phytyl side-chain oxidation [5]
Colesteryl ester transfer protein (CETP)
Gamma-tocopherol
- Most common form of vitamin E in the American diet
- Its plasma and tissue concentrations are generally significantly lower than those of alpha-tocopherol
- More gamma-tocopherol is excreted in urine than alpha-tocopherol
- Suggesting less gamma-tocopherol is needed for use by the body [10]
- Gamma-tocopherol and its major metabolite, gamma-carboxyethyl hydroxychroman (gamma-CEHC)
- May play a role in protecting the body from free radical-induced damage in various conditions of oxidative stress and inflammation
- Two recent randomized, placebo-controlled studies [10]
- Supplementation of smokers with gamma-tocopherol [10]
- Potentiated short-term benefits of smoking cessation (with or without nicotine replacement therapy) on vascular endothelial function [10]
NKAIN3
- Na+/K+ transport membrane protein [5]
- SNP in NKAIN3, the observed association with serum alpha-tocopherol in the supplemented state
- May be partly explained by the role vitamin E plays in
- Preventing loss of Na/K-ATPase activity
- A plasma membrane-bound enzyme essential for the maintenance of cell viability
- And lipid peroxidation [5]
- NKAIN3, rs7834588, was not associated with lipids in recent GWAS meta-analyses [5]
Polymorphisms of the cluster of differentiation 36 (CD36)
- Might modestly influence plasma alpha-tocopherol concentrations
- Especially in people with low triglyceride concentrations (Lecompte et al., 2011)
Single-nucleotide polymorphisms in SCARB1
- Cohort of 128 volunteers
- Gene coding for scavenger receptor B type 1 (SR-BI)
- Related to plasma alpha-tocopherol concentration
- Effect of these variants on alpha-tocopherol distribution in the body (Borel et al., 2007)
SEC14 like protein 2 - CEC14L2
Tocotrienols - especially delta-tocotrienol
- Numerous preclinical studies - might be beneficial in the prevention of chronic diseases
- Shown greater anti-proliferative and pro-apoptotic effects than tocopherols in malignant cell lines
- Dose, formulation, and type of study population [10]
- Affect the bioavailability of tocotrienols
- May undermine their putative efficacy in humans [10]
- Currently no data available on the effectiveness of supplemental tocotrienols in humans [10]
ZNF259
Adhese krevní destiček
- Supplementation with ‘vitamin E’ for two weeks up to 400 IU/day
- Equivalent to 267 mg/day of alpha-tocopherol
- Significant dose-dependent decrease in platelet adhesion (Richardson and Steiner, 1993)
- Oral supplementation with alpha-tocopherol (267–805 mg/day)
- Increase in platelet alpha-tocopherol concentration
- Correlated with a marked inhibition of platelet aggregation (Freedman et al., 1996) [2]
- Limited data on other functions of alpha-tocopherol
- Considers that markers of these functions are not specific to effects of alpha-tocopherol [2]
Antinarodovy
- Induce cell death and reduce cell proliferation [5]
Antioxidant (oxidace)
- Scavenger peroxylových radikálů, singletový kyslík, superoxdové radikály
- Peroxyl radical scavenger
- Especially protects polyunsaturated fatty acids (PUFAs) within membrane phospholipids and plasma lipoproteins [2]
- Inhibice řetězových reakcí lipoperoxidace
- Pro antiox. vlastností tokoferolů důležitá hydroxylová skupina (OH)
- Darují atom vodíku (H) volným radikálům
- Důležité je, že neutralizace volného lipidového radikálu tokoferoly a stop řetězpové rakci proběhne rychleji než oxidace volných MK a okolních proteinů
- Vznikají tokoferolové radikály a dále reagují:
- S dalším tokoferylovým radikálem za vzniku dimeru [1]
- Peroxyl radicals react 1 000 times faster with alpha-tocopherol than with PUFAs (Buettner, 1993)
- Protecting PUFAs within membrane phospholipids
- Preserves intracellular and cellular membrane integrity and stability
- Stability of erythrocytes
- Conductivity in central and peripheral nerves [2]
