Researchers from the Max Delbrueck Center in Germay report promising results for a nutritional supplement derived from green tea. Summary by Dr. LaVonne Veatch Goodman.

The Goal To test whether EGCG (-)-epigallocatechin-3-gallate, a nutritional supplement found in green tea, may be useful in treating Huntington's. Scientists tested the effects of EGCG in laboratory models of HD, including yeast and fruit flies (but not mice or people). They go on to explain how this potential drug is thought to work at a very early part of the disease process.

The Method

Researchers found EGCG by running thousands of natural compounds through a large scale testing procedure that checked each molecule's ability to stop aggregation or clumping of the mutant HD protein. Next they studied the effects of adding EGCG in increasing amounts to mutant HD protein in test tube experiments, then studied the molecule's effect in yeast and fruit fly models of Huntington's.

The Results EGCG decreased aggregation of mutant HD protein in test tube (in vitro) studies with benefit increasing with dose. Most importantly they showed that EGCG decreased formation of oligomers and fibrils, the toxic small fragments thought to start the domino effect disease cascade. The authors showed that EGCG changed the shape of these structures, which made them less toxic. In further studies, the authors showed that EGCG significantly improved survival and decreased aggregate number by 40% in a yeast model of HD. Finally the authors showed that EGCG decreased toxicity in a fruit fly model of HD by 29% and significantly improved motor function.

Why is it Important?EGCG is a nutritional supplement that is available over-the-counter at modest expense and has a good safety record for long term use. Because experts believe that best drugs for HD will be those that target early disease events (Gusella and MacDonald 2006), EGCG should be an especially good drug candidate. It has potential both to delay disease onset, and to slow progression after symptoms develop.

Comments Of course the obvious question is whether those with Huntington's (and those at risk) should take EGCG found in green tea. My comment after reading this and another recent review article (Mandel et al 2005) that catalogues EGCG's activity as free radical scavenger, iron chelator, modulator of pro-survival genes, and stimulator of protective membrane kinase enzymes, etc. is "Why not?"

If you choose to use EGCG, the next question is what dose. My educated guess is that dosages in the range of 600 to 900 mg/day of high quality supplement are reasonable. As always when choosing supplements, make sure the product you use has been tested for content and contaminants, preferably by Consumer Lab or U.S. Pharmacopeia. Based on Consumer Lab testing, I recommend 2 or 3 capsules of Life Extension's Mega Green Tea Extract. Each capsule contains 326 mg of EGCG and can be ordered online at a cost of 21 dollars per 100 capsules. Several other products tested were substandard, containing lower than advertised EGCG dosage and high levels of contaminants. I specifically don't recommend that you try to get an adequate dose of EGCG by drinking green tea, as this would require at least 10 cups a day with high content of caffeine and unknown quantities of EGCG and contaminants.

EGCG is yet another agent to add to the list of potentially helpful HD treatments. It adds to the same old dilemma that HD people know too well: do you wait long years until there is definitive proof that a treatment works or do you spend your money, time, and hope on agents that scientists have shown might work. It's not an easy choice.

The Report

Ehrnhoefer DE, Duennwald M, Markovic P, Wacker JL, Engemann S, Roark M, Legleiter J, Marsh JL, Thompson LM, Lindquist S, Muchowski PJ, Wanker EE. Green tea (-)-epigallocatechin-gallate modulates early events in huntingtin misfolding and reduces toxicity in Huntington's disease models. Hum Mol Genet. 2006 Sep 15;15(18):2743-51. PubMed abstract
References
Gusella JF, Macdonald ME. Huntington's disease: seeing the pathogenic process through a genetic lens. Trends Biochem Sci. 2006 Sep;31(9):533-40. PubMed abstract

Mandel SA, Avramovich-Tirosh Y, Reznichenko L, Zheng H, Weinreb O, Amit T, Youdim MB. Multifunctional activities of green tea catechins in neuroprotection. Modulation of cell survival genes, iron-dependent oxidative stress and PKC signaling pathway. Neurosignals. 2005;14(1-2):46-60. PubMed abstract