Vitamin E is the name of a group of fat-soluble compounds that exert distinctive antioxidant activities. It can be found naturally in many vegetable oils, nuts, seeds and green vegetables, or taken as a dietary supplement.
The compound was discovered in 1922 by two researchers at University of California, Berkeley (Herbert Evans and Katherine Bishop). They noticed when fed a diet heavy in lard, lab rats became infertile. But, when given wheat germ oil, the infertility was reversed. They determined there must be a compound in wheat germ oil (initially termed “anti-sterility factor;” later, it became vitamin E). The official name became “tocopherol” from Greek language: “toco” (child); "phero” (to bring forth); and “ol” (alcohol). Vitamin E is also commonly known as the “oil of fertility” due to the initial findings.
· Molecular Formula: C29H50O2
· Molecular Weight: 430.717 g/mol
· Names: D-alpha tocopherol; dl-alpha tocopherol; (2R)-2,5,7,8-TETRAMETHYL-2-[(4R,8R)-4,8,12-TRIMETHYLTRIDECYL]CHROMAN-6-OL; 2,5,7,8-Tetramethyl-2-(4',8',12'-trimethyltridecyl)-6-chromanol
· Forms: Natural forms: d-alpha tocopherol (alcohol)
· Semi-Synthetic: d-alpha tocopheryl acetate (the ester of tocopherol using acetic acid), d-alpha tocopheryl succinate (by succinylation), d-alpha tocopherol nicotinate, etc.
· Synthetic forms: dl-alpha tocopherol, dl-alpha tocopheryl acetate
As noted earlier, vitamin E is not a singular substance. It is a collective term for a family of eight homologue (stereoisomer) molecules, synthesized naturally by plants: alpha-, beta-, gamma- and delta- tocopherol; and alpha-, beta-, gamma- and delta-tocotrienol. Each form has its own biological activity, the measure of potency or functional use within the body. It is the alpha-tocopherol form that is considered “vitamin E” since it is the most abundant and active form of vitamin E found in humans, and a significant biological antioxidant. However, the term is sometimes used as a general description for all tocopherols and tocotrienols that have alpha-tocopherol activity.
Vitamin E’s primary biological and physiological role is as an antioxidant because of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus. These various E compounds exhibit a varying degree of antioxidant activity, depending on the site and number of methyl groups, and the type of isoprenoids.
In general, vitamin E (alpha-tocopherol) is a fat-soluble compound that acts as an antioxidant, which prevents or slows the production of reactive oxygen species (ROS) compounds, which are formed during the normal process of cellular respiration (or other causes, e.g., fat oxidation, stress, smoking, etc.); better known as the “free radical” theory.
Vitamin E has other important biological functions, too, including:
· Enzymatic activity regulator (e.g., protein kinase C [PKC]);
· Gene expression effects (e.g., down-regulator of CD36 scavenger receptor and scavenger receptor class A [SR-A], and a modulator of connective tissue growth factor [CTGF]);
· Inflammation (maintaining endothelial cell integrity);
· Neurological functions (e.g., a deficiency is usually characterized by neurological problems due to poor nerve conduction); and
· Cell signaling.
In the blood, serum concentrations of alpha-tocopherol depend upon the liver. After various forms of vitamin E are absorbed, the liver tends to preferentially secrete the alpha-tocopherol form. As a result, other vitamin E forms are lower than alpha-tocopherol. The other forms are metabolized and excreted, except for gamma-tocopherol. The most common form of vitamin E in a natural diet is gamma-tocopherol, followed by alpha-tocopherol.
Vitamin E deficiency is rare in humans and generally occurs in persons who cannot absorb dietary fat and in premature, low birth weight infants (birth weights less than 1,500 grams or 3.5 pounds).
A deficiency in vitamin E can cause nerve and muscle damage to the point of loss of feeling in the arms and legs (ataxia), muscle weakness (myopathy), weakened immune system response and vision problems (retinopathy). Vitamin E deficiency can also be linked to disease states, such as Crohn's disease, cystic fibrosis and abetalipoproteinemia, as these are diseases where fat (which includes vitamin E) is not properly absorbed.
