Soy diet worsens heart disease in mice, says University of Colorado at Boulder study

A University of Colorado at Boulder study has shown 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, said CU-Boulder Professor Leslie Leinwand. When the mice in the study were switched to a diet of the milk protein, casein, the condition of the males improved markedly, said Leinwand, chief author of the study.

Female mice carrying the mutation for HCM, 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."

A paper on the subject by Leinwand, Dr. Brian Stauffer, a cardiologist at Denver Health Medical Center and the University of Colorado Health Sciences Center, CU-Boulder research associate John Konhilas and doctoral student Elizabeth Luczak appears in the January issue of the Journal of Clinical Investigation, one of the nation's leading medical journals.

"To our knowledge this is the first report of significant differences in cardiac muscle adaptation due to dietary manipulation," the researchers wrote in 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 HCM than females, she said.

The study mice were bred over generations to carry HCM, 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.

HCM 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 HCM have been identified and several more are being investigated, she said.

Soy foods and diet supplements are perceived to be a huge health benefit to humans, as evidenced by the estimated $4.7 billion spent by consumers on them in 2005, said Leinwand. "I don't think normal, healthy people should be alarmed by the results of this study," said Leinwand. "But we are seeing more cautionary reactions from the medical community in recent years regarding the ingestion of huge quantities of dietary supplements, including soy phytoestrogens."

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."

Currently, the main treatment for end-stage HCM is a heart transplant, she said.

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The CU-Boulder study was funded by a grant from the Heart, Lung and Blood Institute of the National Institutes of Health and the American Heart Association.


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