That morning cup may be doing more than people thought.
Scientists at Texas A&M University say compounds in coffee appear to activate NR4A1, a receptor involved in protecting the body from stress-induced damage. The findings, published in Nutrients, offer what the researchers describe as one of the first direct links between coffee compounds and NR4A1.
“Coffee has well-known health-promoting properties,” said Dr. Stephen Safe, distinguished professor and Sid Kyle Endowed Chair in Veterinary Toxicology in the Texas A&M College of Veterinary Medicine and Biomedical Sciences’ Department of Veterinary Physiology and Pharmacology. “What we’ve shown is that some of those effects may be linked to how coffee compounds interact with this receptor, which is involved in protecting the body from stress-induced damage.”
Researchers said NR4A1 is part of a group of nuclear receptors that help control gene activity when the body is exposed to stress or tissue damage. In earlier research, Safe and his collaborators described NR4A1 as a “nutrient sensor,” meaning it can respond to dietary compounds and contribute to the body’s ability to remain healthy with age.
“If you damage almost any tissue, NR4A1 responds to bring that damage down,” Safe said. “If you take that receptor away, the damage is worse.”
The team said studies have connected NR4A1 with inflammation, metabolism and tissue repair, processes involved in age-related conditions including cancer, neurodegenerative disease and metabolic disorders.
Large observational studies have linked coffee consumption with a reduced risk of Alzheimer’s disease, Parkinson’s disease and metabolic disease. But those studies have largely shown associations, not how coffee might produce protective effects.
Safe and his team proposed that NR4A1 could be part of the answer. The project included researchers from across Texas A&M, including Dr. Robert Chapkin, Dr. Roger Norton, Dr. James Cai and Dr. Shoshana Eitan. Their work helped show coffee’s protective effects in neurological models.
The researchers found that several compounds in coffee can bind to NR4A1 and alter its activity. The most active were polyhydroxy and polyphenolic compounds such as caffeic acid.
“What we’re saying is that at least part of coffee’s health benefits may come through binding and activating this receptor,” Safe said.
In laboratory models, the compounds changed cell behavior in ways associated with disease protection. Researchers said they reduced cellular damage and slowed the growth of cancer cells. When the team removed NR4A1 from the cells, those protective effects disappeared.
The study also suggests caffeine may not be the main source of coffee’s protective effects.
“Caffeine binds the receptor, but it doesn’t do much in our models,” Safe said. “The polyhydroxy and polyphenolic compounds are much more active.”
The researchers said that may help explain why large population studies have linked both caffeinated and decaffeinated coffee with similar health benefits.
Safe cautioned that coffee is chemically complex and likely affects the body through multiple biological routes.
“There are many receptors and many mechanisms involved,” he said. “What we’re showing is that this could be one of the important pathways.”
The study was designed to investigate biological mechanisms. It does not establish direct cause and effect in people or prove that drinking coffee prevents disease.
“There’s still a lot of work to be done,” Safe said. “We’ve made the connection, but we need to better understand how important that connection is.”
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