by Justin Lee

Created on: February 25, 2009

Vitamin E: Gamma not alpha tocopherol is often superior with Cancer and Alzheimer's

Vitamin E is speculated to have beneficial effects for the treatment of cancer. Specially, the vitamin, its isomers, and its analogs have been shown to target mitochondria and signal for apoptosis. Vitamin E and derivatives regulate caspase-independent pathways of apoptosis, and synergistic anticarcinogenic effects have been reported when vitamin E analogs are used in combination with other cancer chemotherapeutic agents.

To date, most research to date has focused on the alpha-tocopherol isomer of vitamin E, but recent evidence suggests that gamma tocopherol may have more potent proapoptotic capabilities.

Gamma-tocopherol is the predominant form of vitamin E in the US diet, but alpha-tocopherol is the only form of vitamin E found in vitamin supplements. The pharmaceutical reasoning is based on knowledge that alpha-tocopherol is preferentially recognized by the alpha-tocopherol transfer protein (alpha-TTP) and is transferred to plasma, while the other vitamin E forms (e.g., gamma-tocopherol) are removed from the circulation (although gamma-Tocopherol is well absorbed and accumulates to a significant degree in some human tissues).

Alpha-TPP metabolizes gamma-Tocopherol to the water-soluble metabolite, gamma-CEHC. Gamma-CEHC, but not alpha-CEHC, exhibits natriuretic (discharge of sodium through urine) activity, which may be physiologically important. Gamma tocopheral is more effective as a trap for lipophilic electrophiles than alpha-tocopherol.
Additionally, gamma-tocopherol possesses antiinflammatory activities that alpha-tocopherol don't (via inhibition of cycooxygenase activity). Moreover, several human and animal epidemiologic studies have shown inverse correlations between gamma-tocopherol levels and prostate cancer incidence (4). These distinguishing features of gamma-tocopherol and its metabolite (gamma-CEHC) suggest that gamma-tocopherol may contribute to human health in a way that alpha-tocopherol cannot.

Unfortunately, excess alpha-tocopherol taken in supplements reduces natural levels of gamma-tocopherol. In contrast, supplementation with gamma-tocopherol increases levels of both alpha and gamma-tocopherol (4). Why pick one when you can have both?

(1) Constantinou et al. 2008 (Constantina Constantinou, Andreas Papas, Andreas I. Constantinou. "Vitamin E and cancer: An insight into the anticancer activities of vitamin E isomers and analogs" International Journal of Cancer. Volume 123, Issue 4, Pages 739-752; Published Online: 29 May 2008)

(2) Wolf 2008 (George Wolf. "How an Increased Intake of Alpha-Tocopherol Can Suppress the Bioavailability of Gamma-Tocopherol" Nutrition Reviews. Volume 64 Issue 6, Pg. 295 299; Published Online: 28 Jun 2008)

(3) Dietrich et al. 2006 (Dietrich M, Traber MG, Jacques PF, Cross CE, Hu Y, Block G. "Does gamma-tocopherol play a role in the primary prevention of heart disease and cancer?" J Am Coll Nutr. 2006 Aug. 25(4):292-9. Available online: http://www.jacn.org/cgi/content/full/25/4/292

(4) Jiang et al. 2001 (Qing Jiang, Stephan Christen, Mark K Shigenaga and Bruce N Ames. "Gamma-Tocopherol, the major form of vitamin E in the US diet, deserves more attention" American Journal of Clinical Nutrition, Vol. 74, No. 6, 714-722, December 2001

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