Omega-3-acid ethyl esters(Trygg Pharma AS)

A new study suggests fish oil may help reduce insulin resistance even in people who aren't obese. In diabetic rats, omega-3 supplementation improved blood sugar levels, cholesterol, and inflammation by shifting immune cells into a more anti-inflammatory mode.Fish oil may have a surprising role in the fight against insulin resistance, especially in a form of type 2 diabetes that is often overlooked. A Brazilian study published in Nutrients found that omega-3 fatty acids from fish oil reduced glucose intolerance and weakened insulin resistance in rats that were not obese but showed a diabetes-like metabolic condition. The work was funded by FAPESP and focused on Goto-Kakizaki rats, a well established animal model used to study non-obese type 2 diabetes. Type 2 diabetes is marked by high blood sugar that occurs when insulin, the hormone that helps move glucose from the blood into cells, does not work effectively. Fish Oil and Insulin Resistance Omega-3 supplements, including fish oil, are often used by people with cardiovascular disease and type 2 diabetes. However, scientists still know much less about how these fatty acids affect insulin resistance when obesity is not involved. That question matters because obesity is one of the strongest risk factors for type 2 diabetes, but it is not the whole story. An estimated 10% to 20% of people with type 2 diabetes worldwide are not obese. For these patients, the biological roots of insulin resistance may differ from the better known obesity-linked pathways. In the study, researchers gave the rats fish oil at a dose of 2 grams per kilogram of body weight (equivalent to 540 mg/g of eicosapentaenoic acid, or EPA, and 100 mg/g of docosahexaenoic acid, or DHA) three times weekly for eight weeks. By the end of the experiment, the treated animals showed lower insulin resistance, better blood sugar control, reduced inflammatory markers, and improvements in several lipid measures, including total cholesterol, LDL ("bad cholesterol") and triglycerides. The results came from preclinical experiments, so they do not prove that fish oil will have the same effects in people. Still, the findings point to inflammation as a powerful target in non-obese diabetes and suggest that omega-3 fatty acids deserve closer study in this group. A Shift in Immune Cells "Our experiments involved Goto-Kakizaki [GK] rats, an animal model for non-obese type 2 diabetes. We found that insulin resistance can be reduced in these animals by modulating the inflammatory response so as to change the pro defense cells [lymphocytes] from a pro-inflammatory state to an anti-inflammatory state. This process parallels the response of obese individuals with insulin resistance to omega-3 fatty acid supplementation," said Rui Curi, Director of Butantan Institute's Education Center, Professor of Interdisciplinary Graduate Studies in Health Sciences at Cruzeiro do Sul University (UNICSUL), and coordinator of the study. Lymphocytes are white blood cells that help direct the adaptive immune response. When their behavior changes, the effects can spread through the immune system and influence other cells involved in inflammation. "In previous studies, we observed alterations in both lymphocytes and macrophages [large white blood cells that often reside in adipose tissue and are part of the innate immune system, engulfing and destroying pathogens] in non-obese rats with insulin resistance. In such cases, these cells produce more pro-inflammatory cytokines, as is central in obese people with diabetes," Curi explained. "The main aim of the study, therefore, was to find out whether supplementation with fish oil [rich in omega-3] could reverse specific alterations in lymphocytes that had been observed in previous research. Our findings increased our knowledge of the link between inflammation and insulin resistance in non-obese animals, confirming that this is a key factor in diabetes even in the absence of obesity," said Renata Gorjão, last author of the article, and Co-Director of UNICSUL's Program of Graduate Studies in Health Sciences. Inflammation Without Obesity The Nutrients study, conducted during the PhD candidacy of Tiago Bertola Lobato, was part of a broader FAPESP-supported project exploring how insulin resistance develops in non-obese animals. Curi noted that obesity is a major diabetes risk factor, but not the only one. In people who develop diabetes without obesity, one leading hypothesis is that genetic factors may play an important role. In another study published in Cells, Curi, Gorjão, and colleagues investigated whether delayed intestinal transit might also contribute