Location: Obesity and Metabolism Research
Title: Inverse association between the omega-3 index and neutrophil-lymphocyte ratio: Pooled results from four supplementation trialsAuthor
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MCBURNEY, MICHAEL - University Of Guelph |
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TINTLE, NATHAN - Fatty Acid Research Institute |
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WESTRA, JASON - University Of Illinois |
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PLOURDE, MELANIE - Universite De Sherbrooke |
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FLOCK, MICHAEL - University Of Pittsburgh |
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MUTCH, DAVID - University Of Guelph |
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Stephensen, Charles |
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Newman, John |
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HARRIS, WILLIAM - University Of South Dakota |
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Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 6/5/2026 Publication Date: 6/10/2026 Citation: Mcburney, M.I., Tintle, N., Westra, J., Plourde, M., Flock, M., Mutch, D., Stephensen, C.B., Newman, J.W., Harris, W.S. 2026. Inverse association between the omega-3 index and neutrophil-lymphocyte ratio: Pooled results from four supplementation trials . Journal of Nutrition. 156(87). https://doi.org/10.1016/j.tjnut.2026.101663. DOI: https://doi.org/10.1016/j.tjnut.2026.101663 Interpretive Summary: The Omega-3 Index (O3I) is a measure of long chain omega-3 fatty acids in the red blood cells that has been inversely correlated with the neutrophil-lymphocyte ratio (NLR), a measure of systemic inflammation, and red blood cell distribution width (RDW), a measure of the variation in red blood cell size. This study evaluated the effects of long chain omega-3 fatty acid interventions on O3I, NLR, and RDW values in healthy adults. Data from 4 controlled, omega-3 supplementation trials (combined n =436 participants) were measured to determine the pooled effect of treatment on changes (') in O3I, NLR and RDW. Additionally, we examined how 'O3I were associated with 'NLR and, separately, 'RDW. An average of ~1g/d of omega-3 fatty acid increased O3I ('O3I =3.28%, p<0.001) and decreased ('NLR = -0.15; p <0.001), but did not effect RDW. 'NLR values were inversely correlated with 'O3I in unadjusted (-0.13, p <0.05) and baseline adjusted (-0.10, p<0.05) models. Therefore, in healthy adults, omega-3 fatty acid supplementation that increases the O3I can reduce the NLR, suggesting a lowering of systemic inflammation. Further clinical trials are needed to determine if the size of this change in NLR can affect clinical outcomes in individuals at increased risk of morbidity and mortality. Technical Abstract: Background: The Omega-3 Index [O3I, blood eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content], has been inversely correlated with neutrophil-lymphocyte ratio (NLR) and red blood cell distribution width (RDW). Objective: This study evaluated the effects of EPA+DHA interventions on O3I, NLR, and RDW values in healthy adults. Methods: In this de novo, individual level analysis, pre- and post-intervention O3I, NLR and RDW values from 4 controlled, omega-3 supplementation trials (combined n =436) were measured to determine the pooled effect of treatment on changes (') in O3I, NLR and RDW. Additionally, we examined how changes in O3I were associated with changes in NLR and, separately, RDW. Effect estimates were obtained using linear mixed effects models, using a statistical significance threshold of 0.05. Results: EPA+DHA supplementation (mean= 1160 mg/d) increased O3I ('O3I =3.28%, p<0.001) whereas O3I levels (n =253) decreased ('O3I= -0.62, p<0.001) in the untreated group (n =183). NLR decreased ('NLR = -0.15; p <0.001) in the group supplemented with EPA+DHA but did not show evidence of change in the untreated group. RDW increased in the untreated group (p <0.01) but did not show evidence of change with EPA+DHA. 'NLR values were inversely correlated with 'O3I in unadjusted (-0.13, p <0.05) and baseline adjusted (-0.10, p<0.05) models. There was no evidence of association of 'O3I with 'RDW. Conclusions: In healthy adults, EPA+DHA supplementation increased the O3I, reduced NLR and 'O3I was inversely correlated with 'NLR. RDW increased 1% in the untreated but there was no relationship between 'RDW and 'O3I. Further clinical trials are needed to determine if O3I causes biologically relevant changes in NLR, and possibly RDW, to affect clinical outcomes in individuals at increased risk of morbidity and mortality. |
