Fish oil: Your genotype may tell you to take it or not

Last Updated on May 1, 2021 by Joseph Gut – thasso

May 01, 2021 – Fish oil supplements are a billion-dollar industry built on a foundation of a huge array of studies, sometimes with contra-dictionary outcomes, indicating a reduction of serum triglycerides (TAGs) but somewhat mixed effects on other circulating cardiovascular biomarkers. Genetic polymorphisms have been associated in the past with blood lipids, including high- and low-density-lipoprotein cholesterol (HDL-C, LDL-C), total cholesterol, and triglycerides (TAGs). Here, the gene-diet interaction effects of fish oil supplementation on these lipids.

Now, new research from a team led by a University of Georgia scientist indicates that taking fish oil may only provide health benefits if you have the right genetic makeup. The study, published in PLOS Genetics, focused on fish oil (and the omega-3 fatty acids it contains) and its effect on triglycerides (TGAs) levels in the blood and as biomarker for cardiovascular disease.

It is known for a few decades that a higher level of omega-3 fatty acids in the blood is associated with a lower risk of heart disease. Hoverver, it seems that fish oil supplementation is not good for everyone, according to the present study.  The effect seems to depend on an individual’s genotype. If you have a specific genetic background, then fish oil supplementation will help lower your triglycerides. But if you do not have that right genotype, taking a fish oil supplement actually increases your triglycerides.

In the present study, the research team examined four blood lipids (fats), namely high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), total cholesterol and triglycerides (TGAs) that all are biomarkers for cardiovascular disease. The data for their sample of 70,000 individuals was taken from UK Biobank, a large-scale cohort study collecting genetic and health information from half a million participants.

The team divided the sample into two groups, those taking fish oil supplements (about 11,000) and those not taking fish oil supplements. Then they performed a genome-wide scan for each group, testing for 8 million genetic variants to compare. After running over 64 million tests, their results revealed a significant genetic variant at the gene GJB2, coding for the gap junction beta-2 protein (GJB2), also known as connexin 26 (Cx26). Thus individuals with the AG genotype who took fish oil decreased their triglycerides. Individuals with the AA genotype who took fish oil slightly increased their triglycerides. A third possible genotype, GG, was not evident in enough study volunteers to draw conclusions.

Determining an individuals genotype is not as far-fetched as it sounds, thanks to direct-to-consumer genetic testing companies. Companies may not report that specific genetic variant yet, but a tech-savvy consumer should be able to download the raw data and look at the specific position to discover his pertinent genotype at the GJB2 locus.. The ID for the variant is rs112803755 (A>G).

Looking at earlier fish oil studies

The study’s findings may also shed light on previous trials, most of which found that fish oil did not provide a benefit in preventing cardiovascular disease. One possible explanation is that those clinical trials didn’t consider the underlying genotypes of the participants. If so, some participants may benefit, and some may not; so if you mix them together and do the analysis, you may not see the impact.

Since now that a specific gene has been identified that can modify an individual’s response to fish oil supplementation, the next step would be directly testing the effects of fish oil on cardiovascular disease.

The resulting option of personalizing and optimizing fish oil supplementation recommendations based on a person’s unique genetic composition could largely improve our understanding of nutrition, and lead to significant improvements in human health and well-being, i.e., in nutrigenomics.

See here a short sequence on fish oil and omega-3 fatty acids: