Circulating de novo lipogenesis fatty acids and all-cause mortality in a prospective Dutch population cohort

Background: Circulating fatty acids (FA) from de novo lipogenesis (DNL) are associated with all-cause mortality in individuals with elevated CVD risk. However, compared to FA early in the DNL synthetic pathway, cis-vaccenic acid, one of the FA distal in the DNL synthetic pathway, has rarely been studied in a general population cohort. We hypothesized that circulating cis-vaccenic acid is more strongly related to all-cause mortality than other circulating DNL-related FA.

Objectives: The primary and secondary objectives of this study were to investigate the prospective associations of plasma levels of cis-vaccenic acid and other DNL-related FA with all-cause mortality in a general population, respectively.

Methods: We included 850 participants (mean ± SD age 53 ± 15 years) from the Dutch Lifelines cohort study. Circulating levels of palmitic (C16:0), palmitoleic (C16:1n7), cis-vaccenic (cis-C18:1n7), stearic (C18:0), oleic acid (C18:1n9) in plasma phospholipids (PL) and triglycerides (TG) were measured by gas chromatography. The associations of circulating cis-C18:1n7 and other DNL-related FA with all-cause mortality were assessed using Cox regression analyses.

Results: During a median follow-up of 9.3 (IQR: 5.4-10.8) years, 34 (4.0%) participants had died. In plasma PL, a 1-SD increase in cis-C18:1n7 was associated with an increased risk of all-cause mortality in univariate and multivariate models (p<0.02 for all), with a HR [95% CI] of 1.60 [1.13-2.25] after adjustment for age and sex.

Conclusions: Circulating plasma PL cis-C18:1n7 was associated with a higher risk for all-cause mortality. More studies are needed in different cohorts to verify and validate our results.

Keywords: Epidemiology; Fatty acids; Lipid metabolism; Lipogenesis; Population studies.