Vitamin E // Tocopherol
Few side effects have been noted in adults taking supplements of less than 2,000 mg natural or synthetic vitamin E daily for a few weeks to a few months.
Side effects occurring as a result of long-term alpha-tocopherol supplementation have not been adequately studied. The most worrisome possibility is that of impaired blood clotting, which may increase the likelihood of bleeding (‘hemorrhage’) in some individuals.
Some physicians recommend discontinuing high-dose vitamin E supplementation one month before elective surgery to decrease the risk of hemorrhage.
Premature infants appear to be especially vulnerable to adverse effects of alpha-tocopherol supplementation, which should be used only under controlled supervision by a pediatrician (71).
According to an US review in 2013, biological mechanisms exist to routinely eliminate potential excess levels of vitamin E, and they make it almost impossible to take a harmful amount (81). Two major systems in the liver were identified that work to control the level of vitamin E in the body, and they routinely excrete excessive amounts. Very high intakes achieved through supplementation only succeed in doubling the tissue levels of vitamin E, which is not harmful. The researchers commented that levels of vitamin E in the body can never become toxic. It is not possible for toxic levels of vitamin E to accumulate in the liver or other tissues, despite concerns that have been expressed about possible health risks from a high intake of vitamin E. Past studies that have alleged adverse consequences from vitamin E have misinterpreted the data, they noted.
Vitamin E supplementation and all-cause mortality
A meta-analysis that combined the results of 19 clinical trials of long-term vitamin E supplementation for various diseases, including heart disease, end-stage kidney (‘renal’) failure and Alzheimer's disease, reported that adults who took supplements of 400 IU/day or more were 6% more likely to die from any cause than those who did not take vitamin E supplements (72). However, experts criticized that most of the research was conducted on patients at high risk of a chronic disease/death and that to generalize these findings to healthy adults is very speculative.
Further breakdown of the risk by vitamin E dose and adjustment for other vitamin and mineral supplements revealed that the increased risk of death was statistically significant only at a very high dose of 2,000 IU/day, which is many times the recommended amount.
In addition, many human long-term studies with higher doses of vitamin E have not reported any adverse effects: three other meta-analyses that combined the results of randomized controlled trials designed to evaluate the efficacy of vitamin E supplementation for the prevention or treatment of cardiovascular diseasefound no evidence that vitamin E supplementation up to 800 IU/day significantly increased or decreased cardiovascular disease mortality or all-cause mortality (73, 74, 75, 79).
At present, there is no convincing evidence that vitamin E supplementation up to 800 IU/day increases the risk of death from cardiovascular disease or other causes.
Vitamin E plus other antioxidants
A meta-analysis of 68 randomized trials found that supplemental vitamin E, singly or in combination with other antioxidant supplements, did not significantly alter the risk of all-cause mortality (76). In 2013, the same authors published a meta-analysis concluding 53 selected clinical trials on primary and secondary prevention. They suggested that vitamin E and beta-carotene in doses higher than the RDA seem to increase mortality (82). For vitamin E a daily dose of up to 5,000 mg was considered, which is five times more than the Tolerable Upper Intake Level (UL). However, experts raised serious doubts about the conclusions as they were drawn from flawed meta-analysis pooling data from trials with varied populations (healthy and diseased individuals) and different methodologies (80) (see also Expert Opinion). In 2011, a meta-analysis assessed the mortality risk in 57 clinical trials with 246’371 participants supplementing vitamin E with doses up to
5,500 IU/day for 1–10 years (83). The analysis showed no relationship between vitamin E intake and the risk of mortality.
Results of a clinical trial in 40 healthy young men gave rise to speculation that antioxidant supplements, vitamin C and vitamin E in particular, may prevent the beneficial effects of exercise (77). Athletic strain generates free radicals in muscle, which are potentially damaging, but on the other hand also evoke the muscle to respond to the oxidative stress. This response includes improved insulin (the hormone responsible for glucose uptake from blood) sensitivity and uptake of glucose into the muscle cells. Hence, physical exercise is thought to potentially prevent or improve diabetes. The authors of this study suggested that antioxidative substances, such as vitamins C and E, block the free radicals and the adaptive response, thereby preventing the beneficial effects of exercise on diabetes parameters.
However, experts commented that the results are of very limited validity as the study was performed in healthy individuals and not in people with existing insulin resistance. In addition, a diabetes-preventing effect of free radicals is highly speculative, whereas long-term damaging effects of free radicals (e.g.atherosclerosis) are better established and can be reduced by antioxidants (see also Expert Opinion).
Tolerable upper intake levels
|Age (years)||UL (mg/day)|
* The UL applies also to women during pregnancy and breast-feeding.
|UL in mg/day
|Infants 0–12 months||Not Possible to Establish*|
|Children 1–3 years||200 mg (300 IU)|
|Children 4–8 years||300 mg (450 IU)|
|Children 9–13 years||600 mg (900 IU)|
|Adolescents 14–18 years||800 mg (1,200 IU)|
|Adults 19 and older||1,000 mg (1,500 IU)|
Because of the potential for interactions, dietary supplements should not be taken with medication without first talking to an experienced healthcare provider.