Vitamin E supplementation

Vitamin E includes two families with eight vitamers:

1) the tocopherols (α,ß,γ,δ)

2) the tocotrienols (α,ß,γ,δ): which are less biologically active compounds with other important biological functions for cells.

he vitamers are named according to the position and number of methyl groups in their ring systems. The most important of them is α-tocopherol in the natural form of the D isomer. DL-α-tocopherol is the synthetic form of vitamin E.

Another form of vitamin E is D-α-tocopheryl acid succinate, also known as dry vitamin E because it can be used in supplements that do not contain a fatty vehicle as an additive.

A good way to supplement tocopherols in a balanced manner is through the combination of mixed tocopherols that supply the following: alpha-tocopherol < 20 %, beta-tocopherol < 10 %, gamma-tocopherol 50 % – 70 % y delta-tocopherol 10 % – 30 %.

Foods with vitamin E

The highest levels of vitamin E (alpha-tocopherol) are found in the following foods: asparagus, avocados, eggs, milk, walnuts, seeds, spinach and other green vegetables, uncooked vegetable oils, and wholegrain foods (Anonymous 2010).

Cooking and processing reduces the vitamin E content of foods by 10% to 60%.

Alpha-tocopherol

The highest content is found in the following:

• Palm, soy, safflower, and peanut oils in significant amounts.
• Olive and sunflower oil.
• Nuts. The highest content is found in the following: almonds, hazelnuts, sunflower seeds, peanuts, pistachios, and Brazil nuts, although all contain alpha-tocopherol.
• Oats and barley.

In smaller amounts:

• Oily fish species.
• Cocoa and chocolate powder.
• Muesli and some breakfast cereals.
• Brown rice.
• Margarine.
• Whole eggs and egg yolks.
• Ground beef.
• Spinach. Soy.
• Mangoes. Pears. Blackberries. Nectarines. Grapes. Apples.

Gamma-tocopherol

The highest content is found in the following::

• Soy, corn, palm, safflower, peanut, and coconut oils, in large amounts. Olive oil does not contain any gamma-tocopherol.
• Nuts and seeds. The highest content is found in sesame seeds. A high content is also found in the following: pecans, walnuts, pistachios, Brazil nuts, and cashews. Smaller amounts: almonds and peanuts. None: hazelnuts and macadamia nuts.
• Legumes, mainly soybeans.

In scant amounts:

• Sunflower oil.
• Wholegrain bread.
• Oats and barley.
• Wholegrain pasta.
• Peanut butter.
• Whole eggs and egg yolks.
• Chicken liver.

Beta-tocopherol

Very few foods contain beta-tocopherol. In very small amounts: oats, red peppers, eggs, almonds, peanuts and peanut butter, and wholegrain bread.

Delta-tocopherol

Very few foods contain delta-tocopherol. In large amounts: soy and palm oil. In very small amounts: oats, soy, sunflower oil, and cashews.

Tocotrienols

Very few foods contain tocotrienols. In large amounts: palm oil and barley. Oats contain alpha-tocotrienol. Nuts do not contain any tocotrienols, and only wholegrain bread and eggs contain alpha- and beta-tocotrienols in small amounts.

Intake and deficiencies

Vitamin E deficiency is common in the population.

• In chronic diseases, natural alpha-tocopherol should be supplied in low doses, as deficiency is common and it is a basic nutrient. Moderate and high doses, however, are not recommended.
• The long-term recommended doses of alpha-tocopherol are 10–20 mg, and 50 mg/day should not be exceeded.
• Supplements should use natural alpha-tocopherol (d-alpha-tocopherol) rather than the synthetic version (dl-alpha-tocopherol). Tocopherols and tocotrienols lower cholesterol but also coenzyme Q10 levels and have not be sufficiently studied.
• Natural alpha-tocopherol has an excellent safety profile, with no side effects, in the recommended forms and doses.

