A high fat, low carb diet reversed heart failure in a mouse model of the condition. A 24-hour fast also led to improvements, mimicking the physiological effects of the diet.

In people with heart failure, the muscle on the right or left side of the heart — or on both sides — weakens. This impairment limits the organ’s ability to pump blood around the body, causing fatigue and shortness of breath, among other symptoms.

The leading causes are high blood pressure, diabetes, and ischemic heart disease, in which the heart muscle becomes starved of oxygen.

The National Heart, Lung, and Blood Institute estimate that about 5.7 million people in the United States have heart failure.

There is currently no cure, but medications and lifestyle changes can improve people’s quality of life and increase their lifespan.

Healthy heart muscle can draw upon a variety of chemical energy sources, depending on the circumstances. One of these is a molecule called pyruvate, which the body generates during the breakdown of the sugar glucose.

However, conditions such as heart failure and diabetes reduce this flexibility, starving the muscle of the fuel it needs to function effectively.

Fuel shuttle

Researchers have now traced this loss of flexibility to a transporter protein that shuttles pyruvate into mitochondria — the so-called power stations of cells.

Known as the mitochondrial pyruvate carrier (MPC) complex, it comprises two subunits: MPC1 and MPC2.

Researchers at the Saint Louis University School of Medicine in St. Louis, MO, led a team who discovered that the production of both subunits is reduced in failing human hearts.

The researchers compared heart tissue samples from people undergoing heart surgery with tissue samples from donor hearts that were healthy but unsuitable for transplant.

They then showed that mice that lack the gene for producing MPC2 steadily develop heart failure over time. Their hearts became outsized, or hypertrophied, and the organs’ ability to pump blood diminished.

Crucially, the scientists found that they could reverse the damage to the animals’ heart muscle by simply feeding them a special diet for 3 weeks.

“Interestingly, this heart failure can be prevented or even reversed by providing a high fat, low carbohydrate ‘ketogenic’ diet,” explains Kyle S. McCommis, Ph.D., assistant professor of biochemistry and molecular biology at the university, who led the research.

“A 24-hour fast in mice, which is also ‘ketogenic,’ also provided significant improvement in heart remodeling,” he adds.

Ketogenic diet

The ketogenic diet has been growing in popularity in recent years, with research suggesting that it has a range of possible health benefits. These include supporting weight loss, improving heart health, and preventing seizures in some types of epilepsy.

By severely restricting the intake of carbohydrates, such as glucose and other sugars and starches, the diet forces the body to break down fat, producing molecules called ketones that it can use as fuel. Intermittent fasting may achieve similar effects, though adhering to the regimen can be challenging.

The new research indicates that a ketogenic diet promotes the breakdown of fatty acids in heart muscle cells. This process produces an alternative fuel called acetyl-CoA, which the mitochondria can use as an energy source instead of pyruvate.

“Thus, these studies suggest that consumption of higher fat and lower carbohydrate diets may be a nutritional therapeutic intervention to treat heart failure,” says McCommis.

The scientists showed that the diet reversed heart failure by promoting the breakdown of fatty acids in mitochondria rather than ketones. Supplying the mitochondria with extra ketones only slightly improved heart failure.

Converging evidence

The findings from this study appear in the journal Nature Metabolism.

Two studies by other research groups, which feature in the same issue, independently show that the MPC transporter protein plays a central role in heart failure.

P. Christian Schulze and Jasmine M. F. Wu, who are both cardiologists from the University Hospital Jena in Germany, have written a comment article for the journal about the three papers.

While several questions remain unanswered about the regulation of MPC levels in healthy and failing hearts, they conclude:

“The current findings suggest a role for specific ketogenic diets as a supportive, nonpharmacologic treatment in people with heart failure.”

The cardiologists speculate that the findings could also inspire the development of new drugs for heart failure that work by boosting the breakdown of fatty acids in heart muscle cells.

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