Two studies using the relatively novel Omega-3 Index, a method of testing blood concentrations of EPA and DHA developed by OmegaQuant, found that this measurement served as a predictive factor for immune and cellular health outcomes in healthy people.
 
The first study discussed how the omega-3 index (O3I) relates to blood cell membrane distribution of EPA and DHA, and found that a higher O3I resulted in an reduced red blood cell distribution width, which has been shown in prior research to be linked to reduced risk for all-cause mortality. Specifically, red blood cell distribution width is associated with membrane fluidity and deformability. This study relied on blood samples from over 25,000 healthy subjects without high inflammatory markers or anemia, and suggested that an O3I of greater than 5.6% may help maintain normal red blood cell structural and functional integrity.
 
The second study examined immune function in blood samples from a population of 28,871 people. It found that because both a low O3I and elevated neutrophil-lymphocyte ratio (NLR, a biomarker of systemic inflammation and innate-adaptive immune system balance) are linked to increased risk for chronic disease and mortality, there may be a causative factor between the two. In a healthy population, an O3I less than 6.6% was associated with increasing NLR, while those samples with higher O3Is than 6.6% had relatively constant low NLR, suggesting a “quiescent, balanced immune system,” the authors noted.
 
These two studies might help to provide support for establishing Dietary Reference Intakes (DRIs) for EPA and DHA, OmegaQuant said. The company noted that the omega-3 content of red blood cell membranes serves as a stable marker for long-term EPA and DHA intake, and that fatty acids sequestered in red blood cell membranes contribute to structural integrity and affect signaling pathways.
 
Red Blood Cell Structure
 
Red blood cell deformability increases with O3I, so researchers in the first study sought out whether it would result in differences to red blood cell (RBC) structure in healthy people.
 
“We used the RBC distribution width (RDW), measured routinely in hematology labs, as our biomarker of interest because it is a standard way of assessing RBC size heterogeneity, which is related to proper cell membrane deformability,” said Michael McBurney, PhD, FCNS-SCN, FASN, lead author of the study and a consulting scientist with the Fatty Acid Research Institute (FARI). “Although RDW is used clinically to diagnose anemia, it has recently been shown to also predict risk of death from multiple diseases – cardiovascular, SARS-COV-2, sepsis, lung disease, and cancer. Instead of sick people, however, we chose to study healthy people. Why? Because we wanted to determine if RBC EPA and DHA levels were associated with RBC structure and function in non-disease states.”
 
The researchers indeed found a relationship, noting that a higher O3I was significantly associated with a lower and therefore better RDW.
 
Immunity
 
Innate immune cells such as neutrophils destroy enzymes and acids from being released by dead or dying cells that can damage adjacent healthy cells, the authors of the study noted. The adaptive system, on the other hand, consists of cells with learned ability to attack cells with certain markers. The neutrophil-lymphocyte ratio (NLR) measures the balance between the innate and adaptive immune system, and also serves as a biomarker of systemic inflammation, and predicts a higher risk of death from multiple chronic diseases. A normal NLR is roughly one through three, with a score above six indicating mild stress and above nine signaling critical illness.
 
“As stated previously, DRIs are reserved for the general, healthy population. Because one of our long-term goals at FARI is to generate scientific support for EPA + EPA DRIs, we also restricted this study to healthy people […] we tried to minimize the chance for critics to claim our findings were disease-related,” McBurney said.
 
Because the results came from healthy, non-inflamed individuals, the researchers said that the observed relationship suggests that blood EPA and DHA levels play a role in maintaining a balanced immune system, and therefore serves as evidence of a nutrient – structure-function relationship in healthy people.
 
“The NLR paper may be particularly important because most nutrition-immune studies measure circulating levels of inflammatory molecules […] making them disease-related findings,” McBurney said. “This is a report of an association between nutrient status and immune function/balance based on cells in healthy people.”
 
“These two reports linking a high omega-3 index with low levels of two novel biomarkers – RDW and NLR – help us understand a little better why omega-3 fatty acids are good for us,” William S. Harris, PhD, FASN, senior author on both studies and president of FARI, said.