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Examining the science and commercial applications of natural bioactives

Perhaps due to the mountain of preclinical evidence, the four letters that have assumed a position on the natural bioactive mantle are EGCG: EpiGalloCatechin Gallate.

This most abundant of the catechins virtually unique to the leaves of Camellia sinensis is present in rank order of concentration in white >/= green > oolong >> black tea but can differ appreciably between tea cultivars.1 However, only recently has the commercial viability of near-pure EGCG preparations been realized. This has fostered incrementally greater research.

One of the most striking research findings of late has been the in vitro characterization of what appears to be a cognate receptor for EGCG, expressed on the surface of human-derived lung and breast cancer cells.2 Additional studies have uncovered a different EGCG-responsive receptor (tNOX) that regulates tumour and normal cell growth.3

What has garnered keen EGCG-centric research attention in vivo has centred upon EGCG?s bioactivity related to adipose tissue and fuel absorption and metabolism. Seminal investigations that compared oral (drinking water) to injected (intraperitoneal; ip) administration of EGCG (over seven days to male and female rats) observed striking and swift reductions in food intake, body weight, and anabolic hormones (testosterone, IGF-I and insulin) with ip delivery, but only mild reductions in food intake with oral ingestion.4 This was attributed to poor oral bioavailability of EGCG.

Later studies funded and conducted by Roche/DSM with their near pure (minimum 94 per cent) EGCG ingredient, Teavigo, have found varying effects. In young female rats, only the highest dose of EGCG (added to a high-fat, high-cholesterol diet) had a favourable impact on blood and liver lipids, yet it had no significant impact upon body weight, food intake or faecal fat excretion after four weeks.5 EGCG supplementation prevented the increased adiposity that accompanies co-treatment with an insulin sensitizer drug (rosiglitazone, a thiazolidinedione) among animals that spontaneously develop type 2 diabetes, yet no reduction in fat mass was reported in these obese, insulin-resistant animals receiving only EGCG.6

Another study by the same group fed young male mice a high-fat and high-sucrose diet with or without EGCG for five months and reported regional fat depots and weight gain to mirror that of mice fed a standard diet, and to be superior to the animals fed the high-fat/sucrose diet but lacking EGCG.7 Notably, both groups of mice on the high-fat/sucrose diet had the same average food intake, suggesting a gut and/or metabolic effect.

In the same study, young male rats were fed a control or high-fat/sucrose diet for five months and then the animals on the latter diet were assigned to an EGCG or non-EGCG supplemented diet for four more weeks. The EGCG group lost body weight relative to their pre-EGCG diet weight of the animals that were switched to the same high diet, but fat depots did not differ between the groups.

What remains to be demonstrated is the long-term safety and efficacy of chronic EGCG supplementation in humans, and its impact upon body composition and glucose disposal. A recent four-week study showed high-dose EGCG (400-800mg/day) to be safe and well tolerated, but no change in body weight was reported.8

Anthony Almada, MSc, is president and chief scientific officer of IMAGINutrition Inc. Respond:

1. Kumar NS and Rajapaksha M. Separation of catechin constituents from five tea cultivars using high-speed counter-current chromatography. J Chromatogr A 2005; 1083:223-8.
2. Tachibana H, et al. A receptor for green tea polyphenol EGCG. Nature Struct Mol Biol 2004; 11:380-1.
3. Yagiz K, et al. Transgenic mice overexpressing the anticancer green tea catechin target, tNOX, respond to EGCG. FASEB J 2005; 19:Abstr. 73.5.
4. Kao Y-H, et al. Modulation of endocrine systems and food intake by green tea epigallocatechin gallate. Endocrinology 2000; 141:980-7.
5. Raederstorff DG, et al. Effect of EGCG on lipid absorption and plasma lipid levels in rats. J Nutr Biochem 2003; 14:326-32.
6. Wang Y, et al. Green tea catechin, EGCG (Teavigo), regulates adipogenesis and prevents TZD-induced weight gain in db/db mice. Int J Obes 2004; 28:S90.
7. Wolfram S, et al. Teavigo (epigallocatechin gallate) supplementation prevents obesity in rodents by reducing adipose tissue mass. Ann Nutr Metab 2005; 49:54-63.
8. Chow H-HS, et al. Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and Polyphenon E in healthy individuals. Clin Cancer Res 2003; 9:3312-9.

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