Omega-3 and Genetics: Predisposition to Low EPA and DHA Levels

When people talk about omega-3 deficiency, they usually mean a low omega-3 index — the share of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in red blood cell membranes. This marker reflects how well the body has been supplied with these acids over roughly the past four months (NIH Office of Dietary Supplements, Omega-3 Fatty Acids, 2024). In research, the omega-3 index is divided into categories from very low (≤4%) to desirable (>8%) (Schuchardt et al., Prog Lipid Res, 2024).

Humans obtain EPA and DHA mainly from fatty fish, seafood, and fish oil. The plant precursor, alpha-linolenic acid (ALA), can also be converted into EPA and DHA, but the rate of this conversion is less than 15% (NIH Office of Dietary Supplements, Omega-3 Fatty Acids, 2024).

EPA and DHA concentrations in the blood differ even among people with similar diets, including fish intake. These differences are linked to genetic variants in the genes involved in the synthesis of these acids (Xu et al., medRxiv, 2026). For example, in a cross-sectional study of more than 437,000 UK Biobank participants, a polygenic score, which combines the contribution of genetic variants across the whole genome, was associated both with baseline omega-3 levels and with the strength of the relationship between fish oil use and those levels (Xu et al., medRxiv, 2026). 

How Common a Low Omega-3 Index Is

The most comprehensive review to date, which pooled more than three hundred studies from 48 countries and regions, showed that in most countries the average omega-3 index is low or very low (Schuchardt et al., Prog Lipid Res, 2024). The desirable level is reached mainly by people in regions with high fish consumption, notably Finland and Iceland. In France and Spain, the omega-3 index is mostly moderate, while in the USA, Canada, the United Kingdom, Ireland, Italy, and Greece it remains low (Schuchardt et al., Prog Lipid Res, 2024).

This difference between countries is attributed to fish intake. For example, in Japan, where a lot of fish is eaten, the EPA and DHA content in red blood cells is roughly twice as high as in Western populations (NIH Office of Dietary Supplements, Omega-3 Fatty Acids, 2024).

How the Body Synthesizes EPA and DHA from ALA, and Which Genes Are Involved

The synthesis of EPA and DHA from ALA is a chain of reactions: enzymes introduce additional double bonds into the molecule (desaturation) and lengthen the carbon chain (elongation), and the process is completed in peroxisomes (Dyall, Front Aging Neurosci, 2015).

The pathway begins with the desaturation of ALA by the enzyme Δ6-desaturase, which is encoded by the gene FADS2 (Fatty Acid Desaturase 2). This step limits the rate of the entire pathway. After the chain is elongated, Δ5-desaturase, encoded by FADS1 (Fatty Acid Desaturase 1), produces EPA (Dyall, Front Aging Neurosci, 2015).

Next, the enzyme elongase-2, encoded by ELOVL2 (ELOVL Fatty Acid Elongase 2), extends EPA to docosapentaenoic acid (DPA) and then to tetracosapentaenoic acid (24:5n-3). A second Δ6-desaturation converts it into tetracosahexaenoic acid (24:6n-3). These steps take place in the endoplasmic reticulum, while the final stage of DHA formation occurs in the peroxisome after transport (Dyall, Front Aging Neurosci, 2015).

The FADS and ELOVL genes encode the desaturases and elongases needed to synthesize EPA and DHA from ALA. Variants in these genes can affect how much EPA and DHA is produced from ALA (Loukil et al., Genes Nutr, 2024).

For more on the FADS variant and its connection to omega-3 in the diet, see the article “Amino Acids and Fatty Acids: When the Diet Doesn't Cover the Needs”.

Which Genes Are Associated with Blood Omega-3 Levels

In a genome-wide association study (GWAS) that compared DNA variants across the genome with levels of omega-3 fatty acids in plasma phospholipids in nearly nine thousand Europeans, the strongest statistical associations were found for variants in the genes FADS1 and FADS2: the less common variants in them were associated with higher ALA and lower EPA and DPA levels. Less common variants in ELOVL2 were associated with higher EPA and DPA and lower DHA levels (Lemaitre et al., PLoS Genet, 2011).

The authors also found a weaker relationship between ALA and EPA levels in carriers of the less common FADS2 variant and interpreted this as a sign of a lower rate of ALA-to-EPA conversion. In their view, this may matter for people who do not eat fish. In other ethnic groups, the association for FADS1 was replicated, while for ELOVL2 it was replicated only partially.

A review of forty studies confirmed the association of FADS variants with EPA and DHA levels, but it was significant in only about half of the studies. The review authors point to possible reasons: the participants' ancestry, age, and diet, and the blood fraction in which the acids were measured. Where an association was found, carriers of the less common variants usually had lower EPA and/or DHA levels (Loukil et al., Genes Nutr, 2024).

The strongest genetic signal in the FADS gene region explains about 2% of the difference in EPA levels between people (Lemaitre et al., PLoS Genet, 2011). A single such variant cannot predict a particular person's omega-3 level, so researchers combine the contribution of many variants into a polygenic score. The authors of the UK Biobank study calculated a polygenic score for total omega-3 and DHA (Xu et al., medRxiv, 2026). It was based on the results of a genome-wide association study that identified DNA variants linked to blood marker levels, including these fatty acids (Karjalainen et al., Nature, 2024). In people of European ancestry, the polygenic score statistically explains 5 to 11% of the variability in blood concentrations of these fatty acids, while eating fatty fish at least once a week explains 6 to 10% (Xu et al., medRxiv, 2026).

