9.2 Vitamin E

Vitamin E

There are 8 different forms of vitamin E: 4 tocopherols and 4 tocotrienols. The difference between tocopherols and tocotrienols is that the former have a saturated tail, while the latter have an unsaturated tail. Within tocopherols and tocotrienols, the difference between the different forms is the position of the methyl groups on the ring. The 4 different forms within the tocopherol and tocotrienols are designated by the Greek letters: alpha, beta, gamma, and delta. The difference in these structures is shown in the figures below. Notice the subtle differences down the left-hand side of the various structures.

Figure 9.21 Structures of the different forms of vitamin E

For reasons that will be covered in a later subsection, the primary form of vitamin E found in the body is alpha-tocopherol (the form discussed in Section 9.13.) The major, and possibly only, function of vitamin E is as an antioxidant. When it serves as an antioxidant it forms an alpha- tocopherol radical, as shown in Figure 9.23.

Figure 9.23 Conversion of alpha-tocopherol to alpha-tocopherol radical2

Alpha-tocopherol is believed to be the first part of the antioxidant network we saw earlier (shown below) where it is oxidized to donate an electron to stabilize reactive oxygen species. Alpha-tocopherol radical can then be reduced by the donation of an electron from ascorbate (vitamin C; also shown in Figure 9.23).

Figure 9.24 The theorized antioxidant network3

To help protect the antioxidant function of alpha-tocopherol in foods and during digestion (by preventing the formation of an alpha-tocopherol radical), some manufacturers have added compounds to the oxidation site of alpha-tocopherol. These are referred to as alpha- tocopherol derivatives. The most common forms are alpha-tocopherol acetate, alpha- tocopherol succinate, and alpha-tocopherol phosphate (Ester-E®).

Alpha-tocopherol derivatives, such as acetate in alpha-tocopherol acetate, are cleaved prior to absorption in the small intestine by enzymes known as esterases, meaning that alpha- tocopherol is absorbed, not the alpha-tocopherol derivative.

The Required Web Link below provides more information on vitamin E.

Required Web LinkVitamin E Fact Sheet

Subsections:

• 9.21 Absorption, Metabolism & Excretion of Vitamin E
• 9.22 Dietary Vitamin E, DRI & IUs
• 9.23 Vitamin E Deficiency & Toxicity

References & Links

• http://en.wikipedia.org/wiki/File:VitE.png
• http://www.life-enhancement.com/magazine/article/2274-break-the-bonds-of-dementia
• Packer L, Weber SU, Rimbach G. (2001) Molecular aspects of alpha-tocotrienol antioxidant action and cell signalling. J Nutr 131(2): 369S-373S

Links

Vitamin E Fact Sheet – https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/

Vitamin E Absorption, Metabolism, & Excretion

In addition to being found naturally in foods, alpha-tocopherol can also be synthesized. It is important to know whether alpha-tocopherol is natural or synthetic because the structures differ between these forms. You might be saying to yourself, “who cares about natural versus synthetic alpha-tocopherol?” However, the small change in their structures makes a big difference in how alpha-tocopherol is maintained in the body.

All forms of vitamin E (tocopherols, tocotrienols) are absorbed equally. Fat-soluble vitamins (A, D, E, & K) are handled like lipids, and thus are incorporated into chylomicrons that have triglycerides removed by lipoprotein lipase (LPL). The chylomicron remnants containing the different forms of vitamin E are then taken up by the liver.

The liver contains a protein called alpha-tocopherol transfer protein (alpha-TTP), which is responsible for maintaining higher levels of alpha-tocopherol in the body. Alpha-TTP preferentially binds to all natural alpha-tocopherol, but only half of the synthetic variations. Thus, natural alpha-tocopherol is more easily metabolized than half of the synthetic variations. Other forms of vitamin E (gamma-tocopherol, tocotrienols) also don’t bind well to alpha-TTP and thus, are found in lower levels than alpha-tocopherol in the body.

Once bound to alpha-TTP, alpha-tocopherol is incorporated into VLDL. From VLDL, vitamin E reaches tissues, with most vitamin E in the body being found in the adipose tissue. There are 2 main routes of vitamin E excretion. The major route of excretion is through bile, that is then excreted in feces. The second route is in the urine after vitamin E is processed to make it more water-soluble.