- Phenolic hydrogen at position 6
- Is the active site for scavenging radicals [2]
- Alpha-Tocopherol scavenges free radicals
- Primarily by hydrogen atom transfer reaction to yield a:
- Non-radical product
- Alpha-tocopherol radical [2]
- Alpha-Tocopherol may also scavenge radicals by
- Electron is transferred from alpha-tocopherol to give a vitamin cation radical
- Undergoes rapid deprotonation to provide an alpha-tocopherol radical [2]
- Alpha-tocopherol scavenges
- Lipid peroxyl radicals
- Lipid hydroperoxide
- Alpha-tocopherol radicals are formed (Niki et al., 1993; Yamauchi, 2007; Niki, 2014) [2]
Tocotrienols and gamma-tocopherol
- Thought to be better scavengers of peroxyl radicals and reactive nitrogen species, respectively, than alpha-tocopherol [10]
The alpha-tocopherol radical
- May react with another radical to give stable products
- Attack lipids
- React with a reducing agent such as ascorbate or ubiquinol to regenerate the vitamin (Packer et al., 1979; Niki et al., 1982)
Vit.C a Selen
- In vivo role is sustaining the antioxidant capacity of alpha-tocopherol
- Interaction of alpha-tocopherol and vitamin C
- Function of oxidised alpha-tocopherol is continuously restored by other antioxidants
- Antioxidant network depends on the supply of aqueous antioxidants and the metabolic activity of cells [2]
Regenerace antioxidační schopnosti (redukce)
- Reduktanty vitamínu E (regenerace vit. E) jsou:
- Ubiquinol,
- Polyfenoly,
- vit. C (nejvýznamnější cesta)
- Význam synergie jednotlivých vitamínů [1]
Separate cluster of the differentiation gene (CD4)
rs3741920 in CD4
- Was associated with a high level of significance [5]
- P = 4.2 × 10-6 [5]
Immunoregulatory potential
- Able to boost host protection against bacterial infection [8]
- Mediation of genetic factors on immune responses after VE supplementation in healthy humans
- Production of cytokines and/or related with the cytokine genes
- TNF,
- IL-6,
- IL-1B
- May influence the activity of membrane proteins and enzymes [10]
- Improve the formation of an adhesive junction (known as immune synapse)
- Between naive T lymphocytes and antigen-presenting cells (APC)
- Eventually prompted T cell activation and proliferation [10]
- Alpha-Tocopherol enhance specifically the T cell-mediated immune response
- That declines with advancing age [10]
- T cell impaired response has been partly associated with
- Reduced capacity of naive T cells to be activated during antigen presentation
- And to produce interleukin-2 (IL-2)
- Proliferate as a result [10]
- Small intervention study in older adults (mean age, 70 years)
- Supplementation with 200 mg/day of all-rac-alpha-tocopherol (equivalent to 100 mg of RRR-alpha-tocopherol) 3 months significantly improved
- Natural killer (NK) cytotoxic activity
- Neutrophil chemotaxis
- Phagocytic response
- Enhanced mitogen-induced lymphocyte proliferation
- Interleukin-2 (IL-2) production compared to baseline [10]
- Daily supplementation of healthy older adults (nad 65 years of age) with 200 mg of all-rac-alpha-tocopherol for 235 days
- Improved T lymphocyte-mediated immunity
- Measured with the delayed-type hypersensitivity (DTH) skin test
- Increased the production of antibodies in response to hepatitis B and tetanus vaccines [10]
- Lower alpha-tocopherol doses
- Failed to improve the DTH response compared to a placebo in another study in healthy participants (ages, 65-80 years) [10]
- A randomized, placebo-controlled trial in 617 nursing home residents (nad 65 years of age)
- Daily supplementation with 200 IU of synthetic alpha-tocopherol (90 mg of RRR-alpha-tocopherol) for 1 year
- Significantly lowered the risk of contracting upper respiratory tract infections
- Especially the common cold
- Had no effect on lower respiratory tract (lung) infections [10]
Reduces carcinogen production
Snížená tvorba aktivního protrombinu
