Vitamin E was discovered in 1922 by Herbert McLean Evans and Katharine Scott Bishop and first isolated in a pure form by Evans and Gladys Anderson Emerson in 1935 at the University of California, Berkeley. Because the vitamin activity was first identified as a dietary fertility factor (in rats) it was given the name "tocopherol" from the Greek words "τόκος" [tókos, birth], and "φέρειν", [phérein, to bear or carry] meaning in sum "to carry a pregnancy," with the ending "-ol" signifying its status as a chemical alcohol. George M. Calhoun, Professor of Greek at the University of California, was credited with helping with the naming process. Erhard Fernholz elucidated its structure in 1938 and shortly afterwards the same year, Paul Karrer and his team first synthesized it.
Bejon, P., Mwacharo, J., Kai, O., Mwangi, T., Milligan, P., Todryk, S., Keating, S., Lang, T., Lowe, B., Gikonyo, C., Molyneux, C., Fegan, G., Gilbert, S. C., Peshu, N., Marsh, K., and Hill, A. V. A phase 2b randomised trial of the candidate malaria vaccines FP9 ME-TRAP and MVA ME-TRAP among children in Kenya. PLoS.Clin Trials 2006;1(6):e29. View abstract.
In East Asia, where polished white rice was the common staple food of the middle class, beriberi resulting from lack of vitamin B1 was endemic. In 1884, Takaki Kanehiro, a British-trained medical doctor of the Imperial Japanese Navy, observed that beriberi was endemic among low-ranking crew who often ate nothing but rice, but not among officers who consumed a Western-style diet. With the support of the Japanese navy, he experimented using crews of two battleships; one crew was fed only white rice, while the other was fed a diet of meat, fish, barley, rice, and beans. The group that ate only white rice documented 161 crew members with beriberi and 25 deaths, while the latter group had only 14 cases of beriberi and no deaths. This convinced Takaki and the Japanese Navy that diet was the cause of beriberi, but they mistakenly believed that sufficient amounts of protein prevented it. That diseases could result from some dietary deficiencies was further investigated by Christiaan Eijkman, who in 1897 discovered that feeding unpolished rice instead of the polished variety to chickens helped to prevent a kind of polyneuritis that was the equivalent of beriberi. The following year, Frederick Hopkins postulated that some foods contained "accessory factors" — in addition to proteins, carbohydrates, fats etc. — that are necessary for the functions of the human body. Hopkins and Eijkman were awarded the Nobel Prize for Physiology or Medicine in 1929 for their discoveries.
The National Health and Nutrition Examination Survey (NHANES), 2005–2006, estimated vitamin D intakes from both food and dietary supplements [4,27]. Average intake levels for males from foods alone ranged from 204 to 288 IU/day depending on life stage group; for females the range was 144 to 276 IU/day. When use of dietary supplements was considered, these mean values were substantially increased (37% of the U.S. population used a dietary supplement containing vitamin D.) The most marked increase was among older women. For women aged 51–70 years, mean intake of vitamin D from foods alone was 156 IU/day, but 404 IU/day with supplements. For women >70 years, the corresponding figures were 180 IU/day to 400 IU/day .
Giannetti, A., Coppini, M., Bertazzoni, M. G., Califano, A., Altieri, E., Pazzaglia, A., Lega, M., Lombardo, M., Pelfini, C., Veller, Fornasa C., Rabbiosi, G., and Cespa, M. Clinical trial of the efficacy and safety of oral etretinate with calcipotriol cream compared with etretinate alone in moderate-severe psoriasis. J Eur.Acad.Dermatol.Venereol. 1999;13(2):91-95. View abstract.
Hino, K., Murakami, Y., Nagai, A., Kitase, A., Hara, Y., Furutani, T., Ren, F., Yamaguchi, Y., Yutoku, K., Yamashita, S., Okuda, M., Okita, M., and Okita, K. Alpha-tocopherol [corrected] and ascorbic acid attenuates the ribavirin [corrected] induced decrease of eicosapentaenoic acid in erythrocyte membrane in chronic hepatitis C patients. J Gastroenterol Hepatol. 2006;21(8):1269-1275. View abstract.
Grobusch, M. P., Lell, B., Schwarz, N. G., Gabor, J., Dornemann, J., Potschke, M., Oyakhirome, S., Kiessling, G. C., Necek, M., Langin, M. U., Klein, Klouwenberg P., Klopfer, A., Naumann, B., Altun, H., Agnandji, S. T., Goesch, J., Decker, M., Salazar, C. L., Supan, C., Kombila, D. U., Borchert, L., Koster, K. B., Pongratz, P., Adegnika, A. A., Glasenapp, I., Issifou, S., and Kremsner, P. G. Intermittent preventive treatment against malaria in infants in Gabon--a randomized, double-blind, placebo-controlled trial. J Infect.Dis 12-1-2007;196(11):1595-1602. View abstract.
Vitamin E is fat soluble, so dietary supplement products are usually in the form of the vitamin dissolved in vegetable oil in a softgel capsule. For alpha-tocopherol, amounts range from 100 to 1000 IU per serving. Smaller amounts are incorporated into multi-vitamin/mineral tablets. Gamma-tocopherol and tocotrienol supplements are also available from dietary supplement companies. The latter are extracts from palm or annatto oils.
Julien, M. R., Gomes, A., Varandas, L., Rodrigues, P., Malveiro, F., Aguiar, P., Kolsteren, P., Stuyft, P., Hildebrand, K., Labadarios, D., and Ferrinho, P. A randomized, double-blind, placebo-controlled clinical trial of vitamin A in Mozambican children hospitalized with nonmeasles acute lower respiratory tract infections. Trop.Med Int Health 1999;4(12):794-800. View abstract.
