Scientists reviewed 132 studies to understand why fish oil and similar supplements work differently for different people. They found that your genes play a big role in how your body processes these healthy fats. Some genetic variations make it harder for your body to use omega-3 and omega-6 fatty acids efficiently. For example, people with certain gene versions convert these fats 40-60% less effectively than others. This research suggests that one-size-fits-all supplement recommendations may not work for everyone, and personalized nutrition based on your genes could be the future of health advice.

The Quick Take

  • What they studied: How different genes affect the way your body uses omega-3 and omega-6 fatty acids (healthy fats found in fish and nuts)
  • Who participated: Analysis of 132 research studies involving approximately 1.4 million adults from around the world
  • Key finding: Your genes significantly control how well your body processes fish oil and similar supplements. People with certain genetic variations may get 40-60% less benefit from these supplements compared to others with different genes
  • What it means for you: Fish oil and omega-3 supplements may work better for some people than others based on their genetics. This suggests future health recommendations might need to be personalized based on your genes rather than giving the same advice to everyone. However, this research is still developing and isn’t yet ready for routine genetic testing in most cases

The Research Details

Researchers conducted a systematic review, which means they searched through thousands of published studies and carefully selected 132 high-quality studies that examined how genes affect omega-3 and omega-6 fat metabolism. They looked for studies that tested whether people with different genetic variations responded differently to fish oil supplements or dietary changes. The studies included came from major medical databases and were published between various years, with a combined total of approximately 1.4 million participants. The researchers organized the studies by quality level (Tier 1 being the highest quality) to help readers understand the strength of the evidence.

The review focused on specific genes known to be involved in fat processing, including FADS1, FADS2, APOE, TCF7L2, and FABP2. These genes contain instructions for making proteins that help your body break down and use fatty acids. By combining results from many studies, the researchers could identify patterns that might not be obvious in single studies.

This approach is important because it helps explain why the same supplement works differently for different people. Previous research on fish oil has shown mixed results—some people benefit greatly while others see little change. By looking at genetic differences, scientists can finally understand why this happens. This knowledge could eventually lead to personalized medicine where doctors recommend supplements based on your individual genetic makeup rather than giving generic advice to everyone.

This systematic review is considered high-quality research because it followed strict scientific guidelines (PRISMA 2020 standards) for how to search and evaluate studies. The researchers looked at studies from multiple major medical databases to reduce bias. They separated studies into quality tiers, with 79 studies rated as the highest quality (Tier 1) and 53 as good quality (Tier 2). The large combined sample size of 1.4 million people across all studies strengthens the findings. However, readers should know that individual studies within the review had varying quality, and some genetic effects were only found in a few studies rather than consistently across many

What the Results Show

The most consistent finding involved two genes called FADS1 and FADS2, which were studied in 38 different research projects involving about 500,000 people. People who carried certain versions of these genes showed about 40-60% lower ability to convert plant-based omega-3 fats into the longer-chain versions that your body actually uses. This means if you have these genetic variations, eating flaxseed or taking certain supplements may not help as much as it would for someone with different genes.

Another major finding involved the APOE gene, examined in 25 studies with about 930,000 participants. People carrying the APOE ε4 version showed 20-31% less response to DHA supplements (a type of omega-3 found in fish). Even more striking, their bodies broke down DHA much faster—about 77% faster than people without this genetic variation. This means the supplement doesn’t stay in their system as long to do its job.

The research also identified other genetic variations with important effects. For example, people with certain versions of the TCF7L2 gene who ate high amounts of omega-3 fats had about 42% lower risk of developing type 2 diabetes. Additionally, people with specific FABP2 gene variations absorbed EPA (another omega-3 type) up to 12 times more efficiently than others.

Beyond the main findings, the review identified that genetic effects often depend on context—meaning the same gene might have different effects depending on diet, lifestyle, or which specific fat you’re consuming. Some genetic variations only showed effects in certain populations or when combined with other factors. The research also suggested that multiple genes work together to influence how your body handles these fats, rather than any single gene being completely responsible

This systematic review builds on decades of nutrition research by finally explaining why previous studies on fish oil supplements have shown such inconsistent results. Earlier research often found that some people benefited greatly from omega-3 supplements while others saw no change, which confused doctors and confused people trying to decide whether to take supplements. This new analysis suggests those conflicting results make sense when you account for genetic differences. The findings support the emerging field of ’nutrigenomics’—the study of how genes and nutrition interact—which has been growing over the past 10-15 years

While this review is comprehensive, it has important limitations. First, many of the individual studies examined were relatively small, and some genetic effects were only found in a few studies rather than consistently across many. Second, most studies focused on people of European ancestry, so the findings may not apply equally to all ethnic groups. Third, the research is still in early stages—genetic testing for these variations isn’t yet standard medical practice, and we don’t fully understand all the genes involved. Finally, genetics is only part of the story; diet, exercise, age, and other factors also significantly influence how well omega-3 supplements work for you

The Bottom Line

Based on this research, the general recommendation remains that omega-3 and omega-6 fats are important for health, and most people should aim to include them in their diet through foods like fish, walnuts, and flaxseed. However, this review suggests that in the future, genetic testing might help determine whether you’re someone who would benefit more from supplements or dietary changes. Currently, this level of personalized recommendation isn’t yet standard practice, but it may become more common in the next 5-10 years as the science develops. If you’re considering fish oil supplements, discuss with your doctor whether they make sense for your individual situation

This research is most relevant to people who have tried fish oil supplements without seeing expected benefits, people with a family history of heart disease or diabetes, and anyone interested in personalized medicine. Healthcare providers and nutritionists should be aware of these genetic factors when counseling patients. People of European ancestry are best represented in this research, so the findings may apply less directly to other populations until more diverse studies are conducted. This research is less immediately relevant to people who get adequate omega-3 and omega-6 fats from their regular diet

If you were to start taking omega-3 supplements, you might expect to see some effects within 4-12 weeks, though this varies greatly by individual and depends partly on your genetics. However, the long-term health benefits of omega-3 fats typically develop over months to years of consistent intake. If genetic testing becomes available and shows you have variations that reduce your ability to use these supplements, you might want to focus on dietary sources instead or discuss alternative approaches with your doctor

Want to Apply This Research?

  • Track your omega-3 and omega-6 intake weekly by logging fish servings, supplement doses, and plant-based sources like nuts and seeds. Measure this in grams per week or servings per week to see if you’re meeting recommended amounts
  • Start by adding one fish meal per week or taking a fish oil supplement consistently for 8-12 weeks while tracking any changes in energy, mood, or inflammation markers like joint pain. Use the app to set reminders for supplement timing and log which sources you’re using
  • Over 3-6 months, track not just intake but also how you feel—energy levels, mood, joint comfort, and skin health. Note any changes and compare them to your baseline. If you eventually get genetic testing, you can use this personal data to see if the genetic predictions match your actual response

This research is a scientific review and does not constitute medical advice. Genetic testing for omega-3 metabolism is not yet standard medical practice and is not recommended for routine use without consulting a healthcare provider. Before starting any new supplement regimen, especially if you take medications or have existing health conditions, consult with your doctor or registered dietitian. The findings presented are based on research trends and may not apply equally to all individuals or populations. This information is for educational purposes and should not replace professional medical guidance.