·   Quercetin stimulates improved heart function in cardiometabolic disease by promoting blood vessel generation.
·   Improved blood vessel integrity plays a key role in quercetin’s beneficial effects for heart function.
·   Quercetin’s positive impact isn’t related to aged cell elimination.

We all know that eating a balanced diet contributes to our health. Across the globe, though, high fat diets are contributing to heart problems associated with metabolic abnormalities referred to as cardiometabolic syndrome. The aging world population in combination with fattening food diets only adds to the increasing incidence of this health complication, which warrants the search for new techniques to protect the heart.

Lerman and colleagues from the Mayo Clinic in Minnesota published a study in Oxidative Medicine and Cellular Longevity showing that treating high fat diet-fed mice with quercetin improved signs of cardiometabolic syndrome. Their findings indicate oral 50 mg/kg quercetin treatment drives the generation of blood vessels and lowers fat accumulation in the hearts of mice fed fatty diets displaying heart dysfunction. Administering quercetin also reduced the heart muscle buildup of harmful oxygen-containing molecules called reactive oxygen species and alleviated heart blood vessel thinning (rarefaction). Interestingly, quercetin’s benefits did not come from eliminating aged, non-proliferating (senescent) cells but instead its stimulation of blood vessel formation. Findings from the study may translate to uncovering how using quercetin could help with human cardiometabolic disease.

What is Quercetin?

Quercetin is a natural, plant-derived compound found in fruits, vegetables, leaves, seeds, and grains and has been promoted for cancer treatment because of its senescent cell-eliminating capabilities. Studies have also shown that quercetin treatment provides beneficial effects for the heart. So, Lerman and colleagues sought to find whether quercetin reduces cardiac dysfunction in mouse cardiometabolic disease by eliminating heart senescent cells.

Quercetin Improves the Heartbeat in Cardiometabolic Disorder

Since previous research has focused on quercetin’s effects in other heart ailments, Lerman and colleagues first demonstrated that quercetin treatment alleviates heart dysfunction in cardiometabolic disease. The Mayo Clinic team found quercetin improved the heartbeat as shown by an increased volume of blood pumped in mice with cardiometabolic disease. This means that administering quercetin mitigates the heart blood pumping dysfunction in this disease.

(Yu et al., 2021 | Oxidative Medicine and Cellular Longevity) Quercetin improves the heartbeat in high fat diet-induced cardiometabolic disorder. A significantly improved ejection fraction, stroke volume, and cardiac output (CO) with quercetin treatment in high fat diet-induced cardiometabolic disorder all indicate that quercetin improves heart dysfunction.

Quercetin Administration Blunts Blood Vessel Thinning and Fat Accumulation

Heart fat accumulation and blood vessel thinning are linked to worsening blood pumping abilities, so Lerman and colleagues examined the high fat diet’s effects on fat aggregation and blood vessel integrity. The researchers found that while the fattening diet induced fat droplet accumulation and blood vessel rarefaction, quercetin treatment blunted these effects. According to these findings, quercetin treatment improves high fat diet-induced heart dysfunction by reducing fat droplet conglomerations and enhancing heart blood vessel integrity.

(Yu et al., 2021 | Oxidative Medicine and Cellular Longevity) Quercetin treatment alleviates lipid accumulation and improves blood vessel integrity in mice with high fat diet-induced cardiometabolic disease. The images in the top figure show lipid droplets in heart muscle labeled dark blue, and a high fat diet induces an accumulation of fat deposits. The top right graph indicates that quercetin treatment alleviates the lipid droplet accumulation in high fat diet-fed mice. The bottom images show blood vessel cells labeled dark blue in heart muscle and that high fat diet-fed mice have substantially less blood vessel cells. Quercetin restores the blood vessel cell numbers in high fat diet-fed mice. The bottom right graph provides a quantification of the blood vessel cell numbers shown in the bottom images, indicating that quercetin rescues the number of blood vessel cells in the cardiometabolic disease heart. CV = Control vehicle; CQ = Control + quercetin; HV = High-fat diet vehicle; HQ = High-fat diet + quercetin

Quercetin Treatment Does Not Eliminate Senescent Cells

To find whether these improvements came from quercetin’s ability to eliminate senescent cells, Lerman and colleagues measured the presence of senescent cells in the heart. They found that high fat diets do not increase the abundance of senescent cells and that quercetin treatment has no effect on senescent cell numbers, suggesting that quercetin’s beneficial effects on cardiometabolic disease do not come from its abilities to eliminate senescent cells.

(Yu et al., 2021 | Oxidative Medicine and Cellular Longevity) Cardiometabolic disorder does not induce senescent cell accumulation, and quercetin administration does not eliminate senescent cells. The images show that heart muscle labeled with the senescent cell marker (SA-β-Gal, Blue-green stain) indicate no difference in senescent cell presence with high fat diet-induced cardiometabolic disease (High-fat + vehicle), and administering quercetin provides no elimination of senescent cells (High-fat + quercetin). Along those lines, the blue-green senescent cell staining intensity was not significantly different between any of these conditions. The graph shows that the senescent cell stain was no different between any of the conditions. CV = Control vehicle; CQ = Control + quercetin; HV = High-fat diet vehicle; HQ = High-fat diet + quercetin

Quercetin Drives the Generation of New Blood Vessels

To further elucidate quercetin’s blood vessel health-promoting effects, the researchers sought to find out whether it could drive blood vessel formation (angiogenesis). They used cells from human umbilical veins to show that quercetin treatment does promote angiogenesis. So, instead of improving heart function in cardiometabolic disease by eliminating senescent cells, quercetin treatment drives angiogenesis to enhance blood vessel integrity and stimulate better heart blood pumping.

Another factor that may have contributed to quercetin’s enhancement of cardiac function could come from it driving the elimination of senescent cells in organs like the kidney or liver and thereby enhancing their function. Improving kidney or liver function with quercetin may help to protect heart function since all organs of the body rely on one another’s functional capacity to some degree.

The Future of Quercetin Research

Future studies may try out different dosing regimens to optimize since Lerman and colleagues used an intermittent quercetin dosing regimen, treating mice every two weeks. More studies are also needed to illuminate additional quercetin heart protective properties and to determine whether the benefits observed in this study apply to humans.