Intake. The vitamin E concentration depends on external inputs. Average intake of vitamin E represents 76% of the NRV in men and 69% in women. 50% of the population has suboptimal intake, particularly in the case of middle-aged men and women over the age of 55 (Aranceta, Serra-Majem et al. 2001).

Deficiencies. In the United States, alpha-tocopherol levels were studied in 16,295 adults and 26% of whites, 41% of Afro-Americans, 28% of Mexican-Americans, and 32% of the rest had levels below 20 micromoles/liter, the value at which the risk of cardiovascular diseases seems to rise (Ford and Sowell 1999).

Nutrients. When selenium intake is reduced, vitamin E needs are greater. If intake of polyunsaturated fatty acids (vegetable oils, fish oils, etc.) is high, vitamin E needs are greater, to prevent their oxidation. High doses of vitamin A increase vitamin E needs.

Common medications. Orlistat, laxatives, and cholestyramine can accentuate a marginal vitamin E deficiency.

Bibliography

• Albanes, D. (2007). “Antioxidant supplements and mortality.” JAMA 298(4): 400; author reply 402-403.
• Anonymous (1994). “The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group.” N Engl J Med 330(15): 1029-1035.
• Anonymous. (2009, 15 Dec 2009). “Vitamin E.” Retrieved 24 Feb, 2010, fromhttp://ods.od.nih.gov/factsheets/VitaminE.asp.
• Anonymous. (2010). “Dietary Reference Intakes (DRIs): Recommended Intakes for Individuals, Vitamins.” Retrieved 24 Feb, 2010.
• Anonymous. (2010). “Search the USDA National Nutrient Database for Standard Reference.” Retrieved 24 Feb, 2010, from http://www.nal.usda.gov/fnic/foodcomp/search/.
• Aranceta, J., L. Serra-Majem, et al. (2001). “Vitamins in Spanish food patterns: the eVe Study.” Public Health Nutr 4(6A): 1317-1323.
• Atkinson, J., R. F. Epand, et al. (2008). “Tocopherols and tocotrienols in membranes: a critical review.” Free Radic Biol Med 44(5): 739-764.
• Azzi, A. (2007). “Molecular mechanism of alpha-tocopherol action.” Free Radic Biol Med 43(1): 16-21.
• Blatt, D. H. and W. A. Pryor (2005). “High-dosage vitamin E supplementation and all-cause mortality.” Ann Intern Med 143(2): 150-151; author reply 156-158.
• Bonnefont-Rousselot, D. (2001). “[Antioxidant and anti-AGE therapeutics: evaluation and perspectives].” J Soc Biol 195(4): 391-398.
• Brigelius-Flohe, R. and K. J. 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 Radic Biol Med 43(1): 2-3.
• Brigelius-Flohe, R. and M. G. Traber (1999). “Vitamin E: function and metabolism.” FASEB J 13(10): 1145-1155.
• Burton, G. W., K. U. Ingold, et al. (1988). “Comparison of free alpha-tocopherol and alpha-tocopheryl acetate as sources of vitamin E in rats and humans.” Lipids 23(9): 834-840.
• Cheeseman, K. H., A. E. Holley, et al. (1995). “Biokinetics in humans of RRR-alpha-tocopherol: the free phenol, acetate ester, and succinate ester forms of vitamin E.” Free Radic Biol Med 19(5): 591-598.
• Das, S., I. Lekli, et al. (2008). “Cardioprotection with palm oil tocotrienols: comparision of different isomers.” Am J Physiol Heart Circ Physiol 294(2): H970-978.
• Devereux, G. (2007). “Early life events in asthma–diet.” Pediatr Pulmonol 42(8): 663-673.
• Fabian E, Pölöskey P, Kósa L, Elmadfa I, Réthy LA (2013). ” Nutritional supplements and plasma antioxidants in chilhood asthma” Wien Klin Wochenschr. May 1
• Ford, E. S. and A. Sowell (1999). “Serum alpha-tocopherol status in the United States population: findings from the Third National Health and Nutrition Examination Survey.” Am J Epidemiol 150(3): 290-300.
• Greenberg, E. R. (2005). “Vitamin E supplements: good in theory, but is the theory good?” Ann Intern Med 142(1): 75-76.
• Herrera, E. and C. Barbas (2001). “Vitamin E: action, metabolism and perspectives.” J Physiol Biochem 57(2): 43-56.
• Horwitt, M. K., W. H. Elliott, et al. (1984). “Serum concentrations of alpha-tocopherol after ingestion of various vitamin E preparations.” Am J Clin Nutr 40(2): 240-245.
• Huang, H. Y., B. Caballero, et al. (2008). Multivitamin/Mineral Supplements and Prevention of Chronic Disease. Evidence Report/Technology Assessment No. 139. (Prepared by The Johns Hopkins University Evidence-based Practice Center under Contract No. 290-02-0018). A. P. N. 06-E012. Rockville, MD, Agency for Healthcare Research and Quality.
