Could a chili pepper derivative used for pain also help fight obesity?

Capsaicin is a natural compound that makes chili peppers spicy. Some of its medical benefits have been known for decades, including its potential to help manage pain. Now scientists believe it may also fight obesity.

A research team at the University of Wyoming School of Pharmacy found that giving capsaicin orally can stimulate an ion channel receptor called TRPV1 (transient receptor potential vanilloid subfamily 1), also known as the capsaicin receptor, and thus can turn unhealthy white fat cells into calorie-burning brown fat, a process descriptively known as "beiging."

Drug developers have included capsaicin in numerous topical analgesics because it works on TRPV1. Former Pfizer CEO Jeffrey Kindler’s Centrexion Therapeutics, for example, is developing a program for injectable capsaicin to treat pain associated with osteoarthritis and Morton’s neuroma. Even though capsaicin activates TRPV1—causing a painful, pungent sensation—constant exposure results in the opposite effect, leading to alleviation of pain.

Past research has also suggested that TRPV1 plays a role in body metabolism. That’s the angle the University of Wyoming team, led by Baskaran Thyagarajan, Ph.D., an associate professor of pharmaceutics and neuroscience, is pursuing.

The researchers coated capsaicin with a polymer, creating a pill that releases capsaicin slowly, Thyagarajan told FierceBiotechResearch. They hoped that prolonged release of the drug, called Metabocin, would burn fat without creating inflammation or other side effects, and therefore enhance the compliance among patients in the future.

Then they tried the drug in mice fed a high-fat diet. The animals maintained weight loss through eight months on the therapy with no evidence of safety problems, Thyagarajan reported at the annual meeting of the Society for the Study of Ingestive Behavior.

"We observed marked improvements in blood sugar and cholesterol levels, insulin response, and symptoms of fatty liver disease," he said in a statement. "It proved safe and was well tolerated by the mice."

Next up, the researchers will carry on with their animal studies to see how long the drug’s weight-loss effect can last. Thyagarajan told FierceBiotechResearch that the team now has preclinical safety and efficacy data in mice, and is now looking for funding to advance their research to humans.

Despite the encouraging preliminary results, the researchers cautioned that it doesn’t mean people can count on devouring jalapeño to lose weight because most of the capsaicin in spicy food is not well absorbed.

Many other scientists are also working on methods for transforming white fat into brown fat. A team led by Joseph Baur, Ph.D., at the University of Pennsylvania previously found that activation of the mTOR pathway promotes the process. And just recently, researchers from the University of Michigan and American University uncovered a signaling pathway called CHRNA2 that prompts beige cells to burn calories.