Omega-3 fatty acids are vital polyunsaturated fats crucial for maintaining optimal health.
Polyunsaturated fats (PUFA) are fatty acids that contain more than one double bond in their carbon chain. These fats are essential components of the diet because the body cannot synthesize them.
The primary types of omega-3s include docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and alpha-linolenic acid (ALA). DHA and EPA, found mainly in fatty fish and algae, are directly involved in numerous physiological processes. ALA, present in plant sources like flaxseed and walnuts, serves as a precursor to DHA and EPA, although its conversion rate in the human body is relatively low (typically less than 1% for the conversion of ALA to DHA, and around 5-10% for ALA to EPA). This conversion involves several enzymatic steps, with genetic factors playing a significant role in this process. We will look at these genetic factors in detail below.
Omega-3s are commonly touted for their health benefits. They are indispensable for cardiovascular health, as they help reduce triglycerides, lower blood pressure, and inhibit plaque formation in arteries. They also play a crucial role in cognitive function, supporting brain structure and function, which is particularly significant for memory and learning. Furthermore, they possess potent anti-inflammatory properties, aiding in the reduction of chronic inflammation and the management of conditions like arthritis.
Omega-3s operate through several mechanisms and pathways. They modulate cell membrane fluidity, which influences receptor function and cellular signaling. Omega-3s also serve as precursors for eicosanoids, bioactive compounds that regulate inflammation and immunity. Additionally, they interact with nuclear receptors to influence gene expression involved in lipid metabolism and inflammatory responses.
Nuclear receptors are proteins within cells that regulate gene expression in response to hormones.
We look at the influence of omega-3 on gene expression in a different article. Here, we focus on the genetic variants that affect omega-3 metabolism and how they impact the body’s ability to produce these essential fatty acids effectively.
Conversion of ALA to EPA and DHA
The conversion of ALA to EPA and DHA relies on enzymatic processes. First, ALA is converted to stearidonic acid (SDA) by the enzyme delta-6 desaturase encoded by the FADS2 gene. Subsequently, stearidonic acid undergoes elongation by elongase enzymes (encoded by ELOVL genes, see below), to form eicosatetraenoic acid (ETA) which is further converted to EPA by the delta-5 desaturase enzyme encoded by the FADS1 gene.
The conversion of EPA to DHA happens in two steps: first, EPA is elongated by the same elongase enzymes to docosapentaenoic acid (DPA), and finally DPA is converted to DHA by delta-6 desaturase enzymes.
Genetic variants affecting omega-3 metabolism
FADS1 and FADS2 (Fatty Acid Desaturase 1 and 2)
Common polymorphisms: rs174537 and rs174546
Genetic polymorphisms in the FADS1 and FADS2 genes can significantly impact the efficiency of these conversion processes. Two common single nucleotide polymorphisms (SNPs) in these genes are rs174537 and rs174546. These polymorphisms are associated with variations in the desaturase activity, affecting the body’s ability to convert ALA to EPA and DHA.
- rs174566: Located near the FADS1 gene, this SNP has been shown to influence the enzyme’s efficiency. Individuals with certain alleles may have a reduced capacity to produce EPA and DHA from ALA, leading to lower levels of these essential fatty acids in the body.
- rs174546: This SNP is situated in the FADS2 gene and also affects desaturase activity. Similar to rs174537, variations in rs174546 can result in differing abilities to synthesize long-chain omega-3s from ALA.
These genetic variations can lead to a decreased conversion efficiency, which may necessitate higher dietary intake of EPA and DHA to achieve optimal health benefits.
ELOVL2 (Elongation of Very Long Chain Fatty Acids)
rs953413
This SNP can affect the activity of the elongation enzyme, influencing the overall efficiency of DHA synthesis. People carrying specific alleles of rs953413 may have altered DHA levels, impacting their ability to maintain sufficient DHA for optimal brain and cardiovascular health.
Summary table
| Gene | rsid | Ref | Alt | Effect |
|---|---|---|---|---|
| FADS1 | rs174566 | A | G | Lowers SDA to EPA conversion |
| FADS2 | rs174576 | C | A | Lowers ALA to SDA conversion. |
| ELOVL2 | rs953413 | G | A | Lowers EPA to DHA conversion. |
Recommendations
For adults, the general recommendation ranges from 250 to 500 mg per day of combined EPA and DHA. Those whose conversion process is compromised due to polymorphisms in the FADS1 and FADS2 genes shouldn’t rely solely on ALA-rich plant sources to their physiological needs. Ensuring an adequate intake of EPA and DHA from direct sources, such as fatty fish or algae supplements, can help mitigate potential deficiencies and support overall health.
References
- de Toro-Martín J et al. A common variant in ARHGEF10 alters delta-6 desaturase activity and influence susceptibility to hypertriglyceridemia
- Kaitlin Roke et al. FADS2 genotype influences whole-body resting fat oxidation in young adult men.
- Lemaitre et al. Genetic loci associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium.