Who Found Vitamin E, and How a Fertility Factor Became an Antioxidant Story

Herbert Evans and Katharine Bishop found vitamin E in 1922 while testing rat diets for reproduction. The compound is now described mainly as an antioxidant, and the high-dose trials give reasons for caution with capsules.

The history of vitamin E starts with rats that would not reproduce. In 1922, Herbert McLean Evans and Katharine Scott Bishop, working at the University of California, Berkeley, found that rats fed a purified diet with lard as their only fat did not reproduce ([UCSF Library](https://history.library.ucsf.edu/kbishop.html)). Lipid extracts from several grains corrected the problem. The team that found vitamin E was studying pregnancy, not oxidation. The antioxidant story came later. **Jump to:** [The 1922 experiments](#what-the-1922-rat-experiments-measured), [Antioxidant chemistry](#from-the-anti-sterility-vitamin-to-antioxidant-chemistry), [High-dose trials](#what-the-large-high-dose-trials-recorded), [Label units](#tocopherol-vitamin-e-and-label-units), [Food versus capsules](#food-versus-capsules), [FAQ](#frequently-asked-questions) ## What the 1922 rat experiments measured The outcome they tracked was reproduction. Evans and Bishop fed rats a semi-synthetic diet in which lard was the sole source of fat, and the rats did not reproduce. A "substance X" in lipid extracts of various grains corrected the defect. The findings appeared in *Science* the same year, under the title "On the existence of a hitherto unrecognized dietary factor essential for reproduction" ([UCSF Library](https://history.library.ucsf.edu/kbishop.html)). Early on, the compound was called the anti-sterility vitamin. The University of California, San Francisco (UCSF) biography of Evans lists the discovery and isolation of vitamin E among four achievements often mentioned as deserving of the Nobel Prize ([UCSF Library](https://history.library.ucsf.edu/evans.html)). ## From the anti-sterility vitamin to antioxidant chemistry The old name points at fertility, but the modern description is about fats. According to the [Linus Pauling Institute](https://lpi.oregonstate.edu/mic/vitamins/vitamin-E), the main function of alpha-tocopherol in humans is as a fat-soluble antioxidant that stops lipid peroxidation, the chain reaction in which free radicals damage fats. The institute says alpha-tocopherol is "uniquely suited to intercept peroxyl radicals," which prevents that chain reaction. A 1989 review by G. W. Burton and K. U. Ingold says alpha-tocopherol has "near optimal activity as a chain-breaking antioxidant." According to PubMed, the paper appeared in *Annals of the New York Academy of Sciences* ([DOI](https://doi.org/10.1111/j.1749-6632.1989.tb14904.x)). The same institute notes that vitamin C can regenerate the oxidized form of vitamin E back to alpha-tocopherol. The [vitamin C history](/blog/history/history-of-vitamin-c-from-scurvy-to-ascorbic-acid) covers how that vitamin was identified. ## What the large high-dose trials recorded According to PubMed, three reports anchor the high-dose record. Each dose below was several times the 15 mg adult recommended dietary allowance (RDA). - **ATBC, 1994.** The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study (ATBC) randomly assigned 29,133 male smokers aged 50 to 69 in southwestern Finland to alpha-tocopherol (50 mg a day), beta carotene (20 mg a day), both, or placebo. Alpha-tocopherol did not reduce lung cancer incidence. The authors also observed more deaths from hemorrhagic stroke (bleeding in the brain) in the alpha-tocopherol group. They wrote that the trial "raises the possibility that these supplements may actually have harmful as well as beneficial effects" ([DOI](https://doi.org/10.1056/NEJM199404143301501)). - **SELECT, 2011.** The Selenium and Vitamin E Cancer Prevention Trial (SELECT) randomized 35,533 men. The vitamin E group took 400 IU (international units) a day of a synthetic form, all-rac-alpha-tocopheryl acetate. Compared with placebo, the hazard ratio for prostate cancer, which compares event rates over follow-up, was 1.17 (99% confidence interval 1.004 to 1.36). The authors concluded that vitamin E "significantly increased the risk of prostate cancer among healthy men" ([DOI](https://doi.org/10.1001/jama.2011.1437)). - **Meta-analysis, 2005.** Miller and colleagues pooled 19 trials with 135,967 participants. Nine of the 11 trials testing 400 IU a day or more showed increased risk of all-cause mortality (death from any cause). The pooled risk difference was 39 per 10,000 persons (95% CI 3 to 74). The authors wrote that doses of 400 IU a day or more "may increase all-cause mortality and should be avoided" ([DOI](https://doi.org/10.7326/0003-4819-142-1-200501040-00110)). All three tested supplements, not foods. ## Tocopherol, vitamin E and label units Vitamin E is a family of eight compounds: alpha-, beta-, gamma-, and delta-tocopherol, plus four tocotrienols (a related family of compounds). Alpha-tocopherol is the only form recognized to meet human requirements ([NIH Office of Dietary Supplements](https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/)). So "tocopherol" names four of the eight, and "vitamin E" names the whole group. The natural form is commonly labeled d-alpha-tocopherol. The synthetic form, commonly labeled