• Huang, H. Y., S. Teutsch, et al. (2007). “Antioxidant supplements and mortality.” JAMA 298(4): 400-401; author reply 402-403.
• Ikeda, S., T. Tohyama, et al. (2003). “Dietary alpha-tocopherol decreases alpha-tocotrienol but not gamma-tocotrienol concentration in rats.” J Nutr 133(2): 428-434.
• Inokuchi, H., H. Hirokane, et al. (2003). “Anti-angiogenic activity of tocotrienol.” Biosci Biotechnol Biochem 67(7): 1623-1627.
• Hathcock, J. N., A. Azzi, et al. (2005). “Vitamins E and C are safe across a broad range of intakes.” Am J Clin Nutr 81(4): 736-745.
• Iuliano, L., F. Micheletta, et al. (2001). “Bioavailability of vitamin E as function of food intake in healthy subjects: effects on plasma peroxide-scavenging activity and cholesterol-oxidation products.” Arterioscler Thromb Vasc Biol 21(10): E34-37.
• Khanna, S., S. Roy, et al. (2005). “Neuroprotective properties of the natural vitamin E alpha-tocotrienol.” Stroke 36(10): 2258-2264.
• Kirmizis, D. and D. Chatzidimitriou (2009). “Antiatherogenic effects of vitamin E: the search for the Holy Grail.” Vasc Health Risk Manag 5: 767-774.
• Lonn, E., J. Bosch, et al. (2005). “Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial.” JAMA 293(11): 1338-1347.
• Malafa, M. P. (2008). “New insights and gains in pancreatic cancer.” Cancer Control 15(4): 276-277.
• Miller, E. R., 3rd, R. Pastor-Barriuso, et al. (2005). “Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality.” Ann Intern Med 142(1): 37-46.
• Munch, G., B. Kuhla, et al. (2003). “Anti-AGEing defences against Alzheimer’s disease.” Biochem Soc Trans 31(Pt 6): 1397-1399.
• Packer, L., S. U. Weber, et al. (2001). “Molecular aspects of alpha-tocotrienol antioxidant action and cell signalling.” J Nutr 131(2): 369S-373S.
• Parker, R. A., B. C. Pearce, et al. (1993). “Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.” J Biol Chem 268(15): 11230-11238.
• Pruthi, S., T. G. Allison, et al. (2001). “Vitamin E supplementation in the prevention of coronary heart disease.” Mayo Clin Proc 76(11): 1131-1136.
• Qureshi, A. A., B. C. Pearce, et al. (1996). “Dietary alpha-tocopherol attenuates the impact of gamma-tocotrienol on hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in chickens.” J Nutr 126(2): 389-394.
• Riccioni, G., M. Barbara, et al. (2007). “Antioxidant vitamin supplementation in asthma.” Ann Clin Lab Sci 37(1): 96-101.
• Rigotti, A. (2007). “Absorption, transport, and tissue delivery of vitamin E.” Mol Aspects Med 28(5-6): 423-436.
• Schaffer, S., W. E. Muller, et al. (2005). “Tocotrienols: constitutional effects in aging and disease.” J Nutr 135(2): 151-154.
• Sen, C. K., S. Khanna, et al. (2004). “Tocotrienol: the natural vitamin E to defend the nervous system?” Ann N Y Acad Sci 1031: 127-142.
• Sen, C. K., S. Khanna, et al. (2006). “Tocotrienols: Vitamin E beyond tocopherols.” Life Sci 78(18): 2088-2098.
• Sen, C. K., S. Khanna, et al. (2000). “Molecular basis of vitamin E action. Tocotrienol potently inhibits glutamate-induced pp60(c-Src) kinase activation and death of HT4 neuronal cells.” J Biol Chem 275(17): 13049-13055.
• Sesso, H. D., J. E. Buring, et al. (2008). “Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians’ Health Study II randomized controlled trial.” JAMA 300(18): 2123-2133.
• Song, B. L. and R. A. DeBose-Boyd (2006). “Insig-dependent ubiquitination and degradation of 3-hydroxy-3-methylglutaryl coenzyme a reductase stimulated by delta- and gamma-tocotrienols.” J Biol Chem 281(35): 25054-25061.
• Stocker, A. (2004). “Molecular mechanisms of vitamin E transport.” Ann N Y Acad Sci 1031: 44-59.
• Traber, M. G. and J. Atkinson (2007). “Vitamin E, antioxidant and nothing more.” Free Radic Biol Med 43(1): 4-15.
• Wang, X. and P. J. Quinn (1999). “Vitamin E and its function in membranes.” Prog Lipid Res 38(4): 309-336.
• Weiser, H., G. Riss, et al. (1996). “Biodiscrimination of the eight alpha-tocopherol stereoisomers results in preferential accumulation of the four 2R forms in tissues and plasma of rats.” J Nutr 126(10): 2539-2549.
• Yoshida, Y., E. Niki, et al. (2003). “Comparative study on the action of tocopherols and tocotrienols as antioxidant: chemical and physical effects.” Chem Phys Lipids 123(1): 63-75.
• Zingg, J. M. and A. Azzi (2004). “Non-antioxidant activities of vitamin E.” Curr Med Chem 11(9): 1113-1133.

