Fish Oil Decreases Inflammatory and Atherogenic Gene Expression

Salmon contains more than 2 grams of omega-3 fatty acids per 100 grams.
Salmon contains more than 2 grams of omega-3 fatty acids per 100 grams. (Photo by Marco Veringa)

While the argument over polyunsaturated fats in general continues, most people consider omega-3 fatty acids to be very beneficial.

The most important omega-3 fatty acids are alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). EPA and DHA are often marketed as good for heart health, and indeed there is a lot of evidence to support this claim. ALA, on the other hand, is much less effective, because it first needs to be converted to EPA and DHA by the body to be usable, and only a very small amount gets converted (link).

One of the best and easiest sources of EPA and DHA is fatty fish such as salmon. Another good option is fish oil or fish liver oil, which contain high amounts of EPA and DHA. While several studies have shown beneficial effects from consuming these omega-3 fatty acids, the mechanism of action has not been clear.

To shed light what EPA and DHA actually do in the human body, a new study looked at changes in gene expression after consuming fish oil (link). In healthy subjects, daily ingestion of fish oil changed the gene expression profile to a more anti-inflammatory and antiatherogenic status.

Study method

The study included 111 healthy elderly subjects (at least 65 years old) who did not take fish oil supplements and ate fish no more than four times a week. They were randomized to receive either fish oil with a low or high omega-3 content or sunflower oil.

The high-dose fish oil contained on average 1,093 mg of EPA and 847 mg of DHA, while the low-dose fish oil provided 226 mg of EPA and 176 mg of DHA. The total amounts omega-3 polyunsaturated fatty acids were 1.94 grams and 0.4 grams, respectively. According to the authors, the higher dose is about the same as eating 10 portions of fatty fish weekly, and the lower dose equals 2 portions weekly.

Results

Consuming the high-dose fish oil resulted in gene expression changes of 1040 genes, whereas sunflower oil changed the expression of 298 genes. Out of these, 140 genes were overlapping, meaning that the combination of EPA+DHA uniquely changed 900 genes. Except for one gene, the direction of change was the same in both groups.

Supplementation with a high dose of EPA+DHA for six months significantly decreased the expression of genes involved in the inflammatory pathways, including eicosanoid synthesis, interleukin signaling, and MAP kinase signaling.

Moreover, a similar effect was seen in processes involved in the formation of atherosclerosis. Decreased gene expression was observed in pathways related to cell adhesion, scavenger receptor activity, and adipogenesis. Participants taking the high-dose fish oil also showed a reduction in oxidative stress. You can find the full figures from the paper here and here.

In the low-dose fish oil group, only a small sample of the genes were measured for changes in expression. The results showed that the lower dose of EPA+DHA also resulted in a down-regulation of genes and that this change was somewhere in between those seen from high dose EPA+DHA and sunflower oil.

Conclusion

Supplementing with 1.9 grams of EPA and DHA (~1.1 g EPA and ~0.8 g DHA) daily resulted in favourable changes in gene expression related to inflammation and atherosclerosis in elderly subjects. Among the genes whose expression was decreased were NF-kappa-beta targets, proinflammatory cytokines, and genes involved eicosanoid synthesis.

These results are in agreement with earlier ex vivo studies and support the idea that EPA and DHA, two omega-3 polyunsaturated fatty acids found in fish, are beneficial in reducing inflammation and preventing atherosclerosis.

For more information on inflammation and fish oil, see these posts:

Swine Flu and Avoiding the Cytokine Storm: What to Eat and What Not to Eat?
Examining Possible Causes for Slower Wound Healing
Green Tea Protects from Arthritis in Rats
Intermittent Fasting with a Condensed Eating Window – Part III: Fasting Blood Glucose, Cortisol & Conclusion