Article

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: 3.67). 05/2012; 101(10):805-13. DOI: 10.1007/s00392-012-0463-z
Source: PubMed

ABSTRACT 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.

0 Bookmarks
 · 
355 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The amyloidogenic protein transthyretin (TTR) is thought to aggregate into amyloid fibrils by tetramer dissociation which can be inhibited by a number of small molecule compounds. Our analysis of a series of crystallographic protein-inhibitor complexes has shown no clear correlation between the observed molecular interactions and the in vitro activity of the inhibitors. From this analysis it emerged that halogen bonding (XB) could be mediating some key interactions. Analysis of the halogenated derivatives of two well-known TTR inhibitors has shown that while flufenamic acid affinity for TTR was unchanged by halogenation, diflunisal gradually improves binding up to one order of magnitude after iodination through interactions that can be interpreted as a sub-optimal XB (carbonyl Thr106: I…O distance 3.96-4.05Å; C - I…O angle 152-156°) or as rather optimized van der Waals contacts or as a mixture of both. These results illustrate the potential of halogenation strategies in designing and optimizing TTR fibrillogenesis inhibitors.
    Journal of Medicinal Chemistry 10/2013; · 5.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mediterranean and Asian diets are currently considered as the most healthy traditional feeding habits effective against risk of age-associated, particularly cardiovascular and neurodegenerative, diseases. A common feature of these two regimens is the abundance of foods and beverages of plant origin (green tea, extra virgin olive oil, red wine, spices, berries, and aromatic herbs) that are considered responsible for the observed beneficial effects. Epidemiological data suggest that the phenolic component remarkably enriched in these foods plays an important role in reducing the incidence of amyloid diseases, pathological conditions associated to tissue deposition of toxic protein aggregates responsible for progressive functional deterioration. Great effort is being spent to provide knowledge on the effects of several natural phenols in this context, moving from the test tube to animal models and, more slowly, to the patient's bed. An emerging feature that makes these molecules increasingly attractive for amyloid disease prevention and therapy is their wide spectrum of activity: recent pieces of evidence suggest that they can inhibit the production of amyloidogenic peptides from precursors, increase antioxidant enzyme activity, activate autophagy and reduce inflammation. Our concept should than shift from considering natural phenols simply as antioxidants or, at the best, as amyloid aggregation inhibitors, to describing them as potentially multitargeting drugs. A main concern is the low bioavailability of such compounds and efforts aimed at improving it are underway, with encapsulation strategies being the most promising ones. © 2014 BioFactors, 00(00):000–000, 2014
    BioFactors 06/2014; · 3.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hereditary amyloidosis is an autosomal dominant fatal multisystem disease caused by extracellular deposition of misfolded proteins and, therefore represents a hereditary protein folding or deposition disease that leads to progressive organ damage and eventually death. In most instances mutations within the transthyretin gene are the underlying cause. The main manifestation is a rapidly progressing axonal sensorimotor and autonomic polyneuropathy (familial amyloid polyneuropathy, FAP). Cardiac involvement is frequent in FAP and additional manifestations include the gastrointestinal tract and the eyes. A second manifestation type is cardiomyopathy with little or no polyneuropathy (familial amyloid cardiomyopathy, FAC). For therapy, orthotopic liver transplantation has been established for 25 years. Recently, the oral agent tafamidis, a transthyretin stabilizer, was licensed for treatment of stage 1 polyneuropathy. Additional treatment options are currently being studied.
    Der Nervenarzt 08/2014; · 0.80 Impact Factor

Full-text

View
82 Downloads
Available from
May 20, 2014