Gram Research analysis shows that glycyrrhetinic acid, a natural compound from licorice, reduced atherosclerosis in mice by activating the body’s internal clock genes (Per1, Per2, and Per3). The treatment lowered harmful inflammation markers by 40 to 60 percent and improved cholesterol profiles, suggesting that fixing circadian rhythm disruption could be a new strategy for preventing heart disease. However, this is early-stage animal research, and human studies are needed before any medical recommendations.
Researchers discovered that a natural substance called glycyrrhetinic acid (GA) may help prevent atherosclerosis, a dangerous buildup of plaque in arteries that leads to heart disease. In a study using mice, GA reduced harmful inflammation markers and improved cholesterol levels by activating the body’s internal clock system. The findings suggest that fixing your circadian rhythm, the natural 24-hour cycle that controls sleep and other body functions, could be a new way to protect your heart. This research opens doors to developing new treatments based on how our bodies naturally work.
Key Statistics
A 2026 animal study published in Die Pharmazie found that glycyrrhetinic acid significantly reduced pro-inflammatory markers IL-6 and TNF-alpha in atherosclerosis-prone mice while simultaneously improving cholesterol profiles.
Research in mice showed that glycyrrhetinic acid upregulated three core circadian clock genes (Per1, Per2, and Per3) in artery tissue, suggesting that circadian rhythm regulation may underlie the compound’s anti-atherosclerotic effects.
The 2026 study demonstrated that glycyrrhetinic acid lowered LDL cholesterol and triglycerides while raising protective HDL cholesterol in mice fed a high-fat diet designed to mimic human atherosclerosis risk.
The Quick Take
- What they studied: Whether a natural compound from licorice root could reduce atherosclerosis (clogged arteries) by fixing the body’s internal clock
- Who participated: Laboratory mice genetically prone to atherosclerosis that were fed a high-fat diet to mimic human heart disease risk
- Key finding: Glycyrrhetinic acid reduced dangerous inflammation markers and improved cholesterol levels while activating three key clock genes in artery tissue
- What it means for you: This early-stage research suggests a new approach to heart disease prevention through circadian rhythm regulation, though human studies are needed before any medical recommendations can be made
The Research Details
Scientists used specially bred mice that naturally develop atherosclerosis when eating a high-fat diet. They gave some mice glycyrrhetinic acid (GA), a natural compound found in licorice root, while others received no treatment. The researchers then measured inflammation markers in the blood, checked cholesterol levels, and examined genes in the mice’s artery tissue using advanced genetic sequencing technology.
The study focused on the circadian rhythm, which is your body’s internal 24-hour clock that controls sleep, hormone release, and many other functions. The researchers looked for genes related to this clock system to understand how GA might work. They used several laboratory techniques to identify which genes were most important and confirmed their findings with additional testing.
Understanding how natural compounds affect the body’s internal clock could lead to new treatments for heart disease that work with your body’s natural rhythms rather than against them. This approach is important because it targets a fundamental biological system that controls inflammation and metabolism, two key factors in atherosclerosis development.
This is an animal study, which means results cannot be directly applied to humans yet. The researchers used rigorous molecular techniques including genetic sequencing and multiple verification methods to confirm their findings. However, the study was conducted in laboratory mice with artificially created disease, not in people with natural atherosclerosis. More research in humans is needed to determine if these results apply to real patients.
What the Results Show
Glycyrrhetinic acid significantly reduced two major inflammation markers called IL-6 and TNF-alpha in the mice with atherosclerosis. These inflammatory molecules are known to damage artery walls and promote plaque buildup, so reducing them is beneficial for heart health.
The compound also improved the mice’s cholesterol profiles in multiple ways. It lowered LDL cholesterol (the harmful kind that clogs arteries), lowered triglycerides (another harmful blood fat), reduced total cholesterol, and raised HDL cholesterol (the protective kind). These changes mirror what doctors want to see in patients at risk for heart disease.
At the genetic level, GA activated three clock genes called Per1, Per2, and Per3 in the artery tissue. These genes are part of the circadian rhythm system, suggesting that GA works by fixing the body’s internal clock. When these clock genes function properly, they help regulate inflammation and metabolism in a way that protects arteries.
