Recently a blog article brought up a 2013 study on mice that raised eyebrows by suggesting that omega-3 fatty acids, which we generally think of as being very health-promoting, might increase a person’s risk of dying even though it reduces inflammation in colitis. The blog article raised concern that omega 3 supplements were dangerous, that you should avoid polyunsaturated fats at all costs, and you should eat high quality seafood. This recent blog article sparked concern among those who rely on fish oil supplements for their anti-inflammatory properties, especially for conditions like inflammatory bowel disease (IBD). But does this more-than-a-decade old mouse study really spell trouble for humans? In this article, we’ll dive into the controversy, explore the general benefits of fish oil, break down the mouse study’s findings, and explain why its alarming results don’t translate to people. We’ll also highlight human studies that reveal omega-3’s role in IBD management.
The Power of Fish Oil: A Quick Overview
Fish oil, rich in omega 3 EPA and DHA, is a nutritional powerhouse with a whole host of health benefits. Research has shown it improves cardiovascular outcomes, enhances brain function, and promotes healthy pregnancies. It’s also been looked into for its ability to improve cancer success rates when combined with other nutrients and has shown surprising benefits in different situations, in spite of occasional skepticism. For a deeper dive into these benefits, check out our previous articles on why you need omega-3s, cardiovascular updates, surprising science when the Omega 3 Index is included, cancer outcomes, debunking myths, and pregnancy benefits.
Given these well-documented advantages, the 2013 mouse study’s suggestion of harm seems puzzling. Let’s unpack its findings and put them in context.
The 2013 Mouse Study: Colitis Improved, but Mice Died Sooner?
The 2013 study, published in PLOS ONE, explored omega-3 supplementation (via fish oil) in mice with chemically induced colitis, a model mimicking aspects of human IBD like Crohn’s disease and ulcerative colitis. The researchers supplemented the mice’s diet with fish oil, as detailed in the study’s methods, to see its effect on inflammation caused by dextran sodium sulfate (DSS).
Key Results
Benefits
Omega-3s reduced colitis severity in several ways. Mice showed lower levels of pro-inflammatory molecules (like TNF-α), improved gut barrier function, and better intestinal tissue health, suggesting a protective effect against inflammation.
Negative Outcome
Surprisingly, mice given omega-3s and exposed to high doses of DSS had higher mortality rates compared to controls. This surprising twist made people wonder about the safety of omega-3 supplementation in severe inflammatory conditions.
At first glance, this sounds alarming. If omega-3s can both reduce inflammation and increase mortality in mice, should humans with IBD be concerned? The answer lies in understanding why these results don’t directly apply to people.
Here is Why Mouse Results Don’t Translate to Humans
The mouse study’s findings, while intriguing, don’t mean fish oil is harmful for humans with IBD. Several critical differences between the study’s design and human physiology explain why the mortality concern is likely not an issue for people.
High Doses of Omega 3s in Mice
The mice received omega-3 doses that, relative to their body weight, were far higher than typical human doses (1–3 g/day of EPA/DHA). These very high doses could have triggered excessive oxidative damage, as these oils are susceptible to peroxidation when insufficient antioxidant protection is provided. In humans, high doses are sometimes associated with mild side effects like diarrhea, but nothing approaching increased mortality. As mice studies are short and allow a graduate student to complete their thesis in a reasonable amount of time, they are an attractive model for research. But should they be used as much as they are?
Acute vs. Chronic Disease
The mouse study used DSS to induce acute, severe colitis, which doesn’t fully mimic the chronic, complicated nature of human IBD. Human IBD involves long-term inflammation, genetic factors, and lifestyle influences, whereas the mouse model created an extreme, short-term inflammatory state. Again, these mouse studies are convenient for graduate students and research groups looking for fast results, but the results often don’t translate to outcomes in people.
Physiological Differences (Mice Aren’t People)
Mice aren’t people. We have major differences in metabolism, immune responses, and gut microbiota. For example, mice are more susceptible to oxidative stress from high omega-3 doses, which may have contributed to the study’s negative outcome. Humans, with different antioxidant defenses and dietary contexts, are less likely to experience similar effects.
Study Limitations
The mouse study didn’t explore long-term effects or varied omega-3 formulations, and the high-DSS condition was an extreme test not reflective of typical human IBD progression. Human studies, with more realistic dosing and conditions, provide a clearer picture of omega-3’s effects.
In short, the mouse study’s mortality finding is likely an artifact of its design—high doses, acute inflammation, and species-specific responses—rather than a signal of danger for humans. It was an artifact, and should be recognized as such.
What Human Studies Really Say About Fish Oil and IBD
Studies in people give a more optimistic picture of omega-3s for IBD, including Crohn’s disease and ulcerative colitis. While not a cure-all, fish oil shows promise in several areas, with no evidence of increased mortality.
Fish Oil for Anti-Inflammatory Effects
A 2019 review of 15 studies (1,189 patients) found that omega-3 supplementation reduced intestinal inflammation, helped induce or maintain remission in ulcerative colitis, and decreased disease activity in Crohn’s disease. Omega-3s produce specialized pro-resolving mediators (like resolvins) that dampen inflammation, supporting their role in IBD management.
Omega 3s for Gut Microbiota Benefits
Omega-3s can reshape the gut microbiome in a positive way, which is a key factor in IBD. A 2017 study of 876 women linked higher DHA and total omega-3 levels to increased gut microbiome diversity, particularly with beneficial bacteria like Lachnospiraceae, which produce anti-inflammatory short-chain fatty acids. A 2020 trial further showed that omega-3s boosted Bifidobacterium and Lactobacillus, which may help counteract the microbial imbalances common in IBD.
Fish Oil for lower IBD: Studies in Populations of People over Time
Large-scale studies suggest omega-3s may lower IBD risk. A 2022 UK Biobank study (447,890 participants) found that fish oil supplementation was associated with a reduced risk of ulcerative colitis, though results were not always statistically significant. A meta-analysis also noted a significant link between higher dietary DHA intake and lower ulcerative colitis risk (pooled effect size: 0.75).
Omega 3s Give Mixed Results for IBS
While IBD (Crohn’s and ulcerative colitis) and irritable bowel syndrome (IBS) are distinct, some studies have explored omega-3s for IBS. Results are mixed, with some trials showing reduced abdominal pain and improved quality of life, while others find no significant benefit. The variability likely stems from differences in dosing, patient populations, and IBS subtypes.
Importantly, human studies report no increased mortality with omega-3 supplementation, even at higher doses. Side effects, when they occur, are typically mild, like gastrointestinal discomfort, and can often be managed by adjusting the dose or formulation.
Conclusion: Blogs for Clicks, not for Facts
So what can we take away from this old 2013 mouse study? While the study was well conducted, it’s basic faults made the research useless for people. There is no indication that omega-3 supplementation in the range used in people (1-4 g EPA+DHA per day) causes any higher risk of dying. Quite the opposite. In this mouse study high doses of fish oil were used in a model for IBS that isn’t like chronic IBS in people. Also, mice aren’t human, so all results, including these ones, have to examine species-specific responses. Studies in people show omega-3s’ potential to reduce inflammation, support a healthy gut microbiome, and possibly lower IBD risk, with pretty consistent benefits for ulcerative colitis. While not a panacea—especially for IBS, where results are less clear—fish oil remains a valuable tool for many IBD patients when used appropriately.
To me it looks like this blog about the mouse study was written more for clicks than for facts. Why bring up an old mouse study that hasn’t been verified by others? Maybe it was to peddle an agenda (low seed oil diet), rather than to rigorously examine the study? At a quick glance it supports the “seed oil bad” viewpoint, but a closer look does nothing of the kind.
