Research shows that DHA and EPA, two omega-3 fatty acids found in fish oil, work together to prevent atherosclerosis by activating genes that improve cholesterol processing and reduce inflammation in blood vessels. According to Gram Research analysis, a 2026 study found that these supplements reversed plaque buildup in arteries, lowered dangerous cholesterol levels, and reduced liver fat more effectively than a standard cholesterol medication in mice with atherosclerosis.
According to Gram Research analysis, a new study shows that two types of omega-3 fatty acids found in fish—DHA and EPA—work together to fight atherosclerosis, a condition where plaque builds up in arteries. Researchers used mice with a genetic predisposition to heart disease and fed them a high-fat diet, then treated some with DHA and EPA supplements. The supplements reversed dangerous cholesterol changes, reduced liver fat buildup, and shrank artery plaque. The fish oils appeared to work better than a common cholesterol medication at protecting the liver. Scientists discovered that DHA and EPA activate specific genes that help the body process cholesterol better and reduce inflammation in blood vessels.
Key Statistics
A 2026 research article published in NPJ Science of Food found that DHA and EPA supplements reversed elevated cholesterol and triglyceride levels in mice with atherosclerosis, while also shrinking the area of plaque buildup in their arteries.
According to a 2026 study, DHA and EPA provided superior liver protection compared to Atorvastatin, a widely-used prescription cholesterol medication, in mice with high-fat diet-induced atherosclerosis.
Research from 2026 identified four specific microRNAs (miR-33a, miR-146a-3p, miR-155, and miR-223-3p) that DHA and EPA modulate to regulate lipid metabolism and reduce inflammation in blood vessels.
A 2026 analysis found that DHA and EPA activated 1,453 genes in the liver related to cholesterol metabolism and bile acid synthesis, while suppressing inflammatory pathways that contribute to atherosclerosis development.
The Quick Take
- What they studied: Whether two omega-3 fatty acids from fish (DHA and EPA) can prevent or reverse atherosclerosis and how they work in the body
- Who participated: Laboratory mice genetically engineered to develop atherosclerosis when eating a high-fat diet, compared to control mice eating normal food
- Key finding: DHA and EPA supplements reversed the buildup of plaque in arteries, lowered dangerous cholesterol levels, reduced fat in the liver, and improved heart function in mice with atherosclerosis
- What it means for you: These findings suggest fish oil supplements containing DHA and EPA may help prevent heart disease in humans, though human studies are still needed to confirm these results. People with high cholesterol or heart disease risk should discuss fish oil supplements with their doctor.
The Research Details
Researchers created mice that naturally develop atherosclerosis (clogged arteries) when eating a high-fat diet. They divided the mice into groups: some ate only the high-fat diet, while others received DHA and EPA supplements along with the high-fat diet. A third group received Atorvastatin, a common cholesterol medication, to compare results. The researchers measured cholesterol levels, examined artery plaque under a microscope, and analyzed liver and heart tissue for fat buildup.
To understand how DHA and EPA work, scientists examined which genes were turned on or off in the liver and arteries of treated versus untreated mice. They also measured tiny molecules called microRNAs that control how genes function. This detailed genetic analysis revealed the specific biological pathways that DHA and EPA activate to fight atherosclerosis.
This type of study is important because it allows researchers to understand the exact mechanisms—the ‘how’ and ‘why’—behind a treatment’s effects. Animal studies provide evidence that supports moving toward human clinical trials, where we can determine if these benefits apply to people.
Understanding the biological mechanisms behind DHA and EPA’s protective effects is crucial because it helps scientists design better treatments and predict which patients might benefit most. This research bridges the gap between knowing that fish oil helps and understanding exactly how it helps, making the evidence stronger for recommending it to patients.
This study used a well-established animal model of atherosclerosis and measured multiple outcomes (cholesterol, plaque size, liver fat, gene expression, and microRNA levels), which strengthens the findings. The researchers compared DHA/EPA to both untreated disease and to a standard medication, providing useful context. However, animal studies don’t always translate directly to humans, so results should be considered preliminary evidence rather than proof that these supplements will work the same way in people.
What the Results Show
Mice receiving DHA and EPA supplements showed dramatic improvements compared to mice eating only the high-fat diet. Their total cholesterol dropped significantly, triglycerides (another type of blood fat) decreased, and the ratio of ‘good’ cholesterol to ‘bad’ cholesterol improved. Most importantly, the area of plaque buildup in their arteries shrank substantially.
The supplements also protected the liver and heart. Mice treated with DHA and EPA had much less fat accumulation in their livers (hepatic steatosis) and less lipid deposition in heart tissue. Liver function tests improved, suggesting the organs were working better. Remarkably, DHA and EPA provided better liver protection than Atorvastatin, a prescription medication widely used to treat high cholesterol.
At the genetic level, DHA and EPA activated genes involved in cholesterol metabolism and bile acid synthesis in the liver—essentially helping the body process and eliminate cholesterol more efficiently. In the arteries, they activated genes related to cholesterol transport and anti-inflammatory signaling. Simultaneously, they suppressed genes involved in inflammation and the adhesion of immune cells to artery walls, reducing the inflammatory damage that drives atherosclerosis.
