Docosahexaenoic Acid Attenuates Cardiovascular Risk Factors via a Decline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Plasma Levels

Lipids. 2016 Jan;51(1):75-83. doi: 10.1007/s11745-015-4099-4. Epub 2015 Nov 30.


Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that regulates cholesterol metabolism by promoting LDL receptor degradation in the liver and has recently been proposed as a therapeutic target in the management of hyperlipidaemia. We investigated the impact of dietary fat on the metabolism of sterols and on plasma PCSK9 concentrations to explore likely clinical usefulness. In a post hoc analysis of a double-blind randomised crossover controlled feeding trial, the Canola Oil Multicenter Intervention Trial (COMIT), volunteers (n = 54) with at least one condition related to metabolic syndrome consumed diets with one of the following treatment oils in beverages: (1) conventional canola oil (Canola); (2) canola oil rich in docosahexanoic acid (DHA) (CanolaDHA); and (3) high-oleic acid canola oil (CanolaOleic). The enrichment in oleic acid resulted in lower plasma cholesterol concentration compared with diets enriched in DHA. Contrarily, DHA-enriched oil significantly decreased plasma PCSK9 and triacylglycerols levels, but increased circulating levels of sterols. The variations in lathosterol, sitosterol, and campesterol indicate that plasma PCSK9 levels are sensitive to changes in cholesterol synthesis and/or absorption. There was a significant correlation between plasma PCSK9 levels and plasma triacylglicerol and apolipoprotein B levels, which was not affected by dietary fat. Therefore, our results suggest that the impact of dietary fats should not be discarded as complementary treatment in the management of patients with hyperlipidaemia. These findings should be considered in the analysis of ongoing studies and may represent a cautionary note in the treatment of patients with cardiovascular risk.

Keywords: Docosahexaenoic acid; Fatty acids; Hyperlipidaemia; PCSK9; Sterols.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apolipoproteins / blood
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / enzymology
  • Cardiovascular Diseases / prevention & control*
  • Cross-Over Studies
  • Diet
  • Docosahexaenoic Acids / pharmacology*
  • Double-Blind Method
  • Energy Intake
  • Fatty Acids, Monounsaturated / chemistry
  • Fatty Acids, Monounsaturated / pharmacology
  • Female
  • Humans
  • Male
  • Oleic Acids / pharmacology
  • Proprotein Convertase 9
  • Proprotein Convertases / blood*
  • Rapeseed Oil
  • Risk Factors
  • Serine Endopeptidases / blood*
  • Sterols / metabolism


  • Apolipoproteins
  • Fatty Acids, Monounsaturated
  • Oleic Acids
  • Rapeseed Oil
  • Sterols
  • Docosahexaenoic Acids
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • Proprotein Convertases
  • Serine Endopeptidases