to insulin resistance in non-obese individuals. "Most obese people have chronic low-level inflammation, which is known to affect the insulin signaling pathways. Adipose tissue, which is augmented in obesity, releases pro-inflammatory cytokines that affect the insulin signaling pathways, promoting insulin resistance. In the non-obese model, this impactful characteristic of adipose tissue is absent, but systemic inflammation is present," Curi said. The group had previously shown systemic inflammation in non-obese GK rats with insulin resistance in a study published in the International Journal of Molecular Sciences. Another paper from the same project reported that anti-inflammatory defenses appear to break down early in non-obese GK rats with insulin resistance. Lymph nodes (part of the immune system) from newly weaned 21-day-old GK pups already showed reduced markers of regulatory T-cells (Tregs, cells with anti-inflammatory characteristics). The researchers also detected other early inflammatory changes. That work was published in FEBS Letters, a journal of the Federation of European Biochemical Societies. How Omega-3s May Help The Nutrients study suggests that fish oil may work by moving immune activity away from a damaging inflammatory pattern and toward a more protective one. "Fish oil supplementation reversed this pro-inflammatory profile, displaying a significant anti-inflammatory effect and reducing polarization of Th1 and Th17 cells [lymphocyte subtypes that perform crucial functions in inflammation], followed by a rise in the percentage of Tregs, which can inhibit the activation of pro-inflammatory lymphocytes. Thus the action of omega-3 fatty acids on lymphocytes, modulating them from a pro-inflammatory state to an anti-inflammatory state, may have triggered the reduction in insulin resistance in these animals," Lobato said. That immune shift is important because insulin resistance is not only a problem of sugar metabolism. It is also deeply connected to inflammation. When inflammatory signals remain elevated, they can interfere with insulin signaling and make it harder for cells to respond to the hormone. The study adds to a growing view of type 2 diabetes as a disease shaped by both metabolism and the immune system. In this case, fish oil appeared to improve blood sugar regulation not simply by changing fat levels, but by changing the inflammatory environment that helps drive insulin resistance. What Later Studies Add Since the Nutrients paper was published, related human research has continued to examine how omega-3 fatty acids may influence early diabetes risk and metabolic health. A 2025 double blind randomized controlled trial in Food and Function tested fish oil supplementation in healthy middle aged and older adults. Over 12 weeks, the fish oil groups had dose related increases in serum EPA and DHA. The researchers also reported decreases in fasting insulin and the HOMA-IR index, a common marker of insulin resistance. Fasting blood glucose trended downward across groups, and several lipid related measures also improved. Another 2024 analysis in Nutrition and Diabetes used modeling data from 161 patients with type 2 diabetes to explore the relationship between omega-3 levels and HbA1c, a longer term marker of blood sugar control. The authors reported a dose related association and proposed that omega-3 intake could be studied in a more individualized way, while also noting that the role of omega-3s in type 2 diabetes remains debated. Together, these studies do not settle the question of whether fish oil should be used to manage diabetes. Human evidence remains mixed, and the Brazilian study was conducted in animals, not people. However, the newer findings are consistent with the idea that omega-3 fatty acids may affect insulin resistance and inflammation in ways worth testing more carefully. More Research Still Needed Despite the promising findings, the researchers stressed that the results should be interpreted cautiously. Animal studies are useful for uncovering biological mechanisms, but clinical trials are needed before scientists can know whether the same strategy works in people with non-obese type 2 diabetes. "These studies involved well-established experimental models that mimic insulin resistance in non-obese individuals. Trials in humans are needed to estimate the ideal dose and the most indicated type of omega-3 fatty acid," Curi said. For now, the study offers a compelling clue: in diabetes, body weight may not be the only driver of insulin resistance. Inflammation can play a central role even without obesity, and fish oil may help reveal how that hidden process can be changed.

