Vitamin E

Vitamin E
Drug class

The α-tocopherol form of vitamin E
Class identifiers
Use Vitamin E deficiency, antioxidant
ATC code A11H
Biological target Reactive oxygen species
Clinical data
Drugs.com MedFacts Natural Products
External links
MeSH D014810
In Wikidata

Vitamin E refers to a group of compounds that include both tocopherols and tocotrienols.[1][2] Of the many different forms of vitamin E, γ-tocopherol is the most common form found in the North American diet.[3] γ-Tocopherol can be found in corn oil, soybean oil, margarine, and dressings.[4][5] α-tocopherol, the most biologically active form of vitamin E, is the second-most common form of vitamin E in the diet. This variant can be found most abundantly in wheat germ oil, sunflower, and safflower oils.[5][6] As a fat-soluble antioxidant, it interrupts the propagation of reactive oxygen species that spread through biological membranes or through a fat when its lipid content undergoes oxidation by reacting with more-reactive lipid radicals to form more stable products.[7][8][9][10] Regular consumption of more than 1,000 mg (1,500 IU) of tocopherols per day[1] may be expected to cause hypervitaminosis E, with an associated risk of vitamin K deficiency and consequently of bleeding problems.

Forms

The nutritional content of vitamin E is defined by α-tocopherol activity. The molecules that contribute α-tocopherol activity are four tocopherols and four tocotrienols, identified by the prefixes alpha- (α-), beta- (β-), gamma- (γ-), and delta- (δ-).[11] Natural tocopherols occur in the RRR-configuration only. The synthetic form contains eight different stereoisomers and is called 'all-rac'-α-tocopherol.[12] Water-soluble forms such as d-alpha-tocopheryl succinate are used as food additive.

α-Tocopherol

Sample of α-tocopherol, one of the various forms of vitamin E

alpha-Tocopherol is an important lipid-soluble antioxidant. It performs its functions as antioxidant in the glutathione peroxidase pathway,[13] and it protects cell membranes from oxidation by reacting with lipid radicals produced in the lipid peroxidation chain reaction.[9][14] This removes the free radical intermediates and prevents the oxidation reaction from continuing. The oxidized α-tocopheroxyl radicals produced in this process may be recycled back to the active reduced form through reduction by other antioxidants, such as ascorbate, retinol or ubiquinol.[15] Other forms of vitamin E have their own unique properties; for example, γ-tocopherol is a nucleophile that can react with electrophilic mutagens.[16]

Tocotrienols

Compared with tocopherols, tocotrienols are sparsely studied.[17][18]

Functions

Vitamin E has many biological functions, including its role as a fat-soluble antioxidant.[1]

So far, most human supplementation studies about vitamin E have used only α-tocopherol. This can affect levels of other forms of vitamin E, e.g. reducing serum γ- and δ-tocopherol concentrations. Moreover, a 2007 clinical study involving α-tocopherol concluded supplementation did not reduce the risk of major cardiovascular events in middle-aged and older men.[30]

Deficiency

Main article: Vitamin E deficiency

Vitamin E deficiency can cause:

Supplementation

Vitamin E supplementation has not been shown to have significant benefit for people who are healthy, and appears to be harmful.[33][34] It does not improve blood sugar control in an unselected group of people with diabetes mellitus[35] or decrease the risk of stroke.[36] Daily supplementation of vitamin E does not decrease the risk of prostate cancer, and may increase it.[1][37] Studies on its role in age-related macular degeneration are ongoing, though if it is of a combination of dietary antioxidants used to treat the condition it may increase the risk.[38] Routine supplementation with vitamin E during pregnancy has been shown to offer no benefit to the mother or the child. Vitamin E has been reported to cause more side effects, such as abdominal pain in pregnant women, and also the increased risk of having early rupture of membranes at term.[39]

Vitamin E, along with β-carotene and vitamin C, has no protective effect on reducing the risk of cataract, cataract extraction, progression of cataract, and slowing the loss of visual acuity.[40]

Clinical applications

Vitamin E and its analogs are used to prevent and repair cell and tissue damage during radiation therapy. Vitamin E with adjuvant Evening Primrose Oil may reduce breast pain.[41]

The use of vitamin E in the treatment of some cancers is beneficial. Vitamin E and its derivatives promote tumor susceptibility of ionizing radiation during cancer treatment.[42]

Toxicity

Main article: Hypervitaminosis E

The LD50, or the toxic dose required to kill 50% of group of rats and mice, respectively is 4000 mg of VitaminE E/kg of rat and 4000 mg of Vitamin E/kg of mouse.[43] Comparatively speaking, and at lethal doses, Vitamin E is less toxic than table salt and acetaminophen and it is more toxic than ethanol and Vitamin C. Vitamin E can act as an anticoagulant, increasing the risk of bleeding problems. As a result, many agencies have set a tolerable upper intake levels (UL) at 1,000 mg (1,500 IU) per day.[1] In combination with certain other drugs such as aspirin, hypervitaminosis E can be life-threatening. Hypervitaminosis E may also counteract vitamin K, leading to a vitamin K deficiency.

Dietary sources

mg/(100 g)
[note 1] 		Some foods with vitamin E content[8]
lowhigh
150 Wheat germ oil
44 Canola/rapeseed oil
41 Sunflower oil
95 Almond oil
34 Safflower oil
26 Almonds
19 Wheat germ
15 Palm oil[44]
15 Hazelnuts
14 Olive oil
12.2 Common purslane[45]
8.33 Peanut
1.53.4 High-value green, leafy vegetables: spinach, turnip, beet greens, collard greens, and dandelion greens[note 2]
2.32 Butter
2 Avocados[46]
1.8 Cocoa butter
1.4 Sesame oil[47]
1.11.5 Asparagus[note 3]
1.5 Kiwifruit (green)
0.90 Cashew nuts
0.781.5 Broccoli[note 4]
0.81 Pumpkin[note 5]
0.260.94 Sweet potato[note 6]
0.9 Mangoes
0.7 Walnuts
0.540.56 Tomatoes[note 7]
0.360.44 Rockfish[note 8]
0.3 Papayas
0.25 Tahini
0.130.22 Low-value green, leafy vegetables: lettuce[note 9]

Dietary Reference Intake

The Food and Nutrition Board (FNB) of the U.S. Institute of Medicine updated Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs) for vitamin E in 2000. The current EAR for vitamin E for women and men ages 14 and up is 12 mg/day. The RDA is 15 mg/day. RDAs are higher than EARs so as to identify amounts that will cover people with higher than average requirements. RDA for pregnancy equals 15 mg/day. RDA for lactation equals 19 mg/day. For infants up to 12 months the Adequate Intake (AI) is 4–5 mg/day and for children ages 1–13 years the RDA increases with age from 6 to 11 mg/day. The FNB also sets Tolerable Upper Intake Levels (ULs) for vitamins and minerals when evidence is sufficient. In the case of vitamin E the UL is 1,000 mg/day.[48] Collectively the EARs, RDAs and ULs are referred to as Dietary Reference Intakes. The European Food Safety Authority reviewed the same safety question and set a UL at 300 mg/day.[49]

For U.S. food and dietary supplement labeling purposes the amount in a serving is expressed as a percent of Daily Value (%DV). For vitamin E labeling purposes 100% of the Daily Value was 30 mg, but as of May 2016 it has been revised to 15 mg. A table of the pre-change adult Daily Values is provided at Reference Daily Intake. Food and supplement companies have until July 28, 2018 to comply with the change.

