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Animals receiving metformin after severe food restriction exhibited better heart health
Carolyn Ecelbarger headshot
Carolyn Ecelbarger, PhD

Long Beach, Calif. (April 21, 2023)—New research results suggest that the widely used diabetes drug metformin may be beneficial for recovering from short periods of severe food insecurity or anorexia. Researchers will present their work this week at the American Physiology Summit, the flagship annual meeting of the American Physiological Society (APS), in Long Beach, California.

Unlike modest food restriction, which is beneficial to overall metabolic health, even short periods of severe food restriction can have long-lasting health effects. It is estimated that 1 to 4% of women will experience severe food intake reduction from the eating disorder anorexia nervosa during their lifetime, and just under 4% of households in the U.S. are estimated to experience periods of severe food restriction due to food insecurity each year.

“Although it is well known that starvation or severely reduced diets can damage organs such as the heart and kidney, scientists don’t understand the underlying molecular causes for the damage, whether it persists and whether it can be reversed,” said research team leader Carolyn Ecelbarger, PhD, an associate professor of medicine from Georgetown University in Washington, D.C. “The hope is that we may be able to intervene, potentially even in a later time frame, and short-circuit the development of chronic disease and organ injury.”

Using a rat model to study the health effects of short periods of severe caloric restriction, the researchers found that a severe reduction in food intake lasting just two weeks caused damage to the heart and kidneys that appeared to be irreversible even after body weight is restored. During a two-month refeeding period during which rats could eat as much as they wanted, some rats also developed signs of prediabetes, such as increased abdominal obesity.

To test whether any of the negative effects from reduced food consumption could be reversed, some rats received metformin for five weeks during a refeeding period. These rats showed reduced abdominal obesity and improvements in some measures of heart health, including cardiac output, which indicates how much blood is pumped out of the heart with each beat.

Cardiac Output scatterplot in ml/min units. CTRL 45. sFR-Refed 40. CTRL + Met 48. sFR-Refed + Met just over 50. Parametrial fat weight scatterplot in g/185 g-bw units. CTRL just below 6, sFR-Refed around 7, CTRL + Met at 6, sFR-Refed + Met just above 6.
Left: Severe food restriction (sFR)-refed rats had reduced cardiac output (measured near end of study) that was restored by metformin (Met). Right: Parametrial (abdominal) fat wet weight was increased in sFR-refed rats and reduced by metformin (#, * = significant difference due to feeding regimen or drug therapy, respectively).

“This strategy could have the potential to positively affect enormous numbers of individuals,” Ecelbarger said. “However, more work is needed to find the best timing and most effective doses for treatment. We are also exploring other drugs, such as [Food and Drug Administration]-approved blood pressure medications.”

NOTE TO JOURNALISTS: The American Physiology Summit will be held April 20–23, 2023, in Long Beach, California. To schedule an interview with the researchers, conference organizers or presenters, contact APS Media Relations or call 301.634.7314. Find more highlights from the meeting in our Summit Newsroom.

Physiology is a broad area of scientific inquiry that focuses on how molecules, cells, tissues and organs function in health and disease. The American Physiological Society connects a global, multidisciplinary community of more than 10,000 biomedical scientists and educators as part of its mission to advance scientific discovery, understand life and improve health. The Society drives collaboration and spotlights scientific discoveries through its 16 scholarly journals and programming that support researchers and educators in their work.

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