Researchers studied how a high-dose fish oil supplement called icosapent ethyl (IPE) affects the body’s cholesterol and fat particles in people with normal cholesterol levels. Over 28 days, 38 healthy volunteers took the supplement while scientists tracked changes in their blood using advanced testing. The supplement quickly increased omega-3 fatty acids in their blood particles and reduced several markers linked to heart disease risk, including triglycerides and harmful cholesterol types. Interestingly, people’s bodies responded differently to the same dose, suggesting that personalized medicine approaches might work better for heart disease prevention in the future.

The Quick Take

  • What they studied: Whether a prescription fish oil supplement (icosapent ethyl) changes the types and amounts of cholesterol and fat particles in the blood, and whether these changes reduce heart disease risk.
  • Who participated: 38 healthy adults with normal cholesterol levels who took the supplement for 28 days, then stopped for 7 days to see if changes reversed.
  • Key finding: The supplement increased omega-3 fatty acids in blood particles by about 4 times within one week and reduced several heart disease risk markers, including triglycerides and harmful cholesterol types. However, each person’s body responded differently to the same dose.
  • What it means for you: This supplement may help reduce heart disease risk in healthy people, but the amount of benefit varies from person to person. This suggests doctors might eventually be able to personalize treatment based on individual responses, though more research is needed before making treatment decisions.

The Research Details

This was a controlled study where 38 healthy volunteers took a high dose of icosapent ethyl (a concentrated form of omega-3 fish oil) for 28 days. Scientists used three different advanced laboratory methods to measure changes in blood fats and cholesterol particles. After the 28-day treatment period, participants stopped taking the supplement for 7 days to see if the changes reversed back to normal.

The researchers measured many different types of cholesterol and fat particles in the blood, not just the basic cholesterol numbers you might see on a standard blood test. They also tested how well these particles stick to certain proteins in blood vessel walls, which is important for understanding heart disease risk.

Because the study was small and only included healthy people with normal cholesterol, the results may not apply to people with high cholesterol or existing heart disease.

Using multiple advanced testing methods allowed researchers to see detailed changes in blood chemistry that standard blood tests would miss. This detailed approach helps explain how the supplement might reduce heart disease risk at the molecular level. Understanding the mechanism is important because it could help doctors predict who will benefit most from the treatment.

The study’s strengths include the use of three independent laboratory methods to confirm findings and careful measurement of many different blood components. The main limitation is the small number of participants (38 people), which means results may not apply to larger populations. The study only included healthy people, so we don’t know if results would be the same in people with high cholesterol or heart disease. The short study period (28 days) shows only immediate effects, not long-term benefits.

What the Results Show

Within just 7 days of taking the supplement, omega-3 fatty acids in blood particles increased about 4-fold on average. When participants stopped taking the supplement, these levels returned to normal within 7 days, showing the effect was directly caused by the treatment.

The supplement changed the composition of cholesterol and fat particles throughout the blood. Specifically, it reduced saturated fats and certain types of polyunsaturated fats while increasing omega-3 content. These changes resulted in lower triglyceride levels (a type of blood fat linked to heart disease) and lower levels of remnant cholesterol (leftover particles after fat digestion).

Importantly, the supplement reduced how well harmful cholesterol particles stuck to proteins in blood vessel walls. This stickiness is thought to be an important step in developing clogged arteries. The reduction in stickiness correlated with lower amounts of harmful cholesterol particles and specific fat molecules previously linked to heart disease.

A 10-year heart disease risk score (a calculation doctors use to estimate future risk) also improved with the supplement, suggesting real potential for reducing heart disease risk.

The study revealed that each person’s body responded differently to the same dose of the supplement. Some people’s blood omega-3 levels increased much more than others, and this variation was related to how much omega-3 they had at the start of the study. People with lower baseline levels showed bigger increases. Despite these differences in how much omega-3 was added, the overall remodeling of cholesterol and fat particles was similar across all participants, suggesting the supplement works through consistent mechanisms even when individual responses vary.

Previous large studies showed that icosapent ethyl reduces heart disease events in people with high triglycerides, but the exact mechanism wasn’t clear. This study provides detailed evidence of how the supplement changes blood chemistry in ways that should reduce heart disease risk. The findings align with the theory that omega-3 fatty acids help by changing the structure and behavior of cholesterol particles, making them less likely to damage blood vessels.

The study was small (only 38 people) and short-term (28 days), so we don’t know if benefits continue long-term or apply to larger populations. All participants were healthy with normal cholesterol levels, so results may not apply to people with high cholesterol, heart disease, or other health conditions. The study didn’t include a control group taking a placebo, though the 7-day washout period (stopping the supplement) helped confirm the supplement caused the changes. The study was conducted in one country and may not represent all populations.

The Bottom Line

Based on this research, icosapent ethyl appears to reduce several heart disease risk markers in healthy people (moderate confidence level). However, this is a small, short-term study, so recommendations should come from your doctor based on your individual risk factors. This supplement is already approved by the FDA for people with high triglycerides, but using it in healthy people requires medical supervision. Talk to your doctor about whether this supplement might be appropriate for you.

This research is most relevant to people interested in heart disease prevention and those with family histories of heart disease. People with high triglycerides or existing heart disease should discuss this supplement with their cardiologist. This study doesn’t provide enough evidence to recommend the supplement for all healthy people, but it suggests potential benefits worth discussing with a healthcare provider. People taking blood thinners or with fish allergies should avoid this supplement.

The supplement’s effects on blood chemistry appear within 7 days, but the long-term benefits for actually preventing heart disease would take months or years to measure. Standard heart disease prevention benefits typically appear over months to years of consistent treatment.

Want to Apply This Research?

  • If taking this supplement under medical supervision, track weekly blood triglyceride levels and heart disease risk score changes. Users could log supplement adherence daily and note any side effects or changes in energy levels.
  • Users could set a daily reminder to take the supplement at the same time each day and track compliance. They could also log dietary omega-3 intake from food sources to understand total omega-3 consumption alongside supplementation.
  • Establish a baseline heart disease risk score and triglyceride level with your doctor, then retest every 4-8 weeks while taking the supplement. Track trends in these markers over 3-6 months to assess individual response, since the study shows people respond differently to the same dose.

This research describes how a fish oil supplement affects blood chemistry in healthy people, but does not prove it prevents heart disease. Icosapent ethyl is a prescription medication that should only be used under doctor supervision. This summary is for educational purposes and should not replace medical advice from your healthcare provider. Before starting any supplement, especially if you take blood thinners, have a fish allergy, or have existing health conditions, consult with your doctor. Individual responses to supplements vary, and what works for one person may not work for another.