History

Vitamin E was discovered in 1922 by Herbert McLean Evans and Katharine Scott Bishop[50] and first isolated in a pure form by Gladys Anderson Emerson in 1935 at the University of California, Berkeley.[51] Erhard Fernholz elucidated its structure in 1938 and shortly afterwards the same year, Paul Karrer and his team first synthesized it.[52]

The first use for vitamin E as a therapeutic agent was conducted in 1938 by Widenbauer, who used wheat germ oil supplement on 17 premature newborn infants suffering from growth failure. Eleven of the original 17 patients recovered and were able to resume normal growth rates.[53]

In 1945, Drs. Evan V. Shute and Wilfred E. Shute, siblings from Ontario, Canada, published the first monograph arguing that megadoses of vitamin E can slow down and even reverse the development of atherosclerosis.[54] Peer-reviewed publications soon followed.[55][56] The same research team also demonstrated, in 1946, that α-tocopherol improved impaired capillary permeability and low platelet counts in experimental and clinical thrombocytopenic purpura.[57]

Later, in 1948, while conducting experiments on alloxan effects on rats, Gyorge and Rose noted rats receiving tocopherol supplements suffered from less hemolysis than those that did not receive tocopherol.[58] In 1949, Gerloczy administered all-rac-α-tocopheryl acetate to prevent and cure edema.[59][60] Methods of administration used were both oral, that showed positive response, and intramuscular, which did not show a response.[53] This early investigative work on the benefits of vitamin E supplementation was the gateway to curing the vitamin E deficiency-caused hemolytic anemia described during the 1960s. Since then, supplementation of infant formulas with vitamin E has eradicated this vitamin’s deficiency as a cause for hemolytic anemia.[53]

Vitamin E supplementation and cardiovascular disease

Vitamin E and atherosclerosis

Atherosclerosis is a disease condition refer to the buildup of plaque, which is a substance containing lipid and cholesterol (mainly the low-density lipoprotein or LDL cholesterol) on the inner layer of the arterial lumen.[61] With the existing plaque, instead of being smooth and elastic, the layers become thickened and irregular and the lumen of the artery become narrower. This vessel-narrowing effect lead to a reduction of blood circulation and can lead to or worsen the condition of hypertension.[62]

There are currently multiple theories explaining factors causing and affecting the cholesterol plaque build up within arteries with the most popular theory indicating that the rate of build up is affected by the oxidation of the LDL cholesterol. LDL cholesterol is one of the five major groups of lipoproteins with one of the physiological roles being lipid transportation. A typical LDL particle contain 2,700 fatty acid molecules and half of them are poly-unsaturated fatty acids, which are very oxidation sensitive.[63] Once the oxidation of LDL occur, it will start a series of undesirable effects starting from the increase production of inflammatory cytokines by stimulating the endothelial cells and monocytes, followed by increased production of tissue factors, production of macrophages and monocytes, which eventually lead to the formation of foam cells and accelerated development of atherosclerosis. With the presence of adequate concentration of vitamin E, which is a very potent fat-soluble antioxidant, it can inhibit the oxidation of LDL, and this inhibition contributes protection against the development of atherosclerosis and can stabilize the existing plaque.[63]

Interpreting the science jargon of the following paragraphs: If human trials are similar enough in design and measurements, a statistical analysis can be conducted on the combined results. This is called a meta-analysis. Controversies arise when different authors disagree on the criteria to use to include or exclude trials. An odds ratio (OR) indicates whether a treatment helped or harmed compared to control. In the first example below, an OR = 0.74 means that the risk of cardiovascular disease was reduced by 26%. An inverse association (the next referenced example) means that the higher the dose, the lower the risk. Odds ratio and relative risk sort of mean the same thing (unless you are a statistician). The paragraphs below are in conflict. The first reports on observing how much vitamin E subjects chose to consume, and their disease outcome. The second describes RCTs, i.e., randomized clinical trials, in which subjects are assigned to get or not get vitamin E, without knowing which group they are in, and tracking results. The conclusion of observational studies is a benefit; the conclusion of RCTs is no benefit. (As indicated by the ORs being close to 1.00, meaning no effect. An OR higher than 1.00 indicates harm.)

According to Asplund (2002)’s [64] meta-analysis, nine cohort studies showed that high intake of tocopherol was associated with a lower risk of CVD events compared with lower intake. The odds ratio (OR) was 0.74 (95% confidential interval (CI): 0.66-0.83). In this study, higher dietary, supplementation and combined vitamin E intake was also associated with lower CHD incidents, as presented in Appendix II. A large cohort study conducted by Rimm et al.[65] in 1993 included 39,919 male health professionals aged between 40 and 75 showed that consumption of more than 60 IU of vitamin E (any form) per day was associated with a lower incidence of CHD compared with less than 7.5 IU/day intake. This study also showed an inverse association between vitamin E supplementation and the incidence of CHD. The relative risk (RR) of at least 100 IU/day for at least two years was 0.63 (95% CI: 0.47-0.84). A European cohort study was conducted by Knekt et al. in 1994. This study also found an inverse relationship between higher vitamin E (any form) intake and lower CHD risk in men and women. In addition, Kushi et al. (1996) discovered an inverse relationship between vitamin E intake and CHD mortality among 34,486 postmenopausal women (RR=0.38, 95% CI: 0.18-0.8; trend: P=0.014).

For the result of RCTs, as mentioned previously, it was controversy. A meta-analysis of 6 RCTs showed no significant association between vitamin E supplementation and CVD mortality; the pooled OR (95% CI) was 1.0 (0.94-1.06) (Vivekananthan et al., 2003). Another meta-analysis of 7 RCTs also showed similar results, with the pooled ORs (95% CI) of cardiovascular events, non-fatal MI, non-fatal stroke, and CVD deaths being 0.98 (0.94-1.03), 1.00 (0.92-1.09), 1.03 (0.93-1.14), and 1.00 (0.94-1.05), respectively [66]

Notes

  1. ↑ "USDA Nutrient Data Laboratory". In notes 2–11, USDA NDL Release 24 numbers are given as mg/(100 g). Low and high values vary some by raw versus cooked and by variety.
  2. ↑ Spinach (2.0 raw, 2.1 cooked), turnip (2.9 raw, 1.9 cooked), beet (1.5 raw, 1.8 cooked), collard (2.3 raw, 0.88 cooked), and dandelion greens (3.4 raw, 2.4 cooked)
  3. ↑ 1.1 raw, 1.5 cooked
  4. ↑ 0.78 raw, 1.5 cooked
  5. ↑ 1. raw, 0.8 cooked
  6. ↑ 0.26 raw, 0.94 boiled
  7. ↑ 0.54 raw, 0.56 cooked
  8. ↑ 0.36 raw, 0.44 cooked
  9. ↑ Lettuce (0.18 iceberg, 0.22 green leaf, 0.13 romaine, 0.15 red leaf, 0.18 butterhead)

