Soy Diet Worsens Heart Disease in Mice

Abstract

We report that dietary modification from a soy-based diet to a casein-based diet radically improves disease indicators and cardiac function in a transgenic mouse model of hypertrophic cardiomyopathy. On a soy diet, males with a mutation in the α-myosin heavy chain gene progress to dilation and heart failure. However, males fed a casein diet no longer deteriorate to severe, dilated cardiomyopathy. Remarkably, their LV size and contractile function are preserved. Further, this diet prevents a number of pathologic indicators in males, including fibrosis, induction of β-myosin heavy chain, inactivation of glycogen synthase kinase 3β (GSK3β), and caspase-3 activation.

The Effects of Biological Sex and Diet on the Development of Heart Failure

“…We used an experimental model of hypertrophic cardiomyopathy (HCM) in which males progress to CHF to address whether the soy diet can influence cardiovascular health. 37,38 In the present study, we report that male mice with HCM that were fed the traditional soy-based diet deteriorate to severe, dilated cardiomyopathy and have a number of pathological indicators, including fibrosis, induction of ␤-myosin heavy chain, inactivation of glycogen synthase kinase-3␤, and activation of caspase-3. 37,38 However, simply changing the diet to a milk-based (nonsoy) diet prevents these phenotypes.…”

“…37,38 In the present study, we report that male mice with HCM that were fed the traditional soy-based diet deteriorate to severe, dilated cardiomyopathy and have a number of pathological indicators, including fibrosis, induction of ␤-myosin heavy chain, inactivation of glycogen synthase kinase-3␤, and activation of caspase-3. 37,38 However, simply changing the diet to a milk-based (nonsoy) diet prevents these phenotypes. 38 Female HCM mice do not exhibit clinical signs of severe cardiac disease on the soy diet, and they are not significantly affected by the dietary change.…”

“…38 Female HCM mice do not exhibit clinical signs of severe cardiac disease on the soy diet, and they are not significantly affected by the dietary change. 38 Next, we tested the hypothesis that phytoestrogens mediate these detrimental effects of soy on HCM by supplementing the casein diet with genistein and daidzein, the most abundant phytoestrogens in soy and the most common components of human soy dietary supplements. 144 Feeding male HCM mice the phytoestrogen-supplemented diet is sufficient to recapitulate the worsened cardiac pathology as seen in male HCM mice eating the soy diet (unpublished observations).…”

“…36,39 In addition, the male mice develop progressive left ventricular dilation and impaired cardiac function, whereas female counterparts show increasing hypertrophy without dilation and maintain adequate ventricular function. 37,38 The progression to a dilated cardiomyopathy seen in males is indicative of the transition from compensated to decompensated cardiac hypertrophy and heart failure, whereas the females remain in a compensated state.…”

“…37,38 However, simply changing the diet to a milk-based (nonsoy) diet prevents these phenotypes. 38 Female HCM mice do not exhibit clinical signs of severe cardiac disease on the soy diet, and they are not significantly affected by the dietary change. 38 Next, we tested the hypothesis that phytoestrogens mediate these detrimental effects of soy on HCM by supplementing the casein diet with genistein and daidzein, the most abundant phytoestrogens in soy and the most common components of human soy dietary supplements.…”