Gamma-Tocopherol:
Its Importance and Unique Properties

When the term "vitamin E" is used, alpha-tocopherol is generally what comes to mind. However, vitamin E is actually a collective term that encompasses 3 other tocopherols (beta, gamma, and delta) in addition to alpha-tocopherol.

These molecules are differentiated by the number and placement of methyl groups on their structure (see figure).

Recent research has been revealing that gamma-tocopherol possesses some unique properties that allow it to function independently from as well as synergistically with alpha-tocopherol.

Alpha-tocopherol is the major form of vitamin E that can be found in blood as well as many tissues in humans. Due to its abundance in the body research has generally focused on alpha-tocopherol, with less emphasis on the other isomers.

However, gamma-tocopherol is the major form of vitamin E consumed in the diet and is found in many plant seeds and the oils made from them.

It has been estimated that gamma-tocopherol represents 70% of the vitamin E consumed in the typical US diet.

Once in the body, the metabolism of alpha and gamma-tocopherol differs significantly. Alpha and gamma-tocopherol are absorbed similarly from the gastrointestinal tract and secreted into chylomicron particles without selective discrimination.

However, when the chylomicron remnant particles are taken up by the liver, alpha-tocopherol is preferentially incorporated into very low-density lipoprotein (VLDL) cholesterol particles. This preferential placement of alpha compared with gamma-tocopherol into VLDL particles is a result of the presence of a protein in the liver called alpha-tocopherol transfer protein.

This protein is able to recognize the stereochemistry of the various tocopherols and has the greatest affinity for the d-alpha form. Consequently, alpha-tocopherol becomes selectively located in VLDL particles, which after circulation and metabolism are transformed in to low-density lipoprotein (LDL) particles.

An interesting note is that supplementation with alpha-tocopherol in the absence of gamma-tocopherol leads to a reduction of both tissue and plasma levels of gamma-tocopherol. Nonetheless, given its presence in chylomicrons, and presence in other lipoprotein particles (albeit it at levels less than alpha-tocopherol) gamma-tocopherol does reach the circulation and plays an important role.

Alpha-tocopherol is generally thought of as the most powerful antioxidant of the various tocopherols, and due to its structure it can more readily donate electrons compared with gamma-tocopherol.

Gamma-tocopherol, however, can better quench certain dangerous reactive nitrogen species such as peroxynitrate and nitrogen dioxide, both of which have been associated with a number of degenerative diseases.

In fact, in relation to alpha-tocopherol it has been reported that gamma-tocopherol is superior in detoxifying nitrogen dioxide to less harmful compounds. In addition to its antioxidant properties, gamma-tocopherol has also been shown to possess anti-inflammatory properties and can inhibit the activity of cyclooxygenase-2 (COX-2) and production of prostaglandin E2. Given the role that inflammation plays in the pathology of cardiovascular disease this finding is particularly important. Some researchers have also reported that gamma but not alpha-tocopherol levels are lower in those with cardiovascular disease compared with control subjects.

Recent work has also brought to light a relationship between gamma-tocopherol and prostate cancer. In a case-control study, the correlation between alpha-tocopherol, gamma-tocopherol, selenium intake and prostate cancer was examined. The researchers found a significant inverse correlation between the intake of gamma-tocopherol and the incidence of prostate cancer (i.e., the greater the intake of gamma-tocopherol, the lower the risk of disease). Most intriguing was that alpha-tocopherol and selenium intake was only protective when gamma-tocopherol intake was also high.

These interesting scientific findings, coupled with the fact that gamma-tocopherol, but not alpha-tocopherol levels have been shown to decline with age in humans give further credibility to the importance of supplementing with a well-rounded mixed tocopherol supplement that contains significant amounts of gamma-tocopherol.

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