References

  1. 1 2 3 4 5 6 "Vitamin E — Health Professional Fact Sheet". Office of Dietary Supplements, US National Institutes of Health. 9 May 2016. Retrieved 5 February 2015.
  2. ↑ Brigelius-Flohé R, Traber MG; Traber (1999). "Vitamin E: function and metabolism". FASEB J. 13 (10): 1145–1155. PMID 10385606.
  3. ↑ Traber, MG (1998). "The biological activity of vitamin E". The Linus Pauling Institute. Retrieved 6 March 2011.
  4. ↑ Bieri JG, Evarts RP; Evarts (1974). "γ-Tocopherol: metabolism, biological activity and significance in human vitamin E nutrition". American Journal of Clinical Nutrition. 27 (9): 980–986. PMID 4472121.
  5. 1 2 3 Brigelius-Flohé R, Traber MG; Traber (1 July 1999). "Vitamin E: function and metabolism". FASEB J. 13 (10): 1145–55. PMID 10385606.
  6. ↑ Reboul E, Richelle M, Perrot E, Desmoulins-Malezet C, Pirisi V, Borel P; Richelle; Perrot; Desmoulins-Malezet; Pirisi; Borel (15 November 2006). "Bioaccessibility of carotenoids and vitamin E from their main dietary sources". Journal of Agricultural and Food Chemistry. 54 (23): 8749–8755. doi:10.1021/jf061818s. PMID 17090117.
  7. ↑ Choe, Eunok; Min, David B (October 2009). "Mechanisms of Antioxidants in the Oxidation of Foods". Comprehensive Reviews in Food Science and Food Safety. 8 (4): 345–358. doi:10.1111/j.1541-4337.2009.00085.x. Retrieved 4 September 2016.
  8. 1 2 3 4 5 6 7 National Institute of Health (4 May 2009). "Vitamin E fact sheet".
  9. 1 2 Herrera E, Barbas C; Barbas (2001). "Vitamin E: action, metabolism and perspectives". Journal of Physiology and Biochemistry. 57 (2): 43–56. doi:10.1007/BF03179812. PMID 11579997.
  10. ↑ Packer L, Weber SU, Rimbach G; Weber; Rimbach (2001). "Molecular aspects of α-tocotrienol antioxidant action and cell signalling". Journal of Nutrition. 131 (2): 369S–73S. PMID 11160563.
  11. ↑ Traber, M.G. "19". In Ross, A. Catherine. Modern Nutrition in Health and Disease (11 ed.). Philadelphia, PA: Lippincott Williams & Wilkins. pp. 293–294. ISBN 9781605474618.
  12. ↑ Traber, MG. "Chapter 15: vitamin E". In Bowman BA and Russell RM. Current Knowledge in Nutrition. I (9 ed.). Washington DC, USA: ILSI. ISBN 978-1-57881-199-1.
  13. ↑ Wefers H, Sies H; Sies (1988). "The protection of ascorbate and glutathione against microsomal lipid peroxidation is dependent on Vitamin E". European Journal of Biochemistry. 174 (2): 353–357. doi:10.1111/j.1432-1033.1988.tb14105.x. PMID 3383850.
  14. 1 2 Traber MG, Atkinson J; Atkinson (2007). "Vitamin E, Antioxidant and Nothing More". Free radical biology & medicine. 43 (1): 4–15. doi:10.1016/j.freeradbiomed.2007.03.024. PMC 2040110Freely accessible. PMID 17561088.
  15. ↑ Wang X, Quinn PJ; Quinn (1999). "Vitamin E and its function in membranes". Progress in Lipid Research. 38 (4): 309–36. doi:10.1016/S0163-7827(99)00008-9. PMID 10793887.
  16. ↑ Brigelius-Flohé R, Traber MG; Traber (1999). "Vit amin E: function and metabolism". FASEB J. 13 (10): 1145–55. PMID 10385606.
  17. ↑ Ahsan, H; Ahad, A; Siddiqui, W. A. (2015). "A review of characterization of tocotrienols from plant oils and foods". Journal of Chemical Biology. 8 (2): 45–59. doi:10.1007/s12154-014-0127-8. PMC 4392014Freely accessible. PMID 25870713.
  18. ↑ "Vitamin E". Mayo Clinic. 2016. Retrieved 12 October 2016.
  19. ↑ Traber MG, Stevens JF; Stevens (2011). "Free Radical Biology and Medicine – Vitamins C and E: Beneficial effects from a mechanistic perspective". Free Radical Biology and Medicine. 51 (5): 1000–13. doi:10.1016/j.freeradbiomed.2011.05.017. PMC 3156342Freely accessible. PMID 21664268.
