Effects of n-3 PUFAs on postprandial variation of metalloproteinases, and inflammatory and insulin resistance parameters in dyslipidemic patients: evaluation with euglycemic clamp and oral fat load

J Clin Lipidol. Nov-Dec 2012;6(6):553-64. doi: 10.1016/j.jacl.2012.02.010. Epub 2012 Feb 27.


Background: The oral fat load (OFL) is considered as one of the most accurate models of postprandial lipoprotein metabolism and it has been widely used to evaluate the postprandial fat load effect on single markers of inflammation.

Objective: To evaluate the effects of n-3 PUFAs, primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), with a content of 400 mg of EPA and 450 mg of DHA in each capsule, on metalloproteinases and inflammatory biomarkers in patients affected by combined dyslipidemia both in a fasting state and after a standardized OFL in a randomized, placebo-controlled trial.

Methods: Placebo or n-3 PUFAs 3 g/day (1 g three times a day during the meals) was administered for 6 months. At the baseline, and after 2, 4, and 6 months we evaluated body mass index (BMI), body weight, fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), blood pressure, lipid profile, soluble intercellular adhesion molecule-1 (sICAM-1), interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), soluble vascular cell adhesion molecule-1 (sVCAM-1), sE-selectin, tumor necrosis factor-α (TNF-α), and metalloproteinases 2 and 9 (MMP-2 and 9). Furthermore, at the baseline and at the end of the study, all patients underwent an euglycemic hyperinsulinemic clamp and an oral fat load.

Results: Tg levels were lower (-54 mg/dL) and high-density lipoprotein cholesterol higher (+6 mg/dL) with n-3 PUFAs compared with placebo; n-3 PUFAs gave lower levels of FPG (-3 mg/dL), sICAM (-25 ng/mL), IL-6 (-0.3 pg/mL), hs-CRP (-0.6 mg/L), sVCAM-1 (-89 ng/mL), sE-selectin (-5.8 ng/mL), TNF-α (-0.3 ng/mL), MMP-2 (-185.1 ng/mL), and MMP-9 (-91.5 ng/mL), and a greater M value (+1.21 μmol/min/kg) compared with placebo. After the OFL, there was a decrease of Tg, MMPs, and all inflammatory parameters with n-3 PUFAs, but not with placebo.

Conclusion: Supplementation with n-3 PUFA resulted in lower levels of FPG, plasma lipids, MMPs, and inflammatory parameters and in a better increase of M value compared to placebo, both in the fasting state and after an OFL.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Blood Glucose / analysis
  • Blood Pressure
  • Body Mass Index
  • Body Weight
  • C-Reactive Protein / metabolism
  • Cholesterol, HDL / blood
  • Dietary Supplements
  • Docosahexaenoic Acids / administration & dosage
  • Docosahexaenoic Acids / pharmacology*
  • Dyslipidemias / drug therapy*
  • Dyslipidemias / metabolism
  • E-Selectin / metabolism
  • Eicosapentaenoic Acid / administration & dosage
  • Eicosapentaenoic Acid / pharmacology*
  • Fasting
  • Female
  • Glucose Clamp Technique / methods
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacology
  • Insulin / blood
  • Insulin Resistance*
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-6 / metabolism
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Middle Aged
  • Postprandial Period*
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Cell Adhesion Molecule-1 / analysis
  • Vascular Cell Adhesion Molecule-1 / metabolism
  • Young Adult


  • Biomarkers
  • Blood Glucose
  • Cholesterol, HDL
  • E-Selectin
  • Hypoglycemic Agents
  • ICAM1 protein, human
  • IL6 protein, human
  • Insulin
  • Interleukin-6
  • SELE protein, human
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Docosahexaenoic Acids
  • C-Reactive Protein
  • Eicosapentaenoic Acid
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9