The research identified specific microRNAs (tiny regulatory molecules) that appear to be key players in how DHA and EPA work: miR-33a, miR-146a-3p, miR-155, and miR-223-3p. These microRNAs regulate genes controlling lipid metabolism and inflammation. The fact that DHA and EPA modified these microRNA levels suggests they work through a coordinated network of biological signals rather than a single pathway. This network-based mechanism may explain why the supplements appear more effective than single-target medications.
Previous research has shown that DHA and EPA reduce atherosclerosis risk, but most studies focused on their effects in a single organ or tissue. This research is novel because it demonstrates cross-organ communication—how changes in the liver influence what happens in the arteries and vice versa. The finding that DHA and EPA outperformed Atorvastatin for liver protection is particularly interesting, as it suggests these natural compounds may have advantages over standard medications for certain aspects of heart disease prevention.
This study used laboratory mice with a genetic modification that makes them prone to atherosclerosis. While this model is useful for research, mice don’t always respond to treatments the same way humans do. The study didn’t specify the exact doses of DHA and EPA used, making it unclear what human equivalent dose would be needed. Additionally, the research examined short-term effects; long-term studies would be needed to determine if benefits persist over time. Finally, this is a controlled laboratory study, not a human clinical trial, so we cannot yet confirm these results apply to people.
The Bottom Line
Based on this research, people at risk for atherosclerosis or heart disease may benefit from discussing fish oil supplements containing DHA and EPA with their healthcare provider. The evidence is moderately strong from animal studies, but human clinical trials are still needed. Current general recommendations suggest 250-500 mg combined DHA and EPA daily for heart health, though individual needs vary. Do not replace prescribed medications like Atorvastatin without medical guidance.
This research is most relevant to people with high cholesterol, family history of heart disease, or existing cardiovascular disease. It may also interest people seeking natural approaches to heart disease prevention. However, people taking blood thinners should consult their doctor before taking fish oil supplements, as there may be interactions. Pregnant women and those with fish allergies should also seek medical advice.
In animal studies, the benefits of DHA and EPA appeared within the timeframe of the experiment, but human studies typically require months to years to show measurable improvements in cholesterol levels and artery health. Most people taking fish oil supplements for heart health should expect to wait 3-6 months before noticing potential benefits, with continued improvement over 1-2 years.
Frequently Asked Questions
Do fish oil supplements actually prevent heart disease?
Research shows DHA and EPA from fish oil reduce atherosclerosis risk by improving cholesterol levels and reducing inflammation. A 2026 study found these supplements reversed plaque buildup in arteries and outperformed standard medication for liver protection in mice, though human trials are still needed to confirm these benefits.
How much DHA and EPA do I need to take daily?
General recommendations suggest 250-500 mg combined DHA and EPA daily for heart health, though individual needs vary based on your cholesterol levels and risk factors. Consult your doctor to determine the appropriate dose for your specific situation.
Is fish oil better than cholesterol medication?
A 2026 study found DHA and EPA provided better liver protection than Atorvastatin in mice, but this doesn’t mean fish oil replaces prescription medications. Many people benefit from combining both approaches. Never stop taking prescribed cholesterol medication without consulting your doctor.
How long does it take to see benefits from fish oil supplements?
Most people should expect 3-6 months before noticing potential improvements in cholesterol levels and artery health from fish oil supplements. Benefits typically continue improving over 1-2 years with consistent use and healthy lifestyle habits.
Can fish oil supplements help if I already have atherosclerosis?
Research suggests DHA and EPA may help reverse existing atherosclerosis by reducing plaque buildup and improving cholesterol metabolism. However, discuss supplementation with your cardiologist, as fish oil may interact with blood thinners and other medications you’re taking.
Want to Apply This Research?
- Log daily DHA/EPA supplement intake (dose in mg) and track quarterly cholesterol levels (total cholesterol, LDL, HDL, triglycerides) to monitor whether supplementation correlates with improvements in your lipid profile
- Set a daily reminder to take a fish oil supplement at the same time each day, and pair this habit with another routine (like breakfast) to build consistency. Track whether you’re meeting your target dose each week
- Create a quarterly review where you compare cholesterol test results over time. Plot trends in total cholesterol and LDL levels to visualize whether supplementation is working for your individual body. Share results with your doctor to adjust dosing if needed
This article summarizes research findings from an animal study and should not be considered medical advice. Fish oil supplements are not approved by the FDA to treat or prevent atherosclerosis or heart disease. Consult your healthcare provider before starting any supplement regimen, especially if you take blood thinners, have fish allergies, are pregnant, or have existing cardiovascular conditions. Do not replace prescribed medications with supplements without medical guidance. Individual results may vary, and animal study findings do not always translate to human outcomes.
This research translation is published by Gram Research, the science division of Gram, an AI-powered nutrition tracking app.