  20. ↑ UHMWPE Biomaterials Handbook, 2nd Edition, Kurtz ed. (2009)
  21. ↑ Schneider C (2005). "Chemistry and biology of vitamin E". Mol Nutr Food Res. 49 (1): 7–30. doi:10.1002/mnfr.200400049. PMID 15580660.
  22. 1 2 Devaraj S, Hugou I, Jialal I; Hugou; Jialal (2001). "-Tocopherol decreases CD36 expression in human monocyte-derived macrophages". J Lipid Res. 42 (4): 521–527. PMID 11290823.
  23. ↑ Azzi A, Stocker A; Stocker (2000). "Vitamin E: non-antioxidant roles". Prog Lipid Res. 39 (3): 231–255. doi:10.1016/S0163-7827(00)00006-0. PMID 10799717.
  24. 1 2 Villacorta L, Graça-Souza AV, Ricciarelli R, Zingg JM, Azzi A; Graça-Souza; Ricciarelli; Zingg; Azzi (2003). "α-Tocopherol induces expression of connective tissue growth factor and antagonizes tumor necrosis factor-α-mediated downregulation in human smooth muscle cells". Circ. Res. 92 (1): 104–110. doi:10.1161/01.RES.0000049103.38175.1B. PMID 12522127.
  25. ↑ Muller DP (2010). "Vitamin E and neurological function. Review". Mol. Nutr. Food Res. 54 (5): 710–718. doi:10.1002/mnfr.200900460. PMID 20183831.
  26. ↑ Dowd P, Zheng ZB; Zheng (1995). "On the mechanism of the anticlotting action of vitamin E quinone". Proc Natl Acad Sci U S A. 92 (18): 8171–8175. Bibcode:1995PNAS...92.8171D. doi:10.1073/pnas.92.18.8171. PMC 41118Freely accessible. PMID 7667263.
  27. ↑ Brigelius-Flohé R, Davies KJ; Davies (2007). "Is vitamin E an antioxidant, a regulator of signal transduction and gene expression, or a 'junk' food? Comments on the two accompanying papers: "Molecular mechanism of alpha-tocopherol action" by A. Azzi and "Vitamin E, antioxidant and nothing more" by M. Traber and J. Atkinson". Free radical biology & medicine. 43 (1): 2–3. doi:10.1016/j.freeradbiomed.2007.05.016. PMID 17561087.
  28. ↑ Atkinson J, Epand RF, Epand RM; Epand; Epand (2008). "Tocopherols and tocotrienols in membranes: a critical review". Free radical biology & medicine. 44 (5): 739–64. doi:10.1016/j.freeradbiomed.2007.11.010. PMID 18160049.
  29. 1 2 Whitney, Ellie; Sharon Rady Rolfes (2011). Peggy Williams, ed. Understanding Nutrition (Twelfth ed.). California: Wadsworth, Cengage Learning. ISBN 0-538-73465-5.
  30. ↑ Sesso HD, Buring JE, Christen WG, Kurth T, Belanger C, MacFadyen J, Bubes V, Manson JE, Glynn RJ, Gaziano JM; Buring; Christen; Kurth; Belanger; MacFadyen; Bubes; Manson; Glynn; Gaziano (2008). "Vitamins E and C in the Prevention of Cardiovascular Disease in Men: The Physicians' Health Study II Randomized Trial". JAMA: the Journal of the American Medical Association. 300 (18): 2123–33. doi:10.1001/jama.2008.600. PMC 2586922Freely accessible. PMID 18997197.
  31. 1 2 3 4 5 Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000.
  32. 1 2 3 4 5 Kowdley KV, Mason JB, Meydani SN, Cornwall S, Grand RJ; Mason; Meydani; Cornwall; Grand (1992). "Vitamin E deficiency and impaired cellular immunity related to intestinal fat malabsorption". Gastroenterology. 102 (6): 2139–42. PMID 1587435.
  33. ↑ Bjelakovic, G; Nikolova, D; Gluud, LL; Simonetti, RG; Gluud, C (14 March 2012). "Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases". The Cochrane database of systematic reviews (3): CD007176. doi:10.1002/14651858.CD007176.pub2. PMID 22419320.
  34. ↑ Haber, David (2006). Health promotion and aging: practical applications for health professionals (4th ed.). New York, NY: Springer Pub. p. 280. ISBN 978-0-8261-8463-4.
