Role of Omega-3 Index Testing in Inflammation & Cardiovascular Health

As our understanding of nutrition evolves, the spotlight on omega-3 fatty acids has intensified, revealing their profound impact on our well-being, particularly in mitigating inflammation and supporting cardiovascular health. Despite their essential health benefits, research from the National Health and Nutrition Examination Survey (NHANES) demonstrates that over 90% of Americans are not meeting recommendations for omega-3 intake. The Omega-3 Index has emerged as an essential tool in preventing and managing inflammatory conditions, providing a snapshot of an individual's omega-3 status and offering tangible data on whether dietary intake aligns with recommended levels.

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What Are Omega-3 Fatty Acids? 

Omega-3 fatty acids are a family of polyunsaturated fats. Polyunsaturated fats are characterized by their chemical structure, specifically the presence of more than one unsaturated carbon bond in their fatty acid chains. Unlike saturated fats, which lack double bonds between carbon atoms, and monounsaturated fats, which have one double bond, polyunsaturated fats contain two or more double bonds. These fats are essential because the human body cannot produce them naturally and must obtain them through the diet. Two primary types of polyunsaturated fats include omega-3 fatty acids and omega-6 fatty acids, which play crucial roles in various physiological functions. Scientists recommend that we eat a balance of 2:1 omega 6:omega three fatty acids in our diet. 

Still, it is estimated that Americans consume closer to 20 times more omega-6 fatty acids than omega-3 fatty acids. Balancing the consumption of polyunsaturated fats as part of a well-rounded diet. There are a few essential types of omega-3 fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the most biologically active forms found predominantly in fatty fish such as salmon, mackerel, and trout, and alpha-linolenic acid (ALA), found primarily in plant oils, walnuts, chia seeds, and flax seeds. ALA can be converted into EPA and DHA, but the conversion rate is limited.

One of omega-3 fatty acids’ pivotal functions is acting as a potent anti-inflammatory agent regulating the body's immune responses. This anti-inflammatory property is particularly significant in mitigating the risk of chronic diseases associated with inflammation, such as autoimmune diseases and cardiovascular disease. Furthermore, these fatty acids are integral components of cell membranes, especially in the brain where DHA is abundant, influencing cognitive function, mood, and brain health.

What is the Omega-3 Index Test? 

The Omega-3 Index, a blood test, is the sum of EPA and DHA in red blood cell membranes expressed as a percentage of the total fatty acids. The red blood cell membrane concentration was chosen, as opposed to using plasma concentration, for example, because omega-3 fatty acids primarily exert their effects from within cell membranes. The omega-3 index is reflective of dietary intake and is a more sensitive marker than relying on nutritional questionnaires and recall. 

The omega-3 index is negatively associated with inflammatory markers such as c-reactive protein (CRP) and interleukin-6 (IL-6), indicating its potential role in mitigating inflammation, a critical factor in cardiovascular health. In the Physicians’ Health Study, the omega-3 index was compared to other established cardiovascular risk factors such as CRP, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, and homocysteine. The omega-3 index performed comparably, if not superiorly, in predicting the risk of coronary heart disease mortality, particularly sudden cardiac death. 

An optimal target level of the Omega-3 Index is 8%, and an undesirable level is less than 4%, with 4–8% considered an intermediate-risk zone. An Omega-3 Index of ≥8% is associated with the greatest cardioprotection, whereas an index of ≤4% was associated with the lowest and highest risk of cardiac events.

Beyond the standard omega-3 index test, some functional labs are available to further assess fatty acid status, such as Ayumetrix’s Omega-3 Index Complete or Mosaic’s Omega-3 Index Complete tests. These tests use dried blood spots for collection and report the omega-3 index, the levels of all 24 fatty acids, the omega-3:omega 6 ratio, and the trans-fat index to provide a more complete picture of one’s fatty acid status.  

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Omega-3 Fatty Acids and Inflammation 

Scientists have shown that maintaining an optimal Omega-3 Index is a powerful defense against chronic and uncontrolled inflammation. Maintaining a proper balance of omega-3s and omega-6s in the diet is critical for balancing the immune system’s inflammatory responses. While scientists recommend a ratio of approximately 2:1 omega-6 to omega-3, the reality is that most Americans consume an estimated 20 times more omega-6s than omega-3s. This imbalance in dietary fatty acids may contribute to the higher rates of chronic inflammatory diseases associated with Western-style diets. 