Reference

1. Traber MG, Elsner A, Brigelius-Floh R. (1998) Synthetic as compared with natural vitamin E is preferentially excreted as alpha-CEHC in human urine: Studies using deuterated alpha- tocopheryl acetates. FEBS Lett 437(1-2): 145-148.

Dietary Vitamin E, DRI & IUs

The best food sources of vitamin E are primarily oils and nuts. The forms of vitamin E that nuts and oils contain varies, with the two major forms being alpha and gamma-tocopherol. Soybean, corn, and flaxseed oils are good sources of gamma-tocopherol. Palm and canola oils contain almost equal amounts of alpha-tocopherol and gamma-tocopherol. Safflower oil, almonds, sunflower oil, and wheat germ oil are good sources of alpha-tocopherol. Beta-tocopherol and delta-tocopherol are found in lower levels in foods. Tocotrienols, for the most part, are not found in high levels in the diet. The various amounts of tocopherols in different nuts and oils are shown in Figure 9.221.

Figure 9.221 Tocopherol distribution in plant products1

Three-fourths of the oil Americans consume is soybean oil. As a result, it is estimated that we consume 2-4 times more gamma-tocopherol than alpha-tocopherol. Europeans consume more sunflower and canola oil, and thus, are believed to consume at least 2 times more alpha- tocopherol than gamma-tocopherol1.

These two forms of vitamin E are of particular interest to researchers. There is evidence that alpha-tocopherol plays a role in increasing prostate cancer, while gamma-tocopherol may

reduce a person’s risk for cardiovascular disease2,3.

Vitamin E DRI & IUs

Before 2001, ALL forms of vitamin E contributed to the RDA and were referred to as alpha- tocopherol equivalents. In 2001, the Dietary Reference Intake (DRI) committee decided only the forms of alpha-tocopherol that were bound by alpha-TTP should be used to estimate the requirement. Thus, other forms of vitamin E (gamma-tocopherol, tocotrienols etc.) do not count toward the requirement, and the unit of measure is now mg of alpha-tocopherol. As a result, soybean, corn, and flaxseed oils, which are good sources of gamma-tocopherol, are no longer considered to be good sources of vitamin E. Refer back to Figure 9.221 for a reminder of the tocopherol content of different nuts and oils.

Another level of complexity is added by the introduction of international units (IU). IUs are a unit that are used to describe the bioactivity of different compounds, including 4 vitamins: A, D,

E, and C. It would be less confusing if these units were not used. However, most supplements use IUs. IUs are not as common on food items.

For vitamin E, IUs are specific for alpha-tocopherol and adjusted accordingly for the different forms (alpha-tocopherol acetate etc.).

References & Links

• Wagner KH, Kamal-Eldin A, Elmadfa I. (2004) Gamma-tocopherol–an underestimated vitamin? Ann Nutr Metab 48(3): 169-188.
• Klein, E. A., Thompson, I. M., Tangen, C. M., Crowley, J. J., Lucia, M. S., Goodman, P. J., … Baker, L. H. (2011). Vitamin E and the Risk of Prostate Cancer: Updated Results of The Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA, 306(14), 1549–1556. http://doi.org/10.1001/jama.2011.1437
• Saremi A, Arora R. (2010). Vitamin E and cardiovascular disease. Am J Ther. 17(3):e56-65. doi: 10.1097/MJT.0b013e31819cdc9a.
• DRI (2000) Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids.

Vitamin E Deficiency & Toxicity

Vitamin E deficiency is extremely rare. Depletion studies require years on a vitamin E-deficient diet to cause deficiency1. Deficiency primarily occurs in people with lipid malabsorption problems or Ataxia with Isolated Vitamin E Deficiency (AVED). Individuals with AVED have a mutation in their alpha-TTP (the liver protein that binds to vitamin E) that prevents it from functioning correctly. The primary symptoms of vitamin E deficiency are neurological problems.

High levels of vitamin E intake do not result in a noted toxicity. However, higher levels of intake are associated with decreased blood coagulation, and potentially an increased risk of prostate cancer. In particular, hemorrhagic stroke has been linked to high vitamin E levels. It is believed that this increased bleeding risk is due to a vitamin E metabolite that has anti-vitamin K (the clotting vitamin) activity. This potential antagonism will be described more in the vitamin K section.

References & Links

1. DRI (2000) Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids.