Omega-3s made simple: New biomarkers offer faster and cost-effective testing

17 Oct 2023 --- Scientists have discovered new biomarkers of the omega-3 index (O3I) to trace levels of the fatty acids in the blood, which makes it easier to extract information critical to cardiovascular and cognitive research.

This information was previously more complicated to gather. The new biomarkers will make it easier to study omega-3 fatty acid nutrition in support of population health, including vulnerable groups.

“Formally, the fraction of eicosatetraenoic acid and docosahexaenoic acid (DHA+EPA) relative to total fatty acids from red blood cells is used for omega 3 index determination. These can vary from 15 to more than 40 fatty acids and are measured by gas chromatography, so it is not often standardized,” Philip Britz-McKibbin, lead author of the study and a professor of chemistry and chemical biology at McMaster University, tells Nutrition Insight.

“In contrast, our method demonstrated that two circulating phospholipid species — for example, intact lipids without the need to fractionate blood or hydrolyze lipids to measure fatty acids — provide a direct method for determination of the omega-3 index that is also well correlated to the O3I measured from red blood cells.”

“We anticipate that our discovery may allow for faster, simpler and more cost-effective approaches for the screening of the O3I using small volumes of blood samples, such as plasma or serum,” explains Britz-McKibbin.

Defined by nutrition
Existing tests to measure the O3I require drawing large volumes of blood and complicated laboratory work to analyze the omega-3 fatty acid content. As a result, most clinicians do not routinely measure the index. The new method facilitates regular screening, allowing clinicians and patients to better understand how much supplementation is needed.

The best properties of the current testing method are that it is simple, more cost-effective, better suited for standardization and more practical for higher throughput screening. 

“Despite the clinical utility of screening for the O3I, classical testing methods require access to red blood cells from large blood draws and complicated methods for the analysis of hydrolyzed fatty acids from the phospholipid fraction of red blood cell membranes,” Britz-McKibbin explains.

“Our test can be part of a routine blood test without special requirements. By directly measuring only two specific biomarkers in a blood sample, we can rapidly assess the O3I without time-consuming and costly sample workup protocols before analysis.”

The body gets omega-3s from the diet because it cannot produce enough of these fatty acids. The key omega-3s, EPA and DHA, come from fish, seafood, enriched foods and supplements. However, until now, it has been difficult and invasive to measure its levels in the blood.

Body responses to omega-3s
A lack of omega-3 is associated with inflammation, cognitive impairment, depression, cardiovascular events, fetal neurodevelopment and premature birth.

“If you have an O3I below 4%, you may have a higher risk for cardiovascular events. Conversely, individuals with an O3I above 8% have a lower risk. But since O3I is a modifiable risk factor, you can change it through diet,” says Britz-McKibbin.

Using newly discovered biomarkers to detect omega-3, researchers have found a convenient way to measure the levels in the bloodstream.

he body’s response to omega-3 supplementation can vary significantly between individuals, with distinct health benefits reported for patients who consumed only EPA, DHA, or a mixture.”

From a consumer standpoint, the method can help determine whether individuals are deficient in omega-3 fatty acid intake, whether they may benefit from omega-3 fatty acid supplementation and what dose is optimal to increase their O3I for therapeutic benefit.  

Surrogate biomarkers of the O3I could allow for improved risk assessment of cardiovascular events and other clinical conditions that further augments the utility of existing lipid blood panels for preventative and population health.

“Despite a widespread deficiency in the dietary intake of omega 3 fatty acids globally that is a modifiable risk factor in cardiovascular health, cognition and other health outcomes, routine testing for the O3I is not widely available to the public as current methods are complicated, time-consuming and not standardized,” notes Britz-McKibbin. 

“Our discovery greatly simplifies this process as only two specific phospholipids can be measured directly from small volumes of blood that can be part of routine screening, for example, blood lipid panels from serum such as triglycerides or HDL-cholesterol.” 

Isolating the omega index
Conducted by researchers from McMaster University and the University of Guelph, the observational study in which participants were given between 3-5 grams of fish oil, EPA or DHA supplements daily was published in the Journal of Lipid Research. The researchers conducted lipid profiling to isolate specific O31 biomarkers from hundreds of detectable circulating lipids.

“Our paper used a higher throughput and untargeted lipid profiling strategy based on multi-segment injection-nonaqueous capillary electrophoresis-mass spectrometry (MSI-NACE-MS) as a way to discover novel circulating lipids from plasma or serum extracts that respond to high-dose fish oil as well as EPA-only and DHA-only supplementation,” Britz-McKibbin notes. 

“As there are thousands of potential lipids in a typical blood extract, we aimed to identify the most significant lipids that incorporate DHA and EPA in two independent randomized placebo-controlled trials.” 

This was important to validate dietary lipid biomarkers that are generalizable to fish oil and pure DHA or EPA supplements, given the growing recognition that these major omega-3 fatty acid nutrients may have distinct therapeutic benefits.

The scientists plan to identify a surrogate biomarker of the O3I, which would eliminate the need to draw blood entirely.

“Testing for the O3I is a complicated procedure, so it’s not routinely available for patient screening, despite the popular use of fish oil supplements and promising clinical evidence of the many health benefits from optimal omega 3 fatty acid nutrition,” says Britz-Mckibbin.

“This should make it much more convenient to do routine testing since dosage levels and product formulations differ widely in their exact omega-3 fatty acid composition.”

Meanwhile, Grøntvedt Biotech launched Ceto3 for its cetoleic acid and omega-3 ingredients. 

Also known as “omega-11,” cetoleic acid has been studied for its ability to convert the plant-based omega-3 alpha-lipoic acid into EPA and DHA in liver cells. The product sourced from Norwegian herring finds applications in the heart and skin health arenas. 

By Inga de Jong