The U.S. Institute of Medicine (IOM) updated its estimated average requirements (EARs) and recommended dietary allowances (RDAs) for vitamin E in 2000. Daily values (DV) are comprised of two sets of reference values for reporting nutrients on nutrition labels—the daily reference values (DRVs) and the reference daily intakes (RDIs). To limit consumer confusion, the single term “daily value” is used to designate both the DRVs and RDIs
FDA issued a final rule on changes to facts panels on May 27, 2016. New values can be used on labels now. The original deadline to comply was July 28, 2018, but was extended to January 1, 2020 for large companies and January 1, 2021 for small companies. In the interim, products with old or new facts panel content will be on market shelves at the same time.
|Nutrient||Old RDI||New RDI||Highest RDA or AI|
|Tocopherol (vitamin E)||30 IU||15 mg (33 IU of synthetic)||15 mg (33 IU of synthetic)|
|0-3 months*||4 mg (6 IU)||4 mg (6 IU)|
|7-12 months*||5 mg (7.5 IU)||5 mg (7.5 IU)|
|1-3 years||6 mg (9 IU)||6 mg (9 IU)|
|4-8 years||7 mg (10.4 IU)||7 mg (10.4 IU)|
|9-13 years||11 mg (16.4 IU)||11 mg (16.4 IU)|
|14+ years||15 mg (22.4 IU)||15 mg (22.4 IU)||15 mg (22.4 IU)||19 mg (28.4 IU)|
To convert from mg to international unit (IU), 1 mg of alpha-tocopherol is equivalent to 1.49 IU of the natural form or 2.22 IU of the synthetic form (dl).
To convert from IU to mg, 1 IU of the natural form is equivalent to 0.67 mg of alpha-tocopherol; 1 IU of the synthetic form (dl) is equivalent to 0.45 mg of alpha-tocopherol.
Tolerable Upper Intake Levels (ULs) for Vitamin E
|1-3 years||200 mg (300 IU||200 mg (300 IU)|
|4-8 years||300 mg (450 IU)||300 mg (450 IU)|
|9-13 years||600 mg (900 IU)||600 mg (900 IU)|
|14-18 years||800 mg (1,200 IU)||800 mg (1,200 IU)||800 mg (1,200 IU)||800 mg (1,200 IU)|
|19+ years||1,000 mg (1,500 UI)||1,000 mg (1,500 UI)||1,000 mg (1,500 UI)||1,000 mg (1,500 UI)|
Source: The Institutes of Medicine
Regular, long-term consumption of more than 1,000 mg (1,500 IU) of tocopherols per day may be expected to cause hypervitaminosis E, with associated risks of: vitamin K deficiency, anticoagulation (bleeding problems), nausea, diarrhea or vision deficiencies.
The results of a November 2004 meta-analysis from Johns Hopkins University were presented at the American Heart Association’s Scientific Sessions in New Orleans (Ann Intern Med. 2005 Jan 4;142(1):37-46). The meta-analysis suggested that taking daily doses of vitamin E exceeding 400 IU can increase the risk of death. The researchers arrived at their conclusion after analyzing death rates in 19 unrelated clinical trials (1993 to 2004) that studied vitamin E supplementation for various health conditions, including more than 136,000 patients in North America, Europe and China. The vitamin E doses used in the different trials ranged from 15 to 2,000 IU per day; the average daily intake was about 400 IU.
The meta-analysis technique used to arrive at the Hopkins’ results raises questions. Vitamin E has no known toxicity, except for an anticoagulant effect that is usually desirable. The analysis had contradictory data, and most patients were over 60 years and had pre-existing health issues. The Hopkins researchers conceded that because of the age and compromised health of the study participants, their findings might not apply to younger, healthier people.
Various clinical trials are inconclusive scientifically as to vitamin E (and dosage amounts) being beneficial, neutral or harmful. It depends upon which study is preferred. Many believe conservatively that supplementation should remain below 400 IU per day, until further clarification is established. Hence the paradox.
Many people state that using vitamin oil applied topically has many beneficial results. Anecdotal reports claim that vitamin E speeds wound healing and improves the cosmetic outcome of scars, burns and other wounds. Some physicians recommend topical vitamin E after skin surgery or resurfacing.
Studies are continually underway to determine whether vitamin E might help prevent or delay the development of some chronic diseases. These include: heart disease, cancer, cataracts and Alzheimer’s disease. As they say, more to come on this.
Robin Koon is executive vice president at Best Formulations, and has more than 35 years of pharmaceutical experience in clinical pharmacy, as a retail drug chain executive, in managed-care and in manufacturing.