Soy Diet Worsens Heart Disease in Mice

Abstract

A soy-rich diet is viewed as being beneficial to health, especially the cardiovascular system. Although Americans spend billions on soy foods and dietary supplements, systematic studies on how genetic characteristics might relate to different diets and how gender might shape this interaction are lacking. The soy-based diet given to lab rodents reportedly prevents cancer and lowers cholesterol levels, but it may also increase androgen levels and decrease thyroid peroxidase. Many effects of a soy diet are ascribed to isoflavones or phytoestrogens. The investigators examined the effect of diet on a genetic mouse model of hypertrophic cardiomyopathy (HCM). Cardiac contractile function is preserved in female mice, which continues to increase their cardiac mass. Male mice, in contrast, develop thin ventricular walls and have poor cardiac contractility. The HCM mouse expresses a mutant myosin heavy chain transgene in the heart. The role of diet was examined by comparing HCM mice with WT (wild type) littermate control mice of both sexes. A standard soy-based diet was compared with a casein-based diet, which in some cases was supplemented with daidzein and genistein, the most prominent isoflavones in soy. The HCM mice had higher ratios of ventricular weight to tibial length than did sex-matched WT control mice fed the same diet. Male animals had larger hearts than females. HCM mice had significantly more hypertrophy on the casein diet than when taking a soy diet. Male HCM animals fed a casein-based diet had greater cardiac hypertrophy than those fed a soy diet. In contrast, diet did not influence cardiac hypertrophy in female HCM animals. Cardiac growth was less in both male and female HCM animals eating the standard soy diet. Adding phytoestrogens to the casein-based diet did not entirely reproduce this phenotype. Mutated male mice developed heart failure on a soy diet but, when fed a casein diet, did not develop severe dilated cardiomyopathy. Left ventricular size and contractile function were preserved in these animals. In addition, the casein diet prevented numerous pathologic changes in male mice, including fibrosis, induction of p-myosin heavy chain, inactivation of glycogen synthase kinase 3β, and markedly elevated caspase-3. The investigators conclude that the dilated cardiac phenotype in male HCM mice fed a soy diet represents augmented growth and increased programmed cell death. Decompensation is associated with a change from a balanced to an unbalanced relationship between cell growth and cell death. These mice exhibit more physiological and less pathologic cardiac growth when given a soy-free diet. Hopefully, further research will suggest novel dietary changes that will prevent the development or progression of hypertrophic cardiac disorders. Such research will focus on identifying specific genetic modifiers that influence the heart's response to diet.