Red blood cell omega-3 fatty acid content is a significant predictor of all-cause mortality

William S. Harris, PhD’ Correspondence information about the author PhD William S. Harris Email the author PhD William S. Harris, Juhua Luo, PhD, James V. Pottala, PhD, Mark A. Espeland, PhD, Karen L. Margolis, MD, MPH, Joann E. Manson, MD, Dr PH, Lu Wang, MD, PhD, Theodore M. Brasky, PhD, Jennifer G. Robinson, MD, MPH

Highlights

  • Relations between red blood cell fatty acids and total mortality were studied in 6501 women.
  • Multivariable adjusted odds ratios per 1 standard deviation increase in fatty acid levels were calculated.
  • There was an 8% reduction in risk associated with higher eicosapentaenoic acid plus docosahexaenoic acid levels.
  • Red blood cell omega-3 fatty acid content is a significant predictor of all-cause mortality.

Background

The prognostic value of circulating polyunsaturated fatty acid (PUFA) levels is unclear.

Objectives

To determine the associations between red blood cell (RBC) PUFA levels and risk for death.

Methods

This prospective cohort study included 6501 women aged 65 to 80 years who participated in the Women’s Health Initiative Memory Study (enrolment began 1996). RBC PUFA levels were measured at baseline and expressed as a percent of total RBC PUFAs. PUFAs of primary interest were the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and their sum (the Omega-3 Index). PUFAs of secondary interest included the 2-major n-6 PUFAs, linoleic acid and arachidonic acid, and the PUFA factor score (a calculated variable including 6 PUFAs that accounts for their intercorrelations). The primary outcome was total mortality through August 2014.

Results

After a median of 14.9 years of follow-up, 1851 women (28.5%) had died. RBC levels of EPA and DHA were higher in the survivors (P < .002 for each). In the fully adjusted models, the hazard ratios (99% confidence intervals) for mortality associated with a 1 standard deviation PUFA increase for total mortality were 0.92 (0.85, 0.98) for the Omega-3 Index, 0.89 (0.82, 0.96) for EPA, 0.93 (0.87, 1.0) for DHA, and 0.76 (0.64, 0.90) for the PUFA factor score. There were no significant associations of alpha-linolenic acid, arachidonic acid or linoleic acid with total mortality.

Conclusions

Higher RBC levels of marine n-3 PUFAs were associated with reduced risk for all-cause mortality. These findings support the beneficial relationship between the Omega-3 Index and health outcomes.

Keywords:

Epidemiology, Prospective cohort study, Eicosapentaenoic acid, Docosahexaenoic acid, Omega-3 fatty acids, Omega-6 fatty acids

ClinicalTrials.gov Identifier: NCT00000611 (WHIMS).

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