Nutrition Notes

Fish Oil’s Role in Insulin Resistance​

With the continual and increasing prevalence of diabetes and other metabolic disorders, finding treatments remains a top priority. To identify beneficial remedies, researchers look to target different potential underlying mechanisms of the disorder. One such possible player in the pathogenesis of insulin resistance is chronic low-grade inflammation.

Fish Oil and Inflammation

Among the many players in inflammatory balance are the omega-3 and omega-6 fatty acids. These essential fatty acids contribute to many body mechanisms (including the inflammatory response) in complex ways still under investigation. In simplified terms, omega-6 fatty acids generally act to stimulate inflammatory responses, and omega-3 fatty acids stimulate anti-inflammatory responses. As such, a higher omega 6 to omega 3 ratio could contribute to chronic inflammation, and studies suggest the ideal ratio somewhere between 4:1 and 1:1. Fish oil supplementation is rich in omega-3 fatty acids and has been shown to provide anti-inflammatory responses among its health benefits. Could this mean fish oil may have the potential to help improve insulin resistance?

Fish Oil and Metabolic Function

One double-blind, randomized, parallel-arm, placebo-controlled study tested the impact of fish oil supplementation on insulin resistance, including a potential sex-dependent effect. The participants in this study did not have diabetes, but they did present with abdominal obesity. The groups took either fish oil (2 g, consisting of 860 mg of DHA and 120 mg of EPA) or a placebo (2 g of corn oil) for 12 weeks. Taking the fish oil led to a significantly lower fasting insulin level, with a change of −1.62 µ IU/L compared to the placebo group. Likewise, the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was significantly reduced, with a change of −0.40 units. There were no significant differences between the sexes. While this population did not have diabetes, insulin resistance is correlated with abdominal obesity.

Additionally, a systematic review and meta-analysis found that while fish oil did not affect insulin sensitivity compared to a placebo in the general population, it did affect those who had at least one symptom of metabolic disorder, particularly in the short-term. In this subgroup analysis, fish oil supplementation led to a 47% reduction in the risk of insulin resistance.

Biological Actions Fundamental to the Benefits

Where does inflammation come into play? Adipose tissue does much more than store excess energy in the form of fat. Adipose tissue also exhibits autocrine, paracrine, and endocrine functions that play a role in glucose homeostasis and immune function. As such, it can also play a role in inflammation, specifically through releasing hypoxia-inducible factor-1. It may also exhibit a two-way relationship. Not only does excess adipose tissue lead to releasing this inflammatory trigger, but chronic inflammation also causes macrophages to activate and fibrosis to occur. This inflammation and immune activation interrupts insulin signaling, resulting in insulin resistance.

In addition to the anti-inflammatory properties, fish oil may impart immunomodulatory effects and creates a healthier adipose tissue, especially in white adipose tissue. Additional potential mechanisms include improving mitochondrial function in skeletal muscle, increased AMPK activation, and the activation of peroxisome proliferator-activated receptor gamma, and reducing endoplasmic reticulum stress, which is associated with inflammation.

More research may be required to continue to elucidate the reasons for the health benefits of fish oil. However, it appears that incorporating fish oil as part of a comprehensive management plan that also includes dietary and lifestyle adjustments may have a positive impact on insulin sensitivity and blood sugar metabolism.


By Kendra Whitmire, MS, CNS