Miracon Science

Vitamin E

Synonym(s): d-alpha-tocopherol, d-alpha-tocopheryl acetate, tocopherol, tocotrienol
Nutrient group: Vitamine, Antioxidants

Sources and physiological effects

Dietary sources

Vitamin E is the collective term for eight naturally occurring tocopherols and tocotrienols. These fat-soluble compounds have different biological activities and complement each other synergistically in their spectra of actions.

High-quality vegetable oils such as rapeseed, safflower, sunflower or corn oil are suitable for meeting daily vitamin E requirements. Nuts such as almonds or hazelnuts also contain vitamin E.

The bioavailability of the fat-soluble tocopherols is essentially determined by the dietary fat absorbed at the same time. While long-chain unsaturated fatty acids impair absorption, it is improved by medium-chain saturated fatty acids.
Physiological effects
Antioxidant
  • Protects polyunsaturated fatty acids in membranes, lipoproteins and depot fats from destruction by lipid peroxidation
  • High affinity to lipid peroxyl radicals and thus acts as a radical scavenger
Sensation of pain
  • Inhibition of cyclooxygenase and leukotriene release
Blood vessels
  • Vasodilative by increasing NO bioavailability and as a cofactor of prostacyclin synthesis
  • Antithrombotic effect through reduced release of adhesion molecules and inhibition of thrombin formation
  • Reduction of cholesterol and LDL oxidation and thus protection against arterial plaque deposition

Immune system
  • Stimulation of humoral and cellular immune response
Blood
  • Inhibition of blood coagulation by inhibition of vitamin K carboxylation

EFSA Health Claims

 

Health claims EFSA opinion
Vitamin E
  • Helps protect cells from oxidative stress
  

Recommended intake

D-A-CH recommended nutrient intake (Reference values EFSA and NHI  )
  Age Tocopherol mg equivalent
Infants (months)
  0-4 3
  4-12 4
Children (years)
  1-4  5
  4-7  8
  7-10  9
  10-13  12
  13-15  13
Teenagers/adults (years) Women Men
  15-19 12 15
  19-25  12  15
  25-51  12  14
  51-65  12  13
  > 65  11  12
Pregnancy  13
Breast-feeding  17
Increased need Alcohol and nicotine abuse, high consumption of polyunsaturated fatty acids, malabsorption (e.g. due to chronic, inflammatory intestinal diseases, short bowel syndrome, pancreatitis), diseases such as diabetes, Alzheimer's disease, cystic fibrosis 
Special groups at risk of deficiency People with diabetes mellitus, Alzheimer's disease, cystic fibrosis 

 

Recommended intake according to food labelling regulations Vitamin E
(=100 % TB marking on label) 12 mg TA
Nutrient safety  
UL
 

Long-term daily intake, where no adverse
health effects are expected

 300 mg/d
NOAEL
 		 Maximum intake, with no observed adverse
effect.		 800 mg/d
Safety European Commission has looked at the safety of vitamin E.

Detailed information

Vitamin E as an antioxidant
Vitamin E is the collective term for eight naturally occurring tocopherols and tocotrienols. These compounds have different biological activity and complement each other synergistically. From a nutritional point of view, all eight natural isomers should preferably be supplemented as they represent different effect spectra. (1). As the most important fat-soluble antioxidant in the human organism and a component of all biological membranes, vitamin E protects polyunsaturated fatty acids (DHA, linoleic acid, etc.) highly effectively from oxidation by aggressive oxygen radicals (2). Vitamin E itself becomes a tocopheroxyl radical, but can be regenerated by vitamin C, ubiquinol, glutathione and selenium (3). In the body, vitamin E acts as a natural anticoagulant by inhibiting the formation of thromboxane A2 and monocyte adhesion to the endothelium, increasing prostacyclin synthesis and improving the bioavailability of vasodilator nitric oxide (NO) (3)(4). In addition to its antioxidant and anticoagulant effects, vitamin E regulates inflammatory processes. It inhibits various enzymes of the arachidonic acid cascade (cyclooxygenase, phospholipase A2 etc.) and reduces unwanted connective tissue proliferations (3).
 
Vitamin E complex in cardiovascular disease prevention
Vitamin E is used preventively, therapeutically and concomitantly for the treatment of cardiovascular diseases. Vitamin E owes its antiatherogenic effect to its antioxidant, membrane stabilizing, platelet aggregation and proliferation inhibiting effects (3). Vitamin E also reduces the oxidation of lipids such as cholesterol and LDL and can therefore positively influence arterial plaque formation (5). Based on epidemiological studies, it is thought that the established preventive effect is not due to the amount of vitamin E, but to the type of vitamin E. A high dose of vitamin E does not lead to a reduced risk of disease, however, a  vitamin E-rich diet including the entire natural vitamin E spectrum does decrease the risk (6). Mixed tocopherols achieve better antithrombotic efficacy than pure alpha-tocopherols (1). In particular, the combination with gamma-tocopherols should increase the anti-inflammatory and antioxidative effects of vitamin E (7). 
 
