Cracking the code: omega-3 and omega-6 fatty acids' impact on glucose metabolism

In a recent study published in the Nutrients journal, researchers explored the impact of omega 3 (ω-3) and omega 6 (ω-6) fatty acids (FAs) on glucose metabolism.

Study: The Effects of Omega 3 and Omega 6 Fatty Acids on Glucose Metabolism: An Updated Review. Image Credit: MarynaOlyak/Shutterstock.comStudy: The Effects of Omega 3 and Omega 6 Fatty Acids on Glucose Metabolism: An Updated Review. Image Credit: MarynaOlyak/


ω-6 and ω-3 FAs are essential dietary polyunsaturated fatty acids (PUFAs) that are derived from linoleic acid (LA) and α-linolenic acid (ALA), respectively. The increased intake of plant-based oils containing omega-6 FAs and a decrease in omega-3 FAs in our diet has resulted in an imbalance between these two types of fatty acids.

Particularly, the eicosapentaenoic (EPA)/arachidonic acid (AA) ratio is believed to be a marker of metabolic dysfunction, with lower levels being linked to the onset of conditions like diabetes mellitus.

The objective of the present study is to review existing literature on the impact of omega-3 and omega-6 FAs on glucose metabolism.

Interaction between PUFAs and glucose metabolism

The global prevalence of type 2 diabetes mellitus (T2DM) has risen 102.9% over the past 30 years. Diet is a significant factor in causing health issues, among other factors like aging, smoking, and lack of physical activity. The quantity and quality of food consumed are believed to be major contributors to these problems.

For example, consuming too much sugar increases the likelihood of developing T2DM. Studies suggest a possible contributing factor is the high intake of vegetable oils containing ω-6 FAs and the low intake of foods rich in ω-3 FAs.

Furthermore, AA can lead to insulin resistance (IR) by creating a proinflammatory state that is conducive to the development of IR via a process that is dependent on tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1 β).

The increased consumption of refined carbohydrates contributes to the production of amino acids and stress on pancreatic cells. Epidemiological studies have shown that populations with a fish-rich diet, which contains ω-3 fatty acids, experience a notable improvement in glucose metabolism.

Also, in vitro studies have shown that EPA treatment can enhance glucose absorption in human skeletal muscle cells. This process appears to be caused by an increase in the movement of glucose transporter 1/4 (GLUT1/4) to the plasma membrane, as well as mechanisms that do not rely on GLUT.

Omega-3 fatty acids can potentially improve insulin resistance by improving mitochondrial function and beta-oxidation, regulating the secretion of adipocytokines, and inhibiting the remodeling of adipose tissue.

The anti-inflammatory effect is a notable positive metabolic outcome of ω-3 FAs. The cytokines TNF-α and IL-1β , which are linked to insulin resistance, are reduced by EPA and docosahexaenoic acid (DHA) through the inhibition of the Nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kB) pathway.

Evidence from existing literature

Multiple meta-analyses have examined how linoleic acid (LA) affects the onset of T2DM. The study found that consuming high amounts of dietary LA and having high LA concentrations in the body were linked to a decreased risk of T2DM, indicating that LA may have a protective effect against the disease.

High LA levels may be due to a high dietary consumption or low ∆5 and ∆6 desaturase activity caused by genetic variants of the enzymes. Some authors also note that LA could have negative metabolic effects as it can be converted into AA, a precursor to the inflammatory cascade. This suggests that a careful interpretation of the positive cardiometabolic effects of LA may be necessary.

The team also found that icosapent ethyl (IPE)-treated mice exhibited reduced weight compared to control-high-fat diet (HFD) mice. Mice treated with IPE showed improved fasting blood insulin and glucose levels, decreased insulin secretion, and better glucose tolerance. The study found that the effects of EPA + DHA treatment on mice were less significant compared to other treatments in all analyzed outcomes.

Also, improved glucose homeostasis was observed with IPE or EPA + DHA treatment, but only when administered during an HFD. The authors proposed that the observed effects could be attributed to increased FA oxidation, decreased hepatic triglycerides (TGs), altered branched-chain amino acid (BCAA) and sphingolipid metabolism, and reduced inflammation.

A study that randomly assigned impaired glucose metabolism (IGM) and coronary artery disease (CAD) patients to either receive EPA or no treatment showed that the EPA group demonstrated a rise in the EPA/AA ratio and experienced significant improvements in lipid profile and glucose homeostasis, with respect to postprandial blood glucose.

The findings suggest that EPA could offer more protection against TD2M in pre-diabetic patients.


According to pre-clinical studies, ω-3 may benefit glucose metabolism due to its insulin-sensitizing and hypoglycemic effects. Clinical trial results remain inconclusive due to the varied nature of the studies included. The inconsistent findings of studies on the effects ω-3 may be attributed to factors such as the source of ω-3, ethnicity, sample size, study duration, and food cooking method.

Studies suggest that high levels of LA may be linked to a lower risk of T2DM, but it is uncertain whether this is due to a decrease in AA production or the inherent effects of LA. A low EPA/AA ratio can indicate poor glycometabolic control and increased inflammation in diabetic and non-diabetic individuals.

Further knowledge about the correlation between glucose metabolism and EPA/AA ratio requires prospective randomized clinical trials.

Journal reference:
Bhavana Kunkalikar

Written by

Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.


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