Dietary intake and biomarkers of linoleic acid and mortality: systematic review and meta-analysis of prospective cohort studies

Am J Clin Nutr. 2020 Jul 1;112(1):150-167. doi: 10.1093/ajcn/nqz349.


Background: Current evidence on associations between intakes of linoleic acid (LA), the predominant n-6 (ω-6) fatty acid, and mortality is inconsistent and has not been summarized by a systematic review and meta-analysis.

Objective: The aim was to perform a systematic review and meta-analysis of prospective cohort studies to examine associations between LA intake and mortality.

Methods: We conducted a comprehensive search of MEDLINE and EMBASE databases through 31 July 2019 for prospective cohort studies reporting associations of LA (assessed by dietary surveys and/or LA concentrations in adipose tissue or blood compartments) with mortality from all causes, cardiovascular disease (CVD), and cancer. Multivariable-adjusted RRs were pooled using random-effects meta-analysis.

Results: Thirty-eight studies reporting 44 prospective cohorts were identified; these included 811,069 participants with dietary intake assessment (170,076 all-cause, 50,786 CVD, and 59,684 cancer deaths) and 65,411 participants with biomarker measurements (9758 all-cause, 6492 CVD, and 1719 cancer deaths). Pooled RRs comparing extreme categories of dietary LA intake (high vs low) were 0.87 (95% CI: 0.81, 0.94; I2 = 67.9%) for total mortality, 0.87 (95% CI: 0.82, 0.92; I2 = 3.7%) for CVD mortality, and 0.89 (95% CI: 0.85, 0.93; I2 = 0%) for cancer mortality. Pooled RRs for each SD increment in LA concentrations in adipose tissue/blood compartments were 0.91 (95% CI: 0.87, 0.95; I2 = 64.1%) for total mortality, 0.89 (95% CI: 0.85, 0.94; I2 = 28.9%) for CVD mortality, and 0.91 (95% CI: 0.84, 0.98; I2 = 26.3%) for cancer mortality. Meta-regressions suggested baseline age and dietary assessment methods as potential sources of heterogeneity for the association between LA and total mortality.

Conclusions: In prospective cohort studies, higher LA intake, assessed by dietary surveys or biomarkers, was associated with a modestly lower risk of mortality from all causes, CVD, and cancer. These data support the potential long-term benefits of PUFA intake in lowering the risk of CVD and premature death.

Keywords: biomarkers; cardiovascular disease; dietary polyunsaturated fatty acid; linoleic acid; mortality.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / mortality*
  • Fatty Acids, Omega-6 / administration & dosage
  • Female
  • Humans
  • Linoleic Acid / administration & dosage*
  • Male
  • Middle Aged
  • Neoplasms / drug therapy
  • Neoplasms / mortality*
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Young Adult


  • Fatty Acids, Omega-6
  • Linoleic Acid