Fish oil has long been praised as brain-boosting, but new research suggests the story may be more complicated. Scientists found that in people with repeated mild head injuries, a key omega-3 fatty acid in fish oil—EPA—may actually interfere with the brain’s ability to repair itself. Instead of helping recovery, it appears to weaken blood vessel stability, disrupt healing signals, and even contribute to harmful protein buildup linked to cognitive decline.A new study from the Medical University of South Carolina is raising fresh concerns about fish oil supplements, especially for people who experience repeated mild traumatic brain injuries. Writing in the journal Cell Reports, researchers report that these widely used supplements, often promoted as protective for the brain, could actually interfere with healing after injury. The research was led by neuroscientist Onder Albayram, Ph.D., an associate professor at MUSC and a member of the National Trauma Society Committee. His team focused on the biological processes involved in repairing blood vessels in the brain after injury. Rising Popularity of Omega-3 Supplements Interest in omega-3 fatty acids, the key components of fish oil, has been growing rapidly. According to Fortune Business Insights, these supplements are now appearing not only in capsules but also in drinks, dairy alternatives, and snack products. That surge in popularity does not surprise Albayram. "Fish oil supplements are everywhere, and people take them for a range of reasons, often without a clear understanding of their long-term effects," he said. "But in terms of neuroscience, we still don't know whether the brain has resilience or resistance to this supplement. That's why ours is the first such study in the field." Albayram collaborated with Eda Karakaya, Ph.D., Adviye Ergul, M.D., Ph.D., and several other researchers at MUSC and partner institutions. Among them was Semir Beyaz, Ph.D., at the Cold Spring Harbor Laboratory Cancer Center in New York. EPA Identified as a Potential Weak Point in Brain Recovery The team discovered what they describe as a context-dependent metabolic vulnerability. In simple terms, this means that changes in how cells use energy may reduce the brain's ability to recover under certain conditions. This vulnerability appears to be linked to the buildup of eicosapentaenoic acid, or EPA, one of the main omega-3 fatty acids found in fish oil. In their experimental models, higher levels of EPA in the brain were associated with weaker repair after injury. Albayram noted that not all omega-3s behave the same way. Docosahexaenoic acid, or DHA, is well known for its beneficial role in the brain and is a major part of neuronal membranes. EPA, however, follows a different pathway. It is less incorporated into brain structures, and its effects can vary depending on how long it is present and the surrounding biological conditions. Because of this, the long-term impact of omega-3 intake on brain recovery and blood vessel adaptation has remained unclear. Experiments Link Diet, Brain Biology, and Recovery To better understand these effects, the researchers used a series of models to connect diet, brain function, and healing. In mice, they examined how long-term fish oil use influenced the brain's response to repeated mild head impacts. Their focus was on signals related to blood vessel stability and repair. They also studied human brain microvascular endothelial cells, which form part of the barrier between the brain and the bloodstream. In these cells, EPA, but not DHA, was linked to reduced repair capacity, aligning with the findings from the animal models. To extend the findings to real-world disease, the team analyzed postmortem brain tissue from individuals diagnosed with chronic traumatic encephalopathy (CTE) who had a history of repeated brain injury. The researchers described the results as having "implications for precision nutrition, therapeutic strategies and the design of dietary interventions targeting brain injury and neurodegeneration." Key Findings From the Study The study identified several major patterns, which are summarized below along with simplified explanations. "In a sensitive brain state modeled in mice, long-term fish oil supplementation revealed a delayed vulnerability. The animals showed poorer neurological and spatial learning performance over time, together with clear evidence of vascular-associated tau accumulation in the cortex, linking impaired recovery to neurovascular dysfunction and perivascular tau pathology," Albayram said. "In the injured cortex, the team observed a coordinated shift in gene programs that normally support vascular stability and repair," Albayram said. "The pattern included reduced expression of genes tied to extracellular matrix organization and endothelial integrity, alongside broader changes consistent with altered lipid handling after injury." Albayram said that in human brain microvascular endothelial cells, EPA did not act as a universal toxin. "Instead, when cells were placed in conditions that encouraged fatty acid engagement, EPA was associated with weaker angiogenic network formation and reduced endothelial barrier integrity, matching key features of the neurovascular repair deficit seen in vivo." "In postmortem cortex from neuropathologically confirmed CTE cases with a history of repetitive brain injury, the researchers found evidence of disrupted fatty acid balance and broad transcriptional changes affecting vascular and metabolic pathways," Albayram said. "This human arm was used to provide translational context, asking whether chronic disease tissue shows convergent signatures of altered lipid handling and reduced vascular stability." What the Findings Mean for Fish Oil Use Albayram stressed that the study should not be interpreted as a blanket warning against fish oil. "I am not saying fish oil is good or bad in some universal way," he said. "What our data highlight is that biology is context-dependent. We need to understand how these supplements behave in the body over time, rather than assuming the same effect applies to everyone." The researchers hope their work encourages a more careful look at omega-3 supplementation, both in clinical settings and among the general public. Their experiments focused on a specific scenario, repeated mild brain injury, and used CTE tissue to provide supporting observations rather than direct proof of cause and effect. "As with any study, there are important boundaries," Albayram said. "In the human CTE tissue, we can observe patterns, but we cannot prove what drove them. We also cannot capture every variable that shapes omega-3 handling in real life, including overall diet, health status and lifestyle." Next Steps in Understanding Omega-3 Effects The team plans to continue investigating how EPA moves through the body, including how it is absorbed, transported, and distributed. They are especially interested in the mechanisms that control fatty acid movement. "This paper is a starting point," Albayram said, "but it is an important one. It opens a new conversation about precision nutrition in neuroscience, and it gives the field a framework to ask better, more testable questions."