Reference values

NRV, PRI, UL for vitamin E

The NRV for alpha-tocopherol is 12 mg. The PRI for adults is 8 mg for women and 12 mg for men. The PRI for vitamin E for a 25-year-old male is 15 mg/day.

The UL for alpha-tocopherol is 300 mg/day.

Vitamin E is a practically non-toxic substance.

Given that vitamin E can act as an anticoagulant and increase the risk of bleeding, many agencies have indicated a maximum upper limit (UL) of 300 mg/day (Anonymous 2009).

The IU of biological activity for vitamin E is obsolete, but some publications and books continue to use it.

1 IU = 0.67 equivalent mg of α-tocopherol

1 mg of α-tocopherol = 1.49 IU

NRV: Nutrient Reference Value. These are the daily amounts recommended for vitamins and minerals (micronutrients only) considered sufficient in the European Union to prevent a deficit in most healthy individuals in the population. They are the values used for labeling and claims.

PRI: Population Reference Intake. These are the reference values for a specific population group, defined as the amount of energy and/or nutrients (macronutrients and micronutrients) recommended to cover the nutritional needs of practically the entire population. They refer to healthy population groups. The values are expressed per person per day, as a 15-day average. To account for individual differences in digestive and metabolic processes, the PRI figure used for each nutrient is the average plus twice the standard deviation (except for energy, for which the average is used), thereby including almost all healthy individuals in the group (97.5%).

UL: Tolerable Upper Intake Level: the maximum level of total daily intake of a nutrient in a context of long-term or chronic consumption which does not pose a risk to health.