In a landmark study, researchers found that caffeine is responsible for triggering a cascade effect that ultimately lowers blood LDL cholesterol — the so-called “bad” cholesterol. High levels of LDL cholesterol are associated with an increased risk of cardiovascular disease.
The team led by Richard Austin and Paul Lebeau of the Hamilton Center for Kidney Research at the St. Joe’s Hamilton in the lead.
They found that caffeine consumption was associated with decreased blood levels of PCSK9. PCSK9 is a protein that reduces the liver’s ability to process excess LDL cholesterol. In the absence of PCSK9, more LDL cholesterol can be rapidly removed from the blood via the LDL receptor located on the surface of the liver.
“These findings now provide the underlying mechanism by which caffeine and its derivatives may decrease PCSK9 levels,” said Austin, senior author of the study and a professor in the Department of Medicine at McMaster University. in the blood and thus reduce the risk of cardiovascular disease.
Specifically, caffeine and its derivatives have been shown to block the activation of a protein called SREBP2, which increases liver PCSK9 expression and its transport into the bloodstream.
Austin added: “Given that SREBP2 is involved in a wide range of cardiometabolic diseases, such as diabetes and fatty liver disease, these findings could have far-reaching implications.
This molecular domino effect is similar to the phenomenon previously described by Austin and Lebeau. In 2021, they discovered how a rare genetic variant in the PCSK9 gene – one that reduces PCSK9 secretion from the liver – leads to lower cholesterol levels and an extended lifespan for carriers of this variant. .
The interdisciplinary team includes researchers from several departments of McMaster University as well as the Libin Cardiology Institute of Alberta at the University of Calgary and the Montreal Clinical Research Institute at the University of Montreal.
Co-author Guillaume Par, who studies the genetics and molecular epidemiology of cardiovascular disease, said: “These findings have many implications when they connect the bioactive compound consumed extensively with cholesterol metabolism at the molecular level.
McMaster, professor of pathology and molecular medicine, said: “This discovery is completely unexpected and shows that common foods and drinks have more complex effects than we thought.
Working with study co-author and pharmacological chemist Jakob Magolan, the team developed novel caffeine derivatives that can reduce blood levels of PCSK9 with much greater potency than caffeine, opening the possibility of further development development of new drugs to lower LDL cholesterol.
“We are excited to pursue this new class of pharmaceuticals – or nutraceuticals – for the treatment and prevention of cardiovascular disease,” said Magolan, associate professor of biochemistry and biomedical sciences at McMaster.
Researchers are also exploring additional health benefits of caffeine and its derivatives beyond those observed in the current study.
“It’s exciting to see yet another potential clinical benefit from caffeine,” said study co-author Mark Tarnopolsky, McMaster professor of medicine, who has demonstrated that caffeine improves neuromuscular function.
“Coffee and tea drinkers have another important health reason to rejoice,” says Austin, minus sugar! “