Anti-inflammatory effect in rheumatic diseases
Inflammatory processes, characteristic of rheumatic diseases, respond well to regular vitamin E supplementation. Antioxidative processes appear to play an important role. A lowered oxidative status in the serum of rheumatoid arthritis patients correlates with the onser of rheumatoid arthritis (8). In a clinical study, osteoarthritis patients were found to have lower tocopherol levels than in healthy subjects. Gamma-tocopherol seems to be of particular importance, since its serum concentration correlates inversely with the occurrence of knee osteoarthritis (9, 19). Vitamin E is used therapeutically due to its modulating influence on the arachidone metabolism during inflammatory processes. It inhibits the formation of proinflammatory cytokines and can therefore positively influence the course of inflammation. Vitamin E (200-500 IU/d) reduces the required NSAID doses (3) during treatment with these drugs. For high intakes of vitamin E, it should be combined with vitamin C and other antioxidants to recycle the resulting radicals.
 
Vitamin E in cancer prevention
Vitamin E compounds act as nutritive protective components in cancer prevention Numerous epidemiological studies indicate that vitamin E reduces the risk of developing certain types of cancer. In animal models, mixed natural tocotrienols show protective effects against the occurrence of prostate tumors (10). Tocotrienols also have the ability to accelerate apoptotic processes in prostate tumors (11)(12). For tocotrienols and certain tocopherols, these properties have also been demonstrated in breast cancer cells (13). Based on these and other studies, tocopherols and tocotrienols are considered to be promising pharmacologically active substances in cancer therapy and prevention.
 
Prevention of neurodegenerative and free-radical-associated diseases
Neurodegenerative diseases of the CNS such as Alzheimer's, epilepsy or tardive dyskinesia are among the leading causes of the need for long-term care in the elderly. Oxidative stress is an important factor in the pathogenesis and progression of these diseases. As a chain-breaking antioxidant, vitamin E has pronounced neuroprotective properties and protects the polyunsaturated fatty acids of the CNS against lipid peroxidations (14). High vitamin E levels have a protective effect, for example, against the risk of developing Alzheimer's type dementia (DAT). In a 6-year study, elderly people (> 80 years) with the highest total tocopherol serum levels or total vitamin E serum levels had a 45% lower DAT risk. High total tocotrienol levels even reduced the DAT disease risk by 54 % (15). The occurrence of diabetes mellitus is also associated with significantly reduced vitamin E levels (16)(17). In age-related macular degeneration (AMD) it has been shown that people with a higher intake of antioxidants such as vitamin E, vitamin C and zinc developed AMD less frequently (18).

Reference values

Parameters substrate reference value Description
Alpha-tocopherol Serum/Plasma women
9.4 - 15.0 mg/l		 Fasting (12 h), store protected from light
men
8.9 - 18.3 mg/l
Interpretation
High values Insufficient intake or increased demand due to increased oxidative stress, digestive disorder with reduced vitamin E absorption from the intestine
Low values Hypervitaminosis due to vitamin preparations, lipid metabolism
Note on the measurement results
alpha-tocopherol is transported in blood plasma bound to lipoproteins. Therefore, a standardization to cholesterol may be useful.
Nutrigenetics
Characteristic gene sites and their effects on vitamin requirements
Gene rsNumber

risk SNP

 Description

Recommended nutrients

TXN

rs2301241

 T

Thioredoxin (TXN) plays an important role in the physiological redox system. Due to a reduced efficiency less vitamin C and coenzyme Q10 is recycled. Vitamin E as an important antioxidant can additionally compensate for adverse effects (20).

Vitamin E,
Coenzyme Q10
and
Vitamin C

Deficiency symptoms

Impact on Symptoms
Risk of disease Increased susceptibility to free-radical-associated diseases such as diabetes mellitus, Alzheimer's disease, AMD
Blood Tendency of hemolysis of erythrocytes
Skin/Hair Premature skin aging due to forced collagen degradation
Age spots and lipofuscin deposits
Alopecia
Nervous system Neuro- and myopathies

Administration

General mode of administration
 
When
 
  • Vitamin E should be taken with or after meals.
  • Higher doses of vitamin E should always be combined with an appropriate amount of vitamin C. Vitamin E acts as a radical scavenger, releasing electrons and becoming a radical itself. Vitamin C recycles the vitamin E radicals.
  • Note: Since vitamin E has an antithrombotic effect, an increased intake in patients who are already taking anticoagulant drugs can lead to a disorder of coagulation ability. For persons with coagulation disorders or before surgery, the extension of the bleeding time must be noted.
Side effects
In high doses (over 800 mg or 1200 I.U.) gastrointestinal complaints (diarrhea, flatulence, nausea) can occur.
Contraindications
No contraindications are known to date.

Interactions

Drug interactions
NSAIDs (ASA, Diclofenac) High doses of vitamin E can increase the blood thinning effect of ASA.
Neuroleptics (haloperidol) Vitamin E can improve the tolerance of haloperidol.
Nutrient interactions
Trace elements Selenium enhances the antioxidant effect of vitamin E.
Vitamin E can counteract the prooxidative activity of iron.
Vitamins High doses of vitamin E reduce the absorption of vitamin A and can inhibit the effect of vitamin K.
Vitamin C regenerates oxidatively consumed vitamin E.
Fatty acids High doses of omega-3 fatty acids can cause a decrease in vitamin E levels.

Description and related substances

Description of the micronutrient
Fat-soluble vitamin
Related substances
D-α-Tocopherol, DL- α-Tocopherol, D- α-Tocopheryl acetate, DL- α-Tocopheryl acetate, D- α-Tocopheryl acid succinate, mixed tocopherols, tocotrienol tocopherols

References

Refeenzen
1 Liu, M. et al. 2003. Mixed tocopherols inhibit platelet aggregation in humans: potential mechanisms. Am J Clin Nutr. 77(3):700-6.
2 Leitzmann, C. et al. Ernährung in Prävention und Therapie: Ein Lehrbuch, 3. vollständig überarbeitete und erweiterte Auflage. Stuttgart: Hippokrates Verlag, 2009.
3 Gröber, U. Mikronährstoffe: Metabolic Tuning – Prävention –Therapie, 3. Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2011.
4 Silva, I. T. et al. 2013. Is plasma alpha-tocopherol associated with electronegative LDL in obese adolescents? J Nutr Sci Vitaminol. 59(2):100-7. doi: 10.3177/jnsv.59.100.
5 Murohara, T. et al. 2004. Inhibition of platelet adherence to mononuclear cells by alpha-tocopherol: role of P-selectin. Circulation. 110(2):141-8.
6 Yuen, K. H. et al. 2011. Effect of Mixed Tocotrienols in Hypercholesterolemic Subjects. Functional Foods in Health and Disease. 1(3):106-117.
7 Sen, C. K. er al. 2006. Tocotrienols: Vitamin E beyond tocopherols. Life Sci. 78(18):2088-98. doi: 10.1016/j.lfs.2005.12.001.
8 Cai, W. C. et al. 2005. Determination of oxidation-reduction level in patients with rheumatoid arthritis. Academic Journal of the First Medical College of PLA. 25(6):749-50.
9 Jordan, J. M. et al. 2004. A case control study of serum tocopherol levels and the alpha to gamma-tocopherol ratio on radiographic knee osteoarthritis. Am J Epidemiol. 159(10):968-77.
10 Barve, A. et al. 2010. Mixed Tocotrienols Inhibits Prostate Carcinogenesis in TRAMP Mice. Nutrition and Cancer. 62(6):789–794.
11 Weinstein, S. J. et al. 2007. Serum and dietary vitamin E in relation to prostate cancer risk. Cancer Epidemiol Biomarkers Prev. 16(6):1253-9. doi: 10.1158/1055-9965.EPI-06-1084.
12 Srivastava, J. K., Gupta, S. 2006. Tocotrienol-rich fraction of palm oil induces cell cycle arrest and apoptosis selectively in human prostate cancer cells. Biochem Biophy Res Commun. 346(2):447-53.
13 Yu, W. et al. 1999. Induction of apoptosis in human breast cancer cells by tocopherols and tocotrienols. Nutr Cancer. 33(1):26–32.
14 Singh, U. et al. 2005. Vitamin E, oxidative stress and inflammation. Annu Rev Nutr. 25:151-74.
15 Mangialasche, F. et al. 2010. High Plasma Levels of Vitamin E Forms and Reduces Alzheimer’s Disease Risk in Advanced Age. Journal of Alzheimer’s Disease. 20(4):1029-37. doi: 10.3233/JAD-2010-091450.
16 Cangemi, R. et al. 2013. Cholesterol-adjusted vitamin E serum levels are associated with cardiovascular events in patients with non-valvular atrial fibrillation. Int J Cardiol. 168(4):3241-3247. doi: 10.1016/j.ijcard.2013.04.142.
17 Lee, I. M. et al. 2005. Vitamin E in the primary prevention of cardiovasculur disease and cancer: the Women’s Health Study: a randomized controlled trial. JAMA. 294(1):56-65.
18 Morris, M. S. et al. 2007. Intake of zinc and antioxidant micronutrients and early age-related maculopathy lesions. Ophthalmic Epidemiol. 14(5):288-98.
19 Li, X. et al. 2016. Vitamin E slows down the progression of osteoarthritis (Review). Exp Ther Med. 12(1):18-22. doi: 10.3892/etm.2016.3322.
20 Mansego, M. L. et al. 2015. The nutrigenetic influence of the interaction between dietary vitamin E and TXN and COMT gene polymorphisms on waist circumference: a case control study. J Transl Med. 13:286. 
 
References Interactions
1 Stargrove, M. B. et al. Herb, Nutrient and Drug Interactions: Clinical Implications and Therapeutic Strategies, 1. Auflage. St. Louis, Missouri: Elsevier Health Sciences, 2008.
2 Gröber, U. Mikronährstoffe: Metabolic Tuning –Prävention –Therapie, 3. Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2011.
3 Gröber, U. Arzneimittel und Mikronährstoffe: Medikationsorientierte Supplementierung, 3. aktualisierte und erweiterte Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2014.
up