For colorectal cancer, a systematic review identified RCTs of vitamin E and placebo followed for 7–10 years. There was a non-significant 11% decrease in relative risk. The SELECT trial (men over 55 years, placebo or 400 IU/day) also reported on colorectal cancer. There was a non-significant 3% increase in adenoma occurrence compared to placebo. The Women's Health Study compared placebo to 600 IU of natural-source vitamin E on alternate days for an average of 10.1 years. There were no significant differences for incidences of all types of cancer, cancer deaths, or for breast, lung or colon cancers.
A worldwide summary of more than one hundred human studies reported a median of 22.1 µmol/L for serum α-tocopherol, and defined α-tocopherol deficiency as less than 12 µmol/L. It cited a recommendation that serum α-tocopherol concentration be ≥30 µmol/L to optimize health benefits. In contrast, the US Dietary Reference Intake text for vitamin E concluded that a plasma concentration of 12 µmol/L was sufficient to achieve normal ex vivo hydrogen peroxide-induced hemolysis. A 2014 review defined less than 9 µmol/L as deficient, 9-12 µmol/L as marginal and greater than 12 µmol/L as adequate.
Ramlau, R., Zatloukal, P., Jassem, J., Schwarzenberger, P., Orlov, S. V., Gottfried, M., Pereira, J. R., Temperley, G., Negro-Vilar, R., Rahal, S., Zhang, J. K., Negro-Vilar, A., and Dziewanowska, Z. E. Randomized phase III trial comparing bexarotene (L1069-49)/cisplatin/vinorelbine with cisplatin/vinorelbine in chemotherapy-naive patients with advanced or metastatic non-small-cell lung cancer: SPIRIT I. J Clin.Oncol. 4-10-2008;26(11):1886-1892. View abstract.
The European Food Safety Authority (EFSA) refers to the collective set of information as Dietary Reference Values, with Population Reference Intake (PRI) instead of RDA, and Average Requirement instead of EAR. AI and UL defined the same as in United States. For women and men ages 10 and older the PRIs are set at 11 and 13 mg/day, respectively. PRI for pregnancy is 11 mg/day, for lactation 11 mg/day. For children ages 1–9 years the PRIs increase with age from 6 to 9 mg/day. These PRIs are lower than the U.S. RDAs. The European Food Safety Authority reviewed the same safety question and set a UL at 300 mg/day. The EU used an effect on blood clotting as a critical effect, identified that no adverse effects were observed in a human trial as 540 mg/day, used an uncertainty factor of 2 to get to a suggest UL of 270 mg/day, then rounded up to 300 mg/day.
Vitamin A is the name of a group of fat-soluble retinoids, including retinol, retinal, and retinyl esters [1-3]. Vitamin A is involved in immune function, vision, reproduction, and cellular communication [1,4,5]. Vitamin A is critical for vision as an essential component of rhodopsin, a protein that absorbs light in the retinal receptors, and because it supports the normal differentiation and functioning of the conjunctival membranes and cornea [2-4]. Vitamin A also supports cell growth and differentiation, playing a critical role in the normal formation and maintenance of the heart, lungs, kidneys, and other organs .
Mazumder S, Taneja S, Bhatia K, Yoshida S, Kaur J, Dube B, Toteja GS, Bahl R, Fontaine O, Martines J, Bhandari N; Neovita India Study Group. Efficacy of early neonatal supplementation with vitamin A to reduce mortality in infancy in Haryana, India (Neovita): a randomised, double-blind, placebo-controlled trial. Lancet. 2015 4;385(9975):1333-42. View abstract.
Li, J. Y., Taylor, P. R., Li, B., Dawsey, S., Wang, G. Q., Ershow, A. G., Guo, W., Liu, S. F., Yang, C. S., Shen, Q., and . Nutrition intervention trials in Linxian, China: multiple vitamin/mineral supplementation, cancer incidence, and disease-specific mortality among adults with esophageal dysplasia. J.Natl.Cancer Inst. 9-15-1993;85(18):1492-1498. View abstract.
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 IU, but as of May 27, 2016 it was revised to 15 mg to bring it into agreement with the RDA. A table of the old and new adult Daily Values is provided at Reference Daily Intake. The original deadline to be in compliance was July 28, 2018, but on September 29, 2017 the FDA released a proposed rule that extended the deadline to January 1, 2020 for large companies and January 1, 2021 for small companies. European Union regulations require that labels declare energy, protein, fat, saturated fat, carbohydrates, sugars, and salt. Voluntary nutrients may be shown if present in significant amounts. Instead of Daily Values, amounts are shown as percent of Reference Intakes (RIs). For vitamin E, 100% RI was set at 12 mg in 2011.
Some vitamins have documented acute or chronic toxicity at larger intakes, which is referred to as hypertoxicity. The European Union and the governments of several countries have established Tolerable upper intake levels (ULs) for those vitamins which have documented toxicity (see table). The likelihood of consuming too much of any vitamin from food is remote, but excessive intake (vitamin poisoning) from dietary supplements does occur. In 2016, overdose exposure to all formulations of vitamins and multi-vitamin/mineral formulations was reported by 63,931 individuals to the American Association of Poison Control Centers with 72% of these exposures in children under the age of five. In the US, analysis of a national diet and supplement survey reported that about 7% of adult supplement users exceeded the UL for folate and 5% of those older than age 50 years exceeded the UL for vitamin A.