Vitamin E supplements: evidence, forms and risks

Vitamin E covers eight fat-soluble compounds: four tocopherols and four tocotrienols. Alpha-tocopherol is the only form counted toward human needs and the most studied. The word "natural" on a label describes an origin, not a superior clinical benefit.

The European Food Safety Authority (EFSA) sets an adequate intake of 13 mg of alpha-tocopherol per day for men and 11 mg for women. The US NIH recommends 15 mg for adults and 19 mg during breastfeeding.

Vegetable oils (sunflower, wheat germ), almonds, hazelnuts, sunflower seeds, avocado, spinach, and broccoli provide it. A varied diet generally covers these needs without a heavily dosed concentrate.

Since vitamin E is fat-soluble, its absorption depends on fat digestion. A disease of the bile ducts, pancreas, or intestine, or digestive surgery, can lead to a deficiency. In these situations, the dose and form are decided with a professional.

That a nutrient limits certain oxidation reactions in the lab justifies studying it, not claiming that a capsule prevents cancer or a heart attack. To find out, you need trials comparing people, doses, and clinical outcomes. Yet large trials have not confirmed the "antioxidant, therefore protective" promise.

The HOPE trial and its HOPE-TOO extension

The HOPE trial included 9,541 people aged 55 or older with vascular disease or diabetes; 3,994 continued into the HOPE-TOO extension. They received 400 IU per day of natural-source vitamin E or a placebo, with a median follow-up of seven years. Vitamin E reduced neither cancers nor major cardiovascular events. However, the risk of heart failure increased by 13% and the risk of hospitalization for heart failure by 21%.

The SELECT trial

In 34,887 healthy men followed for 7 to 12 years, 400 IU per day of vitamin E increased the risk of prostate cancer by 17% compared with placebo. For details on this trial, see the article on selenium.

The mortality meta-analysis

A 2005 meta-analysis pooled 19 trials and 135,967 participants. Beyond 400 IU per day, it observed 39 additional deaths per 10,000 people. The authors concluded that these high doses could increase mortality and should be avoided. No significant increase appeared at low doses.

A label can list natural alpha-tocopherol (d-alpha-tocopherol), synthetic (dl-alpha-tocopherol), mixed tocopherols, or tocotrienols. The two forms of alpha-tocopherol don't have the same international unit equivalence:

• 1 IU of the natural form corresponds to 0.67 mg of alpha-tocopherol.
• 1 IU of the synthetic form corresponds to 0.45 mg of alpha-tocopherol.

A 400 IU capsule therefore provides 180 to 268 mg, more than ten times the needs. Also check multivitamins, fortified oils, and "beauty" or "immunity" products: adding up labels can result in a total dose far higher than originally intended.

High-dose vitamin E slows platelet aggregation and can oppose vitamin K-dependent clotting factors. With an anticoagulant like warfarin or an antiplatelet drug, bleeding risk increases, probably beyond 400 IU per day according to the NIH. The NIH sets the upper limit at 1,000 mg per day for adults, equivalent to 1,500 IU of the natural form or 1,100 IU of the synthetic form.

1. 01Check whether your diet regularly includes vegetable oils, nuts and seeds, and vegetables.
2. 02Identify any situation that could limit absorption.
3. 03List your medications and supplements, particularly those affecting clotting.
4. 04Ask whether supplementation is actually indicated.
5. 05Add up the dose from all products, accounting for the form.
6. 06Reassess instead of automatically extending a course.