New research from an international team of scientists has found an old drug, used for over half a century to treat alcoholism, could be repurposed as a useful anti-obesity medication. The animal study saw the drug prevent obesity and improve metabolic health in mice fed a high-fat diet.
Disulfiram was first approved for human use way back in the early 1950s. It was discovered to inhibit metabolism of acetaldehyde, a toxic compound produced when the liver breaks down alcohol. Acetaldehyde is the thought to be the source of many major negative “hangover” effects caused by alcohol consumption, from headaches to nausea.
So essentially, subjects taking disulfiram would instantly feel significantly negative effects after just one drink of alcohol. Over the past few decades disulfiram for alcohol abuse has been replaced by several newer drugs that focus more on inhibiting pathways in the brain linked to alcoholism.
The new research on disulfiram was led by a pair of scientists from the National Institute of Aging (NIA), a division of the National Institutes of Health (NIH). Inspired by some studies showing disulfiram’s anti-inflammatory effects, Michel Bernier and Rafael de Cabo set out to explore the drug’s specific effects on obesity and metabolism.
“When we first went down this path, we did not know what to expect, but once we started to see data showing dramatic weight loss and leaner body mass in the mice, we turned to each other and couldn’t quite believe our eyes,” says Bernier.
The researchers first fed a group of mice a high-fat diet for 12 weeks, triggering metabolic signs of pre-diabetes and making the animals overweight. Then, the animals were divided into four experimental groups. Two groups were assigned different doses of disulfiram while continuing a high-fat diet, while the other two groups acted as controls, continuing on either a standard or high-fat diet without the additional drug.
The results were impressive, with the animals in both disulfiram groups losing weight and showing blood glucose improvements despite continuing on a high-fat diet. The mice in the high-dose group reportedly lost around 40 percent of their body weight in just four weeks, effectively matching the body weight reductions seen in those mice on a standard diet.
It is unclear exactly how disulfiram generates these anti-obesity effects in the animals, but the researchers hypothesize it is related to the drug’s novel anti-inflammatory properties. An unrelated recent study from researchers at Harvard Medical School and the Boston Children’s Hospital also homed in on disulfiram’s anti-inflammatory effects, finding the drug may have potential as a treatment for sepsis, and possibly the immune-related "cytokine storms" seen in COVID-19 patients.
It is, of course, early days for the research, and clinical trials are currently being planned to explore whether these anti-obesity effects can be replicated in humans. The scientists do note that since disulfiram is already approved for human uses, and known to be relatively safe, these trials could progress rapidly if positive results are observed.
The new research was published in the journal Cell Metabolism.
Source: National Institutes of Health