Blood Omega-3 Levels: How Genetics and Diet Interact

The UK Biobank study compared omega-3 levels in people who regularly took fish oil with those who did not, and tested whether the difference between these groups depends on the polygenic score. Among the 5% of Europeans with the lowest polygenic score, that is, a predisposition to lower omega-3 levels, this difference was about 14% greater than among the 5% of Europeans with the highest score. As the polygenic score increased, the difference became smaller. The same pattern was observed for fatty fish consumption. The result was replicated in an independent sample and with other ways of calculating the polygenic score (Xu et al., medRxiv, 2026).

The authors suggest that in people with a predisposition to lower omega-3 levels, intake of these acids from fish or supplements raises their levels more, whereas when the level is already high, raising it further is harder (Xu et al., medRxiv, 2026). The study cannot prove this assumption: it compares different people at a single point in time and shows only an association, not causation. The dose of fish oil was not taken into account either: the researchers analyzed only whether a person takes it.

So omega-3 levels are associated both with whether a person eats fatty fish and takes fish oil and with their genetic profile. How much fish oil the participants took was not examined in the study: they were only asked whether they take it. 

For more on the genetic reasons behind individual responses to vitamin intake, see the article “Why Vitamin Deficiency Isn't Always Solved by Supplements”.

Genetic Predisposition to Higher or Lower Omega-3 Levels: What a DNA Test Shows

Many factors influence omega-3 levels, from dietary composition to genetic variants linked to fatty acid metabolism. A person's diet can change throughout life. The genetic component, by contrast, is constant: the DNA sequence does not depend on lifestyle and does not change with age. The results of a genetic test are information that remains valid for life and, as new research appears, can be reanalyzed without collecting another sample.

The genetic test “Lipids, Cholesterol and Fatty Acids” assesses the genetic predisposition to a higher or lower than population-average level of four omega-3 fatty acids: alpha-linolenic (ALA), eicosapentaenoic (EPA), docosapentaenoic (DPA), and docosahexaenoic (DHA). This predisposition is calculated as a polygenic score that combines the contribution of many DNA variants. The report also shows the genotype for FADS1, FADS2, and ELOVL2 — the genes that encode the enzymes for EPA and DHA synthesis — and describes what biological significance each variant may have.

Frequently Asked Questions

Can you get enough omega-3 from flaxseed oil or nuts alone?

Plant sources contain ALA, not ready-made EPA and DHA. The body converts only a small fraction of ALA into them (by various estimates, from 5–12% into EPA to less than 1% into DHA), and the efficiency of this conversion also depends on variants in the genes FADS1 and FADS2. Therefore, for people who do not eat fish or seafood, plant sources alone are usually not enough for high blood levels of EPA and DHA.

Does the genetic result change with age or after a change in diet?

A person's genetic profile is unchanged throughout life, so the result of the omega-3 genetic analysis remains constant and does not depend on age or diet. What does change is the actual blood level of EPA and DHA, which needs to be monitored with a laboratory test.

How does the omega-3 index test differ from a lipid panel?

A lipid panel measures the levels of various cholesterol fractions and triglycerides in the blood. The omega-3 index is a separate marker that reflects the share of EPA and DHA among all fatty acids in red blood cell membranes (Harris & von Schacky, Prev Med, 2004). 

Genetic test results are not a diagnosis and not a substitute for a medical consultation. The Apixmed Prism report provides genetic context that complements examination results and helps you make decisions together with your doctor.

Sources

1. Dyall, S. C. (2015). Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA. Frontiers in Aging Neuroscience, 7, 52. https://doi.org/10.3389/fnagi.2015.00052

2. Karjalainen, M. K., Karthikeyan, S., Oliver-Williams, C. et al. (2024). Genome-wide characterization of circulating metabolic biomarkers. Nature, 628(8006), 130–138. https://doi.org/10.1038/s41586-024-07148-y

3. Loukil, I., Mutch, D. M., & Plourde, M. (2024). Genetic association between FADS and ELOVL polymorphisms and the circulating levels of EPA/DHA in humans: a scoping review. Genes & Nutrition, 19, 11. https://doi.org/10.1186/s12263-024-00747-4

4. Schuchardt, J. P., Beinhorn, P., Hu, X. F., Chan, H. M., Roke, K., Bernasconi, A., Hahn, A., Sala Vila, A., Stark, K. D., & Harris, W. S. (2024). Omega-3 world map: 2024 update. Progress in Lipid Research, 95, 101286. https://doi.org/10.1016/j.plipres.2024.101286 

5. Xu, H., Yu, G., Lu, Y., Fuller, H., Song, S., Shen, Y., Chiang, C. W. K., Darst, B. F., & Ye, K. (2026). Polygenic predisposition modifies the associations of fish oil supplementation with circulating omega-3 fatty acids: a cross-sectional gene-diet interaction study in UK Biobank. medRxiv https://doi.org/10.64898/2026.04.29.26352078

6. NIH Office of Dietary Supplements. (2024). Omega-3 Fatty Acids: Fact Sheet for Health Professionals. National Institutes of Health. Last updated: December 17, 2024. https://ods.od.nih.gov/factsheets/Omega3FattyAcids-HealthProfessional/