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Soy diet worsens hypertrophic cardiomyopathy in mice

Researchers at the University of Colorado at Boulder found that the health of mice carrying a genetic mutation for a disease that is the leading cause of sudden cardiac death in people under 30 worsened considerably when the animals were fed a soy-based diet.

Male mice carrying the mutation for hypertrophic cardiomyopathy, or HCM, were severely affected by the soy diet, exhibiting progressively enlarged heart muscles and eventual heart failure.
When the mice in the study were switched to a diet of the milk protein, casein, the condition of the males improved markedly, said Leslie Leinwand, chief author of the study.

Female mice carrying the mutation for hypertrophic cardiomyopathy, which is characterized by the thickening of heart muscle that can obstruct blood flow, were relatively unaffected, she said.

The research team hypothesized that heart deterioration in male mice was due at least in part to plant-based estrogens in the soy food diet that triggered a cascade of biochemical reactions and ultimately increased apoptosis, or programmed cell death, in the heart.

" We were shocked by the results," said Leinwand, chair of the molecular, cellular and developmental biology department and chief study author. " This study shows that at least in mice, diet can have a more profound effect on heart disease than any drug that we could imagine."

The study is published in the Journal of Clinical Investigation ( JCI ).

The CU research team speculated the soy diet affected male mice more severely because the females already had large amounts of estrogen naturally circulating through their bodies, making the proportional increase in estrogen compounds from the soy diet significantly less, said Leinwand. In addition, male mammals, from mice to humans, are more severely affected by the symptoms of hypertrophic cardiomyopathy than females, she said.

The study mice were bred over generations to carry hypertrophic cardiomyopathy, a disease which causes the heart's lower chambers, or ventricles, to thicken and prevents the heart from fully relaxing between heartbeats, said Leinwand. In the latter stages of the disease, the heart's ventricle chamber enlarges, the heart wall thins and the pumping contractions of the heart are impaired, leading to heart failure, she said.

Hypertrophic cardiomyopathy is the leading cause of death in young athletes and affects about one in 500 people, although milder forms of the disease often go undiagnosed, said Leinwand.
To date, 18 genes associated with hypertrophic cardiomyopathy have been identified and several more are being investigated, she said.

Leinwand said plant estrogens have been shown to have a potent effect on living organisms.
While they are sometimes suggested by doctors to treat menopausal symptoms in women, studies have shown that common plant estrogens like Genistein and Daidzein can contribute to reduced fertility in farm animals.

" There are some very complex issues in this study that we don't yet fully understand from a biochemical standpoint," she said. " But the study should help lead to a better understanding of how genes and diet interact."

Source:University of Colorado at Boulder, 2006