Fatty acids are an integral component of cell membrane phospholipids, with specific functional, metabolic, and signaling roles. Released from these membranes, they give rise to produce eicosanoids, which are signaling molecules involved in various physiological processes, including inflammation. Coordinating different immune cells and regulating their activity is crucial for mounting effective and appropriate immune responses. This coordination and regulation is accomplished through the secretion of these chemical signals. The omega-3:omega-6 composition of cell membranes influences eicosanoid signaling. While omega-6 fatty acids like arachidonic acid give rise to pro-inflammatory eicosanoids, omega-3 fatty acids like EPA give rise to anti-inflammatory eicosanoids.

Beyond eicosanoid modulation, omega-3 fatty acids impact inflammation by activating antioxidant signaling pathways and modulating the gut microbiome. They enhance antioxidant enzyme expression, countering inflammatory free radicals. Omega-3’s also shape the gut microbiome towards a composition that promotes the production of short-chain fatty acids (SCFAs), enhances intestinal barrier function, and reduces inflammation.  

Common chronic diseases such as autoimmune diseases, depression, cancer, and coronary heart disease are all characterized by higher levels of inflammatory signaling molecules. Clinical trials in humans have shown that increasing omega-3 fatty acid levels through supplementation provides benefits in autoimmune diseases like rheumatoid arthritis (RA), Crohn’s disease, ulcerative colitis (UC), psoriasis, systemic lupus erythematosus (SLE), and multiple sclerosis (MS). Symptoms of the COVID-19 virus range drastically between individuals, and symptom severity seems at least partially related to the strength of the individual's immune-inflammatory response. Patients with higher omega-3 indices had approximately a 75% lower risk for mortality than those under 5.7%.

Omega-3s and Cardiovascular Health

Research has consistently demonstrated the cardioprotective effects of omega-3 fatty acids, establishing them as crucial components of a heart-healthy lifestyle. Higher levels of omega-3 fatty acids are associated with a reduced risk of various cardiovascular conditions, including heart diseases such as coronary artery disease (CAD) and myocardial infarction (MI), as well as arrhythmias and hypertension (28, 37, 45).

There are several potential mechanisms for their favorable effects on the cardiovascular system. Omega-3 fatty acids improve lipid profiles, lowering triglyceride levels and increasing high-density lipoprotein (HDL) cholesterol levels. High-density lipoproteins remove excess cholesterol from peripheral tissues and transport it back to the liver, preventing the accumulation of cholesterol in the arteries. On the other hand, triglycerides lead to the production of remnant lipoproteins that contribute to plaque formation by stimulating immune cells inside arterial walls and triggering the endothelial cells to produce adhesion molecules and inflammatory mediators. Elevated levels of several inflammation markers, such as C-reactive protein (CRP) and fibrinogen, have been reported in CVD studies, and when these markers’ levels are reduced, CVD’s severity decreases. 

In hypertriglyceridemic patients, omega-3 fatty acid supplementation significantly reduced markers of inflammation and oxidative stress, including oxidized LDL cholesterol (Ox-LDL) and high-sensitivity CRP levels. Omega-3-derived eicosanoids are less vasoconstrictive and reduce platelet aggregation than those derived from omega-6 fatty acids. Endothelial function is also improved by promoting the release of nitric oxide (NO). Nitric oxide signals the relaxation of the smooth muscle cells that line blood vessels. This relaxation, known as vasodilation, expands the vessel diameter, enhancing blood flow and lowering blood pressure. Omega-3s have been shown to modulate the behavior of sodium and potassium channels, which are critical components in generating and conducting electrical signals in the heart. By affecting these channels, omega-3s contribute to the stabilization of the electrical impulses, helping to prevent abnormal rhythms and reduce the risk of arrhythmia.

Interpreting Omega-3 Index Test Results 

Intake of total omega-3 fatty acids in the US is approximately 1.6 grams per day, 0.1-0.2 grams per day from EPA and DHA, and 1.4 grams per day from ALA. However, research suggests that intakes closer to 0.5 to 1.8 grams per day of combined EPA and DHA and 1.5 to 3 grams per day of ALA are beneficial for cardiovascular health. The American Heart Association guidelines recommend including at least two servings of fatty fish per week. Individuals are encouraged to attain these omega-3 fatty acids through a balanced diet but may consider supplementation when dietary intake is insufficient. 