  35. ↑ Abner EL, Schmitt FA, Mendiondo MS, Marcum JL, Kryscio RJ; Schmitt; Mendiondo; Marcum; Kryscio (July 2011). "Vitamin E and all-cause mortality: a meta-analysis". Current aging science. 4 (2): 158–70. doi:10.2174/1874609811104020158. PMC 4030744Freely accessible. PMID 21235492.
  36. ↑ Bin Q, Hu X, Cao Y, Gao F; Hu; Cao; Gao (April 2011). "The role of vitamin E (tocopherol) supplementation in the prevention of stroke. A meta-analysis of 13 randomized controlled trials". Thrombosis and haemostasis. 105 (4): 579–85. doi:10.1160/TH10-11-0729. PMID 21264448.
  37. ↑ Haederle, Michael. "Vitamin E Supplements Raise Risk of Prostate Cancer". Health Discovery. AARP. Retrieved 11 November 2011.
  38. ↑ Olson JH, Erie JC, Bakri SJ; Erie; Bakri (May 2011). "Nutritional supplementation and age-related macular degeneration". Seminars in ophthalmology. 26 (3): 131–6. doi:10.3109/08820538.2011.577131. PMID 21609225.
  39. ↑ Rumbold, Alice; Ota, Erika; Hori, Hiroyuki; Miyazaki, Celine; Crowther, Caroline A. (2015-09-07). "Vitamin E supplementation in pregnancy". The Cochrane Database of Systematic Reviews (9): CD004069. doi:10.1002/14651858.CD004069.pub3. ISSN 1469-493X. PMID 26343254.
  40. ↑ Mathew MC, Ervin AM, Tao J, Davis RM; Ervin; Tao; Davis (2012). "Routine Antioxidant vitamin supplementation for preventing and slowing the progression of age-related cataract". Cochrane Database Syst Rev. 6 (6): CD004567. doi:10.1002/14651858.CD004567.pub2. PMC 4410744Freely accessible. PMID 22696344.
  41. ↑ "Vitamin E and Evening Primrose Oil for Management of Cyclical Mastaglgia: A Randomized Pilot Tudy" (PDF). Alternative Medicine Review. Retrieved September 19, 2015.
  42. ↑ Singh, Pankaj K.; Krishnan, Sunil (2015). "Vitamin E Analogs as Radiation Response Modifiers". Evidence-Based Complementary and Alternative Medicine. 2015: 1–16. doi:10.1155/2015/741301. ISSN 1741-427X.
  43. ↑ Material Safety Data Sheet for Vitamin E, accessdate: September 22, 2015
  44. ↑ "Wolfram Alpha". http://www.wolframalpha.com. External link in |publisher= (help)
  45. ↑ Simopoulos AP, Norman HA, Gillaspy JE, Duke JA (1992). "Common purslane: a source of omega-3 fatty acids and antioxidants". J Am Coll Nutr. 11 (4): 374–82. doi:10.1080/07315724.1992.10718240. PMID 1354675.
  46. ↑ "09038, Avocados, raw, California". National Nutrient Database for Standard Reference, Release 26. United States Department of Agriculture, Agricultural Research Service. Retrieved 14 August 2014.
  47. ↑ http://ndb.nal.usda.gov/ndb/nutrients/report/nutrientsfrm?max=25&offset=0&totCount=0&nutrient1=323&nutrient2=341&nutrient3=342&subset=1&fg=4&sort=c&measureby=g USDA List for Vitamin E in Vegetable Oils
  48. ↑ Institute of Medicine (2000). "Vitamin E". Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids (PDF). Washington, DC: The National Academies Press. pp. 186–283.
  49. ↑ Tolerable Upper Intake Levels For Vitamins And Minerals (PDF), European Food Safety Authority, 2006
  50. ↑ Evans HM, Bishop KS; Bishop (1922). "On the existence of a hitherto unrecognized dietary factor essential for reproduction". Science. 56 (1458): 650–651. Bibcode:1922Sci....56..650E. doi:10.1126/science.56.1458.650. JSTOR 1647181. PMID 17838496.
  51. ↑ Oakes, Elizabeth H. (2007). "Emerson, Gladys Anderson". Encyclopedia of World Scientists. p. 211. ISBN 1438118821{{inconsistent citations}}