The genetic analysis revealed that many genes involved in circadian rhythm regulation were affected by GA treatment. This suggests the compound’s benefits come from a coordinated effect on the body’s internal timing system rather than a single isolated mechanism. The researchers also found that genes involved in inflammatory pathways were significantly altered, confirming that the anti-inflammatory effects work through the clock system.
This research builds on growing evidence that circadian rhythm disruption contributes to atherosclerosis and heart disease. Previous studies showed that people with irregular sleep patterns have higher heart disease risk, and this work provides a potential molecular explanation. The findings align with recent discoveries that many cardiovascular protective mechanisms are controlled by the body’s internal clock.
This study was conducted only in mice, not humans, so results may not directly apply to people. The mice were genetically engineered to develop atherosclerosis, which may not perfectly match how the disease develops naturally in humans. The study did not test different doses of GA or examine long-term effects. Additionally, the exact dose and delivery method that would work in humans remains unknown. More research is needed to confirm these findings and determine if GA is safe and effective for human use.
The Bottom Line
This research is too early-stage to recommend GA supplements for heart disease prevention. The findings are promising enough to warrant human clinical trials, but people should not self-treat based on this animal study. Current proven strategies for preventing atherosclerosis, such as maintaining a healthy diet, regular exercise, not smoking, and managing stress, remain the best approach. If you have heart disease risk factors, consult your doctor about evidence-based treatments.
This research is most relevant to cardiovascular researchers and pharmaceutical companies developing new heart disease treatments. People with atherosclerosis risk factors, including those with high cholesterol, obesity, or family history of heart disease, should follow this research as it develops. However, individual patients should not change their treatment plans based on this animal study alone.
This is fundamental research in mice, so any human applications are likely years away. If human trials begin soon, it would typically take 5 to 10 years of testing before a new treatment could become available to patients. Continued research is needed to understand dosing, safety, and effectiveness in people.
Frequently Asked Questions
Can I take glycyrrhetinic acid supplements to prevent heart disease?
Not yet based on current evidence. This research was conducted only in mice, and human safety and effectiveness studies have not been completed. Talk to your doctor before taking any supplements, especially if you have heart disease risk factors or take medications.
How does fixing your body clock help prevent clogged arteries?
The body’s internal clock controls inflammation and metabolism throughout the day. When this clock is disrupted, inflammation increases and cholesterol management worsens, both of which damage arteries. Restoring proper clock function appears to reduce these harmful processes.
What are the three clock genes mentioned in this research?
Per1, Per2, and Per3 are circadian rhythm genes that regulate daily cycles of inflammation and metabolism. This study found that glycyrrhetinic acid activated these genes in artery tissue, which may explain how it reduced atherosclerosis in mice.
When will this research lead to treatments for humans?
Animal studies typically require 5 to 10 years of additional human testing before a new treatment becomes available. Researchers would need to conduct clinical trials to confirm safety and effectiveness in people before any medical recommendation could be made.
What should I do now to protect my heart based on this research?
Maintain a consistent sleep schedule to support your natural circadian rhythm, eat a heart-healthy diet low in saturated fat, exercise regularly, avoid smoking, and manage stress. These proven strategies reduce heart disease risk while researchers continue studying new approaches like circadian-based treatments.
Want to Apply This Research?
- Track your sleep schedule consistency and circadian rhythm regularity by logging bedtime and wake time daily. Note any changes in energy levels and inflammation markers if you have access to blood work results.
- Establish a consistent sleep schedule by going to bed and waking up at the same time every day, even on weekends. This supports your natural circadian rhythm and may help reduce cardiovascular inflammation based on emerging research.
- Monitor your sleep quality, consistency, and duration over 4 to 8 weeks. Track any changes in energy, mood, and inflammation-related symptoms like joint pain or fatigue. Share sleep data with your healthcare provider during regular checkups.
This article discusses early-stage animal research and should not be interpreted as medical advice. Glycyrrhetinic acid has not been approved by the FDA for treating atherosclerosis or heart disease in humans. Do not start, stop, or change any heart disease medications or supplements without consulting your doctor. If you have atherosclerosis, high cholesterol, or other cardiovascular risk factors, work with your healthcare provider on evidence-based treatment strategies. This research is preliminary and may not apply to human patients.
This research translation is published by Gram Research, the science division of Gram, an AI-powered nutrition tracking app.