Fish and other seafood are components of the Mediterranean diet. The emphasis on healthy fats like monounsaturated fats from olive oil and omega-3 fatty acids in fish contributes to improved lipid profiles. Antioxidants from high intakes of fruits and vegetables combat oxidative stress and inflammation. Multiple studies have shown that this diet reduces cardiovascular risk factors and the rate of cardiovascular events, including MI and stroke. 

Omega-3 fatty acids are present in several dietary supplement formulations, including fish oil, krill oil, cod liver oil, and algae oil. Seafood can contain contaminants like mercury, so choosing high-quality, third-party-tested supplements helps to mitigate the risk of mercury exposure. The dose of omega-3 supplements can vary. For those with existing cardiovascular conditions or with multiple risk factors, higher doses between 1,000-4,000 milligrams may be recommended. These higher doses should only be guided under the supervision of a healthcare provider who can assess each individual’s health status and specific cardiovascular risks.

Enhancing Omega-3 Levels 

Intake of total omega-3 fatty acids in the US is approximately 1.6 grams per day, 0.1-0.2 grams per day from EPA and DHA, and 1.4 grams per day from ALA. However, research suggests that intakes closer to 0.5 to 1.8 grams per day of combined EPA and DHA and 1.5 to 3 grams per day of ALA are beneficial for cardiovascular health. The American Heart Association guidelines recommend including at least two servings of fatty fish per week. Individuals are encouraged to attain these omega-3 fatty acids through a balanced diet but may consider supplementation when dietary intake is insufficient. 

Fish and other seafood are components of the Mediterranean diet. The emphasis on healthy fats like monounsaturated fats from olive oil and omega-3 fatty acids in fish contributes to improved lipid profiles. Antioxidants from high intakes of fruits and vegetables combat oxidative stress and inflammation. Multiple studies have shown that this diet reduces cardiovascular risk factors and the rate of cardiovascular events, including MI and stroke. 

Omega-3 fatty acids are present in several dietary supplement formulations, including fish oil, krill oil, cod liver oil, and algae oil. Seafood can contain contaminants like mercury, so choosing high-quality, third-party-tested supplements helps to mitigate the risk of mercury exposure. The dose of omega-3 accessories can vary. For those with existing cardiovascular conditions or with multiple risk factors, higher doses between 1,000-4,000 milligrams may be recommended. These higher doses should only be guided under the supervision of a healthcare provider who can assess each individual’s health status and specific cardiovascular risks.

Integrating Omega-3 Index Testing into Healthcare 

Healthcare professionals can and should incorporate omega-3 testing into preventative healthcare, particularly for individuals at risk for cardiovascular and other chronic inflammatory diseases. The omega-3 index is a valuable biomarker in providing an objective and accurate assessment of fatty acid status so healthcare professionals can tailor preventative dietary strategies appropriately for each patient. Healthcare professionals regularly check biomarkers such as lipids, glucose, and blood pressure to assess cardiovascular risk. Results are used to institute treatments that modulate these risk factors, and providers continue to track these markers for improvement. The omega-3 index can be utilized in the same way. First, the baseline index should be determined. If greater than 8%, no changes need to be recommended. If less than 8%, especially if less than 4%, recommendations for increasing intake or beginning supplementation can be made. 

Re-testing is recommended at 4-6 month intervals because that is how long it can take the fatty acid concentration of cell membranes to change. By monitoring the omega-3 index over time, providers can track progress and make informed adjustments to health plans. This holistic approach empowers healthcare professionals and patients to proactively address cardiovascular risks and chronic inflammation, fostering a preventive health strategy that is tailored and effective.

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Omega-3 Index Testing: Final Thoughts

The omega-3 index is an invaluable tool in understanding and monitoring omega-3 fatty acid levels to properly manage inflammation and promote cardiovascular health. This precise biomarker provides better insights than relying on dietary recall alone. It allows healthcare practitioners and patients to take a proactive approach to optimize fatty acid intake through nutritional modifications or supplementation, thereby preventing chronic inflammatory conditions and promoting optimal well-being.