Green tea halts progression of cardiac transthyretin amyloidosis: An observational report

Department of Cardiology, Angiology, and Respiratory Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany, .
Clinical Research in Cardiology (Impact Factor: 4.56). 05/2012; 101(10):805-13. DOI: 10.1007/s00392-012-0463-z
Source: PubMed


Treatment options in patients with amyloidotic transthyretin (ATTR) cardiomyopathy are limited. Epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea (GT), inhibits fibril formation from several amyloidogenic proteins in vitro. Thus, it might also halt progression of TTR amyloidosis. This is a single-center observational report on the effects of GT consumption in patients with ATTR cardiomopathy.
19 patients with ATTR cardiomyopathy were evaluated by standard blood tests, echocardiography, and cardiac MRI (n = 9) before and after consumption of GT and/or green tea extracts (GTE) for 12 months.
Five patients were not followed up for reasons of death (n = 2), discontinuation of GT/GTE consumption (n = 2), and heart transplantation (n = 1). After 12 months no increase of left ventricular (LV) wall thickness and LV myocardial mass was observed by echocardiography. In the subgroup of patients evaluated by cardiac MRI a mean decrease of LV myocardial mass (-12.5 %) was detected in all patients. This was accompanied by an increase of mean mitral annular systolic velocity of 9 % in all 14 patients. Total cholesterol (191.9 ± 8.9 vs. 172.7 ± 9.4 mg/dL; p < 0.01) and LDL cholesterol (105.8 ± 7.6 vs. 89.5 ± 8.0 mg/dL; p < 0.01) decreased significantly during the observational period. No serious adverse effects were reported by any of the participants.
Our observation suggests an inhibitory effect of GT and/or GTE on the progression of cardiac amyloidosis. We propose a randomized placebo-controlled investigation to confirm our observation.

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    • "The other two binding sites are found at different monomers in the TTR molecule and may be involved in the oligomerization of TTR tetramers , resulting in the formation of small " off-pathway " aggregates [36] [38] that are innocuous to neuronal cells [10] [38]. Moreover, Kristen and colleagues further supported these observations by showing an inhibitory effect of green tea and/or green tea extract on the progression of cardiac TTR amyloidosis [39]. "
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    ABSTRACT: The transthyretin amyloidoses (ATTR) are devastating diseases characterized by progressive neuropathy and/or cardiomyopathy for which novel therapeutic strategies are needed. We have recently shown that curcumin (diferuloylmethane), the major bioactive polyphenol of turmeric, strongly suppresses TTR fibril formation in vitro, either by stabilization of TTR tetramer or by generating nonfibrillar small intermediates that are innocuous to cultured neuronal cells. In the present study, we aim to assess the effect of curcumin on TTR amyloidogenesis in vivo, using a well characterized mouse model for familial amyloidotic polyneuropathy (FAP). Mice were given 2% (w/w) dietary curcumin or control diet for a six week period. Curcumin supplementation resulted in micromolar steady-state levels in plasma as determined by LC/MS/MS. We show that curcumin binds selectively to the TTR thyroxine-binding sites of the tetramer over all the other plasma proteins. The effect on plasma TTR stability was determined by isoelectric focusing (IEF) and curcumin was found to significantly increase TTR tetramer resistance to dissociation. Most importantly, immunohistochemistry (IHC) analysis of mice tissues demonstrated that curcumin reduced TTR load in as much as 70% and lowered cytotoxicity associated with TTR aggregation by decreasing activation of death receptor Fas/CD95, endoplasmic reticulum (ER) chaperone BiP and 3-nitrotyrosine in tissues. Taken together, our results highlight the potential use of curcumin as a lead molecule for the prevention and treatment of TTR amyloidosis.
    Full-text · Article · Oct 2012 · Biochimica et Biophysica Acta
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    • "After one year of treatment with green tea or green tea extract, 86% of the treated patients presented a decrease of cardiac wall thickness and mass as revealed mainly by cardiac magnetic resonance imaging (CMRI) indicating that green tea, mainly EGCG, halted TTR deposition and increased TTR amyloid deposits clearance. Though a randomized placebo-controlled study is necessary, as proposed by the authors of the study [37], the results point to a positive therapeutic effect of EGCG on TTR amyloidosis , in particular in cardiac forms. Moreover, it must be stressed that EGCG possesses radical scavenging properties and it is relevant as an antioxidant agent [38]. "
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    ABSTRACT: Increasing evidence indicates that accumulation of misfolded proteins in the form of oligomers, protofibrils or amyloid fibrils, and their consequences in triggering intracellular signaling cascades with toxic consequences represent unifying events in many of slowly progressive neurodegenerative disorders. Studies with small compounds or molecules, known to recognize and disrupt amyloidogenic structures, have proven efficient in promoting clearance of protein aggregates in experimental models of systemic and localized forms of amyloidoses. Doxycycline and EGCG were efficient in removing aggregates in pre-clinical studies in a transgenic mouse model for transthyretin (TTR) systemic amyloidosis and represent an opportunity to address mechanisms and key players in deposit removal. Extracellular chaperones, such as clusterin and metalloproteinases play an important role in this process.
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