- Daily supplementation with 1,000 IU (670 mg) of RRR-alpha-tocopherol for 12 weeks
- Decreased gamma-carboxylation of prothrombin
- A vitamin K-dependent factor in the coagulation cascade
Zvýšené riziko krvácení
- Individuals taking anticoagulant drugs like warfarin
- Vitamin K deficient
- Should not take vitamin E supplements without medical supervision [10]
Interakce s PUFA
- Alpha-tocopherol depletion and supplementation in men consuming diets with different PUFA content
- Effect on the percentage of hydrogen peroxide-induced haemolysis (Horwitt et al., 1956; Horwitt, 1960)(Harris and Embree; 1963)
- Minimum intake ratio needed to prevent alpha-tocopherol deficiency
- Range 0.5–0.8 mg alpha-tocopherol/g PUFAs
- Ratio of 0.6 mg alpha-tocopherol/g PUFAs (mainly linoleic acid) in the American diet
- Considered this ratio to be protective against alpha-tocopherol deficiency [2]
- 1970s, in the USA
- Ratio of milligrams of alpha-tocopherol / gram of PUFAs12 in typical breakfasts, lunches and dinners
- Ranged from 0.16 - 0.71, with a mean at 0.43 (Bieri and Evarts, 1973) [2]
- Female students consuming a repetitive series of diets over about 9 months in the USA (Witting and Lee;1975)
- Mean plasma total tocopherol concentration of 1.09 mg/dL13 for a daily mean intake of
- 17.9 g of 18:2 n-6
- 1.6 g of 18:3 n-3
- 7.5 mg RRR-alpha-tocopherol
- Authors thus proposed a ratio of 0.4 mg alpha-tocopherol/g PUFAs
- Ratios were not related to a functional outcome. [2]
- Compositional requirement for RRR-alpha-tocopherol in infant formulae
- SCF (1997) considered the results of an in vitro study (Holman, 1954) and an animal study (Witting and Horwitt, 1964)
- Relative rate of oxidation of fatty acids was 0.025: 1: 2: 4: 6: 8 for the number of double bonds in fatty acids
- Increasing from 1 to 6 [2]
- Tocopherol-deficient rats showed that the
- Relative ratio of fatty acid oxidation was slightly different: 0.3, 2, 3, 4, 5, 6
- For mono-, di-, tri-, tetra-, penta- and hexaenoic fatty acids (Witting and Horwitt, 1964) [2]
- SCF (1997) proposed the relative requirement of RRR-alpha-tocopherol in infant formulae
- According to the degree of unsaturation of PUFAs to be:
- 0.5 mg/g linoleic acid,
- 0.75 mg/alpha-linolenic acid
- 1 mg/g arachidonic acid
- 1.25 mg/g eicosapentaenoic acid
- 1.50 mg/g docosahexaenoic acid [2]
- There is little evidence to support the ratios of 0.4 mg or 0.6 mg of alpha-tocopherol per gram of dietary PUFAs
- Uncertainties in the intake measurements based on which both ratios were proposed.
- Cannot be used for deriving the requirement for alpha-tocopherol [2]
Essentiality for normal reproduction in animals
- Has never been demonstrated in humans (Brigelius-Flohe et al., 2002)
- Human case report has been published on a woman with recurrent spontaneous abortions, that successfully delivered a health baby after administration of 300 mg/day of tocopherol nicotinate (Harada et al., 2005) [2]
rs12272004 SNP
- Previously reported to be associated with serum alpha-tocopherol concentrations (P = 3.9 × 10-7) [5]
- Not highly correlated with the SNP most significantly associated with alpha-tocopherol concentrations (rs964184; linkage disequilibrium r2 = 0.20) [5]
rs1800896
- Located in IL10 gene promoter
- Modulates the production of IL-1beta.
Sirtuin 1
- protein family of NAD+-dependent histone deacetylases
- Involved in various physiological processes
- Energy metabolism
- Protects cells against oxidative stress [8]
- Decreased expression of SIRT1 is related to obesity [8]
- Dietary vitamin E and genetic variants in SIRT1 in relation to BMI
- Elevated risk to having a greater BMI was related to a higher copy number of the most common haplotype
- Alleles A of rs7895833, G of rs1467568, and G of rs497849 among subjects with low VE intake [8]
- V.s. capacity of VE to modify the association between SIRT1 variants and obesity [8]