dl-alpha-tocopherol, is about half as active. The Linus Pauling Institute notes that labels should list milligrams and that older labels used international units (IU). The units convert differently: 1 mg of natural alpha-tocopherol equals 1.49 IU, and 1 mg of synthetic equals 2.22 IU ([NIH ODS](https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/)). ## Food versus capsules The table compares common foods with a 400 IU synthetic supplement dose. | Source | Serving | Alpha-tocopherol (mg) | |---|---|---| | Wheat germ oil | 1 tablespoon | 20.3 | | Sunflower seeds, dry roasted | 1 ounce | 7.4 | | Almonds, dry roasted | 1 ounce | 6.8 | | Sunflower oil | 1 tablespoon | 5.6 | | Spinach, boiled | half cup | 1.9 | | Synthetic supplement dose | 400 IU | 180 | Food values come from [NIH ODS Table 2](https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/). The 180 mg figure uses ODS's conversion of 0.45 mg per IU. Adults need 15 mg a day. U.S. adults 20 and older average 11.5 mg from food for men and 9.5 mg for women, which the [Linus Pauling Institute](https://lpi.oregonstate.edu/mic/vitamins/vitamin-E) calls well below the RDA. The adult upper limit for supplemental vitamin E is 1,000 mg a day (NIH ODS). ## Bottom line Nuts, seeds, and vegetable oils are good sources of vitamin E, and the amounts are modest. If you take a supplement, read the milligram figure, check whether it lists d-alpha or dl-alpha, and compare the number with the 15 mg RDA and the 1,000 mg upper limit. Anyone considering a high-dose product should weigh the trial record above before buying it. ## Frequently asked questions ### What did the 1922 rat experiments actually measure? They measured whether rats could reproduce on a purified diet in which lard was the only fat. The rats did not reproduce. Lipid extracts from several grains corrected the defect, and the active material was called "substance X." The team was asking about pregnancy, not oxidation. The paper appeared in Science that same year ([UCSF Library](https://history.library.ucsf.edu/kbishop.html)). The compound's first name, the anti-sterility vitamin, reflected that fertility result ([UCSF Library](https://history.library.ucsf.edu/evans.html)). ### Is vitamin E the same molecule as tocopherol? Not quite. Tocopherol is one of two families of compounds that make up vitamin E. The other family is the tocotrienols, and together the two families give eight forms. Only alpha-tocopherol is recognized to meet human requirements. According to [NIH ODS](https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/), most vitamin E supplements provide it, so the form you are most likely to find on a label is alpha-tocopherol. ### How did the antioxidant idea replace the fertility idea? It did not erase the fertility result, which still explains the original name. What changed is the description of what the molecule does. The Linus Pauling Institute now describes its main function in humans as a fat-soluble antioxidant that stops lipid peroxidation. According to PubMed, a 1989 review calls alpha-tocopherol a chain-breaking antioxidant with near optimal activity in that role. ### Which form of vitamin E do most supplements contain? Most vitamin E supplements provide alpha-tocopherol, according to [NIH ODS](https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/). Labels commonly say d-alpha-tocopherol for the natural form and dl-alpha-tocopherol for the synthetic form, and the synthetic form is about half as active. Because the two forms convert to IU differently (1.49 IU per mg natural, 2.22 IU per mg synthetic), read the milligram figure on the label rather than the IU figure. ### What did the large high-dose trials find? Three findings matter most. The 1994 ATBC trial found no reduction in lung cancer among male smokers taking 50 mg a day of alpha-tocopherol, and more hemorrhagic stroke deaths in that group. SELECT, published in 2011, reported a higher prostate cancer risk with 400 IU a day, which its authors called a significant increase. The 2005 meta-analysis found higher all-cause mortality in trials of 400 IU a day or more. All three are study results, and all three tested supplements. ### How do food sources compare with capsules? One ounce of dry roasted sunflower seeds supplies 7.4 mg of alpha-tocopherol, about half the 15 mg adult RDA. A 400 IU synthetic supplement dose is 180 mg, twelve times that RDA. Average intake from food for U.S. adults 20 and older is 11.5 mg for men and 9.5 mg for women, below the RDA. The adult upper limit for supplemental vitamin E is 1,000 mg a day, according to NIH ODS. ## Next reads - [CoQ10 monograph](/ingredients/coq10-coenzyme-q10): a separate compound, with its own evidence and label checklist. - [Mitochondrial health guide](/health/mitochondrial-health-complete-guide): the next step for the cell-level picture. - [The 1926 liver diet behind vitamin B12](/blog/history/history-of-vitamin-b12-from-liver-cure-to-cobalamin): another vitamin whose story began in a clinic, years before the 1948 isolation. ### Related reading - [the vitamin D origin story: how rickets turned sunlight into a supplement story](/blog/history/history-of-vitamin-d-from-rickets-to-sunshine-vitamin) - [the vitamin K origin story: how a clotting vitamin became the K2 story](/blog/history/history-of-vitamin-k-from-danish-blood-clotting-to-k2)