  52. ↑ Subcommittee on Vitamin Tolerance, Committee on Animal Nutrition, National Research Council (1987). "Vitamin E, in Vitamin Tolerance of Animals". National Academy of Sciences. Retrieved 22 December 2013.
  53. 1 2 3 Bell EF (1987). "History of vitamin E in infant nutrition". American Journal of Clinical Nutrition. 46 (1 Suppl): 183–186. PMID 3300257.
  54. ↑ Shute, W. E.; Shute, E. V.; et al., Alpha Tocopherol (Vitamin E) in Cardiovascular Disease. Toronto, Ontario, Canada: Ryerson Press, 1945
  55. ↑ Vogelsang A, Shute EV; Shute (June 1946). "Effect of vitamin E in coronary heart disease". Nature. 157 (3997): 772. Bibcode:1946Natur.157..772V. doi:10.1038/157772b0. PMID 21064771.
  56. ↑ Shute EV, Vogelsang AB, Skelton FB, Shute WE; Vogelsang (January 1948). "The influence of vitamin E on vascular disease". Surg Gynecol Obstet. 86 (1): 1–8. PMID 18920873.
  57. ↑ Skelton F, Shute E, Skinner HG, Waud RA; Shute; Skinner; Waud (1946). "Antipurpuric Action of A-Tocopherol (Vitamin E)". Science. 103 (2687): 762. doi:10.1126/science.103.2687.762-b. PMID 17836459.
  58. ↑ György P, Rose CS; Rose (1948). "Effect of dietary factors on early mortality and hemoglobinuria in rats following administration of alloxan". Science. 108 (2817): 716–718. Bibcode:1948Sci...108..716G. doi:10.1126/science.108.2817.716. PMID 17752961.
  59. ↑ Gerloczy F (1949). "Clinical and pathological role of d, 1-alpha tocopherol in premature infants; studies on the treatment of scleroedema". Ann Paediatr. 173 (3): 171–86. PMID 18140084.
  60. ↑ Brion LP, Bell EF, Raghuveer TS; Bell; Raghuveer (2003). Brion, Luc P, ed. "Vitamin E supplementation for prevention of morbidity and mortality in preterm infants". Cochrane Database Syst Rev (4): CD003665. doi:10.1002/14651858.CD003665. PMID 14583988. These observations explain why even a small dose of 5 mg of dl-alpha-tocopheryl acetate provided enterally has proven to be more efficient than larger intramuscular doses (30 mg) in treating scleredema (Gerlóczy 1949)
  61. ↑ American Heart Association, 2015
  62. ↑ Maruyama, K; Iso, H (2014). Overview of the Role of Antioxidant Vitamins as Protection Against Cardiovascular Disease: Implications of Aging. Available from: Aging: Oxidative Stress and Dietary Antioxidants (1 ed.). New York: Elsevier Inc. p. Chapter 21.
  63. 1 2 Simon, E; Gariepy, J; Cogny, A; Moatti, A; Simon, A (2001). "Erythrocyte, but not plasma, vitamin E concentration is associated with carotid intima–media thickening in asymptomatic men at risk for cardiovascular disease". Atherosclerosis. 159 (1): 193–200. doi:10.1016/s0021-9150(01)00493-2. PMID 11689221.
  64. ↑ Asplund, K (2002). "Antioxidant vitamins in the prevention of cardiovascular disease: a systematic review". Journal of Internal Medicine. 251 (5): 372–392. doi:10.1046/j.1365-2796.2002.00973.x. PMID 11982737.
  65. ↑ Rimm, E.B; Stampfer, M.J; Ascherio, A (1993). "Vitamin E consumption and the risk of coronary heart disease in men". New England Journal of Medicine. 328 (20): 1450–6. doi:10.1056/NEJM199305203282004. PMID 8479464.
  66. ↑ Eidelman, R.S; Hollar, D; Hebert, P.R; Lamas, G.A; Hennekens, C.H (2004). "Randomized trials of vitamin E in the treatment and prevention of cardiovascular disease". Archives of Internal Medicine. 164 (14): 1552–6. doi:10.1001/archinte.164.14.1552. PMID 15277288.

Further reading

This article is issued from Wikipedia - version of the 11/29/2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.