Tocopherol

Tocopherols (/toʊˈkɒfəˌrɒl/;[1] TCP) are a class of organic compounds comprising various methylated phenols, many of which have vitamin E activity.

All feature a chromane ring, with a hydroxyl group that can donate a hydrogen atom to reduce free radicals and a hydrophobic side chain that allows for penetration into biological membranes.

Both the tocopherols and tocotrienols occur in α (alpha), β (beta), γ (gamma), and δ (delta) forms, determined by the number and position of methyl groups on the chromanol ring.

[9] The measurement of "vitamin E" activity in international units (IU) was based on fertility enhancement by the prevention of miscarriages in pregnant rats relative to α-tocopherol.

1 IU is also defined as 1 milligram of an equal mix of the eight stereoisomers, which is a racemic mixture called all-rac-α-tocopheryl acetate.

[17] The U.S. Institute of Medicine has set an upper tolerable intake level (UL) for vitamin E at 1,000 mg (1,500 IU) per day.

Adjusting for typical portion sizes, however, for many people in the United States the most important sources of vitamin E include fortified breakfast cereals.

[10] The three unnatural "2R" stereoisomers with natural R configuration at this 2' stereocenter, but S at one of the other centers in the tail (i.e., RSR, RRS, RSS), appear to retain substantial RRR vitamin activity, because they are recognized by the alpha-tocopherol transfer protein, and thus maintained in the plasma, where the other four stereoisomers (SRR, SRS, SSR, and SSS) are not.

Manufacturers also commonly convert the phenol form of the vitamins (with a free hydroxyl group) to esters, using acetic or succinic acid.

[citation needed] Observational studies that measure dietary intake and/or serum concentration, and experimental studies that ideally are randomized clinical trials (RCTs), are two means of examining the effects or lack thereof of a proposed intervention on human health.

[27] In observational studies on vitamin E, an inverse correlation between dietary intake and risk of a disease, or serum concentration and risk of a disease, may be considered suggestive, but any conclusions also should rest on randomized clinical trials of sufficient size and duration to measure clinically significant results.

One concern with correlations is that other nutrients and non-nutrient compounds (such as polyphenols) may be higher in the same diets that are higher in vitamin E. Another concern for the relevance of RCTs described below is that while observational studies are comparing disease risk between low and high dietary intake of naturally occurring vitamin E from food (when worldwide, the adult median dietary intake is 6.2 mg/d for d-α-tocopherol; 10.2 mg/day when all of the tocopherol and tocotrienol isomers are included),[28] the prospective RCTs often used 400 IU/day of synthetic dl-α-tocopherol as the test product, equivalent to 268 mg of α-tocopherol equivalents.

The authors theorized that declining use in these health science aware populations may have been due to publications of studies that showed either no benefits or negative consequences from vitamin E supplements.

[33] That trial compared 500 IU/day of α-tocopherol to placebo for four years and reported no effect on the progression of AMD in people already diagnosed with the condition.

[36] Alzheimer's disease (AD) and vascular dementia are common causes of decline of brain functions that occur with age.

[38] Vascular dementia may be caused by ischemic or hemorrhagic infarcts affecting multiple brain areas, including the anterior cerebral artery territory, the parietal lobes, or the cingulate gyrus.

Vitamin E status (and that of other antioxidant nutrients) is conjectured as having a possible impact on risk of Alzheimer's disease and vascular dementia.

A review of dietary intake studies reported that higher consumption of vitamin E from foods lowered the risk of developing AD by 24%.

[41] In 2017 a consensus statement from the British Association for Psychopharmacology included that until further information is available, vitamin E cannot be recommended for treatment or prevention of Alzheimer's disease.

An inverse relation has been observed between coronary heart disease and the consumption of foods high in vitamin E, and also higher serum concentration of α-tocopherol.

Compared to those in the lowest fifth for reported vitamin E consumption (from food and dietary supplements), those in the highest fifth were at a 34% lower risk of major coronary disease.

A meta-analysis on the effects of α-tocopherol supplementation in RCTs on aspects of cardiovascular health reported that when consumed without any other antioxidant nutrient, the relative risk of heart attack was reduced by 18%.

[60] The U.S. National Institutes of Health also reviewed the literature and concluded there was not sufficient evidence to support the idea that routine use of vitamin E supplements prevents cardiovascular disease or reduces its morbidity and mortality.

[63][64] The U.S. Food and Nutrition Board set a Tolerable upper intake level (UL) at 1,000 mg (1,500 IU) per day derived from animal models that demonstrated bleeding at high doses.

[66] There are reports of vitamin E-induced allergic contact dermatitis from use of vitamin-E derivatives such as tocopheryl linoleate and tocopherol acetate in skin care products.

[67] The amounts of α-tocopherol, other tocopherols and tocotrienols that are components of dietary vitamin E, when consumed from foods, do not appear to cause any interactions with drugs.

Consumption of α-tocopherol as a dietary supplement in amounts in excess of 300 mg/day may lead to interactions with aspirin, warfarin, tamoxifen, and cyclosporine A in ways that alter function.

[68] The U.S. National Institutes of Health, Office of Dietary Supplements, raises a concern that co-administration of vitamin E could counter the mechanisms of anti-cancer radiation therapy and some types of chemotherapy, and so advises against its use in these patient populations.

"It is synthesized from a mixture of toluene and 2,3,5-trimethyl-hydroquinone that reacts with isophytol to all-rac-α-tocopherol, using iron in the presence of hydrogen chloride gas as a catalyst.

As noted in the introduction, the vitamin was given its name by Evans from Greek words meaning "to bear young" with the addition of the -ol as an alcohol.